WorldWideScience

Sample records for exposure reverses genetic

  1. Lassa Virus Reverse Genetics.

    Science.gov (United States)

    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.

  2. Marburg Virus Reverse Genetics Systems

    Directory of Open Access Journals (Sweden)

    Kristina Maria Schmidt

    2016-06-01

    Full Text Available 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.

  3. Reverse genetics in ecological research.

    Directory of Open Access Journals (Sweden)

    Jens Schwachtje

    Full Text Available By precisely manipulating the expression of individual genetic elements thought to be important for ecological performance, reverse genetics has the potential to revolutionize plant ecology. However, untested concerns about possible side-effects of the transformation technique, caused by Agrobacterium infection and tissue culture, on plant performance have stymied research by requiring onerous sample sizes. We compare 5 independently transformed Nicotiana attenuata lines harboring empty vector control (EVC T-DNA lacking silencing information with isogenic wild types (WT, and measured a battery of ecologically relevant traits, known to be important in plant-herbivore interactions: phytohormones, secondary metabolites, growth and fitness parameters under stringent competitive conditions, and transcriptional regulation with microarrays. As a positive control, we included a line silenced in trypsin proteinase inhibitor gene (TPI expression, a potent anti-herbivore defense known to exact fitness costs in its expression, in the analysis. The experiment was conducted twice, with 10 and 20 biological replicates per genotype. For all parameters, we detected no difference between any EVC and WT lines, but could readily detect a fitness benefit of silencing TPI production. A statistical power analyses revealed that the minimum sample sizes required for detecting significant fitness differences between EVC and WT was 2-3 orders of magnitude larger than the 10 replicates required to detect a fitness effect of TPI silencing. We conclude that possible side-effects of transformation are far too low to obfuscate the study of ecologically relevant phenotypes.

  4. Reverse genetics: Its origins and prospects

    Energy Technology Data Exchange (ETDEWEB)

    Berg, P. (Stanford Univ., CA (United States))

    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.

  5. instability and reversal of genetic correlations during selection on ...

    Indian Academy of Sciences (India)

    Unknown

    Instability, disappearance and reversal of patterns of genetic covariation often occur over short evolutionary time frames and as the ... Keywords. evolution; life history; genetic correlation; experimental evolution; growth rate; Drosophila melanogaster. .... factors such as inbreeding depression or G × E interac- tion and isolate ...

  6. Genetic program based data mining to reverse engineer digital logic

    Science.gov (United States)

    Smith, James F., III; Nguyen, Thanh Vu H.

    2006-04-01

    A data mining based procedure for automated reverse engineering and defect discovery has been developed. The data mining algorithm for reverse engineering uses a genetic program (GP) as a data mining function. A genetic program is an algorithm based on the theory of evolution that automatically evolves populations of computer programs or mathematical expressions, eventually selecting one that is optimal in the sense it maximizes a measure of effectiveness, referred to as a fitness function. The system to be reverse engineered is typically a sensor. Design documents for the sensor are not available and conditions prevent the sensor from being taken apart. The sensor is used to create a database of input signals and output measurements. Rules about the likely design properties of the sensor are collected from experts. The rules are used to create a fitness function for the genetic program. Genetic program based data mining is then conducted. This procedure incorporates not only the experts' rules into the fitness function, but also the information in the database. The information extracted through this process is the internal design specifications of the sensor. Uncertainty related to the input-output database and the expert based rule set can significantly alter the reverse engineering results. Significant experimental and theoretical results related to GP based data mining for reverse engineering will be provided. Methods of quantifying uncertainty and its effects will be presented. Finally methods for reducing the uncertainty will be examined.

  7. Incomplete reversibility of platelet inhibition following prolonged exposure to ticagrelor.

    Science.gov (United States)

    Gerrits, A J; Jakubowski, J A; Sugidachi, A; Michelson, A D; Frelinger, A L

    2017-05-01

    Essentials Irreversible platelet inhibition persists after reversibly-binding ticagrelor is discontinued. Reversibility of platelet inhibition by ticagrelor and its active metabolite was assessed. Incomplete recovery was observed after prolonged exposure to ticagrelor. Activated GPIIb-IIIa and P-selectin, not platelet reactivity index, showed irreversibility. Introduction Ticagrelor is described as a reversible P2Y12 antagonist. However, residual platelet inhibition persists after discontinuation of ticagrelor when plasma levels are undetectable. We assessed the reversibility of platelet inhibition by ticagrelor and its active metabolite (T-AM) in comparison with cangrelor and prasugrel's active metabolite (P-AM). Methods Whole blood was treated in vitro with ~ 50% inhibitory concentrations of ticagrelor, T-AM, cangrelor, P-AM and assessed for ADP-stimulated activated GPIIb-IIIa and P-selectin and vasodilator-stimulated phosphoprotein (VASP) platelet reactivity index (PRI) before and after 100-fold dilution. Results Platelets exposed for 30 min to ticagrelor, T-AM or cangrelor showed full recovery of activated GPIIb-IIIa but only partial recovery of P-selectin. Longer exposure (24 h) to the drug decreased reversibility of activated GPIIb-IIIa by ticagrelor (65.1% [49.5-80.6], % of vehicle with 95% confidence interval [CI]) and T-AM (88.8% [79.2-98.3]), but not by cangrelor (101.4% [96.4-106.4]). Compared with 30 min exposure, the reversibility of P-selectin further decreased after 24 h exposure to ticagrelor (from 91.8% [82.1-101.5] to 51.8% [45.5-85.0]), but not T-AM (from 79.0% [67.8-90.3] to 77.4% [61.8-93.1]) or cangrelor (from 76.0% [67.6-84.4] to 76.2% [70.6-81.8]). In contrast, 24 h exposure to ticagrelor, T-AM and cangrelor resulted in full recovery of platelet reactivity as measured by PRI. Platelets exposed to P-AM showed no recovery of ADP reactivity. Conclusions Incomplete recovery after prolonged exposure to ticagrelor, observed by activated GPIIb

  8. Reverse Genetics Approaches for the Development of Influenza Vaccines

    Science.gov (United States)

    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

  9. OryGenesDB: a database for rice reverse genetics

    NARCIS (Netherlands)

    Droc, G.; Ruiz, M.; Larmande, P.; Pereira, A.B.; Piffanelli, P.; Morel, J.B.; Dievart, A.; Courtois, B.; Guiderdoni, E.; Perin, C.

    2006-01-01

    Insertional mutant databases containing Flanking Sequence Tags (FSTs) are becoming key resources for plant functional genomics. We have developed OryGenesDB (http://orygenesdb.cirad.fr/), a database dedicated to rice reverse genetics. Insertion mutants of rice genes are catalogued by Flanking

  10. The reverse genetics applied to fish RNA viruses

    Directory of Open Access Journals (Sweden)

    Biacchesi Stéphane

    2011-01-01

    Full Text Available Abstract Aquaculture has expanded rapidly to become a major economic and food-producing sector worldwide these last 30 years. In parallel, viral diseases have emerged and rapidly spread from farm to farm causing enormous economic losses. The most problematic viruses encountered in the field are mainly, but not exclusively, RNA viruses belonging to the Novirhabdovirus, Aquabirnavirus, Alphavirus and Betanodavirus genera. The recent establishment of reverse genetics systems to recover infectious fish RNA viruses entirely from cDNA has made possible to genetically manipulate the viral genome. These systems have provided powerful tools to study all aspects of the virus biology and virus-host interactions but also gave the opportunity to use these viruses as live vaccines or as gene vectors. This review provides an overview on the recent breakthroughs achieved by using these reverse genetics systems in terms of viral protein function, virulence and host-specificity factor, vaccine development and vector design.

  11. CRISPR: a Versatile Tool for Both Forward and Reverse Genetics Research

    OpenAIRE

    Gurumurthy, Channabasavaiah B.; Grati, M'Hamed; Ohtsuka, Masato; Schilit, Samantha L P; Quadros, Rolen M.; Liu, Xue Zhong

    2016-01-01

    Human genetics research employs the two opposing approaches of forward and reverse genetics. While forward genetics identifies and links a mutation to an observed disease etiology, reverse genetics induces mutations in model organisms to study their role in disease. In most cases, causality for mutations identified by forward genetics is confirmed by reverse genetics through the development of genetically engineered animal models and an assessment of whether the model can recapitulate the dis...

  12. Using a Reversed Exposure Time Calculator for Querying Uncalibrated Archives

    Science.gov (United States)

    Voisin, B.; Micol, A.; Tuairisg, S. Ó.; Butler, R.; Golden, A.; Shearer, A.

    2004-07-01

    Mining large quantities of uncalibrated archives, for specific sources can prove to be a hard task. Even an automated search engine able to use an archive metadata (instrument, a filter, exposure time...) is not completely sufficient. Indeed, without calibration it is difficult to know whether an interesting source can be seen on images without actually looking. Here, we show how a ``reversed'' exposure time calculator can be used to efficiently process the database-stored image descriptors of the ESO/Wide Field Imager (WFI) archive, and compute the corresponding limiting magnitudes. The end result is a more scientific description of the ESO/ST-ECF archive contents, allowing a more astronomer-friendly archive user interface, and hence increasing the archive useability in the context of a Virtual Observatory. This method is developed for improving the Querator search engine of ESO/HST archive, in the context of the EC funded ASTROVIRTEL project.

  13. Genetic Synthesis of New Reversible/Quantum Ternary Comparator

    Directory of Open Access Journals (Sweden)

    DEIBUK, V.

