Strains and stressors: an analysis of touchscreen learning in genetically diverse mouse strains.

PubMed

Graybeal, Carolyn; Bachu, Munisa; Mozhui, Khyobeni; Saksida, Lisa M; Bussey, Timothy J; Sagalyn, Erica; Williams, Robert W; Holmes, Andrew

2014-01-01

Touchscreen-based systems are growing in popularity as a tractable, translational approach for studying learning and cognition in rodents. However, while mouse strains are well known to differ in learning across various settings, performance variation between strains in touchscreen learning has not been well described. The selection of appropriate genetic strains and backgrounds is critical to the design of touchscreen-based studies and provides a basis for elucidating genetic factors moderating behavior. Here we provide a quantitative foundation for visual discrimination and reversal learning using touchscreen assays across a total of 35 genotypes. We found significant differences in operant performance and learning, including faster reversal learning in DBA/2J compared to C57BL/6J mice. We then assessed DBA/2J and C57BL/6J for differential sensitivity to an environmental insult by testing for alterations in reversal learning following exposure to repeated swim stress. Stress facilitated reversal learning (selectively during the late stage of reversal) in C57BL/6J, but did not affect learning in DBA/2J. To dissect genetic factors underlying these differences, we phenotyped a family of 27 BXD strains generated by crossing C57BL/6J and DBA/2J. There was marked variation in discrimination, reversal and extinction learning across the BXD strains, suggesting this task may be useful for identifying underlying genetic differences. Moreover, different measures of touchscreen learning were only modestly correlated in the BXD strains, indicating that these processes are comparatively independent at both genetic and phenotypic levels. Finally, we examined the behavioral structure of learning via principal component analysis of the current data, plus an archival dataset, totaling 765 mice. This revealed 5 independent factors suggestive of "reversal learning," "motivation-related late reversal learning," "discrimination learning," "speed to respond," and "motivation during discrimination." Together, these findings provide a valuable reference to inform the choice of strains and genetic backgrounds in future studies using touchscreen-based tasks.

Manipulations in Maternal Environment Reverse Periodontitis in Genetically Predisposed Rats

PubMed Central

Sluyter, Frans; Breivik, Torbjørn; Cools, Alexander

2002-01-01

The predisposition to develop periodontitis is partly genetically determined in humans as well as in animals. Here we demonstrate, however, that early manipulations in the maternal environment of an animal (rat) model of periodontitis can fully reverse the genetic predisposition to develop periodontitis at adult age. PMID:12093700

The behavioural consequences of sex reversal in dragons

PubMed Central

Li, Hong; Holleley, Clare E.; Elphick, Melanie; Georges, Arthur

2016-01-01

Sex differences in morphology, physiology, and behaviour are caused by sex-linked genes, as well as by circulating sex-steroid levels. Thus, a shift from genotypic to environmental sex determination may create an organism that exhibits a mixture of male-like and female-like traits. We studied a lizard species (Central Bearded Dragon, Pogona vitticeps), in which the high-temperature incubation of eggs transforms genetically male individuals into functional females. Although they are reproductively female, sex-reversed dragons (individuals with ZZ genotype reversed to female phenotype) resemble genetic males rather than females in morphology (relative tail length), general behaviour (boldness and activity level), and thermoregulatory tactics. Indeed, sex-reversed ‘females’ are more male-like in some behavioural traits than are genetic males. This novel phenotype may impose strong selection on the frequency of sex reversal within natural populations, facilitating rapid shifts in sex-determining systems. A single period of high incubation temperatures (generating thermally induced sex reversal) can produce functionally female individuals with male-like (or novel) traits that enhance individual fitness, allowing the new temperature-dependent sex-determining system to rapidly replace the previous genetically based one.

Marburg Virus Reverse Genetics Systems

PubMed Central

Schmidt, Kristina Maria; Mühlberger, Elke

2016-01-01

The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems. PMID:27338448

Marburg Virus Reverse Genetics Systems.

PubMed

Schmidt, Kristina Maria; Mühlberger, Elke

2016-06-22

The highly pathogenic Marburg virus (MARV) is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems.

Developing weighted criteria to evaluate lean reverse logistics through analytical network process

NASA Astrophysics Data System (ADS)

Zagloel, Teuku Yuri M.; Hakim, Inaki Maulida; Krisnawardhani, Rike Adyartie

2017-11-01

Reverse logistics is a part of supply chain that bring materials from consumers back to manufacturer in order to gain added value or do a proper disposal. Nowadays, most companies are still facing several problems on reverse logistics implementation which leads to high waste along reverse logistics processes. In order to overcome this problem, Madsen [Framework for Reverse Lean Logistics to Enable Green Manufacturing, Eco Design 2009: 6th International Symposium on Environmentally Conscious Design and Inverse Manufacturing, Sapporo, 2009] has developed a lean reverse logistics framework as a step to eliminate waste by implementing lean on reverse logistics. However, the resulted framework sets aside criteria used to evaluate its performance. This research aims to determine weighted criteria that can be used as a base on reverse logistics evaluation by considering lean principles. The resulted criteria will ensure reverse logistics are kept off from waste, thus implemented efficiently. Analytical Network Process (ANP) is used in this research to determine the weighted criteria. The result shows that criteria used for evaluation lean reverse logistics are Innovation and Learning (35%), Economic (30%), Process Flow Management (14%), Customer Relationship Management (13%), Environment (6%), and Social (2%).

Cloned cDNA of A/swine/Iowa/15/1930 internal genes as a candidate backbone for reverse genetics vaccine against influenza A viruses.

PubMed

Lekcharoensuk, Porntippa; Wiriyarat, Witthawat; Petcharat, Nantawan; Lekcharoensuk, Chalermpol; Auewarakul, Prasert; Richt, Juergen A

2012-02-14

Reverse genetics viruses for influenza vaccine production usually utilize the internal genes of the egg-adapted A/Puerto Rico/8/34 (PR8) strain. This egg-adapted strain provides high production yield in embryonated eggs but does not necessarily give the best yield in mammalian cell culture. In order to generate a reverse genetics viral backbone that is well-adapted to high growth in mammalian cell culture, a swine influenza isolate A/swine/Iowa/15/30 (H1N1) (rg1930) that was shown to give high yield in Madin-Darby canine kidney (MDCK) cells was used as the internal gene donor for reverse genetics plasmids. In this report, the internal genes from rg1930 were used for construction of reverse genetics viruses carrying a cleavage site-modified hemagglutinin (HA) gene and neuraminidase (NA) gene from a highly pathogenic H5N1 virus. The resulting virus (rg1930H5N1) was low pathogenic in vivo. Inactivated rg1930H5N1 vaccine completely protected chickens from morbidity and mortality after challenge with highly pathogenic H5N1. Protective immunity was obtained when chickens were immunized with an inactivated vaccine consisting of at least 2(9) HA units of the rg1930H5N1 virus. In comparison to the PR8-based reverse genetics viruses carrying the same HA and NA genes from an H5N1 virus, rg1930 based viruses yielded higher viral titers in MDCK and Vero cells. In addition, the reverse genetics derived H3N2 and H5N2 viruses with the rg1930 backbone replicated in MDCK cells better than the cognate viruses with the rgPR8 backbone. It is concluded that this newly established reverse genetics backbone system could serve as a candidate for a master donor strain for development of inactivated influenza vaccines in cell-based systems. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genetic dissection of behavioral flexibility: reversal learning in mice.

PubMed

Laughlin, Rick E; Grant, Tara L; Williams, Robert W; Jentsch, J David

2011-06-01

Behavioral inflexibility is a feature of schizophrenia, attention-deficit/hyperactivity disorder, and behavior addictions that likely results from heritable deficits in the inhibitory control over behavior. Here, we investigate the genetic basis of individual differences in flexibility, measured using an operant reversal learning task. We quantified discrimination acquisition and subsequent reversal learning in a cohort of 51 BXD strains of mice (2-5 mice/strain, n = 176) for which we have matched data on sequence, gene expression in key central nervous system regions, and neuroreceptor levels. Strain variation in trials to criterion on acquisition and reversal was high, with moderate heritability (∼.3). Acquisition and reversal learning phenotypes did not covary at the strain level, suggesting that these traits are effectively under independent genetic control. Reversal performance did covary with dopamine D2 receptor levels in the ventral midbrain, consistent with a similar observed relationship between impulsivity and D2 receptors in humans. Reversal, but not acquisition, is linked to a locus on mouse chromosome 10 with a peak likelihood ratio statistic at 86.2 megabase (p < .05 genome-wide). Variance in messenger RNA levels of select transcripts expressed in neocortex, hippocampus, and striatum correlated with the reversal learning phenotype, including Syn3, Nt5dc3, and Hcfc2. This work demonstrates the clear trait independence between, and genetic control of, discrimination acquisition and reversal and illustrates how globally coherent data sets for a single panel of highly related strains can be interrogated and integrated to uncover genetic sources and molecular and neuropharmacological candidates of complex behavioral traits relevant to human psychopathology. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Strains and Stressors: An Analysis of Touchscreen Learning in Genetically Diverse Mouse Strains

PubMed Central

Graybeal, Carolyn; Bachu, Munisa; Mozhui, Khyobeni; Saksida, Lisa M.; Bussey, Timothy J.; Sagalyn, Erica; Williams, Robert W.; Holmes, Andrew

2014-01-01

Touchscreen-based systems are growing in popularity as a tractable, translational approach for studying learning and cognition in rodents. However, while mouse strains are well known to differ in learning across various settings, performance variation between strains in touchscreen learning has not been well described. The selection of appropriate genetic strains and backgrounds is critical to the design of touchscreen-based studies and provides a basis for elucidating genetic factors moderating behavior. Here we provide a quantitative foundation for visual discrimination and reversal learning using touchscreen assays across a total of 35 genotypes. We found significant differences in operant performance and learning, including faster reversal learning in DBA/2J compared to C57BL/6J mice. We then assessed DBA/2J and C57BL/6J for differential sensitivity to an environmental insult by testing for alterations in reversal learning following exposure to repeated swim stress. Stress facilitated reversal learning (selectively during the late stage of reversal) in C57BL/6J, but did not affect learning in DBA/2J. To dissect genetic factors underlying these differences, we phenotyped a family of 27 BXD strains generated by crossing C57BL/6J and DBA/2J. There was marked variation in discrimination, reversal and extinction learning across the BXD strains, suggesting this task may be useful for identifying underlying genetic differences. Moreover, different measures of touchscreen learning were only modestly correlated in the BXD strains, indicating that these processes are comparatively independent at both genetic and phenotypic levels. Finally, we examined the behavioral structure of learning via principal component analysis of the current data, plus an archival dataset, totaling 765 mice. This revealed 5 independent factors suggestive of “reversal learning,” “motivation-related late reversal learning,” “discrimination learning,” “speed to respond,” and “motivation during discrimination.” Together, these findings provide a valuable reference to inform the choice of strains and genetic backgrounds in future studies using touchscreen-based tasks. PMID:24586288

Reversible conversion of valence-tautomeric copper metal-organic frameworks dependent single-crystal-to-single-crystal oxidation/reduction: a redox-switchable catalyst for C-H bonds activation reaction.

PubMed

Huang, Chao; Wu, Jie; Song, Chuanjun; Ding, Ran; Qiao, Yan; Hou, Hongwei; Chang, Junbiao; Fan, Yaoting

2015-06-28

Upon single-crystal-to-single-crystal (SCSC) oxidation/reduction, reversible structural transformations take place between the anionic porous zeolite-like Cu(I) framework and a topologically equivalent neutral Cu(I)Cu(II) mixed-valent framework. The unique conversion behavior of the Cu(I) framework endowed it as a redox-switchable catalyst for the direct arylation of heterocycle C-H bonds.

Stocking activities for the Arctic charr in Lake Geneva: Genetic effects in space and time.

PubMed

Savary, Romain; Dufresnes, Christophe; Champigneulle, Alexis; Caudron, Arnaud; Dubey, Sylvain; Perrin, Nicolas; Fumagalli, Luca

2017-07-01

Artificial stocking practices are widely used by resource managers worldwide, in order to sustain fish populations exploited by both recreational and commercial activities, but their benefits are controversial. Former practices involved exotic strains, although current programs rather consider artificial breeding of local fishes (supportive breeding). Understanding the complex genetic effects of these management strategies is an important challenge with economic and conservation implications, especially in the context of population declines. In this study, we focus on the declining Arctic charr ( Salvelinus alpinus ) population from Lake Geneva (Switzerland and France), which has initially been restocked with allochtonous fishes in the early eighties, followed by supportive breeding. In this context, we conducted a genetic survey to document the evolution of the genetic diversity and structure throughout the last 50 years, before and after the initiation of hatchery supplementation, using contemporary and historical samples. We show that the introduction of exotic fishes was associated with a genetic bottleneck in the 1980-1990s, a break of Hardy-Weinberg Equilibrium (HWE), a reduction in genetic diversity, an increase in genetic structure among spawning sites, and a change in their genetic composition. Together with better environmental conditions, three decades of subsequent supportive breeding using local fishes allowed to re-establish HWE and the initial levels of genetic variation. However, current spawning sites have not fully recovered their original genetic composition and were extensively homogenized across the lake. Our study demonstrates the drastic genetic consequences of different restocking tactics in a comprehensive spatiotemporal framework and suggests that genetic alteration by nonlocal stocking may be partly reversible through supportive breeding. We recommend that conservation-based programs consider local diversity and implement adequate protocols to limit the genetic homogenization of this Arctic charr population.

Slowly switching between environments facilitates reverse evolution in small populations.

PubMed

Tan, Longzhi; Gore, Jeff

2012-10-01

Natural populations must constantly adapt to ever-changing environmental conditions. A particularly interesting question is whether such adaptations can be reversed by returning the population to an ancestral environment. Such evolutionary reversals have been observed in both natural and laboratory populations. However, the factors that determine the reversibility of evolution are still under debate. The time scales of environmental change vary over a wide range, but little is known about how the rate of environmental change influences the reversibility of evolution. Here, we demonstrate computationally that slowly switching between environments increases the reversibility of evolution for small populations that are subject to only modest clonal interference. For small populations, slow switching reduces the mean number of mutations acquired in a new environment and also increases the probability of reverse evolution at each of these "genetic distances." As the population size increases, slow switching no longer reduces the genetic distance, thus decreasing the evolutionary reversibility. We confirm this effect using both a phenomenological model of clonal interference and also a Wright-Fisher stochastic simulation that incorporates genetic diversity. Our results suggest that the rate of environmental change is a key determinant of the reversibility of evolution, and provides testable hypotheses for experimental evolution. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

A Survey of Statistical Models for Reverse Engineering Gene Regulatory Networks

PubMed Central

Huang, Yufei; Tienda-Luna, Isabel M.; Wang, Yufeng

2009-01-01

Statistical models for reverse engineering gene regulatory networks are surveyed in this article. To provide readers with a system-level view of the modeling issues in this research, a graphical modeling framework is proposed. This framework serves as the scaffolding on which the review of different models can be systematically assembled. Based on the framework, we review many existing models for many aspects of gene regulation; the pros and cons of each model are discussed. In addition, network inference algorithms are also surveyed under the graphical modeling framework by the categories of point solutions and probabilistic solutions and the connections and differences among the algorithms are provided. This survey has the potential to elucidate the development and future of reverse engineering GRNs and bring statistical signal processing closer to the core of this research. PMID:20046885

Experimental evolution and the dynamics of genomic mutation rate modifiers.

PubMed

Raynes, Y; Sniegowski, P D

2014-11-01

Because genes that affect mutation rates are themselves subject to mutation, mutation rates can be influenced by natural selection and other evolutionary forces. The population genetics of mutation rate modifier alleles has been a subject of theoretical interest for many decades. Here, we review experimental contributions to our understanding of mutation rate modifier dynamics. Numerous evolution experiments have shown that mutator alleles (modifiers that elevate the genomic mutation rate) can readily rise to high frequencies via genetic hitchhiking in non-recombining microbial populations. Whereas these results certainly provide an explanatory framework for observations of sporadically high mutation rates in pathogenic microbes and in cancer lineages, it is nonetheless true that most natural populations have very low mutation rates. This raises the interesting question of how mutator hitchhiking is suppressed or its phenotypic effect reversed in natural populations. Very little experimental work has addressed this question; with this in mind, we identify some promising areas for future experimental investigation.

A Dynamic Circuit Hypothesis for the Pathogenesis of Blepharospasm.

PubMed

Peterson, David A; Sejnowski, Terrence J

2017-01-01

Blepharospasm (sometimes called "benign essential blepharospasm," BEB) is one of the most common focal dystonias. It involves involuntary eyelid spasms, eye closure, and increased blinking. Despite the success of botulinum toxin injections and, in some cases, pharmacologic or surgical interventions, BEB treatments are not completely efficacious and only symptomatic. We could develop principled strategies for preventing and reversing the disease if we knew the pathogenesis of primary BEB. The objective of this study was to develop a conceptual framework and dynamic circuit hypothesis for the pathogenesis of BEB. The framework extends our overarching theory for the multifactorial pathogenesis of focal dystonias (Peterson et al., 2010) to incorporate a two-hit rodent model specifically of BEB (Schicatano et al., 1997). We incorporate in the framework three features critical to cranial motor control: (1) the joint influence of motor cortical regions and direct descending projections from one of the basal ganglia output nuclei, the substantia nigra pars reticulata, on brainstem motor nuclei, (2) nested loops composed of the trigeminal blink reflex arc and the long sensorimotor loop from trigeminal nucleus through thalamus to somatosensory cortex back through basal ganglia to the same brainstem nuclei modulating the reflex arc, and (3) abnormalities in the basal ganglia dopamine system that provide a sensorimotor learning substrate which, when combined with patterns of increased blinking, leads to abnormal sensorimotor mappings manifest as BEB. The framework explains experimental data on the trigeminal reflex blink excitability (TRBE) from Schicatano et al. and makes predictions that can be tested in new experimental animal models based on emerging genetics in dystonia, including the recently characterized striatal-specific D1R dopamine transduction alterations caused by the GNAL mutation. More broadly, the model will provide a guide for future efforts to mechanistically link multiple factors in the pathogenesis of BEB and facilitate simulations of how exogenous manipulations of the pathogenic factors could ultimately be used to prevent and reverse the disorder.

A Dynamic Circuit Hypothesis for the Pathogenesis of Blepharospasm

PubMed Central

Peterson, David A.; Sejnowski, Terrence J.

2017-01-01

Blepharospasm (sometimes called “benign essential blepharospasm,” BEB) is one of the most common focal dystonias. It involves involuntary eyelid spasms, eye closure, and increased blinking. Despite the success of botulinum toxin injections and, in some cases, pharmacologic or surgical interventions, BEB treatments are not completely efficacious and only symptomatic. We could develop principled strategies for preventing and reversing the disease if we knew the pathogenesis of primary BEB. The objective of this study was to develop a conceptual framework and dynamic circuit hypothesis for the pathogenesis of BEB. The framework extends our overarching theory for the multifactorial pathogenesis of focal dystonias (Peterson et al., 2010) to incorporate a two-hit rodent model specifically of BEB (Schicatano et al., 1997). We incorporate in the framework three features critical to cranial motor control: (1) the joint influence of motor cortical regions and direct descending projections from one of the basal ganglia output nuclei, the substantia nigra pars reticulata, on brainstem motor nuclei, (2) nested loops composed of the trigeminal blink reflex arc and the long sensorimotor loop from trigeminal nucleus through thalamus to somatosensory cortex back through basal ganglia to the same brainstem nuclei modulating the reflex arc, and (3) abnormalities in the basal ganglia dopamine system that provide a sensorimotor learning substrate which, when combined with patterns of increased blinking, leads to abnormal sensorimotor mappings manifest as BEB. The framework explains experimental data on the trigeminal reflex blink excitability (TRBE) from Schicatano et al. and makes predictions that can be tested in new experimental animal models based on emerging genetics in dystonia, including the recently characterized striatal-specific D1R dopamine transduction alterations caused by the GNAL mutation. More broadly, the model will provide a guide for future efforts to mechanistically link multiple factors in the pathogenesis of BEB and facilitate simulations of how exogenous manipulations of the pathogenic factors could ultimately be used to prevent and reverse the disorder. PMID:28326032

FLP-18 Functions through the G-Protein-Coupled Receptors NPR-1 and NPR-4 to Modulate Reversal Length in Caenorhabditis elegans

PubMed Central

Dahiya, Yogesh; Babu, Kavita

2018-01-01

Animal behavior is critically dependent on the activity of neuropeptides. Reversals, one of the most conspicuous behaviors in Caenorhabditis elegans, plays an important role in determining the navigation strategy of the animal. Our experiments on hermaphrodite C. elegans show the involvement of a neuropeptide FLP-18 in modulating reversal length in these hermaphrodites. We show that FLP-18 controls the reversal length by regulating the activity of AVA interneurons through the G-protein-coupled neuropeptide receptors, NPR-4 and NPR-1. We go on to show that the site of action of these receptors is the AVA interneuron for NPR-4 and the ASE sensory neurons for NPR-1. We further show that mutants in the neuropeptide, flp-18, and its receptors show increased reversal lengths. Consistent with the behavioral data, calcium levels in the AVA neuron of freely reversing C. elegans were significantly higher and persisted for longer durations in flp-18, npr-1, npr-4, and npr-1 npr-4 genetic backgrounds compared with wild-type control animals. Finally, we show that increasing FLP-18 levels through genetic and physiological manipulations causes shorter reversal lengths. Together, our analysis suggests that the FLP-18/NPR-1/NPR-4 signaling is a pivotal point in the regulation of reversal length under varied genetic and environmental conditions. PMID:29712787

Reverse Genetics Approaches for the Development of Influenza Vaccines

PubMed Central

Nogales, Aitor; Martínez-Sobrido, Luis

2016-01-01

Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504

Reinventing the ames test as a quantitative lab that connects classical and molecular genetics.

PubMed

Goodson-Gregg, Nathan; De Stasio, Elizabeth A

2009-01-01

While many institutions use a version of the Ames test in the undergraduate genetics laboratory, students typically are not exposed to techniques or procedures beyond qualitative analysis of phenotypic reversion, thereby seriously limiting the scope of learning. We have extended the Ames test to include both quantitative analysis of reversion frequency and molecular analysis of revertant gene sequences. By giving students a role in designing their quantitative methods and analyses, students practice and apply quantitative skills. To help students connect classical and molecular genetic concepts and techniques, we report here procedures for characterizing the molecular lesions that confer a revertant phenotype. We suggest undertaking reversion of both missense and frameshift mutants to allow a more sophisticated molecular genetic analysis. These modifications and additions broaden the educational content of the traditional Ames test teaching laboratory, while simultaneously enhancing students' skills in experimental design, quantitative analysis, and data interpretation.

An iterative consensus-building approach to revising a genetics/genomics competency framework for nurse education in the UK

PubMed Central

Kirk, Maggie; Tonkin, Emma; Skirton, Heather

2014-01-01

KIRK M., TONKIN E. & SKIRTON H. (2014) An iterative consensus-building approach to revising a genetics/genomics competency framework for nurse education in the UK. Journal of Advanced Nursing 70(2), 405–420. doi: 10.1111/jan.12207 AimTo report a review of a genetics education framework using a consensus approach to agree on a contemporary and comprehensive revised framework. BackgroundAdvances in genomic health care have been significant since the first genetics education framework for nurses was developed in 2003. These, coupled with developments in policy and international efforts to promote nursing competence in genetics, indicated that review was timely. DesignA structured, iterative, primarily qualitative approach, based on a nominal group technique. MethodA meeting convened in 2010 involved stakeholders in UK nursing education, practice and management, including patient representatives (n = 30). A consensus approach was used to solicit participants' views on the individual/family needs identified from real-life stories of people affected by genetic conditions and the nurses' knowledge, skills and attitudes needed to meet those needs. Five groups considered the stories in iterative rounds, reviewing comments from previous groups. Omissions and deficiencies were identified by mapping resulting themes to the original framework. Anonymous voting captured views. Educators at a second meeting developed learning outcomes for the final framework. FindingsDeficiencies in relation to Advocacy, Information management and Ongoing care were identified. All competencies of the original framework were revised, adding an eighth competency to make explicit the need for ongoing care of the individual/family. ConclusionModifications to the framework reflect individual/family needs and are relevant to the nursing role. The approach promoted engagement in a complex issue and provides a framework to guide nurse education in genetics/genomics; however, nursing leadership is crucial to successful implementation. PMID:23879662

The placebo effect: from concepts to genes

PubMed Central

Colagiuri, Ben; Schenk, Lieven A.; Kessler, Michael D.; Dorsey, Susan G.; Colloca, Luana

2017-01-01

Despite its initial treatment as a nuisance variable, the placebo effect is now recognized as a powerful determinant of health across many different diseases and encounters. This is in light of some remarkable findings ranging from demonstrations that the placebo effect significantly modulates the response to active treatments in conditions such as pain, anxiety, Parkinson’s disease, and some surgical procedures. Here, we review pioneering studies and recent advances in behavioral, neurobiological, and genetic influences on the placebo effect. Based on a previous developed conceptual framework, the placebo effect is presented as the product of a general expectancy learning mechanism in which verbal, conditioned and social cues are centrally integrated to change behaviors and outcomes. Examples of the integration of verbal and conditioned cues, such as instructed reversal of placebo effects are also incorporated into this model. We discuss neuroimaging studies that using well-established behavioral paradigms have identified key brain regions and modulatory mechanisms underlying placebo effects. Finally, we present a synthesis of recent genetics studies on the placebo effect, highlighting a promising link between genetic variants in the dopamine, opioid, serotonin, and endocannabinoid pathways and placebo responsiveness. Greater understanding of the behavioral, neurobiological, and genetic influences on the placebo effect is critical for evaluating medical interventions and may allow health professionals to tailor and personalize interventions in order to maximize treatment outcomes in clinical settings. PMID:26272535

Sex reversal triggers the rapid transition from genetic to temperature-dependent sex.

PubMed

Holleley, Clare E; O'Meally, Denis; Sarre, Stephen D; Marshall Graves, Jennifer A; Ezaz, Tariq; Matsubara, Kazumi; Azad, Bhumika; Zhang, Xiuwen; Georges, Arthur

2015-07-02

Sex determination in animals is amazingly plastic. Vertebrates display contrasting strategies ranging from complete genetic control of sex (genotypic sex determination) to environmentally determined sex (for example, temperature-dependent sex determination). Phylogenetic analyses suggest frequent evolutionary transitions between genotypic and temperature-dependent sex determination in environmentally sensitive lineages, including reptiles. These transitions are thought to involve a genotypic system becoming sensitive to temperature, with sex determined by gene-environment interactions. Most mechanistic models of transitions invoke a role for sex reversal. Sex reversal has not yet been demonstrated in nature for any amniote, although it occurs in fish and rarely in amphibians. Here we make the first report of reptile sex reversal in the wild, in the Australian bearded dragon (Pogona vitticeps), and use sex-reversed animals to experimentally induce a rapid transition from genotypic to temperature-dependent sex determination. Controlled mating of normal males to sex-reversed females produces viable and fertile offspring whose phenotypic sex is determined solely by temperature (temperature-dependent sex determination). The W sex chromosome is eliminated from this lineage in the first generation. The instantaneous creation of a lineage of ZZ temperature-sensitive animals reveals a novel, climate-induced pathway for the rapid transition between genetic and temperature-dependent sex determination, and adds to concern about adaptation to rapid global climate change.

An iterative consensus-building approach to revising a genetics/genomics competency framework for nurse education in the UK.

PubMed

Kirk, Maggie; Tonkin, Emma; Skirton, Heather

2014-02-01

To report a review of a genetics education framework using a consensus approach to agree on a contemporary and comprehensive revised framework. Advances in genomic health care have been significant since the first genetics education framework for nurses was developed in 2003. These, coupled with developments in policy and international efforts to promote nursing competence in genetics, indicated that review was timely. A structured, iterative, primarily qualitative approach, based on a nominal group technique. A meeting convened in 2010 involved stakeholders in UK nursing education, practice and management, including patient representatives (n = 30). A consensus approach was used to solicit participants' views on the individual/family needs identified from real-life stories of people affected by genetic conditions and the nurses' knowledge, skills and attitudes needed to meet those needs. Five groups considered the stories in iterative rounds, reviewing comments from previous groups. Omissions and deficiencies were identified by mapping resulting themes to the original framework. Anonymous voting captured views. Educators at a second meeting developed learning outcomes for the final framework. Deficiencies in relation to Advocacy, Information management and Ongoing care were identified. All competencies of the original framework were revised, adding an eighth competency to make explicit the need for ongoing care of the individual/family. Modifications to the framework reflect individual/family needs and are relevant to the nursing role. The approach promoted engagement in a complex issue and provides a framework to guide nurse education in genetics/genomics; however, nursing leadership is crucial to successful implementation. © 2013 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.

Sex Reversal in Birds.

PubMed

Major, Andrew T; Smith, Craig A

2016-01-01

Sexual differentiation in birds is controlled genetically as in mammals, although the sex chromosomes are different. Males have a ZZ sex chromosome constitution, while females are ZW. Gene(s) on the sex chromosomes must initiate gonadal sex differentiation during embryonic life, inducing paired testes in ZZ individuals and unilateral ovaries in ZW individuals. The traditional view of avian sexual differentiation aligns with that expounded for other vertebrates; upon sexual differentiation, the gonads secrete sex steroid hormones that masculinise or feminise the rest of the body. However, recent studies on naturally occurring or experimentally induced avian sex reversal suggest a significant role for direct genetic factors, in addition to sex hormones, in regulating sexual differentiation of the soma in birds. This review will provide an overview of sex determination in birds and both naturally and experimentally induced sex reversal, with emphasis on the key role of oestrogen. We then consider how recent studies on sex reversal and gynandromorphic birds (half male:half female) are shaping our understanding of sexual differentiation in avians and in vertebrates more broadly. Current evidence shows that sexual differentiation in birds is a mix of direct genetic and hormonal mechanisms. Perturbation of either of these components may lead to sex reversal. © 2016 S. Karger AG, Basel.

Efficient and Robust Paramyxoviridae Reverse Genetics Systems

PubMed Central

Beaty, Shannon M.; Won, Sohui T.; Hong, Patrick; Lyons, Michael; Vigant, Frederic; Freiberg, Alexander N.; tenOever, Benjamin R.; Duprex, W. Paul

2017-01-01

ABSTRACT The notoriously low efficiency of Paramyxoviridae reverse genetics systems has posed a limiting barrier to the study of viruses in this family. Previous approaches to reverse genetics have utilized a wide variety of techniques to overcome the technical hurdles. Although robustness (i.e., the number of attempts that result in successful rescue) has been improved in some systems with the use of stable cell lines, the efficiency of rescue (i.e., the proportion of transfected cells that yield at least one successful rescue event) has remained low. We have substantially increased rescue efficiency for representative viruses from all five major Paramyxoviridae genera (from ~1 in 106-107 to ~1 in 102-103 transfected cells) by the addition of a self-cleaving hammerhead ribozyme (Hh-Rbz) sequence immediately preceding the start of the recombinant viral antigenome and the use of a codon-optimized T7 polymerase (T7opt) gene to drive paramyxovirus rescue. Here, we report a strategy for robust, reliable, and high-efficiency rescue of paramyxovirus reverse genetics systems, featuring several major improvements: (i) a vaccinia virus-free method, (ii) freedom to use any transfectable cell type for viral rescue, (iii) a single-step transfection protocol, and (iv) use of the optimal T7 promoter sequence for high transcription levels from the antigenomic plasmid without incorporation of nontemplated G residues. The robustness of our T7opt-HhRbz system also allows for greater latitude in the ratios of transfected accessory plasmids used that result in successful rescue. Thus, our system may facilitate the rescue and interrogation of the increasing number of emerging paramyxoviruses. IMPORTANCE The ability to manipulate the genome of paramyxoviruses and evaluate the effects of these changes at the phenotypic level is a powerful tool for the investigation of specific aspects of the viral life cycle and viral pathogenesis. However, reverse genetics systems for paramyxoviruses are notoriously inefficient, when successful. The ability to efficiently and robustly rescue paramyxovirus reverse genetics systems can be used to answer basic questions about the biology of paramyxoviruses, as well as to facilitate the considerable translational efforts being devoted to developing live attenuated paramyxovirus vaccine vectors. PMID:28405630

Which lessons can we learn from the European Union legal framework of medicines for the regulation of direct-to-consumer genetic tests?

PubMed

van Hellemondt, Rachèl; Hendriks, Aart; Breuning, Martijn

2012-01-01

The legal framework of the European Union (EU) for regulating access to and supply of direct-to-consumer (DTC) genetic tests is very liberal compared to the legal and regulatory framework for (internet) medicines. Nevertheless, both health related products can cause equally serious damage to the well being of individuals. In this contribution we examine whether the legal framework of the EU for the safety and responsible use of (internet) medicines could be an example for regulating access to and supply of DTC genetic tests. The EU laws governing medicines can, notwithstanding their shortcomings, serve as an example for (central) authorising the marketing of DTC genetic tests on the internal market in accordance with strict criteria regarding predictive value and clinical usefulness. Furthermore, a legal framework controlling DTC genetic tests also should introduce system supervision as well as quality criteria with respect to the information to be provided to consumers in order to enhance health protection. However, DTC genetic tests purchased through online ordering are difficult to supervise by any agency. Adequately protecting individuals against questionable testing kits calls for international vigilance and comprehensive measures by the international community. For Europe, it is important to rank the regulation of DTC genetic tests on the European regulatory agenda.

Development of FOCUS-GC: Framework for Outcomes of Clinical Communication Services in Genetic Counseling.

PubMed

Cragun, Deborah; Zierhut, Heather

2018-02-01

Conceptual frameworks bring together existing theories and models in order to identify, consolidate, and fill in gaps between theory, practice, and evidence. Given the vast number of possible outcomes that could be studied in genetic counseling, a framework for organizing outcomes and postulating relationships between communication services and genetic counseling outcomes was sought. Through an iterative approach involving literature review, thematic analysis, and consolidation, outcomes and processes were categorized to create and define components of a conceptual framework. The final product, "Framework for Outcomes of Clinical commUnication Services" (FOCUS) contains the following domains: communication strategy; communication process measures; patient care experience, patient changes, patient health; and family changes. A website was created to allow easier access and ongoing modifications to the framework. In addition, a step-by-step guide and two examples were created to show flexibility in how the framework can be used. FOCUS may help in conceptualizing, organizing and summarizing outcomes research related to risk communication and counseling in genetic service delivery as well as other healthcare settings.

Nanoporous frameworks exhibiting multiple stimuli responsiveness

NASA Astrophysics Data System (ADS)

Kundu, Pintu K.; Olsen, Gregory L.; Kiss, Vladimir; Klajn, Rafal

2014-04-01

Nanoporous frameworks are polymeric materials built from rigid molecules, which give rise to their nanoporous structures with applications in gas sorption and storage, catalysis and others. Conceptually new applications could emerge, should these beneficial properties be manipulated by external stimuli in a reversible manner. One approach to render nanoporous frameworks responsive to external signals would be to immobilize molecular switches within their nanopores. Although the majority of molecular switches require conformational freedom to isomerize, and switching in the solid state is prohibited, the nanopores may provide enough room for the switches to efficiently isomerize. Here we describe two families of nanoporous materials incorporating the spiropyran molecular switch. These materials exhibit a variety of interesting properties, including reversible photochromism and acidochromism under solvent-free conditions, light-controlled capture and release of metal ions, as well reversible chromism induced by solvation/desolvation.

Genome-Wide Association Mapping Combined with Reverse Genetics Identifies New Effectors of Low Water Potential-Induced Proline Accumulation in Arabidopsis1[W][OPEN

PubMed Central

Verslues, Paul E.; Lasky, Jesse R.; Juenger, Thomas E.; Liu, Tzu-Wen; Kumar, M. Nagaraj

2014-01-01

Arabidopsis (Arabidopsis thaliana) exhibits natural genetic variation in drought response, including varying levels of proline (Pro) accumulation under low water potential. As Pro accumulation is potentially important for stress tolerance and cellular redox control, we conducted a genome-wide association (GWAS) study of low water potential-induced Pro accumulation using a panel of natural accessions and publicly available single-nucleotide polymorphism (SNP) data sets. Candidate genomic regions were prioritized for subsequent study using metrics considering both the strength and spatial clustering of the association signal. These analyses found many candidate regions likely containing gene(s) influencing Pro accumulation. Reverse genetic analysis of several candidates identified new Pro effector genes, including thioredoxins and several genes encoding Universal Stress Protein A domain proteins. These new Pro effector genes further link Pro accumulation to cellular redox and energy status. Additional new Pro effector genes found include the mitochondrial protease LON1, ribosomal protein RPL24A, protein phosphatase 2A subunit A3, a MADS box protein, and a nucleoside triphosphate hydrolase. Several of these new Pro effector genes were from regions with multiple SNPs, each having moderate association with Pro accumulation. This pattern supports the use of summary approaches that incorporate clusters of SNP associations in addition to consideration of individual SNP probability values. Further GWAS-guided reverse genetics promises to find additional effectors of Pro accumulation. The combination of GWAS and reverse genetics to efficiently identify new effector genes may be especially applicable for traits difficult to analyze by other genetic screening methods. PMID:24218491

National Science Foundation-sponsored workshop report. Draft plan for soybean genomics.

PubMed

Stacey, Gary; Vodkin, Lila; Parrott, Wayne A; Shoemaker, Randy C

2004-05-01

Recent efforts to coordinate and define a research strategy for soybean (Glycine max) genomics began with the establishment of a Soybean Genetics Executive Committee, which will serve as a communication focal point between the soybean research community and granting agencies. Secondly, a workshop was held to define a strategy to incorporate existing tools into a framework for advancing soybean genomics research. This workshop identified and ranked research priorities essential to making more informed decisions as to how to proceed with large scale sequencing and other genomics efforts. Most critical among these was the need to finalize a physical map and to obtain a better understanding of genome microstructure. Addressing these research needs will require pilot work on new technologies to demonstrate an ability to discriminate between recently duplicated regions in the soybean genome and pilot projects to analyze an adequate amount of random genome sequence to identify and catalog common repeats. The development of additional markers, reverse genetics tools, and bioinformatics is also necessary. Successful implementation of these goals will require close coordination among various working groups.

A Genetic Linkage Map of the Hermaphrodite Teleost Fish Sparus aurata L.

PubMed Central

Franch, Rafaella; Louro, Bruno; Tsalavouta, Matina; Chatziplis, Dimitris; Tsigenopoulos, Costas S.; Sarropoulou, Elena; Antonello, Jenny; Magoulas, Andonis; Mylonas, Constantinos C.; Babbucci, Massimiliano; Patarnello, Tomaso; Power, Deborah M.; Kotoulas, Giorgos; Bargelloni, Luca

2006-01-01

The gilthead sea bream (Sparus aurata L.) is a marine fish of great importance for fisheries and aquaculture. It has also a peculiar sex-determination system, being a protandrous hermaphrodite. Here we report the construction of a first-generation genetic linkage map for S. aurata, based on 204 microsatellite markers. Twenty-six linkage groups (LG) were found. The total map length was 1241.9 cM. The ratio between sex-specific map lengths was 1:1.2 (male:female). Comparison with a preliminary radiation hybrid (RH) map reveals a good concordance, as all markers located in a single LG are located in a single RH group, except for Ad-25 and CId-31. Comparison with the Tetraodon nigroviridis genome revealed a considerable number of evolutionary conserved regions (ECRs) between the two species. The mean size of ECRs was 182 bp (sequence identity 60–90%). Forty-one ECRs have a known chromosomal location in the pufferfish genome. Despite the limited number of anchoring points, significant syntenic relationships were found. The linkage map presented here provides a robust comparative framework for QTL analysis in S. aurata and is a step toward the identification of genetic loci involved both in the determination of economically important traits and in the individual timing of sex reversal. PMID:16951080

Inherited XX sex reversal originating from wild medaka populations.

PubMed

Shinomiya, A; Otake, H; Hamaguchi, S; Sakaizumi, M

2010-11-01

The teleost fish, medaka (Oryzias latipes), has an XX/XY sex-determining mechanism. A Y-linked DM domain gene, DMY, has been isolated by positional cloning as the sex-determining gene in this species. Previously, we conducted a field survey of genotypic sex and found that approximately 1% of wild medaka are sex-reversed (XX males and XY females). Here, we performed genetic analyses of nine spontaneous XX sex-reversed males to elucidate its genetic basis. In all cases, the F(1) progeny were all females, whereas XX males reappeared in the backcross (BC) progeny, suggesting that XX sex reversal is a recessive trait. Although the incidences of sex reversal in the BC progeny were mostly low, 40% were males derived from one XX male. We performed linkage analysis using 55 BC males and located a single major factor, sda-1 (sex-determining autosomal factor-1), controlling sex reversal in an autosomal linkage group. Thus, genes involved in the sex-determining pathway can be isolated from spontaneous mutants in wild populations.

Lassa Virus Reverse Genetics.

PubMed

Martínez-Sobrido, Luis; Paessler, Slobodan; de la Torre, Juan Carlos

2017-01-01

The Old World (OW) arenavirus Lassa (LASV ) is estimated to infect several hundred thousand people yearly in West Africa, resulting in high numbers of Lassa fever (LF), a viral hemorrhagic fever (HF) disease associated with high morbidity and mortality. To date, no licensed vaccines are available to LASV infections, and anti-LASV drug therapy is limited to an off-label use of ribavirin (Rib) that is only partially effective. The development of reverse genetics has provided investigators with a novel and powerful approach for the investigation of the molecular, cell biology, and pathogenesis of LASV. The use of cell-based LASV minigenome (MG) systems has allowed examining the cis- and trans-acting factors involved in genome replication and gene transcription and the identification of novel drugable LASV targets. Likewise, it is now feasible to rescue infectious recombinant (r)LASV entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify antiviral drugs against LASV and the implementation of novel strategies to develop live-attenuated vaccines (LAV). In this chapter we will summarize the state-of-the-art experimental procedures for implementation of LASV reverse genetics. In addition, we will briefly discuss some significant translational research developments that have been made possible upon the development of LASV reverse genetics.

Reverse genetics in high throughput: rapid generation of complete negative strand RNA virus cDNA clones and recombinant viruses thereof.

PubMed

Nolden, T; Pfaff, F; Nemitz, S; Freuling, C M; Höper, D; Müller, T; Finke, Stefan

2016-04-05

Reverse genetics approaches are indispensable tools for proof of concepts in virus replication and pathogenesis. For negative strand RNA viruses (NSVs) the limited number of infectious cDNA clones represents a bottleneck as clones are often generated from cell culture adapted or attenuated viruses, with limited potential for pathogenesis research. We developed a system in which cDNA copies of complete NSV genomes were directly cloned into reverse genetics vectors by linear-to-linear RedE/T recombination. Rapid cloning of multiple rabies virus (RABV) full length genomes and identification of clones identical to field virus consensus sequence confirmed the approache's reliability. Recombinant viruses were recovered from field virus cDNA clones. Similar growth kinetics of parental and recombinant viruses, preservation of field virus characters in cell type specific replication and virulence in the mouse model were confirmed. Reduced titers after reporter gene insertion indicated that the low level of field virus replication is affected by gene insertions. The flexibility of the strategy was demonstrated by cloning multiple copies of an orthobunyavirus L genome segment. This important step in reverse genetics technology development opens novel avenues for the analysis of virus variability combined with phenotypical characterization of recombinant viruses at a clonal level.

Development of a PCR-Based Reverse Genetics System for an Attenuated Duck Tembusu Virus Strain

PubMed Central

Wu, Xiaogang; Shi, Ying; Yan, Dawei; Li, Xuesong; Yan, Pixi; Gao, Xuyuan; Zhang, Yuee; Yu, Lei; Ren, Chaochao; Li, Guoxin; Yan, Liping; Teng, Qiaoyang; Li, Zejun

2016-01-01

The infectious disease caused by the duck Tembusu virus (DTMUV) has resulted in massive economic losses to the Chinese duck industry in China since 2010. Research on the molecular basis of DTMUV pathogenicity has been hampered by the lack of a reliable reverse genetics system for this virus. Here we developed a PCR-based reverse genetics system with high fidelity for the attenuated DTMUV strain FX2010-180P. The rescued virus was characterized by using both indirect immunofluorescence assays (IFA) and whole genome sequencing. The rescued virus (rFX2010-180P) grew to similar titers as compared with the wild-type virus in DF-1 cells, and had similar replication and immunogenicity properties in ducks. To determine whether exogenous proteins could be expressed from DTMUV, both an internal ribosomal entry site (IRES) and the enhanced green fluorescent protein (eGFP) gene were introduced between the NS5 gene and the 3' non-coding sequence of FX2010-180P. A recombinant DTMUV expressing eGFP was rescued, but eGFP expression was unstable after 4 passages in DF-1 cells due to a deletion of 1,294 nucleotides. The establishment of a reliable reverse genetics system for FX2010-180P provides a foundation for future studies of DTMUV. PMID:27248497

Development of a PCR-Based Reverse Genetics System for an Attenuated Duck Tembusu Virus Strain.

PubMed

Wu, Xiaogang; Shi, Ying; Yan, Dawei; Li, Xuesong; Yan, Pixi; Gao, Xuyuan; Zhang, Yuee; Yu, Lei; Ren, Chaochao; Li, Guoxin; Yan, Liping; Teng, Qiaoyang; Li, Zejun

2016-01-01

The infectious disease caused by the duck Tembusu virus (DTMUV) has resulted in massive economic losses to the Chinese duck industry in China since 2010. Research on the molecular basis of DTMUV pathogenicity has been hampered by the lack of a reliable reverse genetics system for this virus. Here we developed a PCR-based reverse genetics system with high fidelity for the attenuated DTMUV strain FX2010-180P. The rescued virus was characterized by using both indirect immunofluorescence assays (IFA) and whole genome sequencing. The rescued virus (rFX2010-180P) grew to similar titers as compared with the wild-type virus in DF-1 cells, and had similar replication and immunogenicity properties in ducks. To determine whether exogenous proteins could be expressed from DTMUV, both an internal ribosomal entry site (IRES) and the enhanced green fluorescent protein (eGFP) gene were introduced between the NS5 gene and the 3' non-coding sequence of FX2010-180P. A recombinant DTMUV expressing eGFP was rescued, but eGFP expression was unstable after 4 passages in DF-1 cells due to a deletion of 1,294 nucleotides. The establishment of a reliable reverse genetics system for FX2010-180P provides a foundation for future studies of DTMUV.

Discovering Knowledge from Noisy Databases Using Genetic Programming.

ERIC Educational Resources Information Center

Wong, Man Leung; Leung, Kwong Sak; Cheng, Jack C. Y.

2000-01-01

Presents a framework that combines Genetic Programming and Inductive Logic Programming, two approaches in data mining, to induce knowledge from noisy databases. The framework is based on a formalism of logic grammars and is implemented as a data mining system called LOGENPRO (Logic Grammar-based Genetic Programming System). (Contains 34…

Reasoning across Ontologically Distinct Levels: Students' Understandings of Molecular Genetics

ERIC Educational Resources Information Center

Duncan, Ravit Golan; Reiser, Brian J.

2007-01-01

In this article we apply a novel analytical framework to explore students' difficulties in understanding molecular genetics--a domain that is particularly challenging to learn. Our analytical framework posits that reasoning in molecular genetics entails mapping across ontologically distinct levels--an information level containing the genetic…

Genetic screens for mutations affecting development of Xenopus tropicalis.

PubMed

Goda, Tadahiro; Abu-Daya, Anita; Carruthers, Samantha; Clark, Matthew D; Stemple, Derek L; Zimmerman, Lyle B

2006-06-01

We present here the results of forward and reverse genetic screens for chemically-induced mutations in Xenopus tropicalis. In our forward genetic screen, we have uncovered 77 candidate phenotypes in diverse organogenesis and differentiation processes. Using a gynogenetic screen design, which minimizes time and husbandry space expenditures, we find that if a phenotype is detected in the gynogenetic F2 of a given F1 female twice, it is highly likely to be a heritable abnormality (29/29 cases). We have also demonstrated the feasibility of reverse genetic approaches for obtaining carriers of mutations in specific genes, and have directly determined an induced mutation rate by sequencing specific exons from a mutagenized population. The Xenopus system, with its well-understood embryology, fate map, and gain-of-function approaches, can now be coupled with efficient loss-of-function genetic strategies for vertebrate functional genomics and developmental genetics.

Reverse-engineering the genetic circuitry of a cancer cell with predicted intervention in chronic lymphocytic leukemia.

PubMed

Vallat, Laurent; Kemper, Corey A; Jung, Nicolas; Maumy-Bertrand, Myriam; Bertrand, Frédéric; Meyer, Nicolas; Pocheville, Arnaud; Fisher, John W; Gribben, John G; Bahram, Seiamak

2013-01-08

Cellular behavior is sustained by genetic programs that are progressively disrupted in pathological conditions--notably, cancer. High-throughput gene expression profiling has been used to infer statistical models describing these cellular programs, and development is now needed to guide orientated modulation of these systems. Here we develop a regression-based model to reverse-engineer a temporal genetic program, based on relevant patterns of gene expression after cell stimulation. This method integrates the temporal dimension of biological rewiring of genetic programs and enables the prediction of the effect of targeted gene disruption at the system level. We tested the performance accuracy of this model on synthetic data before reverse-engineering the response of primary cancer cells to a proliferative (protumorigenic) stimulation in a multistate leukemia biological model (i.e., chronic lymphocytic leukemia). To validate the ability of our method to predict the effects of gene modulation on the global program, we performed an intervention experiment on a targeted gene. Comparison of the predicted and observed gene expression changes demonstrates the possibility of predicting the effects of a perturbation in a gene regulatory network, a first step toward an orientated intervention in a cancer cell genetic program.

Reverse Genetics of Newcastle Disease Virus.

PubMed

Cardenas-Garcia, Stivalis; Afonso, Claudio L

2017-01-01

Reverse genetics allows for the generation of recombinant viruses or vectors used in functional studies, vaccine development, and gene therapy. This technique enables genetic manipulation and cloning of viral genomes, gene mutation through site-directed mutagenesis, along with gene insertion or deletion, among other studies. An in vitro infection-based system including the highly attenuated vaccinia virus Ankara strain expressing the T7 RNA polymerase from bacteriophage T7, with co-transfection of three helper plasmids and a full-length cDNA plasmid, was successfully developed to rescue genetically modified Newcastle disease viruses in 1999. In this chapter, the materials and the methods involved in rescuing Newcastle disease virus (NDV) from cDNA, utilizing site-directed mutagenesis and gene replacement techniques, are described in detail.

Sensitivity of Female Inbreds of Cucumis sativus to Sex Reversion by Gibberellin.

PubMed

Shifriss, O; George, W L

1964-03-27

Two female inbred cucumbers were developed by substituting gene Acr for acr in the genetic backgrounds of the monoecious races Marketer and Tokyo, which exhibit weak and strong male tendency respectively. Marketer females are resistant and Tokyo females are sensitive to sex reversion in response to treatments with gibberellin A(3). Resistance and sensitivity of this type appear to depend upon the genetic system which controls sex tendency.

Reverse Genetics for Newcastle Disease Virus as a Vaccine Vector.

PubMed

Kim, Shin-Hee; Samal, Siba K

2018-02-22

Newcastle disease virus (NDV) is an economically important pathogen in the poultry industry worldwide. Recovery of infectious NDV from cDNA using reverse genetics has made it possible to manipulate the genome of NDV. This has greatly contributed to our understanding of the molecular biology and pathogenesis of NDV. Furthermore, NDV has modular genome and accommodates insertion of a foreign gene as a transcriptional unit, thus enabling NDV as a vaccine vector against diseases of humans and animals. Avirulent NDV strains (e.g., LaSota and B1) have been commonly used as vaccine vectors. In this protocol, we have described reverse genetics of NDV to be used as a vaccine vector by exemplifying the recovery of NDV vectored avian influenza virus vaccine. Specifically, cloning and recovery of NDV expressing the hemagglutinin protein of highly pathogenic influenza virus were explained. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

Population genetic structure and direct observations reveal sex-reversed patterns of dispersal in a cooperative bird.

PubMed

Harrison, Xavier A; York, Jennifer E; Young, Andrew J

2014-12-01

Sex-biased dispersal is pervasive and has diverse evolutionary implications, but the fundamental drivers of dispersal sex biases remain unresolved. This is due in part to limited diversity within taxonomic groups in the direction of dispersal sex biases, which leaves hypothesis testing critically dependent upon identifying rare reversals of taxonomic norms. Here, we use a combination of observational and genetic data to demonstrate a rare reversal of the avian sex bias in dispersal in the cooperatively breeding white-browed sparrow weaver (Plocepasser mahali). Direct observations revealed that (i) natal philopatry was rare, with both sexes typically dispersing locally to breed, and (ii), unusually for birds, males bred at significantly greater distances from their natal group than females. Population genetic analyses confirmed these patterns, as (i) corrected Assignment index (AIc), FST tests and isolation-by-distance metrics were all indicative of longer dispersal distances among males than females, and (ii) spatial autocorrelation analysis indicated stronger within-group genetic structure among females than males. Examining the spatial scale of extra-group mating highlighted that the resulting 'sperm dispersal' could have acted in concert with individual dispersal to generate these genetic patterns, but gamete dispersal alone cannot account entirely for the sex differences in genetic structure observed. That leading hypotheses for the evolution of dispersal sex biases cannot readily account for these sex-reversed patterns of dispersal in white-browed sparrow weavers highlights the continued need for attention to alternative explanations for this enigmatic phenomenon. We highlight the potential importance of sex differences in the distances over which dispersal opportunities can be detected. © 2014 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

The Expertise Reversal Effect Is a Variant of the More General Element Interactivity Effect

ERIC Educational Resources Information Center

Chen, Ouhao; Kalyuga, Slava; Sweller, John

2017-01-01

Within the framework of cognitive load theory, the element interactivity and the expertise reversal effects usually are not treated as closely related effects. We argue that the two effects may be intertwined with the expertise reversal effect constituting a particular example of the element interactivity effect. Specifically, the element…

Missing Links in Genes to Traits: Toward Teaching for an Integrated Framework of Genetics

ERIC Educational Resources Information Center

Pavlova, Iglika V.; Kreher, Scott A.

2013-01-01

Genetics, one of the most influential fields, underlies all of biology and produces discoveries that are in the news daily. However, many students leave introductory biology and genetics courses lacking a coherent framework of knowledge to use in their daily lives. We identify substantial "missing links" in the teaching of foundational…

Forward and reverse mutagenesis in C. elegans

PubMed Central

Kutscher, Lena M.; Shaham, Shai

2014-01-01

Mutagenesis drives natural selection. In the lab, mutations allow gene function to be deciphered. C. elegans is highly amendable to functional genetics because of its short generation time, ease of use, and wealth of available gene-alteration techniques. Here we provide an overview of historical and contemporary methods for mutagenesis in C. elegans, and discuss principles and strategies for forward (genome-wide mutagenesis) and reverse (target-selected and gene-specific mutagenesis) genetic studies in this animal. PMID:24449699

An assessment of heavy ion irradiation mutagenesis for reverse genetics in wheat (Triticum aestivum L.).

PubMed

Fitzgerald, Timothy L; Powell, Jonathan J; Stiller, Jiri; Weese, Terri L; Abe, Tomoko; Zhao, Guangyao; Jia, Jizeng; McIntyre, C Lynne; Li, Zhongyi; Manners, John M; Kazan, Kemal

2015-01-01

Reverse genetic techniques harnessing mutational approaches are powerful tools that can provide substantial insight into gene function in plants. However, as compared to diploid species, reverse genetic analyses in polyploid plants such as bread wheat can present substantial challenges associated with high levels of sequence and functional similarity amongst homoeologous loci. We previously developed a high-throughput method to identify deletions of genes within a physically mutagenized wheat population. Here we describe our efforts to combine multiple homoeologous deletions of three candidate disease susceptibility genes (TaWRKY11, TaPFT1 and TaPLDß1). We were able to produce lines featuring homozygous deletions at two of the three homoeoloci for all genes, but this was dependent on the individual mutants used in crossing. Intriguingly, despite extensive efforts, viable lines possessing homozygous deletions at all three homoeoloci could not be produced for any of the candidate genes. To investigate deletion size as a possible reason for this phenomenon, we developed an amplicon sequencing approach based on synteny to Brachypodium distachyon to assess the size of the deletions removing one candidate gene (TaPFT1) in our mutants. These analyses revealed that genomic deletions removing the locus are relatively large, resulting in the loss of multiple additional genes. The implications of this work for the use of heavy ion mutagenesis for reverse genetic analyses in wheat are discussed.

An Assessment of Heavy Ion Irradiation Mutagenesis for Reverse Genetics in Wheat (Triticum aestivum L.)

PubMed Central

Fitzgerald, Timothy L.; Powell, Jonathan J.; Stiller, Jiri; Weese, Terri L.; Abe, Tomoko; Zhao, Guangyao; Jia, Jizeng; McIntyre, C. Lynne; Li, Zhongyi; Manners, John M.; Kazan, Kemal

2015-01-01

Reverse genetic techniques harnessing mutational approaches are powerful tools that can provide substantial insight into gene function in plants. However, as compared to diploid species, reverse genetic analyses in polyploid plants such as bread wheat can present substantial challenges associated with high levels of sequence and functional similarity amongst homoeologous loci. We previously developed a high-throughput method to identify deletions of genes within a physically mutagenized wheat population. Here we describe our efforts to combine multiple homoeologous deletions of three candidate disease susceptibility genes (TaWRKY11, TaPFT1 and TaPLDß1). We were able to produce lines featuring homozygous deletions at two of the three homoeoloci for all genes, but this was dependent on the individual mutants used in crossing. Intriguingly, despite extensive efforts, viable lines possessing homozygous deletions at all three homoeoloci could not be produced for any of the candidate genes. To investigate deletion size as a possible reason for this phenomenon, we developed an amplicon sequencing approach based on synteny to Brachypodium distachyon to assess the size of the deletions removing one candidate gene (TaPFT1) in our mutants. These analyses revealed that genomic deletions removing the locus are relatively large, resulting in the loss of multiple additional genes. The implications of this work for the use of heavy ion mutagenesis for reverse genetic analyses in wheat are discussed. PMID:25719507

Recovery of infectious classical swine fever virus (CSFV) from full-length genomic cDNA clones by a swine kidney cell line expressing bacteriophage T7 RNA polymerase.

PubMed

van Gennip, H G; van Rijn, P A; Widjojoatmodjo, M N; Moormann, R J

1999-03-01

A new method for the recovery of infectious classical swine fever virus (CSFV) from full-length genomic cDNA clones of the C-strain was developed. Classical reverse genetics is based on transfection of in vitro transcribed RNA to target cells to recover RNA viruses. However, the specific infectivity of such in vitro transcribed RNA in swine kidney cells is usually low. To improve reverse genetics for CSFV, a stable swine kidney cell line was established that expresses cytoplasmic bacteriophage T7 RNA polymerase (SK6.T7). A 200-fold increased virus titre was obtained from SK6.T7 cells transfected with linearized full-length cDNA compared to in vitro transcribed RNA, whereas transfection of circular full-length cDNA resulted in 20-fold increased virus titres. Viruses generated on the SK6.T7 cells are indistinguishable from the viruses generated by the classical reverse genetic procedures. These results show the improved recovery of infectious CSFV directly from full-length cDNAs. Furthermore, the reverse genetic procedures are simplified to a faster, one step protocol. We conclude that the SK6.T7 cell line will be a valuable tool for recovering mutant CSFV and will contribute to future pestivirus research.

Reaching a Consensus on the Definition of Genetic Literacy that Is Required from a Twenty-First-Century Citizen

NASA Astrophysics Data System (ADS)

Boerwinkel, Dirk Jan; Yarden, Anat; Waarlo, Arend Jan

2017-12-01

To determine what knowledge of genetics is needed for decision-making on genetic-related issues, a consensus-reaching approach was used. An international group of 57 experts, involved in teaching, studying, or developing genetic education and communication or working with genetic applications in medicine, agriculture, or forensics, answered the questions: "What knowledge of genetics is relevant to those individuals not professionally involved in science?" and "Why is this knowledge relevant?" The answers were classified in different knowledge components following the PISA 2015 science framework. During a workshop with the participants, the results were discussed and applied to seven cases in which genetic knowledge is relevant for decision-making. The analysis of these discussions resulted in a revised framework consisting of nine conceptual knowledge components, three sociocultural components, and four epistemic components. The framework can be used in curricular decisions; its open character allows for including new technologies and applications and facilitates comparisons of different cases.

A reverse engineering algorithm for neural networks, applied to the subthalamopallidal network of basal ganglia.

PubMed

Floares, Alexandru George

2008-01-01

Modeling neural networks with ordinary differential equations systems is a sensible approach, but also very difficult. This paper describes a new algorithm based on linear genetic programming which can be used to reverse engineer neural networks. The RODES algorithm automatically discovers the structure of the network, including neural connections, their signs and strengths, estimates its parameters, and can even be used to identify the biophysical mechanisms involved. The algorithm is tested on simulated time series data, generated using a realistic model of the subthalamopallidal network of basal ganglia. The resulting ODE system is highly accurate, and results are obtained in a matter of minutes. This is because the problem of reverse engineering a system of coupled differential equations is reduced to one of reverse engineering individual algebraic equations. The algorithm allows the incorporation of common domain knowledge to restrict the solution space. To our knowledge, this is the first time a realistic reverse engineering algorithm based on linear genetic programming has been applied to neural networks.

The art and design of genetic screens: maize

USDA-ARS?s Scientific Manuscript database

Maize (Zea mays) is an excellent model for basic research. Genetic screens have informed our understanding of developmental processes, meiosis, epigenetics and biochemical pathways--not only in maize but also in other cereal crops. We discuss the forward and reverse genetic screens that are possible...

The Effects of Meiosis/Genetics Integration and Instructional Sequence on College Biology Student Achievement in Genetics.

ERIC Educational Resources Information Center

Browning, Mark

The purpose of the research was to manipulate two aspects of genetics instruction in order to measure their effects on college, introductory biology students' achievement in genetics. One instructional sequence that was used dealt first with monohybrid autosomal inheritance patterns, then sex-linkage. The alternate sequence was the reverse.…

Reverse genetics: Its origins and prospects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berg, P.

1991-04-01

The nucleotide sequence of a gene and its flanking segments alone will not tell us how its expression is regulated during development and differentiation, or in response to environmental changes. To comprehend the physiological significance of the molecular details requires biological analysis. Recombinant DNA techniques provide a powerful experimental approach. A strategy termed reverse genetics' utilizes the analysis of the activities of mutant and normal genes and experimentally constructed mutants to explore the relationship between gene structure and function thereby helping elucidate the relationship between genotype and phenotype.

Genetics Home Reference: nephronophthisis

MedlinePlus

... which can include liver fibrosis, heart abnormalities, or mirror image reversal of the position of one or ... Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related ...

A pillar-layered metal-organic framework as luminescent sensor for selective and reversible response of chloroform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Kun; Li, Shuni; Jiang, Yucheng

A new 3D metal-organic framework, namely, (Zn{sub 4}(H{sub 2}BPTC){sub 2}(HCOO){sub 4}){sub n} (SNNU-1, H{sub 4}BPTC=biphenyl-3,3',5,5'-tetracarboxylic acid, SNNU=Shaanxi Normal University) has been solvothermal synthesized. Four independent tetrahedral Zn atoms are connected by organic ligands to form a 2D Zn-H{sub 2}BPTC layer, which is further bridged by in-situ generated HCOO{sup -} to give the 3D pillar-layered framework of SNNU-1. Unique Zn and H{sub 2}BPTC all act as 4-connected nodes leading to a new 4,4,4-connected topological net with point symbol of (4·5·6{sup 2}·8{sup 2})(4·5{sup 2}·6{sup 2}·8)(5{sup 2}·6{sup 3}·7). Notably, intense blue emission band is observed for SNNU-1, which exhibits solvent-dependent effect. Compared tomore » other common organic solvents, chloroform can specially improve the photoluminescent intensity of SNNU-1. Further repeated response and release experiments clearly showed that SNNU-1 can act as luminescent sensor for selective and reversible detection of chloroform. - Graphical abstract: Zn{sup 2+} ions are bridged by aromatic tetracarboxylate ligands and inorganic formate anions to give a microporous pillar layered open-framework, which exhibits not only strong photoluminescence but also selective and reversible luminescent sensing for chloroform. - Highlights: • Novel Zn-tetracarboxylate-formate microporous pillar layered open-framework. • New 4,4,4-connected topology and rod-packing net. • Solvent-dependent photoluminescent intensity. • Selective and reversible response for chloroform.« less

Speciation reversal and biodiversity dynamics with hybridization in changing environments.