    2015-08-01

    Full Text Available Methods of quantum/reversible logic synthesis are based on the use of the binary nature of quantum computing. However, multiple-valued logic is a promising choice for future quantum computer technology due to a number of advantages over binary circuits. In this paper we have developed a synthesis of ternary reversible circuits based on Muthukrishnan-Stroud gates using a genetic algorithm. The method of coding chromosome is presented, and well-grounded choice of algorithm parameters allowed obtaining better circuit schemes of one- and n-qutrit ternary comparators compared with other methods. These parameters are quantum cost of received reversible devices, delay time and number of constant input (ancilla lines. Proposed implementation of the genetic algorithm has led to reducing of the device delay time and the number of ancilla qutrits to 1 and 2n-1 for one- and n-qutrits full comparators, respectively. For designing of n-qutrit comparator we have introduced a complementary device which compares output functions of 1-qutrit comparators.

  14. Reversible circuit synthesis by genetic programming using dynamic gate libraries

    Science.gov (United States)

    Abubakar, Mustapha Y.; Jung, Low Tang; Zakaria, Nordin; Younes, Ahmed; Abdel-Aty, Abdel-Haleem

    2017-06-01

    We have defined a new method for automatic construction of reversible logic circuits by using the genetic programming approach. The choice of the gate library is 100% dynamic. The algorithm is capable of accepting all possible combinations of the following gate types: NOT TOFFOLI, NOT PERES, NOT CNOT TOFFOLI, NOT CNOT SWAP FREDKIN, NOT CNOT TOFFOLI SWAP FREDKIN, NOT CNOT PERES, NOT CNOT SWAP FREDKIN PERES, NOT CNOT TOFFOLI PERES and NOT CNOT TOFFOLI SWAP FREDKIN PERES. Our method produced near optimum circuits in some cases when a particular subset of gate types was used in the library. Meanwhile, in some cases, optimal circuits were produced due to the heuristic nature of the algorithm. We compared the outcomes of our method with several existing synthesis methods, and it was shown that our algorithm performed relatively well compared to the previous synthesis methods in terms of the output efficiency of the algorithm and execution time as well.

  15. Search for genetic virulence markers in viral haemorrhagic septicaemia virus (VHSV) using a reverse genetics approach

    DEFF Research Database (Denmark)

    Stegmann, Anders; Biacchesi, S.; Bremont, M.

    2011-01-01

    VHSV is a negative strand RNA virus causing serious disease in farmed rainbow trout. Although VHSV has been eradicated by stamping out procedures in several fresh water bodies, recently including all streams in Denmark, the wildlife marine reservoir still represents a threat against rainbow trout...... farming. Particularly in Scandinavia, outbreaks of VHS in sea reared rainbow trout have demonstrated that although marine variants of VHSV are considered to be avirulent to rainbow trout, the virus is potentially able to adapt to this host and cause disease. Limited knowledge about the genetic background...... for virulence to rainbow trout makes it difficult to differentiate between dangerous and harmless VHSV variants. With the aim of identification of genetic virulence markers, we have implemented reverse genetics technology for generation of hybrid virus variants. By substituting different regions in the genome...

  16. Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders.

    Directory of Open Access Journals (Sweden)

    Ileena Mitra

    2017-01-01

    Full Text Available Although gene-gene interaction, or epistasis, plays a large role in complex traits in model organisms, genome-wide by genome-wide searches for two-way interaction have limited power in human studies. We thus used knowledge of a biological pathway in order to identify a contribution of epistasis to autism spectrum disorders (ASDs in humans, a reverse-pathway genetic approach. Based on previous observation of increased ASD symptoms in Mendelian disorders of the Ras/MAPK pathway (RASopathies, we showed that common SNPs in RASopathy genes show enrichment for association signal in GWAS (P = 0.02. We then screened genome-wide for interactors with RASopathy gene SNPs and showed strong enrichment in ASD-affected individuals (P < 2.2 x 10-16, with a number of pairwise interactions meeting genome-wide criteria for significance. Finally, we utilized quantitative measures of ASD symptoms in RASopathy-affected individuals to perform modifier mapping via GWAS. One top region overlapped between these independent approaches, and we showed dysregulation of a gene in this region, GPR141, in a RASopathy neural cell line. We thus used orthogonal approaches to provide strong evidence for a contribution of epistasis to ASDs, confirm a role for the Ras/MAPK pathway in idiopathic ASDs, and to identify a convergent candidate gene that may interact with the Ras/MAPK pathway.

  17. Respiratory Syncytial Virus: Virology, Reverse Genetics, and Pathogenesis of Disease

    Science.gov (United States)

    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

  18. Reverse Genetics Plasmid for Cloning Unstable Influenza A Virus Gene Segments

    OpenAIRE

    Zhou, Bin; Jerzak, Greta; Scholes, Derek T.; Donnelly, Matthew E.; Li, Yan; Wentworth, David E.

    2011-01-01

    Reverse genetics approaches that enable the generation of recombinant influenza A viruses entirely from plasmids are invaluable for studies on virus replication, morphogenesis, pathogenesis, or transmission. Furthermore, influenza virus reverse genetics is now critical for the development of new vaccines for this human and animal pathogen. Periodically, influenza gene segments are unstable within plasmids in bacteria. The PB2 gene segment of a highly pathogenic avian H5 influenza virus A/Turk...

  19. Experimenting with sex: four approaches to the genetics of sex reversal before 1950.

    Science.gov (United States)

    Dietrich, Michael R

    2016-04-01

    In the early twentieth century, Tatsuo Aida in Japan, Øjvind Winge in Denmark, Richard Goldschmidt in Germany, and Calvin Bridges in the United States all developed different experimental systems to study the genetics of sex reversal. These locally specific experimental systems grounded these experimenters' understanding of sex reversal as well as their interpretation of claims regarding experimental results and theories. The comparison of four researchers and their experimental systems reveals how those different systems mediated their understanding of genetic phenomena, and influenced their interpretations of sex reversal.

  20. Quantum Genetics in terms of Quantum Reversible Automata and Quantum Computation of Genetic Codes and Reverse Transcription

    CERN Document Server

    Baianu,I C

    2004-01-01

    The concepts of quantum automata and quantum computation are studied in the context of quantum genetics and genetic networks with nonlinear dynamics. In previous publications (Baianu,1971a, b) the formal concept of quantum automaton and quantum computation, respectively, were introduced and their possible implications for genetic processes and metabolic activities in living cells and organisms were considered. This was followed by a report on quantum and abstract, symbolic computation based on the theory of categories, functors and natural transformations (Baianu,1971b; 1977; 1987; 2004; Baianu et al, 2004). The notions of topological semigroup, quantum automaton, or quantum computer, were then suggested with a view to their potential applications to the analogous simulation of biological systems, and especially genetic activities and nonlinear dynamics in genetic networks. Further, detailed studies of nonlinear dynamics in genetic networks were carried out in categories of n-valued, Lukasiewicz Logic Algebra...

  1. Behavioural treatment of tics: Habit reversal and exposure with response prevention

    NARCIS (Netherlands)

    Griendt, J.M.T.M. van de; Verdellen, C.W.J.; Dijk, M.K. van; Verbraak, M.J.P.M.

    2013-01-01

    Behaviour therapy has been shown to be an effective strategy in treating tics; both habit reversal (HR) and exposure and response prevention (ER) are recommended as first-line interventions. This review provides an overview of the history, theoretical concepts and evidence at present for HR and ER.

  2. New analysis of reversal bleach mechanism and catalytic reaction of exposure quantity in silver halide material

    Science.gov (United States)

    Yoon, Byong H.; Kim, Nam; Baek, Woon S.

    1997-04-01

    A new analysis of the reversal bleaching mechanism and the catalytic reaction of exposure quantity in silver halide holographic diffraction gratings is presented. It is turned out that the exposure quantity reacts as a catalyst in the developing process and makes the velocity of developing reaction time fast. The experimental investigation has revealed that the holographic phase gratings with high diffraction efficiencies (> 70%) could be taken, if the developing reaction time be optimized in the 50 approximately 350 [(mu) J/cm2] range of exposure quantity.

  3. Reversal learning and experimenter-administered chronic intermittent ethanol exposure in male rats.

    Science.gov (United States)

    Badanich, Kimberly A; Fakih, Mackinzie E; Gurina, Tatyana S; Roy, Emalie K; Hoffman, Jessica L; Uruena-Agnes, Adriana R; Kirstein, Cheryl L

    2016-10-01

    Chronic alcohol exposure is associated with impaired decision making skills, cognitive deficits, and poor performance on tasks requiring behavioral flexibility. Although oral routes of alcohol administration are commonly used to examine effects of alcohol on various behaviors in rodents, only a few investigations have used intragastric exposures to evaluate ethanol's effects on behavioral flexibility in the adult rat. The aim of the current series of experiments was to determine if behavioral flexibility impairments would be demonstrated across a variety of procedural factors, including route of administration [intraperitoneal injection (i.p.), intragastric gavage (i.g.)], ethanol dose (3-5 g/kg), number of daily exposures (once/day, twice/day), duration of exposure (2-6 weeks), or length of abstinence (5-7 days). Adult male Sprague-Dawley rats were exposed to chronic intermittent ethanol (CIE) or vehicle and evaluated for behavioral intoxication, blood ethanol concentrations (BEC), and performance on a reversal learning odor discrimination task. While all rats displayed behavioral intoxication and elevated BECs, CIE i.p. rats had prolonged elevation in BECs and made the most errors during the reversal learning task. Unexpectedly, CIE i.g. exposures failed to produce deficits during reversal learning tasks regardless of ethanol dose, frequency/duration of exposure, or length of abstinence. Behavioral flexibility deficits resulting from CIE i.p. exposures may be due to the severity and chronicity of alcohol intoxication. Elucidating the impact of ethanol on behavioral flexibility is critical for developing a better understanding of the behavioral consequences of chronic alcohol exposure.