PubMed

Seehausen, Ole; Takimoto, Gaku; Roy, Denis; Jokela, Jukka

2008-01-01

A considerable fraction of the world's biodiversity is of recent evolutionary origin and has evolved as a by-product of, and is maintained by, divergent adaptation in heterogeneous environments. Conservationists have paid attention to genetic homogenization caused by human-induced translocations (e.g. biological invasions and stocking), and to the importance of environmental heterogeneity for the ecological coexistence of species. However, far less attention has been paid to the consequences of loss of environmental heterogeneity to the genetic coexistence of sympatric species. Our review of empirical observations and our theoretical considerations on the causes and consequences of interspecific hybridization suggest that a loss of environmental heterogeneity causes a loss of biodiversity through increased genetic admixture, effectively reversing speciation. Loss of heterogeneity relaxes divergent selection and removes ecological barriers to gene flow between divergently adapted species, promoting interspecific introgressive hybridization. Since heterogeneity of natural environments is rapidly deteriorating in most biomes, the evolutionary ecology of speciation reversal ought to be fully integrated into conservation biology.

Crystal growth, differential gas adsorption, high thermal stability, and reversible coordination of two new barium-organic frameworks, Ba(SBA)(DMF){sub 4} and Ba{sub 2}(BTEC)(H{sub 2}O)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Halake, Shobha; Ok, Kang Min, E-mail: kmok@cau.ac.kr

2015-11-15

Single crystals of two barium-organic framework materials, Ba(SBA)(DMF){sub 4} (CAUMOF-15) and Ba{sub 2}(BTEC)(H{sub 2}O) (CAUMOF-16), have been grown through solvothermal reactions (H{sub 2}SBA=4,4′-sulfonyldibenzoic acid and H{sub 4}BTEC=1,2,4,5-benzenetetracarboxylic acid). The crystal structures of the reported frameworks have been determined by single-crystal X-ray diffraction. The materials have been fully characterized by powder X-ray diffraction (PXRD), elemental analyses, Infrared (IR) spectroscopy, and thermogravimetric analyses (TGA). CAUMOF-15 reveals a three-dimensional open-framework that comprises of an inorganic motif with one-dimensional chains and the SBA linkers. CAUMOF-16 shows another three-dimensional backbone consisting of layers of edge-shared BaO{sub 9} and BaO{sub 10} polyhedra, and BTEC pillars. Bothmore » of the 3D frameworks exhibit relatively high thermal stabilities. The PXRD and IR spectral data confirm that CAUMOF-15 and CAUMOF-16 reveal reversible coordinations of the respective solvent molecules, DMF and H{sub 2}O. Gas adsorption properties towards nitrogen, hydrogen, and carbon dioxide have been also investigated. - Graphical abstract: Crystals of two new barium-organic frameworks, Ba(SBA)(DMF){sub 4} and Ba{sub 2}(BTEC)(H{sub 2}O), exhibiting a differential gas adsorption, a high thermal stability, and a reversible coordination of solvent molecules have been grown. - Highlights: • Crystals of two new 3D Ba-MOFs are grown. • The two Ba-MOFs reveal very high thermal stabilities up to ca. 400 °C. • Ba(SBA)(DMF){sub 4} exhibits differential gas adsorption properties. • The two Ba-MOFs show reversible coordination of the solvent molecules.« less

An Association Mapping Framework To Account for Potential Sex Difference in Genetic Architectures.

PubMed

Kang, Eun Yong; Lee, Cue Hyunkyu; Furlotte, Nicholas A; Joo, Jong Wha J; Kostem, Emrah; Zaitlen, Noah; Eskin, Eleazar; Han, Buhm

2018-05-11

Over the past few years, genome-wide association studies have identified many trait-associated loci that have different effects on females and males, which increased attention to the genetic architecture differences between the sexes. The between-sex differences in genetic architectures can cause a variety of phenomena such as differences in the effect sizes at trait-associated loci, differences in the magnitudes of polygenic background effects, and differences in the phenotypic variances. However, current association testing approaches for dealing with sex, such as including sex as a covariate, cannot fully account for these phenomena and can be suboptimal in statistical power. We present a novel association mapping framework, MetaSex, that can comprehensively account for the genetic architecture differences between the sexes. Through simulations and applications to real data, we show that our framework has superior performance than previous approaches in association mapping. Copyright © 2018, Genetics.

FLP-18 Functions through the G-Protein-Coupled Receptors NPR-1 and NPR-4 to Modulate Reversal Length in Caenorhabditis elegans.

PubMed

Bhardwaj, Ashwani; Thapliyal, Saurabh; Dahiya, Yogesh; Babu, Kavita

2018-05-16

Animal behavior is critically dependent on the activity of neuropeptides. Reversals, one of the most conspicuous behaviors in Caenorhabditis elegans , plays an important role in determining the navigation strategy of the animal. Our experiments on hermaphrodite C. elegans show the involvement of a neuropeptide FLP-18 in modulating reversal length in these hermaphrodites. We show that FLP-18 controls the reversal length by regulating the activity of AVA interneurons through the G-protein-coupled neuropeptide receptors, NPR-4 and NPR-1. We go on to show that the site of action of these receptors is the AVA interneuron for NPR-4 and the ASE sensory neurons for NPR-1. We further show that mutants in the neuropeptide, flp-18 , and its receptors show increased reversal lengths. Consistent with the behavioral data, calcium levels in the AVA neuron of freely reversing C. elegans were significantly higher and persisted for longer durations in flp-18 , npr-1 , npr-4 , and npr-1 npr-4 genetic backgrounds compared with wild-type control animals. Finally, we show that increasing FLP-18 levels through genetic and physiological manipulations causes shorter reversal lengths. Together, our analysis suggests that the FLP-18/NPR-1/NPR-4 signaling is a pivotal point in the regulation of reversal length under varied genetic and environmental conditions. SIGNIFICANCE STATEMENT In this study, we elucidate the circuit and molecular machinery required for normal reversal behavior in hermaphrodite Caenorhabditis elegans We delineate the circuit and the neuropeptide receptors required for maintaining reversal length in C. elegans Our work sheds light on the importance of a single neuropeptide, FLP-18, and how change in levels in this one peptide could allow the animal to change the length of its reversal, thereby modulating how the C. elegans explores its environment. We also go on to show that FLP-18 functions to maintain reversal length through the neuropeptide receptors NPR-4 and NPR-1. Our study will allow for a better understanding of the complete repertoire of behaviors shown by freely moving animals as they explore their environment. Copyright © 2018 the authors 0270-6474/18/384641-14$15.00/0.

Hybrid algorithms for fuzzy reverse supply chain network design.

PubMed

Che, Z H; Chiang, Tzu-An; Kuo, Y C; Cui, Zhihua

2014-01-01

In consideration of capacity constraints, fuzzy defect ratio, and fuzzy transport loss ratio, this paper attempted to establish an optimized decision model for production planning and distribution of a multiphase, multiproduct reverse supply chain, which addresses defects returned to original manufacturers, and in addition, develops hybrid algorithms such as Particle Swarm Optimization-Genetic Algorithm (PSO-GA), Genetic Algorithm-Simulated Annealing (GA-SA), and Particle Swarm Optimization-Simulated Annealing (PSO-SA) for solving the optimized model. During a case study of a multi-phase, multi-product reverse supply chain network, this paper explained the suitability of the optimized decision model and the applicability of the algorithms. Finally, the hybrid algorithms showed excellent solving capability when compared with original GA and PSO methods.

Hybrid Algorithms for Fuzzy Reverse Supply Chain Network Design

PubMed Central

Che, Z. H.; Chiang, Tzu-An; Kuo, Y. C.

2014-01-01

In consideration of capacity constraints, fuzzy defect ratio, and fuzzy transport loss ratio, this paper attempted to establish an optimized decision model for production planning and distribution of a multiphase, multiproduct reverse supply chain, which addresses defects returned to original manufacturers, and in addition, develops hybrid algorithms such as Particle Swarm Optimization-Genetic Algorithm (PSO-GA), Genetic Algorithm-Simulated Annealing (GA-SA), and Particle Swarm Optimization-Simulated Annealing (PSO-SA) for solving the optimized model. During a case study of a multi-phase, multi-product reverse supply chain network, this paper explained the suitability of the optimized decision model and the applicability of the algorithms. Finally, the hybrid algorithms showed excellent solving capability when compared with original GA and PSO methods. PMID:24892057

The strains recommended for use in the bacterial reverse mutation test (OECD guideline 471) can be certified as non-genetically modified organisms.

PubMed

Sugiyama, Kei-Ichi; Yamada, Masami; Awogi, Takumi; Hakura, Atsushi

2016-01-01

The bacterial reverse mutation test, commonly called Ames test, is used worldwide. In Japan, the genetically modified organisms (GMOs) are regulated under the Cartagena Domestic Law, and organisms obtained by self-cloning and/or natural occurrence would be exempted from the law case by case. The strains of Salmonella typhimurium and Escherichia coli recommended for use in the bacterial reverse mutation test (OECD guideline 471), have been considered as non-GMOs because they can be constructed by self-cloning or naturally occurring bacterial strains, or do not disturb the biological diversity. The present article explains the reasons why these tester strains should be classified as non-GMOs.

[Computer aided design for fixed partial denture framework based on reverse engineering technology].

PubMed

Sun, Yu-chun; Lü, Pei-jun; Wang, Yong

2006-03-01

To explore a computer aided design (CAD) route for the framework of domestic fixed partial denture (FPD) and confirm the suitable method of 3-D CAD. The working area of a dentition model was scanned with a 3-D mechanical scanner. Using the reverse engineering (RE) software, margin and border curves were extracted and several reference curves were created to ensure the dimension and location of pontic framework that was taken from the standard database. The shoulder parts of the retainers were created after axial surfaces constructed. The connecting areas, axial line and curving surface of the framework connector were finally created. The framework of a three-unit FPD was designed with RE technology, which showed smooth surfaces and continuous contours. The design route is practical. The result of this study is significant in theory and practice, which will provide a reference for establishing the computer aided design/computer aided manufacture (CAD/CAM) system of domestic FPD.

Mean-field studies of time reversal breaking states in super-heavy nuclei with the Gogny force

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robledo, L. M., E-mail: luis.robledo@uam.es

2015-10-15

Recent progress on the description of time reversal breaking (odd mass and multi-quasiparticle excitation) states in super-heavy nuclei within a mean field framework and using several flavors of the Gogny interaction is reported. The study includes ground and excited states in selected odd mass isotopes of nobelium and mendelevium as well as high K isomeric states in {sup 254}No. These are two and four-quasiparticle excitations that are treated in the same self-consistent HFB plus blocking framework as the odd mass states.

Dynamic constitutional frameworks for DNA biomimetic recognition.

PubMed

Catana, Romina; Barboiu, Mihail; Moleavin, Ioana; Clima, Lilia; Rotaru, Alexandru; Ursu, Elena-Laura; Pinteala, Mariana

2015-02-07

Linear and cross-linked dynamic constitutional frameworks generated from reversibly interacting linear PEG/core constituents and cationic sites shed light on the dominant coiling versus linear DNA binding behaviours, closer to the histone DNA binding wrapping mechanism.

Automated Design Framework for Synthetic Biology Exploiting Pareto Optimality.

PubMed

Otero-Muras, Irene; Banga, Julio R

2017-07-21

In this work we consider Pareto optimality for automated design in synthetic biology. We present a generalized framework based on a mixed-integer dynamic optimization formulation that, given design specifications, allows the computation of Pareto optimal sets of designs, that is, the set of best trade-offs for the metrics of interest. We show how this framework can be used for (i) forward design, that is, finding the Pareto optimal set of synthetic designs for implementation, and (ii) reverse design, that is, analyzing and inferring motifs and/or design principles of gene regulatory networks from the Pareto set of optimal circuits. Finally, we illustrate the capabilities and performance of this framework considering four case studies. In the first problem we consider the forward design of an oscillator. In the remaining problems, we illustrate how to apply the reverse design approach to find motifs for stripe formation, rapid adaption, and fold-change detection, respectively.

Direct and reverse secret-key capacities of a quantum channel.

PubMed

Pirandola, Stefano; García-Patrón, Raul; Braunstein, Samuel L; Lloyd, Seth

2009-02-06

We define the direct and reverse secret-key capacities of a memoryless quantum channel as the optimal rates that entanglement-based quantum-key-distribution protocols can reach by using a single forward classical communication (direct reconciliation) or a single feedback classical communication (reverse reconciliation). In particular, the reverse secret-key capacity can be positive for antidegradable channels, where no forward strategy is known to be secure. This property is explicitly shown in the continuous variable framework by considering arbitrary one-mode Gaussian channels.

Risks Associated With Lentiviral Vector Exposures and Prevention Strategies

PubMed Central

Schlimgen, Ryan; Howard, John; Wooley, Dawn; Thompson, Maureen; Baden, Lindsey R.; Yang, Otto O.; Christiani, David C.; Mostoslavsky, Gustavo; Diamond, David V.; Duane, Elizabeth Gilman; Byers, Karen; Winters, Thomas; Gelfand, Jeffrey A.; Fujimoto, Gary; Hudson, T. Warner; Vyas, Jatin M.

2016-01-01

Lentiviral vectors (LVVs) are powerful genetic tools that are being used with greater frequency in biomedical laboratories and clinical trials. Adverse events reported from initial clinical studies provide a basis for risk assessment of occupational exposures, yet many questions remain about the potential harm that LVVs may cause. We review those risks and provide a framework for principal investigators, Institutional Biosafety Committees, and occupational health professionals to assess and communicate the risks of exposure to staff. We also provide recommendations to federal research and regulatory agencies for tracking LVV exposures to evaluate long-term outcomes. U.S. Food and Drug Administration approved antiviral drugs for HIV have theoretical benefits in LVV exposures, although evidence to support their use is currently limited. If treatment is appropriate, we recommend a 7-day treatment with an integrase inhibitor with or without a reverse transcriptase inhibitor within 72 hours of exposure. PMID:27930472

Genetic correlations and the evolution of photoperiodic time measurement within a local population of the pitcher-plant mosquito, Wyeomyia smithii

PubMed Central

Bradshaw, W E; Emerson, K J; Holzapfel, C M

2012-01-01

The genetic relationship between the daily circadian clock and the seasonal photoperiodic timer remains a subject of intense controversy. In Wyeomyia smithii, the critical photoperiod (an overt expression of the photoperiodic timer) evolves independently of the rhythmic response to the Nanda–Hamner protocol (an overt expression of the daily circadian clock) over a wide geographical range in North America. Herein, we focus on these two processes within a single local population in which there is a negative genetic correlation between them. We show that antagonistic selection against this genetic correlation rapidly breaks it down and, in fact, reverses its sign, showing that the genetic correlation is due primarily to linkage and not to pleiotropy. This rapid reversal of the genetic correlation within a small, single population means that it is difficult to argue that circadian rhythmicity forms the necessary, causal basis for the adaptive divergence of photoperiodic time measurement within populations or for the evolution of photoperiodic time measurement among populations over a broad geographical gradient of seasonal selection. PMID:22072069

Genetically modified organisms: an analysis of the regulatory framework currently employed within the European Union.

PubMed

Gent, R N

1999-09-01

Genetic engineering technology is starting to bring many commercial products to the market. These genetically modified organisms (GMOs) and their derived products are subject to topical debate as to their benefits and risks. The strengths and weaknesses of the regulatory framework that controls their development and application is central to the question of whether this technology poses significant risk to the public health during this critical phase of its evolution. A critical review was carried out of the legal framework regulating the contained use, deliberate release and some aspects of consumer protection relevant to the control of GMOs in Europe and the United Kingdom. The current legal framework is failing to provide a speed of adaptation commensurate with the development of the science of genetic engineering; failing to properly respond to democratic control; failing to resolve significant conflict between the protection of free markets and protection of public health and the environment; and failing to implement obligations on biodiversity. The present legal framework must be replaced. Current European Union proposals for new standards of regulation are welcome, but provide only for further incremental change, and do not address some significant fundamental flaws in our current laws.

How is genetic testing evaluated? A systematic review of the literature.

PubMed

Pitini, Erica; De Vito, Corrado; Marzuillo, Carolina; D'Andrea, Elvira; Rosso, Annalisa; Federici, Antonio; Di Maria, Emilio; Villari, Paolo

2018-05-01

Given the rapid development of genetic tests, an assessment of their benefits, risks, and limitations is crucial for public health practice. We performed a systematic review aimed at identifying and comparing the existing evaluation frameworks for genetic tests. We searched PUBMED, SCOPUS, ISI Web of Knowledge, Google Scholar, Google, and gray literature sources for any documents describing such frameworks. We identified 29 evaluation frameworks published between 2000 and 2017, mostly based on the ACCE Framework (n = 13 models), or on the HTA process (n = 6), or both (n = 2). Others refer to the Wilson and Jungner screening criteria (n = 3) or to a mixture of different criteria (n = 5). Due to the widespread use of the ACCE Framework, the most frequently used evaluation criteria are analytic and clinical validity, clinical utility and ethical, legal and social implications. Less attention is given to the context of implementation. An economic dimension is always considered, but not in great detail. Consideration of delivery models, organizational aspects, and consumer viewpoint is often lacking. A deeper analysis of such context-related evaluation dimensions may strengthen a comprehensive evaluation of genetic tests and support the decision-making process.

On valuing patches: Estimating contributions to metapopulation growth with reverse-time capture-recapture modelling

USGS Publications Warehouse

Sanderlin, J.S.; Waser, P.M.; Hines, J.E.; Nichols, J.D.

2012-01-01

Metapopulation ecology has historically been rich in theory, yet analytical approaches for inferring demographic relationships among local populations have been few. We show how reverse-time multi-state capture-recapture models can be used to estimate the importance of local recruitment and interpopulation dispersal to metapopulation growth. We use 'contribution metrics' to infer demographic connectedness among eight local populations of banner-tailed kangaroo rats, to assess their demographic closure, and to investigate sources of variation in these contributions. Using a 7 year dataset, we show that: (i) local populations are relatively independent demographically, and contributions to local population growth via dispersal within the system decline with distance; (ii) growth contributions via local survival and recruitment are greater for adults than juveniles, while contributions involving dispersal are greater for juveniles; (iii) central populations rely more on local recruitment and survival than peripheral populations; (iv) contributions involving dispersal are not clearly related to overall metapopulation density; and (v) estimated contributions from outside the system are unexpectedly large. Our analytical framework can classify metapopulations on a continuum between demographic independence and panmixia, detect hidden population growth contributions, and make inference about other population linkage forms, including rescue effects and source-sink structures. Finally, we discuss differences between demographic and genetic population linkage patterns for our system. ?? 2011 The Royal Society.

Improving the Reverse Logistics Respecting Principles of Sustainable Development in an Industrial Company

NASA Astrophysics Data System (ADS)

Fidlerová, Helena; Mĺkva, Miroslava

2016-06-01

Reverse logistics, the movement of materials back up the supply chain, is recognised by many organisations as an opportunity for adding value. The paper considers the theoretical framework and the conception of reverse logistics in literature and practice. The objective of the article is to propose tangible solutions which eliminate the imbalances in reverse logistics and improve the waste management in the company. The case study focuses on the improvement in the process of waste packaging in the context of sustainable development as a part of reverse logistics in the surveyed industrial company in Slovakia.

Intermediate-type vancomycin resistance (VISA) in genetically-distinct Staphylococcus aureus isolates is linked to specific, reversible metabolic alterations.

PubMed

Alexander, Elizabeth L; Gardete, Susana; Bar, Haim Y; Wells, Martin T; Tomasz, Alexander; Rhee, Kyu Y

2014-01-01

Intermediate (VISA-type) vancomycin resistance in Staphylococcus aureus has been associated with a range of physiologic and genetic alterations. Previous work described the emergence of VISA-type resistance in two clonally-distinct series of isolates. In both series (the first belonging to MRSA clone ST8-USA300, and the second to ST5-USA100), resistance was conferred by a single mutation in yvqF (a negative regulator of the vraSR two-component system associated with vancomycin resistance). In the USA300 series, resistance was reversed by a secondary mutation in vraSR. In this study, we combined systems-level metabolomic profiling with statistical modeling techniques to discover specific, reversible metabolic alterations associated with the VISA phenotype.

Rescue of a Plant Negative-Strand RNA Virus from Cloned cDNA: Insights into Enveloped Plant Virus Movement and Morphogenesis.

PubMed

Wang, Qiang; Ma, Xiaonan; Qian, ShaSha; Zhou, Xin; Sun, Kai; Chen, Xiaolan; Zhou, Xueping; Jackson, Andrew O; Li, Zhenghe

2015-10-01

Reverse genetics systems have been established for all major groups of plant DNA and positive-strand RNA viruses, and our understanding of their infection cycles and pathogenesis has benefitted enormously from use of these approaches. However, technical difficulties have heretofore hampered applications of reverse genetics to plant negative-strand RNA (NSR) viruses. Here, we report recovery of infectious virus from cloned cDNAs of a model plant NSR, Sonchus yellow net rhabdovirus (SYNV). The procedure involves Agrobacterium-mediated transcription of full-length SYNV antigenomic RNA and co-expression of the nucleoprotein (N), phosphoprotein (P), large polymerase core proteins and viral suppressors of RNA silencing in Nicotiana benthamiana plants. Optimization of core protein expression resulted in up to 26% recombinant SYNV (rSYNV) infections of agroinfiltrated plants. A reporter virus, rSYNV-GFP, engineered by inserting a green fluorescence protein (GFP) gene between the N and P genes was able to express GFP during systemic infections and after repeated plant-to-plant mechanical passages. Deletion analyses with rSYNV-GFP demonstrated that SYNV cell-to-cell movement requires the sc4 protein and suggested that uncoiled nucleocapsids are infectious movement entities. Deletion analyses also showed that the glycoprotein is not required for systemic infection, although the glycoprotein mutant was defective in virion morphogenesis. Taken together, we have developed a robust reverse genetics system for SYNV that provides key insights into morphogenesis and movement of an enveloped plant virus. Our study also provides a template for developing analogous systems for reverse genetic analysis of other plant NSR viruses.

Rescue of a Plant Negative-Strand RNA Virus from Cloned cDNA: Insights into Enveloped Plant Virus Movement and Morphogenesis

PubMed Central

Zhou, Xin; Sun, Kai; Chen, Xiaolan; Zhou, Xueping; Jackson, Andrew O.; Li, Zhenghe

2015-01-01

Reverse genetics systems have been established for all major groups of plant DNA and positive-strand RNA viruses, and our understanding of their infection cycles and pathogenesis has benefitted enormously from use of these approaches. However, technical difficulties have heretofore hampered applications of reverse genetics to plant negative-strand RNA (NSR) viruses. Here, we report recovery of infectious virus from cloned cDNAs of a model plant NSR, Sonchus yellow net rhabdovirus (SYNV). The procedure involves Agrobacterium-mediated transcription of full-length SYNV antigenomic RNA and co-expression of the nucleoprotein (N), phosphoprotein (P), large polymerase core proteins and viral suppressors of RNA silencing in Nicotiana benthamiana plants. Optimization of core protein expression resulted in up to 26% recombinant SYNV (rSYNV) infections of agroinfiltrated plants. A reporter virus, rSYNV-GFP, engineered by inserting a green fluorescence protein (GFP) gene between the N and P genes was able to express GFP during systemic infections and after repeated plant-to-plant mechanical passages. Deletion analyses with rSYNV-GFP demonstrated that SYNV cell-to-cell movement requires the sc4 protein and suggested that uncoiled nucleocapsids are infectious movement entities. Deletion analyses also showed that the glycoprotein is not required for systemic infection, although the glycoprotein mutant was defective in virion morphogenesis. Taken together, we have developed a robust reverse genetics system for SYNV that provides key insights into morphogenesis and movement of an enveloped plant virus. Our study also provides a template for developing analogous systems for reverse genetic analysis of other plant NSR viruses. PMID:26484673

Undoing Suggestive Influence on Memory: The Reversibility of the Eyewitness Misinformation Effect

ERIC Educational Resources Information Center

Oeberst, Aileen; Blank, Hartmut

2012-01-01

Presenting inconsistent postevent information about a witnessed incident typically decreases the accuracy of memory reports concerning that event (the "misinformation effect"). Surprisingly, the "reversibility" of the effect (after an initial occurrence) has remained largely unexplored. Based on a "memory conversion" theoretical framework and…

Development of a reverse genetics system to generate a recombinant Ebola virus Makona expressing a green fluorescent protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albariño, César G., E-mail: calbarino@cdc.gov; Wiggleton Guerrero, Lisa; Lo, Michael K.

Previous studies have demonstrated the potential application of reverse genetics technology in studying a broad range of aspects of viral biology, including gene regulation, protein function, cell entry, and pathogenesis. Here, we describe a highly efficient reverse genetics system used to generate recombinant Ebola virus (EBOV) based on a recent isolate from a human patient infected during the 2014–2015 outbreak in Western Africa. We also rescued a recombinant EBOV expressing a fluorescent reporter protein from a cleaved VP40 protein fusion. Using this virus and an inexpensive method to quantitate the expression of the foreign gene, we demonstrate its potential usefulnessmore » as a tool for screening antiviral compounds and measuring neutralizing antibodies. - Highlights: • Recombinant Ebola virus (EBOV) derived from Makona variant was rescued. • New protocol for viral rescue allows 100% efficiency. • Modified EBOV expresses a green fluorescent protein from a VP40-fused protein. • Modified EBOV was tested as tool to screen antiviral compounds and measure neutralizing antibodies.« less

“Better Not to Know?”: Justifiable Limits on the Right to Information in the Realm of DTC Genetic Testing. An Analysis of the European and Spanish Legal Framework.

PubMed

Martínez Otero, Juan María

2017-04-01

The rapid advance of genetics increases the availability in the market of different genetic tests, which can be acquired directly by consumers without the intermediation of a healthcare professional. Both the European and the Spanish legal framework have restricted the access to these direct-to-consumer (DTC) genetic tests on the grounds of different reasons, such as the protection of consumers or the preservation of public health. The present article discusses these legal restrictions under the light of the right to information.

Software For Genetic Algorithms

NASA Technical Reports Server (NTRS)

Wang, Lui; Bayer, Steve E.

1992-01-01

SPLICER computer program is genetic-algorithm software tool used to solve search and optimization problems. Provides underlying framework and structure for building genetic-algorithm application program. Written in Think C.

Operationalizing the Reciprocal Engagement Model of Genetic Counseling Practice: a Framework for the Scalable Delivery of Genomic Counseling and Testing.

PubMed

Schmidlen, Tara; Sturm, Amy C; Hovick, Shelly; Scheinfeldt, Laura; Scott Roberts, J; Morr, Lindsey; McElroy, Joseph; Toland, Amanda E; Christman, Michael; O'Daniel, Julianne M; Gordon, Erynn S; Bernhardt, Barbara A; Ormond, Kelly E; Sweet, Kevin

2018-02-19

With the advent of widespread genomic testing for diagnostic indications and disease risk assessment, there is increased need to optimize genetic counseling services to support the scalable delivery of precision medicine. Here, we describe how we operationalized the reciprocal engagement model of genetic counseling practice to develop a framework of counseling components and strategies for the delivery of genomic results. This framework was constructed based upon qualitative research with patients receiving genomic counseling following online receipt of potentially actionable complex disease and pharmacogenomics reports. Consultation with a transdisciplinary group of investigators, including practicing genetic counselors, was sought to ensure broad scope and applicability of these strategies for use with any large-scale genomic testing effort. We preserve the provision of pre-test education and informed consent as established in Mendelian/single-gene disease genetic counseling practice. Following receipt of genomic results, patients are afforded the opportunity to tailor the counseling agenda by selecting the specific test results they wish to discuss, specifying questions for discussion, and indicating their preference for counseling modality. The genetic counselor uses these patient preferences to set the genomic counseling session and to personalize result communication and risk reduction recommendations. Tailored visual aids and result summary reports divide areas of risk (genetic variant, family history, lifestyle) for each disease to facilitate discussion of multiple disease risks. Post-counseling, session summary reports are actively routed to both the patient and their physician team to encourage review and follow-up. Given the breadth of genomic information potentially resulting from genomic testing, this framework is put forth as a starting point to meet the need for scalable genetic counseling services in the delivery of precision medicine.

Building of Reusable Reverse Logistics Model and its Optimization Considering the Decision of Backorder or Next Arrival of Goods

NASA Astrophysics Data System (ADS)

Lee, Jeong-Eun; Gen, Mitsuo; Rhee, Kyong-Gu; Lee, Hee-Hyol

This paper deals with the building of the reusable reverse logistics model considering the decision of the backorder or the next arrival of goods. The optimization method to minimize the transportation cost and to minimize the volume of the backorder or the next arrival of goods occurred by the Just in Time delivery of the final delivery stage between the manufacturer and the processing center is proposed. Through the optimization algorithms using the priority-based genetic algorithm and the hybrid genetic algorithm, the sub-optimal delivery routes are determined. Based on the case study of a distilling and sale company in Busan in Korea, the new model of the reusable reverse logistics of empty bottles is built and the effectiveness of the proposed method is verified.

copia-like retrotransposons are ubiquitous among plants.

PubMed Central

Voytas, D F; Cummings, M P; Koniczny, A; Ausubel, F M; Rodermel, S R

1992-01-01

Transposable genetic elements are assumed to be a feature of all eukaryotic genomes. Their identification, however, has largely been haphazard, limited principally to organisms subjected to molecular or genetic scrutiny. We assessed the phylogenetic distribution of copia-like retrotransposons, a class of transposable element that proliferates by reverse transcription, using a polymerase chain reaction assay designed to detect copia-like element reverse transcriptase sequences. copia-like retrotransposons were identified in 64 plant species as well as the photosynthetic protist Volvox carteri. The plant species included representatives from 9 of 10 plant divisions, including bryophytes, lycopods, ferns, gymnosperms, and angiosperms. DNA sequence analysis of 29 cloned PCR products and of a maize retrotransposon cDNA confirmed the identity of these sequences as copia-like reverse transcriptase sequences, thereby demonstrating that this class of retrotransposons is a ubiquitous component of plant genomes. Images PMID:1379734

Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017.

PubMed

Giri, Veda N; Knudsen, Karen E; Kelly, William K; Abida, Wassim; Andriole, Gerald L; Bangma, Chris H; Bekelman, Justin E; Benson, Mitchell C; Blanco, Amie; Burnett, Arthur; Catalona, William J; Cooney, Kathleen A; Cooperberg, Matthew; Crawford, David E; Den, Robert B; Dicker, Adam P; Eggener, Scott; Fleshner, Neil; Freedman, Matthew L; Hamdy, Freddie C; Hoffman-Censits, Jean; Hurwitz, Mark D; Hyatt, Colette; Isaacs, William B; Kane, Christopher J; Kantoff, Philip; Karnes, R Jeffrey; Karsh, Lawrence I; Klein, Eric A; Lin, Daniel W; Loughlin, Kevin R; Lu-Yao, Grace; Malkowicz, S Bruce; Mann, Mark J; Mark, James R; McCue, Peter A; Miner, Martin M; Morgan, Todd; Moul, Judd W; Myers, Ronald E; Nielsen, Sarah M; Obeid, Elias; Pavlovich, Christian P; Peiper, Stephen C; Penson, David F; Petrylak, Daniel; Pettaway, Curtis A; Pilarski, Robert; Pinto, Peter A; Poage, Wendy; Raj, Ganesh V; Rebbeck, Timothy R; Robson, Mark E; Rosenberg, Matt T; Sandler, Howard; Sartor, Oliver; Schaeffer, Edward; Schwartz, Gordon F; Shahin, Mark S; Shore, Neal D; Shuch, Brian; Soule, Howard R; Tomlins, Scott A; Trabulsi, Edouard J; Uzzo, Robert; Vander Griend, Donald J; Walsh, Patrick C; Weil, Carol J; Wender, Richard; Gomella, Leonard G

2018-02-01

Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease.

Cyber-Warfare: Jus Post Bellum

DTIC Science & Technology

2015-03-01

used to design a cyber - warfare jus post bellum framework. It also analyzes analogies to traditional warfare in the damage assessment and aid provided...and the ability to contain and reverse cyberattacks. This thesis proposes a cyber - warfare jus post bellum framework, with emphasis on prevention and

Pore Breathing of Metal-Organic Frameworks by Environmental Transmission Electron Microscopy.

PubMed

Parent, Lucas R; Pham, C Huy; Patterson, Joseph P; Denny, Michael S; Cohen, Seth M; Gianneschi, Nathan C; Paesani, Francesco

2017-10-11

Metal-organic frameworks (MOFs) have emerged as a versatile platform for the rational design of multifunctional materials, combining large specific surface areas with flexible, periodic frameworks that can undergo reversible structural transitions, or "breathing", upon temperature and pressure changes, and through gas adsorption/desorption processes. Although MOF breathing can be inferred from the analysis of adsorption isotherms, direct observation of the structural transitions has been lacking, and the underlying processes of framework reorganization in individual MOF nanocrystals is largely unknown. In this study, we describe the characterization and elucidation of these processes through the combination of in situ environmental transmission electron microscopy (ETEM) and computer simulations. This combined approach enables the direct monitoring of the breathing behavior of individual MIL-53(Cr) nanocrystals upon reversible water adsorption and temperature changes. The ability to characterize structural changes in single nanocrystals and extract lattice level information through in silico correlation provides fundamental insights into the relationship between pore size/shape and host-guest interactions.

Effects of a fruit-vegetable dietary pattern on oxidative stress and genetic damage in coke oven workers: a cross-sectional study.

PubMed

Xie, Zheng; Lin, Haijiang; Fang, Renfei; Shen, Weiwei; Li, Shuguang; Chen, Bo

2015-05-06

Coke oven workers (COWs) are exposed to high level of genotoxic chemicals that induce oxidative stress and genetic damage. The dietary intake of certain types of foods may reverse these effects. We conducted a cross-sectional study with 51 topside COWs, 79 other COWs, and 67 controls, to assess the effects of dietary patterns on oxidative stress and genetic damage. Compared to the controls, both topside and other COWs had significantly higher urinary 1-hydroxypyrene levels, serum oxidant levels [malondialdehyde, (MDA)], and genetic damage [micronucleus (MN) frequency & 8-oxo-2'-deoxyguanosine (8-OH-dG)], but lower antioxidant levels [superoxide dismutase (SOD) and glutathione peroxidase, (GPx)]. The fruit-vegetable (FV) dietary pattern was positively correlated with serum SOD levels and negative correlated with serum MDA, MN frequency, and urinary 8-OH-dG. COWs with an FV patter in the highest quartile (Q4) had significantly increased antioxidant levels (SOD and GPx) and decreased oxidant levels (MDA) and genetic damage (MN frequency and 8-OH-dG) than those with an FV pattern in the lowest quartile (Q1). Compared to control subjects, COWs had increased oxidative stress and genetic damage. A FV dietary pattern may reverse oxidative stress and genetic damage in COWs.

Multi-scale genetic dynamic modelling II: application to synthetic biology: an algorithmic Markov chain based approach.

PubMed

Kirkilionis, Markus; Janus, Ulrich; Sbano, Luca

2011-09-01

We model in detail a simple synthetic genetic clock that was engineered in Atkinson et al. (Cell 113(5):597-607, 2003) using Escherichia coli as a host organism. Based on this engineered clock its theoretical description uses the modelling framework presented in Kirkilionis et al. (Theory Biosci. doi: 10.1007/s12064-011-0125-0 , 2011, this volume). The main goal of this accompanying article was to illustrate that parts of the modelling process can be algorithmically automatised once the model framework we called 'average dynamics' is accepted (Sbano and Kirkilionis, WMI Preprint 7/2007, 2008c; Kirkilionis and Sbano, Adv Complex Syst 13(3):293-326, 2010). The advantage of the 'average dynamics' framework is that system components (especially in genetics) can be easier represented in the model. In particular, if once discovered and characterised, specific molecular players together with their function can be incorporated. This means that, for example, the 'gene' concept becomes more clear, for example, in the way the genetic component would react under different regulatory conditions. Using the framework it has become a realistic aim to link mathematical modelling to novel tools of bioinformatics in the future, at least if the number of regulatory units can be estimated. This should hold in any case in synthetic environments due to the fact that the different synthetic genetic components are simply known (Elowitz and Leibler, Nature 403(6767):335-338, 2000; Gardner et al., Nature 403(6767):339-342, 2000; Hasty et al., Nature 420(6912):224-230, 2002). The paper illustrates therefore as a necessary first step how a detailed modelling of molecular interactions with known molecular components leads to a dynamic mathematical model that can be compared to experimental results on various levels or scales. The different genetic modules or components are represented in different detail by model variants. We explain how the framework can be used for investigating other more complex genetic systems in terms of regulation and feedback.

New Algorithm and Software (BNOmics) for Inferring and Visualizing Bayesian Networks from Heterogeneous Big Biological and Genetic Data

PubMed Central

Gogoshin, Grigoriy; Boerwinkle, Eric

2017-01-01

Abstract Bayesian network (BN) reconstruction is a prototypical systems biology data analysis approach that has been successfully used to reverse engineer and model networks reflecting different layers of biological organization (ranging from genetic to epigenetic to cellular pathway to metabolomic). It is especially relevant in the context of modern (ongoing and prospective) studies that generate heterogeneous high-throughput omics datasets. However, there are both theoretical and practical obstacles to the seamless application of BN modeling to such big data, including computational inefficiency of optimal BN structure search algorithms, ambiguity in data discretization, mixing data types, imputation and validation, and, in general, limited scalability in both reconstruction and visualization of BNs. To overcome these and other obstacles, we present BNOmics, an improved algorithm and software toolkit for inferring and analyzing BNs from omics datasets. BNOmics aims at comprehensive systems biology—type data exploration, including both generating new biological hypothesis and testing and validating the existing ones. Novel aspects of the algorithm center around increasing scalability and applicability to varying data types (with different explicit and implicit distributional assumptions) within the same analysis framework. An output and visualization interface to widely available graph-rendering software is also included. Three diverse applications are detailed. BNOmics was originally developed in the context of genetic epidemiology data and is being continuously optimized to keep pace with the ever-increasing inflow of available large-scale omics datasets. As such, the software scalability and usability on the less than exotic computer hardware are a priority, as well as the applicability of the algorithm and software to the heterogeneous datasets containing many data types—single-nucleotide polymorphisms and other genetic/epigenetic/transcriptome variables, metabolite levels, epidemiological variables, endpoints, and phenotypes, etc. PMID:27681505

New Algorithm and Software (BNOmics) for Inferring and Visualizing Bayesian Networks from Heterogeneous Big Biological and Genetic Data.

PubMed

Gogoshin, Grigoriy; Boerwinkle, Eric; Rodin, Andrei S

2017-04-01

Bayesian network (BN) reconstruction is a prototypical systems biology data analysis approach that has been successfully used to reverse engineer and model networks reflecting different layers of biological organization (ranging from genetic to epigenetic to cellular pathway to metabolomic). It is especially relevant in the context of modern (ongoing and prospective) studies that generate heterogeneous high-throughput omics datasets. However, there are both theoretical and practical obstacles to the seamless application of BN modeling to such big data, including computational inefficiency of optimal BN structure search algorithms, ambiguity in data discretization, mixing data types, imputation and validation, and, in general, limited scalability in both reconstruction and visualization of BNs. To overcome these and other obstacles, we present BNOmics, an improved algorithm and software toolkit for inferring and analyzing BNs from omics datasets. BNOmics aims at comprehensive systems biology-type data exploration, including both generating new biological hypothesis and testing and validating the existing ones. Novel aspects of the algorithm center around increasing scalability and applicability to varying data types (with different explicit and implicit distributional assumptions) within the same analysis framework. An output and visualization interface to widely available graph-rendering software is also included. Three diverse applications are detailed. BNOmics was originally developed in the context of genetic epidemiology data and is being continuously optimized to keep pace with the ever-increasing inflow of available large-scale omics datasets. As such, the software scalability and usability on the less than exotic computer hardware are a priority, as well as the applicability of the algorithm and software to the heterogeneous datasets containing many data types-single-nucleotide polymorphisms and other genetic/epigenetic/transcriptome variables, metabolite levels, epidemiological variables, endpoints, and phenotypes, etc.

Exploring the genetic counselor's role in facilitating meaning-making: rare disease diagnoses.

PubMed

Helm, Benjamin M

2015-04-01

The main goal of the constructivist meaning-making framework is to encourage grief adaptation through the search for meaning in loss. Strategies to help patients construct meaning from their experiences may lead to positive adaptation. This strategy has been used in contemporary grief counseling, but it may also be beneficial in the genetic counseling scenario. The diagnosis of a rare genetic disorder often has considerable psychosocial impact as patients and families describe feelings of isolation and hopelessness. Negative experiences with healthcare providers often reinforce these feelings. Genetic counselors continue to provide education and psychosocial support to patients and families with rare genetic disorders, and meaning-making strategies may provide a framework for which to help patients and families adapt to these challenging diagnoses. In this paper I explore the background of meaning-making counseling strategy and describe an experience in which it was used for counseling a family with a child with Mowat-Wilson syndrome. I show how a meaning-making framework can help families explore and construct meaning from their experiences and encourage positive adaptation. I also address the possible limitations of this strategy and the need to share additional experiences with this counseling framework. Meaning-making can be another tool for genetic counselors to help guide families in their grief and adaptation to rare disease diagnoses. I also describe qualities and aspects of counseling through the lens of meaning-making and stress the importance of addressing psychosocial dimensions of rare disease diagnoses.

Virus fitness differences observed between two naturally occurring isolates of Ebola virus Makona variant using a reverse genetics approach.

PubMed

Albariño, César G; Guerrero, Lisa Wiggleton; Chakrabarti, Ayan K; Kainulainen, Markus H; Whitmer, Shannon L M; Welch, Stephen R; Nichol, Stuart T

2016-09-01

During the large outbreak of Ebola virus disease that occurred in Western Africa from late 2013 to early 2016, several hundred Ebola virus (EBOV) genomes have been sequenced and the virus genetic drift analyzed. In a previous report, we described an efficient reverse genetics system designed to generate recombinant EBOV based on a Makona variant isolate obtained in 2014. Using this system, we characterized the replication and fitness of 2 isolates of the Makona variant. These virus isolates are nearly identical at the genetic level, but have single amino acid differences in the VP30 and L proteins. The potential effects of these differences were tested using minigenomes and recombinant viruses. The results obtained with this approach are consistent with the role of VP30 and L as components of the EBOV RNA replication machinery. Moreover, the 2 isolates exhibited clear fitness differences in competitive growth assays. Published by Elsevier Inc.

Neuroimaging, Genetics, and Clinical Data Sharing in Python Using the CubicWeb Framework

PubMed Central

Grigis, Antoine; Goyard, David; Cherbonnier, Robin; Gareau, Thomas; Papadopoulos Orfanos, Dimitri; Chauvat, Nicolas; Di Mascio, Adrien; Schumann, Gunter; Spooren, Will; Murphy, Declan; Frouin, Vincent

2017-01-01

In neurosciences or psychiatry, the emergence of large multi-center population imaging studies raises numerous technological challenges. From distributed data collection, across different institutions and countries, to final data publication service, one must handle the massive, heterogeneous, and complex data from genetics, imaging, demographics, or clinical scores. These data must be both efficiently obtained and downloadable. We present a Python solution, based on the CubicWeb open-source semantic framework, aimed at building population imaging study repositories. In addition, we focus on the tools developed around this framework to overcome the challenges associated with data sharing and collaborative requirements. We describe a set of three highly adaptive web services that transform the CubicWeb framework into a (1) multi-center upload platform, (2) collaborative quality assessment platform, and (3) publication platform endowed with massive-download capabilities. Two major European projects, IMAGEN and EU-AIMS, are currently supported by the described framework. We also present a Python package that enables end users to remotely query neuroimaging, genetics, and clinical data from scripts. PMID:28360851

Neuroimaging, Genetics, and Clinical Data Sharing in Python Using the CubicWeb Framework.

PubMed

Grigis, Antoine; Goyard, David; Cherbonnier, Robin; Gareau, Thomas; Papadopoulos Orfanos, Dimitri; Chauvat, Nicolas; Di Mascio, Adrien; Schumann, Gunter; Spooren, Will; Murphy, Declan; Frouin, Vincent

2017-01-01

In neurosciences or psychiatry, the emergence of large multi-center population imaging studies raises numerous technological challenges. From distributed data collection, across different institutions and countries, to final data publication service, one must handle the massive, heterogeneous, and complex data from genetics, imaging, demographics, or clinical scores. These data must be both efficiently obtained and downloadable. We present a Python solution, based on the CubicWeb open-source semantic framework, aimed at building population imaging study repositories. In addition, we focus on the tools developed around this framework to overcome the challenges associated with data sharing and collaborative requirements. We describe a set of three highly adaptive web services that transform the CubicWeb framework into a (1) multi-center upload platform, (2) collaborative quality assessment platform, and (3) publication platform endowed with massive-download capabilities. Two major European projects, IMAGEN and EU-AIMS, are currently supported by the described framework. We also present a Python package that enables end users to remotely query neuroimaging, genetics, and clinical data from scripts.

Toward a unifying framework for evolutionary processes.

PubMed

Paixão, Tiago; Badkobeh, Golnaz; Barton, Nick; Çörüş, Doğan; Dang, Duc-Cuong; Friedrich, Tobias; Lehre, Per Kristian; Sudholt, Dirk; Sutton, Andrew M; Trubenová, Barbora

2015-10-21

The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Situational State Balances and Participation Motivation in Youth Sport: A Reversal Theory Perspective

ERIC Educational Resources Information Center

Sit, Cindy H. P.; Lindner, Koenraad J.

2006-01-01

Background: Reversal theory (Apter, 1982, 1989, ) is one of the motivational frameworks which attempts to examine human subjective experiences and behaviours. There are four dyads of metamotivational states (telic-paratelic, conformist-negativistic, autic-alloic, and mastery-sympathy) and individuals may prefer to be in one rather than the other…

An Electrically Switchable Metal-Organic Framework

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernandez, CA; Martin, PC; Schaef, T

2014-08-19

Crystalline metal organic framework (MOF) materials containing interconnected porosity can be chemically modified to promote stimulus-driven (light, magnetic or electric fields) structural transformations that can be used in a number of devices. Innovative research strategies are now focused on understanding the role of chemical bond manipulation to reversibly alter the free volume in such structures of critical importance for electro-catalysis, molecular electronics, energy storage technologies, sensor devices and smart membranes. In this letter, we study the mechanism for which an electrically switchable MOF composed of Cu(TCNQ) (TCNQ = 7,7,8,8-tetracyanoquinodimethane) transitions from a high-resistance state to a conducting state in amore » reversible fashion by an applied potential. The actual mechanism for this reversible electrical switching is still not understood even though a number of reports are available describing the application of electric-field-induced switching of Cu(TCNQ) in device fabrication.« less

An Electrically Switchable Metal-Organic Framework

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernandez, Carlos A.; Martin, Paul F.; Schaef, Herbert T.

2014-08-19

Crystalline metal organic framework (MOF) materials containing interconnected porosity can be chemically modified to promote stimulus-driven (light, magnetic or electric fields) structural transformations that can be used in a number of devices. Innovative research strategies are now focused on understanding the role of chemical bond manipulation to reversibly alter the free volume in such structures of critical importance for electro-catalysis, molecular electronics, energy storage technologies, sensor devices and smart membranes. In this letter, we study the mechanism for which an electrically switchable MOF composed of Cu(TCNQ) (TCNQ 5 7,7,8,8-tetracyanoquinodimethane) transitions from a high-resistance state to a conducting state in amore » reversible fashion by an applied potential. The actual mechanism for this reversible electrical switching is still not understood even though a number of reports are available describing the application of electric-field-induced switching of Cu(TCNQ) in device fabrication.« less

An Electrically Switchable Metal-Organic Framework

NASA Astrophysics Data System (ADS)

Fernandez, Carlos A.; Martin, Paul C.; Schaef, Todd; Bowden, Mark E.; Thallapally, Praveen K.; Dang, Liem; Xu, Wu; Chen, Xilin; McGrail, B. Peter

2014-08-01

Crystalline metal organic framework (MOF) materials containing interconnected porosity can be chemically modified to promote stimulus-driven (light, magnetic or electric fields) structural transformations that can be used in a number of devices. Innovative research strategies are now focused on understanding the role of chemical bond manipulation to reversibly alter the free volume in such structures of critical importance for electro-catalysis, molecular electronics, energy storage technologies, sensor devices and smart membranes. In this letter, we study the mechanism for which an electrically switchable MOF composed of Cu(TCNQ) (TCNQ = 7,7,8,8-tetracyanoquinodimethane) transitions from a high-resistance state to a conducting state in a reversible fashion by an applied potential. The actual mechanism for this reversible electrical switching is still not understood even though a number of reports are available describing the application of electric-field-induced switching of Cu(TCNQ) in device fabrication.

A Temperature‐Responsive Smart Europium Metal‐Organic Framework Switch for Reversible Capture and Release of Intrinsic Eu3+ Ions

PubMed Central

Zhu, Min; Song, Xue‐Zhi; Zhao, Shu‐Na; Meng, Xing; Wu, Lan‐Lan; Wang, Cheng

2015-01-01

Stimuli‐responsive structural transformations are emerging as a scaffold to develop a charming class of smart materials. A EuL metal‐organic framework (MOF) undergoes a reversible temperature‐stimulated single‐crystal to single‐crystal transformation, showing a specific behavior of fast capture/release of free Eu3+ in the channels at low and room temperatures. At room temperature, compound 1a is obtained with one free carboxylate group severing as further hook, featuring one‐dimensional square channels filled with intrinsic free europium ions. Trigged by lowering the ambient temperature, 1b is gained. In 1b, the intrinsic free europium ions can be fast captured by the carboxylate‐hooks anchored in the framework, resulting in the structural change and its channel distortion. To the best of our knowledge, this is the first report of such a rapid and reversible switch stemming from dynamic control between noncovalent and covalent Eu–ligand interactions. Utilizing EuL MOF to detect highly explosive 2,4,6‐trinitrophenol at room temperature and low temperature provides a glimpse into the potential of this material in fluorescence sensors. PMID:27980931

Gonadal sex differentiation and effects of dietary methyltestosterone treatment in sablefish (Anoplopoma fimbria).

PubMed

Luckenbach, J Adam; Fairgrieve, William T

2016-02-01

Methods for sex control are needed to establish monosex aquaculture of sablefish (Anoplopoma fimbria). Here we conducted the first characterization of sex differentiation by histology and hormonal sex reversal experiment in sablefish. Ovarian differentiation was first discernible at ~80 mm fork length (FL) and characterized by development of lamellar structures and onset of meiosis. Testes exhibited a dual-lobe appearance over much of their length and remained non-meiotic until males were ≥520 mm FL (2 years post-fertilization). Juveniles with undifferentiated gonads were provided diets containing 0 (control), 5 or 50 mg 17α-methyltestosterone (MT)/kg for 2 months. Following treatment, controls possessed either ovaries or non-meiotic testes, whereas MT-treated fish exhibited meiotic testes (60% of the fish), intersex gonads (~30%), or gonads that appeared sterile (~10%). A genetic sex marker revealed that all intersex fish were genetic females, although other females appeared to be completely sex reversed (i.e., neomales). One year after treatment, MT-treated fish possessed non-meiotic testes similar to control males or intersex gonads with reduced ovarian features, presumably due to atresia following MT withdrawal. Milt collected from neomales and genetic males 3 years post-treatment permitted sperm motility analyses; however, neomale sperm were virtually immotile. These results demonstrated that sablefish are differentiated gonochorists and that MT treatment from 76 to 196 mm FL induced permanent masculinization of a portion of the genetic females, but acquisition of sperm motility was impaired. Earlier administration of MT may be necessary to sex reverse a higher proportion of genetic females and reduce negative effects on fertility.

A Multi-Stage Reverse Logistics Network Problem by Using Hybrid Priority-Based Genetic Algorithm

NASA Astrophysics Data System (ADS)

Lee, Jeong-Eun; Gen, Mitsuo; Rhee, Kyong-Gu

Today remanufacturing problem is one of the most important problems regarding to the environmental aspects of the recovery of used products and materials. Therefore, the reverse logistics is gaining become power and great potential for winning consumers in a more competitive context in the future. This paper considers the multi-stage reverse Logistics Network Problem (m-rLNP) while minimizing the total cost, which involves reverse logistics shipping cost and fixed cost of opening the disassembly centers and processing centers. In this study, we first formulate the m-rLNP model as a three-stage logistics network model. Following for solving this problem, we propose a Genetic Algorithm pri (GA) with priority-based encoding method consisting of two stages, and introduce a new crossover operator called Weight Mapping Crossover (WMX). Additionally also a heuristic approach is applied in the 3rd stage to ship of materials from processing center to manufacturer. Finally numerical experiments with various scales of the m-rLNP models demonstrate the effectiveness and efficiency of our approach by comparing with the recent researches.

Novel norovirus in dogs with diarrhea.

PubMed

Mesquita, João Rodrigo; Barclay, Leslie; Nascimento, Maria São José; Vinjé, Jan

2010-06-01

To identify the prevalence and genetic variability of noroviruses in dogs, we tested fecal samples by using reverse transcription-PCR. We found canine norovirus in 40% and 9% of dogs with and without diarrhea, respectively. The virus was genetically unrelated to other noroviruses and constitutes a tentative new genogroup.

African Swine Fever Virus NP868R Capping Enzyme Promotes Reovirus Rescue during Reverse Genetics by Promoting Reovirus Protein Expression, Virion Assembly, and RNA Incorporation into Infectious Virions

PubMed Central

Eaton, Heather E.; Kobayashi, Takeshi; Dermody, Terence S.; Johnston, Randal N.

2017-01-01

ABSTRACT Reoviruses, like many eukaryotic viruses, contain an inverted 7-methylguanosine (m7G) cap linked to the 5′ nucleotide of mRNA. The traditional functions of capping are to promote mRNA stability, protein translation, and concealment from cellular proteins that recognize foreign RNA. To address the role of mRNA capping during reovirus replication, we assessed the benefits of adding the African swine fever virus NP868R capping enzyme during reovirus rescue. C3P3, a fusion protein containing T7 RNA polymerase and NP868R, was found to increase protein expression 5- to 10-fold compared to T7 RNA polymerase alone while enhancing reovirus rescue from the current reverse genetics system by 100-fold. Surprisingly, RNA stability was not increased by C3P3, suggesting a direct effect on protein translation. A time course analysis revealed that C3P3 increased protein synthesis within the first 2 days of a reverse genetics transfection. This analysis also revealed that C3P3 enhanced processing of outer capsid μ1 protein to μ1C, a previously described hallmark of reovirus assembly. Finally, to determine the rate of infectious-RNA incorporation into new virions, we developed a new recombinant reovirus S1 gene that expressed the fluorescent protein UnaG. Following transfection of cells with UnaG and infection with wild-type virus, passage of UnaG through progeny was significantly enhanced by C3P3. These data suggest that capping provides nontraditional functions to reovirus, such as promoting assembly and infectious-RNA incorporation. IMPORTANCE Our findings expand our understanding of how viruses utilize capping, suggesting that capping provides nontraditional functions to reovirus, such as promoting assembly and infectious-RNA incorporation, in addition to enhancing protein translation. Beyond providing mechanistic insight into reovirus replication, our findings also show that reovirus reverse genetics rescue is enhanced 100-fold by the NP868R capping enzyme. Since reovirus shows promise as a cancer therapy, efficient reovirus reverse genetics rescue will accelerate production of recombinant reoviruses as candidates to enhance therapeutic potency. NP868R-assisted reovirus rescue will also expedite production of recombinant reovirus for mechanistic insights into reovirus protein function and structure. PMID:28298603

Ligand interaction scan: a general method for engineering ligand-sensitive protein alleles.

PubMed

Erster, Oran; Eisenstein, Miriam; Liscovitch, Mordechai

2007-05-01

The ligand interaction scan (LIScan) method is a general procedure for engineering small molecule ligand-regulated forms of a protein that is complementary to other 'reverse' genetic and chemical-genetic methods for drug-target validation. It involves insertional mutagenesis by a chemical-genetic 'switch', comprising a genetically encoded peptide module that binds with high affinity to a small-molecule ligand. We demonstrated the method with TEM-1 beta-lactamase, using a tetracysteine hexapeptide insert and a biarsenical fluorescein ligand (FlAsH).

Redefining genomic privacy: trust and empowerment.

PubMed

Erlich, Yaniv; Williams, James B; Glazer, David; Yocum, Kenneth; Farahany, Nita; Olson, Maynard; Narayanan, Arvind; Stein, Lincoln D; Witkowski, Jan A; Kain, Robert C

2014-11-01

Fulfilling the promise of the genetic revolution requires the analysis of large datasets containing information from thousands to millions of participants. However, sharing human genomic data requires protecting subjects from potential harm. Current models rely on de-identification techniques in which privacy versus data utility becomes a zero-sum game. Instead, we propose the use of trust-enabling techniques to create a solution in which researchers and participants both win. To do so we introduce three principles that facilitate trust in genetic research and outline one possible framework built upon those principles. Our hope is that such trust-centric frameworks provide a sustainable solution that reconciles genetic privacy with data sharing and facilitates genetic research.

Redefining Genomic Privacy: Trust and Empowerment

PubMed Central

Erlich, Yaniv; Williams, James B.; Glazer, David; Yocum, Kenneth; Farahany, Nita; Olson, Maynard; Narayanan, Arvind; Stein, Lincoln D.; Witkowski, Jan A.; Kain, Robert C.

2014-01-01

Fulfilling the promise of the genetic revolution requires the analysis of large datasets containing information from thousands to millions of participants. However, sharing human genomic data requires protecting subjects from potential harm. Current models rely on de-identification techniques in which privacy versus data utility becomes a zero-sum game. Instead, we propose the use of trust-enabling techniques to create a solution in which researchers and participants both win. To do so we introduce three principles that facilitate trust in genetic research and outline one possible framework built upon those principles. Our hope is that such trust-centric frameworks provide a sustainable solution that reconciles genetic privacy with data sharing and facilitates genetic research. PMID:25369215

Sex Reversal in Reptiles: Reproductive Oddity or Powerful Driver of Evolutionary Change?

PubMed

Holleley, Clare E; Sarre, Stephen D; O'Meally, Denis; Georges, Arthur

2016-01-01

Is sex a product of genes, the environment, or both? In this review, we describe the diversity of sex-determining mechanisms in reptiles, with a focus on systems that display gene-environment interactions. We summarise the field and laboratory-based evidence for the occurrence of environmental sex reversal in reptiles and ask whether this is a widespread evolutionary mechanism affecting the evolution of sex chromosomes and speciation in vertebrates. Sex determination systems exist across a continuum of genetic and environmental influences, blurring the lines between what was once considered a strict dichotomy between genetic sex determination and temperature-dependent sex determination. Across this spectrum, we identify the potential for sex reversal in species with clearly differentiated heteromorphic sex chromosomes (Pogona vitticeps, Bassiana duperreyi, Eremias multiocellata, Gekko japonicus), weakly differentiated homomorphic sex chromosomes (Niveoscincus ocellatus), and species with only a weak heritable predisposition for sex (Emys orbicularis, Trachemys scripta). We argue that sex reversal is widespread in reptiles (Testudines, Lacertidae, Agamidae, Scincidae, Gekkonidae) and has the potential to have an impact on individual fitness, resulting in reproductively, morphologically, and behaviourally unique phenotypes. Sex reversal is likely to be a powerful evolutionary force responsible for generating and maintaining lability and diversity in reptile sex-determining modes. © 2016 S. Karger AG, Basel.

Coherent and Noncoherent Joint Processing of Sonar for Detection of Small Targets in Shallow Water.

PubMed

Pan, Xiang; Jiang, Jingning; Li, Si; Ding, Zhenping; Pan, Chen; Gong, Xianyi

2018-04-10

A coherent-noncoherent joint processing framework is proposed for active sonar to combine diversity gain and beamforming gain for detection of a small target in shallow water environments. Sonar utilizes widely-spaced arrays to sense environments and illuminate a target of interest from multiple angles. Meanwhile, it exploits spatial diversity for time-reversal focusing to suppress reverberation, mainly strong bottom reverberation. For enhancement of robustness of time-reversal focusing, an adaptive iterative strategy is utilized in the processing framework. A probing signal is firstly transmitted and echoes of a likely target are utilized as steering vectors for the second transmission. With spatial diversity, target bearing and range are estimated using a broadband signal model. Numerical simulations show that the novel sonar outperforms the traditional phased-array sonar due to benefits of spatial diversity. The effectiveness of the proposed framework has been validated by localization of a small target in at-lake experiments.

Evolutionary history of Lissotriton helveticus: multilocus assessment of ancestral vs. recent colonization of the Iberian Peninsula.

PubMed

Recuero, Ernesto; García-París, Mario

2011-07-01

The Pleistocene was characterized by climatic changes that greatly altered the distribution of organisms. Population extinctions, bottlenecks, isolation, range expansions and contractions were often associated with glaciations, leaving signatures in the spatial patterns of genetic diversity across species. Lissotriton helveticus belongs to a Pan-European lineage of newts that were strongly affected by glaciations and represent an excellent model to analyse the effect of generalized climatic changes in phylogeographic patterns. We studied the genetic diversity of the species using data from two mitochondrial and three nuclear genes analyzed in a Bayesian phylogenetic framework to investigate the historical processes shaping spatial patterns of genetic diversity. Mitochondrial haplotypes cluster in four different groups present in the Iberian Peninsula and of Pleistocene origin, probably by allopatric fragmentation. Nuclear genes present no obvious geographic structure patterns, suggesting gene flow and generalized incomplete lineage sorting. Populations north of the Pyrenees are closely related to those from northeastern Iberia, suggesting recent range expansion from this region. Historical demographic analyses indicate a demographic expansion starting about 100,000years ago and more recent population declines. Compared to other Lissotriton species, L. helveticus includes only relatively young genetic lineages, suggesting a Central European pre-Pleistocene distribution followed by complete extirpation of the species during glaciations in that area. Historical demographic trends in the Iberian Peninsula are reversed with respect to the more Mediterranean species Lissotriton boscai, indicating different responses of both species to climate changes. Diversity patterns among Lissotriton species seem to be defined by four main factors: ancestral distributions, colonization capabilities, interactions with other species and effective population sizes. Differences in these factors define two types of species, referred to as "R" (refugia) and "S" (sanctuaries) that explain part of the diversity in patterns of genetic diversity created by glaciations in Western Europe. Copyright © 2011 Elsevier Inc. All rights reserved.

Climate-driven shifts in adult sex ratios via sex reversals: the type of sex determination matters.

PubMed

Bókony, Veronika; Kövér, Szilvia; Nemesházi, Edina; Liker, András; Székely, Tamás

2017-09-19

Sex reversals whereby individuals of one genetic sex develop the phenotype of the opposite sex occur in ectothermic vertebrates with genetic sex-determination systems that are sensitive to extreme temperatures during sexual differentiation. Recent rises in global temperatures have led researchers to predict that sex reversals will become more common, resulting in the distortion of many populations' sex ratios. However, it is unclear whether susceptibility to climate-driven sex-ratio shifts depends on the type of sex determination that varies across species. First, we show here using individual-based theoretical models that XX/XY (male-heterogametic) and ZZ/ZW (female-heterogametic) sex-determination systems can respond differentially to temperature-induced sex reversals. Interestingly, the impacts of climate warming on adult sex ratio (ASR) depend on the effects of both genotypic and phenotypic sex on survival and reproduction. Second, we analyse the temporal changes of ASR in natural amphibian populations using data from the literature, and find that ASR shifted towards males in ZZ/ZW species over the past 60 years, but did not change significantly in XX/XY species. Our results highlight the fact that we need a better understanding of the interactions between genetic and environmental sex-determining mechanisms to predict the responses of ectotherms to climate change and the associated extinction risks.This article is part of the themed issue 'Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies'. © 2017 The Author(s).