  4. Bacterial bioluminescence response to long-term exposure to reverse osmosis treated effluents from dye industries.

    Science.gov (United States)

    Ravindran, J; Manikandan, B; Shirodkar, P V; Francis, K X; Mani Murali, R; Vethamony, P

    2014-10-01

    The bacterial bioluminescence assay is one of the novel means for toxicity detection. The bioluminescence response of 2 marine bioluminescent bacteria was tested upon their long-term exposure to 9 different reverse osmosis (RO) rejects with varying chemical composition sampled from various dye industries. Bioluminescent bacteria were cultured in the RO reject samples, at different concentrations, and their growth rate and luminescence was measured for 24 h. The RO reject samples caused sublethal effects upon exposure and retarded the growth of bacteria, confirming their toxic nature. Further, continuation of the exposure showed that the initial luminescence, though reduced, recovered and increased beyond the control cultures irrespective of cell density, and finally decreased once again. The present study emphasizes the need of evolving a long-term exposure assay and shows that the method followed in this study is suitable to evaluate the toxicants that exert delayed toxicity, using lower concentrations of toxicants as well as coloured samples.

  5. Effects of Repeated Cocaine Exposure on Habit Learning and Reversal by N-Acetylcysteine

    Science.gov (United States)

    Corbit, Laura H; Chieng, Billy C; Balleine, Bernard W

    2014-01-01

    Exposure to drugs of abuse can result in a loss of control over both drug- and nondrug-related actions by accelerating the transition from goal-directed to habitual control, an effect argued to reflect changes in glutamate homeostasis. Here we examined whether exposure to cocaine accelerates habit learning and used in vitro electrophysiology to investigate its effects on measures of synaptic plasticity in the dorsomedial (DMS) and dorsolateral (DLS) striatum, areas critical for actions and habits, respectively. We then administered N-acetylcysteine (NAC) in an attempt to normalize glutamate homeostasis and hence reverse the cellular and behavioral effects of cocaine exposure. Rats received daily injections of cocaine (30 mg/kg) for 6 days and were then trained to lever press for a food reward. We used outcome devaluation and whole-cell patch-clamp electrophysiology to assess the behavioral and cellular effects of cocaine exposure. We then examined the ability of NAC to reverse the effects of cocaine exposure on these measures. Cocaine treatment produced a deficit in goal-directed action, as assessed by outcome devaluation, and increased the frequency of spontaneous and miniature excitatory postsynaptic currents (EPSCs) in the DMS but not in the DLS. Importantly, NAC treatment both normalized EPSC frequency and promoted goal-directed control in cocaine-treated rats. The promotion of goal-directed control has the potential to improve treatment outcomes in human cocaine addicts. PMID:24531561

  6. Vascular Dysfunction in Patients with Chronic Arsenosis Can Be Reversed by Reduction of Arsenic Exposure

    OpenAIRE

    Pi, Jingbo; Yamauchi, Hiroshi; Sun, Guifan; Yoshida, Takahiko; Aikawa, Hiroyuki; Fujimoto, Wataru; Iso, Hiroyasu; Cui, Renzhe; Waalkes, Michael P.; Kumagai, Yoshito

    2004-01-01

    Chronic arsenic exposure causes vascular diseases associated with systematic dysfunction of endogenous nitric oxide. Replacement of heavily arsenic-contaminated drinking water with low-arsenic water is a potential intervention strategy for arsenosis, although the reversibility of arsenic intoxication has not established. In the present study, we examined urinary excretion of cyclic guanosine 3′,5′-monophosphate (cGMP), a second messenger of the vasoactive effects of nitric oxide, and signs an...

  7. Postnatal sulfur dioxide exposure reversibly alters parasympathetic regulation of heart rate.

    Science.gov (United States)

    Woerman, Amanda L; Mendelowitz, David

    2013-08-01

    Perinatal sulfur dioxide exposure disrupts parasympathetic regulation of cardiovascular activity. Here, we examine the relative risks of prenatal versus postnatal exposure to the air pollutant and the reversibility of the cardiovascular effects. Two groups of animals were used for this study. For prenatal exposure, pregnant Sprague-Dawley dams were exposed to 5 parts per million sulfur dioxide for 1 hour daily throughout gestation and with their pups after birth to medical-grade air through 6 days postnatal. For postnatal exposure, dams were exposed to air, and after delivery along with their pups to 5 parts per million sulfur dioxide through postnatal day 6. ECGs were recorded from pups on postnatal day 5 to examine changes in heart rate. Whole-cell patch-clamp electrophysiology was used to examine changes in neurotransmission to cardiac vagal neurons in the nucleus ambiguus on sulfur dioxide exposure. Postnatal sulfur dioxide exposure diminished glutamatergic neurotransmission to cardiac vagal neurons by 40.9% and increased heart rate, whereas prenatal exposure altered neither of these properties. When postnatal exposure concluded on postnatal day 5, excitatory neurotransmission remained decreased through day 6 and returned to basal levels by day 7. ECGs showed that heart rate remained elevated through day 6 and recovered by day 7. On activation of the parasympathetic diving reflex, the response was significantly blunted by postnatal sulfur dioxide exposure through day 7 but recovered by day 8. Postnatal, but not prenatal, exposure to sulfur dioxide can disrupt parasympathetic regulation of cardiovascular activity. Neonates can recover from these effects within 2 to 3 days of discontinued exposure.

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

    Science.gov (United States)

    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.

  9. Application of reverse genetics for producing attenuated vaccine strains against highly pathogenic avian influenza viruses.

    Science.gov (United States)

    Uchida, Yuko; Takemae, Nobuhiro; Saito, Takehiko

    2014-08-01

    In this study, reverse genetics was applied to produce vaccine candidate strains against highly pathogenic avian influenza viruses (HPAIVs) of the H5N1 subtype. The H5 subtype vaccine strains were generated by a reverse genetics method in a biosafety level 2 facility. The strain contained the HA gene from the H5N1 subtype HPAIV attenuated by genetic modification at the cleavage site, the NA gene derived from the H5N1 subtype HPAI or the H5N3 subtype of avian influenza virus and internal genes from A/Puerto Rico/8/34. Vaccination with an inactivated recombinant virus with oil-emulsion completely protected chickens from a homologous viral challenge with a 640 HAU or 3,200 HAU/vaccination dose. Vaccination with a higher dose of antigen, 3,200 HAU, was effective at increasing survival and efficiently reduced viral shedding even when challenged by a virus of a different HA clade. The feasibility of differentiation of infected from vaccinated animals (DIVA) was demonstrated against a challenge with H5N1 HPAIVs when the recombinant H5N3 subtype viruses were used as the antigens of the vaccine. Our study demonstrated that the use of reverse genetics would be an option to promptly produce an inactivated vaccine with better matching of antigenicity to a circulating strain.

  10. Wet heat exposure: a potentially reversible cause of low semen quality in infertile men

    Directory of Open Access Journals (Sweden)

    Shai Shefi

    2007-02-01

    Full Text Available OBJECTIVE: To evaluate the recovery of semen quality in a cohort of infertile men after known hyperthermic exposure to hot tubs, hot baths or whirlpool baths. MATERIALS AND METHODS: A consecutive cohort of infertile men had a history remarkable for wet heat exposure in the forms of hot tubs, Jacuzzi or hot baths. Clinical characteristics and exposure parameters were assessed before exposure was discontinued, and semen parameters analyzed before and after discontinuation of hyperthermic exposure. A significant seminal response to withdrawal of hyperthermia was defined as > 200% increase in the total motile sperm count (TMC = volume x concentration x motile fraction during follow-up after cessation of wet heat exposure. RESULTS: Eleven infertile men (mean age 36.5 years, range 31-44 exposed to hyperthermia were evaluated pre and post-exposure. Five patients (45% responded favorably to cessation of heat exposure and had a mean increase in total motile sperm counts of 491%. This increase was largely the result of a statistically significant increase in sperm motility from a mean of 12% at baseline to 34% post-intervention (p = 0.02. Among non-responders, a smoking history revealed a mean of 5.6 pack-years, compared to 0.11 pack-years among responders. The prevalence of varicoceles was similar in both cohorts. CONCLUSIONS: The toxic effect of hyperthermia on semen quality may be reversible in some infertile men. We observed that the seminal response to exposure elimination varies biologically among individuals and can be profound in magnitude. Among non-responders, other risk factors that could explain a lack of response to elimination of hyperthermia should be considered.

  11. Construction and characterisation of a complete reverse genetics system of dengue virus type 3

    Directory of Open Access Journals (Sweden)

    Jefferson Jose da Silva Santos

    2013-12-01

    Full Text Available Dengue virulence and fitness are important factors that determine disease outcome. However, dengue virus (DENV molecular biology and pathogenesis are not completely elucidated. New insights on those mechanisms have been facilitated by the development of reverse genetic systems in the past decades. Unfortunately, instability of flavivirus genomes cloned in Escherichia coli has been a major problem in these systems. Here, we describe the development of a complete reverse genetics system, based on the construction of an infectious clone and replicon for a low passage DENV-3 genotype III of a clinical isolate. Both constructs were assembled into a newly designed yeast- E. coli shuttle vector by homologous recombination technique and propagated in yeast to prevent any possible genome instability in E. coli . RNA transcripts derived from the infectious clone are infectious upon transfection into BHK-21 cells even after repeated passages of the plasmid in yeast. Transcript-derived DENV-3 exhibited growth kinetics, focus formation size comparable to original DENV-3 in mosquito C6/36 cell culture. In vitro characterisation of DENV-3 replicon confirmed its identity and ability to replicate transiently in BHK-21 cells. The reverse genetics system reported here is a valuable tool that will facilitate further molecular studies in DENV replication, virus attenuation and pathogenesis.

  12. Investigating the importance of co-expressed rotavirus proteins in the development of a selection-free rotavirus reverse genetics system / Johannes Frederik Wentzel

    OpenAIRE

    Wentzel, Johannes Frederik

    2014-01-01

    Reverse genetics is an innovative molecular biology tool that enables the manipulation of viral genomes at the cDNA level in order to generate particular mutants or artificial viruses. The reverse genetics system for the influenza virus is arguably one of the best illustrations of the potential power of this technology. This reverse genetics system is the basis for the ability to regularly adapt influenza vaccines strains. Today, reverse genetic systems have been developed for ...

  13. Vitamin E Reversed Apoptosis of Cardiomyocytes Induced by Exposure to High Dose Formaldehyde During Mice Pregnancy.

    Science.gov (United States)

    Wu, Dongyuan; Jiang, Zhirong; Gong, Bing; Dou, Yue; Song, Mingxuan; Song, Xiaoxia; Tian, Yu

    2017-10-21

    In this study, we investigated the protection effect of Vitamin E (Vit E) on formaldehyde (FA) exposure during pregnancy induced apoptosis of cardiomyocytes, and used an HL-1 cell line to confirmed the findings in vivo.Pregnant mice received different doses of FA (0.5 mg/kg, 1.0 mg/kg, 1.5 mg/kg, 0.1 μg Vit E, or 1.5 mg/kg + 0.1 μg Vit E). TUNEL staining was used to reveal the apoptosis in cardiomyocytes, and SOD, MDA, GSH, Livin, and Caspase-3 in cardiomyocytes were detected by ELISA, RT-PCR, and Western blot. For in vitro study, HL-1 cells were treated with vehicle, 5 μmol/L FA, 25 μmol/L FA, 50 μmol/L FA, 10 mg/L Vit. E, and 50 μmol/L FA+ 10 mg/L Vit E, respectively. CCK-8 assay and flow cytometry were used to evaluate cell vitality and apoptosis. A high dose of FA exposure led to cytotoxicity in both pregnant mice and offspring, as TUNEL staining revealed a significant apoptosis of cardiomyocytes, and the alternation in SOD, GSH, MDA, Livin, and Caspase-3 was found in cardiomyocytes. 0.1 μg Vit. E could reverse high doses of FA exposure induced apoptosis of cardiomyocytes in both pregnant mice and offspring. The in vitro study revealed that FA exposure induced a decrease of cell viability and increased cell apoptosis, as well as oxidative stress in HL-1 cells with alternation in SOD, GSH, MDA, Livin, and Caspase-3.This study revealed a high dose of FA induced oxidative stress and apoptosis of cardiomyocytes in both pregnant mice and offspring, and Vit E supplement during pregnancy reversed the systemic and myocardial toxicity of FA.

  14. Effects of Short-Term Hypergravity Exposure are Reversible in Triticum aestivum L. Caryopses

    Science.gov (United States)

    Dixit, Jyotsana P.; Jagtap, Sagar S.; Kamble, Shailendra M.; Vidyasagar, Pandit B.

    2017-10-01

    Short-term hypergravity exposure is shown to retard seed germination, growth and photosynthesis in wheat caryopses. This study investigates the reversibility of effects of short-term hypergravity on imbibed wheat ( Triticum aestivum var L.) caryopses. After hypergravity exposure (500 × g - 2500 × g for 10 min) on a centrifuge, exposed caryopses were kept under normal gravity (1 × g) up to six days and then sown on agar. Results of the present study showed that percentage germination and growth were completely restored for DAY 6 compared to DAY 0. Restoration of germination and growth was accompanied by increased α-amylase activity. The specific activity of antioxidative enzyme viz. catalase and guaiacol peroxidase was lowered on DAY 6 compared to DAY 0 suggesting an alleviation of oxidative cellular damage against hypergravity stress. Chlorophyll pigment recovery along with chlorophyll fluorescence (PI and Fv/Fm) on DAY 6 indicates a transient rather than permanent damage of the photosynthetic apparatus. Thus, our findings demonstrate that short-term hypergravity effects are reversible in wheat caryopses. The metabolic cause of restoration of seed germination and growth upon transferring the caryopses to normal gravity is performed by a reactivation of carbohydrate- metabolizing enzymes, α-amylase and alleviation of oxidative stress damage with subsequent recovery of chlorophyll biosynthesis and photosynthetic activity.

  15. Cow's milk exposure and asthma in a newborn cohort: repeated ascertainment indicates reverse causation.

    Science.gov (United States)

    Fussman, Chris; Todem, David; Forster, Johannes; Arshad, Hassan; Urbanek, Radvan; Karmaus, Wilfried

    2007-03-01

    The effect of cow's milk consumption on childhood asthma has been debated for several years. This study attempts to provide further insight into this association through the use of a longitudinal study design. Newborns from parents with atopic history were recruited from Germany, Austria, and England (n = 696). For five repeated ascertainments, information was collected on cow's milk exposure, incidence of doctor-diagnosed asthma, and confounders. Generalized estimation equations, incorporating different models (concurrent, delayed, combined, and reverse causation), were used to determine this association. No association between cow's milk consumption and childhood asthma was found for the concurrent effects model (OR = 0.81, 95% confidence interval [CI]: 0.55, 1.20). In the delayed effects model, the direction of the association varied with time of follow-up. Thus, we stratified by period, which resulted in a significant protective delayed effect at 36 months (OR = 0.18, 95% CI = 0.06, 0.49). However, reverse causation negated this finding since the presence of asthma in prior months led to a reduction in further exposure to cow's milk (OR = 0.40, 95% CI = 0.16, 0.99). Hence, cow's milk consumption does not protect against childhood asthma. The apparent protection of cow's milk against asthma may result from parents of asthmatic children avoiding cow's milk, rather than actual prophylaxis.

  16. Natural Genetic Variation of Xanthomonas campestris pv. campestris Pathogenicity on Arabidopsis Revealed by Association and Reverse Genetics

    Science.gov (United States)

    Guy, Endrick; Genissel, Anne; Hajri, Ahmed; Chabannes, Matthieu; David, Perrine; Carrere, Sébastien; Lautier, Martine; Roux, Brice; Boureau, Tristan; Arlat, Matthieu; Poussier, Stéphane; Noël, Laurent D.

    2013-01-01

    ABSTRACT The pathogenic bacterium Xanthomonas campestris pv. campestris, the causal agent of black rot of Brassicaceae, manipulates the physiology and the innate immunity of its hosts. Association genetic and reverse-genetic analyses of a world panel of 45 X. campestris pv. campestris strains were used to gain understanding of the genetic basis of the bacterium’s pathogenicity to Arabidopsis thaliana. We found that the compositions of the minimal predicted type III secretome varied extensively, with 18 to 28 proteins per strain. There were clear differences in aggressiveness of those X. campestris pv. campestris strains on two Arabidopsis natural accessions. We identified 3 effector genes (xopAC, xopJ5, and xopAL2) and 67 amplified fragment length polymorphism (AFLP) markers that were associated with variations in disease symptoms. The nature and distribution of the AFLP markers remain to be determined, but we observed a low linkage disequilibrium level between predicted effectors and other significant markers, suggesting that additional genetic factors make a meaningful contribution to pathogenicity. Mutagenesis of type III effectors in X. campestris pv. campestris confirmed that xopAC functions as both a virulence and an avirulence gene in Arabidopsis and that xopAM functions as a second avirulence gene on plants of the Col-0 ecotype. However, we did not detect the effect of any other effector in the X. campestris pv. campestris 8004 strain, likely due to other genetic background effects. These results highlight the complex genetic basis of pathogenicity at the pathovar level and encourage us to challenge the agronomical relevance of some virulence determinants identified solely in model strains. PMID:23736288

  17. PERFORMANCES OF POPULATIONS OF SEX REVERSED TILAPIA AND GENETICALLY MALE TILAPIA IN FINGERLING PONDS

    Directory of Open Access Journals (Sweden)

    Didik Ariyanto

    2009-12-01

    Full Text Available One of the most popular techniques in mass production of all or nearly all male tilapia population is through sex reversal. However, cross mating of YY super male with regular brood-stock is gaining popularity and has been practiced by aqua-culturists. This study was conducted to evaluate the performance of 2 populations of sex reversed tilapia (sex reversed with dietary application of 17-α methyl testosterone, SRT-1, and sex reversed with dietary administration of imidazole, SRT-2 and 1 population of genetically male tilapia (GMT derived from YY super male until the end of fingerling rearing period. Mixed sex tilapia (MST derived from normal mating was used as the control population. The results showed that the daily growth rates of SRT-1, SRT-2, GMT, and MST were 0.12, 0.11, 0.20, and 0.07 g/day, with survival rates were 57.83%, 64.67%, 39.67%, and 68.78%, respectively. The GMT has higher harvest yield than the other populations; SRT-1 (+15.73%, SRT-2 (+6.37%, and MST (+20.82%.