Heuristic Identification of Biological Architectures for Simulating Complex Hierarchical Genetic Interactions

PubMed Central

Moore, Jason H; Amos, Ryan; Kiralis, Jeff; Andrews, Peter C

2015-01-01

Simulation plays an essential role in the development of new computational and statistical methods for the genetic analysis of complex traits. Most simulations start with a statistical model using methods such as linear or logistic regression that specify the relationship between genotype and phenotype. This is appealing due to its simplicity and because these statistical methods are commonly used in genetic analysis. It is our working hypothesis that simulations need to move beyond simple statistical models to more realistically represent the biological complexity of genetic architecture. The goal of the present study was to develop a prototype genotype–phenotype simulation method and software that are capable of simulating complex genetic effects within the context of a hierarchical biology-based framework. Specifically, our goal is to simulate multilocus epistasis or gene–gene interaction where the genetic variants are organized within the framework of one or more genes, their regulatory regions and other regulatory loci. We introduce here the Heuristic Identification of Biological Architectures for simulating Complex Hierarchical Interactions (HIBACHI) method and prototype software for simulating data in this manner. This approach combines a biological hierarchy, a flexible mathematical framework, a liability threshold model for defining disease endpoints, and a heuristic search strategy for identifying high-order epistatic models of disease susceptibility. We provide several simulation examples using genetic models exhibiting independent main effects and three-way epistatic effects. PMID:25395175

Immersion of fry in 17-Alpha Methyltestosterone can be highly effective for sex reversal in rainbow trout

USDA-ARS?s Scientific Manuscript database

17-alpha methyltestosterone (MT) is currently used to sex reverse genetic female rainbow trout into phenotypic males, commonly referred to as neomales. Neomales are primarily generated to propagate all-female lines. The MT is most commonly administered orally, fed during the first 6-9 weeks after sw...

Novel Structure of Ty3 Reverse Transcriptase | Center for Cancer Research

Cancer.gov

Retrotransposons are mobile genetic elements that self amplify via a single-stranded RNA intermediate, which is converted to double-stranded DNA by an encoded reverse transcriptase (RT) with both DNA polymerase (pol) and ribonuclease H (RNase) activities. Categorized by whether they contain flanking long terminal repeat (LTR) sequences, retrotransposons play a critical role in

Sexual and somatic development of wood frog tadpoles along a thermal gradient.

PubMed

Lambert, Max R; Smylie, Meredith S; Roman, Amber J; Freidenburg, L Kealoha; Skelly, David K

2018-02-01

All amphibian species are known to have genetic sex determination. However, a variety of environmental conditions can moderate sexual differentiation, in some cases leading to sex reversal and skewed sex ratios. While there has been a recent focus on chemically-induced sex reversal in amphibians, temperature can also influence sexual differentiation. Building upon a classic 1929 study by Emil Witschi, we assessed temperature-mediated sex reversal. Witschi found that the wood frog sex ratio is 100% male at a high temperature (32°C) compared to a 50:50 sex ratio at 20°C. This pattern is consistent with multiple models of environmentally mediated sexual differentiation in vertebrates. To better understand thermally mediated sex reversal, we raised wood frogs at temperature increments of ∼1°C between 19 and 34°C. Mirroring earlier findings, wood frog metamorph sex ratios are indistinguishable from 50:50 at the lowest temperature and entirely male at the highest temperatures. In between, sex ratios become increasingly male-dominated as temperatures increase, implying a steadily increasing tendency toward female-to-male sex reversal in warmer environments. There was no evidence of a threshold temperature effect on reversal patterns. We also show that, compared to males, females metamorphose larger and later in cooler conditions but earlier and smaller under warmer conditions. While the ecological relevance in this species is unknown, these results conform to the Charnov-Bull model of sex determination (in which female-to-male sex reversal can increase fitness to genetic females at higher temperatures), suggesting the system would reward further study. © 2018 Wiley Periodicals, Inc.

Polygenic risk and the development and course of asthma: Evidence from a 4-decade longitudinal study

PubMed Central

Belsky, DW; Sears, MR; Hancox, RJ; Harrington, HL; Houts, R; Moffitt, TE; Sugden, K; Williams, B; Poulton, R; Caspi, A

2013-01-01

BACKGROUND Genome-wide association studies (GWAS) have discovered loci that predispose to asthma. To integrate these new discoveries with emerging models of asthma pathobiology, research is needed to test how genetic discoveries relate to developmental and biological characteristics of asthma. METHODS We derived a multi-locus profile of genetic risk from published GWAS of asthma case status. We then tested associations between this “genetic risk score” and developmental and biological characteristics of asthma in a population-based long-running birth cohort, the Dunedin Longitudinal Study (n=1,037). We evaluated asthma onset, persistence, atopy, airway hyperresponsiveness, incompletely reversible airflow obstruction, and asthma-related school and work absenteeism and hospitalization during 9 prospective assessments spanning ages 9–38 years, when 95% of surviving cohort members were seen. INTERPRETATION Cohort members at higher genetic risk experienced asthma onset earlier in life (HR=1.12 [1.01–1.26]). Childhood-onset asthma cases at higher genetic risk were more likely to become life-course-persistent asthma cases (RR=1.36 [1.14–1.63]). Asthma cases at higher genetic risk more often manifested atopy (RR=1.07 [1.01–1.14]), airway hyperresponsiveness (RR=1.16 [1.03–1.32]), and incompletely reversible airflow obstruction (RR=1.28 [1.04–1.57]). They were also more likely to miss school or work due to asthma (IRR=1.38 [1.02–1.86]) and to be hospitalized with breathing problems (HR=1.38 [1.07–1.79]). Genotypic information about asthma risk was independent of and additive to information derived from cohort members’ family histories of asthma. CONCLUSIONS Findings from this population study confirm that GWAS-discoveries for asthma associate with a childhood-onset phenotype and advance asthma genetics beyond the original GWAS-discoveries in three ways: (1) We show that genetic risks predict which childhood-onset asthma cases remit and which become life-course-persistent cases, although these predictions are not sufficiently sensitive or specific to support immediate clinical translation; (2) We elucidate a biological profile of the asthma that arises from these genetic risks: asthma characterized by atopy and airway hyperresponsiveness and leading to incompletely reversible airflow obstruction; and (3) We describe the real-life impact of GWAS-discoveries by quantifying genetic associations with missed school and work and hospitalization. PMID:24429243

Phylodynamic Inference with Kernel ABC and Its Application to HIV Epidemiology.

PubMed

Poon, Art F Y

2015-09-01

The shapes of phylogenetic trees relating virus populations are determined by the adaptation of viruses within each host, and by the transmission of viruses among hosts. Phylodynamic inference attempts to reverse this flow of information, estimating parameters of these processes from the shape of a virus phylogeny reconstructed from a sample of genetic sequences from the epidemic. A key challenge to phylodynamic inference is quantifying the similarity between two trees in an efficient and comprehensive way. In this study, I demonstrate that a new distance measure, based on a subset tree kernel function from computational linguistics, confers a significant improvement over previous measures of tree shape for classifying trees generated under different epidemiological scenarios. Next, I incorporate this kernel-based distance measure into an approximate Bayesian computation (ABC) framework for phylodynamic inference. ABC bypasses the need for an analytical solution of model likelihood, as it only requires the ability to simulate data from the model. I validate this "kernel-ABC" method for phylodynamic inference by estimating parameters from data simulated under a simple epidemiological model. Results indicate that kernel-ABC attained greater accuracy for parameters associated with virus transmission than leading software on the same data sets. Finally, I apply the kernel-ABC framework to study a recent outbreak of a recombinant HIV subtype in China. Kernel-ABC provides a versatile framework for phylodynamic inference because it can fit a broader range of models than methods that rely on the computation of exact likelihoods. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The Regression Hypothesis as a Framework for First Language Attrition

ERIC Educational Resources Information Center

Keijzer, Merel

2010-01-01

In an attempt to explain first language attrition in emigrant populations, this paper investigates the explanatory power of a framework that has--until now--received little attention: the regression hypothesis (Jakobson, 1941). This hypothesis predicts that the order of attrition is the reverse of the order of acquisition. The regression…

iNJclust: Iterative Neighbor-Joining Tree Clustering Framework for Inferring Population Structure.

PubMed

Limpiti, Tulaya; Amornbunchornvej, Chainarong; Intarapanich, Apichart; Assawamakin, Anunchai; Tongsima, Sissades

2014-01-01

Understanding genetic differences among populations is one of the most important issues in population genetics. Genetic variations, e.g., single nucleotide polymorphisms, are used to characterize commonality and difference of individuals from various populations. This paper presents an efficient graph-based clustering framework which operates iteratively on the Neighbor-Joining (NJ) tree called the iNJclust algorithm. The framework uses well-known genetic measurements, namely the allele-sharing distance, the neighbor-joining tree, and the fixation index. The behavior of the fixation index is utilized in the algorithm's stopping criterion. The algorithm provides an estimated number of populations, individual assignments, and relationships between populations as outputs. The clustering result is reported in the form of a binary tree, whose terminal nodes represent the final inferred populations and the tree structure preserves the genetic relationships among them. The clustering performance and the robustness of the proposed algorithm are tested extensively using simulated and real data sets from bovine, sheep, and human populations. The result indicates that the number of populations within each data set is reasonably estimated, the individual assignment is robust, and the structure of the inferred population tree corresponds to the intrinsic relationships among populations within the data.

Assessing the benefits and risks of translocations in changing environments: a genetic perspective

PubMed Central

Weeks, Andrew R; Sgro, Carla M; Young, Andrew G; Frankham, Richard; Mitchell, Nicki J; Miller, Kim A; Byrne, Margaret; Coates, David J; Eldridge, Mark D B; Sunnucks, Paul; Breed, Martin F; James, Elizabeth A; Hoffmann, Ary A

2011-01-01

Translocations are being increasingly proposed as a way of conserving biodiversity, particularly in the management of threatened and keystone species, with the aims of maintaining biodiversity and ecosystem function under the combined pressures of habitat fragmentation and climate change. Evolutionary genetic considerations should be an important part of translocation strategies, but there is often confusion about concepts and goals. Here, we provide a classification of translocations based on specific genetic goals for both threatened species and ecological restoration, separating targets based on ‘genetic rescue’ of current population fitness from those focused on maintaining adaptive potential. We then provide a framework for assessing the genetic benefits and risks associated with translocations and provide guidelines for managers focused on conserving biodiversity and evolutionary processes. Case studies are developed to illustrate the framework. PMID:22287981

The needs of salmon and steelhead in balancing their conservation and use

USGS Publications Warehouse

Burger, Carl V.; Knudsen, E. Eric; Steward, Cleveland R.; MacDonald, Donald D.; Williams, Jack E.; Reiser, Dudley W.

1999-01-01

Over the past 100 years, Pacific salmon Oncorhynchus spp. and steelhead trout O. mykiss populations in the Pacific Northwest have experienced dramatic declines as a result of human population growth and associated development of the region's natural resources. Any strategy to reverse those declines will depend on achieving consensus among a diverse group of stakeholders willing to (1) restore damaged habitats and watersheds; (2) consider the biological needs of salmonid fishes; and (3) understand, conserve, and manage existing levels of biodiversity within an ecosystem context. The objective of this chapter is to review and summarize the needs of Pacific salmon and steelhead trout from perspectives that promote their sustainability and perpetuity, and, within that context, provide a framework, for the development of a sustainable fisheries strategy. Although volumes of information are available on the life histories and habitat requirements of Pacific salmonids, new concepts have begun to address the importance of habitat complexity, genetic diversity among locally adapted populations, and the need for appropriate units of conservation. Habitat variability and complexity are the templates that produce diverse, locally adapted populations of Pacific salmon and steelhead trout. Molded by conditions in the environments they colonized, salmon and steelhead have unique adaptations they may have taken hundred i?? perhaps thousands i?? of years to evolve. Any strategy to reverse the declines of salmon and steelhead must focus on conserving both current levels of genetic diversity as well as restoration and maintenance of habitats compatible with the specific needs of individual populations. An argument can be made that we know enough already about the needs of our salmon and steelhead to allow us to make appropriate decisions. There is strong need to integrate what we know about local salmonid adaptations and habitat needs with conservation and management strategies that address the problems we have created. It may be possible to have healthy, sustainable salmonid populations coastwide if we do not wait too long to make up our minds.

Isolation of mtpim Proves Tnt1 a Useful Reverse Genetics Tool in Medicago truncatula and Uncovers New Aspects of AP1-Like Functions in Legumes1

PubMed Central

Benlloch, Reyes; d'Erfurth, Isabelle; Ferrandiz, Cristina; Cosson, Viviane; Beltrán, José Pío; Cañas, Luis Antonio; Kondorosi, Adam; Madueño, Francisco; Ratet, Pascal

2006-01-01

Comparative studies help shed light on how the huge diversity in plant forms found in nature has been produced. We use legume species to study developmental differences in inflorescence architecture and flower ontogeny with classical models such as Arabidopsis thaliana or Antirrhinum majus. Whereas genetic control of these processes has been analyzed mostly in pea (Pisum sativum), Medicago truncatula is emerging as a promising alternative system for these studies due to the availability of a range of genetic tools. To assess the use of the retrotransposon Tnt1 for reverse genetics in M. truncatula, we screened a small Tnt1-mutagenized population using degenerate primers for MADS-box genes, known controllers of plant development. We describe here the characterization of mtpim, a new mutant caused by the insertion of Tnt1 in a homolog to the PROLIFERATING INFLORESCENCE MERISTEM (PIM)/APETALA1 (AP1)/SQUAMOSA genes. mtpim shows flower-to-inflorescence conversion and altered flowers with sepals transformed into leaves, indicating that MtPIM controls floral meristem identity and flower development. Although more extreme, this phenotype resembles the pea pim mutants, supporting the idea that M. truncatula could be used to complement analysis of reproductive development already initiated in pea. In fact, our study reveals aspects not shown by analysis of pea mutants: that the mutation in the AP1 homolog interferes with the specification of floral organs from common primordia and causes conversion of sepals into leaves, in addition to true conversion of flowers into inflorescences. The isolation of mtpim represents a proof of concept demonstrating that Tnt1 populations can be efficiently used in reverse genetics screenings in M. truncatula. PMID:16963524

Discussing options between patients and health care professionals in genetic diagnosis: ethical and legal criteria

PubMed Central

Nicolás, Pilar

2007-01-01

The specific characteristics of genetic data lead to ethical-legal conflicts in the framework of genetic diagnosis. Several international organisations, including UNESCO and the Council of Europe, have enacted rules referring to the use of genetic information. This paper discusses possible legal and ethical criteria that could be used in genetic testing. PMID:19725990

Modern vitiligo genetics sheds new light on an ancient disease

PubMed Central

SPRITZ, Richard A.

2013-01-01

Vitiligo is a complex disorder in which autoimmune destruction of melanocytes results in white patches of skin and overlying hair. Over the past several years, extensive genetic studies have outlined a biological framework of vitiligo pathobiology that underscores its relationship to other autoimmune diseases. This biological framework offers insight into both vitiligo pathogenesis and perhaps avenues towards more effective approaches to treatment and even disease prevention. PMID:23668538

The Case against Preadoption Genetic Testing.

ERIC Educational Resources Information Center

Freundlich, Madelyn D.

1998-01-01

Examines the medical, psychosocial, and ethical considerations concerning presymptomatic genetic testing in evaluating children for adoption. Offers an ethical framework for rejecting such a practice. (JPB)

Some thoughts on essence placeholders, interactionism, and heritability: reply to Haslam (2011) and Turkheimer (2011).

PubMed

Dar-Nimrod, Ilan; Heine, Steven J

2011-09-01

In the target article (Dar-Nimrod & Heine, 2011), we provided a social-cognitive framework which identified genetic essentialist biases and their implications. In their commentaries, Haslam (2011) and Turkheimer (2011) indicated their general agreement with this framework but highlighted some important points for consideration. Haslam suggested that neuroessentialism is a comparable kind of essentialist bias and identified similarities with the genetic essentialism framework. In response, we acknowledge similarities but also identify qualitative and quantitative differences between genetic essentialism and other kinds of essentialist biases. Turkheimer challenged us to extend our discussion to address the question of how should people respond to genetic etiological information, critiqued the use of heritability coefficients, and identified a new construct (1 - rMZ), which may be termed a free-will coefficient. In response, we emphasize the need to transform interactionist explanations from being empty platitudes to becoming the default conceptual framework; we wholeheartedly accept his critical view of heritability coefficient estimates (but acknowledge a more limited utility for them); and we are intrigued by his conceptual interest in identifying free-will coefficients yet warn against falling into pitfalls similar to those that were stumbled into in the past. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Reverse genetics of measles virus and resulting multivalent recombinant vaccines: applications of recombinant measles viruses.

PubMed

Billeter, M A; Naim, H Y; Udem, S A

2009-01-01

An overview is given on the development of technologies to allow reverse genetics of RNA viruses, i.e., the rescue of viruses from cDNA, with emphasis on nonsegmented negative-strand RNA viruses (Mononegavirales), as exemplified for measles virus (MV). Primarily, these technologies allowed site-directed mutagenesis, enabling important insights into a variety of aspects of the biology of these viruses. Concomitantly, foreign coding sequences were inserted to (a) allow localization of virus replication in vivo through marker gene expression, (b) develop candidate multivalent vaccines against measles and other pathogens, and (c) create candidate oncolytic viruses. The vector use of these viruses was experimentally encouraged by the pronounced genetic stability of the recombinants unexpected for RNA viruses, and by the high load of insertable genetic material, in excess of 6 kb. The known assets, such as the small genome size of the vector in comparison to DNA viruses proposed as vectors, the extensive clinical experience of attenuated MV as vaccine with a proven record of high safety and efficacy, and the low production cost per vaccination dose are thus favorably complemented.

Extracting genetic alteration information for personalized cancer therapy from ClinicalTrials.gov

PubMed Central

Xu, Jun; Lee, Hee-Jin; Zeng, Jia; Wu, Yonghui; Zhang, Yaoyun; Huang, Liang-Chin; Johnson, Amber; Holla, Vijaykumar; Bailey, Ann M; Cohen, Trevor; Meric-Bernstam, Funda; Bernstam, Elmer V

2016-01-01

Objective: Clinical trials investigating drugs that target specific genetic alterations in tumors are important for promoting personalized cancer therapy. The goal of this project is to create a knowledge base of cancer treatment trials with annotations about genetic alterations from ClinicalTrials.gov. Methods: We developed a semi-automatic framework that combines advanced text-processing techniques with manual review to curate genetic alteration information in cancer trials. The framework consists of a document classification system to identify cancer treatment trials from ClinicalTrials.gov and an information extraction system to extract gene and alteration pairs from the Title and Eligibility Criteria sections of clinical trials. By applying the framework to trials at ClinicalTrials.gov, we created a knowledge base of cancer treatment trials with genetic alteration annotations. We then evaluated each component of the framework against manually reviewed sets of clinical trials and generated descriptive statistics of the knowledge base. Results and Discussion: The automated cancer treatment trial identification system achieved a high precision of 0.9944. Together with the manual review process, it identified 20 193 cancer treatment trials from ClinicalTrials.gov. The automated gene-alteration extraction system achieved a precision of 0.8300 and a recall of 0.6803. After validation by manual review, we generated a knowledge base of 2024 cancer trials that are labeled with specific genetic alteration information. Analysis of the knowledge base revealed the trend of increased use of targeted therapy for cancer, as well as top frequent gene-alteration pairs of interest. We expect this knowledge base to be a valuable resource for physicians and patients who are seeking information about personalized cancer therapy. PMID:27013523

Extracting genetic alteration information for personalized cancer therapy from ClinicalTrials.gov.

PubMed

Xu, Jun; Lee, Hee-Jin; Zeng, Jia; Wu, Yonghui; Zhang, Yaoyun; Huang, Liang-Chin; Johnson, Amber; Holla, Vijaykumar; Bailey, Ann M; Cohen, Trevor; Meric-Bernstam, Funda; Bernstam, Elmer V; Xu, Hua

2016-07-01

Clinical trials investigating drugs that target specific genetic alterations in tumors are important for promoting personalized cancer therapy. The goal of this project is to create a knowledge base of cancer treatment trials with annotations about genetic alterations from ClinicalTrials.gov. We developed a semi-automatic framework that combines advanced text-processing techniques with manual review to curate genetic alteration information in cancer trials. The framework consists of a document classification system to identify cancer treatment trials from ClinicalTrials.gov and an information extraction system to extract gene and alteration pairs from the Title and Eligibility Criteria sections of clinical trials. By applying the framework to trials at ClinicalTrials.gov, we created a knowledge base of cancer treatment trials with genetic alteration annotations. We then evaluated each component of the framework against manually reviewed sets of clinical trials and generated descriptive statistics of the knowledge base. The automated cancer treatment trial identification system achieved a high precision of 0.9944. Together with the manual review process, it identified 20 193 cancer treatment trials from ClinicalTrials.gov. The automated gene-alteration extraction system achieved a precision of 0.8300 and a recall of 0.6803. After validation by manual review, we generated a knowledge base of 2024 cancer trials that are labeled with specific genetic alteration information. Analysis of the knowledge base revealed the trend of increased use of targeted therapy for cancer, as well as top frequent gene-alteration pairs of interest. We expect this knowledge base to be a valuable resource for physicians and patients who are seeking information about personalized cancer therapy. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Food Chain Algorithm for Capacitated Vehicle Routing Problem with Recycling in Reverse Logistics

NASA Astrophysics Data System (ADS)

Song, Qiang; Gao, Xuexia; Santos, Emmanuel T.

2015-12-01

This paper introduces the capacitated vehicle routing problem with recycling in reverse logistics, and designs a food chain algorithm for it. Some illustrative examples are selected to conduct simulation and comparison. Numerical results show that the performance of the food chain algorithm is better than the genetic algorithm, particle swarm optimization as well as quantum evolutionary algorithm.

An integrated open framework for thermodynamics of reactions that combines accuracy and coverage.

PubMed

Noor, Elad; Bar-Even, Arren; Flamholz, Avi; Lubling, Yaniv; Davidi, Dan; Milo, Ron

2012-08-01

The laws of thermodynamics describe a direct, quantitative relationship between metabolite concentrations and reaction directionality. Despite great efforts, thermodynamic data suffer from limited coverage, scattered accessibility and non-standard annotations. We present a framework for unifying thermodynamic data from multiple sources and demonstrate two new techniques for extrapolating the Gibbs energies of unmeasured reactions and conditions. Both methods account for changes in cellular conditions (pH, ionic strength, etc.) by using linear regression over the ΔG(○) of pseudoisomers and reactions. The Pseudoisomeric Reactant Contribution method systematically infers compound formation energies using measured K' and pK(a) data. The Pseudoisomeric Group Contribution method extends the group contribution method and achieves a high coverage of unmeasured reactions. We define a continuous index that predicts the reversibility of a reaction under a given physiological concentration range. In the characteristic physiological range 3μM-3mM, we find that roughly half of the reactions in Escherichia coli's metabolism are reversible. These new tools can increase the accuracy of thermodynamic-based models, especially in non-standard pH and ionic strengths. The reversibility index can help modelers decide which reactions are reversible in physiological conditions. Freely available on the web at: http://equilibrator.weizmann.ac.il. Website implemented in Python, MySQL, Apache and Django, with all major browsers supported. The framework is open-source (code.google.com/p/milo-lab), implemented in pure Python and tested mainly on Linux. ron.milo@weizmann.ac.il Supplementary data are available at Bioinformatics online.

An integrated open framework for thermodynamics of reactions that combines accuracy and coverage

PubMed Central

Noor, Elad; Bar-Even, Arren; Flamholz, Avi; Lubling, Yaniv; Davidi, Dan; Milo, Ron

2012-01-01

Motivation: The laws of thermodynamics describe a direct, quantitative relationship between metabolite concentrations and reaction directionality. Despite great efforts, thermodynamic data suffer from limited coverage, scattered accessibility and non-standard annotations. We present a framework for unifying thermodynamic data from multiple sources and demonstrate two new techniques for extrapolating the Gibbs energies of unmeasured reactions and conditions. Results: Both methods account for changes in cellular conditions (pH, ionic strength, etc.) by using linear regression over the ΔG○ of pseudoisomers and reactions. The Pseudoisomeric Reactant Contribution method systematically infers compound formation energies using measured K′ and pKa data. The Pseudoisomeric Group Contribution method extends the group contribution method and achieves a high coverage of unmeasured reactions. We define a continuous index that predicts the reversibility of a reaction under a given physiological concentration range. In the characteristic physiological range 3μM–3mM, we find that roughly half of the reactions in Escherichia coli's metabolism are reversible. These new tools can increase the accuracy of thermodynamic-based models, especially in non-standard pH and ionic strengths. The reversibility index can help modelers decide which reactions are reversible in physiological conditions. Availability: Freely available on the web at: http://equilibrator.weizmann.ac.il. Website implemented in Python, MySQL, Apache and Django, with all major browsers supported. The framework is open-source (code.google.com/p/milo-lab), implemented in pure Python and tested mainly on Linux. Contact: ron.milo@weizmann.ac.il Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:22645166

Genetic education and the challenge of genomic medicine: development of core competences to support preparation of health professionals in Europe

PubMed Central

Skirton, Heather; Lewis, Celine; Kent, Alastair; Coviello, Domenico A

2010-01-01

The use of genetics and genomics within a wide range of health-care settings requires health professionals to develop expertise to practise appropriately. There is a need for a common minimum standard of competence in genetics for health professionals in Europe but because of differences in professional education and regulation between European countries, setting curricula may not be practical. Core competences are used as a basis for health professional education in many fields and settings. An Expert Group working under the auspices of the EuroGentest project and European Society of Human Genetics Education Committee agreed that a pragmatic solution to the need to establish common standards for education and practice in genetic health care was to agree to a set of core competences that could apply across Europe. These were agreed through an exhaustive process of consultation with relevant health professionals and patient groups. Sets of competences for practitioners working in primary, secondary and tertiary care have been agreed and were approved by the European Society of Human Genetics. The competences provide an appropriate framework for genetics education of health professionals across national boundaries, and the suggested learning outcomes are available to guide development of curricula that are appropriate to the national context, educational system and health-care setting of the professional involved. Collaboration between individuals from many European countries and professions has resulted in an adaptable framework for both pre-registration and continuing professional education. This competence framework has the potential to improve the quality of genetic health care for patients globally. PMID:20442748

Cultural transmission and the evolution of human behaviour: a general approach based on the Price equation.

PubMed

El Mouden, C; André, J-B; Morin, O; Nettle, D

2014-02-01

Transmitted culture can be viewed as an inheritance system somewhat independent of genes that is subject to processes of descent with modification in its own right. Although many authors have conceptualized cultural change as a Darwinian process, there is no generally agreed formal framework for defining key concepts such as natural selection, fitness, relatedness and altruism for the cultural case. Here, we present and explore such a framework using the Price equation. Assuming an isolated, independently measurable culturally transmitted trait, we show that cultural natural selection maximizes cultural fitness, a distinct quantity from genetic fitness, and also that cultural relatedness and cultural altruism are not reducible to or necessarily related to their genetic counterparts. We show that antagonistic coevolution will occur between genes and culture whenever cultural fitness is not perfectly aligned with genetic fitness, as genetic selection will shape psychological mechanisms to avoid susceptibility to cultural traits that bear a genetic fitness cost. We discuss the difficulties with conceptualizing cultural change using the framework of evolutionary theory, the degree to which cultural evolution is autonomous from genetic evolution, and the extent to which cultural change should be seen as a Darwinian process. We argue that the nonselection components of evolutionary change are much more important for culture than for genes, and that this and other important differences from the genetic case mean that different approaches and emphases are needed for cultural than genetic processes. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

Genetic education and the challenge of genomic medicine: development of core competences to support preparation of health professionals in Europe.

PubMed

Skirton, Heather; Lewis, Celine; Kent, Alastair; Coviello, Domenico A

2010-09-01

The use of genetics and genomics within a wide range of health-care settings requires health professionals to develop expertise to practise appropriately. There is a need for a common minimum standard of competence in genetics for health professionals in Europe but because of differences in professional education and regulation between European countries, setting curricula may not be practical. Core competences are used as a basis for health professional education in many fields and settings. An Expert Group working under the auspices of the EuroGentest project and European Society of Human Genetics Education Committee agreed that a pragmatic solution to the need to establish common standards for education and practice in genetic health care was to agree to a set of core competences that could apply across Europe. These were agreed through an exhaustive process of consultation with relevant health professionals and patient groups. Sets of competences for practitioners working in primary, secondary and tertiary care have been agreed and were approved by the European Society of Human Genetics. The competences provide an appropriate framework for genetics education of health professionals across national boundaries, and the suggested learning outcomes are available to guide development of curricula that are appropriate to the national context, educational system and health-care setting of the professional involved. Collaboration between individuals from many European countries and professions has resulted in an adaptable framework for both pre-registration and continuing professional education. This competence framework has the potential to improve the quality of genetic health care for patients globally.

A reverse genetics system for enterovirus D68 using human RNA polymerase I.

PubMed

Pan, Minglei; Gao, Shuai; Zhou, Zhenwei; Zhang, Keke; Liu, Sihua; Wang, Zhiyun; Wang, Tao

2018-05-17

Human enterovirus D68 (EV-D68) is a highly contagious virus, which causes respiratory tract infections. However, no effective vaccines are currently available for controlling EV-D68 infection. Here, we developed a reverse genetics system to recover EV-D68 minireplicons and infectious EV-D68 from transfected plasmids using the RNA polymerase I (Pol I) promoter. The EV-D68 minireplicons contained the luciferase reporter gene, which flanked by the non-coding regions of the EV-D68 RNA. The luciferase signals could be detected in cells after transfection and Pol I promoter-mediated luciferase signal was significantly stronger than that mediated by the T7 promoter. Furthermore, recombinant viruses were generated by transfecting plasmids that contained the genomic RNA segments of EV-D68, under the control of Pol I promoter into 293T cells or RD cells. On plaque morphology and growth kinetics, the rescued virus and parental virus were indistinguishable. In addition, we showed that the G394C mutation disrupts the viral 5'-UTR structure and suppresses the viral cap-independent translation. This reverse genetics system for EV-D68 recovery can greatly facilitate research into EV-D68 biology. Moreover, this system could accelerate the development of EV-D68 vaccines and anti-EV-D68 drugs.

Arenavirus reverse genetics for vaccine development

PubMed Central

Ortiz-Riaño, Emilio; Cheng, Benson Yee Hin; Carlos de la Torre, Juan

2013-01-01

Arenaviruses are important human pathogens with no Food and Drug Administration (FDA)-licensed vaccines available and current antiviral therapy being limited to an off-label use of the nucleoside analogue ribavirin of limited prophylactic efficacy. The development of reverse genetics systems represented a major breakthrough in arenavirus research. However, rescue of recombinant arenaviruses using current reverse genetics systems has been restricted to rodent cells. In this study, we describe the rescue of recombinant arenaviruses from human 293T cells and Vero cells, an FDA-approved line for vaccine development. We also describe the generation of novel vectors that mediate synthesis of both negative-sense genome RNA and positive-sense mRNA species of lymphocytic choriomeningitis virus (LCMV) directed by the human RNA polymerases I and II, respectively, within the same plasmid. This approach reduces by half the number of vectors required for arenavirus rescue, which could facilitate virus rescue in cell lines approved for human vaccine production but that cannot be transfected at high efficiencies. We have shown the feasibility of this approach by rescuing both the Old World prototypic arenavirus LCMV and the live-attenuated vaccine Candid#1 strain of the New World arenavirus Junín. Moreover, we show the feasibility of using these novel strategies for efficient rescue of recombinant tri-segmented both LCMV and Candid#1. PMID:23364194

MINIGENOMES, TRANSCRIPTION AND REPLICATION COMPETENT VIRUS-LIKE PARTICLES AND BEYOND: REVERSE GENETICS SYSTEMS FOR FILOVIRUSES AND OTHER NEGATIVE STRANDED HEMORRHAGIC FEVER VIRUSES

PubMed Central

Hoenen, Thomas; Groseth, Allison; de Kok-Mercado, Fabian; Kuhn, Jens H.; Wahl-Jensen, Victoria

2012-01-01

Reverse-genetics systems are powerful tools enabling researchers to study the replication cycle of RNA viruses, including filoviruses and other hemorrhagic fever viruses, as well as to discover new antivirals. They include full-length clone systems as well as a number of life cycle modeling systems. Full-length clone systems allow for the generation of infectious, recombinant viruses, and thus are an important tool for studying the virus replication cycle in its entirety. In contrast, life cycle modeling systems such as minigenome and transcription and replication competent virus-like particle systems can be used to simulate and dissect parts of the virus life cycle outside of containment facilities. Minigenome systems are used to model viral genome replication and transcription, whereas transcription and replication competent virus-like particle systems also model morphogenesis and budding as well as infection of target cells. As such, these modeling systems have tremendous potential to further the discovery and screening of new antivirals targeting hemorrhagic fever viruses. This review provides an overview of currently established reverse genetics systems for hemorrhagic fever-causing negative-sense RNA viruses, with a particular emphasis on filoviruses, and the potential application of these systems for antiviral research. PMID:21699921

Reverse Genetics System Demonstrates that Rotavirus Nonstructural Protein NSP6 Is Not Essential for Viral Replication in Cell Culture.

PubMed

Komoto, Satoshi; Kanai, Yuta; Fukuda, Saori; Kugita, Masanori; Kawagishi, Takahiro; Ito, Naoto; Sugiyama, Makoto; Matsuura, Yoshiharu; Kobayashi, Takeshi; Taniguchi, Koki

2017-11-01

The use of overlapping open reading frames (ORFs) to synthesize more than one unique protein from a single mRNA has been described for several viruses. Segment 11 of the rotavirus genome encodes two nonstructural proteins, NSP5 and NSP6. The NSP6 ORF is present in the vast majority of rotavirus strains, and therefore the NSP6 protein would be expected to have a function in viral replication. However, there is no direct evidence of its function or requirement in the viral replication cycle yet. Here, taking advantage of a recently established plasmid-only-based reverse genetics system that allows rescue of recombinant rotaviruses entirely from cloned cDNAs, we generated NSP6-deficient viruses to directly address its significance in the viral replication cycle. Viable recombinant NSP6-deficient viruses could be engineered. Single-step growth curves and plaque formation of the NSP6-deficient viruses confirmed that NSP6 expression is of limited significance for RVA replication in cell culture, although the NSP6 protein seemed to promote efficient virus growth. IMPORTANCE Rotavirus is one of the most important pathogens of severe diarrhea in young children worldwide. The rotavirus genome, consisting of 11 segments of double-stranded RNA, encodes six structural proteins (VP1 to VP4, VP6, and VP7) and six nonstructural proteins (NSP1 to NSP6). Although specific functions have been ascribed to each of the 12 viral proteins, the role of NSP6 in the viral replication cycle remains unknown. In this study, we demonstrated that the NSP6 protein is not essential for viral replication in cell culture by using a recently developed plasmid-only-based reverse genetics system. This reverse genetics approach will be successfully applied to answer questions of great interest regarding the roles of rotaviral proteins in replication and pathogenicity, which can hardly be addressed by conventional approaches. Copyright © 2017 American Society for Microbiology.

Yb3O(OH)6Cl·2H2O: an anion-exchangeable hydroxide with a cationic inorganic framework structure.

PubMed

Goulding, Helen V; Hulse, Sarah E; Clegg, William; Harrington, Ross W; Playford, Helen Y; Walton, Richard I; Fogg, Andrew M

2010-10-06

The first anion-exchangeable framework hydroxide, Yb(3)O(OH)(6)Cl·2H(2)O, has been synthesized hydrothermally. This material has a three-dimensional cationic ytterbium oxyhydroxide framework with one-dimensional channels running through the structure in which the chloride anions and water molecules are located. The framework is thermally stable below 200 °C and can be reversibly dehydrated and rehydrated with no loss of crystallinity. Additionally, it is able to undergo anion-exchange reactions with small ions such as carbonate, oxalate, and succinate with retention of the framework structure.

Plastid, nuclear and reverse transcriptase sequences in the mitochondrial genome of Oenothera: is genetic information transferred between organelles via RNA?

PubMed Central

Schuster, W; Brennicke, A

1987-01-01

We describe an open reading frame (ORF) with high homology to reverse transcriptase in the mitochondrial genome of Oenothera. This ORF displays all the characteristics of an active plant mitochondrial gene with a possible ribosome binding site and 39% T in the third codon position. It is located between a sequence fragment from the plastid genome and one of nuclear origin downstream from the gene encoding subunit 5 of the NADH dehydrogenase. The nuclear derived sequence consists of 528 nucleotides from the small ribosomal RNA and contains an expansion segment unique to nuclear rRNAs. The plastid sequence contains part of the ribosomal protein S4 and the complete tRNA(Ser). The observation that only transcribed sequences have been found i more than one subcellular compartment in higher plants suggests that interorganellar transfer of genetic information may occur via RNA and subsequent local reverse transcription and genomic integration. PMID:14650433

Reverse transcription-polymerase chain reaction molecular testing of cytology specimens: Pre-analytic and analytic factors.

PubMed

Bridge, Julia A

2017-01-01

The introduction of molecular testing into cytopathology laboratory practice has expanded the types of samples considered feasible for identifying genetic alterations that play an essential role in cancer diagnosis and treatment. Reverse transcription-polymerase chain reaction (RT-PCR), a sensitive and specific technical approach for amplifying a defined segment of RNA after it has been reverse-transcribed into its DNA complement, is commonly used in clinical practice for the identification of recurrent or tumor-specific fusion gene events. Real-time RT-PCR (quantitative RT-PCR), a technical variation, also permits the quantitation of products generated during each cycle of the polymerase chain reaction process. This review addresses qualitative and quantitative pre-analytic and analytic considerations of RT-PCR as they relate to various cytologic specimens. An understanding of these aspects of genetic testing is central to attaining optimal results in the face of the challenges that cytology specimens may present. Cancer Cytopathol 2017;125:11-19. © 2016 American Cancer Society. © 2016 American Cancer Society.

Unraveling the Mystery of the Origin of Mathematical Problems: Using a Problem-Posing Framework with Prospective Mathematics Teachers

ERIC Educational Resources Information Center

Contreras, Jose

2007-01-01

In this article, I model how a problem-posing framework can be used to enhance our abilities to systematically generate mathematical problems by modifying the attributes of a given problem. The problem-posing model calls for the application of the following fundamental mathematical processes: proving, reversing, specializing, generalizing, and…

White Skin, Black Friend: A Fanonian Application to Theorize Racial Fetish in Teacher Education

ERIC Educational Resources Information Center

Matias, Cheryl E.

2016-01-01

In "Black Skin, white masks" (1967, Grove Press), Franz Fanon uses a psychoanalytic framework to theorize the inferiority-dependency complex of Black men in response to the colonial racism of white men. Applying his framework in reverse, this theoretical article psychoanalyzes the white psyche and emotionality with respect to the…

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-off on Phenotype Robustness in Biological Networks Part I: Gene Regulatory Networks in Systems and Evolutionary Biology

PubMed Central

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties observed in biological systems at different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be enough to confer intrinsic robustness in order to tolerate intrinsic parameter fluctuations, genetic robustness for buffering genetic variations, and environmental robustness for resisting environmental disturbances. With this, the phenotypic stability of biological network can be maintained, thus guaranteeing phenotype robustness. This paper presents a survey on biological systems and then develops a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation in systems and evolutionary biology. Further, from the unifying mathematical framework, it was discovered that the phenotype robustness criterion for biological networks at different levels relies upon intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness. When this is true, the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in systems and evolutionary biology can also be investigated through their corresponding phenotype robustness criterion from the systematic point of view. PMID:23515240

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-off on Phenotype Robustness in Biological Networks Part I: Gene Regulatory Networks in Systems and Evolutionary Biology.

PubMed

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties observed in biological systems at different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be enough to confer intrinsic robustness in order to tolerate intrinsic parameter fluctuations, genetic robustness for buffering genetic variations, and environmental robustness for resisting environmental disturbances. With this, the phenotypic stability of biological network can be maintained, thus guaranteeing phenotype robustness. This paper presents a survey on biological systems and then develops a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation in systems and evolutionary biology. Further, from the unifying mathematical framework, it was discovered that the phenotype robustness criterion for biological networks at different levels relies upon intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness. When this is true, the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in systems and evolutionary biology can also be investigated through their corresponding phenotype robustness criterion from the systematic point of view.

Evaluation of a reverse-hybridization StripAssay for the detection of genetic polymorphisms leading to acenocoumarol sensitivity.

PubMed

Gialeraki, Argyri; Markatos, Christos; Grouzi, Elisabeth; Merkouri, Efrosyni; Travlou, Anthi; Politou, Marianna

2010-04-01

Acenocoumarol is mainly catabolized by CYP2C9 isoform of cytochrome P450 (CYP) liver complex and exerts its anticoagulant effect through the inhibition of Vitamin K Epoxide Reductase (VKOR). The most important genetic polymorphisms which lead to an impaired enzymatic activity and therefore predispose to acenocoumarol sensitivity, are considered to be CYP2C9*2 (Arg144Cys), CYP2C9*3 (Ile359Leu) and VKORC1-1639G>A, respectively. In this study we compared the results of the PGXThrombo StripAssay kit (ViennaLab Diagnostics,Vienna, Austria) with direct DNA sequencing and in house Restriction Fragment Length Polymorphisms (RFLP) for the detection of the aforementioned Single Nucleotide Polymorphisms (SNPs). The reverse hybridization StripAssay was found to be equally effective with RFLP and direct DNA sequencing for the detection of CYP2C9*2 and CYP2C9*3 polymorphisms, respectively. The comparison of the RFLP reference method with the reverse hybridization StripAssay for the detection of VKORC1-1639 G>A polymorphism showed that the reverse hybridization StripAsssay might misclassify some A/A homozygotes as heterozygotes. Optimization of the hybridization procedures may eliminate the extra low signal band observed in some samples at the reverse hybridization StripAssay and improve its diagnostic value.

Genetic Testing for Minors: Comparison between Italian and British Guidelines

PubMed Central

Tozzo, Pamela; Caenazzo, Luciana; Rodriguez, Daniele

2012-01-01

Genetic testing in children raises many important ethical, legal, and social issues. One of the main concerns is the ethically inappropriate genetic testing of minors. Various European countries established professional guidelines which reflect the different countries perspectives regarding the main ethical issues involved. In this paper, we analyze the Italian and the British guidelines by highlighting differences and similarities. We discuss presymptomatic, predictive, and carrier testing because we consider them to be the more ethically problematic types of genetic testing in minors. In our opinion, national guidelines should take into account the different needs in clinical practice. At the same time, in the case of genetic testing the national and supranational protection of minors could be strengthened by approving guidelines based on a common framework of principles and values. We suggest that the Oviedo Convention could represent an example of such a common framework or, at least, it could lead to articulate it. PMID:22567400

Incorporating genetic sampling in long-term monitoring and adaptive management in the San Diego County Management Strategic Plan Area, Southern California

USGS Publications Warehouse

Vandergast, Amy G.

2017-06-02

Habitat and species conservation plans usually rely on monitoring to assess progress towards conservation goals. Southern California, USA, is a hotspot of biodiversity and home to many federally endangered and threatened species. Here, several regional multi-species conservation plans have been implemented to balance development and conservation goals, including in San Diego County. In the San Diego County Management Strategic Plan Area (MSPA), a monitoring framework for the preserve system has been developed with a focus on species monitoring, vegetation monitoring, threats monitoring and abiotic monitoring. Genetic sampling over time (genetic monitoring) has proven useful in gathering species presence and abundance data and detecting population trends, particularly related to species and threats monitoring objectives. This report reviews genetic concepts and techniques of genetics that relate to monitoring goals and outlines components of a genetic monitoring scheme that could be applied in San Diego or in other monitoring frameworks throughout the Nation.

MONITORING MYCOTOXIN PRODUCTION AT THE GENETIC LEVEL ON VARIOUS GROWTH SUBSTRATES USING QUANTITATIVE REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION?EXPERIMENT DESIGN

EPA Science Inventory

The paper describes a method of analyzing the production of mycotoxins at the genetic level by monitoring the intracellular levels of messenger RNA (mRNA). Initial work will focus on threshing out the mycotoxin gene clusters in Stachybotrys chartarum followed by analysis of toxin...

Are we there yet? Tracking the development of new model systems

Treesearch

A. Abzhanov; C. Extavour; A. Groover; S. Hodges; H. Hoekstra; E. Kramer; A. Monteiro

2008-01-01

It is increasingly clear that additional ‘model’ systems are needed to elucidate the genetic and developmental basis of organismal diversity. Whereas model system development previously required enormous investment, recent advances including the decreasing cost of DNA sequencing and the power of reverse genetics to study gene function are greatly facilitating...

COTIP: Cotton TILLING Platform, a Resource for Plant Improvement and Reverse Genetic Studies

PubMed Central

Aslam, Usman; Cheema, Hafiza M. N.; Ahmad, Sheraz; Khan, Iqrar A.; Malik, Waqas; Khan, Asif A.

2016-01-01

Cotton is cultivated worldwide for its white fiber, of which around 90% is tetraploid upland cotton (Gossypium hirsutum L.) carrying both A and D genome. Since centuries, yield increasing efforts for the cotton crop by conventional breeding approaches have caused an extensive erosion of natural genetic variability. Mutation based improvement strategies provide an effective way of creating new allelic variations. Targeting Induced Local Lesions IN Genomes (TILLING) provides a mutation based reverse genetic strategy to create and evaluate induced genetic variability at DNA level. Here, we report development and testing of TILLING populations of allotetraploid cotton (G. hirsutum) for functional genomic studies and mutation based enrichment of cotton genetic resources. Seed of two cotton cultivars “PB-899 and PB-900” were mutagenized with 0.3 and 0.2% (v/v) ethyl methanesulfonate, respectively. The phenotyping of M1 and M2 populations presented numerous mutants regarding the branching pattern, leaf morphology, disease resistance, photosynthetic lesions and flower sterility. Molecular screening for point mutations was performed by TILLING PCR aided CEL1 mismatch cleavage. To estimate the mutation frequency in the mutant genomes, five gene classes were TILLed in 8000 M2 plants of each var. “PB-899” and “PB-900.” These include actin (GhACT), Pectin Methyl Esterase (GhPME), sucrose synthase (GhSUS), resistance gene analog, and defense response gene (DRGs). The var. PB-899 was harboring 47% higher mutation induction rate than PB-900. The highest rate of mutation frequency was identified for NAC-TF5 (EU706348) of DRGs class, ranging from 1/58 kb in PB-899 to 1/105 kb in PB-900. The mutation screening assay revealed the presence of significant proportion of induced mutations in cotton TILLING populations such as 1/153 kb and 1/326 kb in var. “PB-899” and “PB-900,” respectively. The establishment of a cotton TILLING platform (COTIP) and data obtained from the resource TILLING population suggest its effectiveness in widening the genetic bases of cotton for improvement and utilizing it for subsequent reverse genetic studies of various genes. PMID:28082993

Genetic Instability at the Agouti Locus of the Mouse (Mus Musculus). I. Increased Reverse Mutation Frequency to the A(w) Allele in a/a Heterozygotes

PubMed Central

Sandulache, R.; Neuhauser-Klaus, A.; Favor, J.

1994-01-01

We have compiled the reverse mutation rate data to the white bellied agouti (A(w)) allele in heterozygous A/a mice and shown it to be increased by a factor of at least 350 in comparison to the reverse mutation rate in homozygous a/a mice. Employing tightly linked flanking restriction fragment length polymorphism DNA markers, we have shown that reversion to A(w) is associated with crossing over in the vicinity of the agouti locus. The non-agouti (a) allele has been recently shown to contain an 11-kb insert within the first intron of the agouti gene. Together with our present results, these observations suggest possible mechanisms to explain the reversion events. PMID:7982562

Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology

PubMed Central

Brudey, Karine; Driscoll, Jeffrey R; Rigouts, Leen; Prodinger, Wolfgang M; Gori, Andrea; Al-Hajoj, Sahal A; Allix, Caroline; Aristimuño, Liselotte; Arora, Jyoti; Baumanis, Viesturs; Binder, Lothar; Cafrune, Patricia; Cataldi, Angel; Cheong, Soonfatt; Diel, Roland; Ellermeier, Christopher; Evans, Jason T; Fauville-Dufaux, Maryse; Ferdinand, Séverine; de Viedma, Dario Garcia; Garzelli, Carlo; Gazzola, Lidia; Gomes, Harrison M; Guttierez, M Cristina; Hawkey, Peter M; van Helden, Paul D; Kadival, Gurujaj V; Kreiswirth, Barry N; Kremer, Kristin; Kubin, Milan; Kulkarni, Savita P; Liens, Benjamin; Lillebaek, Troels; Ly, Ho Minh; Martin, Carlos; Martin, Christian; Mokrousov, Igor; Narvskaïa, Olga; Ngeow, Yun Fong; Naumann, Ludmilla; Niemann, Stefan; Parwati, Ida; Rahim, Zeaur; Rasolofo-Razanamparany, Voahangy; Rasolonavalona, Tiana; Rossetti, M Lucia; Rüsch-Gerdes, Sabine; Sajduda, Anna; Samper, Sofia; Shemyakin, Igor G; Singh, Urvashi B; Somoskovi, Akos; Skuce, Robin A; van Soolingen, Dick; Streicher, Elisabeth M; Suffys, Philip N; Tortoli, Enrico; Tracevska, Tatjana; Vincent, Véronique; Victor, Tommie C; Warren, Robin M; Yap, Sook Fan; Zaman, Khadiza; Portaels, Françoise; Rastogi, Nalin; Sola, Christophe

2006-01-01

Background The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database. Results The fourth international spoligotyping database, SpolDB4, describes 1939 shared-types (STs) representative of a total of 39,295 strains from 122 countries, which are tentatively classified into 62 clades/lineages using a mixed expert-based and bioinformatical approach. The SpolDB4 update adds 26 new potentially phylogeographically-specific MTC genotype families. It provides a clearer picture of the current MTC genomes diversity as well as on the relationships between the genetic attributes investigated (spoligotypes) and the infra-species classification and evolutionary history of the species. Indeed, an independent Naïve-Bayes mixture-model analysis has validated main of the previous supervised SpolDB3 classification results, confirming the usefulness of both supervised and unsupervised models as an approach to understand MTC population structure. Updated results on the epidemiological status of spoligotypes, as well as genetic prevalence maps on six main lineages are also shown. Our results suggests the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network. Conclusion Our results broaden the knowledge of the global phylogeography of the MTC complex. SpolDB4 should be a very useful tool to better define the identity of a given MTC clinical isolate, and to better analyze the links between its current spreading and previous evolutionary history. The building and mining of extended MTC polymorphic genetic databases is in progress. PMID:16519816

Exploring Conceptual Change in Genetics Using a Multidimensional Interpretive Framework.

ERIC Educational Resources Information Center

Venville, Grady J.; Treagust, David F.

1998-01-01

Changes in grade 10 students' (n=79) conceptions of genes during genetics instruction was studied from multiple perspectives. Ontologically, most students moved from passive to active models of genes. Affectively, students were interested in genetics but unmotivated by microscopic mechanistic explanations; however, teaching approaches were…

Ecological speciation in the tropics: insights from comparative genetic studies in Amazonia

PubMed Central

Beheregaray, Luciano B.; Cooke, Georgina M.; Chao, Ning L.; Landguth, Erin L.

2015-01-01

Evolution creates and sustains biodiversity via adaptive changes in ecologically relevant traits. Ecologically mediated selection contributes to genetic divergence both in the presence or absence of geographic isolation between populations, and is considered an important driver of speciation. Indeed, the genetics of ecological speciation is becoming increasingly studied across a variety of taxa and environments. In this paper we review the literature of ecological speciation in the tropics. We report on low research productivity in tropical ecosystems and discuss reasons accounting for the rarity of studies. We argue for research programs that simultaneously address biogeographical and taxonomic questions in the tropics, while effectively assessing relationships between reproductive isolation and ecological divergence. To contribute toward this goal, we propose a new framework for ecological speciation that integrates information from phylogenetics, phylogeography, population genomics, and simulations in evolutionary landscape genetics (ELG). We introduce components of the framework, describe ELG simulations (a largely unexplored approach in ecological speciation), and discuss design and experimental feasibility within the context of tropical research. We then use published genetic datasets from populations of five codistributed Amazonian fish species to assess the performance of the framework in studies of tropical speciation. We suggest that these approaches can assist in distinguishing the relative contribution of natural selection from biogeographic history in the origin of biodiversity, even in complex ecosystems such as Amazonia. We also discuss on how to assess ecological speciation using ELG simulations that include selection. These integrative frameworks have considerable potential to enhance conservation management in biodiversity rich ecosystems and to complement historical biogeographic and evolutionary studies of tropical biotas. PMID:25653668

Coherent and Noncoherent Joint Processing of Sonar for Detection of Small Targets in Shallow Water

PubMed Central

Jiang, Jingning; Li, Si; Ding, Zhenping; Pan, Chen; Gong, Xianyi

2018-01-01

A coherent-noncoherent joint processing framework is proposed for active sonar to combine diversity gain and beamforming gain for detection of a small target in shallow water environments. Sonar utilizes widely-spaced arrays to sense environments and illuminate a target of interest from multiple angles. Meanwhile, it exploits spatial diversity for time-reversal focusing to suppress reverberation, mainly strong bottom reverberation. For enhancement of robustness of time-reversal focusing, an adaptive iterative strategy is utilized in the processing framework. A probing signal is firstly transmitted and echoes of a likely target are utilized as steering vectors for the second transmission. With spatial diversity, target bearing and range are estimated using a broadband signal model. Numerical simulations show that the novel sonar outperforms the traditional phased-array sonar due to benefits of spatial diversity. The effectiveness of the proposed framework has been validated by localization of a small target in at-lake experiments. PMID:29642637

The impact of sex-role reversal on the diversity of the major histocompatibility complex: insights from the seahorse (Hippocampus abdominalis).

PubMed

Bahr, Angela; Wilson, Anthony B

2011-05-10

Both natural and sexual selection are thought to influence genetic diversity, but the study of the relative importance of these two factors on ecologically-relevant traits has traditionally focused on species with conventional sex-roles, with male-male competition and female-based mate choice. With its high variability and significance in both immune function and olfactory-mediated mate choice, the major histocompatibility complex (MHC/MH) is an ideal system in which to evaluate the relative contributions of these two selective forces to genetic diversity. Intrasexual competition and mate choice are both reversed in sex-role reversed species, and sex-related differences in the detection and use of MH-odor cues are expected to influence the intensity of sexual selection in such species. The seahorse, Hippocampus abdominalis, has an exceptionally highly developed form of male parental care, with female-female competition and male mate choice. Here, we demonstrate that the sex-role reversed seahorse has a single MH class II beta-chain gene and that the diversity of the seahorse MHIIβ locus and its pattern of variation are comparable to those detected in species with conventional sex roles. Despite the presence of only a single gene copy, intralocus MHIIβ allelic diversity in this species exceeds that observed in species with multiple copies of this locus. The MHIIβ locus of the seahorse exhibits a novel expression domain in the male brood pouch. The high variation found at the seahorse MHIIβ gene indicates that sex-role reversed species are capable of maintaining the high MHC diversity typical in most vertebrates.Whether such species have evolved the capacity to use MH-odor cues during mate choice is presently being investigated using mate choice experiments. If this possibility can be rejected, such systems would offer an exceptional opportunity to study the effects of natural selection in isolation, providing powerful comparative models for understanding the relative importance of selective factors in shaping patterns of genetic variation.

Genetics in the 21st Century: The Benefits & Challenges of Incorporating a Project-Based Genetics Unit in Biology Classrooms

ERIC Educational Resources Information Center

Alozie, Nonye; Eklund, Jennifer; Rogat, Aaron; Krajcik, Joseph

2010-01-01

How can science instruction help students and teachers engage in relevant genetics content that stimulates learning and heightens curiosity? Project-based science can enhance learning and thinking in science classrooms. We describe how we use project-based science features as a framework for a genetics unit, discuss some of the challenges…

Reverse Genetics and High Throughput Sequencing Methodologies for Plant Functional Genomics

PubMed Central

Ben-Amar, Anis; Daldoul, Samia; Reustle, Götz M.; Krczal, Gabriele; Mliki, Ahmed

2016-01-01

In the post-genomic era, increasingly sophisticated genetic tools are being developed with the long-term goal of understanding how the coordinated activity of genes gives rise to a complex organism. With the advent of the next generation sequencing associated with effective computational approaches, wide variety of plant species have been fully sequenced giving a wealth of data sequence information on structure and organization of plant genomes. Since thousands of gene sequences are already known, recently developed functional genomics approaches provide powerful tools to analyze plant gene functions through various gene manipulation technologies. Integration of different omics platforms along with gene annotation and computational analysis may elucidate a complete view in a system biology level. Extensive investigations on reverse genetics methodologies were deployed for assigning biological function to a specific gene or gene product. We provide here an updated overview of these high throughout strategies highlighting recent advances in the knowledge of functional genomics in plants. PMID:28217003

The pINDUCER lentiviral toolkit for inducible RNA interference in vitro and in vivo

PubMed Central

Meerbrey, Kristen L.; Hu, Guang; Kessler, Jessica D.; Roarty, Kevin; Fang, Justin E.; Herschkowitz, Jason I.; Burrows, Anna E.; Ciccia, Alberto; Sun, Tingting; Schmitt, Earlene M.; Bernardi, Ronald J.; Fu, Xiaoyong; Bland, Christopher S.; Cooper, Thomas A.; Schiff, Rachel; Rosen, Jeffrey M.; Westbrook, Thomas F.; Elledge, Stephen J.

2011-01-01

The discovery of RNAi has revolutionized loss-of-function genetic studies in mammalian systems. However, significant challenges still remain to fully exploit RNAi for mammalian genetics. For instance, genetic screens and in vivo studies could be broadly improved by methods that allow inducible and uniform gene expression control. To achieve this, we built the lentiviral pINDUCER series of expression vehicles for inducible RNAi in vivo. Using a multicistronic design, pINDUCER vehicles enable tracking of viral transduction and shRNA or cDNA induction in a broad spectrum of mammalian cell types in vivo. They achieve this uniform temporal, dose-dependent, and reversible control of gene expression across heterogenous cell populations via fluorescence-based quantification of reverse tet-transactivator expression. This feature allows isolation of cell populations that exhibit a potent, inducible target knockdown in vitro and in vivo that can be used in human xenotransplantation models to examine cancer drug targets. PMID:21307310

A reverse genetics approach identifies novel mutants in light responses and anthocyanin metabolism in petunia.

PubMed

Berenschot, Amanda S; Quecini, Vera

2014-01-01

Flower color and plant architecture are important commercially valuable features for ornamental petunias (Petunia x hybrida Vilm.). Photoperception and light signaling are the major environmental factors controlling anthocyanin and chlorophyll biosynthesis and shade-avoidance responses in higher plants. The genetic regulators of these processes were investigated in petunia by in silico analyses and the sequence information was used to devise a reverse genetics approach to probe mutant populations. Petunia orthologs of photoreceptor, light-signaling components and anthocyanin metabolism genes were identified and investigated for functional conservation by phylogenetic and protein motif analyses. The expression profiles of photoreceptor gene families and of transcription factors regulating anthocyanin biosynthesis were obtained by bioinformatic tools. Two mutant populations, generated by an alkalyting agent and by gamma irradiation, were screened using a phenotype-independent, sequence-based method by high-throughput PCR-based assay. The strategy allowed the identification of novel mutant alleles for anthocyanin biosynthesis (CHALCONE SYNTHASE) and regulation (PH4), and for light signaling (CONSTANS) genes.

DNA-launched live-attenuated vaccines for biodefense applications

PubMed Central

Pushko, Peter; Lukashevich, Igor S.; Weaver, Scott C.; Tretyakova, Irina

2016-01-01

Summary A novel vaccine platform uses DNA immunization to launch live-attenuated virus vaccines in vivo. This technology has been applied for vaccine development against positive-strand RNA viruses with global public health impact including alphaviruses and flaviviruses. The DNA-launched vaccine represents the recombinant plasmid that encodes the full-length genomic RNA of live-attenuated virus downstream from a eukaryotic promoter. When administered in vivo, the genomic RNA of live-attenuated virus is transcribed. The RNA initiates limited replication of a genetically defined, live-attenuated vaccine virus in the tissues of the vaccine recipient, thereby inducing a protective immune response. This platform combines the strengths of reverse genetics, DNA immunization and the advantages of live-attenuated vaccines, resulting in a reduced chance of genetic reversions, increased safety, and improved immunization. With this vaccine technology, the field of DNA vaccines is expanded from those that express subunit antigens to include a novel type of DNA vaccines that launch live-attenuated viruses. PMID:27055100

Preparation and Analysis of Cyclodextrin-Based Metal-Organic Frameworks: Laboratory Experiments Adaptable for High School through Advanced Undergraduate Students

ERIC Educational Resources Information Center

Smith, Merry K.; Angle, Samantha R.; Northrop, Brian H.

2015-01-01

?-Cyclodextrin can assemble in the presence of KOH or RbOH into metal-organic frameworks (CD-MOFs) with applications in gas adsorption and environmental remediation. Crystalline CD-MOFs are grown by vapor diffusion and their reversible adsorption of CO[subscript 2](g) is analyzed both qualitatively and quantitatively. The experiment can be…

Psychological Aspects of Genetic Approach to Teaching Mathematics

ERIC Educational Resources Information Center

Safuanov, Ildar S.

2004-01-01

In this theoretical essay the psychological aspects of genetic approach to teaching mathematics (mainly at universities) are discussed. Analysis of the history and modern state of genetic teaching shows that its psychological aspects may be explained using both Vygotskian and Piagetian frameworks. Experience of practice of mathematical education…

Genetic Algorithms and Local Search

NASA Technical Reports Server (NTRS)

Whitley, Darrell

1996-01-01

The first part of this presentation is a tutorial level introduction to the principles of genetic search and models of simple genetic algorithms. The second half covers the combination of genetic algorithms with local search methods to produce hybrid genetic algorithms. Hybrid algorithms can be modeled within the existing theoretical framework developed for simple genetic algorithms. An application of a hybrid to geometric model matching is given. The hybrid algorithm yields results that improve on the current state-of-the-art for this problem.

Viral metagenomics, protein structure, and reverse genetics: Key strategies for investigating coronaviruses.

PubMed

Johnson, Bryan A; Graham, Rachel L; Menachery, Vineet D

2018-04-01

Viral metagenomics, modeling of protein structure, and manipulation of viral genetics are key approaches that have laid the foundations of our understanding of coronavirus biology. In this review, we discuss the major advances each method has provided and discuss how future studies should leverage these strategies synergistically to answer novel questions. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic Detection and Isolation of Crimean-Congo hemorrhagic fever virus, Kosovo, Yugoslavia

PubMed Central

Boźović, Bojana; Pavlidou, Vassiliki; Papadimitriou, Evangelia; Pelemis, Mijomir; Antoniadis, Aantonis

2002-01-01

Crimean-Congo hemorrhagic fever virus (C-CHFV) strains were isolated from a fatal case and the attending physician in Kosovo, Yugoslavia. Early, rapid diagnosis of the disease was achieved by reverse transcription-polymerase chain reaction. The physician was successfully treated with oral ribavirin. These cases yielded the first genetically studied C-CHFV human isolates in the Balkans. PMID:12141973

An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function.