  18. Incomplete Reversibility of Estimated Glomerular Filtration Rate Decline Following Tenofovir Disoproxil Fumarate Exposure

    Science.gov (United States)

    Jose, Sophie; Hamzah, Lisa; Campbell, Lucy J.; Hill, Teresa; Fisher, Martin; Leen, Clifford; Gilson, Richard; Walsh, John; Nelson, Mark; Hay, Phillip; Johnson, Margaret; Chadwick, David; Nitsch, Dorothea; Jones, Rachael; Sabin, Caroline A.; Post, Frank A.; Ainsworth, Jonathan; Anderson, Jane; Babiker, Abdel; Chadwick, David; Delpech, Valerie; Dunn, David; Fisher, Martin; Gazzard, Brian; Gilson, Richard; Gompels, Mark; Hay, Phillip; Hill, Teresa; Johnson, Margaret; Kegg, Stephen; Leen, Clifford; Nelson, Mark; Orkin, Chloe; Palfreeman, Adrian; Phillips, Andrew; Pillay, Deenan; Post, Frank; Sabin, Caroline; Sachikonye, Memory; Schwenk, Achim; Walsh, John; Hill, Teresa; Huntington, Susie; Josie, Sophie; Phillips, Andrew; Sabin, Caroline; Thornton, Alicia; Dunn, David; Glabay, Adam; Orkin, C.; Garrett, N.; Lynch, J.; Hand, J.; de Souza, C.; Fisher, M.; Perry, N.; Tilbury, S.; Churchill, D.; Gazzard, B.; Nelson, M.; Waxman, M.; Asboe, D.; Mandalia, S.; Delpech, V.; Anderson, J.; Munshi, S.; Korat, H.; Poulton, M.; Taylor, C.; Gleisner, Z.; Campbell, L.; Babiker, Abdel; Dunn, David; Glabay, Adam; Gilson, R.; Brima, N.; Williams, I.; Schwenk, A.; Ainsworth, J.; Wood, C.; Miller, S.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Puradiredja, D.; Walsh, J.; Weber, J.; Ramzan, F.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Gompels, M.; Allan, S.; Palfreeman, A.; Moore, A.; Chadwick, D.; Wakeman, K.; Kegg, Stephen; Main, Paul; Mitchell; Hunter; Sachikonye, Memory; Hay, Phillip; Dhillon, Mandip

    2014-01-01

    Background. Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. Methods. Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. Results. We observed declines in the eGFR during TDF exposure (mean slopes, −15.7 mL/minute/1.73 m2/year [95% confidence interval {CI}, −20.5 to −10.9] during the first 3 months and −3.1 mL/minute/1.73 m2/year [95% CI, −4.6 to −1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m2/year [95% CI, 8.9–16.1] during the first 3 months and 0.8 mL/minute/1.73 m2/year [95% CI, .1–1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. Conclusions. This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided. PMID:24585896

  19. Deciphering the Genic Basis of Yeast Fitness Variation by Simultaneous Forward and Reverse Genetics.

    Science.gov (United States)

    Maclean, Calum J; Metzger, Brian P H; Yang, Jian-Rong; Ho, Wei-Chin; Moyers, Bryan; Zhang, Jianzhi

    2017-10-01

    The budding yeast Saccharomyces cerevisiae is the best studied eukaryote in molecular and cell biology, but its utility for understanding the genetic basis of phenotypic variation in natural populations is limited by inefficient association mapping due to strong and complex population structure. To overcome this challenge, we generated genome sequences for 85 strains and performed a comprehensive population genomic survey of a total of 190 diverse strains. We identified considerable variation in population structure among chromosomes and identified 181 genes that are absent from the reference genome. Many of these nonreference genes are expressed and we functionally confirmed that two of these genes confer increased resistance to antifungals. Next, we simultaneously measured the growth rates of over 4,500 laboratory strains, each of which lacks a nonessential gene, and 81 natural strains across multiple environments using unique DNA barcode present in each strain. By combining the genome-wide reverse genetic information gained from the gene deletion strains with a genome-wide association analysis from the natural strains, we identified genomic regions associated with fitness variation in natural populations. To experimentally validate a subset of these associations, we used reciprocal hemizygosity tests, finding that while the combined forward and reverse genetic approaches can identify a single causal gene, the phenotypic consequences of natural genetic variation often follow a complicated pattern. The resources and approach provided outline an efficient and reliable route to association mapping in yeast and significantly enhance its value as a model for understanding the genetic mechanisms underlying phenotypic variation and evolution in natural populations. © The Author 2017. 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.

  20. Reverse genetics techniques: engineering loss and gain of gene function in plants.

    Science.gov (United States)

    Gilchrist, Erin; Haughn, George

    2010-03-01

    Genetic analysis represents a powerful tool that establishes a direct link between the biochemical function of a gene product and its role in vivo. Genome sequencing projects have identified large numbers of plant genes for which no role has yet been defined. To address this problem a number of techniques have been developed, over the last 15 years, to enable researchers to identify plants with mutations in genes of known sequence. These reverse genetic approaches include RNAi and related technologies and screening of populations mutagenised by insertion (PCR), deletion (PCR) and point mutation (TILLING), each with its own strengths and weaknesses. The development of next-generation sequencing techniques now allows such screening to be done by sequencing. In the future, it is likely that the genomes of thousands of plants from mutagenised populations will be sequenced allowing for the identification of plants with mutations in specific genes to be done in silico.

  1. Reversible antibiotic tolerance induced in Staphylococcus aureus by concurrent drug exposure

    DEFF Research Database (Denmark)

    Haaber, Jakob Krause; Friberg, Cathrine; McCreary, Mark

    2015-01-01

    antibiotic that targets the coinfecting pathogen. While investigating factors that affect bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus to vancomycin is reduced by concurrent exposure to colistin, a cationic peptide antimicrobial employed to treat infections by Gram......UNLABELLED: Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to increasing use of the glycopeptide antibiotic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may necessitate concurrent treatment with a second......] strains). As colistin-induced vancomycin tolerance is reversible, it may not be detected by routine sensitivity testing and may be responsible for treatment failure at vancomycin doses expected to be clinically effective based on such routine testing. IMPORTANCE: Commonly, antibiotic resistance...

  2. Exposure to Cooking Fumes and Acute Reversible Decrement in Lung Functional Capacity

    Directory of Open Access Journals (Sweden)

    Masoud Neghab

    2017-10-01

    Full Text Available Background: Being exposed to cooking fumes, kitchen workers are occupationally at risk of multiple respiratory hazards. No conclusive evidence exists as to whether occupational exposure to these fumes is associated with acute and chronic pulmonary effects and symptoms of respiratory diseases. Objective: To quantify the exposure levels and evaluate possible chronic and acute pulmonary effects associated with exposure to cooking fumes. Methods: In this cross-sectional study, 60 kitchen workers exposed to cooking fumes and 60 unexposed employees were investigated. The prevalence of respiratory symptoms among these groups was determined through completion of a standard questionnaire. Pulmonary function parameters were also measured before and after participants' work shift. Moreover, air samples were collected and analyzed to quantify their aldehyde, particle, and volatile organic contents. Results: The mean airborne concentrations of formaldehyde, acetaldehyde, and acrolein was 0.45 (SD 0.41, 0.13 (0.1, and 1.56 (0.41 mg/m3, respectively. The mean atmospheric concentrations of PM1, PM2.5, PM7, PM10, and total volatile organic compounds (TVOCs was 3.31 (2.6, 12.21 (5.9, 44.16 (16.6, 57 (21.55 μg/m3, and 1.31 (1.11 mg/m3, respectively. All respiratory symptoms were significantly (p<0.05 more prevalent in exposed group. No significant difference was noted between the pre-shift mean of spirometry parameters of exposed and unexposed group. However, exposed workers showed cross-shift decrease in most spirometry parameters, significantly lower than the pre-shift values and those of the comparison group. Conclusion: Exposure to cooking fumes is associated with a significant increase in the prevalence of respiratory symptoms as well as acute reversible decrease in lung functional capacity.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 M 1 and M 2 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 M 2 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

  5. S100A1 Genetically Targeted Therapy Reverses Dysfunction of Human Failing Cardiomyocytes

    Science.gov (United States)

    Brinks, Henriette; Rohde, David; Voelkers, Mirko; Qiu, Gang; Pleger, Sven T.; Herzog, Nicole; Rabinowitz, Joseph; Ruhparwar, Arjang; Silvestry, Scott; Lerchenmüller, Carolin; Mather, Paul J.; Eckhart, Andrea D.; Katus, Hugo A.; Carrel, Thierry; Koch, Walter J.; Most, Patrick

    2013-01-01

    Objectives This study investigated the hypothesis whether S100A1 gene therapy can improve pathological key features in human failing ventricular cardiomyocytes (HFCMs). Background Depletion of the Ca2+-sensor protein S100A1 drives deterioration of cardiac performance toward heart failure (HF) in experimental animal models. Targeted repair of this molecular defect by cardiac-specific S100A1 gene therapy rescued cardiac performance, raising the immanent question of its effects in human failing myocardium. Methods Enzymatically isolated HFCMs from hearts with severe systolic HF were subjected to S100A1 and control adenoviral gene transfer and contractile performance, calcium handling, signaling, and energy homeostasis were analyzed by video-edge-detection, FURA2-based epifluorescent microscopy, phosphorylation site-specific antibodies, and mitochondrial assays, respectively. Results Genetically targeted therapy employing the human S100A1 cDNA normalized decreased S100A1 protein levels in HFCMs, reversed both contractile dysfunction and negative force-frequency relationship, and improved contractile reserve under beta-adrenergic receptor (β-AR) stimulation independent of cAMP-dependent (PKA) and calmodulin-dependent (CaMKII) kinase activity. S100A1 reversed underlying Ca2+ handling abnormalities basally and under β-AR stimulation shown by improved SR Ca2+ handling, intracellular Ca2+ transients, diastolic Ca2+ overload, and diminished susceptibility to arrhythmogenic SR Ca2+ leak, respectively. Moreover, S100A1 ameliorated compromised mitochondrial function and restored the phosphocreatine/adenosine-triphosphate ratio. Conclusions Our results demonstrate for the first time the therapeutic efficacy of genetically reconstituted S100A1 protein levels in HFCMs by reversing pathophysiological features that characterize human failing myocardium. Our findings close a gap in our understanding of S100A1’s effects in human cardiomyocytes and strengthen the rationale for

  6. Immunotoxicity in green mussels under perfluoroalkyl substance (PFAS) exposure: Reversible response and response model development.

    Science.gov (United States)

    Liu, Changhui; Gin, Karina Yew-Hoong

    2018-02-05

    The immunotoxicity of 4 commonly detected perfluoroalkyl substances (PFASs), namely, perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) was investigated by measuring biomarkers of the immune profile of green mussels, Perna viridis. The biomarkers included neutral red retention, phagocytosis, and spontaneous cytotoxicity, all of which were tested on mussel hemocytes. Hemocytes are an important component of the invertebrate immune system. We found that exposure to PFASs could lead to reduced hemocyte cell viability and suppress immune function by up to 50% of normal performance within the experimental exposure range. The results indicate that PFASs have an immunotoxic potential and thus could pose severe health risks to aquatic organisms. The reported immunotoxicity is likely to result from the compounds' direct and indirect interactions with the hemocyte membrane, and therefore likely to affect the functionality of these cells. The immunotoxic response was found to be related to the organism's burden of PFASs, and was reversible when the compounds were removed from the test organisms. Based on this relationship, models using an organism's PFAS concentration and bioaccumulation factor (BAF) as the independent variables were established to quantify PFAS-induced immunotoxicity. The models help us to gain a better understanding of the toxic mechanism of PFASs, and provide a tool to evaluate adverse effects for the whole group of compounds with one mathematical equation. Environ Toxicol Chem 2018;9999:1-8. © 2018 SETAC. © 2018 SETAC.

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

    Science.gov (United States)

    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.

  8. Bone response to fluoride exposure is influenced by genetics.

    Directory of Open Access Journals (Sweden)

    Cláudia A N Kobayashi

    Full Text Available Genetic factors influence the effects of fluoride (F on amelogenesis and bone homeostasis but the underlying molecular mechanisms remain undefined. A label-free proteomics approach was employed to identify and evaluate changes in bone protein expression in two mouse strains having different susceptibilities to develop dental fluorosis and to alter bone quality. In vivo bone formation and histomorphometry after F intake were also evaluated and related to the proteome. Resistant 129P3/J and susceptible A/J mice were assigned to three groups given low-F food and water containing 0, 10 or 50 ppmF for 8 weeks. Plasma was evaluated for alkaline phosphatase activity. Femurs, tibiae and lumbar vertebrae were evaluated using micro-CT analysis and mineral apposition rate (MAR was measured in cortical bone. For quantitative proteomic analysis, bone proteins were extracted and analyzed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS, followed by label-free semi-quantitative differential expression analysis. Alterations in several bone proteins were found among the F treatment groups within each mouse strain and between the strains for each F treatment group (ratio ≥1.5 or ≤0.5; p<0.05. Although F treatment had no significant effects on BMD or bone histomorphometry in either strain, MAR was higher in the 50 ppmF 129P3/J mice than in the 50 ppmF A/J mice treated with 50 ppmF showing that F increased bone formation in a strain-specific manner. Also, F exposure was associated with dose-specific and strain-specific alterations in expression of proteins involved in osteogenesis and osteoclastogenesis. In conclusion, our findings confirm a genetic influence in bone response to F exposure and point to several proteins that may act as targets for the differential F responses in this tissue.

  9. Prenatal mercury exposure, neurodevelopment and apolipoprotein E genetic polymorphism.

    Science.gov (United States)

    Snoj Tratnik, Janja; Falnoga, Ingrid; Trdin, Ajda; Mazej, Darja; Fajon, Vesna; Miklavčič, Ana; Kobal, Alfred B; Osredkar, Joško; Sešek Briški, Alenka; Krsnik, Mladen; Neubauer, David; Kodrič, Jana; Stropnik, Staša; Gosar, David; Lešnik Musek, Petra; Marc, Janja; Jurkovič Mlakar, Simona; Petrović, Oleg; Vlašić-Cicvarić, Inge; Prpić, Igor; Milardović, Ana; Radić Nišević, Jelena; Vuković, Danijela; Fišić, Elizabeta; Špirić, Zdravko; Horvat, Milena

    2017-01-01

    The aim of the present study was to evaluate the association between prenatal exposure to mercury (Hg) and neurodevelopment of the child, taking into account genetic polymorphism of apolipoprotein E (Apoe) and other relevant confounders. Six hundred and one mother-child pairs were recruited from the central Slovenia region and 243 from Rijeka, on the Croatian coast of the northern Adriatic. The total Hg in cord blood, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessment at 18 months of age and Apoe genotyping was performed on 361 children; 237 of them were from Slovenia and 124 from Croatia. The results showed negative association between low-to-moderate Hg exposure in children with normal neurodevelopmental outcome and cognitive and fine motor scores at 18 months of age as assessed by Bayley III. The Hg-related decrease in cognitive score was observed only in children carrying at least one Apoe ε4 allele, while the decrease in fine motor scores was independent of the Apoe genotype. Adjusting for selenium (Se) and lead (Pb) levels, a positive association between Se and the language score and a negative association between Pb and the motor score was observed, but not in the subgroup of children carrying the ε4 allele. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

    Directory of Open Access Journals (Sweden)

    Li Pinghua

    2012-05-01

    Full Text Available Abstract 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

  11. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

    Science.gov (United States)

    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

  12. Liver growth factor treatment reverses emphysema previously established in a cigarette smoke exposure mouse model.

    Science.gov (United States)

    Pérez-Rial, Sandra; Del Puerto-Nevado, Laura; Girón-Martínez, Alvaro; Terrón-Expósito, Raúl; Díaz-Gil, Juan J; González-Mangado, Nicolás; Peces-Barba, Germán

    2014-11-01

    Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease largely associated with cigarette smoke exposure (CSE) and characterized by pulmonary and extrapulmonary manifestations, including systemic inflammation. Liver growth factor (LGF) is an albumin-bilirubin complex with demonstrated antifibrotic, antioxidant, and antihypertensive actions even at extrahepatic sites. We aimed to determine whether short LGF treatment (1.7 μg/mouse ip; 2 times, 2 wk), once the lung damage was established through the chronic CSE, contributes to improvement of the regeneration of damaged lung tissue, reducing systemic inflammation. We studied AKR/J mice, divided into three groups: control (air-exposed), CSE (chronic CSE), and CSE + LGF (LGF-treated CSE mice). We assessed pulmonary function, morphometric data, and levels of various systemic inflammatory markers to test the LGF regenerative capacity in this system. Our results revealed that the lungs of the CSE animals showed pulmonary emphysema and inflammation, characterized by increased lung compliance, enlargement of alveolar airspaces, systemic inflammation (circulating leukocytes and serum TNF-α level), and in vivo lung matrix metalloproteinase activity. LGF treatment was able to reverse all these parameters, decreasing total cell count in bronchoalveolar lavage fluid and T-lymphocyte infiltration in peripheral blood observed in emphysematous mice and reversing the decrease in monocytes observed in chronic CSE mice, and tends to reduce the neutrophil population and serum TNF-α level. In conclusion, LGF treatment normalizes the physiological and morphological parameters and levels of various systemic inflammatory biomarkers in a chronic CSE AKR/J model, which may have important pathophysiological and therapeutic implications for subjects with stable COPD. Copyright © 2014 the American Physiological Society.

  13. A reverse genetics cell-based evaluation of genes linked to healthy human tissue age.

    Science.gov (United States)

    Crossland, Hannah; Atherton, Philip J; Strömberg, Anna; Gustafsson, Thomas; Timmons, James A

    2017-01-01

    We recently developed a binary (i.e., young vs. old) classifier using human muscle RNA profiles that accurately distinguished the age of multiple tissue types. Pathway analysis did not reveal regulators of these 150 genes, so we used reverse genetics and pharmacologic methods to explore regulation of gene expression. Using small interfering RNA, well-studied age-related factors (i.e., rapamycin, resveratrol, TNF-α, and staurosporine), quantitative real-time PCR and clustering analysis, we studied gene-gene interactions in human skeletal muscle and renal epithelial cells. Individual knockdown of 10 different age genes yielded a consistent pattern of gene expression in muscle and renal cells, similar to in vivo. Potential epigenetic interactions included HIST1H3E knockdown, leading to decreased PHF19 and PCDH9, and increased ICAM5 in muscle and renal cells, while ICAM5 knockdown reduced HIST1H3E expression. Resveratrol, staurosporine, and TNF-α significantly regulated the in vivo aging genes, while only rapamycin perturbed the healthy-age gene expression signature in a manner consistent with in vivo. In vitro coordination of gene expression for this in vivo tissue age signature indicates a degree of direct coordination, and the observed link with mTOR activity suggests a direct link between a robust biomarker of healthy neuromuscular age and a major axis of life span in model systems.-Crossland, H., Atherton, P. J., Strömberg, A., Gustafsson, T., Timmons, J. A. A reverse genetics cell-based evaluation of genes linked to healthy human tissue age. © The Author(s).

  14. Prenatal Methylmercury Exposure and Genetic Predisposition to Cognitive Deficit at Age 8 Years

    DEFF Research Database (Denmark)

    Julvez, Jordi; Smith, George Davey; Golding, Jean

    2013-01-01

    Cognitive consequences at school age associated with prenatal methylmercury (MeHg) exposure may need to take into account nutritional and sociodemographic cofactors as well as relevant genetic polymorphisms.......Cognitive consequences at school age associated with prenatal methylmercury (MeHg) exposure may need to take into account nutritional and sociodemographic cofactors as well as relevant genetic polymorphisms....

  15. Mammalian Reverse Genetics without Crossing Reveals Nr3a as a Short-Sleeper Gene

    Directory of Open Access Journals (Sweden)

    Genshiro A. Sunagawa

    2016-01-01

    Full Text Available The identification of molecular networks at the system level in mammals is accelerated by next-generation mammalian genetics without crossing, which requires both the efficient production of whole-body biallelic knockout (KO mice in a single generation and high-performance phenotype analyses. Here, we show that the triple targeting of a single gene using the CRISPR/Cas9 system achieves almost perfect KO efficiency (96%–100%. In addition, we developed a respiration-based fully automated non-invasive sleep phenotyping system, the Snappy Sleep Stager (SSS, for high-performance (95.3% accuracy sleep/wake staging. Using the triple-target CRISPR and SSS in tandem, we reliably obtained sleep/wake phenotypes, even in double-KO mice. By using this system to comprehensively analyze all of the N-methyl-D-aspartate (NMDA receptor family members, we found Nr3a as a short-sleeper gene, which is verified by an independent set of triple-target CRISPR. These results demonstrate the application of mammalian reverse genetics without crossing to organism-level systems biology in sleep research.