PubMed

Li, Hao; Wang, Xu; Rukina, Daria; Huang, Qingyao; Lin, Tao; Sorrentino, Vincenzo; Zhang, Hongbo; Bou Sleiman, Maroun; Arends, Danny; McDaid, Aaron; Luan, Peiling; Ziari, Naveed; Velázquez-Villegas, Laura A; Gariani, Karim; Kutalik, Zoltan; Schoonjans, Kristina; Radcliffe, Richard A; Prins, Pjotr; Morgenthaler, Stephan; Williams, Robert W; Auwerx, Johan

2018-01-24

Identifying genetic and environmental factors that impact complex traits and common diseases is a high biomedical priority. Here, we developed, validated, and implemented a series of multi-layered systems approaches, including (expression-based) phenome-wide association, transcriptome-/proteome-wide association, and (reverse-) mediation analysis, in an open-access web server (systems-genetics.org) to expedite the systems dissection of gene function. We applied these approaches to multi-omics datasets from the BXD mouse genetic reference population, and identified and validated associations between genes and clinical and molecular phenotypes, including previously unreported links between Rpl26 and body weight, and Cpt1a and lipid metabolism. Furthermore, through mediation and reverse-mediation analysis we established regulatory relations between genes, such as the co-regulation of BCKDHA and BCKDHB protein levels, and identified targets of transcription factors E2F6, ZFP277, and ZKSCAN1. Our multifaceted toolkit enabled the identification of gene-gene and gene-phenotype links that are robust and that translate well across populations and species, and can be universally applied to any populations with multi-omics datasets. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Genetically attenuated Trypanosoma cruzi parasites as a potential vaccination tool

PubMed Central

Brandan, Cecilia Pérez; Basombrío, Miguel Ángel

2012-01-01

Chagas disease is the clinical manifestation of the infection produced by the parasite Trypanosoma cruzi. Currently there is no vaccine to prevent this disease and the protection attained with vaccines containing non-replicating parasites is limited. Genetically attenuated trypanosomatid parasites can be obtained by deletion of selected genes. Gene deletion takes advantage of the fact that this parasite can undergo homologous recombination between endogenous and foreign DNA sequences artificially introduced in the cells. This approach facilitated the discovery of several unknown gene functions, as well as allowing us to speculate about the potential for genetically attenuated live organisms as experimental immunogens. Vaccination with live attenuated parasites has been used effectively in mice to reduce parasitemia and histological damage, and in dogs, to prevent vector-delivered infection in the field. However, the use of live parasites as immunogens is controversial due to the risk of reversion to a virulent phenotype. Herein, we present our results from experiments on genetic manipulation of two T. cruzi strains to produce parasites with impaired replication and infectivity, and using the mutation of the dhfr-ts gene as a safety device against reversion to virulence. PMID:22705838

A Novel ‘Gene Insertion/Marker Out’ (GIMO) Method for Transgene Expression and Gene Complementation in Rodent Malaria Parasites

PubMed Central

Sajid, Mohammed; Chevalley-Maurel, Séverine; Ramesar, Jai; Klop, Onny; Franke-Fayard, Blandine M. D.; Janse, Chris J.; Khan, Shahid M.

2011-01-01

Research on the biology of malaria parasites has greatly benefited from the application of reverse genetic technologies, in particular through the analysis of gene deletion mutants and studies on transgenic parasites that express heterologous or mutated proteins. However, transfection in Plasmodium is limited by the paucity of drug-selectable markers that hampers subsequent genetic modification of the same mutant. We report the development of a novel ‘gene insertion/marker out’ (GIMO) method for two rodent malaria parasites, which uses negative selection to rapidly generate transgenic mutants ready for subsequent modifications. We have created reference mother lines for both P. berghei ANKA and P. yoelii 17XNL that serve as recipient parasites for GIMO-transfection. Compared to existing protocols GIMO-transfection greatly simplifies and speeds up the generation of mutants expressing heterologous proteins, free of drug-resistance genes, and requires far fewer laboratory animals. In addition we demonstrate that GIMO-transfection is also a simple and fast method for genetic complementation of mutants with a gene deletion or mutation. The implementation of GIMO-transfection procedures should greatly enhance Plasmodium reverse-genetic research. PMID:22216235

Do researchers have an obligation to actively look for genetic incidental findings?

PubMed

Gliwa, Catherine; Berkman, Benjamin E

2013-01-01

The rapid growth of next-generation genetic sequencing has prompted debate about the responsibilities of researchers toward genetic incidental findings. Assuming there is a duty to disclose significant incidental findings, might there be an obligation for researchers to actively look for these findings? We present an ethical framework for analyzing whether there is a positive duty to look for genetic incidental findings. Using the ancillary care framework as a guide, we identify three main criteria that must be present to give rise to an obligation to look: high benefit to participants, lack of alternative access for participants, and reasonable burden on researchers. Our analysis indicates that there is no obligation to look for incidental findings today, but during the ongoing translation of genomic analysis from research to clinical care, this obligation may arise.

Do Researchers Have an Obligation to Actively Look for Genetic Incidental Findings?

PubMed Central

Gliwa, Catherine; Berkman, Benjamin E.

2014-01-01

The rapid growth of next-generation genetic sequencing has prompted debate about the responsibilities of researchers toward genetic incidental findings. Assuming there is a duty to disclose significant incidental findings, might there be an obligation for researchers to actively look for these findings? We present an ethical framework for analyzing whether there is a positive duty to look for genetic incidental findings. Using the ancillary care framework as a guide, we identify three main criteria that must be present to give rise to an obligation to look: high benefit to participants, lack of alternative access for participants, and reasonable burden on researchers. Our analysis indicates that there is no obligation to look for incidental findings today, but during the ongoing translation of genomic analysis from research to clinical care, this obligation may arise. PMID:23391059

International cooperation and networking in genetic health care provision: issues arising from the genetic services plan for the Emilia-Romagna region, Italy.

PubMed

Calzolari, E; Baroncini, A

2005-01-01

The aims of this report are to describe the genetic plan for Emilia-Romagna, a region in Italy, and to contribute to the international exchange of information on developing and applying policy frameworks to provide high-quality and comprehensive genetic health care in the publicly funded health systems. At the present time there is no national policy for genetic medicine in Italy, and only two regions, Emilia-Romagna and Liguria, have formally agreed to a strategic plan for health care in genetics. The current provision of genetic services in Emilia-Romagna is described focusing on the intra- and inter-organizational linkages to ensure a comprehensive system of coordinated activities. Strengths and implementation areas are highlighted. Points that must be solved within the regional or national context are the definition of the level of assistance required in genetic medicine, the formal professional recognition of the genetic counselor and the adjustment of the billing mechanisms to the complexities of clinical genetic services. Issues that need to be addressed at a wider level include full assessment of genetic tests before their introduction into clinical practice, networking to provide tests for the rarest genetic diseases, consensus on fundamental terminology and clinical and administrative data sets to promote a cohesive framework for the flow of information throughout the health care systems with respect to genetics. Copyright 2005 S. Karger AG, Basel.

Drawing the line on genetic intervention in humans.

PubMed Central

Kaura, D R

1996-01-01

Because the science of genetics can have such profound effects on medicine and mankind, society must define the characteristics of a moral framework within which to make decisions about genetic issues. University of Manitoba medical student Deepak Kaura, who claimed third prize in CMAJ's 1995 Logie Medical Ethics Essay Contest, examines the ethics of genetic intervention in humans. Images p928-a PMID:8634976

The media and genetically modified foods: evidence in support of social amplification of risk.

PubMed

Frewer, Lynn J; Miles, Susan; Marsh, Roy

2002-08-01

Empirical examinations of the "social amplification of risk" framework are rare, partly because of the difficulties in predicting when conditions likely to result in amplification effects will occur. This means that it is difficult to examine changes in risk perception that are contemporaneous with increases and/or decreases in social or media discussion of the risks associated with a particular risk event. However, the collection of attitude data before, during, and after the increased reporting of the risks of genetically modified food in the United Kingdom (spring 1999) has demonstrated that people's risk perceptions do increase and decrease in line with what might be expected upon examination of the amplification and attenuation mechanisms integral to the framework. Perceptions of benefit, however, appeared to be permanently depressed by negative reporting about genetically modified food. Trust in regulatory institutions with responsibility for protecting the public was not affected. It was concluded that the social amplification of risk framework is a useful framework for beginning to explain the potential impact on risk perceptions of a risk event, particularly if that risk event is presented to the public as a new hazard occurring in a crisis context.

A Unified Framework for Association Analysis with Multiple Related Phenotypes

PubMed Central

Stephens, Matthew

2013-01-01

We consider the problem of assessing associations between multiple related outcome variables, and a single explanatory variable of interest. This problem arises in many settings, including genetic association studies, where the explanatory variable is genotype at a genetic variant. We outline a framework for conducting this type of analysis, based on Bayesian model comparison and model averaging for multivariate regressions. This framework unifies several common approaches to this problem, and includes both standard univariate and standard multivariate association tests as special cases. The framework also unifies the problems of testing for associations and explaining associations – that is, identifying which outcome variables are associated with genotype. This provides an alternative to the usual, but conceptually unsatisfying, approach of resorting to univariate tests when explaining and interpreting significant multivariate findings. The method is computationally tractable genome-wide for modest numbers of phenotypes (e.g. 5–10), and can be applied to summary data, without access to raw genotype and phenotype data. We illustrate the methods on both simulated examples, and to a genome-wide association study of blood lipid traits where we identify 18 potential novel genetic associations that were not identified by univariate analyses of the same data. PMID:23861737

Cognitive Frames of Reference and Strategic Thinking

DTIC Science & Technology

1991-04-05

Elliot Jaques and T. 0. Jacobs, whose Stratified Systems Theory (SST) links leadership requirements to organizational functions. SST emphasizes the...reverse if necessary and identify by block number) Using Stratified Systems Theory and the research on expertise as a conceptual framework, this study...Stratified Systems Theory and the research on expertise as a conceptual framework, this study explored the differences in the structure and content of the

Multi-scale genetic dynamic modelling I : an algorithm to compute generators.

PubMed

Kirkilionis, Markus; Janus, Ulrich; Sbano, Luca

2011-09-01

We present a new approach or framework to model dynamic regulatory genetic activity. The framework is using a multi-scale analysis based upon generic assumptions on the relative time scales attached to the different transitions of molecular states defining the genetic system. At micro-level such systems are regulated by the interaction of two kinds of molecular players: macro-molecules like DNA or polymerases, and smaller molecules acting as transcription factors. The proposed genetic model then represents the larger less abundant molecules with a finite discrete state space, for example describing different conformations of these molecules. This is in contrast to the representations of the transcription factors which are-like in classical reaction kinetics-represented by their particle number only. We illustrate the method by considering the genetic activity associated to certain configurations of interacting genes that are fundamental to modelling (synthetic) genetic clocks. A largely unknown question is how different molecular details incorporated via this more realistic modelling approach lead to different macroscopic regulatory genetic models which dynamical behaviour might-in general-be different for different model choices. The theory will be applied to a real synthetic clock in a second accompanying article (Kirkilioniset al., Theory Biosci, 2011).

The Application of a Homologous Recombination Assay Revealed Amino Acid Residues in an LTR-Retrotransposon That Were Critical for Integration

PubMed Central

Atwood, Angela; Choi, Jeannie; Levin, Henry L.

1998-01-01

Retroviruses and their relatives, the LTR-retrotransposons, possess an integrase protein (IN) that is required for the insertion of reverse transcripts into the genome of host cells. Schizosaccharomyces pombe is the host of Tf1, an LTR-retrotransposon with integration activity that can be studied by using techniques of yeast genetics. In this study, we sought to identify amino acid substitutions in Tf1 that specifically affected the integration step of transposition. In addition to seeking amino acid substitutions in IN, we also explored the possibility that other Tf1 proteins contributed to integration. By comparing the results of genetic assays that monitored both transposition and reverse transcription, we were able to seek point mutations throughout Tf1 that blocked transposition but not the synthesis of reverse transcripts. These mutant versions of Tf1 were candidates of elements that possessed defects in the integration step of transposition. Five mutations in Tf1 that resulted in low levels of integration were found to be located in the IN protein: two substitutions in the N-terminal Zn domain, two in the catalytic core, and one in the C-terminal domain. These results suggested that each of the three IN domains was required for Tf1 transposition. The potential role of these five amino acid residues in the function of IN is discussed. Two of the mutations that reduced integration mapped to the RNase H (RH) domain of Tf1 reverse transcriptase. The Tf1 elements with the RH mutations produced high levels of reverse transcripts, as determined by recombination and DNA blot analysis. These results indicated that the RH of Tf1 possesses a function critical for transposition that is independent of the accumulation of reverse transcripts. PMID:9445033

GoldenBraid 2.0: A Comprehensive DNA Assembly Framework for Plant Synthetic Biology1[C][W][OA

PubMed Central

Sarrion-Perdigones, Alejandro; Vazquez-Vilar, Marta; Palací, Jorge; Castelijns, Bas; Forment, Javier; Ziarsolo, Peio; Blanca, José; Granell, Antonio; Orzaez, Diego

2013-01-01

Plant synthetic biology aims to apply engineering principles to plant genetic design. One strategic requirement of plant synthetic biology is the adoption of common standardized technologies that facilitate the construction of increasingly complex multigene structures at the DNA level while enabling the exchange of genetic building blocks among plant bioengineers. Here, we describe GoldenBraid 2.0 (GB2.0), a comprehensive technological framework that aims to foster the exchange of standard DNA parts for plant synthetic biology. GB2.0 relies on the use of type IIS restriction enzymes for DNA assembly and proposes a modular cloning schema with positional notation that resembles the grammar of natural languages. Apart from providing an optimized cloning strategy that generates fully exchangeable genetic elements for multigene engineering, the GB2.0 toolkit offers an ever-growing open collection of DNA parts, including a group of functionally tested, premade genetic modules to build frequently used modules like constitutive and inducible expression cassettes, endogenous gene silencing and protein-protein interaction tools, etc. Use of the GB2.0 framework is facilitated by a number of Web resources that include a publicly available database, tutorials, and a software package that provides in silico simulations and laboratory protocols for GB2.0 part domestication and multigene engineering. In short, GB2.0 provides a framework to exchange both information and physical DNA elements among bioengineers to help implement plant synthetic biology projects. PMID:23669743

GoldenBraid 2.0: a comprehensive DNA assembly framework for plant synthetic biology.

PubMed

Sarrion-Perdigones, Alejandro; Vazquez-Vilar, Marta; Palací, Jorge; Castelijns, Bas; Forment, Javier; Ziarsolo, Peio; Blanca, José; Granell, Antonio; Orzaez, Diego

2013-07-01

Plant synthetic biology aims to apply engineering principles to plant genetic design. One strategic requirement of plant synthetic biology is the adoption of common standardized technologies that facilitate the construction of increasingly complex multigene structures at the DNA level while enabling the exchange of genetic building blocks among plant bioengineers. Here, we describe GoldenBraid 2.0 (GB2.0), a comprehensive technological framework that aims to foster the exchange of standard DNA parts for plant synthetic biology. GB2.0 relies on the use of type IIS restriction enzymes for DNA assembly and proposes a modular cloning schema with positional notation that resembles the grammar of natural languages. Apart from providing an optimized cloning strategy that generates fully exchangeable genetic elements for multigene engineering, the GB2.0 toolkit offers an evergrowing open collection of DNA parts, including a group of functionally tested, premade genetic modules to build frequently used modules like constitutive and inducible expression cassettes, endogenous gene silencing and protein-protein interaction tools, etc. Use of the GB2.0 framework is facilitated by a number of Web resources that include a publicly available database, tutorials, and a software package that provides in silico simulations and laboratory protocols for GB2.0 part domestication and multigene engineering. In short, GB2.0 provides a framework to exchange both information and physical DNA elements among bioengineers to help implement plant synthetic biology projects.

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology

PubMed Central

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental disturbances, is also proposed, together with a simulation example. PMID:23515190

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology.

PubMed

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental disturbances, is also proposed, together with a simulation example.

Framework to Delay Corn Rootworm Resistance

EPA Pesticide Factsheets

This proposed framework is intended to delay the corn rootworm pest becoming resistant to corn genetically engineered to produce Bt proteins, which kill corn rootworms but do not affect people or wildlife. It includes requirements on Bt corn manufacturers.

Reverse Ecology: from systems to environments and back.

PubMed

Levy, Roie; Borenstein, Elhanan

2012-01-01

The structure of complex biological systems reflects not only their function but also the environments in which they evolved and are adapted to. Reverse Ecology-an emerging new frontier in Evolutionary Systems Biology-aims to extract this information and to obtain novel insights into an organism's ecology. The Reverse Ecology framework facilitates the translation of high-throughput genomic data into large-scale ecological data, and has the potential to transform ecology into a high-throughput field. In this chapter, we describe some of the pioneering work in Reverse Ecology, demonstrating how system-level analysis of complex biological networks can be used to predict the natural habitats of poorly characterized microbial species, their interactions with other species, and universal patterns governing the adaptation of organisms to their environments. We further present several studies that applied Reverse Ecology to elucidate various aspects of microbial ecology, and lay out exciting future directions and potential future applications in biotechnology, biomedicine, and ecological engineering.

Engineering Values into Genetic Engineering: A Proposed Analytic Framework for Scientific Social Responsibility

PubMed Central

Cho, Mildred K.

2016-01-01

Recent experiments have been used to “edit” genomes of various plant, animal and other species, including humans, with unprecedented precision. Furthermore, editing Cas9 endonuclease gene with a gene encoding the desired guide RNA into an organism, adjacent to an altered gene, could create a “gene drive” that could spread a trait through an entire population of organisms. These experiments represent advances along a spectrum of technological abilities that genetic engineers have been working on since the advent of recombinant DNA techniques. The scientific and bioethics communities have built substantial literatures about the ethical and policy implications of genetic engineering, especially in the age of bioterrorism. However, recent CRISPr/Cas experiments have triggered a rehashing of previous policy discussions, suggesting that the scientific community requires guidance on how to think about social responsibility. We propose a framework to enable analysis of social responsibility, using two examples of genetic engineering experiments. PMID:26632356

Exploring the post-genomic world: differing explanatory and manipulatory functions of post-genomic sciences

PubMed Central

Holmes, Christina; Carlson, Siobhan M.; McDonald, Fiona; Jones, Mavis; Graham, Janice

2016-01-01

Richard Lewontin proposed that the ability of a scientific field to create a narrative for public understanding garners it social relevance. This article applies Lewontin's conceptual framework of the functions of science (manipulatory and explanatory) to compare and explain the current differences in perceived societal relevance of genetics/genomics and proteomics. We provide three examples to illustrate the social relevance and strong cultural narrative of genetics/genomics for which no counterpart exists for proteomics. We argue that the major difference between genetics/genomics and proteomics is that genomics has a strong explanatory function, due to the strong cultural narrative of heredity. Based on qualitative interviews and observations of proteomics conferences, we suggest that the nature of proteins, lack of public understanding, and theoretical complexity exacerbates this difference for proteomics. Lewontin's framework suggests that social scientists may find that omics sciences affect social relations in different ways than past analyses of genetics. PMID:27134568

Engineering Values Into Genetic Engineering: A Proposed Analytic Framework for Scientific Social Responsibility.

PubMed

Sankar, Pamela L; Cho, Mildred K

2015-01-01

Recent experiments have been used to "edit" genomes of various plant, animal and other species, including humans, with unprecedented precision. Furthermore, editing the Cas9 endonuclease gene with a gene encoding the desired guide RNA into an organism, adjacent to an altered gene, could create a "gene drive" that could spread a trait through an entire population of organisms. These experiments represent advances along a spectrum of technological abilities that genetic engineers have been working on since the advent of recombinant DNA techniques. The scientific and bioethics communities have built substantial literatures about the ethical and policy implications of genetic engineering, especially in the age of bioterrorism. However, recent CRISPr/Cas experiments have triggered a rehashing of previous policy discussions, suggesting that the scientific community requires guidance on how to think about social responsibility. We propose a framework to enable analysis of social responsibility, using two examples of genetic engineering experiments.

Exploring the post-genomic world: differing explanatory and manipulatory functions of post-genomic sciences.

PubMed

Holmes, Christina; Carlson, Siobhan M; McDonald, Fiona; Jones, Mavis; Graham, Janice

2016-01-02

Richard Lewontin proposed that the ability of a scientific field to create a narrative for public understanding garners it social relevance. This article applies Lewontin's conceptual framework of the functions of science (manipulatory and explanatory) to compare and explain the current differences in perceived societal relevance of genetics/genomics and proteomics. We provide three examples to illustrate the social relevance and strong cultural narrative of genetics/genomics for which no counterpart exists for proteomics. We argue that the major difference between genetics/genomics and proteomics is that genomics has a strong explanatory function, due to the strong cultural narrative of heredity. Based on qualitative interviews and observations of proteomics conferences, we suggest that the nature of proteins, lack of public understanding, and theoretical complexity exacerbates this difference for proteomics. Lewontin's framework suggests that social scientists may find that omics sciences affect social relations in different ways than past analyses of genetics.

Prediction and Prevention of Parasitic Diseases Using a Landscape Genomics Framework.

PubMed

Schwabl, Philipp; Llewellyn, Martin S; Landguth, Erin L; Andersson, Björn; Kitron, Uriel; Costales, Jaime A; Ocaña, Sofía; Grijalva, Mario J

2017-04-01

Substantial heterogeneity exists in the dispersal, distribution and transmission of parasitic species. Understanding and predicting how such features are governed by the ecological variation of landscape they inhabit is the central goal of spatial epidemiology. Genetic data can further inform functional connectivity among parasite, host and vector populations in a landscape. Gene flow correlates with the spread of epidemiologically relevant phenotypes among parasite and vector populations (e.g., virulence, drug and pesticide resistance), as well as invasion and re-invasion risk where parasite transmission is absent due to current or past intervention measures. However, the formal integration of spatial and genetic data ('landscape genetics') is scarcely ever applied to parasites. Here, we discuss the specific challenges and practical prospects for the use of landscape genetics and genomics to understand the biology and control of parasitic disease and present a practical framework for doing so. Copyright © 2016 Elsevier Ltd. All rights reserved.

Novel Structure of Ty3 Reverse Transcriptase | Center for Cancer Research

Cancer.gov

Retrotransposons are mobile genetic elements that self amplify via a single-stranded RNA intermediate, which is converted to double-stranded DNA by an encoded reverse transcriptase (RT) with both DNA polymerase (pol) and ribonuclease H (RNase) activities. Categorized by whether they contain flanking long terminal repeat (LTR) sequences, retrotransposons play a critical role in the architecture of eukaryotic genomes and are the evolutionary origin of retroviruses, including human immunodeficiency virus (HIV).

Mechanism-based strategies for protein thermostabilization.

PubMed

Mozhaev, V V

1993-03-01

Strategies for stabilizing enzymes can be derived from a two-step model of irreversible inactivation that involves preliminary reversible unfolding, followed by an irreversible step. Reversible unfolding is best prevented by covalent immobilization, whereas methods such as covalent modification of amino acid residues or 'medium engineering' (by the addition of low-molecular-weight compounds) are effective against irreversible 'incorrect' refolding. Genetic modification of the protein sequence is the most effective approach for preventing chemical deterioration.

Genetic and Genomic Toolbox of Zea mays

PubMed Central

Nannas, Natalie J.; Dawe, R. Kelly

2015-01-01

Maize has a long history of genetic and genomic tool development and is considered one of the most accessible higher plant systems. With a fully sequenced genome, a suite of cytogenetic tools, methods for both forward and reverse genetics, and characterized phenotype markers, maize is amenable to studying questions beyond plant biology. Major discoveries in the areas of transposons, imprinting, and chromosome biology came from work in maize. Moving forward in the post-genomic era, this classic model system will continue to be at the forefront of basic biological study. In this review, we outline the basics of working with maize and describe its rich genetic toolbox. PMID:25740912

Research on Duplication Dynamics and Evolutionary Stable of Reverse Supply Chain

NASA Astrophysics Data System (ADS)

Huizhong, Dong; Hongli, Song

An evolutionary game model of Reverse Supply Chain(RSC) is established based on duplication dynamics function and evolutionary stable strategy. Using the model framework, this paper provides insights into a deeper understanding on how each supplier make strategic decision independently in reverse supply chain to determine their performance. The main conclusion is as follow: Under the market mechanism, not unless the extra income derived from the implementation of RSC exceeds zero point would the suppliers implement RSC strategy. When those suppliers are passive to RSC, the effective solution is that the government takes macro-control measures, for example, to force those suppliers implement RSC through punishment mechanism.

Development and Validation of the Learning Progression-Based Assessment of Modern Genetics in a High School Context

ERIC Educational Resources Information Center

Todd, Amber; Romine, William L.; Cook Whitt, Katahdin

2017-01-01

We describe the development, validation, and use of the "Learning Progression-Based Assessment of Modern Genetics" (LPA-MG) in a high school biology context. Items were constructed based on a current learning progression framework for genetics (Shea & Duncan, 2013; Todd & Kenyon, 2015). The 34-item instrument, which was tied to…

Production of infectious dromedary camel hepatitis E virus by a reverse genetic system: Potential for zoonotic infection.

PubMed

Li, Tian-Cheng; Zhou, Xianfeng; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Nakamura, Tomofumi; Takeda, Naokazu; Wakita, Takaji

2016-12-01

The pathogenicity, epidemiology and replication mechanism of dromedary camel hepatitis E virus (DcHEV), a novel hepatitis E virus (HEV), has been unclear. Here we used a reverse genetic system to produce DcHEV and examined the possibility of zoonotic infection. Capped genomic RNA derived from a synthetic DcHEV cDNA was transfected into human hepatocarcinoma cells PLC/PRF/5. The DcHEV capsid protein and RNA were detected by an enzyme-linked immunosorbent assay (ELISA) or RT-qPCR. A neutralization test for DcHEV was carried out by using antisera against HEV-like particles. DcHEV was used to inoculate two cynomolgus monkeys to examine the potential for cross-species infection. The transfection of PLC/PRF/5 cells with capped DcHEV RNA resulted in the production of infectious DcHEV. The genome sequence analysis demonstrated that both nucleotide and amino acid changes accumulated during the passages in PLC/PRF/5 cells. The cynomolgus monkeys showed serological signs of infection when DcHEV was intravenously inoculated. DcHEV was neutralized by not only anti-DcHEV-LPs antibody, but also anti-genotype 1 (G1), G3 and G4 HEV-LPs antibodies. Moreover, the monkeys immunized with DcHEV escaped the G3 HEV challenge, indicating that the serotype of DcHEV is similar to those of other human HEVs. Infectious DcHEV was produced using a reverse genetic system and propagated in PLC/PRF/5 cells. The antigenicity and immunogenicity of DcHEV are similar to those of G1, G3 and G4 HEV. DcHEV was experimentally transmitted to primates, demonstrating the possibility of a zoonotic infection by DcHEV. Dromedary camel hepatitis E virus (DcHEV) was produced by a reverse genetic system and grows well in PLC/PRF/5 cells. Cynomolgus monkeys experimentally infected with DcHEV indicated serological signs of infection, suggesting that DcHEV has the potential to cause zoonotic HEV infection. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Reverse cascade screening of newborns for hereditary haemochromatosis: a model for other late onset diseases?

PubMed

Cadet, E; Capron, D; Gallet, M; Omanga-Léké, M-L; Boutignon, H; Julier, C; Robson, K J H; Rochette, J

2005-05-01

Genetic testing can determine those at risk for hereditary haemochromatosis (HH) caused by HFE mutations before the onset of symptoms. However, there is no optimum screening strategy, mainly owing to the variable penetrance in those who are homozygous for the HFE Cys282Tyr (C282Y) mutation. The objective of this study was to identify the majority of individuals at serious risk of developing HFE haemochromatosis before they developed life threatening complications. We first estimated the therapeutic penetrance of the C282Y mutation in people living in la Somme, France, using genetic, demographic, biochemical, and follow up data. We examined the benefits of neonatal screening on the basis of increased risk to relatives of newborns carrying one or two copies of the C282Y mutation. Between 1999 and 2002, we screened 7038 newborns from two maternity hospitals in the north of France for the C282Y and His63Asp (H63D) mutations in the HFE gene, using bloodspots collected on Guthrie cards. Family studies and genetic counselling were undertaken, based on the results of the baby's genotype. In la Somme, we found that 24% of the adults homozygous for the C282Y mutation required at least 5 g iron to be removed to restore normal iron parameters (that is, the therapeutic penetrance). In the reverse cascade screening study, we identified 19 C282Y homozygotes (1/370), 491 heterozygotes (1/14) and 166 compound heterozygotes (1/42) in 7038 newborns tested. The reverse cascade screening strategy resulted in 80 adults being screened for both mutations. We identified 10 previously unknown C282Y homozygotes of whom six (four men and two women) required venesection. Acceptance of neonatal screening was high; parents understood the risks of having HH and the benefits of early detection, but a number of parents were reluctant to take the test themselves. Neonatal screening for HH is straightforward. Reverse cascade screening increased the efficiency of detecting affected adults with undiagnosed haemochromatosis. This strategy allows almost complete coverage for HH and could be a model for efficient screening for other late onset genetic diseases.

The human genome as public: Justifications and implications.

PubMed

Bayefsky, Michelle J

2017-03-01

Since the human genome was decoded, great emphasis has been placed on the unique, personal nature of the genome, along with the benefits that personalized medicine can bring to individuals and the importance of safeguarding genetic privacy. As a result, an equally important aspect of the human genome - its common nature - has been underappreciated and underrepresented in the ethics literature and policy dialogue surrounding genetics and genomics. This article will argue that, just as the personal nature of the genome has been used to reinforce individual rights and justify important privacy protections, so too the common nature of the genome can be employed to support protections of the genome at a population level and policies designed to promote the public's wellbeing. In order for public health officials to have the authority to develop genetics policies for the sake of the public good, the genome must have not only a common, but also a public, dimension. This article contends that DNA carries a public dimension through the use of two conceptual frameworks: the common heritage (CH) framework and the common resource (CR) framework. Both frameworks establish a public interest in the human genome, but the CH framework can be used to justify policies aimed at preserving and protecting the genome, while the CR framework can be employed to justify policies for utilizing the genome for the public benefit. A variety of possible policy implications are discussed, with special attention paid to the use of large-scale genomics databases for public health research. © Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

A Systematic Bayesian Integration of Epidemiological and Genetic Data

PubMed Central

Lau, Max S. Y.; Marion, Glenn; Streftaris, George; Gibson, Gavin

2015-01-01

Genetic sequence data on pathogens have great potential to inform inference of their transmission dynamics ultimately leading to better disease control. Where genetic change and disease transmission occur on comparable timescales additional information can be inferred via the joint analysis of such genetic sequence data and epidemiological observations based on clinical symptoms and diagnostic tests. Although recently introduced approaches represent substantial progress, for computational reasons they approximate genuine joint inference of disease dynamics and genetic change in the pathogen population, capturing partially the joint epidemiological-evolutionary dynamics. Improved methods are needed to fully integrate such genetic data with epidemiological observations, for achieving a more robust inference of the transmission tree and other key epidemiological parameters such as latent periods. Here, building on current literature, a novel Bayesian framework is proposed that infers simultaneously and explicitly the transmission tree and unobserved transmitted pathogen sequences. Our framework facilitates the use of realistic likelihood functions and enables systematic and genuine joint inference of the epidemiological-evolutionary process from partially observed outbreaks. Using simulated data it is shown that this approach is able to infer accurately joint epidemiological-evolutionary dynamics, even when pathogen sequences and epidemiological data are incomplete, and when sequences are available for only a fraction of exposures. These results also characterise and quantify the value of incomplete and partial sequence data, which has important implications for sampling design, and demonstrate the abilities of the introduced method to identify multiple clusters within an outbreak. The framework is used to analyse an outbreak of foot-and-mouth disease in the UK, enhancing current understanding of its transmission dynamics and evolutionary process. PMID:26599399

Legislation on direct-to-consumer genetic testing in seven European countries.

PubMed

Borry, Pascal; van Hellemondt, Rachel E; Sprumont, Dominique; Jales, Camilla Fittipaldi Duarte; Rial-Sebbag, Emmanuelle; Spranger, Tade Matthias; Curren, Liam; Kaye, Jane; Nys, Herman; Howard, Heidi

2012-07-01

An increasing number of private companies are now offering direct-to-consumer (DTC) genetic testing services. Although a lot of attention has been devoted to the regulatory framework of DTC genetic testing services in the USA, only limited information about the regulatory framework in Europe is available. We will report on the situation with regard to the national legislation on DTC genetic testing in seven European countries (Belgium, the Netherlands, Switzerland, Portugal, France, Germany, the United Kingdom). The paper will address whether these countries have legislation that specifically address the issue of DTC genetic testing or have relevant laws that is pertinent to the regulatory control of these services in their countries. The findings show that France, Germany, Portugal and Switzerland have specific legislation that defines that genetic tests can only be carried out by a medical doctor after the provision of sufficient information concerning the nature, meaning and consequences of the genetic test and after the consent of the person concerned. In the Netherlands, some DTC genetic tests could fall under legislation that provides the Minister the right to refuse to provide a license to operate if a test is scientifically unsound, not in accordance with the professional medical practice standards or if the expected benefit is not in balance with the (potential) health risks. Belgium and the United Kingdom allow the provision of DTC genetic tests.

Legislation on direct-to-consumer genetic testing in seven European countries

PubMed Central

Borry, Pascal; van Hellemondt, Rachel E; Sprumont, Dominique; Jales, Camilla Fittipaldi Duarte; Rial-Sebbag, Emmanuelle; Spranger, Tade Matthias; Curren, Liam; Kaye, Jane; Nys, Herman; Howard, Heidi

2012-01-01

An increasing number of private companies are now offering direct-to-consumer (DTC) genetic testing services. Although a lot of attention has been devoted to the regulatory framework of DTC genetic testing services in the USA, only limited information about the regulatory framework in Europe is available. We will report on the situation with regard to the national legislation on DTC genetic testing in seven European countries (Belgium, the Netherlands, Switzerland, Portugal, France, Germany, the United Kingdom). The paper will address whether these countries have legislation that specifically address the issue of DTC genetic testing or have relevant laws that is pertinent to the regulatory control of these services in their countries. The findings show that France, Germany, Portugal and Switzerland have specific legislation that defines that genetic tests can only be carried out by a medical doctor after the provision of sufficient information concerning the nature, meaning and consequences of the genetic test and after the consent of the person concerned. In the Netherlands, some DTC genetic tests could fall under legislation that provides the Minister the right to refuse to provide a license to operate if a test is scientifically unsound, not in accordance with the professional medical practice standards or if the expected benefit is not in balance with the (potential) health risks. Belgium and the United Kingdom allow the provision of DTC genetic tests. PMID:22274578

Genomic Insight into Mechanisms of Reversion of Antibiotic Resistance in Multidrug Resistant Mycobacterium tuberculosis Induced by a Nanomolecular Iodine-Containing Complex FS-1.

PubMed

Ilin, Aleksandr I; Kulmanov, Murat E; Korotetskiy, Ilya S; Islamov, Rinat A; Akhmetova, Gulshara K; Lankina, Marina V; Reva, Oleg N

2017-01-01

Drug induced reversion of antibiotic resistance is a promising way to combat multidrug resistant infections. However, lacking knowledge of mechanisms of drug resistance reversion impedes employing this approach in medicinal therapies. Induction of antibiotic resistance reversion by a new anti-tuberculosis drug FS-1 has been reported. FS-1 was used in this work in combination with standard anti-tuberculosis antibiotics in an experiment on laboratory guinea pigs infected with an extensively drug resistant (XDR) strain Mycobacterium tuberculosis SCAID 187.0. During the experimental trial, genetic changes in the population were analyzed by sequencing of M. tuberculosis isolates followed by variant calling. In total 11 isolates obtained from different groups of infected animals at different stages of disease development and treatment were sequenced. It was found that despite the selective pressure of antibiotics, FS-1 caused a counter-selection of drug resistant variants that speeded up the recovery of the infected animals from XDR tuberculosis. Drug resistance mutations reported in the genome of the initial strain remained intact in more sensitive isolates obtained in this experiment. Variant calling in the sequenced genomes revealed that the drug resistance reversion could be associated with a general increase in genetic heterogeneity of the population of M. tuberculosis . Accumulation of mutations in PpsA and PpsE subunits of phenolpthiocerol polyketide synthase was observed in the isolates treated with FS-1 that may indicate an increase of persisting variants in the population. It was hypothesized that FS-1 caused an active counter-selection of drug resistant variants from the population by aggravating the cumulated fitness cost of the drug resistance mutations. Action of FS-1 on drug resistant bacteria exemplified the theoretically predicted induced synergy mechanism of drug resistance reversion. An experimental model to study the drug resistance reversion phenomenon is hereby introduced.

Photoswitchable nanoporous films by loading azobenzene in metal-organic frameworks of type HKUST-1.

PubMed

Müller, Kai; Wadhwa, Jasmine; Singh Malhi, Jasleen; Schöttner, Ludger; Welle, Alexander; Schwartz, Heidi; Hermann, Daniela; Ruschewitz, Uwe; Heinke, Lars

2017-07-13

Photoswitchable metal-organic frameworks (MOFs) enable the dynamic remote control of their key properties. Here, a readily producible approach is presented where photochromic molecules, i.e. azobenzene (AB) and o-tetrafluoroazobenzene (tfAB), are loaded in MOF films of type HKUST-1. These nanoporous films, which can be reversibly switched with UV/visible or only visible light, have remote-controllable guest uptake properties.

Insights from human genetic studies of lung and organ fibrosis.

PubMed

Garcia, Christine Kim

2018-01-02

Genetic investigations of fibrotic diseases, including those of late onset, often yield unanticipated insights into disease pathogenesis. This Review focuses on pathways underlying lung fibrosis that are generalizable to other organs. Herein, we discuss genetic variants subdivided into those that shorten telomeres, activate the DNA damage response, change resident protein expression or function, or affect organelle activity. Genetic studies provide a window into the downstream cascade of maladaptive responses and pathways that lead to tissue fibrosis. In addition, these studies reveal interactions between genetic variants, environmental factors, and age that influence the phenotypic spectrum of disease. The discovery of forces counterbalancing inherited risk alleles identifies potential therapeutic targets, thus providing hope for future prevention or reversal of fibrosis.

Toward understanding of the role of reversibility of phenotypic switching in the evolution of resistance to therapy

NASA Astrophysics Data System (ADS)

Horvath, D.; Brutovsky, B.

2018-06-01

Reversibility of state transitions is intensively studied topic in many scientific disciplines over many years. In cell biology, it plays an important role in epigenetic variation of phenotypes, known as phenotypic plasticity. More interestingly, the cell state reversibility is probably crucial in the adaptation of population phenotypic heterogeneity to environmental fluctuations by evolving bet-hedging strategy, which might confer to cancer cells resistance to therapy. In this article, we propose a formalization of the evolution of highly reversible states in the environments of periodic variability. Two interrelated models of heterogeneous cell populations are proposed and their behavior is studied. The first model captures selection dynamics of the cell clones for the respective levels of phenotypic reversibility. The second model focuses on the interplay between reversibility and drug resistance in the particular case of cancer. Overall, our results show that the threshold dependencies are emergent features of the investigated model with eventual therapeutic relevance. Presented examples demonstrate importance of taking into account cell to cell heterogeneity within a system of clones with different reversibility quantified by appropriately chosen genetic and epigenetic entropy measures.

Superior Cathode Performance of Nitrogen-Doped Graphene Frameworks for Lithium Ion Batteries.

PubMed

Xiong, Dongbin; Li, Xifei; Bai, Zhimin; Shan, Hui; Fan, Linlin; Wu, Chunxia; Li, Dejun; Lu, Shigang

2017-03-29

Development of alternative cathode materials is of highly desirable for sustainable and cost-efficient lithium-ion batteries (LIBs) in energy storage fields. In this study, for the first time, we report tunable nitrogen-doped graphene with active functional groups for cathode utilization of LIBs. When employed as cathode materials, the functionalized graphene frameworks with a nitrogen content of 9.26 at% retain a reversible capacity of 344 mAh g -1 after 200 cycles at a current density of 50 mA g -1 . More surprisingly, when conducted at a high current density of 1 A g -1 , this cathode delivers a high reversible capacity of 146 mAh g -1 after 1000 cycles. Our current research demonstrates the effective significance of nitrogen doping on enhancing cathode performance of functionalized graphene for LIBs.

Future of Environmental Research in the Age of Epigenomics and Exposomics

PubMed Central

Holland, Nina

2016-01-01

Environmental research and public health in the 21st century face serious challenges such as increased air pollution and global warming, widespread use of potentially harmful chemicals including pesticides, plasticizers, and other endocrine disruptors, and radical changes in nutrition and lifestyle typical of modern societies. In particular, exposure to environmental and occupational toxicants may contribute to the occurrence of adverse birth outcomes, neurodevelopmental deficits, and increased risk of cancer and other multifactorial diseases such as diabetes and asthma. Rapidly evolving methodologies of exposure assessment and the conceptual framework of the Exposome, first introduced in 2005, are new frontiers of environmental research. Metabolomics and adductomics provide remarkable opportunities for a better understanding of exposure and prediction of potential adverse health outcomes. Metabolomics, the study of metabolism at the whole-body level, involves assessment of the total repertoire of small molecules present in a biological sample, shedding light on interactions between gene expression, protein expression and the environment. Advances in genomics, transcriptomics and epigenomics are generating multidimensional structures of biomarkers of effect and susceptibility, increasingly important for the understanding of molecular mechanisms and the emergence of personalized medicine. Epigenetic mechanisms, particularly DNA methylation and miRNA expression, attract increasing attention as potential links between the genetic and environmental determinants of health and disease. Unlike genetics, epigenetic mechanisms could be reversible and an understanding of their role may lead to better protection of susceptible populations and improved public health. PMID:27768585

Reverse Micelle Based Synthesis of Microporous Materials in Microgravity

NASA Technical Reports Server (NTRS)

Dutta, Prabir K.

1995-01-01

Formation of zincophosphates from zinc and phosphate containing reverse micelles (water droplets in hexane) has been examined. The frameworks formed resemble that made by conventional hydrothermal synthesis. Dynamics of crystal growth are however quite different, and form the main focus of this study. In particular, the formation of zincophosphate with the sodalite framework was examined in detail. The intramicellar pH was found to have a strong influence on crystal growth. Crystals with a cubic morphology were formed directly from the micelles, without an apparent intermediate amorphous phase over a period of four days by a layer-bylayer growth at the intramicellar pH of 7.6. At a pH of 6.8, an amorphous precipitate rapidly sediments in hours. Sodalite was eventually formed from this settled phase via surface diffusion and reconstruction within four days. With a rotating cell, it was possible to minimize sedimentation and crystals were found to grow epitaxially from the spherical, amorphous particles. Intermediate pH's of 7.2 led to formation of aggregated sodalite crystals prior to settling, again without any indication of an intermediate amorphous phase. These diverse pathways were possible due to changes in intramicellar supersaturation conditions by minor changes in pH. In contrast, conventional syntheses in this pH range all proceeded by similar crystallization pathways through an amorphous gel. This study establishes that synthesis of microporous frameworks is not only possible in reverse micellar systems, but they also allow examination of possible crystallization pathways.

EPI-743 reverses the progression of the pediatric mitochondrial disease--genetically defined Leigh Syndrome.

PubMed

Martinelli, Diego; Catteruccia, Michela; Piemonte, Fiorella; Pastore, Anna; Tozzi, Giulia; Dionisi-Vici, Carlo; Pontrelli, Giuseppe; Corsetti, Tiziana; Livadiotti, Susanna; Kheifets, Viktoria; Hinman, Andrew; Shrader, William D; Thoolen, Martin; Klein, Matthew B; Bertini, Enrico; Miller, Guy

2012-11-01

Genetically defined Leigh syndrome is a rare, fatal inherited neurodegenerative disorder that predominantly affects children. No treatment is available. EPI-743 is a novel small molecule developed for the treatment of Leigh syndrome and other inherited mitochondrial diseases. In compassionate use cases and in an FDA Expanded Access protocol, children with Leigh syndrome treated with EPI-743 demonstrated objective signs of neurologic and neuromuscular improvement. To confirm these initial findings, a phase 2A open label trial of EPI-743 for children with genetically-confirmed Leigh syndrome was conducted and herein we report the results. A single arm clinical trial was performed in children with genetically defined Leigh syndrome. Subjects were treated for 6 months with EPI-743 three times daily and all were eligible for a treatment extension phase. The primary objective of the trial was to arrest disease progression as assessed by neuromuscular and quality of life metrics. Results were compared to the reported natural history of the disease. Ten consecutive children, ages 1-13 years, were enrolled; they possessed seven different genetic defects. All children exhibited reversal of disease progression regardless of genetic determinant or disease severity. The primary endpoints--Newcastle Pediatric Mitochondrial Disease Scale, the Gross Motor Function Measure, and PedsQL Neuromuscular Module--demonstrated statistically significant improvement (p<0.05). In addition, all children had an improvement of one class on the Movement Disorder-Childhood Rating Scale. No significant drug-related adverse events were recorded. In comparison to the natural history of Leigh syndrome, EPI-743 improves clinical outcomes in children with genetically confirmed Leigh syndrome. Copyright © 2012 Elsevier Inc. All rights reserved.

Efficient assembly of full-length infectious clone of Brazilian IBDV isolate by homologous recombination in yeast

PubMed Central

Silva, J.V.J.; Arenhart, S.; Santos, H.F.; Almeida-Queiroz, S.R.; Silva, A.N.M.R.; Trevisol, I.M.; Bertani, G.R.; Gil, L.H.V.G.

2014-01-01

The Infectious Bursal Disease Virus (IBDV) causes immunosuppression in young chickens. Advances in molecular virology and vaccines for IBDV have been achieved by viral reverse genetics (VRG). VRG for IBDV has undergone changes over time, however all strategies used to generate particles of IBDV involves multiple rounds of amplification and need of in vitro ligation and restriction sites. The aim of this research was to build the world’s first VRG for IBDV by yeast-based homologous recombination; a more efficient, robust and simple process than cloning by in vitro ligation. The wild type IBDV (Wt-IBDV-Br) was isolated in Brazil and had its genome cloned in pJG-CMV-HDR vector by yeast-based homologous recombination. The clones were transfected into chicken embryo fibroblasts and the recovered virus (IC-IBDV-Br) showed genetic stability and similar phenotype to Wt-IBDV-Br, which were observed by nucleotide sequence, focus size/morphology and replication kinetics, respectively. Thus, IBDV reverse genetics by yeast-based homologous recombination provides tools to IBDV understanding and vaccines/viral vectors development. PMID:25763067

Epigenetic understanding of gene-environment interactions in psychiatric disorders: a new concept of clinical genetics

PubMed Central

2012-01-01

Epigenetics is a mechanism that regulates gene expression independently of the underlying DNA sequence, relying instead on the chemical modification of DNA and histone proteins. Although environmental and genetic factors were thought to be independently associated with disorders, several recent lines of evidence suggest that epigenetics bridges these two factors. Epigenetic gene regulation is essential for normal development, thus defects in epigenetics cause various rare congenital diseases. Because epigenetics is a reversible system that can be affected by various environmental factors, such as drugs, nutrition, and mental stress, the epigenetic disorders also include common diseases induced by environmental factors. In this review, we discuss the nature of epigenetic disorders, particularly psychiatric disorders, on the basis of recent findings: 1) susceptibility of the conditions to environmental factors, 2) treatment by taking advantage of their reversible nature, and 3) transgenerational inheritance of epigenetic changes, that is, acquired adaptive epigenetic changes that are passed on to offspring. These recently discovered aspects of epigenetics provide a new concept of clinical genetics. PMID:22414323

[Biosafety issues and public concerns on recombinant influenza viruses generated in the laboratories].

PubMed

Jia, Xiaojuan; Huang, Liqin; Liu, Wenjun

2013-12-01

Understanding inter-species transmission of influenza viruses is an important research topic. Scientists try to identify and evaluate the functional factors determining the host range of influenza viruses by generating the recombinant viruses through reverse genetics in laboratories, which reveals the viruses' molecular mechanisms of infection and transmission in different species. Therefore, the reverse genetic method is a very important tool for further understanding the biology of influenza viruses and will provide the insight for the prevention and treatment of infections and transmission. However, these recombinant influenza viruses generated in laboratories will become the potential threat to the public health and the environment. In this paper, we discussed the biological safety issues of recombinant influenza viruses and suggested we should set up protocols for risk management on research activities related to recombinant highly pathogenic influenza viruses.

Generation of Recombinant Ebola Viruses Using Reverse Genetics.

PubMed

Groseth, Allison

2017-01-01

Reverse genetics systems encompass a wide array of tools aimed at recapitulating some or all of the virus life cycle. In their most complete form, full-length clone systems allow us to use plasmid-encoded versions of the ribonucleoprotein (RNP) components to initiate the transcription and replication of a plasmid-encoded version of the complete viral genome, thereby initiating the complete virus life cycle and resulting in infectious virus. As such this approach is ideal for the generation of tailor-made recombinant filoviruses, which can be used to study virus biology. In addition, the generation of tagged and particularly fluorescent or luminescent viruses can be applied as tools for both diagnostic applications and for screening to identify novel countermeasures. Here we describe the generation and basic characterization of recombinant Ebola viruses rescued from cloned cDNA using a T7-driven system.

The impact of sex-role reversal on the diversity of the major histocompatibility complex: Insights from the seahorse (Hippocampus abdominalis)

PubMed Central

2011-01-01

Background Both natural and sexual selection are thought to influence genetic diversity, but the study of the relative importance of these two factors on ecologically-relevant traits has traditionally focused on species with conventional sex-roles, with male-male competition and female-based mate choice. With its high variability and significance in both immune function and olfactory-mediated mate choice, the major histocompatibility complex (MHC/MH) is an ideal system in which to evaluate the relative contributions of these two selective forces to genetic diversity. Intrasexual competition and mate choice are both reversed in sex-role reversed species, and sex-related differences in the detection and use of MH-odor cues are expected to influence the intensity of sexual selection in such species. The seahorse, Hippocampus abdominalis, has an exceptionally highly developed form of male parental care, with female-female competition and male mate choice. Results Here, we demonstrate that the sex-role reversed seahorse has a single MH class II beta-chain gene and that the diversity of the seahorse MHIIβ locus and its pattern of variation are comparable to those detected in species with conventional sex roles. Despite the presence of only a single gene copy, intralocus MHIIβ allelic diversity in this species exceeds that observed in species with multiple copies of this locus. The MHIIβ locus of the seahorse exhibits a novel expression domain in the male brood pouch. Conclusions The high variation found at the seahorse MHIIβ gene indicates that sex-role reversed species are capable of maintaining the high MHC diversity typical in most vertebrates. Whether such species have evolved the capacity to use MH-odor cues during mate choice is presently being investigated using mate choice experiments. If this possibility can be rejected, such systems would offer an exceptional opportunity to study the effects of natural selection in isolation, providing powerful comparative models for understanding the relative importance of selective factors in shaping patterns of genetic variation. PMID:21569286

A nursing theory-guided framework for genetic and epigenetic research.

PubMed

Maki, Katherine A; DeVon, Holli A

2018-04-01

The notion that genetics, through natural selection, determines innate traits has led to much debate and divergence of thought on the impact of innate traits on the human phenotype. The purpose of this synthesis was to examine how innate theory informs genetic research and how understanding innate theory through the lens of Martha Rogers' theory of unitary human beings can offer a contemporary view of how innate traits can inform epigenetic and genetic research. We also propose a new conceptual model for genetic and epigenetic research. The philosophical, theoretical, and research literatures were examined for this synthesis. We have merged philosophical and conceptual phenomena from innate theory with the theory of unitary beings into the University of Illinois at Chicago model for genetic and epigenetic research. Innate traits are the cornerstone of the framework but may be modified epigenetically by biological, physiological, psychological, and social determinants as they are transcribed. These modifiers serve as important links between the concept of innate traits and epigenetic modifications, and, like the theory of unitary human beings, the process is understood in the context of individual and environmental interaction that has the potential to evolve as the determinants change. © 2018 John Wiley & Sons Ltd.

Energy Consumption Forecasting Using Semantic-Based Genetic Programming with Local Search Optimizer.

PubMed

Castelli, Mauro; Trujillo, Leonardo; Vanneschi, Leonardo

2015-01-01

Energy consumption forecasting (ECF) is an important policy issue in today's economies. An accurate ECF has great benefits for electric utilities and both negative and positive errors lead to increased operating costs. The paper proposes a semantic based genetic programming framework to address the ECF problem. In particular, we propose a system that finds (quasi-)perfect solutions with high probability and that generates models able to produce near optimal predictions also on unseen data. The framework blends a recently developed version of genetic programming that integrates semantic genetic operators with a local search method. The main idea in combining semantic genetic programming and a local searcher is to couple the exploration ability of the former with the exploitation ability of the latter. Experimental results confirm the suitability of the proposed method in predicting the energy consumption. In particular, the system produces a lower error with respect to the existing state-of-the art techniques used on the same dataset. More importantly, this case study has shown that including a local searcher in the geometric semantic genetic programming system can speed up the search process and can result in fitter models that are able to produce an accurate forecasting also on unseen data.

Using needs-based frameworks for evaluating new technologies: an application to genetic tests.

PubMed

Rogowski, Wolf H; Schleidgen, Sebastian

2015-02-01

Given the multitude of newly available genetic tests in the face of limited healthcare budgets, the European Society of Human Genetics assessed how genetic services can be prioritized fairly. Using (health) benefit maximizing frameworks for this purpose has been criticized on the grounds that rather than maximization, fairness requires meeting claims (e.g. based on medical need) equitably. This study develops a prioritization score for genetic tests to facilitate equitable allocation based on need-based claims. It includes attributes representing health need associated with hereditary conditions (severity and progression), a genetic service's suitability to alleviate need (evidence of benefit and likelihood of positive result) and costs to meet the needs. A case study for measuring the attributes is provided and a suggestion is made how need-based claims can be quantified in a priority function. Attribute weights can be informed by data from discrete-choice experiments. Further work is needed to measure the attributes across the multitude of genetic tests and to determine appropriate weights. The priority score is most likely to be considered acceptable if developed within a decision process which meets criteria of procedural fairness and if the priority score is interpreted as "strength of recommendation" rather than a fixed cut-off value. Copyright © 2014. Published by Elsevier Ireland Ltd.

Selfish genetic elements and the gene’s-eye view of evolution

PubMed Central

2016-01-01

During the last few decades, we have seen an explosion in the influx of details about the biology of selfish genetic elements. Ever since the early days of the field, the gene’s-eye view of Richard Dawkins, George Williams, and others, has been instrumental to make sense of new empirical observations and to the generation of new hypotheses. However, the close association between selfish genetic elements and the gene’s-eye view has not been without critics and several other conceptual frameworks have been suggested. In particular, proponents of multilevel selection models have used selfish genetic elements to criticize the gene’s-eye view. In this paper, I first trace the intertwined histories of the study of selfish genetic elements and the gene’s-eye view and then discuss how their association holds up when compared with other proposed frameworks. Next, using examples from transposable elements and the major transitions, I argue that different models highlight separate aspects of the evolution of selfish genetic elements and that the productive way forward is to maintain a plurality of perspectives. Finally, I discuss how the empirical study of selfish genetic elements has implications for other conceptual issues associated with the gene’s-eye view, such as agential thinking, adaptationism, and the role of fitness maximizing models in evolution. PMID:29491953

Mining the human genome after Association for Molecular Pathology v. Myriad Genetics

PubMed Central

Evans, Barbara J

2014-01-01

The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved—but still imperfect—framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics. Genet Med 16 7, 504–509. PMID:24357850

Expanding the framework of the holism/reductionism debate in neo-Darwinism: the case of Theodosius Dobzhansky and Bernhard Rensch.

PubMed

Delisle, Richard G

2008-01-01

The holism/reductionism debate in evolutionary biology has often been analysed as involving two main phenomenological levels within neo-Darwinism: genetic and organismic. This analytical framework assumes that explanation in evolution is either found in the field of genetics or the field of organismic biology. It is argued here that this framework is far too restrictive to incorporate what at least some founding members of neo-Darwinism had in mind in their search for the ultimate cause of evolution. Dobzhansky's "super-holism" locates this drive in the highest possible entity imaginable--an ontologically unified evolutionary cosmos--while Rensch's ontological "super-reductionism," on the other hand, places it at the lowest possible entity of microphysics, that is, at the level of an energetic field of protopsychical nature. Not only it is suggested that a much-expanded framework is required for analysing the holism/reductionism debate in neo-Darwinism, but also that this new framework may have implications for the conceptualization of the neo-Darwinian movement itself.

DyNAvectors: dynamic constitutional vectors for adaptive DNA transfection.

PubMed

Clima, Lilia; Peptanariu, Dragos; Pinteala, Mariana; Salic, Adrian; Barboiu, Mihail

2015-12-25

Dynamic constitutional frameworks, based on squalene, PEG and PEI components, reversibly connected to core centers, allow the efficient identification of adaptive vectors for good DNA transfection efficiency and are well tolerated by mammalian cells.

Acute effects of cocaine and cannabis on reversal learning as a function of COMT and DRD2 genotype.

PubMed

Spronk, Desirée B; Van der Schaaf, Marieke E; Cools, Roshan; De Bruijn, Ellen R A; Franke, Barbara; van Wel, Janelle H P; Ramaekers, Johannes G; Verkes, Robbert J

2016-01-01

Long-term cannabis and cocaine use has been associated with impairments in reversal learning. However, how acute cannabis and cocaine administration affect reversal learning in humans is not known. In this study, we aimed to establish the acute effects of administration of cannabis and cocaine on valence-dependent reversal learning as a function of DRD2 Taq1A (rs1800497) and COMT Val108/158Met (rs4680) genotype. A double-blind placebo-controlled randomized 3-way crossover design was used. Sixty-one regular poly-drug users completed a deterministic reversal learning task under the influence of cocaine, cannabis, and placebo that enabled assessment of both reward- and punishment-based reversal learning. Proportion correct on the reversal learning task was increased by cocaine, but decreased by cannabis. Effects of cocaine depended on the DRD2 genotype, as increases in proportion correct were seen only in the A1 carriers, and not in the A2/A2 homozygotes. COMT genotype did not modulate drug-induced effects on reversal learning. These data indicate that acute administration of cannabis and cocaine has opposite effects on reversal learning. The effects of cocaine, but not cannabis, depend on interindividual genetic differences in the dopamine D2 receptor gene.

The first genetic map of a synthesized allohexaploid Brassica with A, B and C genomes based on simple sequence repeat markers.

PubMed

Yang, S; Chen, S; Geng, X X; Yan, G; Li, Z Y; Meng, J L; Cowling, W A; Zhou, W J

2016-04-01

We present the first genetic map of an allohexaploid Brassica species, based on segregating microsatellite markers in a doubled haploid mapping population generated from a hybrid between two hexaploid parents. This study reports the first genetic map of trigenomic Brassica. A doubled haploid mapping population consisting of 189 lines was obtained via microspore culture from a hybrid H16-1 derived from a cross between two allohexaploid Brassica lines (7H170-1 and Y54-2). Simple sequence repeat primer pairs specific to the A genome (107), B genome (44) and C genome (109) were used to construct a genetic linkage map of the population. Twenty-seven linkage groups were resolved from 274 polymorphic loci on the A genome (109), B genome (49) and C genome (116) covering a total genetic distance of 3178.8 cM with an average distance between markers of 11.60 cM. This is the first genetic framework map for the artificially synthesized Brassica allohexaploids. The linkage groups represent the expected complement of chromosomes in the A, B and C genomes from the original diploid and tetraploid parents. This framework linkage map will be valuable for QTL analysis and future genetic improvement of a new allohexaploid Brassica species, and in improving our understanding of the genetic control of meiosis in new polyploids.

From Healthcare to Warfare and Reverse: How Should We Regulate Dual-Use Neurotechnology?

PubMed

Ienca, Marcello; Jotterand, Fabrice; Elger, Bernice S

2018-01-17

Recent advances in military-funded neurotechnology and novel opportunities for misusing neurodevices show that the problem of dual use is inherent to neuroscience. This paper discusses how the neuroscience community should respond to these dilemmas and delineates a neuroscience-specific biosecurity framework. This neurosecurity framework involves calibrated regulation, (neuro)ethical guidelines, and awareness-raising activities within the scientific community. Copyright © 2017 Elsevier Inc. All rights reserved.

Nemesis Autonomous Test System

NASA Technical Reports Server (NTRS)

Barltrop, Kevin J.; Lee, Cin-Young; Horvath, Gregory A,; Clement, Bradley J.

2012-01-01

A generalized framework has been developed for systems validation that can be applied to both traditional and autonomous systems. The framework consists of an automated test case generation and execution system called Nemesis that rapidly and thoroughly identifies flaws or vulnerabilities within a system. By applying genetic optimization and goal-seeking algorithms on the test equipment side, a "war game" is conducted between a system and its complementary nemesis. The end result of the war games is a collection of scenarios that reveals any undesirable behaviors of the system under test. The software provides a reusable framework to evolve test scenarios using genetic algorithms using an operation model of the system under test. It can automatically generate and execute test cases that reveal flaws in behaviorally complex systems. Genetic algorithms focus the exploration of tests on the set of test cases that most effectively reveals the flaws and vulnerabilities of the system under test. It leverages advances in state- and model-based engineering, which are essential in defining the behavior of autonomous systems. It also uses goal networks to describe test scenarios.

Using IBMs to Investigate Spatially-dependent Processes in Landscape Genetics Theory

EPA Science Inventory

Much of landscape and conservation genetics theory has been derived using non-spatialmathematical models. Here, we use a mechanistic, spatially-explicit, eco-evolutionary IBM to examine the utility of this theoretical framework in landscapes with spatial structure. Our analysis...

Demographic and genetic consequences of disturbed sex determination.

PubMed

Wedekind, Claus

2017-09-19

During sex determination, genetic and/or environmental factors determine the cascade of processes of gonad development. Many organisms, therefore, have a developmental window in which their sex determination can be sensitive to, for example, unusual temperatures or chemical pollutants. Disturbed environments can distort population sex ratios and may even cause sex reversal in species with genetic sex determination. The resulting genotype-phenotype mismatches can have long-lasting effects on population demography and genetics. I review the theoretical and empirical work in this context and explore in a simple population model the role of the fitness v yy of chromosomally aberrant YY genotypes that are a consequence of environmentally induced feminization. Low v yy is mostly beneficial for population growth. During feminization, low v yy reduces the proportion of genetic males and hence accelerates population growth, especially at low rates of feminization and at high fitness costs of the feminization itself (i.e. when feminization would otherwise not affect population dynamics much). When sex reversal ceases, low v yy mitigates the negative effects of feminization and can even prevent population extinction. Little is known about v yy in natural populations. The available models now need to be parametrized in order to better predict the long-term consequences of disturbed sex determination.This article is part of the themed issue 'Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies'. © 2017 The Author(s).

Genetics Home Reference: core binding factor acute myeloid leukemia

MedlinePlus

... the CBFB gene. One such rearrangement, called an inversion , involves breakage of a chromosome in two places; ... is reversed and reinserted into the chromosome. The inversion involved in CBF-AML (written as inv(16)) ...

Critical indices for reversible gamma-alpha phase transformation in metallic cerium

NASA Astrophysics Data System (ADS)

Soldatova, E. D.; Tkachenko, T. B.

1980-08-01

Critical indices for cerium have been determined within the framework of the pseudobinary solution theory along the phase equilibrium curve, the critical isotherm, and the critical isobar. The results obtained verify the validity of relationships proposed by Rushbrook (1963), Griffiths (1965), and Coopersmith (1968). It is concluded that reversible gamma-alpha transformation in metallic cerium is a critical-type transformation, and cerium has a critical point on the phase diagram similar to the critical point of the liquid-vapor system.

Operational formulation of time reversal in quantum theory

NASA Astrophysics Data System (ADS)

Oreshkov, Ognyan; Cerf, Nicolas J.

2015-10-01

The symmetry of quantum theory under time reversal has long been a subject of controversy because the transition probabilities given by Born’s rule do not apply backward in time. Here, we resolve this problem within a rigorous operational probabilistic framework. We argue that reconciling time reversal with the probabilistic rules of the theory requires a notion of operation that permits realizations through both pre- and post-selection. We develop the generalized formulation of quantum theory that stems from this approach and give a precise definition of time-reversal symmetry, emphasizing a previously overlooked distinction between states and effects. We prove an analogue of Wigner’s theorem, which characterizes all allowed symmetry transformations in this operationally time-symmetric quantum theory. Remarkably, we find larger classes of symmetry transformations than previously assumed, suggesting a possible direction in the search for extensions of known physics.

Mapping genetic variations to three-dimensional protein structures to enhance variant interpretation: a proposed framework.

PubMed

Glusman, Gustavo; Rose, Peter W; Prlić, Andreas; Dougherty, Jennifer; Duarte, José M; Hoffman, Andrew S; Barton, Geoffrey J; Bendixen, Emøke; Bergquist, Timothy; Bock, Christian; Brunk, Elizabeth; Buljan, Marija; Burley, Stephen K; Cai, Binghuang; Carter, Hannah; Gao, JianJiong; Godzik, Adam; Heuer, Michael; Hicks, Michael; Hrabe, Thomas; Karchin, Rachel; Leman, Julia Koehler; Lane, Lydie; Masica, David L; Mooney, Sean D; Moult, John; Omenn, Gilbert S; Pearl, Frances; Pejaver, Vikas; Reynolds, Sheila M; Rokem, Ariel; Schwede, Torsten; Song, Sicheng; Tilgner, Hagen; Valasatava, Yana; Zhang, Yang; Deutsch, Eric W

2017-12-18

The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to discuss unmet needs. The overarching goal of the workshop was to address the question: what can be done together as a community to advance the integration of genetic variants and 3D protein structures that could not be done by a single investigator or laboratory? Here we describe the workshop outcomes, review the state of the field, and propose the development of a framework with which to promote progress in this arena. The framework will include a set of standard formats, common ontologies, a common application programming interface to enable interoperation of the resources, and a Tool Registry to make it easy to find and apply the tools to specific analysis problems. Interoperability will enable integration of diverse data sources and tools and collaborative development of variant effect prediction methods.

The near demise and subsequent revival of classical genetics for investigating Caenorhabditis elegans embryogenesis: RNAi meets next-generation DNA sequencing.

PubMed

Bowerman, Bruce

2011-10-01

Molecular genetic investigation of the early Caenorhabditis elegans embryo has contributed substantially to the discovery and general understanding of the genes, pathways, and mechanisms that regulate and execute developmental and cell biological processes. Initially, worm geneticists relied exclusively on a classical genetics approach, isolating mutants with interesting phenotypes after mutagenesis and then determining the identity of the affected genes. Subsequently, the discovery of RNA interference (RNAi) led to a much greater reliance on a reverse genetics approach: reducing the function of known genes with RNAi and then observing the phenotypic consequences. Now the advent of next-generation DNA sequencing technologies and the ensuing ease and affordability of whole-genome sequencing are reviving the use of classical genetics to investigate early C. elegans embryogenesis.

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

1996-01-01

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myoribers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postmitotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

NASA Technical Reports Server (NTRS)

Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

1996-01-01

Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

GENET note no. 1

NASA Technical Reports Server (NTRS)

Yeh, J. W.

1971-01-01

The general features of the GENET system for simulating networks are described. A set of features is presented which are desirable for network simulations and which are expected to be achieved by this system. Among these features are: (1) two level network modeling; and (2) problem oriented operations. Several typical network systems are modeled in GENET framework to illustrate various of the features and to show its applicability.

From Metal-Organic Framework to Porous Carbon Polyhedron: Toward Highly Reversible Lithium Storage.

PubMed

Peng, Hai-Jun; Hao, Gui-Xia; Chu, Zhao-Hua; Cui, Ying-Lin; Lin, Xiao-Ming; Cai, Yue-Peng

2017-08-21

By application of a newly designed T-shaped ligand 5-(4-pyridin-4-yl-benzoylamino)isophthalic acid (H 2 PBAI) to assemble with Zn(II) ions under solvothermal conditions, a novel porous polyhedral metal-organic framework (Zn-PBAI) with pcu topology has been obtained. When treated as a precursor by annealing of Zn-PBAI at various temperatures, porous carbon polyhedra (PCP) were prepared and tested as an anode material for lithium-ion batteries. The results show that PCP carbonized at 1000 °C (PCP-1000) manifest the highest reversible specific capacity of about 1125 mAh g -1 at a current of 500 mA g -1 after 200 cycles, which is supposed to benefit from the large accessible specific area and high electric conductivity. Moreover, PCP-1000 electrode materials also exhibit superior cyclic stability and good rate capacity.

CONCEPTUAL FRAMEWORK FOR THE CHEMICAL EFFECTS IN BIOLOGICAL SYSTEMS (CEBS) TOXICOGENOMICS KNOWLEDGE BASE

EPA Science Inventory

Conceptual Framework for the Chemical Effects in Biological Systems (CEBS) T oxicogenomics Knowledge Base

Abstract
Toxicogenomics studies how the genome is involved in responses to environmental stressors or toxicants. It combines genetics, genome-scale mRNA expressio...

Statistical framework for detection of genetically modified organisms based on Next Generation Sequencing.

PubMed

Willems, Sander; Fraiture, Marie-Alice; Deforce, Dieter; De Keersmaecker, Sigrid C J; De Loose, Marc; Ruttink, Tom; Herman, Philippe; Van Nieuwerburgh, Filip; Roosens, Nancy

2016-02-01

Because the number and diversity of genetically modified (GM) crops has significantly increased, their analysis based on real-time PCR (qPCR) methods is becoming increasingly complex and laborious. While several pioneers already investigated Next Generation Sequencing (NGS) as an alternative to qPCR, its practical use has not been assessed for routine analysis. In this study a statistical framework was developed to predict the number of NGS reads needed to detect transgene sequences, to prove their integration into the host genome and to identify the specific transgene event in a sample with known composition. This framework was validated by applying it to experimental data from food matrices composed of pure GM rice, processed GM rice (noodles) or a 10% GM/non-GM rice mixture, revealing some influential factors. Finally, feasibility of NGS for routine analysis of GM crops was investigated by applying the framework to samples commonly encountered in routine analysis of GM crops. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evolution of an adenine-copper cluster to a highly porous cuboidal framework: solution-phase ripening and gas-adsorption properties.

PubMed

Venkatesh, V; Pachfule, Pradip; Banerjee, Rahul; Verma, Sandeep

2014-09-15

The synthesis and directed evolution of a tetranuclear copper cluster, supported by 8-mercapto-N9-propyladenine ligand, to a highly porous three-dimensional cubic framework in the solid state is reported. The structure of this porous framework was unambiguously characterized by X-ray crystallography. The framework contains about 62 % solvent-accessible void; the presence of a free exocyclic amino group in the porous framework facilitates reversible adsorption of gas and solvent molecules. Oriented growth of framework in solution was also tracked by force and scanning electron microscopy studies, leading to identification of an intriguing ripening process, over a period of 30 days, which also revealed formation of cuboidal aggregates in solution. The elemental composition of these cuboidal aggregates was ascertained by EDAX analysis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetic Screening: A Unique Game of Survival

ERIC Educational Resources Information Center

Kurvink, Karen; Bowser, Jessica

2004-01-01

A creative learning game that helps students reinforce basic genetic information and facilitate the identification and understanding of the more subtle issues is presented. The basic framework of the game was conceived by a business major taking non-biology major course 'heredity and society-intertwining legacy.

Preimplantation diagnosis to create 'saviour siblings': a critical discussion of the current and future legal frameworks in South Africa.

PubMed

Strode, Ann; Soni, Sheetal

2011-12-14

Pre-implantation genetic diagnosis (PGD) is a technology used in conjunction with in vitro fertilisation to screen embryos for genetic conditions prior to transfer. It was initially developed to screen mutations for severe, irreversible, genetic conditions. Currently, PGD makes it possible to select against more than 100 different genetic conditions. It has been proposed as a method for creating a tissue-matched child who can in turn serve as a compatible stem cell donor to save a sick sibling in need of a stem cell transplant. The advantage of this method is that it provides genetic information before implantation of an embryo into the womb, making it possible to ensure that only tissue-matched embryos are transferred to the uterus. A couple can therefore avoid the difficult choice of either terminating the pregnancy at a later point if the fetus is not a match, or extending their family again in the hope that their next child will be tissue compatible. Many people have expressed disapproval of the use of PGD for this purpose, and it is associated with many conflicting interests including religion, ethics as well as legal regulation. In order to manage these issues some jurisdictions have created legal frameworks to regulate the use of this technology. Many of these are modelled on the UK's Human Fertilisation and Embryology Authority and its guardian legislation. This paper critiques the current and future South African legal framework to establish whether it is able to adequately regulate the use of PGD as well as guard against misuse of the technology. It concludes that changes are required to the future framework in order to ensure that it regulates the circumstances in which PGD may occur and that the Minister of Health should act expediently in finalising draft regulations which will regulate PGD in the future.

Automated external defibrillators in the hospital: A case of medical reversal.

PubMed

Stewart, John A

2018-05-01

Automated external defibrillators (AEDs) emerged in the 1980s as an important innovation in pre-hospital emergency cardiac care (ECC). In the years since, the American Heart Association (AHA) and the International Liaison Committee for Resuscitation (ILCOR) have promoted AED technology for use in hospitals as well, resulting in the widespread purchase and use of AED-capable defibrillators. In-hospital use of AEDs now appears to have decreased survival from cardiac arrests. This article will look at the use of AEDs in hospitals as a case of "medical reversal." Medical reversal occurs when an accepted, widely used treatment is found to be ineffective or even harmful. This article will discuss the issue of AEDs in the hospital using a conceptual framework provided by recent work on medical reversal. It will go on to consider the implications of the reversal for in-hospital resuscitation programs and emergency medicine more generally. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Mendelian randomization in nutritional epidemiology

PubMed Central

Qi, Lu

2013-01-01

Nutritional epidemiology aims to identify dietary and lifestyle causes for human diseases. Causality inference in nutritional epidemiology is largely based on evidence from studies of observational design, and may be distorted by unmeasured or residual confounding and reverse causation. Mendelian randomization is a recently developed methodology that combines genetic and classical epidemiological analysis to infer causality for environmental exposures, based on the principle of Mendel’s law of independent assortment. Mendelian randomization uses genetic variants as proxiesforenvironmentalexposuresofinterest.AssociationsderivedfromMendelian randomization analysis are less likely to be affected by confounding and reverse causation. During the past 5 years, a body of studies examined the causal effects of diet/lifestyle factors and biomarkers on a variety of diseases. The Mendelian randomization approach also holds considerable promise in the study of intrauterine influences on offspring health outcomes. However, the application of Mendelian randomization in nutritional epidemiology has some limitations. PMID:19674341

Transposable elements in sexual and ancient asexual taxa

PubMed Central

Arkhipova, Irina; Meselson, Matthew

2000-01-01

Sexual reproduction allows deleterious transposable elements to proliferate in populations, whereas the loss of sex, by preventing their spread, has been predicted eventually to result in a population free of such elements [Hickey, D. A. (1982) Genetics 101, 519–531]. We tested this expectation by screening representatives of a majority of animal phyla for LINE-like and gypsy-like reverse transcriptases and mariner/Tc1-like transposases. All species tested positive for reverse transcriptases except rotifers of the class Bdelloidea, the largest eukaryotic taxon in which males, hermaphrodites, and meiosis are unknown and for which ancient asexuality is supported by molecular genetic evidence. Mariner-like transposases are distributed sporadically among species and are present in bdelloid rotifers. The remarkable lack of LINE-like and gypsy-like retrotransposons in bdelloids and their ubiquitous presence in other taxa support the view that eukaryotic retrotransposons are sexually transmitted nuclear parasites and that bdelloid rotifers evolved asexually. PMID:11121049

Exploring Post-Treatment Reversion of Antimicrobial Resistance in Enteric Bacteria of Food Animals as a Resistance Mitigation Strategy.

PubMed

Volkova, Victoriya V; KuKanich, Butch; Riviere, Jim E

2016-11-01

Antimicrobial drug use in food animals is associated with an elevation in relative abundance of bacteria resistant to the drug among the animal enteric bacteria. Some of these bacteria are potential foodborne pathogens. Evidence suggests that at least in the enteric nontype-specific Escherichia coli, after treatment the resistance abundance reverts to the background pre-treatment levels, without further interventions. We hypothesize that it is possible to define the distribution of the time period after treatment within which resistance to the administered drug, and possibly other drugs in case of coselection, in fecal bacteria of the treated animals returns to the background pre-treatment levels. Furthermore, it is possible that a novel resistance mitigation strategy for microbiological food safety could be developed based on this resistance reversion phenomenon. The strategy would be conceptually similar to existing antimicrobial drug withdrawal periods, which is a well-established and accepted mitigation strategy for avoiding violative drug residues in the edible products from the treated animals. For developing resistance-relevant withdrawals, a mathematical framework can be used to join the necessary pharmacological, microbiological, and animal production components to project the distributions of the post-treatment resistance reversion periods in the production animal populations for major antimicrobial drug classes in use. The framework can also help guide design of empirical studies into the resistance-relevant withdrawal periods and development of mitigation approaches to reduce the treatment-associated elevation of resistance in animal enteric bacteria. We outline this framework, schematically and through exemplar equations, and how its components could be formulated.

Time-reversal imaging for classification of submerged elastic targets via Gibbs sampling and the Relevance Vector Machine.

PubMed

Dasgupta, Nilanjan; Carin, Lawrence

2005-04-01

Time-reversal imaging (TRI) is analogous to matched-field processing, although TRI is typically very wideband and is appropriate for subsequent target classification (in addition to localization). Time-reversal techniques, as applied to acoustic target classification, are highly sensitive to channel mismatch. Hence, it is crucial to estimate the channel parameters before time-reversal imaging is performed. The channel-parameter statistics are estimated here by applying a geoacoustic inversion technique based on Gibbs sampling. The maximum a posteriori (MAP) estimate of the channel parameters are then used to perform time-reversal imaging. Time-reversal implementation requires a fast forward model, implemented here by a normal-mode framework. In addition to imaging, extraction of features from the time-reversed images is explored, with these applied to subsequent target classification. The classification of time-reversed signatures is performed by the relevance vector machine (RVM). The efficacy of the technique is analyzed on simulated in-channel data generated by a free-field finite element method (FEM) code, in conjunction with a channel propagation model, wherein the final classification performance is demonstrated to be relatively insensitive to the associated channel parameters. The underlying theory of Gibbs sampling and TRI are presented along with the feature extraction and target classification via the RVM.

Product-to-parent reversion processes: Stream-hyporheic spiraling increases ecosystem exposure and environmental persistence

NASA Astrophysics Data System (ADS)

Ward, A. S.; Cwiertny, D. M.; Kolodziej, E. P.

2014-12-01

The product-to-parent reversion of metabolites of trenbolone acetate (TBA), a steroidal growth promoter used widely in beef cattle production, was recently observed to occur in environmental waters. The rapid forward reaction is by direct photolysis (i.e., photohydration), with the much slower reversion reaction occurring via dehydration in the dark. The objective of this study is to quantify the potential effect of this newly discovered reversible process on TBA metabolite concentrations and total bioactivity exposure in fluvial systems. Here, we demonstrate increased persistence of TBA metabolites in the stream and hyporheic zone due to the reversion process, increasing chronic and acute exposure to these endocrine-active compounds along a stream. The perpetually dark hyporheic zone is a key location for reversion in the system, ultimately providing a source of the parent compound to the stream and increasing mean in-stream concentration of 17α-trenbolone (17α-TBOH) by 40% of the input concentration under representative fluvial conditions. As such, regulatory frameworks for compounds undergoing product-to-parent reversion will require new approaches for assessing total exposure to bioactive compounds. Further, we demonstrate generalized cases for prediction of exposure for species with product-to-parent reversion in stream-hyporheic systems.

Testicular Differentiation Occurs in Absence of R-spondin1 and Sox9 in Mouse Sex Reversals

PubMed Central

Pauper, Eva; Gregoire, Elodie P.; Klopfenstein, Muriel; de Rooij, Dirk G.; Mark, Manuel; Schedl, Andreas; Ghyselinck, Norbert B.; Chaboissier, Marie-Christine

2012-01-01

In mammals, male sex determination is governed by SRY-dependent activation of Sox9, whereas female development involves R-spondin1 (RSPO1), an activator of the WNT/beta-catenin signaling pathway. Genetic analyses in mice have demonstrated Sry and Sox9 to be both required and sufficient to induce testicular development. These genes are therefore considered as master regulators of the male pathway. Indeed, female-to-male sex reversal in XX Rspo1 mutant mice correlates with Sox9 expression, suggesting that this transcription factor induces testicular differentiation in pathological conditions. Unexpectedly, here we show that testicular differentiation can occur in XX mutants lacking both Rspo1 and Sox9 (referred to as XX Rspo1KOSox9cKO ), indicating that Sry and Sox9 are dispensable to induce female-to-male sex reversal. Molecular analyses show expression of both Sox8 and Sox10, suggesting that activation of Sox genes other than Sox9 can induce male differentiation in Rspo1KOSox9cKO mice. Moreover, since testis development occurs in XY Rspo1KOSox9cKO mice, our data show that Rspo1 is the main effector for male-to-female sex reversal in XY Sox9cKO mice. Thus, Rspo1 is an essential activator of ovarian development not only in normal situations, but also in sex reversal situations. Taken together these data demonstrate that both male and female sex differentiation is induced by distinct, active, genetic pathways. The dogma that considers female differentiation as a default pathway therefore needs to be definitively revised. PMID:23300469

Regulation of Sex Determination in Mice by a Non-coding Genomic Region

PubMed Central

Arboleda, Valerie A.; Fleming, Alice; Barseghyan, Hayk; Délot, Emmanuèle; Sinsheimer, Janet S.; Vilain, Eric

2014-01-01

To identify novel genomic regions that regulate sex determination, we utilized the powerful C57BL/6J-YPOS (B6-YPOS) model of XY sex reversal where mice with autosomes from the B6 strain and a Y chromosome from a wild-derived strain, Mus domesticus poschiavinus (YPOS), show complete sex reversal. In B6-YPOS, the presence of a 55-Mb congenic region on chromosome 11 protects from sex reversal in a dose-dependent manner. Using mouse genetic backcross designs and high-density SNP arrays, we narrowed the congenic region to a 1.62-Mb genomic region on chromosome 11 that confers 80% protection from B6-YPOS sex reversal when one copy is present and complete protection when two copies are present. It was previously believed that the protective congenic region originated from the 129S1/SviMJ (129) strain. However, genomic analysis revealed that this region is not derived from 129 and most likely is derived from the semi-inbred strain POSA. We show that the small 1.62-Mb congenic region that protects against B6-YPOS sex reversal is located within the Sox9 promoter and promotes the expression of Sox9, thereby driving testis development within the B6-YPOS background. Through 30 years of backcrossing, this congenic region was maintained, as it promoted male sex determination and fertility despite the female-promoting B6-YPOS genetic background. Our findings demonstrate that long-range enhancer regions are critical to developmental processes and can be used to identify the complex interplay between genome variants, epigenetics, and developmental gene regulation. PMID:24793290

Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model.

PubMed

Goebel-Goody, S M; Wilson-Wallis, E D; Royston, S; Tagliatela, S M; Naegele, J R; Lombroso, P J

2012-07-01

Fragile X syndrome (FXS), the most common inherited form of intellectual disability and prevailing known genetic basis of autism, is caused by an expansion in the Fmr1 gene that prevents transcription and translation of fragile X mental retardation protein (FMRP). FMRP binds to and controls translation of mRNAs downstream of metabotropic glutamate receptor (mGluR) activation. Recent work shows that FMRP interacts with the transcript encoding striatal-enriched protein tyrosine phosphatase (STEP; Ptpn5). STEP opposes synaptic strengthening and promotes synaptic weakening by dephosphorylating its substrates, including ERK1/2, p38, Fyn and Pyk2, and subunits of N-methyl-d-aspartate (NMDA) and AMPA receptors. Here, we show that basal levels of STEP are elevated and mGluR-dependent STEP synthesis is absent in Fmr1(KO) mice. We hypothesized that the weakened synaptic strength and behavioral abnormalities reported in FXS may be linked to excess levels of STEP. To test this hypothesis, we reduced or eliminated STEP genetically in Fmr1(KO) mice and assessed mice in a battery of behavioral tests. In addition to attenuating audiogenic seizures and seizure-induced c-Fos activation in the periaqueductal gray, genetically reducing STEP in Fmr1(KO) mice reversed characteristic social abnormalities, including approach, investigation and anxiety. Loss of STEP also corrected select nonsocial anxiety-related behaviors in Fmr1(KO) mice, such as light-side exploration in the light/dark box. Our findings indicate that genetically reducing STEP significantly diminishes seizures and restores select social and nonsocial anxiety-related behaviors in Fmr1(KO) mice, suggesting that strategies to inhibit STEP activity may be effective for treating patients with FXS. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Distinct virulence of Rift Valley fever phlebovirus strains from different genetic lineages in a mouse model.

PubMed

Ikegami, Tetsuro; Balogh, Aaron; Nishiyama, Shoko; Lokugamage, Nandadeva; Saito, Tais B; Morrill, John C; Shivanna, Vinay; Indran, Sabarish V; Zhang, Lihong; Smith, Jennifer K; Perez, David; Juelich, Terry L; Morozov, Igor; Wilson, William C; Freiberg, Alexander N; Richt, Juergen A

2017-01-01

Rift Valley fever phlebovirus (RVFV) causes high rates of abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral transmission occurs via mosquito vectors in endemic areas, which necessitates regular vaccination of susceptible livestock animals to prevent the RVF outbreaks. Although ZH501 strain has been used as a challenge strain for past vaccine efficacy studies, further characterization of other RVFV strains is important to optimize ruminant and nonhuman primate RVFV challenge models. This study aimed to characterize the virulence of wild-type RVFV strains belonging to different genetic lineages in outbred CD1 mice. Mice were intraperitoneally infected with 1x103 PFU of wild-type ZH501, Kenya 9800523, Kenya 90058, Saudi Arabia 200010911, OS1, OS7, SA75, Entebbe, or SA51 strains. Among them, mice infected with SA51, Entebbe, or OS7 strain showed rapid dissemination of virus in livers and peracute necrotic hepatitis at 2-3 dpi. Recombinant SA51 (rSA51) and Zinga (rZinga) strains were recovered by reverse genetics, and their virulence was also tested in CD1 mice. The rSA51 strain reproduced peracute RVF disease in mice, whereas the rZinga strain showed a similar virulence with that of rZH501 strain. This study showed that RVFV strains in different genetic lineages display distinct virulence in outbred mice. Importantly, since wild-type RVFV strains contain defective-interfering RNA or various genetic subpopulations during passage from original viral isolations, recombinant RVFV strains generated by reverse genetics will be better suitable for reproducible challenge studies for vaccine development as well as pathological studies.

Distinct virulence of Rift Valley fever phlebovirus strains from different genetic lineages in a mouse model

PubMed Central

Balogh, Aaron; Nishiyama, Shoko; Lokugamage, Nandadeva; Saito, Tais B.; Morrill, John C.; Shivanna, Vinay; Indran, Sabarish V.; Zhang, Lihong; Smith, Jennifer K.; Perez, David; Juelich, Terry L.; Morozov, Igor; Wilson, William C.; Freiberg, Alexander N.; Richt, Juergen A.

2017-01-01

Rift Valley fever phlebovirus (RVFV) causes high rates of abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral transmission occurs via mosquito vectors in endemic areas, which necessitates regular vaccination of susceptible livestock animals to prevent the RVF outbreaks. Although ZH501 strain has been used as a challenge strain for past vaccine efficacy studies, further characterization of other RVFV strains is important to optimize ruminant and nonhuman primate RVFV challenge models. This study aimed to characterize the virulence of wild-type RVFV strains belonging to different genetic lineages in outbred CD1 mice. Mice were intraperitoneally infected with 1x103 PFU of wild-type ZH501, Kenya 9800523, Kenya 90058, Saudi Arabia 200010911, OS1, OS7, SA75, Entebbe, or SA51 strains. Among them, mice infected with SA51, Entebbe, or OS7 strain showed rapid dissemination of virus in livers and peracute necrotic hepatitis at 2–3 dpi. Recombinant SA51 (rSA51) and Zinga (rZinga) strains were recovered by reverse genetics, and their virulence was also tested in CD1 mice. The rSA51 strain reproduced peracute RVF disease in mice, whereas the rZinga strain showed a similar virulence with that of rZH501 strain. This study showed that RVFV strains in different genetic lineages display distinct virulence in outbred mice. Importantly, since wild-type RVFV strains contain defective-interfering RNA or various genetic subpopulations during passage from original viral isolations, recombinant RVFV strains generated by reverse genetics will be better suitable for reproducible challenge studies for vaccine development as well as pathological studies. PMID:29267298

The remarkable frequency of human immunodeficiency virus type 1 genetic recombination.

PubMed

Onafuwa-Nuga, Adewunmi; Telesnitsky, Alice

2009-09-01

The genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from a combination of point mutations and genetic recombination, and rates of both processes are unusually high. This review focuses on the mechanisms and outcomes of HIV-1 genetic recombination and on the parameters that make recombination so remarkably frequent. Experimental work has demonstrated that the process that leads to recombination--a copy choice mechanism involving the migration of reverse transcriptase between viral RNA templates--occurs several times on average during every round of HIV-1 DNA synthesis. Key biological factors that lead to high recombination rates for all retroviruses are the recombination-prone nature of their reverse transcription machinery and their pseudodiploid RNA genomes. However, HIV-1 genes recombine even more frequently than do those of many other retroviruses. This reflects the way in which HIV-1 selects genomic RNAs for coencapsidation as well as cell-to-cell transmission properties that lead to unusually frequent associations between distinct viral genotypes. HIV-1 faces strong and changeable selective conditions during replication within patients. The mode of HIV-1 persistence as integrated proviruses and strong selection for defective proviruses in vivo provide conditions for archiving alleles, which can be resuscitated years after initial provirus establishment. Recombination can facilitate drug resistance and may allow superinfecting HIV-1 strains to evade preexisting immune responses, thus adding to challenges in vaccine development. These properties converge to provide HIV-1 with the means, motive, and opportunity to recombine its genetic material at an unprecedented high rate and to allow genetic recombination to serve as one of the highest barriers to HIV-1 eradication.

Compressed Genotyping

PubMed Central

Erlich, Yaniv; Gordon, Assaf; Brand, Michael; Hannon, Gregory J.; Mitra, Partha P.

2011-01-01

Over the past three decades we have steadily increased our knowledge on the genetic basis of many severe disorders. Nevertheless, there are still great challenges in applying this knowledge routinely in the clinic, mainly due to the relatively tedious and expensive process of genotyping. Since the genetic variations that underlie the disorders are relatively rare in the population, they can be thought of as a sparse signal. Using methods and ideas from compressed sensing and group testing, we have developed a cost-effective genotyping protocol to detect carriers for severe genetic disorders. In particular, we have adapted our scheme to a recently developed class of high throughput DNA sequencing technologies. The mathematical framework presented here has some important distinctions from the ’traditional’ compressed sensing and group testing frameworks in order to address biological and technical constraints of our setting. PMID:21451737

Reviving the Mediterranean Olive Community

ERIC Educational Resources Information Center

Zaferatos, Nicholas C.

2011-01-01

This article presents the findings of a collaborative investigation by six nongovernment organisations (NGOs) from five European-Mediterranean countries to identify a framework for reversing rural marginalisation in Mediterranean communities through sustainable forms of community-based agricultural development. The project brought together…

The evolution of personalized cancer genetic counseling in the era of personalized medicine.

PubMed

Vig, Hetal S; Wang, Catharine

2012-09-01

Practice changes in cancer genetic counseling have occurred to meet the demand for cancer genetic services. As cancer genetics continues to impact not only prevention strategies but also treatment decisions, current cancer genetic counseling models will need to be tailored to accommodate emerging clinical indications. These clinical indications include: surgical prophylactic bilateral mastectomy candidates, PARP-inhibitor candidates, patients with abnormal tumor screening results for Lynch syndrome, and post-test counseling patients (after genetic testing is ordered by another healthcare provider). A more personalized, multidisciplinary approach to selecting the best framework, for a given clinical indication, may become increasingly necessary in this era of personalized medicine.

Nursing and genetic biobanks.

PubMed

Sanner, Jennifer E; Yu, Erica; Udtha, Malini; Williams, Pamela Holtzclaw

2013-12-01

Biobanks function as vital components in genetic research, which often requires large disease-based or population-based biospecimens and clinical data to study complex or rare diseases. Genetic biobanks aim to provide resources for translational research focusing on rapidly moving scientific findings from the laboratory into health care practice. The nursing profession must evolve as genetic biobanking practices advance. Nursing involvement in genetic biobanking practices comes with a distinct set of educational, ethical, and practice competencies. In response to these growing competency standards, nursing science developed a conceptual framework and continues to study ethical considerations to guide genetic biobanking initiatives. Copyright © 2013 Elsevier Inc. All rights reserved.

The Performance of Short-Term Heart Rate Variability in the Detection of Congestive Heart Failure

PubMed Central

Barros, Allan Kardec; Ohnishi, Noboru

2016-01-01

Congestive heart failure (CHF) is a cardiac disease associated with the decreasing capacity of the cardiac output. It has been shown that the CHF is the main cause of the cardiac death around the world. Some works proposed to discriminate CHF subjects from healthy subjects using either electrocardiogram (ECG) or heart rate variability (HRV) from long-term recordings. In this work, we propose an alternative framework to discriminate CHF from healthy subjects by using HRV short-term intervals based on 256 RR continuous samples. Our framework uses a matching pursuit algorithm based on Gabor functions. From the selected Gabor functions, we derived a set of features that are inputted into a hybrid framework which uses a genetic algorithm and k-nearest neighbour classifier to select a subset of features that has the best classification performance. The performance of the framework is analyzed using both Fantasia and CHF database from Physionet archives which are, respectively, composed of 40 healthy volunteers and 29 subjects. From a set of nonstandard 16 features, the proposed framework reaches an overall accuracy of 100% with five features. Our results suggest that the application of hybrid frameworks whose classifier algorithms are based on genetic algorithms has outperformed well-known classifier methods. PMID:27891509

An in vitro recombination-based reverse genetic system for rapid mutagenesis of structural genes of the Japanese encephalitis virus.

PubMed

Du, Ruikun; Wang, Manli; Hu, Zhihong; Wang, Hualin; Deng, Fei

2015-10-01

Japanese encephalitis virus (JEV) is one of the most common pathogens of severe viral encephalitis, which is a severe threat to human health. Despite instability of the JEV genome in bacteria, many strategies have been developed to establish molecular clone systems of JEV, providing convenient tools for studying the virus life cycle and virus-host interactions. In this study, we adapted an In-Fusion enzyme-based in vitro recombination method to construct a reverse genetic system of JEV, thereby providing a rapid approach to introduce mutations into the structural genes. A truncated genome without the structural genes was constructed as the backbone, and the complementary segment containing the structural genes was recombined in vitro, which was then transfected directly into virus-permissive cells. The progeny of the infectious virus was successfully detected in the supernatant of the transfected cells, and showed an identical phenotype to its parental virus. To provide a proof-of-principle, the 12 conserved cysteine residues in the envelope (E) protein of JEV were respectively mutated using this approach, and all mutations resulted in a complete failure to generate infectious virus. However, a leucine-tophenylanine mutation at amino acid 107 of the E protein did not interfere with the production of the infectious virus. These results suggested that all 12 cysteines in the E protein are essential for the JEV life cycle. In summary, a novel reverse genetic system of JEV was established for rapidly introducing mutations into structural genes, which will serve as a useful tool for functional studies.

Epigenetics meets endocrinology

PubMed Central

Zhang, Xiang; Ho, Shuk-Mei

2014-01-01

Although genetics determines endocrine phenotypes, it cannot fully explain the great variability and reversibility of the system in response to environmental changes. Evidence now suggests that epigenetics, i.e. heritable but reversible changes in gene function without changes in nucleotide sequence, links genetics and environment in shaping endocrine function. Epigenetic mechanisms, including DNA methylation, histone modification, and microRNA, partition the genome into active and inactive domains based on endogenous and exogenous environmental changes and developmental stages, creating phenotype plasticity that can explain interindividual and population endocrine variability. We will review the current understanding of epigenetics in endocrinology, specifically, the regulation by epigenetics of the three levels of hormone action (synthesis and release, circulating and target tissue levels, and target-organ responsiveness) and the epigenetic action of endocrine disruptors. We will also discuss the impacts of hormones on epigenetics. We propose a three-dimensional model (genetics, environment, and developmental stage) to explain the phenomena related to progressive changes in endocrine functions with age, the early origin of endocrine disorders, phenotype discordance between monozygotic twins, rapid shifts in disease patterns among populations experiencing major lifestyle changes such as immigration, and the many endocrine disruptions in contemporary life. We emphasize that the key for understanding epigenetics in endocrinology is the identification, through advanced high-throughput screening technologies, of plasticity genes or loci that respond directly to a specific environmental stimulus. Investigations to determine whether epigenetic changes induced by today's lifestyles or environmental `exposures' can be inherited and are reversible should open doors for applying epigenetics to the prevention and treatment of endocrine disorders. PMID:21322125

Reversible immortalisation enables genetic correction of human muscle progenitors and engineering of next-generation human artificial chromosomes for Duchenne muscular dystrophy.

PubMed

Benedetti, Sara; Uno, Narumi; Hoshiya, Hidetoshi; Ragazzi, Martina; Ferrari, Giulia; Kazuki, Yasuhiro; Moyle, Louise Anne; Tonlorenzi, Rossana; Lombardo, Angelo; Chaouch, Soraya; Mouly, Vincent; Moore, Marc; Popplewell, Linda; Kazuki, Kanako; Katoh, Motonobu; Naldini, Luigi; Dickson, George; Messina, Graziella; Oshimura, Mitsuo; Cossu, Giulio; Tedesco, Francesco Saverio

2018-02-01

Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combination of large-capacity vectors, such as human artificial chromosomes (HACs), with stem/progenitor cells may overcome this limitation. We previously reported amelioration of the dystrophic phenotype in mice transplanted with murine muscle progenitors containing a HAC with the entire dystrophin locus (DYS-HAC). However, translation of this strategy to human muscle progenitors requires extension of their proliferative potential to withstand clonal cell expansion after HAC transfer. Here, we show that reversible cell immortalisation mediated by lentivirally delivered excisable hTERT and Bmi1 transgenes extended cell proliferation, enabling transfer of a novel DYS-HAC into DMD satellite cell-derived myoblasts and perivascular cell-derived mesoangioblasts. Genetically corrected cells maintained a stable karyotype, did not undergo tumorigenic transformation and retained their migration ability. Cells remained myogenic in vitro (spontaneously or upon MyoD induction) and engrafted murine skeletal muscle upon transplantation. Finally, we combined the aforementioned functions into a next-generation HAC capable of delivering reversible immortalisation, complete genetic correction, additional dystrophin expression, inducible differentiation and controllable cell death. This work establishes a novel platform for complex gene transfer into clinically relevant human muscle progenitors for DMD gene therapy. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

The Role of Drosophila Merlin in the Control of Mitosis Exit and Development

DTIC Science & Technology

2006-07-01

schwannomas and is associated with mutations in the tumor suppressor gene called the neurofibromatosis type 2 (NF2) gene (Chang et al., 2005; Neff...been shown to associate with endocytic compartments and because mutations in the genes , such as clathrin and ff16, that are known to be important... mutations in the Drosophila homologues of the human Neurofibromatosis 2 and yeast CDC42 genes using a simple and efficient reverse-genetic method. Genetics

Practical aspects of mutagenicity testing strategy: an industrial perspective.

PubMed

Gollapudi, B B; Krishna, G

2000-11-20

Genetic toxicology studies play a central role in the development and marketing of new chemicals for pharmaceutical, agricultural, industrial, and consumer use. During the discovery phase of product development, rapid screening tests that require minimal amounts of test materials are used to assist in the design and prioritization of new molecules. At this stage, a modified Salmonella reverse mutation assay and an in vitro micronucleus test with mammalian cell culture are frequently used for screening. Regulatory genetic toxicology studies are conducted with a short list of compounds using protocols that conform to various international guidelines. A set of four assays usually constitutes the minimum test battery that satisfies global requirements. This set includes a bacterial reverse mutation assay, an in vitro cytogenetic test with mammalian cell culture, an in vitro gene mutation assay in mammalian cell cultures, and an in vivo rodent bone marrow micronucleus test. Supplementary studies are conducted in certain instances either as a follow-up to the findings from this initial testing battery and/or to satisfy a regulatory requirement. Currently available genetic toxicology assays have helped the scientific and industrial community over the past several decades in evaluating the mutagenic potential of chemical agents. The emerging field of toxicogenomics has the potential to redefine our ability to study the response of cells to genetic damage and hence our ability to study threshold phenomenon.

Next-generation AAV vectors for clinical use: an ever-accelerating race.

PubMed

Weinmann, Jonas; Grimm, Dirk

2017-10-01

During the past five decades, it has become evident that Adeno-associated virus (AAV) represents one of the most potent, most versatile, and thus most auspicious platforms available for gene delivery into cells, animals and, ultimately, humans. Particularly attractive is the ease with which the viral capsid-the major determinant of virus-host interaction including cell specificity and antibody recognition-can be modified and optimized at will. This has motivated countless researchers to develop high-throughput technologies in which genetically engineered AAV capsid libraries are subjected to a vastly hastened emulation of natural evolution, with the aim to enrich novel synthetic AAV capsids displaying superior features for clinical application. While the power and potential of these forward genetics approaches is undisputed, they are also inherently challenging as success depends on a combination of library quality, fidelity, and complexity. Here, we will describe and discuss two original, very exciting strategies that have emerged over the last three years and that promise to alleviate at least some of these concerns, namely, (i) a reverse genetics approach termed "ancestral AAV sequence reconstruction," and (ii) AAV genome barcoding as a technology that can advance both, forward and reverse genetics stratagems. Notably, despite the conceptual differences of these two technologies, they pursue the same goal which is tailored acceleration of AAV evolution and thus winning the race for the next-generation AAV vectors for clinical use.

Integration of maternal genome into the neonate genome through breast milk mRNA transcripts and reverse transcriptase.

PubMed

Irmak, M Kemal; Oztas, Yesim; Oztas, Emin

2012-06-07

Human milk samples contain microvesicles similar to the retroviruses. These microvesicles contain mRNA transcripts and possess reverse transcriptase activity. They contain about 14,000 transcripts representing the milk transcriptome. Microvesicles are also enriched with proteins related to "caveolar-mediated endocytosis signaling" pathway. It has recently been reported that microvesicles could be transferred to other cells by endocytosis and their RNA content can be translated and be functional in their new location. A significant percentage of the mammalian genome appears to be the product of reverse transcription, containing sequences whose characteristics point to RNA as a template precursor. These are mobile elements that move by way of transposition and are called retrotransposons. We thought that retrotransposons may stem from about 14,000 transcriptome of breast milk microvesicles, and reviewed the literature.The enhanced acceptance of maternal allografts in children who were breast-fed and tolerance to the maternal MHC antigens after breastfeeding may stem from RNAs of the breast milk microvesicles that can be taken up by the breastfed infant and receiving maternal genomic information. We conclude that milk microvesicles may transfer genetic signals from mother to neonate during breastfeeding. Moreover, transfer of wild type RNA from a healthy wet-nurse to the suckling neonate through the milk microvesicles and its subsequent reverse transcription and integration into the neonate genome could result in permanent correction of the clinical manifestations in genetic diseases.

Integration of maternal genome into the neonate genome through breast milk mRNA transcripts and reverse transcriptase

PubMed Central

2012-01-01

Human milk samples contain microvesicles similar to the retroviruses. These microvesicles contain mRNA transcripts and possess reverse transcriptase activity. They contain about 14,000 transcripts representing the milk transcriptome. Microvesicles are also enriched with proteins related to “caveolar-mediated endocytosis signaling” pathway. It has recently been reported that microvesicles could be transferred to other cells by endocytosis and their RNA content can be translated and be functional in their new location. A significant percentage of the mammalian genome appears to be the product of reverse transcription, containing sequences whose characteristics point to RNA as a template precursor. These are mobile elements that move by way of transposition and are called retrotransposons. We thought that retrotransposons may stem from about 14,000 transcriptome of breast milk microvesicles, and reviewed the literature. The enhanced acceptance of maternal allografts in children who were breast-fed and tolerance to the maternal MHC antigens after breastfeeding may stem from RNAs of the breast milk microvesicles that can be taken up by the breastfed infant and receiving maternal genomic information. We conclude that milk microvesicles may transfer genetic signals from mother to neonate during breastfeeding. Moreover, transfer of wild type RNA from a healthy wet-nurse to the suckling neonate through the milk microvesicles and its subsequent reverse transcription and integration into the neonate genome could result in permanent correction of the clinical manifestations in genetic diseases. PMID:22676860

Reconciling genetic evolution and the associative learning account of mirror neurons through data-acquisition mechanisms.

PubMed

Lotem, Arnon; Kolodny, Oren

2014-04-01

An associative learning account of mirror neurons should not preclude genetic evolution of its underlying mechanisms. On the contrary, an associative learning framework for cognitive development should seek heritable variation in the learning rules and in the data-acquisition mechanisms that construct associative networks, demonstrating how small genetic modifications of associative elements can give rise to the evolution of complex cognition.

Assessment of genetic and nongenetic interactions for the prediction of depressive symptomatology: an analysis of the Wisconsin Longitudinal Study using machine learning algorithms.

PubMed

Roetker, Nicholas S; Page, C David; Yonker, James A; Chang, Vicky; Roan, Carol L; Herd, Pamela; Hauser, Taissa S; Hauser, Robert M; Atwood, Craig S

2013-10-01

We examined depression within a multidimensional framework consisting of genetic, environmental, and sociobehavioral factors and, using machine learning algorithms, explored interactions among these factors that might better explain the etiology of depressive symptoms. We measured current depressive symptoms using the Center for Epidemiologic Studies Depression Scale (n = 6378 participants in the Wisconsin Longitudinal Study). Genetic factors were 78 single nucleotide polymorphisms (SNPs); environmental factors-13 stressful life events (SLEs), plus a composite proportion of SLEs index; and sociobehavioral factors-18 personality, intelligence, and other health or behavioral measures. We performed traditional SNP associations via logistic regression likelihood ratio testing and explored interactions with support vector machines and Bayesian networks. After correction for multiple testing, we found no significant single genotypic associations with depressive symptoms. Machine learning algorithms showed no evidence of interactions. Naïve Bayes produced the best models in both subsets and included only environmental and sociobehavioral factors. We found no single or interactive associations with genetic factors and depressive symptoms. Various environmental and sociobehavioral factors were more predictive of depressive symptoms, yet their impacts were independent of one another. A genome-wide analysis of genetic alterations using machine learning methodologies will provide a framework for identifying genetic-environmental-sociobehavioral interactions in depressive symptoms.

Mining the human genome after Association for Molecular Pathology v. Myriad Genetics.

PubMed

Evans, Barbara J

2014-07-01

The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved--but still imperfect--framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics.

Moral landscapes and everyday life in families with Huntington's disease: aligning ethnographic description and bioethics.

PubMed

Huniche, Lotte

2011-06-01

This article is concerned with understanding moral aspects of everyday life in families with Huntington's Disease (HD). It draws on findings from an empirical research project in Denmark in 1998-2002 involving multi-sited ethnography to argue that medical genetics provides a particular framework for conducting life in an HD family. A framework that implies that being informed and making use of genetic services expresses greater moral responsibility than conducting life without drawing on these resources. The moral imperative of engagement in medical genetics is challenged here by two pieces of ethnographic analysis. The first concerns a person who, as described by a family member, does not engage with medical genetics but who brings to the fore other culturally legitimate concerns, priorities and areas of responsibility. The second figures a genetic counselling session where neither the knowledge nor the imagined solutions of medical genetics are as unproblematic and straightforward as might be thought. To assist our understanding of the moral aspects of living with severe familial disease, the ethnographic analysis is aligned with bioethical reflections that place the concrete concerns of those personally involved centre stage in the development of theoretical stances that aim to assist reflections in practice. Copyright © 2010 Elsevier Ltd. All rights reserved.

Solving TSP problem with improved genetic algorithm

NASA Astrophysics Data System (ADS)

Fu, Chunhua; Zhang, Lijun; Wang, Xiaojing; Qiao, Liying

2018-05-01

The TSP is a typical NP problem. The optimization of vehicle routing problem (VRP) and city pipeline optimization can use TSP to solve; therefore it is very important to the optimization for solving TSP problem. The genetic algorithm (GA) is one of ideal methods in solving it. The standard genetic algorithm has some limitations. Improving the selection operator of genetic algorithm, and importing elite retention strategy can ensure the select operation of quality, In mutation operation, using the adaptive algorithm selection can improve the quality of search results and variation, after the chromosome evolved one-way evolution reverse operation is added which can make the offspring inherit gene of parental quality improvement opportunities, and improve the ability of searching the optimal solution algorithm.

"What's the difference?" women's wheelchair basketball, reverse integration, and the question(ing) of disability.

PubMed

Spencer-Cavaliere, Nancy; Peers, Danielle

2011-10-01

The inclusion of able-bodied athletes within disability sport, a phenomenon known as reverse integration, has sparked significant debate within adapted physical activity. Although researchers and practitioners have taken up positions for or against reverse integration, there is a lack of supporting research on the experiences of athletes who already play in such settings. In this study, we explore how competitive female athletes who have a disability experience reverse integration in Canadian wheelchair basketball. Athletic identity was used as the initial conceptual framework to guide semistructured interviews with nine participants. The results suggest that participation in this context contributed to positive athletic identities. Interviews also pointed to the unexpected theme of "what's the difference?" that this sporting context provided a space for the questioning and creative negotiation of the categories of disability and able-bodiedness. Methodologically, this paper also explores the possibilities and challenges of inter- worldview and insider-outsider research collaboration.

Genetics and recent human evolution.

PubMed

Templeton, Alan R

2007-07-01

Starting with "mitochondrial Eve" in 1987, genetics has played an increasingly important role in studies of the last two million years of human evolution. It initially appeared that genetic data resolved the basic models of recent human evolution in favor of the "out-of-Africa replacement" hypothesis in which anatomically modern humans evolved in Africa about 150,000 years ago, started to spread throughout the world about 100,000 years ago, and subsequently drove to complete genetic extinction (replacement) all other human populations in Eurasia. Unfortunately, many of the genetic studies on recent human evolution have suffered from scientific flaws, including misrepresenting the models of recent human evolution, focusing upon hypothesis compatibility rather than hypothesis testing, committing the ecological fallacy, and failing to consider a broader array of alternative hypotheses. Once these flaws are corrected, there is actually little genetic support for the out-of-Africa replacement hypothesis. Indeed, when genetic data are used in a hypothesis-testing framework, the out-of-Africa replacement hypothesis is strongly rejected. The model of recent human evolution that emerges from a statistical hypothesis-testing framework does not correspond to any of the traditional models of human evolution, but it is compatible with fossil and archaeological data. These studies also reveal that any one gene or DNA region captures only a small part of human evolutionary history, so multilocus studies are essential. As more and more loci became available, genetics will undoubtedly offer additional insights and resolutions of human evolution.

Soul on Silicon.

ERIC Educational Resources Information Center

Kurzweil, Raymond C.

1994-01-01

Summarizes recent advances in computer simulation and "reverse engineering" technologies, highlighting the Human Genome Project to scan the human genetic code; artificial retina chips to copy the human retina's neural organization; high-speed, high-resolution Magnetic Resonance Imaging scanners; and the virtual book. Discusses…

Crime and Child-Rearing.

ERIC Educational Resources Information Center

Roth, Byron M.

1996-01-01

Examines the notion that heredity plays a powerful role in criminal behavior, including genetic evidence that can allow for antisocial behavior. Reviews suggestions for reversing rising crime rates in light of the hereditary connection, policy development, family cohesion, and child raising. (GR)

Universal Influenza B Virus Genomic Amplification Facilitates Sequencing, Diagnostics, and Reverse Genetics

PubMed Central

Zhou, Bin; Lin, Xudong; Wang, Wei; Halpin, Rebecca A.; Bera, Jayati; Stockwell, Timothy B.; Barr, Ian G.

2014-01-01

Although human influenza B virus (IBV) is a significant human pathogen, its great genetic diversity has limited our ability to universally amplify the entire genome for subsequent sequencing or vaccine production. The generation of sequence data via next-generation approaches and the rapid cloning of viral genes are critical for basic research, diagnostics, antiviral drugs, and vaccines to combat IBV. To overcome the difficulty of amplifying the diverse and ever-changing IBV genome, we developed and optimized techniques that amplify the complete segmented negative-sense RNA genome from any IBV strain in a single tube/well (IBV genomic amplification [IBV-GA]). Amplicons for >1,000 diverse IBV genomes from different sample types (e.g., clinical specimens) were generated and sequenced using this robust technology. These approaches are sensitive, robust, and sequence independent (i.e., universally amplify past, present, and future IBVs), which facilitates next-generation sequencing and advanced genomic diagnostics. Importantly, special terminal sequences engineered into the optimized IBV-GA2 products also enable ligation-free cloning to rapidly generate reverse-genetics plasmids, which can be used for the rescue of recombinant viruses and/or the creation of vaccine seed stock. PMID:24501036

Updating the Micro-Tom TILLING platform.

PubMed

Okabe, Yoshihiro; Ariizumi, Tohru; Ezura, Hiroshi

2013-03-01

The dwarf tomato variety Micro-Tom is regarded as a model system for functional genomics studies in tomato. Various tomato genomic tools in the genetic background of Micro-Tom have been established, such as mutant collections, genome information and a metabolomic database. Recent advances in tomato genome sequencing have brought about a significant need for reverse genetics tools that are accessible to the larger community, because a great number of gene sequences have become available from public databases. To meet the requests from the tomato research community, we have developed the Micro-Tom Targeting-Induced Local Lesions IN Genomes (TILLING) platform, which is comprised of more than 5000 EMS-mutagenized lines. The platform serves as a reverse genetics tool for efficiently identifying mutant alleles in parallel with the development of Micro-Tom mutant collections. The combination of Micro-Tom mutant libraries and the TILLING approach enables researchers to accelerate the isolation of desirable mutants for unraveling gene function or breeding. To upgrade the genomic tool of Micro-Tom, the development of a new mutagenized population is underway. In this paper, the current status of the Micro-Tom TILLING platform and its future prospects are described.

The Cyber Military Revolution and the Need for a New Framework of War

DTIC Science & Technology

2012-04-16

upon a better ability to discover and synthesize linkages and relationships between the variables and factors observed, one’s genetic heritage, social...system. The inclusion of the proposed revised framework of war in the capstone joint doctrine guidance document would provide a rubric of warfare

The Piirto Pyramid of Talent Development: A Conceptual Framework for Talking about Talent.

ERIC Educational Resources Information Center

Piirto, Jane

2000-01-01

This article presents the "Piirto Pyramid" framework for identification of talent potential. It explains how the pyramid identifies influences that are significant in the development of talents, including genetics, personality attributes, cognitive ability, talent, vocational, and environmental. Examples using Roy Rogers and Michelangelo are…

An Evolutionary Framework for Behavioral Research.

ERIC Educational Resources Information Center

Freedman, D. G.

The author proposes a framework for the study of behavior and personality that takes into account phylogeny (development of genetically related groups of organisms) as well as ontogeny (course of development of an individual organism). The adaptive function of behavior is stressed. The author states that individual personality is a unique…

Molecular Genetic Analysis of Chlamydia Species.

PubMed

Sixt, Barbara S; Valdivia, Raphael H

2016-09-08

Species of Chlamydia are the etiologic agent of endemic blinding trachoma, the leading cause of bacterial sexually transmitted diseases, significant respiratory pathogens, and a zoonotic threat. Their dependence on an intracellular growth niche and their peculiar developmental cycle are major challenges to elucidating their biology and virulence traits. The last decade has seen tremendous advances in our ability to perform a molecular genetic analysis of Chlamydia species. Major achievements include the generation of large collections of mutant strains, now available for forward- and reverse-genetic applications, and the introduction of a system for plasmid-based transformation enabling complementation of mutations; expression of foreign, modified, or reporter genes; and even targeted gene disruptions. This review summarizes the current status of the molecular genetic toolbox for Chlamydia species and highlights new insights into their biology and new challenges in the nascent field of Chlamydia genetics.

Theobroma cacao: A genetically integrated physical map and genome-scale comparative synteny analysis

USDA-ARS?s Scientific Manuscript database

A comprehensive integrated genomic framework is considered a centerpiece of genomic research. In collaboration with the USDA-ARS (SHRS) and Mars Inc., the Clemson University Genomics Institute (CUGI) has developed a genetically anchored physical map of the T. cacao genome. Three BAC libraries contai...

MULTI-OBJECTIVE OPTIMAL DESIGN OF GROUNDWATER REMEDIATION SYSTEMS: APPLICATION OF THE NICHED PARETO GENETIC ALGORITHM (NPGA). (R826614)

EPA Science Inventory

A multiobjective optimization algorithm is applied to a groundwater quality management problem involving remediation by pump-and-treat (PAT). The multiobjective optimization framework uses the niched Pareto genetic algorithm (NPGA) and is applied to simultaneously minimize the...

Filling the knowledge gap: Integrating quantitative genetics and genomics in graduate education and outreach

USDA-ARS?s Scientific Manuscript database

The genomics revolution provides vital tools to address global food security. Yet to be incorporated into livestock breeding, molecular techniques need to be integrated into a quantitative genetics framework. Within the U.S., with shrinking faculty numbers with the requisite skills, the capacity to ...

The group II intron maturase: a reverse transcriptase and splicing factor go hand in hand.

PubMed

Zhao, Chen; Pyle, Anna Marie

2017-12-01

The splicing of group II introns in vivo requires the assistance of a multifunctional intron encoded protein (IEP, or maturase). Each IEP is also a reverse-transcriptase enzyme that enables group II introns to behave as mobile genetic elements. During splicing or retro-transposition, each group II intron forms a tight, specific complex with its own encoded IEP, resulting in a highly reactive holoenzyme. This review focuses on the structural basis for IEP function, as revealed by recent crystal structures of an IEP reverse transcriptase domain and cryo-EM structures of an IEP-intron complex. These structures explain how the same IEP scaffold is utilized for intron recognition, splicing and reverse transcription, while providing a physical basis for understanding the evolutionary transformation of the IEP into the eukaryotic splicing factor Prp8. Copyright © 2017 Elsevier Ltd. All rights reserved.

Storytellers as partners in developing a genetics education resource for health professionals

PubMed Central

Kirk, Maggie; Tonkin, Emma; Skirton, Heather; McDonald, Kevin; Cope, Buddug; Morgan, Rhian

2013-01-01

Summary Advances in genetics are bringing unprecedented opportunities for understanding health and disease, developing new therapies and changes in healthcare practice. Many nurses and midwives lack competence and confidence in integrating genetics into professional practice. One approach to enhance understanding of genetics is to simulate clinical exposure through storytelling. Stories are acknowledged as a powerful learning tool, being understandable and memorable, stimulating critical thinking, and linking theory to practice. Telling Stories, Understanding Real Life Genetics is a freely accessible website that sets people's stories within an education framework. The links between the stories and professional practice are made explicit and additional features support learning and teaching. Care of the storytellers within an ethical framework is of paramount importance. Storytellers are viewed as partners in the project. The challenges encountered include preserving the authentic voice and dignity of the storyteller. Project team members have also experienced ‘professional shame’ when negative experiences have been recounted, and the stories have had an impact on the team. The experience of working with storytellers has been positive. The storytellers want to be heard so that others will benefit from their stories. They serve as a reminder of why this work is important. PMID:22197414

Predicting the genetic consequences of future climate change: The power of coupling spatial demography, the coalescent, and historical landscape changes.

PubMed

Brown, Jason L; Weber, Jennifer J; Alvarado-Serrano, Diego F; Hickerson, Michael J; Franks, Steven J; Carnaval, Ana C

2016-01-01

Climate change is a widely accepted threat to biodiversity. Species distribution models (SDMs) are used to forecast whether and how species distributions may track these changes. Yet, SDMs generally fail to account for genetic and demographic processes, limiting population-level inferences. We still do not understand how predicted environmental shifts will impact the spatial distribution of genetic diversity within taxa. We propose a novel method that predicts spatially explicit genetic and demographic landscapes of populations under future climatic conditions. We use carefully parameterized SDMs as estimates of the spatial distribution of suitable habitats and landscape dispersal permeability under present-day, past, and future conditions. We use empirical genetic data and approximate Bayesian computation to estimate unknown demographic parameters. Finally, we employ these parameters to simulate realistic and complex models of responses to future environmental shifts. We contrast parameterized models under current and future landscapes to quantify the expected magnitude of change. We implement this framework on neutral genetic data available from Penstemon deustus. Our results predict that future climate change will result in geographically widespread declines in genetic diversity in this species. The extent of reduction will heavily depend on the continuity of population networks and deme sizes. To our knowledge, this is the first study to provide spatially explicit predictions of within-species genetic diversity using climatic, demographic, and genetic data. Our approach accounts for climatic, geographic, and biological complexity. This framework is promising for understanding evolutionary consequences of climate change, and guiding conservation planning. © 2016 Botanical Society of America.

Genetic manipulation for inherited neurodegenerative diseases: myth or reality?

PubMed Central

Yu-Wai-Man, Patrick

2016-01-01

Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation. PMID:27002113

Reverse Engineering of Genome-wide Gene Regulatory Networks from Gene Expression Data

PubMed Central

Liu, Zhi-Ping

2015-01-01

Transcriptional regulation plays vital roles in many fundamental biological processes. Reverse engineering of genome-wide regulatory networks from high-throughput transcriptomic data provides a promising way to characterize the global scenario of regulatory relationships between regulators and their targets. In this review, we summarize and categorize the main frameworks and methods currently available for inferring transcriptional regulatory networks from microarray gene expression profiling data. We overview each of strategies and introduce representative methods respectively. Their assumptions, advantages, shortcomings, and possible improvements and extensions are also clarified and commented. PMID:25937810

Acylphloroglucinol biosynthesis in strawberry fruit

USDA-ARS?s Scientific Manuscript database

Phenolics have health-promoting properties and are a major group of metabolites in fruit crops. Through reverse genetic analysis of the functions of four ripening-related genes in the octoploid strawberry, Fragaria ×ananassa, we discovered four acylphloroglucinol (APG)-glucosides as native strawberr...

Reinventing potato at the diploid level

USDA-ARS?s Scientific Manuscript database

The outcrossing polyploidy nature of cultivated potato has hindered the use of genomics resources to dissect the genetic basis of agronomically important traits. Reversion to the diploid level allows us to apply powerful tools toward this effort. Parthenogenesis generates diploid cultivated potato, ...

Polyglot Programming in Applications Used for Genetic Data Analysis

PubMed Central

Nowak, Robert M.

2014-01-01

Applications used for the analysis of genetic data process large volumes of data with complex algorithms. High performance, flexibility, and a user interface with a web browser are required by these solutions, which can be achieved by using multiple programming languages. In this study, I developed a freely available framework for building software to analyze genetic data, which uses C++, Python, JavaScript, and several libraries. This system was used to build a number of genetic data processing applications and it reduced the time and costs of development. PMID:25197633

Polyglot programming in applications used for genetic data analysis.

PubMed

Nowak, Robert M

2014-01-01

Applications used for the analysis of genetic data process large volumes of data with complex algorithms. High performance, flexibility, and a user interface with a web browser are required by these solutions, which can be achieved by using multiple programming languages. In this study, I developed a freely available framework for building software to analyze genetic data, which uses C++, Python, JavaScript, and several libraries. This system was used to build a number of genetic data processing applications and it reduced the time and costs of development.

A substitution in the transmembrane region of the glycoprotein leads to an unstable attenuation of Machupo virus.

PubMed

Patterson, Michael; Koma, Takaaki; Seregin, Alexey; Huang, Cheng; Miller, Milagros; Smith, Jennifer; Yun, Nadezhda; Smith, Jeanon; Paessler, Slobodan

2014-09-01

Machupo virus (MACV) is the etiologic agent of Bolivian hemorrhagic fever (BHF). Utilizing a reverse-genetics system recently developed, we report the rescue of a rationally modified recombinant MACV containing a single mutation in the transmembrane region of the glycoprotein. Following challenge of susceptible mice, we identified a significant reduction in virulence in the novel virus. We also identified an instability leading to reversion of the single mutation to a wild-type genotype. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Forensic interpretation of molecular variation on networks of disease transmission and genetic inheritance.

PubMed

Velsko, Stephan P; Osburn, Joanne; Allen, Jonathan

2014-11-01

This paper describes the inference-on-networks (ION) framework for forensic interpretat ION of molecular typing data in cases involving allegations of infectious microbial transmission, association of disease outbreaks with alleged sources, and identifying familial relationships using mitochondrial or Y chromosomal DNA. The framework is applicable to molecular typing data obtained using any technique, including those based on electrophoretic separations. A key insight is that the networks associated with disease transmission or DNA inheritance can be used to define specific testable relationships and avoid the ambiguity and subjectivity associated with the criteria used for inferring genetic relatedness now in use. We discuss specific applications of the framework to the 2003 severe acute respiratory syndrome (SARS) outbreak in Singapore and the 2001 foot-and-mouth disease virus (FMDV) outbreak in Great Britain. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

PRESAGE: PRivacy-preserving gEnetic testing via SoftwAre Guard Extension.

PubMed

Chen, Feng; Wang, Chenghong; Dai, Wenrui; Jiang, Xiaoqian; Mohammed, Noman; Al Aziz, Md Momin; Sadat, Md Nazmus; Sahinalp, Cenk; Lauter, Kristin; Wang, Shuang

2017-07-26

Advances in DNA sequencing technologies have prompted a wide range of genomic applications to improve healthcare and facilitate biomedical research. However, privacy and security concerns have emerged as a challenge for utilizing cloud computing to handle sensitive genomic data. We present one of the first implementations of Software Guard Extension (SGX) based securely outsourced genetic testing framework, which leverages multiple cryptographic protocols and minimal perfect hash scheme to enable efficient and secure data storage and computation outsourcing. We compared the performance of the proposed PRESAGE framework with the state-of-the-art homomorphic encryption scheme, as well as the plaintext implementation. The experimental results demonstrated significant performance over the homomorphic encryption methods and a small computational overhead in comparison to plaintext implementation. The proposed PRESAGE provides an alternative solution for secure and efficient genomic data outsourcing in an untrusted cloud by using a hybrid framework that combines secure hardware and multiple crypto protocols.

A rapid method for establishment of a reverse genetics system for canine parvovirus.

PubMed

Yu, Yongle; Su, Jun; Wang, Jigui; Xi, Ji; Mao, Yaping; Hou, Qiang; Zhang, Xiaomei; Liu, Weiquan

2017-12-01

Canine parvovirus (CPV) is an important and highly prevalent pathogen of dogs that causes acute hemorrhagic enteritis disease. Here, we describe a rapid method for the construction and characterization of a full-length infectious clone (rCPV) of CPV. Feline kidney (F81) cells were transfected with rCPV incorporating an engineered EcoR I site that served as a genetic marker. The rescued virus was indistinguishable from that of wild-type virus in its biological properties.

Pressure-induced reversible amorphization and an amorphous–amorphous transition in Ge2Sb2Te5 phase-change memory material

PubMed Central

Sun, Zhimei; Zhou, Jian; Pan, Yuanchun; Song, Zhitang; Mao, Ho-Kwang; Ahuja, Rajeev

2011-01-01

Ge2Sb2Te5 (GST) is a technologically very important phase-change material that is used in digital versatile disks-random access memory and is currently studied for the use in phase-change random access memory devices. This type of data storage is achieved by the fast reversible phase transition between amorphous and crystalline GST upon heat pulse. Here we report pressure-induced reversible crystalline-amorphous and polymorphic amorphous transitions in NaCl structured GST by ab initio molecular dynamics calculations. We have showed that the onset amorphization of GST starts at approximately 18 GPa and the system become completely random at approximately 22 GPa. This amorphous state has a cubic framework (c-amorphous) of sixfold coordinations. With further increasing pressure, the c-amorphous transforms to a high-density amorphous structure with trigonal framework (t-amorphous) and an average coordination number of eight. The pressure-induced amorphization is investigated to be due to large displacements of Te atoms for which weak Te–Te bonds exist or vacancies are nearby. Upon decompressing to ambient conditions, the original cubic crystalline structure is restored for c-amorphous, whereas t-amorphous transforms to another amorphous phase that is similar to the melt-quenched amorphous GST. PMID:21670255

Pressure-induced reversible amorphization and an amorphous-amorphous transition in Ge₂Sb₂Te₅ phase-change memory material.