  16. Reversing the mere exposure effect in spider fearfuls: Preliminary evidence of sensitization.

    Science.gov (United States)

    Becker, Eni S; Rinck, Mike

    2016-12-01

    A mere exposure effect (MEE) is said to occur when individuals' liking of a suboptimally and repeatedly presented stimulus increases compared to never-presented stimuli, while they are unable to indicate which stimuli were previously presented and which were not. In two experiments, we used the MEE to study automatic evaluative processes in highly spider-fearful individuals (SFs). Pictures of spiders and butterflies were repeatedly presented suboptimally to SFs and to non-anxious controls (NACs). In Experiment 1, both groups showed the MEE for butterflies, preferring previously presented butterfly pictures over new ones. For spider pictures, only NACs showed an MEE, whereas SFs showed no preference. Experiment 2 involved a more unpleasant presentation situation, because for each picture, participants had the difficult task to indicate what had been presented to them. This led to a reversed MEE for spiders in SFs: They preferred new spider pictures over previously presented ones. In both experiments, no evidence was observed for the ability to differentiate between old an new pictures. The results are tentatively explained within Zajonc' theory of the MEE, and they are related to the concept of sensitization in anxiety disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Lactation-induced reduction in hippocampal neurogenesis is reversed by repeated stress exposure.

    Science.gov (United States)

    Hillerer, Katharina M; Neumann, Inga D; Couillard-Despres, Sebastien; Aigner, Ludwig; Slattery, David A

    2014-06-01

    The peripartum period is a time of high susceptibility for mood and anxiety disorders, some of which have recently been associated with alterations in hippocampal neurogenesis. Several factors including stress, aging, and, perhaps unexpectedly, lactation have been shown to decrease hippocampal neurogenesis. Intriguingly, lactation is also a time of reduced stress responsivity suggesting that the effect of stress on neurogenic processes may differ during this period. Therefore, the aim of the present study was to assess the effect of repeated stress during lactation [2 h restraint stress from lactation day (LD) 2 to LD13] on brain weight, hippocampal volume, cell proliferation and survival, and on neuronal and astroglial differentiation. In addition to confirming the known lactation-associated decrease in cell proliferation and survival, we could reveal that stress reversed the lactation-induced decrease in cell proliferation, while it did not affect survival of newly born cells, nor the number of mature neurons , nor did it alter immature neuron production or the number of astroglial cells in lactation. Stress exposure increased relative brain weight and hippocampal volume mirroring the observed changes in neurogenesis. Interestingly, hippocampal volume and relative brain weight were lower in lactation as compared to nulliparous females under nonstressed conditions. This study assessed the effect of stress during lactation on hippocampal neurogenesis and indicates that stress interferes with important peripartum adaptations at the level of the hippocampus. © 2014 Wiley Periodicals, Inc.

  18. Reversibility of endocrine disruption in zebrafish (Danio rerio) after discontinued exposure to the estrogen 17α-ethinylestradiol

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, Lisa, E-mail: lisa.baumann@vetsuisse.unibe.ch [Centre for Fish and Wildlife Health, Vetsuisse Faculty, University of Bern, PO Box 8466, CH-3001 Bern (Switzerland); Aquatic Ecology and Toxicology Section, Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany); Knörr, Susanne, E-mail: susanne.knoerr@gmx.de [Aquatic Ecology and Toxicology Section, Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany); Keiter, Susanne, E-mail: susanne.keiter@cos.uni-heidelberg.de [Aquatic Ecology and Toxicology Section, Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany); Rehberger, Kristina, E-mail: k.rehberger@stud.uni-heidelberg.de [Aquatic Ecology and Toxicology Section, Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany); Volz, Sina, E-mail: s.volz@stud.uni-heidelberg.de [Aquatic Ecology and Toxicology Section, Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany); Schiller, Viktoria, E-mail: schiller@molbiotech.rwth-aachen.de [Fraunhofer Institute for Molecular Biology and Applied Ecology, Forckenbeckstr. 6, D-52074 Aachen (Germany); Fenske, Martina, E-mail: martina.fenske@ime.fraunhofer.de [Fraunhofer Institute for Molecular Biology and Applied Ecology, Forckenbeckstr. 6, D-52074 Aachen (Germany); Holbech, Henrik, E-mail: hol@biology.sdu.dk [Department of Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M (Denmark); Segner, Helmut, E-mail: helmut.segner@vetsuisse.unibe.ch [Centre for Fish and Wildlife Health, Vetsuisse Faculty, University of Bern, PO Box 8466, CH-3001 Bern (Switzerland); Braunbeck, Thomas, E-mail: braunbeck@uni-hd.de [Aquatic Ecology and Toxicology Section, Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany)

    2014-08-01

    The aim of the present study was to investigate the persistence of the feminizing effects of discontinued 17α-ethinylestradiol (EE2) exposure on zebrafish (Danio rerio). An exposure scenario covering the sensitive phase of sexual differentiation, as well as final gonad maturation was chosen to examine the estrogenic effects on sexual development of zebrafish. Two exposure scenarios were compared: continuous exposure to environmentally relevant concentrations (0.1–10 ng/L EE2) up to 100 days post-hatch (dph) and developmental exposure up to 60 dph, followed by 40 days of depuration in clean water. The persistence of effects was investigated at different biological organization levels from mRNA to population-relevant endpoints to cover a broad range of important parameters. EE2 had a strong feminizing and inhibiting effect on the sexual development of zebrafish. Brain aromatase (cyp19b) mRNA expression showed no clear response, but vitellogenin levels were significantly elevated, gonad maturation and body growth were inhibited in both genders, and sex ratios were skewed towards females and undifferentiated individuals. To a large extent, all of these effects were reversed after 40 days of recovery, leading to the conclusion that exposure to the estrogen EE2 results in very strong, but reversible underdevelopment and feminization of zebrafish. The present study is the first to show this reversibility at different levels of organization, which gives better insight into the mechanistic basis of estrogenic effects in zebrafish. - Highlights: • Zebrafish were exposed to 17α-ethinylestradiol during their sexual differentiation. • Reversibility of effects was investigated after depuration of 40 days. • Morphological and physiological parameters were compared. • Zebrafish were able to recover at all different levels from mRNA to population.

  19. Reversibility of endocrine disruption in zebrafish (Danio rerio) after discontinued exposure to the estrogen 17α-ethinylestradiol

    DEFF Research Database (Denmark)

    Baumann, Lisa; Knörr, Susanne; Keiter, Susanne

    2014-01-01

    showed no clear response, but vitellogenin levelswere significantly elevated, gonadmaturation and body growth were inhibited in both genders, and sex ratioswere skewed towards females and undifferentiated individuals. To a large extent, all of these effects were reversed after 40 days of recovery......The aim of the present study was to investigate the persistence of the feminizing effects of discontinued 17α-ethinylestradiol (EE2) exposure on zebrafish (Danio rerio). An exposure scenario covering the sensitive phase of sexual differentiation, as well as final gonad maturation was chosen...... to examine the estrogenic effects on sexual development of zebrafish. Two exposure scenarioswere compared: continuous exposure to environmentally relevant concentrations (0.1–10 ng/L EE2) up to 100 days post-hatch (dph) and developmental exposure up to 60 dph, followed by 40 days of depuration in clean water...

  20. Requirements and comparative analysis of reverse genetics for bluetongue virus (BTV) and African horse sickness virus (AHSV).

    Science.gov (United States)

    van Rijn, Piet A; van de Water, Sandra G P; Feenstra, Femke; van Gennip, René G P

    2016-07-02

    Bluetongue virus (BTV) and African horse sickness virus (AHSV) are distinct arthropod borne virus species in the genus Orbivirus (Reoviridae family), causing the notifiable diseases Bluetongue and African horse sickness of ruminants and equids, respectively. Reverse genetics systems for these orbiviruses with their ten-segmented genome of double stranded RNA have been developed. Initially, two subsequent transfections of in vitro synthesized capped run-off RNA transcripts resulted in the recovery of BTV. Reverse genetics has been improved by transfection of expression plasmids followed by transfection of ten RNA transcripts. Recovery of AHSV was further improved by use of expression plasmids containing optimized open reading frames. Plasmids containing full length cDNA of the 10 genome segments for T7 promoter-driven production of full length run-off RNA transcripts and expression plasmids with optimized open reading frames (ORFs) were used. BTV and AHSV were rescued using reverse genetics. The requirement of each expression plasmid and capping of RNA transcripts for reverse genetics were studied and compared for BTV and AHSV. BTV was recovered by transfection of VP1 and NS2 expression plasmids followed by transfection of a set of ten capped RNAs. VP3 expression plasmid was also required if uncapped RNAs were transfected. Recovery of AHSV required transfection of VP1, VP3 and NS2 expression plasmids followed by transfection of capped RNA transcripts. Plasmid-driven expression of VP4, 6 and 7 was also needed when uncapped RNA transcripts were used. Irrespective of capping of RNA transcripts, NS1 expression plasmid was not needed for recovery, although NS1 protein is essential for virus propagation. Improvement of reverse genetics for AHSV was clearly demonstrated by rescue of several mutants and reassortants that were not rescued with previous methods. A limited number of expression plasmids is required for rescue of BTV or AHSV using reverse genetics, making the

  1. Reverse Genetics of SARS-Related Coronavirus Using Vaccinia Virus-Based Recombination

    Science.gov (United States)

    Zevenhoven, Jessika C.; Weber, Friedemann; Züst, Roland; Kuri, Thomas; Dijkman, Ronald; Chang, Guohui; Siddell, Stuart G.; Snijder, Eric J.; Thiel, Volker; Davidson, Andrew D.