PubMed

Sun, Zhimei; Zhou, Jian; Pan, Yuanchun; Song, Zhitang; Mao, Ho-Kwang; Ahuja, Rajeev

2011-06-28

Ge(2)Sb(2)Te(5) (GST) is a technologically very important phase-change material that is used in digital versatile disks-random access memory and is currently studied for the use in phase-change random access memory devices. This type of data storage is achieved by the fast reversible phase transition between amorphous and crystalline GST upon heat pulse. Here we report pressure-induced reversible crystalline-amorphous and polymorphic amorphous transitions in NaCl structured GST by ab initio molecular dynamics calculations. We have showed that the onset amorphization of GST starts at approximately 18 GPa and the system become completely random at approximately 22 GPa. This amorphous state has a cubic framework (c-amorphous) of sixfold coordinations. With further increasing pressure, the c-amorphous transforms to a high-density amorphous structure with trigonal framework (t-amorphous) and an average coordination number of eight. The pressure-induced amorphization is investigated to be due to large displacements of Te atoms for which weak Te-Te bonds exist or vacancies are nearby. Upon decompressing to ambient conditions, the original cubic crystalline structure is restored for c-amorphous, whereas t-amorphous transforms to another amorphous phase that is similar to the melt-quenched amorphous GST.

Prediction and prevention of parasitic diseases using a landscape genomics framework

PubMed Central

Schwabl, Philipp; Llewellyn, Martin; Landguth, Erin L.; Andersson, Björn; Kitron, Uriel; Costales, Jaime A.; Ocaña, Sofía; Grijalva, Mario J.

2016-01-01

Summary Substantial heterogeneity exists in the dispersal, distribution and transmission of parasitic species. Understanding and predicting how such features are governed by the ecological variation of landscape they inhabit is the central goal of spatial epidemiology. Genetic data can further inform functional connectivity among parasite, host and vector populations in a landscape. Gene flow correlates with the spread of epidemiologically relevant phenotypes among parasite and vector populations (e.g., virulence, drug and pesticide resistance), as well as invasion and re-invasion risk where parasite transmission is absent due to current or past intervention measures. However, the formal integration of spatial and genetic data (‘landscape genetics’) is scarcely ever applied to parasites. Here, we discuss the specific challenges and practical prospects for the use of landscape genetics and genomics to understand the biology and control of parasitic disease and present a practical framework for doing so. PMID:27863902

Sex Reversal in C57BL/6J XY Mice Caused by Increased Expression of Ovarian Genes and Insufficient Activation of the Testis Determining Pathway

PubMed Central

Correa, Stephanie M.; Washburn, Linda L.; Kahlon, Ravi S.; Musson, Michelle C.; Bouma, Gerrit J.; Eicher, Eva M.; Albrecht, Kenneth H.

2012-01-01

Sex reversal can occur in XY humans with only a single functional WT1 or SF1 allele or a duplication of the chromosome region containing WNT4. In contrast, XY mice with only a single functional Wt1, Sf1, or Wnt4 allele, or mice that over-express Wnt4 from a transgene, reportedly are not sex-reversed. Because genetic background plays a critical role in testis differentiation, particularly in C57BL/6J (B6) mice, we tested the hypothesis that Wt1, Sf1, and Wnt4 are dosage sensitive in B6 XY mice. We found that reduced Wt1 or Sf1 dosage in B6 XYB6 mice impaired testis differentiation, but no ovarian tissue developed. If, however, a YAKR chromosome replaced the YB6 chromosome, these otherwise genetically identical B6 XY mice developed ovarian tissue. In contrast, reduced Wnt4 dosage increased the amount of testicular tissue present in Sf1+/− B6 XYAKR, Wt1+/− B6 XYAKR, B6 XYPOS, and B6 XYAKR fetuses. We propose that Wt1B6 and Sf1B6 are hypomorphic alleles of testis-determining pathway genes and that Wnt4B6 is a hypermorphic allele of an ovary-determining pathway gene. The latter hypothesis is supported by the finding that expression of Wnt4 and four other genes in the ovary-determining pathway are elevated in normal B6 XX E12.5 ovaries. We propose that B6 mice are sensitive to XY sex reversal, at least in part, because they carry Wt1B6 and/or Sf1B6 alleles that compromise testis differentiation and a Wnt4B6 allele that promotes ovary differentiation and thereby antagonizes testis differentiation. Addition of a “weak” Sry allele, such as the one on the YPOS chromosome, to the sensitized B6 background results in inappropriate development of ovarian tissue. We conclude that Wt1, Sf1, and Wnt4 are dosage-sensitive in mice, this dosage-sensitivity is genetic background-dependant, and the mouse strains described here are good models for the investigation of human dosage-sensitive XY sex reversal. PMID:22496664

Crystal conversion between metal-organic frameworks with different crystal topologies for efficient crystal design on two-dimensional substrates

NASA Astrophysics Data System (ADS)

Tsuruoka, Takaaki; Inoue, Kohei; Miyanaga, Ayumi; Tobiishi, Kaho; Ohhashi, Takashi; Hata, Manami; Takashima, Yohei; Akamatsu, Kensuke

2018-04-01

Crystal conversion of metal-organic frameworks (MOFs) between different crystal topologies on a polymer substrate has been successfully achieved by localized dissolution of MOF crystals followed by a rapid self-assembly of framework components. Upon addition of the desired organic linkers to the reaction system containing MOF crystals on the substrate, reversible crystal conversion between the [Cu2(btc)3]n and [Cu2(ndc)2(dabco)]n frameworks (btc = 1,3,5-benzene tricarboxylate, ndc = 1,4-naphthalene dicarboxylate, dabco = 1,4-diazabicyclo[2.2.2]octane) could be routinely achieved in high yields. Most surprisingly, in the case of conversion from the [Cu2(ndc)2(dabco)]n to [Cu2(btc)3]n frameworks, the [Cu2(btc)3]n crystals with unique shapes (cuboctahedron and truncated cube) could be prepared using butanol as a reaction medium.

Mechanism of cell alignment in groups of Myxococcus xanthus bacteria

NASA Astrophysics Data System (ADS)

Balgam, Rajesh; Igoshin, Oleg

2015-03-01

Myxococcus xanthus is a model for studying self-organization in bacteria. These flexible cylindrical bacteria move along. In groups, M. xanthus cells align themselves into dynamic cell clusters but the mechanism underlying their formation is unknown. It has been shown that steric interactions can cause alignment in self-propelled hard rods but it is not clear how flexibility and reversals affect the alignment and cluster formation. We have investigated cell alignment process using our biophysical model of M. xanthus cell in an agent-based simulation framework under realistic cell flexibility values. We observed that flexible model cells can form aligned cell clusters when reversals are suppressed but these clusters disappeared when reversals frequency becomes similar to the observed value. However, M. xanthus cells follow slime (polysaccharide gel like material) trails left by other cells and we show that implementing this into our model rescues cell clustering for reversing cells. Our results show that slime following along with periodic cell reversals act as positive feedback to reinforce existing slime trails and recruit more cells. Furthermore, we have observed that mechanical cell alignment combined with slime following is sufficient to explain the distinct clustering patterns of reversing and non-reversing cells as observed in recent experiments. This work is supported by NSF MCB 0845919 and 1411780.

Reversing gestational undernutrition via kick-starting early growth

USDA-ARS?s Scientific Manuscript database

Poor maternal nutrition enhances chronic disease risk in the offspring. The conceptual framework for this association is provided by the developmental origins of health and disease (DoHAD) hypothesis which suggests that unfavorable prenatal and postnatal environments, lead to permanent alterations i...

Thermal Conductivity of Liquid Water from Reverse Nonequilibrium Ab Initio Molecular Dynamics

NASA Astrophysics Data System (ADS)

Tsuchida, Eiji

2018-02-01

We report on a theoretical framework for calculating the thermal conductivity of liquid water from first principles with the aid of the linear scaling method. We also discuss the possibility of obtaining equilibrium properties from a nonequilibrium trajectory.

Two-fluid dynamo relaxation and momentum transport induced by CHI on HIST

NASA Astrophysics Data System (ADS)

Nagata, Masayoshi; Hirono, Hidetoshi; Hanao, Takafumi; Hyobu, Takahiro; Ito, Kengo; Matsumoto, Keisuke; Nakayama, Takashi; Oki, Nobuharu; Kikuchi, Yusuke; Fukumoto, Naoyuki

2013-10-01

Non-inductive current drive by using Multi-pulsing coaxial helicity injection was studied on HIST. In the double-pulsing CHI experiment, we have examined two-fluid effects by reversing polarity of the bias poloidal coil current. In the ST magnetic configurations with the right-handed magnetic field (positive CHI), there are a diamagnetic structure in the open flux column region and a paramagnetic structure in the closed flux region. It is naturally understood that the direction of the poloidal magnetic field (toroidal current) is reversed in reversing the polarity of the bias flux from positive to negative. However, the poloidal current is surprisingly reversed in reversing the magnetic helicity polarity. The direction of the poloidal current is opposite in the each region. The toroidal flow is reversed, but a shear profile of the poloidal flow is not changed significantly. In this configuration, the diamagnetic structure appears in the closed flux region. Thus, not only Jt×Bp but also Jp×Bt force contributes on pressure balance leading to a higher beta. We are studying a more general helicity conservation that constrains the interaction between flows and magnetic fields and momentum transport in the two-fluid framework.

Conceptual Variation in the Depiction of Gene Function in Upper Secondary School Textbooks

ERIC Educational Resources Information Center

Gericke, Niklas Markus; Hagberg, Mariana

2010-01-01

This paper explores conceptual variation in the depiction of gene function in upper secondary school textbooks. Historically, concepts in genetics have developed in various scientific frameworks, which has led to a level of incommensurability as concepts have changed over time within their respective frameworks. Since students may have…

Some Thoughts on Essence Placeholders, Interactionism, and Heritability: Reply to Haslam (2011) and Turkheimer (2011)

ERIC Educational Resources Information Center

Dar-Nimrod, Ilan; Heine, Steven J.

2011-01-01

In the target article (Dar-Nimrod & Heine, 2011), we provided a social-cognitive framework which identified genetic essentialist biases and their implications. In their commentaries, Haslam (2011) and Turkheimer (2011) indicated their general agreement with this framework but highlighted some important points for consideration. Haslam…

ActionMap: A web-based software that automates loci assignments to framework maps.

PubMed

Albini, Guillaume; Falque, Matthieu; Joets, Johann

2003-07-01

Genetic linkage computation may be a repetitive and time consuming task, especially when numerous loci are assigned to a framework map. We thus developed ActionMap, a web-based software that automates genetic mapping on a fixed framework map without adding the new markers to the map. Using this tool, hundreds of loci may be automatically assigned to the framework in a single process. ActionMap was initially developed to map numerous ESTs with a small plant mapping population and is limited to inbred lines and backcrosses. ActionMap is highly configurable and consists of Perl and PHP scripts that automate command steps for the MapMaker program. A set of web forms were designed for data import and mapping settings. Results of automatic mapping can be displayed as tables or drawings of maps and may be exported. The user may create personal access-restricted projects to store raw data, settings and mapping results. All data may be edited, updated or deleted. ActionMap may be used either online or downloaded for free (http://moulon.inra.fr/~bioinfo/).

ActionMap: a web-based software that automates loci assignments to framework maps

PubMed Central

Albini, Guillaume; Falque, Matthieu; Joets, Johann

2003-01-01

Genetic linkage computation may be a repetitive and time consuming task, especially when numerous loci are assigned to a framework map. We thus developed ActionMap, a web-based software that automates genetic mapping on a fixed framework map without adding the new markers to the map. Using this tool, hundreds of loci may be automatically assigned to the framework in a single process. ActionMap was initially developed to map numerous ESTs with a small plant mapping population and is limited to inbred lines and backcrosses. ActionMap is highly configurable and consists of Perl and PHP scripts that automate command steps for the MapMaker program. A set of web forms were designed for data import and mapping settings. Results of automatic mapping can be displayed as tables or drawings of maps and may be exported. The user may create personal access-restricted projects to store raw data, settings and mapping results. All data may be edited, updated or deleted. ActionMap may be used either online or downloaded for free (http://moulon.inra.fr/~bioinfo/). PMID:12824426

46,XX males: a case series based on clinical and genetics evaluation.

PubMed

Mohammadpour Lashkari, F; Totonchi, M; Zamanian, M R; Mansouri, Z; Sadighi Gilani, M A; Sabbaghian, M; Mohseni Meybodi, A

2017-09-01

46,XX male sex reversal syndrome is one of the rarest sex chromosomal aberrations. The presence of SRY gene on one of the X chromosomes is the most frequent cause of this syndrome. Based on Y chromosome profile, there are SRY-positive and SRY-negative forms. The purpose of our study was to report first case series of Iranian patients and describe the different clinical appearances based on their genetic component. From the 8,114 azoospermic and severe oligozoospermic patients referred to Royan institute, we diagnosed 57 cases as sex reversal patients. Based on the endocrinological history, we performed karyotyping, SRY and AZF microdeletion screening. Patients had a female karyotype. According to available hormonal reports of 37 patients, 16 cases had low levels of testosterone (43.2%). On the other hand, 15 males were SRY positive (90.2%), while they lacked the spermatogenic factors encoding genes on Yq. Commencing the testicular differentiation in males, the SRY gene is considered to be very important in this process. Due to homogeneous results of karyotyping and AZF deletion, there are both positive and negative SRY cases that show similar sex reversal phenotypes. Evidences show that there could be diverse phenotypic differences that could be raised from various reasons. © 2016 Blackwell Verlag GmbH.

Genetic testing: medico-legal issues.

PubMed

Bird, Sara

2014-07-01

The availability and frequency of genetic testing is increasing. Genetic testing poses some unique ethical and legal issues for medical practitioners because of the potential to identify genetic variants that carry implications for the risk of disease in the future for the patient and their relatives. The regulatory framework within which genetic testing is provided in Australia is also changing. This article examines some medico-legal issues associated with genetic testing that general practitioners (GPs) are likely encounter in their practices. There is inevitable involvement of the GP in the long term care of a patient (and possibly their family) following genetic testing, regardless of whether or not the GP has ordered the testing. Cases are presented to illustrate some of the medico-legal issues that may arise from direct-to-consumer genetic testing, information disclosure to genetic relatives and requests for parentage testing.

A model for 'reverse innovation' in health care.

PubMed

Depasse, Jacqueline W; Lee, Patrick T

2013-08-30

'Reverse innovation,' a principle well established in the business world, describes the flow of ideas from emerging to more developed economies. There is strong and growing interest in applying this concept to health care, yet there is currently no framework for describing the stages of reverse innovation or identifying opportunities to accelerate the development process. This paper combines the business concept of reverse innovation with diffusion of innovation theory to propose a model for reverse innovation as a way to innovate in health care. Our model includes the following steps: (1) identifying a problem common to lower- and higher-income countries; (2) innovation and spread in the low-income country (LIC); (3) crossover to the higher-income country (HIC); and (4) innovation and spread in the HIC. The crucial populations in this pathway, drawing from diffusion of innovation theory, are LIC innovators, LIC early adopters, and HIC innovators. We illustrate the model with three examples of current reverse innovations. We then propose four sets of specific actions that forward-looking policymakers, entrepreneurs, health system leaders, and researchers may take to accelerate the movement of promising solutions through the reverse innovation pipeline: (1) identify high-priority problems shared by HICs and LICs; (2) create slack for change, especially for LIC innovators, LIC early adopters, and HIC innovators; (3) create spannable social distances between LIC early adopters and HIC innovators; and (4) measure reverse innovation activity globally.

Product-to-parent reversion increases ecosystem exposure to and environmental persistence of 17α-trenbolone

NASA Astrophysics Data System (ADS)

Ward, Adam; Cwiertny, David; Kolodziej, Edward; Brehm, Colleen

2016-04-01

The product-to-parent reversion of metabolites of trenbolone acetate (TBA), a steroidal growth promoter used widely in beef cattle production, was recently observed to occur in environmental waters. The rapid forward reaction is by direct photolysis (i.e., photohydration), with the much slower reversion reaction occurring via dehydration in the dark. The objective of this study is to quantify the potential effect of this newly discovered reversible process on TBA metabolite concentrations and total bioactivity exposure in fluvial systems. Here, we demonstrate increased persistence of TBA metabolites in the stream and hyporheic zone due to the reversion process, increasing chronic and acute exposure to these endocrine-active compounds along a stream. The perpetually dark hyporheic zone is a key location for reversion in the system, ultimately providing a source of the parent compound to the stream and increasing mean in-stream concentration of 17α-trenbolone (17α-TBOH) by 40% of the input concentration under representative fluvial conditions. We demonstrate generalized cases for prediction of exposure for species with product-to-parent reversion in stream-hyporheic systems. Recognizing this risk, regulatory frameworks for compounds undergoing product-to-parent reversion will require new approaches for assessing total exposure to bioactive compounds. We discuss the role of regulating "joint" or "mixture" bioactivity as an emerging paradigm for more meaningful management of micropollutants.

Generating Alternative Engineering Designs by Integrating Desktop VR with Genetic Algorithms

ERIC Educational Resources Information Center

Chandramouli, Magesh; Bertoline, Gary; Connolly, Patrick

2009-01-01

This study proposes an innovative solution to the problem of multiobjective engineering design optimization by integrating desktop VR with genetic computing. Although, this study considers the case of construction design as an example to illustrate the framework, this method can very much be extended to other engineering design problems as well.…

Understanding Genetics: Analysis of Secondary Students' Conceptual Status

ERIC Educational Resources Information Center

Tsui, Chi-Yan; Treagust, David F.

2007-01-01

This article explores the conceptual change of students in Grades 10 and 12 in three Australian senior high schools when the teachers included computer multimedia to a greater or lesser extent in their teaching of a genetics course. The study, underpinned by a multidimensional conceptual-change framework, used an interpretive approach and a…

The Sociopolitical Importance of Genetic, Phenomenological Approaches to Science Teaching and Learning

ERIC Educational Resources Information Center

Bazzul, Jesse

2015-01-01

This article discusses Wolff-Michael Roth's theoretical framework for a phenomenological, genetic approach to science teaching and learning based on the work of Edmund Husserl. This approach advocates the inclusion of student lifeworlds in science education and underlines the importance of thinking about subjectivity in both science and science…

New optimization model for routing and spectrum assignment with nodes insecurity

NASA Astrophysics Data System (ADS)

Xuan, Hejun; Wang, Yuping; Xu, Zhanqi; Hao, Shanshan; Wang, Xiaoli

2017-04-01

By adopting the orthogonal frequency division multiplexing technology, elastic optical networks can provide the flexible and variable bandwidth allocation to each connection request and get higher spectrum utilization. The routing and spectrum assignment problem in elastic optical network is a well-known NP-hard problem. In addition, information security has received worldwide attention. We combine these two problems to investigate the routing and spectrum assignment problem with the guaranteed security in elastic optical network, and establish a new optimization model to minimize the maximum index of the used frequency slots, which is used to determine an optimal routing and spectrum assignment schemes. To solve the model effectively, a hybrid genetic algorithm framework integrating a heuristic algorithm into a genetic algorithm is proposed. The heuristic algorithm is first used to sort the connection requests and then the genetic algorithm is designed to look for an optimal routing and spectrum assignment scheme. In the genetic algorithm, tailor-made crossover, mutation and local search operators are designed. Moreover, simulation experiments are conducted with three heuristic strategies, and the experimental results indicate that the effectiveness of the proposed model and algorithm framework.

Vitamin C reverses hypogonadal bone loss

USDA-ARS?s Scientific Manuscript database

Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, ...

Reversal learning as a measure of impulsive and compulsive behavior in addictions.

PubMed

Izquierdo, Alicia; Jentsch, J David

2012-01-01

Our ability to measure the cognitive components of complex decision-making across species has greatly facilitated our understanding of its neurobiological mechanisms. One task in particular, reversal learning, has proven valuable in assessing the inhibitory processes that are central to executive control. Reversal learning measures the ability to actively suppress reward-related responding and to disengage from ongoing behavior, phenomena that are biologically and descriptively related to impulsivity and compulsivity. Consequently, reversal learning could index vulnerability for disorders characterized by impulsivity such as proclivity for initial substance abuse as well as the compulsive aspects of dependence. Though we describe common variants and similar tasks, we pay particular attention to discrimination reversal learning, its supporting neural circuitry, neuropharmacology and genetic determinants. We also review the utility of this task in measuring impulsivity and compulsivity in addictions. We restrict our review to instrumental, reward-related reversal learning studies as they are most germane to addiction. The research reviewed here suggests that discrimination reversal learning may be used as a diagnostic tool for investigating the neural mechanisms that mediate impulsive and compulsive aspects of pathological reward-seeking and -taking behaviors. Two interrelated mechanisms are posited for the neuroadaptations in addiction that often translate to poor reversal learning: frontocorticostriatal circuitry dysregulation and poor dopamine (D2 receptor) modulation of this circuitry. These data suggest new approaches to targeting inhibitory control mechanisms in addictions.

The genetic rescue of two bottlenecked South Island robin populations using translocations of inbred donors.

PubMed

Heber, S; Varsani, A; Kuhn, S; Girg, A; Kempenaers, B; Briskie, J

2013-02-07

Populations forced through bottlenecks typically lose genetic variation and exhibit inbreeding depression. 'Genetic rescue' techniques that introduce individuals from outbred populations can be highly effective in reversing the deleterious effects of inbreeding, but have limited application for the majority of endangered species, which survive only in a few bottlenecked populations. We tested the effectiveness of using highly inbred populations as donors to rescue two isolated and bottlenecked populations of the South Island robin (Petroica australis). Reciprocal translocations significantly increased heterozygosity and allelic diversity. Increased genetic diversity was accompanied by increased juvenile survival and recruitment, sperm quality, and immunocompetence of hybrid individuals (crosses between the two populations) compared with inbred control individuals (crosses within each population). Our results confirm that the implementation of 'genetic rescue' using bottlenecked populations as donors provides a way of preserving endangered species and restoring their viability when outbred donor populations no longer exist.

Technical approaches for mouse models of human disease.

PubMed

Justice, Monica J; Siracusa, Linda D; Stewart, A Francis

2011-05-01

The mouse is the leading organism for disease research. A rich resource of genetic variation occurs naturally in inbred and special strains owing to spontaneous mutations. However, one can also obtain desired gene mutations by using the following processes: targeted mutations that eliminate function in the whole organism or in a specific tissue; forward genetic screens using chemicals or transposons; or the introduction of exogenous transgenes as DNAs, bacterial artificial chromosomes (BACs) or reporter constructs. The mouse is the only mammal that provides such a rich resource of genetic diversity coupled with the potential for extensive genome manipulation, and is therefore a powerful application for modeling human disease. This poster review outlines the major genome manipulations available in the mouse that are used to understand human disease: natural variation, reverse genetics, forward genetics, transgenics and transposons. Each of these applications will be essential for understanding the diversity that is being discovered within the human population.

Preimplantation genetic diagnosis (PGD) according to medical ethics and medical law

PubMed Central

Lutz, Emine Elif Vatanoğlu

2012-01-01

Assisted reproductive techniques not only nourish great and sometimes illusive hopes of couples who yearn for babies, but also spark new debates by reversing opinions, beliefs and values. Applications made to infertility clinics are increasing due to the influences such as broadcasts made by the media concerning assisted reproductive techniques and other infertility treatments, increase in the knowledge that people have about these problems, late marriages and postponement of childbearing age owing to sociological changes. Pre-implantation genetic diagnosis (PGD) is a technique applied to couples who are known to carry genetic diseases or who have children with genetic diseases. This technique is conducted by doctors in Turkey for its important contribution to decreasing the risk of genetic diseases and in order to raise healthy generations. In this paper, the general ethical debates and the legal situation in Turkey will be discussed. PMID:24627675

A Model Framework to Estimate Impact and Cost of Genetics-Based Sterile Insect Methods for Dengue Vector Control

PubMed Central

Alphey, Nina; Alphey, Luke; Bonsall, Michael B.

2011-01-01

Vector-borne diseases impose enormous health and economic burdens and additional methods to control vector populations are clearly needed. The Sterile Insect Technique (SIT) has been successful against agricultural pests, but is not in large-scale use for suppressing or eliminating mosquito populations. Genetic RIDL technology (Release of Insects carrying a Dominant Lethal) is a proposed modification that involves releasing insects that are homozygous for a repressible dominant lethal genetic construct rather than being sterilized by irradiation, and could potentially overcome some technical difficulties with the conventional SIT technology. Using the arboviral disease dengue as an example, we combine vector population dynamics and epidemiological models to explore the effect of a program of RIDL releases on disease transmission. We use these to derive a preliminary estimate of the potential cost-effectiveness of vector control by applying estimates of the costs of SIT. We predict that this genetic control strategy could eliminate dengue rapidly from a human community, and at lower expense (approximately US$ 2∼30 per case averted) than the direct and indirect costs of disease (mean US$ 86–190 per case of dengue). The theoretical framework has wider potential use; by appropriately adapting or replacing each component of the framework (entomological, epidemiological, vector control bio-economics and health economics), it could be applied to other vector-borne diseases or vector control strategies and extended to include other health interventions. PMID:21998654

Methodological framework for projecting the potential loss of intraspecific genetic diversity due to global climate change

PubMed Central

2012-01-01

Background While research on the impact of global climate change (GCC) on ecosystems and species is flourishing, a fundamental component of biodiversity – molecular variation – has not yet received its due attention in such studies. Here we present a methodological framework for projecting the loss of intraspecific genetic diversity due to GCC. Methods The framework consists of multiple steps that combines 1) hierarchical genetic clustering methods to define comparable units of inference, 2) species accumulation curves (SAC) to infer sampling completeness, and 3) species distribution modelling (SDM) to project the genetic diversity loss under GCC. We suggest procedures for existing data sets as well as specifically designed studies. We illustrate the approach with two worked examples from a land snail (Trochulus villosus) and a caddisfly (Smicridea (S.) mucronata). Results Sampling completeness was diagnosed on the third coarsest haplotype clade level for T. villosus and the second coarsest for S. mucronata. For both species, a substantial species range loss was projected under the chosen climate scenario. However, despite substantial differences in data set quality concerning spatial sampling and sampling depth, no loss of haplotype clades due to GCC was predicted for either species. Conclusions The suggested approach presents a feasible method to tap the rich resources of existing phylogeographic data sets and guide the design and analysis of studies explicitly designed to estimate the impact of GCC on a currently still neglected level of biodiversity. PMID:23176586

Considerations for Using Genetic and Epigenetic Information in Occupational Health Risk Assessment and Standard Setting

PubMed Central

Schulte, P. A.; Whittaker, C.; Curran, C. P.

2015-01-01

Risk assessment forms the basis for both occupational health decision-making and the development of occupational exposure limits (OELs). Although genetic and epigenetic data have not been widely used in risk assessment and ultimately, standard setting, it is possible to envision such uses. A growing body of literature demonstrates that genetic and epigenetic factors condition biological responses to occupational and environmental hazards or serve as targets of them. This presentation addresses the considerations for using genetic and epigenetic information in risk assessments, provides guidance on using this information within the classic risk assessment paradigm, and describes a framework to organize thinking about such uses. The framework is a 4 × 4 matrix involving the risk assessment functions (hazard identification, dose-response modeling, exposure assessment, and risk characterization) on one axis and inherited and acquired genetic and epigenetic data on the other axis. The cells in the matrix identify how genetic and epigenetic data can be used for each risk assessment function. Generally, genetic and epigenetic data might be used as endpoints in hazard identification, as indicators of exposure, as effect modifiers in exposure assessment and dose-response modeling, as descriptors of mode of action, and to characterize toxicity pathways. Vast amounts of genetic and epigenetic data may be generated by high-throughput technologies. These data can be useful for assessing variability and reducing uncertainty in extrapolations, and they may serve as the foundation upon which identification of biological perturbations would lead to a new paradigm of toxicity pathway-based risk assessments. PMID:26583908

Enterovirus A71 DNA-Launched Infectious Clone as a Robust Reverse Genetic Tool

PubMed Central

Tan, Chee Wah; Tee, Han Kang; Lee, Michelle Hui Pheng; Sam, I-Ching; Chan, Yoke Fun

2016-01-01

Enterovirus A71 (EV-A71) causes major outbreaks of hand, foot and mouth disease, and is occasionally associated with neurological complications and death in children. Reverse genetics is widely used in the field of virology for functional study of viral genes. For EV-A71, such tools are limited to clones that are transcriptionally controlled by T7/SP6 bacteriophage promoter. This is often time-consuming and expensive. Here, we describe the development of infectious plasmid DNA-based EV-A71 clones, for which EV-A71 genome expression is under transcriptional control by the CMV-intermediate early promoter and SV40 transcriptional-termination signal. Transfection of this EV-A71 infectious DNA produces good virus yield similar to in vitro-transcribed EV-A71 infectious RNA, 6.4 and 5.8 log10PFU/ml, respectively. Infectious plasmid with enhanced green fluorescence protein and Nano luciferase reporter genes also produced good virus titers, with 4.3 and 5.0 log10 PFU/ml, respectively. Another infectious plasmid with both CMV and T7 promoters was also developed for easy manipulation of in vitro transcription or direct plasmid transfection. Transfection with either dual-promoter infectious plasmid DNA or infectious RNA derived from this dual-promoter clone produced infectious viral particles. Incorporation of hepatitis delta virus ribozyme, which yields precise 3’ ends of the DNA-launched EV-A71 genomic transcripts, increased infectious viral production. In contrast, the incorporation of hammerhead ribozyme in the DNA-launched EV-A71 resulted in lower virus yield, but improved the virus titers for T7 promoter-derived infectious RNA. This study describes rapid and robust reverse genetic tools for EV-A71. PMID:27617744

A Point Mutation in the Rhesus Rotavirus VP4 Protein Generated through a Rotavirus Reverse Genetics System Attenuates Biliary Atresia in the Murine Model.

PubMed

Mohanty, Sujit K; Donnelly, Bryan; Dupree, Phylicia; Lobeck, Inna; Mowery, Sarah; Meller, Jaroslaw; McNeal, Monica; Tiao, Greg

2017-08-01

Rotavirus infection is one of the most common causes of diarrheal illness in humans. In neonatal mice, rhesus rotavirus (RRV) can induce biliary atresia (BA), a disease resulting in inflammatory obstruction of the extrahepatic biliary tract and intrahepatic bile ducts. We previously showed that the amino acid arginine (R) within the sequence SRL (amino acids 445 to 447) in the RRV VP4 protein is required for viral binding and entry into biliary epithelial cells. To determine if this single amino acid (R) influences the pathogenicity of the virus, we generated a recombinant virus with a single amino acid mutation at this site through a reverse genetics system. We demonstrated that the RRV mutant (RRV VP4-R446G ) produced less symptomatology and replicated to lower titers both in vivo and in vitro than those seen with wild-type RRV, with reduced binding in cholangiocytes. Our results demonstrate that a single amino acid change in the RRV VP4 gene influences cholangiocyte tropism and reduces pathogenicity in mice. IMPORTANCE Rotavirus is the leading cause of diarrhea in humans. Rhesus rotavirus (RRV) can also lead to biliary atresia (a neonatal human disease) in mice. We developed a reverse genetics system to create a mutant of RRV (RRV VP4-R446G ) with a single amino acid change in the VP4 protein compared to that of wild-type RRV. In vitro , the mutant virus had reduced binding and infectivity in cholangiocytes. In vivo , it produced fewer symptoms and lower mortality in neonatal mice, resulting in an attenuated form of biliary atresia. Copyright © 2017 American Society for Microbiology.

Development of a Reverse Genetic System for Infectious Salmon Anemia Virus: Rescue of Recombinant Fluorescent Virus by Using Salmon Internal Transcribed Spacer Region 1 as a Novel Promoter

PubMed Central

Toro-Ascuy, Daniela; Tambley, Carolina; Beltran, Carolina; Mascayano, Carolina; Sandoval, Nicolas; Olivares, Eduardo; Medina, Rafael A.; Spencer, Eugenio

2014-01-01

Infectious salmon anemia (ISA) is a serious disease of marine-farmed Atlantic salmon (Salmo salar) caused by ISA virus (ISAV), belonging to the genus Isavirus, family Orthomyxoviridae. There is an urgent need to understand the virulence factors and pathogenic mechanisms of ISAV and to develop new vaccine approaches. Using a recombinant molecular biology approach, we report the development of a plasmid-based reverse genetic system for ISAV, which includes the use of a novel fish promoter, the Atlantic salmon internal transcribed spacer region 1 (ITS-1). Salmon cells cotransfected with pSS-URG-based vectors expressing the eight viral RNA segments and four cytomegalovirus (CMV)-based vectors that express the four proteins of the ISAV ribonucleoprotein complex allowed the generation of infectious recombinant ISAV (rISAV). We generated three recombinant viruses, wild-type rISAV901_09 and rISAVrS6-NotI-HPR containing a NotI restriction site and rISAVS6/EGFP-HPR harboring the open reading frame of enhanced green fluorescent protein (EGFP), both within the highly polymorphic region (HPR) of segment 6. All rescued viruses showed replication activity and cytopathic effect in Atlantic salmon kidney-infected cells. The fluorescent recombinant viruses also showed a characteristic cytopathic effect in salmon cells, and the viruses replicated to a titer of 6.5 × 105 PFU/ml, similar to that of the wild-type virus. This novel reverse genetics system offers a powerful tool to study the molecular biology of ISAV and to develop a new generation of ISAV vaccines to prevent and mitigate ISAV infection, which has had a profound effect on the salmon industry. PMID:25480750

Model-based conservation planning of the genetic diversity of Phellodendron amurense Rupr due to climate change

PubMed Central

Wan, Jizhong; Wang, Chunjing; Yu, Jinghua; Nie, Siming; Han, Shijie; Zu, Yuangang; Chen, Changmei; Yuan, Shusheng; Wang, Qinggui

2014-01-01

Climate change affects both habitat suitability and the genetic diversity of wild plants. Therefore, predicting and establishing the most effective and coherent conservation areas is essential for the conservation of genetic diversity in response to climate change. This is because genetic variance is a product not only of habitat suitability in conservation areas but also of efficient protection and management. Phellodendron amurense Rupr. is a tree species (family Rutaceae) that is endangered due to excessive and illegal harvesting for use in Chinese medicine. Here, we test a general computational method for the prediction of priority conservation areas (PCAs) by measuring the genetic diversity of P. amurense across the entirety of northeast China using a single strand repeat analysis of twenty microsatellite markers. Using computational modeling, we evaluated the geographical distribution of the species, both now and in different future climate change scenarios. Different populations were analyzed according to genetic diversity, and PCAs were identified using a spatial conservation prioritization framework. These conservation areas were optimized to account for the geographical distribution of P. amurense both now and in the future, to effectively promote gene flow, and to have a long period of validity. In situ and ex situ conservation, strategies for vulnerable populations were proposed. Three populations with low genetic diversity are predicted to be negatively affected by climate change, making conservation of genetic diversity challenging due to decreasing habitat suitability. Habitat suitability was important for the assessment of genetic variability in existing nature reserves, which were found to be much smaller than the proposed PCAs. Finally, a simple set of conservation measures was established through modeling. This combined molecular and computational ecology approach provides a framework for planning the protection of species endangered by climate change. PMID:25165526

ExpoCast Framework for Rapid Exposure Forecasts (ISES ExpoDat symposium presentation)

EPA Science Inventory

The U.S. E.P.A. ExpoCast project uses high throughput exposure models (simulation) and any easily-obtained exposure heuristics to generate forward predictions of potential exposures from chemical properties. By comparison with exposures inferred via reverse pharmacokinetic modeli...

A Conceptual Framework for Predicting the Toxicity of Reactive Chemicals: Modeling Soft Electrophilicity

EPA Science Inventory

Although the literature is replete with QSAR models developed for many toxic effects caused by reversible chemical interactions, the development of QSARs for the toxic effects of reactive chemicals lacks a consistent approach. While limitations exit, an appropriate starting-point...

Inequality reversal: Effects of the savings propensity and correlated returns

NASA Astrophysics Data System (ADS)

Chakrabarti, Anindya S.; Chakrabarti, Bikas K.

2010-09-01

In the last decade, a large body of literature has been developed to explain the universal features of inequality in terms of income and wealth. By now, it is established that the distributions of income and wealth in various economies show a number of statistical regularities. There are several models to explain such static features of inequality in a unifying framework, and the kinetic exchange models in particular provide one such framework. Here we focus on the dynamic features of inequality. In the process of development and growth, inequality in an economy in terms of income and wealth follows a particular pattern of rising in the initial stage followed by an eventual fall. This inverted U-shaped curve is known as the Kuznets Curve. We examine the possibilities of such behavior of an economy in the context of a generalized kinetic exchange model. It is shown that under some specific conditions, our model economy indeed shows inequality reversal.

Reversing Conventional Reactivity of Mixed Oxo/Alkyl Rare-Earth Complexes: Non-Redox Oxygen Atom Transfer.

PubMed

Hong, Jianquan; Tian, Haiwen; Zhang, Lixin; Zhou, Xigeng; Del Rosal, Iker; Weng, Linhong; Maron, Laurent

2018-01-22

The preferential substitution of oxo ligands over alkyl ones of rare-earth complexes is commonly considered as "impossible" due to the high oxophilicity of metal centers. Now, it has been shown that simply assembling mixed methyl/oxo rare-earth complexes to a rigid trinuclear cluster framework cannot only enhance the activity of the Ln-oxo bond, but also protect the highly reactive Ln-alkyl bond, thus providing a previously unrecognized opportunity to selectively manipulate the oxo ligand in the presence of numerous reactive functionalities. Such trimetallic cluster has proved to be a suitable platform for developing the unprecedented non-redox rare-earth-mediated oxygen atom transfer from ketones to CS 2 and PhNCS. Controlled experiments and computational studies shed light on the driving force for these reactions, emphasizing the importance of the sterical accessibility and multimetallic effect of the cluster framework in promoting reversal of reactivity of rare-earth oxo complexes. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ensemble of hybrid genetic algorithm for two-dimensional phase unwrapping

NASA Astrophysics Data System (ADS)

Balakrishnan, D.; Quan, C.; Tay, C. J.

2013-06-01

The phase unwrapping is the final and trickiest step in any phase retrieval technique. Phase unwrapping by artificial intelligence methods (optimization algorithms) such as hybrid genetic algorithm, reverse simulated annealing, particle swarm optimization, minimum cost matching showed better results than conventional phase unwrapping methods. In this paper, Ensemble of hybrid genetic algorithm with parallel populations is proposed to solve the branch-cut phase unwrapping problem. In a single populated hybrid genetic algorithm, the selection, cross-over and mutation operators are applied to obtain new population in every generation. The parameters and choice of operators will affect the performance of the hybrid genetic algorithm. The ensemble of hybrid genetic algorithm will facilitate to have different parameters set and different choice of operators simultaneously. Each population will use different set of parameters and the offspring of each population will compete against the offspring of all other populations, which use different set of parameters. The effectiveness of proposed algorithm is demonstrated by phase unwrapping examples and advantages of the proposed method are discussed.

A Symbiotic Framework for coupling Machine Learning and Geosciences in Prediction and Predictability

NASA Astrophysics Data System (ADS)

Ravela, S.

2017-12-01

In this presentation we review the two directions of a symbiotic relationship between machine learning and the geosciences in relation to prediction and predictability. In the first direction, we develop ensemble, information theoretic and manifold learning framework to adaptively improve state and parameter estimates in nonlinear high-dimensional non-Gaussian problems, showing in particular that tractable variational approaches can be produced. We demonstrate these applications in the context of autonomous mapping of environmental coherent structures and other idealized problems. In the reverse direction, we show that data assimilation, particularly probabilistic approaches for filtering and smoothing offer a novel and useful way to train neural networks, and serve as a better basis than gradient based approaches when we must quantify uncertainty in association with nonlinear, chaotic processes. In many inference problems in geosciences we seek to build reduced models to characterize local sensitivies, adjoints or other mechanisms that propagate innovations and errors. Here, the particular use of neural approaches for such propagation trained using ensemble data assimilation provides a novel framework. Through these two examples of inference problems in the earth sciences, we show that not only is learning useful to broaden existing methodology, but in reverse, geophysical methodology can be used to influence paradigms in learning.

46,XY female sex reversal syndrome with bilateral gonadoblastoma and dysgerminoma.

PubMed

DU, Xue; Zhang, Xuhong; Li, Yongmei; Han, Yukun

2014-10-01

Sex reversal syndrome is a rare congenital condition of complete or disordered gonadal development leading to discordance between the genetic, gonadal and phenotypic sexes, including 46,XX and 46,XY. The gonadoblastoma on the Y-chromosome (GBY) region is associated with an increased risk of developing type II germ cell tumors/cancer. The present study reports a unique case of a phenotypically normal female (age 17 years), presenting with primary amenorrhea and later diagnosed with 46,XY female sex reversal syndrome. Following bilateral gonadectomy, bilateral gonadoblastoma and dysgerminoma were diagnosed. Thus, estrogen replacement therapy was administered periodically to promote the development of secondary sexual characteristics and menstruation, and to prevent osteoporosis. A four year follow-up showed no tumor recurrence and a regular menstrual cycle in this patient.

A Systems Approach to Designing Effective Clinical Trials Using Simulations

PubMed Central

Fusaro, Vincent A.; Patil, Prasad; Chi, Chih-Lin; Contant, Charles F.; Tonellato, Peter J.

2013-01-01

Background Pharmacogenetics in warfarin clinical trials have failed to show a significant benefit compared to standard clinical therapy. This study demonstrates a computational framework to systematically evaluate pre-clinical trial design of target population, pharmacogenetic algorithms, and dosing protocols to optimize primary outcomes. Methods and Results We programmatically created an end-to-end framework that systematically evaluates warfarin clinical trial designs. The framework includes options to create a patient population, multiple dosing strategies including genetic-based and non-genetic clinical-based, multiple dose adjustment protocols, pharmacokinetic/pharmacodynamics (PK/PD) modeling and international normalization ratio (INR) prediction, as well as various types of outcome measures. We validated the framework by conducting 1,000 simulations of the CoumaGen clinical trial primary endpoints. The simulation predicted a mean time in therapeutic range (TTR) of 70.6% and 72.2% (P = 0.47) in the standard and pharmacogenetic arms, respectively. Then, we evaluated another dosing protocol under the same original conditions and found a significant difference in TTR between the pharmacogenetic and standard arm (78.8% vs. 73.8%; P = 0.0065), respectively. Conclusions We demonstrate that this simulation framework is useful in the pre-clinical assessment phase to study and evaluate design options and provide evidence to optimize the clinical trial for patient efficacy and reduced risk. PMID:23261867

Exploiting the Brachypodium Tool Box in cereal and grass research

USDA-ARS?s Scientific Manuscript database

It is now a decade since Brachypodium distachyon was suggested as a model species for temperate grasses and cereals. Since then transformation protocols, large expressed sequence tag (EST) populations, tools for forward and reverse genetic screens, highly refined cytogenetic probes, germplasm coll...

Determining mutation density using Restriction Enzyme Sequence Comparative Analysis (RESCAN)

USDA-ARS?s Scientific Manuscript database

The average mutation density of a mutant population is a major consideration when developing resources for the efficient, cost-effective implementation of reverse genetics methods such as Targeting of Induced Local Lesions in Genomes (TILLING). Reliable estimates of mutation density can be achieved ...

Virus-induced gene silencing (VIGS) in barley seedling leaves

USDA-ARS?s Scientific Manuscript database

Virus-induced gene silencing (VIGS) is one of the most potent reverse genetics technologies for gene functional characterization. This method exploits a dsRNA-mediated antiviral defense mechanism in plants. Using this method allows researchers to generate rapid phenotypic data in a relatively rapid ...

Expressing foreign genes by Newcastle disease virus for cancer therapy

USDA-ARS?s Scientific Manuscript database

An interesting aspect of Newcastle disease virus (NDV) is the ability to selectively replicate in tumor cells. Recently, using reverse genetics technology to enhance the oncolytic properties and therapeutic potential of NDV for tumor therapy has become popular in immunocompetent carcinoma tumor mod...

Naturally selecting solutions: the use of genetic algorithms in bioinformatics.

PubMed

Manning, Timmy; Sleator, Roy D; Walsh, Paul

2013-01-01

For decades, computer scientists have looked to nature for biologically inspired solutions to computational problems; ranging from robotic control to scheduling optimization. Paradoxically, as we move deeper into the post-genomics era, the reverse is occurring, as biologists and bioinformaticians look to computational techniques, to solve a variety of biological problems. One of the most common biologically inspired techniques are genetic algorithms (GAs), which take the Darwinian concept of natural selection as the driving force behind systems for solving real world problems, including those in the bioinformatics domain. Herein, we provide an overview of genetic algorithms and survey some of the most recent applications of this approach to bioinformatics based problems.

The reverse evolution from multicellularity to unicellularity during carcinogenesis.

PubMed

Chen, Han; Lin, Fangqin; Xing, Ke; He, Xionglei

2015-03-09

Theoretical reasoning suggests that cancer may result from a knockdown of the genetic constraints that evolved for the maintenance of metazoan multicellularity. By characterizing the whole-life history of a xenograft tumour, here we show that metastasis is driven by positive selection for general loss-of-function mutations on multicellularity-related genes. Expression analyses reveal mainly downregulation of multicellularity-related genes and an evolving expression profile towards that of embryonic stem cells, the cell type resembling unicellular life in its capacity of unlimited clonal proliferation. Also, the emergence of metazoan multicellularity ~600 Myr ago is accompanied by an elevated birth rate of cancer genes, and there are more loss-of-function tumour suppressors than activated oncogenes in a typical tumour. These data collectively suggest that cancer represents a loss-of-function-driven reverse evolution back to the unicellular 'ground state'. This cancer evolution model may account for inter-/intratumoural genetic heterogeneity, could explain distant-organ metastases and hold implications for cancer therapy.

Reverse genetics of Mononegavirales: How they work, new vaccines, and new cancer therapeutics

PubMed Central

Pfaller, Christian K.; Cattaneo, Roberto; Schnell, Matthias J.

2015-01-01

The order Mononegavirales includes five families: Bornaviridae, Filoviridae, Nyamaviridae, Paramyxoviridae, and Rhabdoviridae. The genome of these viruses is one molecule of negative-sense single strand RNA coding for five to ten genes in a conserved order. The RNA is not infectious until packaged by the nucleocapsid protein and transcribed by the polymerase and co-factors. Reverse genetics approaches have answered fundamental questions about the biology of Mononegavirales. The lack of icosahedral symmetry and modular organization in the genome of these viruses has facilitated engineering of viruses expressing fluorescent proteins, and these fluorescent proteins have provided important insights about the molecular and cellular basis of tissue tropism and pathogenesis. Studies have assessed the relevance for virulence of different receptors and the interactions with cellular proteins governing the innate immune responses. Research has also analyzed the mechanisms of attenuation. Based on these findings, ongoing clinical trials are exploring new live attenuated vaccines and the use of viruses re-engineered as cancer therapeutics. PMID:25702088

Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days.

PubMed

de Fabritus, Lauriane; Nougairède, Antoine; Aubry, Fabien; Gould, Ernest A; de Lamballerie, Xavier

2016-01-01

Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re-encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding regions respectively. Both re-encoded viruses were attenuated when compared with WT virus using a laboratory mouse model and the relative level of attenuation increased with the degree of re-encoding. Moreover, all infected animals produced neutralizing antibodies. This novel, rapid and efficient approach to engineering attenuated viruses could potentially expedite the development of safe and effective new-generation live attenuated vaccines.

Conservation of social effects (Ψ) between two species of Drosophila despite reversal of sexual dimorphism.

PubMed

Signor, Sarah A; Abbasi, Mohammad; Marjoram, Paul; Nuzhdin, Sergey V

2017-12-01

Indirect genetic effects (IGEs) describe the effect of the genes of social partners on the phenotype of a focal individual. Here, we measure indirect genetic effects using the "coefficient of interaction" (Ψ) to test whether Ψ evolved between Drosophila melanogaster and D. simulans . We compare Ψ for locomotion between ethanol and nonethanol environments in both species, but only D. melanogaster utilizes ethanol ecologically. We find that while sexual dimorphism for locomotion has been reversed in D. simulans , there has been no evolution of social effects between these two species. What did evolve was the interaction between genotype-specific Ψ and the environment, as D. melanogaster  varies unpredictably between environments and D. simulans  does not. In this system, this suggests evolutionary lability of sexual dimorphism but a conservation of social effects, which brings forth interesting questions about the role of the social environment in sexual selection.

Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast

PubMed Central

Oud, Bart; Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

2012-01-01

Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. PMID:22152095

Genetic Network Inference: From Co-Expression Clustering to Reverse Engineering

NASA Technical Reports Server (NTRS)

Dhaeseleer, Patrik; Liang, Shoudan; Somogyi, Roland

2000-01-01

Advances in molecular biological, analytical, and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-duster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e., who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting, and bioengineering.

Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast.

PubMed

Oud, Bart; van Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

2012-03-01

Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Access and benefits sharing of genetic resources and associated traditional knowledge in northern Canada: understanding the legal environment and creating effective research agreements

PubMed Central

Geary, Janis; Jardine, Cynthia G.; Guebert, Jenilee; Bubela, Tania

2013-01-01

Background Research in northern Canada focused on Aboriginal peoples has historically benefited academia with little consideration for the people being researched or their traditional knowledge (TK). Although this attitude is changing, the complexity of TK makes it difficult to develop mechanisms to preserve and protect it. Protecting TK becomes even more important when outside groups become interested in using TK or materials with associated TK. In the latter category are genetic resources, which may have commercial value and are the focus of this article. Objective This article addresses access to and use of genetic resources and associated TK in the context of the historical power-imbalances in research relationships in Canadian north. Design Review. Results Research involving genetic resources and TK is becoming increasingly relevant in northern Canada. The legal framework related to genetic resources and the cultural shift of universities towards commercial goals in research influence the environment for negotiating research agreements. Current guidelines for research agreements do not offer appropriate guidelines to achieve mutual benefit, reflect unequal bargaining power or take the relationship between parties into account. Conclusions Relational contract theory may be a useful framework to address the social, cultural and legal hurdles inherent in creating research agreements. PMID:23986896

Dealing with the genetic load in bacterial synthetic biology circuits: convergences with the Ohm's law

PubMed Central

Carbonell-Ballestero, M.; Garcia-Ramallo, E.; Montañez, R.; Rodriguez-Caso, C.; Macía, J.

2016-01-01

Synthetic biology seeks to envision living cells as a matter of engineering. However, increasing evidence suggests that the genetic load imposed by the incorporation of synthetic devices in a living organism introduces a sort of unpredictability in the design process. As a result, individual part characterization is not enough to predict the behavior of designed circuits and thus, a costly trial-error process is eventually required. In this work, we provide a new theoretical framework for the predictive treatment of the genetic load. We mathematically and experimentally demonstrate that dependences among genes follow a quantitatively predictable behavior. Our theory predicts the observed reduction of the expression of a given synthetic gene when an extra genetic load is introduced in the circuit. The theory also explains that such dependence qualitatively differs when the extra load is added either by transcriptional or translational modifications. We finally show that the limitation of the cellular resources for gene expression leads to a mathematical formulation that converges to an expression analogous to the Ohm's law for electric circuits. Similitudes and divergences with this law are outlined. Our work provides a suitable framework with predictive character for the design process of complex genetic devices in synthetic biology. PMID:26656950

Access and benefits sharing of genetic resources and associated traditional knowledge in northern Canada: understanding the legal environment and creating effective research agreements.

PubMed

Geary, Janis; Jardine, Cynthia G; Guebert, Jenilee; Bubela, Tania

2013-01-01

Research in northern Canada focused on Aboriginal peoples has historically benefited academia with little consideration for the people being researched or their traditional knowledge (TK). Although this attitude is changing, the complexity of TK makes it difficult to develop mechanisms to preserve and protect it. Protecting TK becomes even more important when outside groups become interested in using TK or materials with associated TK. In the latter category are genetic resources, which may have commercial value and are the focus of this article. This article addresses access to and use of genetic resources and associated TK in the context of the historical power-imbalances in research relationships in Canadian north. Review. Research involving genetic resources and TK is becoming increasingly relevant in northern Canada. The legal framework related to genetic resources and the cultural shift of universities towards commercial goals in research influence the environment for negotiating research agreements. Current guidelines for research agreements do not offer appropriate guidelines to achieve mutual benefit, reflect unequal bargaining power or take the relationship between parties into account. Relational contract theory may be a useful framework to address the social, cultural and legal hurdles inherent in creating research agreements.

An analysis of mobile genetic elements in three Plasmodium species and their potential impact on the nucleotide composition of the P. falciparum genome.

PubMed

Durand, Pierre M; Oelofse, Andries J; Coetzer, Theresa L

2006-11-04

The completed genome sequences of the malaria parasites P. falciparum, P. y. yoelii and P. vivax have revealed some unusual features. P. falciparum contains the most AT rich genome sequenced so far--over 90% in some regions. In comparison, P. y. yoelii is approximately 77% and P. vivax is approximately 55% AT rich. The evolutionary reasons for these findings are unknown. Mobile genetic elements have a considerable impact on genome evolution but a thorough investigation of these elements in Plasmodium has not been undertaken. We therefore performed a comprehensive genome analysis of these elements and their derivatives in the three Plasmodium species. Whole genome analysis was performed using bioinformatic methods. Forty potential protein encoding sequences with features of transposable elements were identified in P. vivax, eight in P. y. yoelii and only six in P. falciparum. Further investigation of the six open reading frames in P. falciparum revealed that only one is potentially an active mobile genetic element. Most of the open reading frames identified in all three species are hypothetical proteins. Some represent annotated host proteins such as the putative telomerase reverse transcriptase genes in P. y. yoelii and P. falciparum. One of the P. vivax open reading frames identified in this study demonstrates similarity to telomerase reverse transcriptase and we conclude it to be the orthologue of this gene. There is a divergence in the frequencies of mobile genetic elements in the three Plasmodium species investigated. Despite the limitations of whole genome analytical methods, it is tempting to speculate that mobile genetic elements might have been a driving force behind the compositional bias of the P. falciparum genome.

Educators' Challenge: Healthy Mothers, Healthy Babies. A Framework for Curriculum Development in Responsible Childbearing, Pre-school through High School.

ERIC Educational Resources Information Center

Zeyen, Dorothy Dolph

A framework of concepts in nutrition, environmental factors, genetics, and human growth and development is presented as a background for developing elementary and secondary curricula on responsible childbearing. Aspects of the four subject areas are outlined for instruction at five education levels: preschool through kindergarten, primary, upper…

A consensus framework map of durum wheat (Triticum durum Desf.) suitable for linkage disequilibrium analysis and genome-wide association mapping

USDA-ARS?s Scientific Manuscript database

Genomics applications in durum (Triticum durum Desf.) wheat have the potential to boost exploitation of genetic resources and to advance understanding of the genetics of important complex traits (e.g. resilience to environmental and biotic stresses). A dense and accurate consensus map specific for ...

Mapping of quantitative trait loci controlling adaptive traits in coastal Douglas-fir

Treesearch

Nicholas C. Wheeler; Kathleen D. Jermstad; Konstantin V. Krutovsky; Sally N. Aitken; Glenn T. Howe; Jodie Krakowski; David B. Neale

2005-01-01

Quantitative trait locus (QTL) analyses are used by geneticists to characterize the genetic architecture of quantitative traits, provide a foundation for marker-aided-selection (MAS), and provide a framework for positional selection of candidate genes. The most useful QTL for breeding applications are those that have been verified in time, space, and/or genetic...

Ecological transition predictably associated with gene degeneration.

PubMed

Wessinger, Carolyn A; Rausher, Mark D

2015-02-01

Gene degeneration or loss can significantly contribute to phenotypic diversification, but may generate genetic constraints on future evolutionary trajectories, potentially restricting phenotypic reversal. Such constraints may manifest as directional evolutionary trends when parallel phenotypic shifts consistently involve gene degeneration or loss. Here, we demonstrate that widespread parallel evolution in Penstemon from blue to red flowers predictably involves the functional inactivation and degeneration of the enzyme flavonoid 3',5'-hydroxylase (F3'5'H), an anthocyanin pathway enzyme required for the production of blue floral pigments. Other types of genetic mutations do not consistently accompany this phenotypic shift. This pattern may be driven by the relatively large mutational target size of degenerative mutations to this locus and the apparent lack of associated pleiotropic effects. The consistent degeneration of F3'5'H may provide a mechanistic explanation for the observed asymmetry in the direction of flower color evolution in Penstemon: Blue to red transitions are common, but reverse transitions have not been observed. Although phenotypic shifts in this system are likely driven by natural selection, internal constraints may generate predictable genetic outcomes and may restrict future evolutionary trajectories. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetic Code Optimization for Cotranslational Protein Folding: Codon Directional Asymmetry Correlates with Antiparallel Betasheets, tRNA Synthetase Classes.

PubMed

Seligmann, Hervé; Warthi, Ganesh

2017-01-01

A new codon property, codon directional asymmetry in nucleotide content (CDA), reveals a biologically meaningful genetic code dimension: palindromic codons (first and last nucleotides identical, codon structure XZX) are symmetric (CDA = 0), codons with structures ZXX/XXZ are 5'/3' asymmetric (CDA = - 1/1; CDA = - 0.5/0.5 if Z and X are both purines or both pyrimidines, assigning negative/positive (-/+) signs is an arbitrary convention). Negative/positive CDAs associate with (a) Fujimoto's tetrahedral codon stereo-table; (b) tRNA synthetase class I/II (aminoacylate the 2'/3' hydroxyl group of the tRNA's last ribose, respectively); and (c) high/low antiparallel (not parallel) betasheet conformation parameters. Preliminary results suggest CDA-whole organism associations (body temperature, developmental stability, lifespan). Presumably, CDA impacts spatial kinetics of codon-anticodon interactions, affecting cotranslational protein folding. Some synonymous codons have opposite CDA sign (alanine, leucine, serine, and valine), putatively explaining how synonymous mutations sometimes affect protein function. Correlations between CDA and tRNA synthetase classes are weaker than between CDA and antiparallel betasheet conformation parameters. This effect is stronger for mitochondrial genetic codes, and potentially drives mitochondrial codon-amino acid reassignments. CDA reveals information ruling nucleotide-protein relations embedded in reversed (not reverse-complement) sequences (5'-ZXX-3'/5'-XXZ-3').

New Generation Live Vaccines against Human Respiratory Syncytial Virus Designed by Reverse Genetics

PubMed Central

Collins, Peter L.; Murphy, Brian R.

2005-01-01

Development of a live pediatric vaccine against human respiratory syncytial virus (RSV) is complicated by the need to immunize young infants and the difficulty in balancing attenuation and immunogenicity. The ability to introduce desired mutations into infectious virus by reverse genetics provides a method for identifying and designing highly defined attenuating mutations. These can be introduced in combinations as desired to achieve gradations of attenuation. Attenuation is based on several strategies: multiple independent temperature-sensitive point mutations in the polymerase, a temperature-sensitive point mutation in a transcription signal, a set of non–temperature-sensitive mutations involving several genes, deletion of a viral RNA synthesis regulatory protein, and deletion of viral IFN α/β antagonists. The genetic stability of the live vaccine can be increased by judicious choice of mutations. The virus also can be engineered to increase the level of expression of the protective antigens. Protective antigens from antigenically distinct RSV strains can be added or swapped to increase the breadth of coverage. Alternatively, the major RSV protective antigens can be expressed from transcription units added to an attenuated parainfluenza vaccine virus, making a bivalent vaccine. This would obviate the difficulties inherent in the fragility and inefficient in vitro growth of RSV, simplifying vaccine design and use. PMID:16113487

Reverse Engineering Field Isolates of Myxoma Virus Demonstrates that Some Gene Disruptions or Losses of Function Do Not Explain Virulence Changes Observed in the Field

PubMed Central

Liu, June; Cattadori, Isabella M.; Sim, Derek G.; Eden, John-Sebastian; Read, Andrew F.

2017-01-01

ABSTRACT The coevolution of myxoma virus (MYXV) and wild European rabbits in Australia and Europe is a paradigm for the evolution of a pathogen in a new host species. Genomic analyses have identified the mutations that have characterized this evolutionary process, but defining causal mutations in the pathways from virulence to attenuation and back to virulence has not been possible. Using reverse genetics, we examined the roles of six selected mutations found in Australian field isolates of MYXV that fall in known or potential virulence genes. Several of these mutations occurred in genes previously identified as virulence genes in whole-gene knockout studies. Strikingly, no single or double mutation among the mutations tested had an appreciable impact on virulence. This suggests either that virulence evolution was defined by amino acid changes other than those analyzed here or that combinations of multiple mutations, possibly involving epistatic interactions or noncoding sequences, have been critical in the ongoing evolution of MYXV virulence. In sum, our results show that single-gene knockout studies of a progenitor virus can have little power to predict the impact of individual mutations seen in the field. The genetic determinants responsible for this canonical case of virulence evolution remain to be determined. IMPORTANCE The species jump of myxoma virus (MYXV) from the South American tapeti to the European rabbit populations of Australia and Europe is a canonical example of host-pathogen coevolution. Detailed molecular studies have identified multiple genes in MYXV that are critical for virulence, and genome sequencing has revealed the evolutionary history of MYXV in Australia and Europe. However, it has not been possible to categorically identify the key mutations responsible for the attenuation of or reversion to virulence during this evolutionary process. Here we use reverse genetics to examine the role of mutations in viruses isolated early and late in the Australian radiation of MYXV. Surprisingly, none of the candidate mutations that we identified as likely having roles in attenuation proved to be important for virulence. This indicates that considerable caution is warranted when interpreting the possible role of individual mutations during virulence evolution. PMID:28768866

Application of Attachment Theory to the Study of Sexual Abuse.

ERIC Educational Resources Information Center

Alexander, Pamela C.

1992-01-01

Attachment theory provides useful conceptual framework for understanding familial antecedents and long-term consequences of sexual abuse. Themes associated with insecure parent-child attachment (rejection, role reversal/parentification, and fear/unresolved trauma) are frequently found in dynamics of families characterized by sexual abuse, and…

High rate, long cycle life battery electrode materials with an open framework structure

DOEpatents

Wessells, Colin; Huggins, Robert; Cui, Yi; Pasta, Mauro

2015-02-10

A battery includes a cathode, an anode, and an aqueous electrolyte disposed between the cathode and the anode and including a cation A. At least one of the cathode and the anode includes an electrode material having an open framework crystal structure into which the cation A is reversibly inserted during operation of the battery. The battery has a reference specific capacity when cycled at a reference rate, and at least 75% of the reference specific capacity is retained when the battery is cycled at 10 times the reference rate.

An inexact reverse logistics model for municipal solid waste management systems.

PubMed

Zhang, Yi Mei; Huang, Guo He; He, Li

2011-03-01

This paper proposed an inexact reverse logistics model for municipal solid waste management systems (IRWM). Waste managers, suppliers, industries and distributors were involved in strategic planning and operational execution through reverse logistics management. All the parameters were assumed to be intervals to quantify the uncertainties in the optimization process and solutions in IRWM. To solve this model, a piecewise interval programming was developed to deal with Min-Min functions in both objectives and constraints. The application of the model was illustrated through a classical municipal solid waste management case. With different cost parameters for landfill and the WTE, two scenarios were analyzed. The IRWM could reflect the dynamic and uncertain characteristics of MSW management systems, and could facilitate the generation of desired management plans. The model could be further advanced through incorporating methods of stochastic or fuzzy parameters into its framework. Design of multi-waste, multi-echelon, multi-uncertainty reverse logistics model for waste management network would also be preferred. Copyright © 2010 Elsevier Ltd. All rights reserved.

Multifunctional Metal-Organic Frameworks Based on Redox-Active Rhenium Octahedral Clusters.

PubMed

Litvinova, Yulia M; Gayfulin, Yakov M; Kovalenko, Konstantin A; Samsonenko, Denis G; van Leusen, Jan; Korolkov, Ilya V; Fedin, Vladimir P; Mironov, Yuri V

2018-02-19

The redox-active rhenium octahedral cluster unit [Re 6 Se 8 (CN) 6 ] 4- was combined with Gd 3+ ions and dicarboxylate linkers in novel types of metal-organic frameworks (MOFs) that display a set of functional properties. The hydrolytically stable complexes [{Gd(H 2 O) 3 } 2 (L)Re 6 Se 8 (CN) 6 ]·nH 2 O (1, L = furan-2,5-dicarboxylate, fdc; 2, L = thiophene-2,5-dicarboxylate, tdc) exhibit a 3D framework of trigonal symmetry where 1D chains of [{Gd(H 2 O) 3 } 2 (L)] 4+ are connected by [Re 6 Se 8 (CN) 6 ] 4- clusters. Frameworks contain spacious channels filled with H 2 O. Solvent molecules can be easily removed under vacuum to produce permanently porous solids with high volumetric CO 2 uptake and remarkable CO 2 /N 2 selectivity at room temperature. The frameworks demonstrate an ability for reversible redox transformations of the cluster fragment. The orange powders of compounds 1 and 2 react with Br 2 , yielding dark-green powders of [{Gd(H 2 O) 3 } 2 (L)Re 6 Se 8 (CN) 6 ]Br·nH 2 O (3, L = fdc; 4, L = tdc). Compounds 3 and 4 are isostructural with 1 and 2 and also have permanently porous frameworks but display different optical, magnetic, and sorption properties. In particular, oxidation of the cluster fragment "switches off" its luminescence in the red region, and the incorporation of Br - leads to a decrease of the solvent-accessible volume in the channels of 3 and 4. Finally, the green powders of 3 and 4 can be reduced back to the orange powders of 1 and 2 by reaction with hydrazine, thus displaying a rare ability for fully reversible chemical redox transitions. Compounds 1-4 are mentioned as a new class of redox-active cluster-based MOFs with potential usage as multifunctional materials for gas separation and chemical contamination sensors.

A novel framework of tissue membrane systems for image fusion.

PubMed

Zhang, Zulin; Yi, Xinzhong; Peng, Hong

2014-01-01

This paper proposes a tissue membrane system-based framework to deal with the optimal image fusion problem. A spatial domain fusion algorithm is given, and a tissue membrane system of multiple cells is used as its computing framework. Based on the multicellular structure and inherent communication mechanism of the tissue membrane system, an improved velocity-position model is developed. The performance of the fusion framework is studied with comparison of several traditional fusion methods as well as genetic algorithm (GA)-based and differential evolution (DE)-based spatial domain fusion methods. Experimental results show that the proposed fusion framework is superior or comparable to the other methods and can be efficiently used for image fusion.

Competences, education and support for new roles in cancer genetics services: outcomes from the cancer genetics pilot projects.

PubMed

Bennett, Catherine; Burton, Hilary; Farndon, Peter

2007-01-01

In 2004 the Department of Health in collaboration with Macmillan Cancer Support set up service development projects to pilot the integration of genetics in mainstream medicine in the area of cancer genetics.In developing these services, new roles and responsibilities were devised that required supporting programmes of education and training. The NHS National Genetics Education and Development Centre has worked with the projects to draw together their experience in these aspects. New roles include the Cancer Family Nurse Specialist, in which a nurse working in a cancer setting was trained to identify and manage genetic or family history concerns, and the Genetic Risk Assessment Practitioner--a small team of practitioners working within a secondary care setting to deliver a standardised risk assessment pathway. Existing roles were also adapted for a different setting, in particular the use of genetic counsellors working in a community ethnic minority setting. These practitioners undertook a range of clinical activities that can be mapped directly to the 'UK National Workforce Competences for Genetics in Clinical Practice for Non-genetics Healthcare Staff' framework developed by Skills for Health and the NHS National Genetics Education and Development Centre (2007; draft competence framework). The main differences between the various roles were in the ordering of genetic tests and the provision of advice on invasive preventive options such as mastectomy. Those involved in service development also needed to develop competences in project management, business skills, audit and evaluation, working with users, general management (personnel, multi-agency work and marketing), educational supervision, IT, public and professional outreach, and research. Important resources to support the development of new roles and competences included pathways and guidelines, a formal statement of competences, a recognised syllabus, appropriate and timely courses, the availability of a mentor, supervision and opportunities to discuss cases, a formal assessment of learning and continuing support from specialist genetics services. This represents a current resource gap that will be of concern to cancer networks and a challenge to providers of educational resources and regional genetics services.

RNAi Screening in Spodoptera frugiperda.

PubMed

Ghosh, Subhanita; Singh, Gatikrushna; Sachdev, Bindiya; Kumar, Ajit; Malhotra, Pawan; Mukherjee, Sunil K; Bhatnagar, Raj K

2016-01-01

RNA interference is a potent and precise reverse genetic approach to carryout large-scale functional genomic studies in a given organism. During the past decade, RNAi has also emerged as an important investigative tool to understand the process of viral pathogenesis. Our laboratory has successfully generated transgenic reporter and RNAi sensor line of Spodoptera frugiperda (Sf21) cells and developed a reversal of silencing assay via siRNA or shRNA guided screening to investigate RNAi factors or viral pathogenic factors with extraordinary fidelity. Here we describe empirical approaches and conceptual understanding to execute successful RNAi screening in Spodoptera frugiperda 21-cell line.

Regional Management Units for Marine Turtles: A Novel Framework for Prioritizing Conservation and Research across Multiple Scales

PubMed Central

Wallace, Bryan P.; DiMatteo, Andrew D.; Hurley, Brendan J.; Finkbeiner, Elena M.; Bolten, Alan B.; Chaloupka, Milani Y.; Hutchinson, Brian J.; Abreu-Grobois, F. Alberto; Amorocho, Diego; Bjorndal, Karen A.; Bourjea, Jerome; Bowen, Brian W.; Dueñas, Raquel Briseño; Casale, Paolo; Choudhury, B. C.; Costa, Alice; Dutton, Peter H.; Fallabrino, Alejandro; Girard, Alexandre; Girondot, Marc; Godfrey, Matthew H.; Hamann, Mark; López-Mendilaharsu, Milagros; Marcovaldi, Maria Angela; Mortimer, Jeanne A.; Musick, John A.; Nel, Ronel; Pilcher, Nicolas J.; Seminoff, Jeffrey A.; Troëng, Sebastian; Witherington, Blair; Mast, Roderic B.

2010-01-01

Background Resolving threats to widely distributed marine megafauna requires definition of the geographic distributions of both the threats as well as the population unit(s) of interest. In turn, because individual threats can operate on varying spatial scales, their impacts can affect different segments of a population of the same species. Therefore, integration of multiple tools and techniques — including site-based monitoring, genetic analyses, mark-recapture studies and telemetry — can facilitate robust definitions of population segments at multiple biological and spatial scales to address different management and research challenges. Methodology/Principal Findings To address these issues for marine turtles, we collated all available studies on marine turtle biogeography, including nesting sites, population abundances and trends, population genetics, and satellite telemetry. We georeferenced this information to generate separate layers for nesting sites, genetic stocks, and core distributions of population segments of all marine turtle species. We then spatially integrated this information from fine- to coarse-spatial scales to develop nested envelope models, or Regional Management Units (RMUs), for marine turtles globally. Conclusions/Significance The RMU framework is a solution to the challenge of how to organize marine turtles into units of protection above the level of nesting populations, but below the level of species, within regional entities that might be on independent evolutionary trajectories. Among many potential applications, RMUs provide a framework for identifying data gaps, assessing high diversity areas for multiple species and genetic stocks, and evaluating conservation status of marine turtles. Furthermore, RMUs allow for identification of geographic barriers to gene flow, and can provide valuable guidance to marine spatial planning initiatives that integrate spatial distributions of protected species and human activities. In addition, the RMU framework — including maps and supporting metadata — will be an iterative, user-driven tool made publicly available in an online application for comments, improvements, download and analysis. PMID:21253007

40 CFR 798.5265 - The salmonella typhimurium reverse mutation assay.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., exogenous glucose 6-phosphate dehydrogenase, NADH and excess of glucose-6-phosphate. (5) Control groups—(i... (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798... number of spontaneous revertants in an untreated and/or vehicle control culture. (2) Description. Several...

40 CFR 798.5265 - The salmonella typhimurium reverse mutation assay.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., exogenous glucose 6-phosphate dehydrogenase, NADH and excess of glucose-6-phosphate. (5) Control groups—(i... (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798... number of spontaneous revertants in an untreated and/or vehicle control culture. (2) Description. Several...

40 CFR 798.5265 - The salmonella typhimurium reverse mutation assay.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., exogenous glucose 6-phosphate dehydrogenase, NADH and excess of glucose-6-phosphate. (5) Control groups—(i... (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798... number of spontaneous revertants in an untreated and/or vehicle control culture. (2) Description. Several...

40 CFR 798.5265 - The salmonella typhimurium reverse mutation assay.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., exogenous glucose 6-phosphate dehydrogenase, NADH and excess of glucose-6-phosphate. (5) Control groups—(i... (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798... number of spontaneous revertants in an untreated and/or vehicle control culture. (2) Description. Several...

40 CFR 798.5265 - The salmonella typhimurium reverse mutation assay.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., exogenous glucose 6-phosphate dehydrogenase, NADH and excess of glucose-6-phosphate. (5) Control groups—(i... (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Genetic Toxicity § 798... number of spontaneous revertants in an untreated and/or vehicle control culture. (2) Description. Several...

Mycobacterium tuberculosis in Wild Asian Elephants, Southern India.

PubMed

Zachariah, Arun; Pandiyan, Jeganathan; Madhavilatha, G K; Mundayoor, Sathish; Chandramohan, Bathrachalam; Sajesh, P K; Santhosh, Sam; Mikota, Susan K

2017-03-01

We tested 3 ild Asian elephants (Elephas maximus) in southern India and confirmed infection in 3 animals with Mycobacterium tuberculosis, an obligate human pathogen, by PCR and genetic sequencing. Our results indicate that tuberculosis may be spilling over from humans (reverse zoonosis) and emerging in wild elephants.

Next-generation sequencing for targeted discovery of rare mutations in rice

USDA-ARS?s Scientific Manuscript database

Advances in DNA sequencing (i.e., next-generation sequencing, NGS) have greatly increased the power and efficiency of detecting rare mutations in large mutant populations. Targeting Induced Local Lesions in Genomes (TILLING) is a reverse genetics approach for identifying gene mutations resulting fro...

Characterization of cis-Acting RNA Elements of Zika Virus by Using a Self-Splicing Ribozyme-Dependent Infectious Clone.

PubMed

Liu, Zhong-Yu; Yu, Jiu-Yang; Huang, Xing-Yao; Fan, Hang; Li, Xiao-Feng; Deng, Yong-Qiang; Ji, Xue; Cheng, Meng-Li; Ye, Qing; Zhao, Hui; Han, Jian-Feng; An, Xiao-Ping; Jiang, Tao; Zhang, Bo; Tong, Yi-Gang; Qin, Cheng-Feng

2017-11-01

Zika virus (ZIKV) has caused significant outbreaks and epidemics in the Americas recently, raising global concern due to its ability to cause microcephaly and other neurological complications. A stable and efficient infectious clone of ZIKV is urgently needed. However, the instability and toxicity of flavivirus cDNA clones in Escherichia coli hosts has hindered the development of ZIKV infectious clones. Here, using a novel self-splicing ribozyme-based strategy, we generated a stable infectious cDNA clone of a contemporary ZIKV strain imported from Venezuela to China in 2016. The constructed clone contained a modified version of the group II self-splicing intron P.li.LSUI2 near the junction between the E and NS1 genes, which were removed from the RNA transcripts by an easy-to-establish in vitro splicing reaction. Transfection of the spliced RNAs into BHK-21 cells led to the production of infectious progeny virus that resembled the parental virus. Finally, potential cis -acting RNA elements in ZIKV genomic RNA were identified based on this novel reverse genetics system, and the critical role of 5'-SLA promoter and 5'-3' cyclization sequences were characterized by a combination of different assays. Our results provide another stable and reliable reverse genetics system for ZIKV that will help study ZIKV infection and pathogenesis, and the novel self-splicing intron-based strategy could be further expanded for the construction of infectious clones from other emerging and reemerging flaviviruses. IMPORTANCE The ongoing Zika virus (ZIKV) outbreaks have drawn global concern due to the unexpected causal link to fetus microcephaly and other severe neurological complications. The infectious cDNA clones of ZIKV are critical for the research community to study the virus, understand the disease, and inform vaccine design and antiviral screening. A panel of existing technologies have been utilized to develop ZIKV infectious clones. Here, we successfully generated a stable infectious clone of a 2016 ZIKV strain using a novel self-splicing ribozyme-based technology that abolished the potential toxicity of ZIKV cDNA clones to the E. coli host. Moreover, two crucial cis -acting replication elements (5'-SLA and 5'-CS) of ZIKV were first identified using this novel reverse genetics system. This novel self-splicing ribozyme-based reverse genetics platform will be widely utilized in future ZIKV studies and provide insight for the development of infectious clones of other emerging viruses. Copyright © 2017 American Society for Microbiology.

Characterization of cis-Acting RNA Elements of Zika Virus by Using a Self-Splicing Ribozyme-Dependent Infectious Clone

PubMed Central

Liu, Zhong-Yu; Yu, Jiu-Yang; Huang, Xing-Yao; Fan, Hang; Li, Xiao-Feng; Deng, Yong-Qiang; Ji, Xue; Cheng, Meng-Li; Ye, Qing; Zhao, Hui; Han, Jian-Feng; An, Xiao-Ping; Jiang, Tao; Zhang, Bo; Tong, Yi-Gang

2017-01-01

ABSTRACT Zika virus (ZIKV) has caused significant outbreaks and epidemics in the Americas recently, raising global concern due to its ability to cause microcephaly and other neurological complications. A stable and efficient infectious clone of ZIKV is urgently needed. However, the instability and toxicity of flavivirus cDNA clones in Escherichia coli hosts has hindered the development of ZIKV infectious clones. Here, using a novel self-splicing ribozyme-based strategy, we generated a stable infectious cDNA clone of a contemporary ZIKV strain imported from Venezuela to China in 2016. The constructed clone contained a modified version of the group II self-splicing intron P.li.LSUI2 near the junction between the E and NS1 genes, which were removed from the RNA transcripts by an easy-to-establish in vitro splicing reaction. Transfection of the spliced RNAs into BHK-21 cells led to the production of infectious progeny virus that resembled the parental virus. Finally, potential cis-acting RNA elements in ZIKV genomic RNA were identified based on this novel reverse genetics system, and the critical role of 5′-SLA promoter and 5′-3′ cyclization sequences were characterized by a combination of different assays. Our results provide another stable and reliable reverse genetics system for ZIKV that will help study ZIKV infection and pathogenesis, and the novel self-splicing intron-based strategy could be further expanded for the construction of infectious clones from other emerging and reemerging flaviviruses. IMPORTANCE The ongoing Zika virus (ZIKV) outbreaks have drawn global concern due to the unexpected causal link to fetus microcephaly and other severe neurological complications. The infectious cDNA clones of ZIKV are critical for the research community to study the virus, understand the disease, and inform vaccine design and antiviral screening. A panel of existing technologies have been utilized to develop ZIKV infectious clones. Here, we successfully generated a stable infectious clone of a 2016 ZIKV strain using a novel self-splicing ribozyme-based technology that abolished the potential toxicity of ZIKV cDNA clones to the E. coli host. Moreover, two crucial cis-acting replication elements (5′-SLA and 5′-CS) of ZIKV were first identified using this novel reverse genetics system. This novel self-splicing ribozyme-based reverse genetics platform will be widely utilized in future ZIKV studies and provide insight for the development of infectious clones of other emerging viruses. PMID:28814522

PT-Flax (phenotyping and TILLinG of flax): development of a flax (Linum usitatissimum L.) mutant population and TILLinG platform for forward and reverse genetics.

PubMed

Chantreau, Maxime; Grec, Sébastien; Gutierrez, Laurent; Dalmais, Marion; Pineau, Christophe; Demailly, Hervé; Paysant-Leroux, Christine; Tavernier, Reynald; Trouvé, Jean-Paul; Chatterjee, Manash; Guillot, Xavier; Brunaud, Véronique; Chabbert, Brigitte; van Wuytswinkel, Olivier; Bendahmane, Abdelhafid; Thomasset, Brigitte; Hawkins, Simon

2013-10-15

Flax (Linum usitatissimum L.) is an economically important fiber and oil crop that has been grown for thousands of years. The genome has been recently sequenced and transcriptomics are providing information on candidate genes potentially related to agronomically-important traits. In order to accelerate functional characterization of these genes we have generated a flax EMS mutant population that can be used as a TILLinG (Targeting Induced Local Lesions in Genomes) platform for forward and reverse genetics. A population of 4,894 M2 mutant seed families was generated using 3 different EMS concentrations (0.3%, 0.6% and 0.75%) and used to produce M2 plants for subsequent phenotyping and DNA extraction. 10,839 viable M2 plants (4,033 families) were obtained and 1,552 families (38.5%) showed a visual developmental phenotype (stem size and diameter, plant architecture, flower-related). The majority of these families showed more than one phenotype. Mutant phenotype data are organised in a database and can be accessed and searched at UTILLdb (http://urgv.evry.inra.fr/UTILLdb). Preliminary screens were also performed for atypical fiber and seed phenotypes. Genomic DNA was extracted from 3,515 M2 families and eight-fold pooled for subsequent mutant detection by ENDO1 nuclease mis-match cleavage. In order to validate the collection for reverse genetics, DNA pools were screened for two genes coding enzymes of the lignin biosynthesis pathway: Coumarate-3-Hydroxylase (C3H) and Cinnamyl Alcohol Dehydrogenase (CAD). We identified 79 and 76 mutations in the C3H and CAD genes, respectively. The average mutation rate was calculated as 1/41 Kb giving rise to approximately 9,000 mutations per genome. Thirty-five out of the 52 flax cad mutant families containing missense or codon stop mutations showed the typical orange-brown xylem phenotype observed in CAD down-regulated/mutant plants in other species. We have developed a flax mutant population that can be used as an efficient forward and reverse genetics tool. The collection has an extremely high mutation rate that enables the detection of large numbers of independant mutant families by screening a comparatively low number of M2 families. The population will prove to be a valuable resource for both fundamental research and the identification of agronomically-important genes for crop improvement in flax.

PT-Flax (phenotyping and TILLinG of flax): development of a flax (Linum usitatissimum L.) mutant population and TILLinG platform for forward and reverse genetics

PubMed Central

2013-01-01

Background Flax (Linum usitatissimum L.) is an economically important fiber and oil crop that has been grown for thousands of years. The genome has been recently sequenced and transcriptomics are providing information on candidate genes potentially related to agronomically-important traits. In order to accelerate functional characterization of these genes we have generated a flax EMS mutant population that can be used as a TILLinG (Targeting Induced Local Lesions in Genomes) platform for forward and reverse genetics. Results A population of 4,894 M2 mutant seed families was generated using 3 different EMS concentrations (0.3%, 0.6% and 0.75%) and used to produce M2 plants for subsequent phenotyping and DNA extraction. 10,839 viable M2 plants (4,033 families) were obtained and 1,552 families (38.5%) showed a visual developmental phenotype (stem size and diameter, plant architecture, flower-related). The majority of these families showed more than one phenotype. Mutant phenotype data are organised in a database and can be accessed and searched at UTILLdb (http://urgv.evry.inra.fr/UTILLdb). Preliminary screens were also performed for atypical fiber and seed phenotypes. Genomic DNA was extracted from 3,515 M2 families and eight-fold pooled for subsequent mutant detection by ENDO1 nuclease mis-match cleavage. In order to validate the collection for reverse genetics, DNA pools were screened for two genes coding enzymes of the lignin biosynthesis pathway: Coumarate-3-Hydroxylase (C3H) and Cinnamyl Alcohol Dehydrogenase (CAD). We identified 79 and 76 mutations in the C3H and CAD genes, respectively. The average mutation rate was calculated as 1/41 Kb giving rise to approximately 9,000 mutations per genome. Thirty-five out of the 52 flax cad mutant families containing missense or codon stop mutations showed the typical orange-brown xylem phenotype observed in CAD down-regulated/mutant plants in other species. Conclusions We have developed a flax mutant population that can be used as an efficient forward and reverse genetics tool. The collection has an extremely high mutation rate that enables the detection of large numbers of independant mutant families by screening a comparatively low number of M2 families. The population will prove to be a valuable resource for both fundamental research and the identification of agronomically-important genes for crop improvement in flax. PMID:24128060

Identification and applications of the Petunia class II Act1/dTph1 transposable element system.

PubMed

Gerats, Tom; Zethof, Jan; Vandenbussche, Michiel

2013-01-01

Transposable genetic elements are considered to be ubiquitous. Despite this, their mutagenic capacity has been exploited in only a few species. The main plant species are maize, Antirrhinum, and Petunia. Representatives of all three major groups of class II elements, viz., hAT-, CACTA- and Mutator-like elements, have been identified in Petunia. Here we focus on the research "history" of the Petunia two-element Act1-dTph1 system and the development of its application in forward- and reverse-genetics studies.

A model for ‘reverse innovation’ in health care

PubMed Central

2013-01-01

‘Reverse innovation,’ a principle well established in the business world, describes the flow of ideas from emerging to more developed economies. There is strong and growing interest in applying this concept to health care, yet there is currently no framework for describing the stages of reverse innovation or identifying opportunities to accelerate the development process. This paper combines the business concept of reverse innovation with diffusion of innovation theory to propose a model for reverse innovation as a way to innovate in health care. Our model includes the following steps: (1) identifying a problem common to lower- and higher-income countries; (2) innovation and spread in the low-income country (LIC); (3) crossover to the higher-income country (HIC); and (4) innovation and spread in the HIC. The crucial populations in this pathway, drawing from diffusion of innovation theory, are LIC innovators, LIC early adopters, and HIC innovators. We illustrate the model with three examples of current reverse innovations. We then propose four sets of specific actions that forward-looking policymakers, entrepreneurs, health system leaders, and researchers may take to accelerate the movement of promising solutions through the reverse innovation pipeline: (1) identify high-priority problems shared by HICs and LICs; (2) create slack for change, especially for LIC innovators, LIC early adopters, and HIC innovators; (3) create spannable social distances between LIC early adopters and HIC innovators; and (4) measure reverse innovation activity globally. PMID:24001367

Genetic stability of Rift Valley fever virus MP-12 vaccine during serial passages in culture cells.

PubMed

Lokugamage, Nandadeva; Ikegami, Tetsuro

2017-01-01

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa which affects both ruminants and humans. RVF causes serious damage to the livestock industry and is also a threat to public health. The Rift Valley fever virus has a segmented negative-stranded RNA genome consisting of Large (L)-, Medium (M)-, and Small (S)-segments. The live-attenuated MP-12 vaccine is immunogenic in livestock and humans, and is conditionally licensed for veterinary use in the U.S. The MP-12 strain encodes 23 mutations (nine amino acid substitutions) and is attenuated through a combination of mutations in the L-, M-, and S-segments. Among them, the M-U795C, M-A3564G, and L-G3104A mutations contribute to viral attenuation through the L- and M-segments. The M-U795C, M-A3564G, L-U533C, and L-G3750A mutations are also independently responsible for temperature-sensitive (ts) phenotype. We hypothesized that a serial passage of the MP-12 vaccine in culture cells causes reversions of the MP-12 genome. The MP-12 vaccine and recombinant rMP12-ΔNSs16/198 were serially passaged 25 times. Droplet digital PCR analysis revealed that the reversion occurred at L-G3750A during passages of MP-12 in Vero or MRC-5 cells. The reversion also occurred at M-A3564G and L-U533C of rMP12-ΔNSs16/198 in Vero cells. Reversion mutations were not found in MP-12 or the variant, rMP12-TOSNSs, in the brains of mice with encephalitis. This study characterized genetic stability of the MP-12 vaccine and the potential risk of reversion mutation at the L-G3750A ts mutation after excessive viral passages in culture cells.

Multivariate selection and intersexual genetic constraints in a wild bird population.

PubMed

Poissant, J; Morrissey, M B; Gosler, A G; Slate, J; Sheldon, B C

2016-10-01

When selection differs between the sexes for traits that are genetically correlated between the sexes, there is potential for the effect of selection in one sex to be altered by indirect selection in the other sex, a situation commonly referred to as intralocus sexual conflict (ISC). While potentially common, ISC has rarely been studied in wild populations. Here, we studied ISC over a set of morphological traits (wing length, tarsus length, bill depth and bill length) in a wild population of great tits (Parus major) from Wytham Woods, UK. Specifically, we quantified the microevolutionary impacts of ISC by combining intra- and intersex additive genetic (co)variances and sex-specific selection estimates in a multivariate framework. Large genetic correlations between homologous male and female traits combined with evidence for sex-specific multivariate survival selection suggested that ISC could play an appreciable role in the evolution of this population. Together, multivariate sex-specific selection and additive genetic (co)variance for the traits considered accounted for additive genetic variance in fitness that was uncorrelated between the sexes (cross-sex genetic correlation = -0.003, 95% CI = -0.83, 0.83). Gender load, defined as the reduction in a population's rate of adaptation due to sex-specific effects, was estimated at 50% (95% CI = 13%, 86%). This study provides novel insights into the evolution of sexual dimorphism in wild populations and illustrates how quantitative genetics and selection analyses can be combined in a multivariate framework to quantify the microevolutionary impacts of ISC. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

iGWAS: Integrative Genome-Wide Association Studies of Genetic and Genomic Data for Disease Susceptibility Using Mediation Analysis.

PubMed

Huang, Yen-Tsung; Liang, Liming; Moffatt, Miriam F; Cookson, William O C M; Lin, Xihong

2015-07-01

Genome-wide association studies (GWAS) have been a standard practice in identifying single nucleotide polymorphisms (SNPs) for disease susceptibility. We propose a new approach, termed integrative GWAS (iGWAS) that exploits the information of gene expressions to investigate the mechanisms of the association of SNPs with a disease phenotype, and to incorporate the family-based design for genetic association studies. Specifically, the relations among SNPs, gene expression, and disease are modeled within the mediation analysis framework, which allows us to disentangle the genetic effect on a disease phenotype into two parts: an effect mediated through a gene expression (mediation effect, ME) and an effect through other biological mechanisms or environment-mediated mechanisms (alternative effect, AE). We develop omnibus tests for the ME and AE that are robust to underlying true disease models. Numerical studies show that the iGWAS approach is able to facilitate discovering genetic association mechanisms, and outperforms the SNP-only method for testing genetic associations. We conduct a family-based iGWAS of childhood asthma that integrates genetic and genomic data. The iGWAS approach identifies six novel susceptibility genes (MANEA, MRPL53, LYCAT, ST8SIA4, NDFIP1, and PTCH1) using the omnibus test with false discovery rate less than 1%, whereas no gene using SNP-only analyses survives with the same cut-off. The iGWAS analyses further characterize that genetic effects of these genes are mostly mediated through their gene expressions. In summary, the iGWAS approach provides a new analytic framework to investigate the mechanism of genetic etiology, and identifies novel susceptibility genes of childhood asthma that were biologically meaningful. © 2015 WILEY PERIODICALS, INC.

A Novel Multi-Sensor Environmental Perception Method Using Low-Rank Representation and a Particle Filter for Vehicle Reversing Safety

PubMed Central

Zhang, Zutao; Li, Yanjun; Wang, Fubing; Meng, Guanjun; Salman, Waleed; Saleem, Layth; Zhang, Xiaoliang; Wang, Chunbai; Hu, Guangdi; Liu, Yugang

2016-01-01

Environmental perception and information processing are two key steps of active safety for vehicle reversing. Single-sensor environmental perception cannot meet the need for vehicle reversing safety due to its low reliability. In this paper, we present a novel multi-sensor environmental perception method using low-rank representation and a particle filter for vehicle reversing safety. The proposed system consists of four main steps, namely multi-sensor environmental perception, information fusion, target recognition and tracking using low-rank representation and a particle filter, and vehicle reversing speed control modules. First of all, the multi-sensor environmental perception module, based on a binocular-camera system and ultrasonic range finders, obtains the distance data for obstacles behind the vehicle when the vehicle is reversing. Secondly, the information fusion algorithm using an adaptive Kalman filter is used to process the data obtained with the multi-sensor environmental perception module, which greatly improves the robustness of the sensors. Then the framework of a particle filter and low-rank representation is used to track the main obstacles. The low-rank representation is used to optimize an objective particle template that has the smallest L-1 norm. Finally, the electronic throttle opening and automatic braking is under control of the proposed vehicle reversing control strategy prior to any potential collisions, making the reversing control safer and more reliable. The final system simulation and practical testing results demonstrate the validity of the proposed multi-sensor environmental perception method using low-rank representation and a particle filter for vehicle reversing safety. PMID:27294931

A Novel Multi-Sensor Environmental Perception Method Using Low-Rank Representation and a Particle Filter for Vehicle Reversing Safety.

PubMed

Zhang, Zutao; Li, Yanjun; Wang, Fubing; Meng, Guanjun; Salman, Waleed; Saleem, Layth; Zhang, Xiaoliang; Wang, Chunbai; Hu, Guangdi; Liu, Yugang

2016-06-09

Environmental perception and information processing are two key steps of active safety for vehicle reversing. Single-sensor environmental perception cannot meet the need for vehicle reversing safety due to its low reliability. In this paper, we present a novel multi-sensor environmental perception method using low-rank representation and a particle filter for vehicle reversing safety. The proposed system consists of four main steps, namely multi-sensor environmental perception, information fusion, target recognition and tracking using low-rank representation and a particle filter, and vehicle reversing speed control modules. First of all, the multi-sensor environmental perception module, based on a binocular-camera system and ultrasonic range finders, obtains the distance data for obstacles behind the vehicle when the vehicle is reversing. Secondly, the information fusion algorithm using an adaptive Kalman filter is used to process the data obtained with the multi-sensor environmental perception module, which greatly improves the robustness of the sensors. Then the framework of a particle filter and low-rank representation is used to track the main obstacles. The low-rank representation is used to optimize an objective particle template that has the smallest L-1 norm. Finally, the electronic throttle opening and automatic braking is under control of the proposed vehicle reversing control strategy prior to any potential collisions, making the reversing control safer and more reliable. The final system simulation and practical testing results demonstrate the validity of the proposed multi-sensor environmental perception method using low-rank representation and a particle filter for vehicle reversing safety.

Heritable Environmental Variance Causes Nonlinear Relationships Between Traits: Application to Birth Weight and Stillbirth of Pigs

PubMed Central

Mulder, Herman A.; Hill, William G.; Knol, Egbert F.

2015-01-01

There is recent evidence from laboratory experiments and analysis of livestock populations that not only the phenotype itself, but also its environmental variance, is under genetic control. Little is known about the relationships between the environmental variance of one trait and mean levels of other traits, however. A genetic covariance between these is expected to lead to nonlinearity between them, for example between birth weight and survival of piglets, where animals of extreme weights have lower survival. The objectives were to derive this nonlinear relationship analytically using multiple regression and apply it to data on piglet birth weight and survival. This study provides a framework to study such nonlinear relationships caused by genetic covariance of environmental variance of one trait and the mean of the other. It is shown that positions of phenotypic and genetic optima may differ and that genetic relationships are likely to be more curvilinear than phenotypic relationships, dependent mainly on the environmental correlation between these traits. Genetic correlations may change if the population means change relative to the optimal phenotypes. Data of piglet birth weight and survival show that the presence of nonlinearity can be partly explained by the genetic covariance between environmental variance of birth weight and survival. The framework developed can be used to assess effects of artificial and natural selection on means and variances of traits and the statistical method presented can be used to estimate trade-offs between environmental variance of one trait and mean levels of others. PMID:25631318

Multi-stimuli-responsive organometallic gels based on ferrocene-linked poly(aryl ether) dendrons: reversible redox switching and Pb2+-ion sensing.

PubMed

Lakshmi, Neelakandan Vidhya; Mandal, Dipendu; Ghosh, Sundargopal; Prasad, Edamana

2014-07-14

We describe the design, synthesis, and "stimuli-responsive" study of ferrocene-linked Fréchet-type [poly(aryl ether)]-dendron-based organometallic gels, in which the ferrocene moiety is attached to the dendron framework through an acyl hydrazone linkage. The low-molecular-weight gelators (LMWGs) form robust gels in both polar and non-polar solvent/solvent mixtures. The organometallic gels undergo stimuli-responsive behavior through 1) thermal, 2) chemical, and 3) electrochemical methods. Among them, conditions 1 and 3 lead to seamlessly reversible with repeated cycles of identical efficiency. Results indicate that the flexible nature of the poly(aryl ether) dendron framework plays a key role in retaining the reversible electrochemical behavior of ferrocene moiety in the LMWGs. Further, the organometallic gelators have exhibited unique selectivity towards Pb(2+) ions (detection limit ≈10(-8)  M). The metal ion-sensing results in a gel-sol phase transition associated with a color change visible to the naked eye. Most importantly, decomplexing the metal ion from the system leads to the regeneration of the initial gel morphology, indicating the restoring ability of the organometallic gel. The metal-ligand binding nature has been analyzed by using (1)H NMR spectroscopy, mass spectrometry, and DFT calculations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Localized past, globalized future: towards an effective bioethical framework using examples from population genetics and medical tourism.

PubMed

Widdows, Heather

2011-02-01

This paper suggests that many of the pressing dilemmas of bioethics are global and structural in nature. Accordingly, global ethical frameworks are required which recognize the ethically significant factors of all global actors. To this end, ethical frameworks must recognize the rights and interests of both individuals and groups (and the interrelation of these). The paper suggests that the current dominant bioethical framework is inadequate to this task as it is over-individualist and therefore unable to give significant weight to the ethical demands of groups (and by extension communal and public goods). It will explore this theme by considering the inadequacy of informed consent (the 'global standard' of bioethics) to address two pressing global bioethical issues: medical tourism and population genetics. Using these examples it will show why consent is inadequate to address all the significant features of these ethical dilemmas. Four key failures will be explored, namely, • That the rights and interests of those related (and therefore affected) are neglected; • That consent fails to take account of the context and commitments of individuals which may constitute inducement and coercion; • That consent alone does not have the ethical weight to negate exploitation or make an unjust action just ('the fallacy of sufficiency'); • That consent is a single one-off act which is inappropriate for the types of decision being made. It will conclude by suggesting that more appropriate models are emerging, particularly in population genetics, which can supplement consent. © 2010 Blackwell Publishing Ltd.

African American Women and Obesity through the Prism of Race

ERIC Educational Resources Information Center

Knox-Kazimierczuk, Francoise; Geller, Karly; Sellers, Sherrill; Taliaferro Baszile, Denise; Smith-Shockley, Meredith

2018-01-01

Background: There are minimal studies focusing on African American women and obesity, and there are even fewer studies examining obesity through a critical race theoretical framework. African American obesity research has largely focused on individual and community interventions, which have not been sufficient to reverse the obesity epidemic.…

Plant-soil feedbacks and the reversal of desertification with climate change

USDA-ARS?s Scientific Manuscript database

Our objective was to provide a conceptual framework for perennial grass recovery in a series of wet years, which includes both plant-soil feedbacks that increase available water to grasses and effects of precipitation on a sequence of recovery-related processes. We tested hypotheses based on this fr...

How the Timing and Quality of Early Experiences Influence the Development of Brain Architecture

ERIC Educational Resources Information Center

Fox, Sharon E.; Levitt, Pat; Nelson, Charles A., III.

2010-01-01

Early life events can exert a powerful influence on both the pattern of brain architecture and behavioral development. In this study a conceptual framework is provided for considering how the structure of early experience gets "under the skin." The study begins with a description of the genetic framework that lays the foundation for brain…

Environmental change, phenotypic plasticity, and genetic compensation.

PubMed

Grether, Gregory F

2005-10-01

When a species encounters novel environmental conditions, some phenotypic characters may develop differently than in the ancestral environment. Most environmental perturbations of development are likely to reduce fitness, and thus selection would usually be expected to favor genetic changes that restore the ancestral phenotype. I propose the term "genetic compensation" to refer to this form of adaptive evolution. Genetic compensation is a subset of genetic accommodation and the reverse of genetic assimilation. When genetic compensation has occurred along a spatial environmental gradient, the mean trait values of populations in different environments may be more similar in the field than when representatives of the same populations are raised in a common environment (i.e., countergradient variation). If compensation is complete, genetic divergence between populations may be cryptic, that is, not detectable in the field. Here I apply the concept of genetic compensation to three examples involving carotenoid-based sexual coloration and then use these and other examples to discuss the concept in a broader context. I show that genetic compensation may lead to a cryptic form of reproductive isolation between populations evolving in different environments, may explain some puzzling cases in which heritable traits exposed to strong directional selection fail to show the expected evolutionary response, and may complicate efforts to monitor populations for signs of environmental deterioration.

Luminescence quenching by reversible ionization or exciplex formation/dissociation.

PubMed

Ivanov, Anatoly I; Burshtein, Anatoly I

2008-11-20

The kinetics of fluorescence quenching by both charge transfer and exciplex formation is investigated, with an emphasis on the reversibility and nonstationarity of the reactions. The Weller elementary kinetic scheme of bimolecular geminate ionization and the Markovian rate theory are shown to lead to identical results, provided the rates of the forward and backward reactions account for the numerous recontacts during the reaction encounter. For excitation quenching by the reversible exciplex formation, the Stern-Volmer constant is specified in the framework of the integral encounter theory. The bulk recombination affecting the Stern-Volmer quenching constant makes it different for pulse excited and stationary luminescence. The theory approves that the free energy gap laws for ionization and exciplex formation are different and only the latter fits properly the available data (for lumiflavin quenching by aliphatic amines and aromatic donors) in the endergonic region.

Thermoelectric energy converters under a trade-off figure of merit with broken time-reversal symmetry

NASA Astrophysics Data System (ADS)

Iyyappan, I.; Ponmurugan, M.

2017-09-01

We study the performance of a three-terminal thermoelectric device such as heat engine and refrigerator with broken time-reversal symmetry by applying the unified trade-off figure of merit (\\dotΩ criterion) which accounts for both useful energy and losses. For the heat engine, we find that a thermoelectric device working under the maximum \\dotΩ criterion gives a significantly better performance than a device working at maximum power output. Within the framework of linear irreversible thermodynamics such a direct comparison is not possible for refrigerators, however, our study indicates that, for refrigerator, the maximum cooling load gives a better performance than the maximum \\dotΩ criterion for a larger asymmetry. Our results can be useful to choose a suitable optimization criterion for operating a real thermoelectric device with broken time-reversal symmetry.

Time-Reversal Generation of Rogue Waves

NASA Astrophysics Data System (ADS)

Chabchoub, Amin; Fink, Mathias

2014-03-01

The formation of extreme localizations in nonlinear dispersive media can be explained and described within the framework of nonlinear evolution equations, such as the nonlinear Schrödinger equation (NLS). Within the class of exact NLS breather solutions on a finite background, which describe the modulational instability of monochromatic wave trains, the hierarchy of rational solutions localized in both time and space is considered to provide appropriate prototypes to model rogue wave dynamics. Here, we use the time-reversal invariance of the NLS to propose and experimentally demonstrate a new approach to constructing strongly nonlinear localized waves focused in both time and space. The potential applications of this time-reversal approach include remote sensing and motivated analogous experimental analysis in other nonlinear dispersive media, such as optics, Bose-Einstein condensates, and plasma, where the wave motion dynamics is governed by the NLS.

Nemo: an evolutionary and population genetics programming framework.

PubMed

Guillaume, Frédéric; Rougemont, Jacques

2006-10-15

Nemo is an individual-based, genetically explicit and stochastic population computer program for the simulation of population genetics and life-history trait evolution in a metapopulation context. It comes as both a C++ programming framework and an executable program file. Its object-oriented programming design gives it the flexibility and extensibility needed to implement a large variety of forward-time evolutionary models. It provides developers with abstract models allowing them to implement their own life-history traits and life-cycle events. Nemo offers a large panel of population models, from the Island model to lattice models with demographic or environmental stochasticity and a variety of already implemented traits (deleterious mutations, neutral markers and more), life-cycle events (mating, dispersal, aging, selection, etc.) and output operators for saving data and statistics. It runs on all major computer platforms including parallel computing environments. The source code, binaries and documentation are available under the GNU General Public License at http://nemo2.sourceforge.net.

Island phytophagy: explaining the remarkable diversity of plant-feeding insects

PubMed Central

Joy, Jeffrey B.; Crespi, Bernard J.

2012-01-01

Plant-feeding insects have undergone unparalleled diversification among different plant taxa, yet explanations for variation in their diversity lack a quantitative, predictive framework. Island biogeographic theory has been applied to spatially discrete habitats but not to habitats, such as host plants, separated by genetic distance. We show that relationships between the diversity of gall-inducing flies and their host plants meet several fundamental predictions from island biogeographic theory. First, plant-taxon genetic distinctiveness, an integrator for long-term evolutionary history of plant lineages, is a significant predictor of variance in the diversity of gall-inducing flies among host-plant taxa. Second, range size and structural complexity also explain significant proportions of the variance in diversity of gall-inducing flies among different host-plant taxa. Third, as with other island systems, plant-lineage age does not predict species diversity. Island biogeographic theory, applied to habitats defined by genetic distance, provides a novel, comprehensive framework for analysing and explaining the diversity of plant-feeding insects and other host-specific taxa. PMID:22553094

Island phytophagy: explaining the remarkable diversity of plant-feeding insects.

PubMed

Joy, Jeffrey B; Crespi, Bernard J

2012-08-22

Plant-feeding insects have undergone unparalleled diversification among different plant taxa, yet explanations for variation in their diversity lack a quantitative, predictive framework. Island biogeographic theory has been applied to spatially discrete habitats but not to habitats, such as host plants, separated by genetic distance. We show that relationships between the diversity of gall-inducing flies and their host plants meet several fundamental predictions from island biogeographic theory. First, plant-taxon genetic distinctiveness, an integrator for long-term evolutionary history of plant lineages, is a significant predictor of variance in the diversity of gall-inducing flies among host-plant taxa. Second, range size and structural complexity also explain significant proportions of the variance in diversity of gall-inducing flies among different host-plant taxa. Third, as with other island systems, plant-lineage age does not predict species diversity. Island biogeographic theory, applied to habitats defined by genetic distance, provides a novel, comprehensive framework for analysing and explaining the diversity of plant-feeding insects and other host-specific taxa.

Genetically Modified Food in Perspective: An Inquiry-Based Curriculum to Help Middle School Students Make Sense of Tradeoffs. Research Report

ERIC Educational Resources Information Center

Seethaler, Sherry; Linn, Marcia

2004-01-01

To understand how students learn about science controversy, this study examines students' reasoning about tradeoffs in the context of a technology-enhanced curriculum about genetically modified food. The curriculum was designed and refined based on the Scaffolded Knowledge Integration Framework to help students sort and integrate their initial…

The Influence of Self-Efficacy Beliefs and Metacognitive Prompting on Genetics Problem Solving Ability among High School Students in Kenya

ERIC Educational Resources Information Center

Aurah, Catherine Muhonja

2013-01-01

Within the framework of social cognitive theory, the influence of self-efficacy beliefs and metacognitive prompting on genetics problem solving ability among high school students in Kenya was examined through a mixed methods research design. A quasi-experimental study, supplemented by focus group interviews, was conducted to investigate both the…

Informing a Learning Progression in Genetics: Which Should Be Taught First, Mendelian Inheritance or the Central Dogma of Molecular Biology?

ERIC Educational Resources Information Center

Duncan, Ravit Golan; Castro-Faix, Moraima; Choi, Jinnie

2016-01-01

The Framework for Science Education and the Next Generation Science Standards in the USA emphasize learning progressions (LPs) that support conceptual coherence and the gradual building of knowledge over time. In the domain of genetics there are two independently developed alternative LPs. In essence, the difference between the two progressions…

Ethical considerations in forensic genetics research on tissue samples collected post-mortem in Cape Town, South Africa.

PubMed

Heathfield, Laura J; Maistry, Sairita; Martin, Lorna J; Ramesar, Raj; de Vries, Jantina

2017-11-29

The use of tissue collected at a forensic post-mortem for forensic genetics research purposes remains of ethical concern as the process involves obtaining informed consent from grieving family members. Two forensic genetics research studies using tissue collected from a forensic post-mortem were recently initiated at our institution and were the first of their kind to be conducted in Cape Town, South Africa. This article discusses some of the ethical challenges that were encountered in these research projects. Among these challenges was the adaptation of research workflows to fit in with an exceptionally busy service delivery that is operating with limited resources. Whilst seeking guidance from the literature regarding research on deceased populations, it was noted that next of kin of decedents are not formally recognised as a vulnerable group in the existing ethical and legal frameworks in South Africa. The authors recommend that research in the forensic mortuary setting is approached using guidance for vulnerable groups, and the benefit to risk standard needs to be strongly justified. Lastly, when planning forensic genetics research, consideration must be given to the potential of uncovering incidental findings, funding to validate these findings and the feedback of results to family members; the latter of which is recommended to occur through a genetic counsellor. It is hoped that these experiences will contribute towards a formal framework for conducting forensic genetic research in medico-legal mortuaries in South Africa.

Lower genetic variability of HIV-1 and antiretroviral drug resistance in pregnant women from the state of Pará, Brazil.

PubMed

Machado, Luiz Fernando Almeida; Costa, Iran Barros; Folha, Maria Nazaré; da Luz, Anderson Levy Bessa; Vallinoto, Antonio Carlos Rosário; Ishak, Ricardo; Ishak, Marluisa Oliveira Guimarães

2017-04-12

The present study aimed to describe the genetic diversity of HIV-1, as well as the resistance profile of the viruses identified in HIV-1 infected pregnant women under antiretroviral therapy in the state of Pará, Northern Brazil. Blood samples were collected from 45 HIV-1 infected pregnant to determine the virus subtypes according to the HIV-1 protease (PR) gene and part of the HIV-1 reverse transcriptase (RT) gene by sequencing the nucleotides of these regions. Drug resistance mutations and susceptibility to antiretroviral drugs were analyzed by the Stanford HIV Drug Resistance Database. Out of 45 samples, only 34 could be amplified for PR and 30 for RT. Regarding the PR gene, subtypes B (97.1%) and C (2.9%) were identified; for the RT gene, subtypes B (90.0%), F (6.7%), and C (3.3%) were detected. Resistance to protease inhibitors (PI) was identified in 5.8% of the pregnant, and mutations conferring resistance to nucleoside reverse transcriptase inhibitors were found in 3.3%, while mutations conferring resistance to non-nucleoside reverse transcriptase inhibitors were found in 3.3%. These results showed a low frequency of strains resistant to antiretroviral drugs, the prevalence of subtypes B and F, and the persistent low transmission of subtype C in pregnant of the state of Pará, Brazil.

Epigenetic events associated with breast cancer and their prevention by dietary components targeting the epigenome

USDA-ARS?s Scientific Manuscript database

Aberrant epigenetic alterations in the genome such as DNA methylation and chromatin remodeling play a significant role in breast cancer development. Since epigenetic alterations are considered to be more easily reversible compared to genetic changes, epigenetic therapy is potentially very useful in ...

Comparison of peanut gentics and physical maps provided insights on collinearity, reversions and translocations

USDA-ARS?s Scientific Manuscript database

Genetic and physical maps are the valuable resources for peanut research community in understanding genome organization and serving as the basis for map-based cloning and marker-assisted selection. Physical maps of two diploid wild peanut progenitor species, Arachis duranensis (A genome) and A. ipae...

Zeolitic imidazolate framework-7: Novel ammonia atmosphere-assisted synthesis, thermal and chemical durability, phase reversibility and potential as highly efficient nanophotocatalyst

NASA Astrophysics Data System (ADS)

Ebrahimi, Arash; Mansournia, Mohammadreza

2018-07-01

This is the first representation of novel sodalite zeolitic imidazolate framework-7 (ZIF-7) which has been made in ethanolic solution at room temperature via an ammonia atmosphere. High thermal stability up to 400 °C is representative of great persistence which has been proved by XRD and TG data. Chemical durability of the as-made ZIF-7 especially at boiled DMF exhibited by XRD patterns can present it as an interesting material without structural alteration after treatment in such harsh condition. Reversible phase transformation of ZIF-7 was totally checked by immersing in ethanol and DMF indicated that the framework can maintain its structural flexibility under heat and solvent treatment. Moreover, the "gate-opening" phenomenon performed by CO2 adsorption-desorption reveals structural breathing effect of ZIF-7 framework that makes it as potential material in CO2 adsorption/separation. In the end, the sacrificial metal-doped (Mn2+, Ni2+, Cu2+, Cd2+ and Ag+) ZIF-7 precursors were applied for preparation of their corresponded metal-doped ZnO as the heterogeneous catalyst to degrade Rhodamine-B (RhB) dye in water under UV-irradiation (up to 99% within 90 min by 0.5% Ag-ZnO (S15)). The recyclability experiment after 5 runs for the optimized catalyst demonstrated that the metal-doped ZnO can be operated consecutively without remarkable decreasing in its activity. These observations exhibit the excellent and beneficial properties of metal-doped ZnO can be as heterogeneous photocatalyst for the removal of organic contaminants in water.

HuR interacts with human immunodeficiency virus type 1 reverse transcriptase, and modulates reverse transcription in infected cells

PubMed Central

Lemay, Julie; Maidou-Peindara, Priscilla; Bader, Thomas; Ennifar, Eric; Rain, Jean-Christophe; Benarous, Richard; Liu, Lang Xia

2008-01-01

Reverse transcription of the genetic material of human immunodeficiency virus type 1 (HIV-1) is a critical step in the replication cycle of this virus. This process, catalyzed by reverse transcriptase (RT), is well characterized at the biochemical level. However, in infected cells, reverse transcription occurs in a multiprotein complex – the reverse transcription complex (RTC) – consisting of viral genomic RNA associated with viral proteins (including RT) and, presumably, as yet uncharacterized cellular proteins. Very little is known about the cellular proteins interacting with the RTC, and with reverse transcriptase in particular. We report here that HIV-1 reverse transcription is affected by the levels of a nucleocytoplasmic shuttling protein – the RNA-binding protein HuR. A direct protein-protein interaction between RT and HuR was observed in a yeast two-hybrid screen and confirmed in vitro by homogenous time-resolved fluorescence (HTRF). We mapped the domain interacting with HuR to the RNAse H domain of RT, and the binding domain for RT to the C-terminus of HuR, partially overlapping the third RRM RNA-binding domain of HuR. HuR silencing with specific siRNAs greatly impaired early and late steps of reverse transcription, significantly inhibiting HIV-1 infection. Moreover, by mutagenesis and immunoprecipitation studies, we could not detect the binding of HuR to the viral RNA. These results suggest that HuR may be involved in and may modulate the reverse transcription reaction of HIV-1, by an as yet unknown mechanism involving a protein-protein interaction with HIV-1 RT. PMID:18544151

Protocol vulnerability detection based on network traffic analysis and binary reverse engineering.

PubMed

Wen, Shameng; Meng, Qingkun; Feng, Chao; Tang, Chaojing

2017-01-01

Network protocol vulnerability detection plays an important role in many domains, including protocol security analysis, application security, and network intrusion detection. In this study, by analyzing the general fuzzing method of network protocols, we propose a novel approach that combines network traffic analysis with the binary reverse engineering method. For network traffic analysis, the block-based protocol description language is introduced to construct test scripts, while the binary reverse engineering method employs the genetic algorithm with a fitness function designed to focus on code coverage. This combination leads to a substantial improvement in fuzz testing for network protocols. We build a prototype system and use it to test several real-world network protocol implementations. The experimental results show that the proposed approach detects vulnerabilities more efficiently and effectively than general fuzzing methods such as SPIKE.

Mathematical modeling of erythrocyte chimerism informs genetic intervention strategies for sickle cell disease.

PubMed

Altrock, Philipp M; Brendel, Christian; Renella, Raffaele; Orkin, Stuart H; Williams, David A; Michor, Franziska

2016-09-01

Recent advances in gene therapy and genome-engineering technologies offer the opportunity to correct sickle cell disease (SCD), a heritable disorder caused by a point mutation in the β-globin gene. The developmental switch from fetal γ-globin to adult β-globin is governed in part by the transcription factor (TF) BCL11A. This TF has been proposed as a therapeutic target for reactivation of γ-globin and concomitant reduction of β-sickle globin. In this and other approaches, genetic alteration of a portion of the hematopoietic stem cell (HSC) compartment leads to a mixture of sickling and corrected red blood cells (RBCs) in periphery. To reverse the sickling phenotype, a certain proportion of corrected RBCs is necessary; the degree of HSC alteration required to achieve a desired fraction of corrected RBCs remains unknown. To address this issue, we developed a mathematical model describing aging and survival of sickle-susceptible and normal RBCs; the former can have a selective survival advantage leading to their overrepresentation. We identified the level of bone marrow chimerism required for successful stem cell-based gene therapies in SCD. Our findings were further informed using an experimental mouse model, where we transplanted mixtures of Berkeley SCD and normal murine bone marrow cells to establish chimeric grafts in murine hosts. Our integrative theoretical and experimental approach identifies the target frequency of HSC alterations required for effective treatment of sickling syndromes in humans. Our work replaces episodic observations of such target frequencies with a mathematical modeling framework that covers a large and continuous spectrum of chimerism conditions. Am. J. Hematol. 91:931-937, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Inferring Regulatory Networks from Experimental Morphological Phenotypes: A Computational Method Reverse-Engineers Planarian Regeneration

PubMed Central

Lobo, Daniel; Levin, Michael

2015-01-01

Transformative applications in biomedicine require the discovery of complex regulatory networks that explain the development and regeneration of anatomical structures, and reveal what external signals will trigger desired changes of large-scale pattern. Despite recent advances in bioinformatics, extracting mechanistic pathway models from experimental morphological data is a key open challenge that has resisted automation. The fundamental difficulty of manually predicting emergent behavior of even simple networks has limited the models invented by human scientists to pathway diagrams that show necessary subunit interactions but do not reveal the dynamics that are sufficient for complex, self-regulating pattern to emerge. To finally bridge the gap between high-resolution genetic data and the ability to understand and control patterning, it is critical to develop computational tools to efficiently extract regulatory pathways from the resultant experimental shape phenotypes. For example, planarian regeneration has been studied for over a century, but despite increasing insight into the pathways that control its stem cells, no constructive, mechanistic model has yet been found by human scientists that explains more than one or two key features of its remarkable ability to regenerate its correct anatomical pattern after drastic perturbations. We present a method to infer the molecular products, topology, and spatial and temporal non-linear dynamics of regulatory networks recapitulating in silico the rich dataset of morphological phenotypes resulting from genetic, surgical, and pharmacological experiments. We demonstrated our approach by inferring complete regulatory networks explaining the outcomes of the main functional regeneration experiments in the planarian literature; By analyzing all the datasets together, our system inferred the first systems-biology comprehensive dynamical model explaining patterning in planarian regeneration. This method provides an automated, highly generalizable framework for identifying the underlying control mechanisms responsible for the dynamic regulation of growth and form. PMID:26042810

A conceptual evolutionary aseismic decision support framework for hospitals

NASA Astrophysics Data System (ADS)

Hu, Yufeng; Dargush, Gary F.; Shao, Xiaoyun

2012-12-01

In this paper, aconceptual evolutionary framework for aseismic decision support for hospitalsthat attempts to integrate a range of engineering and sociotechnical models is presented. Genetic algorithms are applied to find the optimal decision sets. A case study is completed to demonstrate how the frameworkmay applytoa specific hospital.The simulations show that the proposed evolutionary decision support framework is able to discover robust policy sets in either uncertain or fixed environments. The framework also qualitatively identifies some of the characteristicbehavior of the critical care organization. Thus, by utilizing the proposedframework, the decision makers are able to make more informed decisions, especially toenhance the seismic safety of the hospitals.

Breaking the rules: sex roles and genetic mating system of the pheasant coucal.

PubMed

Maurer, G; Double, M C; Milenkaya, O; Süsser, M; Magrath, R D

2011-10-01

Generally in birds, the classic sex roles of male competition and female choice result in females providing most offspring care while males face uncertain parentage. In less than 5% of species, however, reversed courtship sex roles lead to predominantly male care and low extra-pair paternity. These role-reversed species usually have reversed sexual size dimorphism and polyandry, confirming that sexual selection acts most strongly on the sex with the smaller parental investment and accordingly higher potential reproductive rate. We used parentage analyses and observations from three field seasons to establish the social and genetic mating system of pheasant coucals, Centropus phasianinus, a tropical nesting cuckoo, where males are much smaller than females and provide most parental care. Pheasant coucals are socially monogamous and in this study males produced about 80% of calls in the dawn chorus, implying greater male sexual competition. Despite the substantial male investments, extra-pair paternity was unusually high for a socially monogamous, duetting species. Using two or more mismatches to determine extra-pair parentage, we found that 11 of 59 young (18.6%) in 10 of 21 broods (47.6%) were not sired by their putative father. Male incubation, starting early in the laying sequence, may give the female opportunity and reason to seek these extra-pair copulations. Monogamy, rather than the polyandry and sex-role reversal typical of its congener, C. grillii, may be the result of the large territory size, which could prevent females from monopolising multiple males. The pheasant coucal's exceptional combination of classic sex-roles and male-biased care for extra-pair young is hard to reconcile with current sexual selection theory, but may represent an intermediate stage in the evolution of polyandry or an evolutionary remnant of polyandry.

Computational discovery and in vivo validation of hnf4 as a regulatory gene in planarian regeneration.

PubMed

Lobo, Daniel; Morokuma, Junji; Levin, Michael

2016-09-01

Automated computational methods can infer dynamic regulatory network models directly from temporal and spatial experimental data, such as genetic perturbations and their resultant morphologies. Recently, a computational method was able to reverse-engineer the first mechanistic model of planarian regeneration that can recapitulate the main anterior-posterior patterning experiments published in the literature. Validating this comprehensive regulatory model via novel experiments that had not yet been performed would add in our understanding of the remarkable regeneration capacity of planarian worms and demonstrate the power of this automated methodology. Using the Michigan Molecular Interactions and STRING databases and the MoCha software tool, we characterized as hnf4 an unknown regulatory gene predicted to exist by the reverse-engineered dynamic model of planarian regeneration. Then, we used the dynamic model to predict the morphological outcomes under different single and multiple knock-downs (RNA interference) of hnf4 and its predicted gene pathway interactors β-catenin and hh Interestingly, the model predicted that RNAi of hnf4 would rescue the abnormal regenerated phenotype (tailless) of RNAi of hh in amputated trunk fragments. Finally, we validated these predictions in vivo by performing the same surgical and genetic experiments with planarian worms, obtaining the same phenotypic outcomes predicted by the reverse-engineered model. These results suggest that hnf4 is a regulatory gene in planarian regeneration, validate the computational predictions of the reverse-engineered dynamic model, and demonstrate the automated methodology for the discovery of novel genes, pathways and experimental phenotypes. michael.levin@tufts.edu. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Mesoscale pattern formation of self-propelled rods with velocity reversal

NASA Astrophysics Data System (ADS)

Großmann, Robert; Peruani, Fernando; Bär, Markus

2016-11-01

We study self-propelled particles with velocity reversal interacting by uniaxial (nematic) alignment within a coarse-grained hydrodynamic theory. Combining analytical and numerical continuation techniques, we show that the physics of this active system is essentially controlled by the reversal frequency. In particular, we find that elongated, high-density, ordered patterns, called bands, emerge via subcritical bifurcations from spatially homogeneous states. Our analysis reveals further that the interaction of bands is weakly attractive and, consequently, bands fuse upon collision in analogy with nonequilibrium nucleation processes. Moreover, we demonstrate that a renormalized positive line tension can be assigned to stable bands below a critical reversal rate, beyond which they are transversally unstable. In addition, we discuss the kinetic roughening of bands as well as their nonlinear dynamics close to the threshold of transversal instability. Altogether, the reduction of the multiparticle system onto the dynamics of bands provides a unified framework to understand the emergence and stability of nonequilibrium patterns in this self-propelled particle system. In this regard, our results constitute a proof of principle in favor of the hypothesis in microbiology that velocity reversal of gliding rod-shaped bacteria regulates the transitions between various self-organized patterns observed during the bacterial life cycle.

Origin and evolution of SINEs in eukaryotic genomes.

PubMed

Kramerov, D A; Vassetzky, N S

2011-12-01

Short interspersed elements (SINEs) are one of the two most prolific mobile genomic elements in most of the higher eukaryotes. Although their biology is still not thoroughly understood, unusual life cycle of these simple elements amplified as genomic parasites makes their evolution unique in many ways. In contrast to most genetic elements including other transposons, SINEs emerged de novo many times in evolution from available molecules (for example, tRNA). The involvement of reverse transcription in their amplification cycle, huge number of genomic copies and modular structure allow variation mechanisms in SINEs uncommon or rare in other genetic elements (module exchange between SINE families, dimerization, and so on.). Overall, SINE evolution includes their emergence, progressive optimization and counteraction to the cell's defense against mobile genetic elements.

Our retroviral heritage.

PubMed

Patience, C; Wilkinson, D A; Weiss, R A

1997-03-01

Darwin could not have foretold that we are descended from viruses as well as from apes. While there is clear evidence that viral diseases, such as polio and rabies, affected ancient civilizations, viruses were not defined until the early years of this century, shortly after the rediscovery of mendelian genetics. That retroviral genomes can oscillate between infectious and genetic modes of transmission seemed preposterous before the discovery of reverse transcription in 1970. Those of us who had earlier provided mendelian evidence for germ-line transmission of retroviruses were subject of friendly ridicule. Today, the shunting of genetic elements between chromosomes and RNA, and the generation of processed pseudogenes, seems commonplace. It is timely, however, to revisit the topic of human endogenous retroviruses-the subject of this article.

Genetic markers as instrumental variables.

PubMed

von Hinke, Stephanie; Davey Smith, George; Lawlor, Debbie A; Propper, Carol; Windmeijer, Frank

2016-01-01

The use of genetic markers as instrumental variables (IV) is receiving increasing attention from economists, statisticians, epidemiologists and social scientists. Although IV is commonly used in economics, the appropriate conditions for the use of genetic variants as instruments have not been well defined. The increasing availability of biomedical data, however, makes understanding of these conditions crucial to the successful use of genotypes as instruments. We combine the econometric IV literature with that from genetic epidemiology, and discuss the biological conditions and IV assumptions within the statistical potential outcomes framework. We review this in the context of two illustrative applications. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

PubMed Central

2012-01-01

Background Foot-and-mouth disease (FMD) is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong) posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East–South Asia (ME-SA), Southeast Asia (SEA), Cathay (CHY)) in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance. Results The present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes. Conclusions Some amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the wild O/HN/CHA/93 virus. Thus, the full-length cDNA clone of FMDV can be a useful tool to develop genetically engineered FMDV vaccine candidates to help control porcinophilic FMD epidemics in China. PMID:22591597

Synthetic plant defense elicitors

PubMed Central

Bektas, Yasemin; Eulgem, Thomas

2015-01-01

To defend themselves against invading pathogens plants utilize a complex regulatory network that coordinates extensive transcriptional and metabolic reprogramming. Although many of the key players of this immunity-associated network are known, the details of its topology and dynamics are still poorly understood. As an alternative to forward and reverse genetic studies, chemical genetics-related approaches based on bioactive small molecules have gained substantial popularity in the analysis of biological pathways and networks. Use of such molecular probes can allow researchers to access biological space that was previously inaccessible to genetic analyses due to gene redundancy or lethality of mutations. Synthetic elicitors are small drug-like molecules that induce plant defense responses, but are distinct from known natural elicitors of plant immunity. While the discovery of some synthetic elicitors had already been reported in the 1970s, recent breakthroughs in combinatorial chemical synthesis now allow for inexpensive high-throughput screens for bioactive plant defense-inducing compounds. Along with powerful reverse genetics tools and resources available for model plants and crop systems, comprehensive collections of new synthetic elicitors will likely allow plant scientists to study the intricacies of plant defense signaling pathways and networks in an unparalleled fashion. As synthetic elicitors can protect crops from diseases, without the need to be directly toxic for pathogenic organisms, they may also serve as promising alternatives to conventional biocidal pesticides, which often are harmful for the environment, farmers and consumers. Here we are discussing various types of synthetic elicitors that have been used for studies on the plant immune system, their modes-of-action as well as their application in crop protection. PMID:25674095

A Flexible Computational Framework Using R and Map-Reduce for Permutation Tests of Massive Genetic Analysis of Complex Traits.

PubMed

Mahjani, Behrang; Toor, Salman; Nettelblad, Carl; Holmgren, Sverker

2017-01-01

In quantitative trait locus (QTL) mapping significance of putative QTL is often determined using permutation testing. The computational needs to calculate the significance level are immense, 10 4 up to 10 8 or even more permutations can be needed. We have previously introduced the PruneDIRECT algorithm for multiple QTL scan with epistatic interactions. This algorithm has specific strengths for permutation testing. Here, we present a flexible, parallel computing framework for identifying multiple interacting QTL using the PruneDIRECT algorithm which uses the map-reduce model as implemented in Hadoop. The framework is implemented in R, a widely used software tool among geneticists. This enables users to rearrange algorithmic steps to adapt genetic models, search algorithms, and parallelization steps to their needs in a flexible way. Our work underlines the maturity of accessing distributed parallel computing for computationally demanding bioinformatics applications through building workflows within existing scientific environments. We investigate the PruneDIRECT algorithm, comparing its performance to exhaustive search and DIRECT algorithm using our framework on a public cloud resource. We find that PruneDIRECT is vastly superior for permutation testing, and perform 2 ×10 5 permutations for a 2D QTL problem in 15 hours, using 100 cloud processes. We show that our framework scales out almost linearly for a 3D QTL search.

Genetic mating systems and reproductive natural histories of fishes: lessons for ecology and evolution.

PubMed

Avise, John C; Jones, Adam G; Walker, DeEtte; DeWoody, J Andrew

2002-01-01

Fish species have diverse breeding behaviors that make them valuable for testing theories on genetic mating systems and reproductive tactics. Here we review genetic appraisals of paternity and maternity in wild fish populations. Behavioral phenomena quantified by genetic markers in various species include patterns of multiple mating by both sexes; frequent cuckoldry by males and rare cuckoldry by females in nest-tending species; additional routes to surrogate parentage via nest piracy and egg-thievery; egg mimicry by nest-tending males; brood parasitism by helper males in cooperative breeders; clutch mixing in oral brooders; kinship in schooling fry of broadcast spawners; sperm storage by dams in female-pregnant species; and sex-role reversal, polyandry, and strong sexual selection on females in some male-pregnant species. Additional phenomena addressed by genetic parentage analyses in fishes include clustered mutations, filial cannibalism, and local population size. All results are discussed in the context of relevant behavioral and evolutionary theory.

Gene silencing in non-model insects: Overcoming hurdles using symbiotic bacteria for trauma-free sustainable delivery of RNA interference: Sustained RNA interference in insects mediated by symbiotic bacteria: Applications as a genetic tool and as a biocide.

PubMed

Whitten, Miranda; Dyson, Paul

2017-03-01

Insight into animal biology and development provided by classical genetic analysis of the model organism Drosophila melanogaster was an incentive to develop advanced genetic tools for this insect. But genetic systems for the over one million other known insect species are largely undeveloped. With increasing information about insect genomes resulting from next generation sequencing, RNA interference is now the method of choice for reverse genetics, although it is constrained by the means of delivery of interfering RNA. A recent advance to ensure sustained delivery with minimal experimental intervention or trauma to the insect is to exploit commensal bacteria for symbiont-mediated RNA interference. This technology not only offers an efficient means for RNA interference in insects in laboratory conditions, but also has potential for use in the control of human disease vectors, agricultural pests and pathogens of beneficial insects. © 2017 WILEY Periodicals, Inc.

Complex Ancient Genetic Structure and Cultural Transitions in Southern African Populations.

PubMed

Montinaro, Francesco; Busby, George B J; Gonzalez-Santos, Miguel; Oosthuitzen, Ockie; Oosthuitzen, Erika; Anagnostou, Paolo; Destro-Bisol, Giovanni; Pascali, Vincenzo L; Capelli, Cristian

2017-01-01

The characterization of the structure of southern African populations has been the subject of numerous genetic, medical, linguistic, archaeological, and anthropological investigations. Current diversity in the subcontinent is the result of complex events of genetic admixture and cultural contact between early inhabitants and migrants that arrived in the region over the last 2000 years. Here, we analyze 1856 individuals from 91 populations, comprising novel and published genotype data, to characterize the genetic ancestry profiles of 631 individuals from 51 southern African populations. Combining both local ancestry and allele frequency based analyses, we identify a tripartite, ancient, Khoesan-related genetic structure. This structure correlates neither with linguistic affiliation nor subsistence strategy, but with geography, revealing the importance of isolation-by-distance dynamics in the area. Fine-mapping of these components in southern African populations reveals admixture and cultural reversion involving several Khoesan groups, and highlights that Bantu speakers and Coloured individuals have different mixtures of these ancient ancestries. Copyright © 2017 Montinaro et al.

TALENs and CRISPR/Cas9 fuel genetically engineered clinically relevant Xenopus tropicalis tumor models.

PubMed

Naert, Thomas; Van Nieuwenhuysen, Tom; Vleminckx, Kris

2017-01-01

The targeted nuclease revolution (TALENs, CRISPR/Cas9) now allows Xenopus researchers to rapidly generate custom on-demand genetic knockout models. These novel methods to perform reverse genetics are unprecedented and are fueling a wide array of human disease models within the aquatic diploid model organism Xenopus tropicalis (X. tropicalis). This emerging technology review focuses on the tools to rapidly generate genetically engineered X. tropicalis models (GEXM), with a focus on establishment of genuine genetic and clinically relevant cancer models. We believe that due to particular advantageous characteristics, outlined within this review, GEXM will become a valuable alternative animal model for modeling human cancer. Furthermore, we provide perspectives of how GEXM will be used as a platform for elucidation of novel therapeutic targets and for preclinical drug validation. Finally, we also discuss some future prospects on how the recent expansions and adaptations of the CRISPR/Cas9 toolbox might influence and push forward X. tropicalis cancer research. © 2017 Wiley Periodicals, Inc.

Recent Advances in Human Genetics and Epigenetics of Adiposity: Pathway to Precision Medicine?

PubMed

Fall, Tove; Mendelson, Michael; Speliotes, Elizabeth K

2017-05-01

Obesity is a heritable trait that contributes to substantial global morbidity and mortality. Here, we summarize findings from the past decade of genetic and epigenetic research focused on unravelling the underpinnings of adiposity. More than 140 genetic regions now are known to influence adiposity traits. The genetics of general adiposity, as measured by body mass index, and that of abdominal obesity, as measured by waist-to-hip ratio, have distinct biological backgrounds. Gene expression associated with general adiposity is enriched in the nervous system. In contrast, genes associated with abdominal adiposity function in adipose tissue. Recent population-based epigenetic analyses have highlighted additional distinct loci. We discuss how associated genetic variants can lead to understanding causal mechanisms, and to disentangling reverse causation in epigenetic analyses. Discoveries emerging from population genomics are identifying new disease markers and potential novel drug targets to better define and combat obesity and related diseases. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Assessment of Genetic and Nongenetic Interactions for the Prediction of Depressive Symptomatology: An Analysis of the Wisconsin Longitudinal Study Using Machine Learning Algorithms

PubMed Central

Roetker, Nicholas S.; Yonker, James A.; Chang, Vicky; Roan, Carol L.; Herd, Pamela; Hauser, Taissa S.; Hauser, Robert M.

2013-01-01

Objectives. We examined depression within a multidimensional framework consisting of genetic, environmental, and sociobehavioral factors and, using machine learning algorithms, explored interactions among these factors that might better explain the etiology of depressive symptoms. Methods. We measured current depressive symptoms using the Center for Epidemiologic Studies Depression Scale (n = 6378 participants in the Wisconsin Longitudinal Study). Genetic factors were 78 single nucleotide polymorphisms (SNPs); environmental factors—13 stressful life events (SLEs), plus a composite proportion of SLEs index; and sociobehavioral factors—18 personality, intelligence, and other health or behavioral measures. We performed traditional SNP associations via logistic regression likelihood ratio testing and explored interactions with support vector machines and Bayesian networks. Results. After correction for multiple testing, we found no significant single genotypic associations with depressive symptoms. Machine learning algorithms showed no evidence of interactions. Naïve Bayes produced the best models in both subsets and included only environmental and sociobehavioral factors. Conclusions. We found no single or interactive associations with genetic factors and depressive symptoms. Various environmental and sociobehavioral factors were more predictive of depressive symptoms, yet their impacts were independent of one another. A genome-wide analysis of genetic alterations using machine learning methodologies will provide a framework for identifying genetic–environmental–sociobehavioral interactions in depressive symptoms. PMID:23927508

Research on classified real-time flood forecasting framework based on K-means cluster and rough set.

PubMed

Xu, Wei; Peng, Yong

2015-01-01

This research presents a new classified real-time flood forecasting framework. In this framework, historical floods are classified by a K-means cluster according to the spatial and temporal distribution of precipitation, the time variance of precipitation intensity and other hydrological factors. Based on the classified results, a rough set is used to extract the identification rules for real-time flood forecasting. Then, the parameters of different categories within the conceptual hydrological model are calibrated using a genetic algorithm. In real-time forecasting, the corresponding category of parameters is selected for flood forecasting according to the obtained flood information. This research tests the new classified framework on Guanyinge Reservoir and compares the framework with the traditional flood forecasting method. It finds that the performance of the new classified framework is significantly better in terms of accuracy. Furthermore, the framework can be considered in a catchment with fewer historical floods.

Barriers to the use of genetic information for the development of new epilepsy treatments.

PubMed

Ferraro, Thomas N

2016-01-01

Genetic analysis is providing new information on the biological basis of epilepsy at a rapid pace; this article identifies factors acting as major barriers to use of these data for therapy development. Disease heterogeneity is a primary obstacle since so many genes can cause or predispose to epilepsy and the clinical presentation of epilepsy is so diverse, thus making it difficult to define the most therapeutically relevant targets. Further, many epilepsy genes affect brain development, an observation that represents a barrier unto itself given the challenge of reversing or preventing genetically mediated alterations of brain pathway formation. Finally, the lack of appropriate models for testing new therapies is also recognized as a fundamental limitation. Overcoming these barriers will be aided by full characterization of the genetic landscape of epilepsy, elucidation of key pathway points for therapeutic intervention and creation of unique experimental models to validate results.

Convergent functional genomics in addiction research - a translational approach to study candidate genes and gene networks.

PubMed

Spanagel, Rainer

2013-01-01

Convergent functional genomics (CFG) is a translational methodology that integrates in a Bayesian fashion multiple lines of evidence from studies in human and animal models to get a better understanding of the genetics of a disease or pathological behavior. Here the integration of data sets that derive from forward genetics in animals and genetic association studies including genome wide association studies (GWAS) in humans is described for addictive behavior. The aim of forward genetics in animals and association studies in humans is to identify mutations (e.g. SNPs) that produce a certain phenotype; i.e. "from phenotype to genotype". Most powerful in terms of forward genetics is combined quantitative trait loci (QTL) analysis and gene expression profiling in recombinant inbreed rodent lines or genetically selected animals for a specific phenotype, e.g. high vs. low drug consumption. By Bayesian scoring genomic information from forward genetics in animals is then combined with human GWAS data on a similar addiction-relevant phenotype. This integrative approach generates a robust candidate gene list that has to be functionally validated by means of reverse genetics in animals; i.e. "from genotype to phenotype". It is proposed that studying addiction relevant phenotypes and endophenotypes by this CFG approach will allow a better determination of the genetics of addictive behavior.

Development of an innovative immunoassay for CP4EPSPS and Cry1AB genetically modified protein detection and quantification.

PubMed

Ermolli, M; Prospero, A; Balla, B; Querci, M; Mazzeo, A; Van Den Eede, G

2006-09-01

An innovative immunoassay, called enzyme-linked immunoabsorbant assay (ELISA) Reverse, based on a new conformation of the solid phase, was developed. The solid support was expressly designed to be immersed directly in liquid samples to detect the presence of protein targets. Its application is proposed in those cases where a large number of samples have to be screened simultaneously or when the simultaneous detection of different proteins is required. As a first application, a quantitative immunoassay for Cry1AB protein in genetically modified maize was optimized. The method was tested using genetically modified organism concentrations from 0.1 to 2.0%. The limit of detection and limit of quantitation of the method were determined as 0.0056 and 0.0168 (expressed as the percentage of genetically modified organisms content), respectively. A qualitative multiplex assay to assess the presence of two genetically modified proteins simultaneously was also established for the case of the Cry1AB and the CP4EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) present in genetically modified maize and soy, respectively.

Gene Drive for Mosquito Control: Where Did It Come from and Where Are We Headed?

PubMed Central

Macias, Vanessa M.; Ohm, Johanna R.; Rasgon, Jason L.

2017-01-01

Mosquito-borne pathogens place an enormous burden on human health. The existing toolkit is insufficient to support ongoing vector-control efforts towards meeting disease elimination and eradication goals. The perspective that genetic approaches can potentially add a significant set of tools toward mosquito control is not new, but the recent improvements in site-specific gene editing with CRISPR/Cas9 systems have enhanced our ability to both study mosquito biology using reverse genetics and produce genetics-based tools. Cas9-mediated gene-editing is an efficient and adaptable platform for gene drive strategies, which have advantages over innundative release strategies for introgressing desirable suppression and pathogen-blocking genotypes into wild mosquito populations; until recently, an effective gene drive has been largely out of reach. Many considerations will inform the effective use of new genetic tools, including gene drives. Here we review the lengthy history of genetic advances in mosquito biology and discuss both the impact of efficient site-specific gene editing on vector biology and the resulting potential to deploy new genetic tools for the abatement of mosquito-borne disease. PMID:28869513

US system of oversight for genetic testing: a report from the Secretary's Advisory Committee on Genetics, Health and Society.

PubMed

Ferreira-Gonzalez, Andrea; Teutsch, Steven; Williams, Marc S; Au, Sylvia M; Fitzgerald, Kevin T; Miller, Paul Steven; Fomous, Cathy

2008-09-01

As genetic testing technology is integrated into healthcare, increasingly detailed information about individual and population genetic variation is available to patients and providers. Health professionals use genetic testing to diagnose or assess the risk of disease in individuals, families and populations and to guide healthcare decisions. Consumers are beginning to explore personalized genomic services in an effort to learn more about their risk for common diseases. Scientific and technological advances in genetic testing, as with any newly introduced medical technology, present certain challenges to existing frameworks of oversight. In addition, the growing use of genetic testing will require a significant investment in evidence-based assessments to understand the validity and utility of these tests in clinical and personal decisionmaking. To optimize the use of genetic testing in healthcare, all sectors of the oversight system need to be strengthened and yet remain flexible in order to adapt to advances that will inevitably increase the range of genetic tests and methodologies.

A data protection framework for trans-European genetic research projects.

PubMed

Claerhout, Brecht; Forgó, Nikolaus; Krügel, Tina; Arning, Marian; De Moor, Georges

2008-01-01

The paper proposes a data protection framework for trans-European medical research projects, which is based on a technical security infrastructure as well as on organizational measures and contractual obligations. It mainly relies on pseudonymization, an internal Data Protection Authority and on a Trusted Third Party. The outcome is an environment that combines both good research conditions and an extensive protection of patients' privacy.

Small geographic range but not panmictic: how forests structure the endangered Point Arena mountain beaver (Aplodontia rufa nigra)

Treesearch

William J. Zielinski; Fredrick V. Schlexer; Sean A. Parks; Kristine L. Pilgrim; Michael K. Schwartz

2012-01-01

The landscape genetics framework is typically applied to broad regions that occupy only small portions of a species' range. Rarely is the entire range of a taxon the subject of study. We examined the landscape genetic structure of the endangered Point Arena mountain beaver (Aplodontia rufa nigra), whose isolated geographic range is found in a...

The Journal of the Naval Postgraduate School Center for Homeland Defense and Security. Volume 6. Issue 3

DTIC Science & Technology

2010-09-01

genetic relationships between kin.33 Regardless of the underlying mechanism, individual symbiotic relationships can confer multiple benefits to the...allocation guidelines for homeland security and emergency management policymakers. The framework provides an operationally relevant rubric for...S. Wells, The Journey of Man: A Genetic Odyssey (Princeton, NJ: Princeton University Press, 2002). 4 A. Jakubowicz, “Anglo-multiculturalism

Bright, Multi-responsive, Sky-Blue Platinum(II) Phosphors Based on a Tetradentate Chelating Framework.

PubMed

Liu, Lijie; Wang, Xiang; Wang, Nan; Peng, Tai; Wang, Suning

2017-07-24

A new class of highly efficient and stable, blue-phosphorescent Pt II complexes based on a tetradentate chelating framework has been found to exhibit highly sensitive and reversible responses to multiple external stimuli including temperature, pressure, and UV irradiation with distinct phosphorescent color switching-from blue to red or white. Intermolecular excimer formation is the main origin of this intriguing multi-response phenomenon. Highly efficient singlet-oxygen sensitization by the Pt II compounds yields UV-light-induced phosphorescence enhancement and color switching. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reversible capture and release of Cl 2 and Br 2 with a redox-active metal–organic framework

DOE PAGES

Tulchinsky, Yuri; Hendon, Christopher H.; Lomachenko, Kirill A.; ...

2017-03-28

Extreme toxicity, corrosiveness, and volatility pose serious challenges for the safe storage and transportation of elemental chlorine and bromine, which play critical roles in the chemical industry. Solid materials capable of forming stable nonvolatile compounds upon reaction with elemental halogens may partially mitigate these challenges by allowing safe halogen release on demand. Here we demonstrate that elemental halogens quantitatively oxidize coordinatively unsaturated Co(II) ions in a robust azolate metal-organic framework (MOF) to produce stable and safe-to-handle Co(III) materials featuring terminal Co(III)-halogen bonds. Thermal treatment of the oxidized MOF causes homolytic cleavage of the Co(III)-halogen bonds, reduction to Co(II), and concomitantmore » release of elemental halogens. The reversible chemical storage and thermal release of elemental halogens occur with no significant losses of structural integrity, as the parent cobaltous MOF retains its crystallinity and porosity even after three oxidation/reduction cycles. Finally, these results highlight a material operating via redox mechanism that may find utility in the storage and capture of other noxious and corrosive gases.« less

Amine-Functionalized Covalent Organic Framework for Efficient SO2 Capture with High Reversibility.

PubMed

Lee, Gang-Young; Lee, Joohyeon; Vo, Huyen Thanh; Kim, Sangwon; Lee, Hyunjoo; Park, Taiho

2017-04-03

Removing sulfur dioxide (SO 2 ) from exhaust flue gases of fossil fuel power plants is an important issue given the toxicity of SO 2 and subsequent environmental problems. To address this issue, we successfully developed a new series of imide-linked covalent organic frameworks (COFs) that have high mesoporosity with large surface areas to support gas flowing through channels; furthermore, we incorporated 4-[(dimethylamino)methyl]aniline (DMMA) as the modulator to the imide-linked COF. We observed that the functionalized COFs serving as SO 2 adsorbents exhibit outstanding molar SO 2 sorption capacity, i.e., PI-COF-m10 record 6.30 mmol SO 2 g -1 (40 wt%). To our knowledge, it is firstly reported COF as SO 2 sorbent to date. We also observed that the adsorbed SO 2 is completely desorbed in a short time period with remarkable reversibility. These results suggest that channel-wall functional engineering could be a facile and powerful strategy for developing mesoporous COFs for high-performance reproducible gas storage and separation.

Synthesis, structural characterization and high pressure phase transitions of monolithium hydronium sulfate

NASA Astrophysics Data System (ADS)

Banerjee, Debasis; Plonka, Anna M.; Kim, Sun Jin; Xu, Wenqian; Parise, John B.

2013-01-01

A three dimensional lithium hydronium sulfate LiSO4·H3O [1], [space group Pna21a=8.7785(12) Å, b=9.1297(12) Å, c=5.2799(7) Å, V=423.16(10) Å3] was synthesized via solvothermal methods using 1,5-naphthalenedisulfonic acid (1,5-NSA) as the source of sulfate ions. The structure of [1], determined by single crystal X-ray diffraction techniques, consists of corner sharing LiO4 and SO4 tetrahedra, forming an anionic 3-D open framework that is charge balanced by hydronium ions positioned within channels running along [001] and forming strong H-bonding with the framework oxygen atoms. Compound [1] undergoes two reversible phase transitions, involving reorientation of SO42- ions at pressures of approximately 2.5 and 5 GPa at room temperature, as evident from characteristic discontinuous frequency drops in the ν1 mode of the Raman spectra. Additionally, compound [1] forms dense β-lithium sulfate at 300 °C, as evident from temperature dependent powder XRD and combined reversible TGA-DSC experiments.

Introduction to focus issue: quantitative approaches to genetic networks.

PubMed

Albert, Réka; Collins, James J; Glass, Leon

2013-06-01

All cells of living organisms contain similar genetic instructions encoded in the organism's DNA. In any particular cell, the control of the expression of each different gene is regulated, in part, by binding of molecular complexes to specific regions of the DNA. The molecular complexes are composed of protein molecules, called transcription factors, combined with various other molecules such as hormones and drugs. Since transcription factors are coded by genes, cellular function is partially determined by genetic networks. Recent research is making large strides to understand both the structure and the function of these networks. Further, the emerging discipline of synthetic biology is engineering novel gene circuits with specific dynamic properties to advance both basic science and potential practical applications. Although there is not yet a universally accepted mathematical framework for studying the properties of genetic networks, the strong analogies between the activation and inhibition of gene expression and electric circuits suggest frameworks based on logical switching circuits. This focus issue provides a selection of papers reflecting current research directions in the quantitative analysis of genetic networks. The work extends from molecular models for the binding of proteins, to realistic detailed models of cellular metabolism. Between these extremes are simplified models in which genetic dynamics are modeled using classical methods of systems engineering, Boolean switching networks, differential equations that are continuous analogues of Boolean switching networks, and differential equations in which control is based on power law functions. The mathematical techniques are applied to study: (i) naturally occurring gene networks in living organisms including: cyanobacteria, Mycoplasma genitalium, fruit flies, immune cells in mammals; (ii) synthetic gene circuits in Escherichia coli and yeast; and (iii) electronic circuits modeling genetic networks using field-programmable gate arrays. Mathematical analyses will be essential for understanding naturally occurring genetic networks in diverse organisms and for providing a foundation for the improved development of synthetic genetic networks.

Introduction to Focus Issue: Quantitative Approaches to Genetic Networks

NASA Astrophysics Data System (ADS)

Albert, Réka; Collins, James J.; Glass, Leon

2013-06-01

All cells of living organisms contain similar genetic instructions encoded in the organism's DNA. In any particular cell, the control of the expression of each different gene is regulated, in part, by binding of molecular complexes to specific regions of the DNA. The molecular complexes are composed of protein molecules, called transcription factors, combined with various other molecules such as hormones and drugs. Since transcription factors are coded by genes, cellular function is partially determined by genetic networks. Recent research is making large strides to understand both the structure and the function of these networks. Further, the emerging discipline of synthetic biology is engineering novel gene circuits with specific dynamic properties to advance both basic science and potential practical applications. Although there is not yet a universally accepted mathematical framework for studying the properties of genetic networks, the strong analogies between the activation and inhibition of gene expression and electric circuits suggest frameworks based on logical switching circuits. This focus issue provides a selection of papers reflecting current research directions in the quantitative analysis of genetic networks. The work extends from molecular models for the binding of proteins, to realistic detailed models of cellular metabolism. Between these extremes are simplified models in which genetic dynamics are modeled using classical methods of systems engineering, Boolean switching networks, differential equations that are continuous analogues of Boolean switching networks, and differential equations in which control is based on power law functions. The mathematical techniques are applied to study: (i) naturally occurring gene networks in living organisms including: cyanobacteria, Mycoplasma genitalium, fruit flies, immune cells in mammals; (ii) synthetic gene circuits in Escherichia coli and yeast; and (iii) electronic circuits modeling genetic networks using field-programmable gate arrays. Mathematical analyses will be essential for understanding naturally occurring genetic networks in diverse organisms and for providing a foundation for the improved development of synthetic genetic networks.

Nocturnal Reversed Flows Above Parallel Ridges in Perdigão, Portugal

NASA Astrophysics Data System (ADS)

Krishnamurthy, R.; Fernando, H. J.; Leo, L. S.; Vassallo, D.; Hocut, C. M.; Creegan, E.; Rodriguez, C. V.; Palma, J. L.

2017-12-01

Prediction of topographically forced or induced wind events is extremely important for dispersion modeling and wind energy studies in complex terrain. To improve the current understanding of micro-scale processes over complex terrain, a large-scale field experiment was conducted in Perdigão, Portugal from May 1st, 2017 to June 15th, 2017. Measurements over a periodic valley were performed using 52 meteorological met-masts, 30 Doppler Lidars (scanning & vertical profilers), 2 tethered lifting systems and other remote sensing instruments (Sodar-rass, wind profilers & radiometer), and radiosondes were released every 6 hours over the period of study. The observations showed several cases of flow reversals confined to a thin layer of 70 - 100 m above the ridge under stably stratified conditions. These flow reversals were mostly observed during the lee wave formation over the periodic valley. It was observed that the flow reversal occurs predominantly under two atmospheric conditions: a) presence of large recirculation zones on the lee side of the hill causing a pressure gradient between the lee-side floor and the mountain ridge, and b) local change in the horizontal pressure gradient due to differential heating rates of the neighboring valley atmospheres. Microscale flow simulations could capture these observed flow reversals. Based on the network of tower instruments and remote sensing devices, the development, structure and occurrences of the flow reversals are being analyzed and quantified. Since these flow reversals are observed within the rotor swept area of modern wind turbines, they would drastically increase the fatigue loads on wind turbine blades. This presentation will include reversed flow observations from several synchronized scanning Doppler Lidars and meteorological towers and a theoretical framework for reverse flow over parallel valleys.

An integrated conceptual framework for selecting reverse logistics providers in the presence of vagueness

NASA Astrophysics Data System (ADS)

Fırdolaş, Tugba; Önüt, Semih; Kongar, Elif

2005-11-01

In recent years, relating organization's attitude towards sustainable development, environmental management is gaining an increasing interest among researchers in supply chain management. With regard to a long term requirement of a shift from a linear economy towards a cycle economy, businesses should be motivated to embrace change brought about by consumers, government, competition, and ethical responsibility. To achieve business goals and objectives, a company must reply to increasing consumer demand for "green" products and implement environmentally responsible plans. Reverse logistics is an activity within organizations delegated to the customer service function, where customers with warranted or defective products would return them to their supplier. Emergence of reverse logistics enables to provide a competitive advantage and significant return on investment with an indirect effect on profitability. Many organizations are hiring third-party providers to implement reverse logistics programs designed to retain value by getting products back. Reverse logistics vendors play an important role in helping organizations in closing the loop for products offered by the organizations. In this regard, the selection of third-party providers issue is increasingly becoming an area of reverse logistics concept and practice. This study aims to assist managers in determining which third-party logistics provider to collaborate in the reverse logistics process with an alternative approach based on an integrated model using neural networks and fuzzy logic. An illustrative case study is discussed and the best provider is identified through the solution of this model.

Amino acid substitutions in the neuraminidase protein of an H9N2 avian influenza virus affect its airborne transmission in chickens.

PubMed

Lv, Jing; Wei, Liangmeng; Yang, Yan; Wang, Bingxiao; Liang, Wei; Gao, Yuwei; Xia, Xianzhu; Gao, Lili; Cai, Yumei; Hou, Peiqiang; Yang, Huili; Wang, Airong; Huang, Rong; Gao, Jing; Chai, Tongjie

2015-04-18

Cases of H9N2 avian influenza virus (AIV) in poultry are increasing throughout many Eurasian countries, and co-infections with other pathogens have resulted in high morbidity and mortality in poultry. Few studies have investigated the genetic factors of virus airborne transmission which determine the scope of this epidemic. In this study, we used specific-pathogen-free chickens housed in isolators to investigate the airborne transmissibility of five recombinant H9N2 AIV rescued by reverse genetic technology. The results show that airborne transmission of A/Chicken/Shandong/01/2008 (SD01) virus was related to the neuraminidase (NA) gene, and four amino acid mutations (D368E, S370L, E313K and G381D) within the head region of the SD01 NA, reduced virus replication in the respiratory tract of chickens, reduced virus NA activity, and resulted in a loss of airborne transmission ability in chickens. Similarly, reverse mutations of these four amino acids in the NA protein of r01/NASS virus, conferred an airborne transmission ability to the recombinant virus. We conclude that these four NA residues may be significant genetic markers for evaluating potential disease outbreak of H9N2 AIV, and propose that immediate attention should be paid to the airborne transmission of this virus.

Development and evaluation of a culture-independent method for source determination of fecal wastes in surface and storm waters using reverse transcriptase-PCR detection of FRNA coliphage genogroup gene sequences.

PubMed

Paar, Jack; Doolittle, Mark M; Varma, Manju; Siefring, Shawn; Oshima, Kevin; Haugland, Richard A

2015-05-01

A method, incorporating recently improved reverse transcriptase-PCR primer/probe assays and including controls for detecting interferences in RNA recovery and analysis, was developed for the direct, culture-independent detection of genetic markers from FRNA coliphage genogroups I, II & IV in water samples. Results were obtained from an initial evaluation of the performance of this method in analyses of waste water, ambient surface water and stormwater drain and outfall samples from predominantly urban locations. The evaluation also included a comparison of the occurrence of the FRNA genetic markers with genetic markers from general and human-related bacterial fecal indicators determined by current or pending EPA-validated qPCR methods. Strong associations were observed between the occurrence of the putatively human related FRNA genogroup II marker and the densities of the bacterial markers in the stormwater drain and outfall samples. However fewer samples were positive for FRNA coliphage compared to either the general bacterial fecal indicator or the human-related bacterial fecal indicator markers particularly for ambient water samples. Together, these methods show promise as complementary tools for the identification of contaminated storm water drainage systems as well as the determination of human and non-human sources of contamination. Published by Elsevier B.V.

Single-Vector, Single-Injection Recombinant Vesicular Stomatitis Virus Vaccines Against High-Containment Viruses.

PubMed

Whitt, Michael A; Geisbert, Thomas W; Mire, Chad E

2016-01-01

There are many avenues for making an effective vaccine against viruses. Depending on the virus these can include one of the following: inactivation of whole virions; attenuation of viruses; recombinant viral proteins; non-replication-competent virus particles; or surrogate virus vector systems such as vesicular stomatitis virus (VSV). VSV is a prototypic enveloped animal virus that has been used for over four decades to study virus replication, entry, and assembly due to its ability to replicate to high titers in a wide variety of mammalian and insect cells. The use of reverse genetics to recover infectious and single-cycle replicating VSV from plasmid DNA transfected in cell culture began a revolution in the study of recombinant VSV (rVSV). This platform can be manipulated to study the viral genetic sequences and proteins important in the virus life cycle. Additionally, foreign genes can be inserted between naturally occurring or generated start/stop signals and polyadenylation sites within the VSV genome. VSV has a tolerance for foreign gene expression which has led to numerous rVSVs reported in the literature. Of particular interest are the very effective single-dose rVSV vaccine vectors against high-containment viruses such as filoviruses, henipaviruses, and arenaviruses. Herein we describe the methods for selecting foreign antigenic genes, selecting the location within the VSV genome for insertion, generation of rVSV using reverse genetics, and proper vaccine study designs.

A doxycycline-dependent human immunodeficiency virus type 1 replicates in vivo without inducing CD4+ T-cell depletion

PubMed Central

Legrand, Nicolas; van der Velden, Gisela J.; Fang, Raphaël Ho Tsong; Douaisi, Marc; Weijer, Kees; Das, Atze T.; Blom, Bianca; Uittenbogaart, Christel H.; Berkhout, Ben

2012-01-01

A novel genetic approach for the control of virus replication was used for the design of a conditionally replicating human immunodeficiency virus (HIV) variant, HIV-rtTA. HIV-rtTA gene expression and virus replication are strictly dependent on the presence of a non-toxic effector molecule, doxycycline (dox), and thus can be turned on and off at will in a graded and reversible manner. The in vivo replication capacity, pathogenicity and genetic stability of this HIV-rtTA variant were evaluated in a humanized mouse model of haematopoiesis that harbours lymphoid and myeloid components of the human immune system (HIS). Infection of dox-fed BALB Rag/γc HIS (BRG-HIS) mice with HIV-rtTA led to the establishment of a productive infection without CD4+ T-cell depletion. The virus did not show any sign of escape from dox control for up to 10 weeks after the onset of infection. No reversion towards a functional Tat–transactivating responsive (TAR) RNA element axis was observed, confirming the genetic stability of the HIV-rtTA variant in vivo. These results demonstrate the proof of concept that HIV-rtTA replicates efficiently in vivo. HIV-rtTA is a promising tool for fundamental research to study virus–host interactions in vivo in a controlled fashion. PMID:22647372

Assessing the Causality between Blood Pressure and Retinal Vascular Caliber through Mendelian Randomisation

NASA Astrophysics Data System (ADS)

Li, Ling-Jun; Liao, Jiemin; Cheung, Carol Yim-Lui; Ikram, M. Kamran; Shyong, Tai E.; Wong, Tien-Yin; Cheng, Ching-Yu

2016-02-01

We aimed to determine the association between blood pressure (BP) and retinal vascular caliber changes that were free from confounders and reverse causation by using Mendelian randomisation. A total of 6528 participants from a multi-ethnic cohort (Chinese, Malays, and Indians) in Singapore were included in this study. Retinal arteriolar and venular caliber was measured by a semi-automated computer program. Genotyping was done using Illumina 610-quad chips. Meta-analysis of association between BP, and retinal arteriolar and venular caliber across three ethnic groups was performed both in conventional linear regression and Mendelian randomisation framework with a genetic risk score of BP as an instrumental variable. In multiple linear regression models, each 10 mm Hg increase in systolic BP, diastolic BP, and mean arterial BP (MAP) was associated with significant decreases in retinal arteriolar caliber of a 1.4, 3.0, and 2.6 μm, and significant decreases in retinal venular caliber of a 0.6, 0.7, and 0.9 μm, respectively. In a Mendelian randomisation model, only associations between DBP and MAP and retinal arteriolar narrowing remained yet its significance was greatly reduced. Our data showed weak evidence of a causal relationship between elevated BP and retinal arteriolar narrowing.

SteinerNet: a web server for integrating ‘omic’ data to discover hidden components of response pathways

PubMed Central

Tuncbag, Nurcan; McCallum, Scott; Huang, Shao-shan Carol; Fraenkel, Ernest

2012-01-01

High-throughput technologies including transcriptional profiling, proteomics and reverse genetics screens provide detailed molecular descriptions of cellular responses to perturbations. However, it is difficult to integrate these diverse data to reconstruct biologically meaningful signaling networks. Previously, we have established a framework for integrating transcriptional, proteomic and interactome data by searching for the solution to the prize-collecting Steiner tree problem. Here, we present a web server, SteinerNet, to make this method available in a user-friendly format for a broad range of users with data from any species. At a minimum, a user only needs to provide a set of experimentally detected proteins and/or genes and the server will search for connections among these data from the provided interactomes for yeast, human, mouse, Drosophila melanogaster and Caenorhabditis elegans. More advanced users can upload their own interactome data as well. The server provides interactive visualization of the resulting optimal network and downloadable files detailing the analysis and results. We believe that SteinerNet will be useful for researchers who would like to integrate their high-throughput data for a specific condition or cellular response and to find biologically meaningful pathways. SteinerNet is accessible at http://fraenkel.mit.edu/steinernet. PMID:22638579

Time-reversal MUSIC imaging of extended targets.

PubMed

Marengo, Edwin A; Gruber, Fred K; Simonetti, Francesco

2007-08-01

This paper develops, within a general framework that is applicable to rather arbitrary electromagnetic and acoustic remote sensing systems, a theory of time-reversal "MUltiple Signal Classification" (MUSIC)-based imaging of extended (nonpoint-like) scatterers (targets). The general analysis applies to arbitrary remote sensing geometry and sheds light onto how the singular system of the scattering matrix relates to the geometrical and propagation characteristics of the entire transmitter-target-receiver system and how to use this effect for imaging. All the developments are derived within exact scattering theory which includes multiple scattering effects. The derived time-reversal MUSIC methods include both interior sampling, as well as exterior sampling (or enclosure) approaches. For presentation simplicity, particular attention is given to the time-harmonic case where the informational wave modes employed for target interrogation are purely spatial, but the corresponding generalization to broadband fields is also given. This paper includes computer simulations illustrating the derived theory and algorithms.

A Toolkit for bulk PCR-based marker design from next-generation sequence data: application for development of a framework linkage map in bulb onion (Allium cepa L.)

PubMed Central

2012-01-01

Background Although modern sequencing technologies permit the ready detection of numerous DNA sequence variants in any organisms, converting such information to PCR-based genetic markers is hampered by a lack of simple, scalable tools. Onion is an example of an under-researched crop with a complex, heterozygous genome where genome-based research has previously been hindered by limited sequence resources and genetic markers. Results We report the development of generic tools for large-scale web-based PCR-based marker design in the Galaxy bioinformatics framework, and their application for development of next-generation genetics resources in a wide cross of bulb onion (Allium cepa L.). Transcriptome sequence resources were developed for the homozygous doubled-haploid bulb onion line ‘CUDH2150’ and the genetically distant Indian landrace ‘Nasik Red’, using 454™ sequencing of normalised cDNA libraries of leaf and shoot. Read mapping of ‘Nasik Red’ reads onto ‘CUDH2150’ assemblies revealed 16836 indel and SNP polymorphisms that were mined for portable PCR-based marker development. Tools for detection of restriction polymorphisms and primer set design were developed in BioPython and adapted for use in the Galaxy workflow environment, enabling large-scale and targeted assay design. Using PCR-based markers designed with these tools, a framework genetic linkage map of over 800cM spanning all chromosomes was developed in a subset of 93 F2 progeny from a very large F2 family developed from the ‘Nasik Red’ x ‘CUDH2150’ inter-cross. The utility of tools and genetic resources developed was tested by designing markers to transcription factor-like polymorphic sequences. Bin mapping these markers using a subset of 10 progeny confirmed the ability to place markers within 10 cM bins, enabling increased efficiency in marker assignment and targeted map refinement. The major genetic loci conditioning red bulb colour (R) and fructan content (Frc) were located on this map by QTL analysis. Conclusions The generic tools developed for the Galaxy environment enable rapid development of sets of PCR assays targeting sequence variants identified from Illumina and 454 sequence data. They enable non-specialist users to validate and exploit large volumes of next-generation sequence data using basic equipment. PMID:23157543

A toolkit for bulk PCR-based marker design from next-generation sequence data: application for development of a framework linkage map in bulb onion (Allium cepa L.).

PubMed

Baldwin, Samantha; Revanna, Roopashree; Thomson, Susan; Pither-Joyce, Meeghan; Wright, Kathryn; Crowhurst, Ross; Fiers, Mark; Chen, Leshi; Macknight, Richard; McCallum, John A

2012-11-19

Although modern sequencing technologies permit the ready detection of numerous DNA sequence variants in any organisms, converting such information to PCR-based genetic markers is hampered by a lack of simple, scalable tools. Onion is an example of an under-researched crop with a complex, heterozygous genome where genome-based research has previously been hindered by limited sequence resources and genetic markers. We report the development of generic tools for large-scale web-based PCR-based marker design in the Galaxy bioinformatics framework, and their application for development of next-generation genetics resources in a wide cross of bulb onion (Allium cepa L.). Transcriptome sequence resources were developed for the homozygous doubled-haploid bulb onion line 'CUDH2150' and the genetically distant Indian landrace 'Nasik Red', using 454™ sequencing of normalised cDNA libraries of leaf and shoot. Read mapping of 'Nasik Red' reads onto 'CUDH2150' assemblies revealed 16836 indel and SNP polymorphisms that were mined for portable PCR-based marker development. Tools for detection of restriction polymorphisms and primer set design were developed in BioPython and adapted for use in the Galaxy workflow environment, enabling large-scale and targeted assay design. Using PCR-based markers designed with these tools, a framework genetic linkage map of over 800cM spanning all chromosomes was developed in a subset of 93 F(2) progeny from a very large F(2) family developed from the 'Nasik Red' x 'CUDH2150' inter-cross. The utility of tools and genetic resources developed was tested by designing markers to transcription factor-like polymorphic sequences. Bin mapping these markers using a subset of 10 progeny confirmed the ability to place markers within 10 cM bins, enabling increased efficiency in marker assignment and targeted map refinement. The major genetic loci conditioning red bulb colour (R) and fructan content (Frc) were located on this map by QTL analysis. The generic tools developed for the Galaxy environment enable rapid development of sets of PCR assays targeting sequence variants identified from Illumina and 454 sequence data. They enable non-specialist users to validate and exploit large volumes of next-generation sequence data using basic equipment.

An overview of C. elegans biology.

PubMed

Strange, Kevin

2006-01-01

The establishment of Caenorhabditis elegans as a "model organism" began with the efforts of Sydney Brenner in the early 1960s. Brenner's focus was to find a suitable animal model in which the tools of genetic analysis could be used to define molecular mechanisms of development and nervous system function. C. elegans provides numerous experimental advantages for such studies. These advantages include a short life cycle, production of large numbers of offspring, easy and inexpensive laboratory culture, forward and reverse genetic tractability, and a relatively simple anatomy. This chapter will provide a brief overview of C. elegans biology.

The ethical framework for performing research with rare inherited neurometabolic disease patients.

PubMed

Giannuzzi, Viviana; Devlieger, Hugo; Margari, Lucia; Odlind, Viveca Lena; Ragab, Lamis; Bellettato, Cinzia Maria; D'Avanzo, Francesca; Lampe, Christina; Cassis, Linda; Cortès-Saladelafont, Elisenda; Cazorla, Ángels Garcia; Barić, Ivo; Cvitanović-Šojat, Ljerka; Fumić, Ksenija; Dali, Christine I; Bartoloni, Franco; Bonifazi, Fedele; Scarpa, Maurizio; Ceci, Adriana

2017-03-01

The need for performing clinical trials to develop well-studied and appropriate medicines for inherited neurometabolic disease patients faces ethical concerns mainly raising from four aspects: the diseases are rare; include young and very young patients; the neurological impairment may compromise the capability to provide 'consent'; and the genetic nature of the disease leads to further ethical implications. This work is intended to identify the ethical provisions applicable to clinical research involving these patients and to evaluate if these cover the ethical issues. Three searches have been performed on the European regulatory/legal framework, the literature and European Union-funded projects. The European legal framework offers a number of ethical provisions ruling the clinical research on paediatric, rare, inherited diseases with neurological symptoms. In the literature, relevant publications deal with informed consent, newborn genetic screenings, gene therapy and rights/interests of research participants. Additional information raised from European projects on sharing patients' data from different countries, the need to fill the gap of the regulatory framework and to improve information to stakeholders and patients/families. Several recommendations and guidelines on ethical aspects are applicable to the inherited neurometabolic disease research in Europe, even though they suffer from the lack of a common ethical approach. What is Known: • When planning and conducting clinical trials, sponsors and researchers know that clinical trials are to be performed according to well-established ethical rules, and patients should be aware about their rights. • In the cases of paediatric patients, vulnerable patients unable to provide consent, genetic diseases' further rules apply. What is New: • This work discusses which ethical rules apply to ensure protection of patient's rights if all the above-mentioned features coexist. • This work shows available data and information on how these rules have been applied.

The Tgm9-induced indexed insertional mutant collection to conduct community-based reverse genetics studies in soybean

USDA-ARS?s Scientific Manuscript database

Until now, functional analyses of soybean genes have been very arduous because of the lack of a rapid transformation procedure. Recently identified the active endogenous type II transposable element, Tgm9, excises from insertion sites and restores wild-type phenotypes. Thus, this element provides a ...

Recoding structural glycoprotein E2 in classical swine fever virus (CSFV) produces complete virus attenuation in swine and protects infected animals against disease

USDA-ARS?s Scientific Manuscript database

Controlling classical swine fever (CSF) involves vaccination in endemic regions and preemptive slaughter of infected swine herds during epidemics. Generally, live attenuated vaccines induce solid immunity. Using diverse approaches, reverse genetics has been useful in developing classical swine fever...

Diet-influenced chromatin modification and expression of chemopreventive genes by the soy peptide, lunasin

USDA-ARS?s Scientific Manuscript database

Epigenetic silencing of tumor suppressors and pro-apoptosis genes in cancer cells, unlike genetic mutations, can potentially be reversed by the use of DNA demethylating agents (to remove methylation marks on the DNA) and HDAC inhibitors (to increase histone acetylation). It is now well established t...

PhOBF1, a petunia OCS element binding factor, plays an important role in antiviral RNA silencing

USDA-ARS?s Scientific Manuscript database

Virus-induced gene silencing (VIGS) is a common strategy of reverse genetics for characterizing function of genes in plant. The detailed mechanism governing RNA silencing efficiency triggered by virus is largely unclear. Here, we revealed that a petunia (Petunia hybrida) ocs element binding factor, ...

Evidence of a tick RNAi pathway by comparative genomics and reverse genetics screen of targets with known loss-of-function phenotypes in Drosophila

USDA-ARS?s Scientific Manuscript database

The Arthropods are a diverse group of organisms including Chelicerata (ticks, mites, spiders), Crustacea (crabs, shrimps), and Insecta (flies, mosquitoes, beetles, silkworm). The cattle tick, Rhipicephalus (Boophilus) microplus, is an economically significant ectoparasite of cattle affecting cattle...

77 FR 54584 - Final Action Under the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-05

... National Institutes of Health (NIH) Office of Biotechnology Activities, Office of Science Policy (NIH/OBA... in the life sciences, such as directed molecular evolution and viral reverse genetics, has the... synthetic biology), and (2) a recommendation from the National Science Advisory Board for Biosecurity (NSABB...

A plasmid-based reverse genetics system for influenza A virus.

PubMed Central

Pleschka, S; Jaskunas, R; Engelhardt, O G; Zürcher, T; Palese, P; García-Sastre, A

1996-01-01

A reverse genetics system for negative-strand RNA viruses was first successfully developed for influenza viruses. This technology involved the transfection of in vitro-reconstituted ribonucleoprotein (RNP) complexes into influenza virus-infected cells. We have now developed a method that allows intracellular reconstitution of RNP complexes from plasmid-based expression vectors. Expression of a viral RNA-like transcript is achieved from a plasmid containing a truncated human polymerase I (polI) promoter and a ribozyme sequence that generates the desired 3' end by autocatalytic cleavage. The polI-driven plasmid is cotransfected into human 293 cells with polII-responsive plasmids that express the viral PB1, PB2, PA, and NP proteins. This exclusively plasmid-driven system results in the efficient transcription and replication of the viral RNA-like reporter and allows the study of cis- and trans-acting signals involved in the transcription and replication of influenza virus RNAs. Using this system, we have also been able to rescue a synthetic neuraminidase gene into a recombinant influenza virus. This method represents a convenient alternative to the previously established RNP transfection system. PMID:8648766

Reverse Engineering a Signaling Network Using Alternative Inputs

PubMed Central

Tanaka, Hiromasa; Yi, Tau-Mu

2009-01-01

One of the goals of systems biology is to reverse engineer in a comprehensive fashion the arrow diagrams of signal transduction systems. An important tool for ordering pathway components is genetic epistasis analysis, and here we present a strategy termed Alternative Inputs (AIs) to perform systematic epistasis analysis. An alternative input is defined as any genetic manipulation that can activate the signaling pathway instead of the natural input. We introduced the concept of an “AIs-Deletions matrix” that summarizes the outputs of all combinations of alternative inputs and deletions. We developed the theory and algorithms to construct a pairwise relationship graph from the AIs-Deletions matrix capturing both functional ordering (upstream, downstream) and logical relationships (AND, OR), and then interpreting these relationships into a standard arrow diagram. As a proof-of-principle, we applied this methodology to a subset of genes involved in yeast mating signaling. This experimental pilot study highlights the robustness of the approach and important technical challenges. In summary, this research formalizes and extends classical epistasis analysis from linear pathways to more complex networks, facilitating computational analysis and reconstruction of signaling arrow diagrams. PMID:19898612

Recovery of infectious type Asia1 foot-and-mouth disease virus from suckling mice directly inoculated with an RNA polymerase I/II-driven unidirectional transcription plasmid.

PubMed

Lian, Kaiqi; Yang, Fan; Zhu, Zixiang; Cao, Weijun; Jin, Ye; Li, Dan; Zhang, Keshan; Guo, Jianhong; Zheng, Haixue; Liu, Xiangtao

2015-10-02

We developed an RNA polymerase (pol) I- and II-driven plasmid-based reverse genetics system to rescue infectious foot-and-mouth disease virus (FMDV) from cloned cDNA. In this plasmid-based transfection, the full-length viral cDNA was flanked by hammerhead ribozyme (HamRz) and hepatitis delta ribozyme (HdvRz) sequences, which were arranged downstream of the two promoters (cytomegalovirus (CMV) and pol I promoter) and upstream of the terminators and polyadenylation signal, respectively. The utility of this method was demonstrated by the recovery of FMDV Asia1 HN/CHA/06 in BHK-21 cells transfected with cDNA plasmids. Furthermore, infectious FMDV Asia1 HN/CHA/06 could be rescued from suckling mice directly inoculated with cDNA plasmids. Thus, this reverse genetics system can be applied to fundamental research and vaccine studies, most notably to rescue those viruses for which there is currently an absence of a suitable cell culture system. Copyright © 2015 Elsevier B.V. All rights reserved.

Alternative reverse genetics system for influenza viruses based on a synthesized swine 45S rRNA promoter.

PubMed

Wang, Kai; Huang, Qi; Yang, Zhiwei; Qi, Kezong; Liu, Hongmei; Chen, Hongjun

2017-08-01

We generated an alternative reverse genetics (RG) system based on a synthesized swine 45S rRNA promoter to rescue the H3N2 subtype swine influenza virus. All eight flanking segment cassettes of A/swine/Henan/7/2010 (H3N2) were amplified with ambisense expression elements from RG plasmids. All segments were then recombined with the pHC2014 vector, which contained the synthesized swine 45S rRNA promoter (spol1) and its terminal sequence (t1) in a pcDNA3 backbone. As a result, we obtained a set of RG plasmids carrying the corresponding eight-segment cassettes. We efficiently generated the H3N2 virus after transfection into 293T/PK15, PK15, and 293T cells. The efficiency of spol1-driven influenza virus rescue in PK15 cells was similar to that in 293T cells by titration using the human pol1 RG system. Our approach suggests that an alternative spol1-based RG system can produce influenza viruses.

Respiratory Syncytial Virus: Virology, Reverse Genetics, and Pathogenesis of Disease

PubMed Central

Fearns, Rachel; Graham, Barney S.

2016-01-01

Human respiratory syncytial virus (RSV) is an enveloped, nonsegmented negative-strand RNA virus of family Paramyxoviridae. RSV is the most complex member of the family in terms of the number of genes and proteins. It is also relatively divergent and distinct from the prototype members of the family. In the past 30 years, we have seen a tremendous increase in our understanding of the molecular biology of RSV based on a succession of advances involving molecular cloning, reverse genetics, and detailed studies of protein function and structure. Much remains to be learned. RSV disease is complex and variable, and the host and viral factors that determine tropism and disease are poorly understood. RSV is notable for a historic vaccine failure in the 1960s involving a formalin-inactivated vaccine that primed for enhanced disease in RSV naïve recipients. Live vaccine candidates have been shown to be free of this complication. However, development of subunit or other protein-based vaccines for pediatric use is hampered by the possibility of enhanced disease and the difficulty of reliably demonstrating its absence in preclinical studies. PMID:24362682

Obesity-programmed mice are rescued by early genetic intervention

PubMed Central

Bumaschny, Viviana F.; Yamashita, Miho; Casas-Cordero, Rodrigo; Otero-Corchón, Verónica; de Souza, Flávio S.J.; Rubinstein, Marcelo; Low, Malcolm J.

2012-01-01

Obesity is a chronic metabolic disorder affecting half a billion people worldwide. Major difficulties in managing obesity are the cessation of continued weight loss in patients after an initial period of responsiveness and rebound to pretreatment weight. It is conceivable that chronic weight gain unrelated to physiological needs induces an allostatic regulatory state that defends a supranormal adipose mass despite its maladaptive consequences. To challenge this hypothesis, we generated a reversible genetic mouse model of early-onset hyperphagia and severe obesity by selectively blocking the expression of the proopiomelanocortin gene (Pomc) in hypothalamic neurons. Eutopic reactivation of central POMC transmission at different stages of overweight progression normalized or greatly reduced food intake in these obesity-programmed mice. Hypothalamic Pomc rescue also attenuated comorbidities such as hyperglycemia, hyperinsulinemia, and hepatic steatosis and normalized locomotor activity. However, effectiveness of treatment to normalize body weight and adiposity declined progressively as the level of obesity at the time of Pomc induction increased. Thus, our study using a novel reversible monogenic obesity model reveals the critical importance of early intervention for the prevention of subsequent allostatic overload that auto-perpetuates obesity. PMID:23093774

Reversal of a Neurospora Translocation by Crossing over Involving Displaced Rdna, and Methylation of the Rdna Segments That Result from Recombination

PubMed Central

Perkins, David D.; Metzenberg, Robert L.; Raju, Namboori B.; Selker, Eric U.; Barry, Edward G.

1986-01-01

In translocation OY321 of Neurospora crassa, the nucleolus organizer is divided into two segments, a proximal portion located interstitially in one interchange chromosome, and a distal portion now located terminally on another chromosome, linkage group I. In crosses of Translocation x Translocation, exceptional progeny are recovered nonselectively in which the chromosome sequence has apparently reverted to Normal. Genetic, cytological, and molecular evidence indicates that reversion is the result of meiotic crossing over between homologous displaced rDNA repeats. Marker linkages are wild type in these exceptional progeny. They differ from wild type, however, in retaining an interstitial block of rRNA genes which can be demonstrated cytologically by the presence of a second, small interstitial nucleolus and genetically by linkage of an rDNA restriction site polymorphism to the mating-type locus in linkage group I. The interstitial rDNA is more highly methylated than the terminal rDNA. The mechanism by which methylation enzymes distinguish between interstitial rDNA and terminal rDNA is unknown. Some hypotheses are considered. PMID:2947829

Partial and Full PCR-Based Reverse Genetics Strategy for Influenza Viruses

PubMed Central

Chen, Hongjun; Ye, Jianqiang; Xu, Kemin; Angel, Matthew; Shao, Hongxia; Ferrero, Andrea; Sutton, Troy; Perez, Daniel R.

2012-01-01

Since 1999, plasmid-based reverse genetics (RG) systems have revolutionized the way influenza viruses are studied. However, it is not unusual to encounter cloning difficulties for one or more influenza genes while attempting to recover virus de novo. To overcome some of these shortcomings we sought to develop partial or full plasmid-free RG systems. The influenza gene of choice is assembled into a RG competent unit by virtue of overlapping PCR reactions containing a cDNA copy of the viral gene segment under the control of RNA polymerase I promoter (pol1) and termination (t1) signals – herein referred to as Flu PCR amplicons. Transfection of tissue culture cells with either HA or NA Flu PCR amplicons and 7 plasmids encoding the remaining influenza RG units, resulted in efficient virus rescue. Likewise, transfections including both HA and NA Flu PCR amplicons and 6 RG plasmids also resulted in efficient virus rescue. In addition, influenza viruses were recovered from a full set of Flu PCR amplicons without the use of plasmids. PMID:23029501

Genetic quality and sexual selection: an integrated framework for good genes and compatible genes.

PubMed

Neff, Bryan D; Pitcher, Trevor E

2005-01-01

Why are females so choosy when it comes to mating? This question has puzzled and marveled evolutionary and behavioral ecologists for decades. In mating systems in which males provide direct benefits to the female or her offspring, such as food or shelter, the answer seems straightforward--females should prefer to mate with males that are able to provide more resources. The answer is less clear in other mating systems in which males provide no resources (other than sperm) to females. Theoretical models that account for the evolution of mate choice in such nonresource-based mating systems require that females obtain a genetic benefit through increased offspring fitness from their choice. Empirical studies of nonresource-based mating systems that are characterized by strong female choice for males with elaborate sexual traits (like the large tail of peacocks) suggest that additive genetic benefits can explain only a small percentage of the variation in fitness. Other research on genetic benefits has examined nonadditive effects as another source of genetic variation in fitness and a potential benefit to female mate choice. In this paper, we review the sexual selection literature on genetic quality to address five objectives. First, we attempt to provide an integrated framework for discussing genetic quality. We propose that the term 'good gene' be used exclusively to refer to additive genetic variation in fitness, 'compatible gene' be used to refer to nonadditive genetic variation in fitness, and 'genetic quality' be defined as the sum of the two effects. Second, we review empirical approaches used to calculate the effect size of genetic quality and discuss these approaches in the context of measuring benefits from good genes, compatible genes and both types of genes. Third, we discuss biological mechanisms for acquiring and promoting offspring genetic quality and categorize these into three stages during breeding: (i) precopulatory (mate choice); (ii) postcopulatory, prefertilization (sperm utilization); and (iii) postcopulatory, postfertilization (differential investment). Fourth, we present a verbal model of the effect of good genes sexual selection and compatible genes sexual selection on population genetic variation in fitness, and discuss the potential trade-offs that might exist between mate choice for good genes and mate choice for compatible genes. Fifth, we discuss some future directions for research on genetic quality and sexual selection.

Multilayer Optimization of Heterogeneous Networks Using Grammatical Genetic Programming.

PubMed

Fenton, Michael; Lynch, David; Kucera, Stepan; Claussen, Holger; O'Neill, Michael

2017-09-01

Heterogeneous cellular networks are composed of macro cells (MCs) and small cells (SCs) in which all cells occupy the same bandwidth. Provision has been made under the third generation partnership project-long term evolution framework for enhanced intercell interference coordination (eICIC) between cell tiers. Expanding on previous works, this paper instruments grammatical genetic programming to evolve control heuristics for heterogeneous networks. Three aspects of the eICIC framework are addressed including setting SC powers and selection biases, MC duty cycles, and scheduling of user equipments (UEs) at SCs. The evolved heuristics yield minimum downlink rates three times higher than a baseline method, and twice that of a state-of-the-art benchmark. Furthermore, a greater number of UEs receive transmissions under the proposed scheme than in either the baseline or benchmark cases.

Technological innovations in forensic genetics: social, legal and ethical aspects.

PubMed

Wienroth, Matthias; Morling, Niels; Williams, Robin

2014-01-01

This paper discusses the nature of four waves of technological innovations in forensic genetics alongside the social, legal and ethical aspect of these innovations. It emphasises the way in which technological advances and their socio-legal frameworks are co-produced, shaping technology expectations, social identities, and legal institutions. It also considers how imagined and actual uses of forensic genetic technologies are entangled with assertions about social order, affirmations of common values and civil rights, and promises about security and justice. Our comments seek to encourage the participation of scientific actors in the development of anticipatory governance deliberations concerning the widening application of forensic genetics in an increasing number of criminal and civil jurisdictions.

Effects of methyl testosterone exposure on sexual differentiation in medaka, Oryzias latipes

USGS Publications Warehouse

Papoulias, D.M.; Noltie, Douglas B.; Tillitt, D.E.

2000-01-01

Studies were conducted to characterize effects of a known androgen on sexual differentiation and development of medaka, Oryzias latipes (d-rR strain), at two life stages. Embryos were injected with graded doses of methyl testosterone (MT) prior to epiboly. The occurrence of sex-reversal, and the gonadosomatic index (GSI) were evaluated in adults. Primary germ cells were counted and gonad volumes calculated for larvae to determine if sex-reversal could be detected at an early life stage. Sex-reversal of genetic females to phenotypic males was observed at both life stages. The GSI for phenotypic females was greater than for phenotypic males, while the GSI in XX males was similar to XY males. MT appeared to reduce the GSI of XX females exposed to MT but not sex-reversed. Our results indicate that embryonic exposure to androgens influences sexual development in medaka. Utilizing the d-rR strain of medaka allows detection of an effect as early as 2 weeks after chemical exposure making this a useful tool to screen chemicals for effects on sexual differentiation. Copyright (C) 2000.

Reversal learning and resurgence of operant behavior in zebrafish (Danio rerio).

PubMed

Kuroda, Toshikazu; Mizutani, Yuto; Cançado, Carlos R X; Podlesnik, Christopher A

2017-09-01

Zebrafish are used extensively as vertebrate animal models in biomedical research for having such features as a fully sequenced genome and transparent embryo. Yet, operant-conditioning studies with this species are scarce. The present study investigated reversal learning and resurgence of operant behavior in zebrafish. A target response (approaching a sensor) was reinforced in Phase 1. In Phase 2, the target response was extinguished while reinforcing an alternative response (approaching a different sensor). In Phase 3, extinction was in effect for the target and alternative responses. Reversal learning was demonstrated when responding tracked contingency changes between Phases 1 and 2. Moreover, resurgence occurred in 10 of 13 fish in Phase 3: Target response rates increased transiently and exceeded rates of an unreinforced control response. The present study provides the first evidence with zebrafish supporting reversal learning between discrete operant responses and a laboratory model of relapse. These findings open the possibility to assessing genetic influences of operant behavior generally and in models of relapse (e.g., resurgence, renewal, reinstatement). Copyright © 2017 Elsevier B.V. All rights reserved.

Reversible surgical model of biliary inflammation and obstructive jaundice in mice.

PubMed

Kirkland, Jacob G; Godfrey, Cody B; Garrett, Ryan; Kakar, Sanjay; Yeh, Benjamin M; Corvera, Carlos U

2010-12-01

Common bile duct (CBD) ligation is used in animal models to induce biliary inflammation, fibrosis, and cholestatic liver injury, but results in a high early postoperative mortality rate, probably from traumatic pancreatitis. We modified the CBD ligation model in mice by placing a small metal clip across the lower end of the CBD. To reverse biliary obstruction, a suture was incorporated within the clip during its placement. The suture and clip were removed on postoperative d 5 or 10 for biliary decompression. After 5 d of biliary obstruction, the gallbladder showed an 8-fold increase in wall thickness and a 17-fold increase in tissue myeloperoxidase activity. Markedly elevated serum levels of alkaline phosphatase and bilirubin indicated injury to the biliary epithelium and hepatocytes. Early postoperative (d 0-2) survival was 100% and later (d 3-5) survival was 85% (n=54 mice). We successfully reversed biliary obstruction in 20 mice (37%). Overall survival after reversal was 70%. In surviving mice, biliary decompression was complete, inflammation was reduced, and jaundice resolved. Histologic features confirmed reduced epithelial damage, edema, and neutrophil infiltration. Our technique minimized postoperative death, maintained an effective inflammatory response, and was easily reversible without requiring repeat laparotomy. This reversible model can be used to further define molecular mechanisms of biliary inflammation, fibrosis, and liver injury in genetically altered mice. Copyright © 2010. Published by Elsevier Inc.

[Practical guidelines for genetic testing in cardiovascular diseases].

PubMed

Reinhard, W; Trenkwalder, T; Schunkert, H

2017-08-01

In the last decade, genetic testing for cardiovascular disorders has become more and more relevant. Progress in molecular genetics has led to new opportunities for diagnostics, improved risk prediction and could lead to novel therapeutic approaches. Genetic diagnostic testing is relevant for both confirming a diagnosis as well as deciding on therapeutic consequences, if applicable. Furthermore, predictive testing in family members for specific cardiovascular diseases is now a standard procedure in holistic patient management. The process of genetic testing as well as documentation requirements and discussion of test results with patients are subject to legal regulations. These regulations might be confusing for clinical practitioners/cardiologists. The aim of this article is to provide a clinical framework for genetic testing. First, we explain the legal and ethical background. Second, we illustrate the process of genetic testing step by step and present updates on remuneration. Finally, we discuss the significance of genetic testing and specific disease indications in cardiology.