    2012-01-01

    Severe acute respiratory syndrome (SARS) is a zoonotic disease caused by SARS-related coronavirus (SARS-CoV) that emerged in 2002 to become a global health concern. Although the original outbreak was controlled by classical public health measures, there is a real risk that another SARS-CoV could re-emerge from its natural reservoir, either in its original form or as a more virulent or pathogenic strain; in which case, the virus would be difficult to control in the absence of any effective antiviral drugs or vaccines. Using the well-studied SARS-CoV isolate HKU-39849, we developed a vaccinia virus-based SARS-CoV reverse genetic system that is both robust and biosafe. The SARS-CoV genome was cloned in separate vaccinia virus vectors, (vSARS-CoV-5prime and vSARS-CoV-3prime) as two cDNAs that were subsequently ligated to create a genome-length SARS-CoV cDNA template for in vitro transcription of SARS-CoV infectious RNA transcripts. Transfection of the RNA transcripts into permissive cells led to the recovery of infectious virus (recSARS-CoV). Characterization of the plaques produced by recSARS-CoV showed that they were similar in size to the parental SARS-CoV isolate HKU-39849 but smaller than the SARS-CoV isolate Frankfurt-1. Comparative analysis of replication kinetics showed that the kinetics of recSARS-CoV replication are similar to those of SARS-CoV Frankfurt-1, although the titers of virus released into the culture supernatant are approximately 10-fold less. The reverse genetic system was finally used to generate a recSARS-CoV reporter virus expressing Renilla luciferase in order to facilitate the analysis of SARS-CoV gene expression in human dendritic cells (hDCs). In parallel, a Renilla luciferase gene was also inserted into the genome of human coronavirus 229E (HCoV-229E). Using this approach, we demonstrate that, in contrast to HCoV-229E, SARS-CoV is not able to mediate efficient heterologous gene expression in hDCs. PMID:22412934

  2. Reverse genetics of SARS-related coronavirus using vaccinia virus-based recombination.

    Directory of Open Access Journals (Sweden)

    Sjoerd H E van den Worm

    Full Text Available Severe acute respiratory syndrome (SARS is a zoonotic disease caused by SARS-related coronavirus (SARS-CoV that emerged in 2002 to become a global health concern. Although the original outbreak was controlled by classical public health measures, there is a real risk that another SARS-CoV could re-emerge from its natural reservoir, either in its original form or as a more virulent or pathogenic strain; in which case, the virus would be difficult to control in the absence of any effective antiviral drugs or vaccines. Using the well-studied SARS-CoV isolate HKU-39849, we developed a vaccinia virus-based SARS-CoV reverse genetic system that is both robust and biosafe. The SARS-CoV genome was cloned in separate vaccinia virus vectors, (vSARS-CoV-5prime and vSARS-CoV-3prime as two cDNAs that were subsequently ligated to create a genome-length SARS-CoV cDNA template for in vitro transcription of SARS-CoV infectious RNA transcripts. Transfection of the RNA transcripts into permissive cells led to the recovery of infectious virus (recSARS-CoV. Characterization of the plaques produced by recSARS-CoV showed that they were similar in size to the parental SARS-CoV isolate HKU-39849 but smaller than the SARS-CoV isolate Frankfurt-1. Comparative analysis of replication kinetics showed that the kinetics of recSARS-CoV replication are similar to those of SARS-CoV Frankfurt-1, although the titers of virus released into the culture supernatant are approximately 10-fold less. The reverse genetic system was finally used to generate a recSARS-CoV reporter virus expressing Renilla luciferase in order to facilitate the analysis of SARS-CoV gene expression in human dendritic cells (hDCs. In parallel, a Renilla luciferase gene was also inserted into the genome of human coronavirus 229E (HCoV-229E. Using this approach, we demonstrate that, in contrast to HCoV-229E, SARS-CoV is not able to mediate efficient heterologous gene expression in hDCs.

  3. Partial and Full PCR-Based Reverse Genetics Strategy for Influenza Viruses

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  5. Reveal, A General Reverse Engineering Algorithm for Inference of Genetic Network Architectures

    Science.gov (United States)

    Liang, Shoudan; Fuhrman, Stefanie; Somogyi, Roland

    1998-01-01

    Given the immanent gene expression mapping covering whole genomes during development, health and disease, we seek computational methods to maximize functional inference from such large data sets. Is it possible, in principle, to completely infer a complex regulatory network architecture from input/output patterns of its variables? We investigated this possibility using binary models of genetic networks. Trajectories, or state transition tables of Boolean nets, resemble time series of gene expression. By systematically analyzing the mutual information between input states and output states, one is able to infer the sets of input elements controlling each element or gene in the network. This process is unequivocal and exact for complete state transition tables. We implemented this REVerse Engineering ALgorithm (REVEAL) in a C program, and found the problem to be tractable within the conditions tested so far. For n = 50 (elements) and k = 3 (inputs per element), the analysis of incomplete state transition tables (100 state transition pairs out of a possible 10(exp 15)) reliably produced the original rule and wiring sets. While this study is limited to synchronous Boolean networks, the algorithm is generalizable to include multi-state models, essentially allowing direct application to realistic biological data sets. The ability to adequately solve the inverse problem may enable in-depth analysis of complex dynamic systems in biology and other fields.

  6. A Reverse Genetics Platform That Spans the Zika Virus Family Tree

    Directory of Open Access Journals (Sweden)

    Douglas G. Widman

    2017-03-01

    Full Text Available Zika virus (ZIKV, a mosquito-borne flavivirus discovered in 1947, has only recently caused large outbreaks and emerged as a significant human pathogen. In 2015, ZIKV was detected in Brazil, and the resulting epidemic has spread throughout the Western Hemisphere. Severe complications from ZIKV infection include neurological disorders such as Guillain-Barré syndrome in adults and a variety of fetal abnormalities, including microcephaly, blindness, placental insufficiency, and fetal demise. There is an urgent need for tools and reagents to study the pathogenesis of epidemic ZIKV and for testing vaccines and antivirals. Using a reverse genetics platform, we generated six ZIKV infectious clones and derivative viruses representing diverse temporal and geographic origins. These include three versions of MR766, the prototype 1947 strain (with and without a glycosylation site in the envelope protein, and H/PF/2013, a 2013 human isolate from French Polynesia representative of the virus introduced to Brazil. In the course of synthesizing a clone of a circulating Brazilian strain, phylogenetic studies identified two distinct ZIKV clades in Brazil. We reconstructed viable clones of strains SPH2015 and BeH819015, representing ancestral members of each clade. We assessed recombinant virus replication, binding to monoclonal antibodies, and virulence in mice. This panel of molecular clones and recombinant virus isolates will enable targeted studies of viral determinants of pathogenesis, adaptation, and evolution, as well as the rational attenuation of contemporary outbreak strains to facilitate the design of vaccines and therapeutics.

  7. Design and optimization of desalination reverse osmosis plants driven by renewable energies using genetic algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Bourouni, K.; Ben M' Barek, T. [Energetique des Batiments et Systeme Solaire, Ecole Nationale d' Ingenieurs de Tunis, BP 37, Le Belvedere 1002 Tunis (Tunisia); Al Taee, A. [University of Surrey, Guidford, Surrey (United Kingdom)

    2011-03-15

    Renewable energy sources (RES) for powering desalination processes is a promising option especially in remote and arid regions where the use of conventional energy is costly or unavailable. Reverse Osmosis (RO) is one of the most suitable desalination processes to be coupled with different renewable energy sources such as solar and wind. If RES/RO systems are optimally designed, some combinations can be cost effective and reliable. However, the design of such systems is complex because of uncertain renewable energy supplies, load demands and the non-linear characteristics of some components. In such system, different scenarios can be suggested; i.e combinations of PV panels, type and number of batteries, type and number of turbines, etc. Therefore, it is difficult to determine the optimal configuration with classical techniques. The development of a tool to integrate all parameters involved and compare between the possible scenarios is very important. This paper presents a new model based on the Genetic Algorithms allowing the generation of several individuals (possible solutions) for coupling small RO unit to RES. A particular interest is focused on the hybrid systems (PV/WIND/Batteries/RO). The objective function to minimize corresponds to the total water cost (Capital cost plus Operational costs). Finally, a case study of PV/RO unit, installed since 2007 in Ksar Ghilene village in southern Tunisia, is presented. (author)

  8. Partial and full PCR-based reverse genetics strategy for influenza viruses.

    Directory of Open Access Journals (Sweden)

    Hongjun Chen

    Full Text Available 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.

  9. Brief exposure of embryos to steroids or aromatase inhibitor induces sex reversal in Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Gennotte, Vincent; Mafwila Kinkela, Patrick; Ulysse, Bernard; Akian Djétouan, Dieudonné; Bere Sompagnimdi, Frédéric; Tomson, Thomas; Mélard, Charles; Rougeot, Carole

    2015-01-01

    This study aimed to develop sex reversal procedures targeting the embryonic period as tools to study the early steps of sex differentiation in Nile tilapia with XX, XY, and YY sexual genotypes. XX eggs were exposed to masculinizing treatments with androgens (17α-methyltestosterone, 11-ketotestosterone) or aromatase inhibitor (Fadrozole), whereas XY and YY eggs were subjected to feminizing treatments with estrogen analog (17α-ethynylestradiol). All treatments consisted of a single or double 4-hr immersion applied between 1 and 36 hour post-fertilization (hpf). Concentrations of active substances were 1000 or 2000 μg l(-1) in XX and XY, and 2000 or 6500 μg l(-1) in YY. Masculinizing treatments of XX embryos achieved a maximal sex reversal rate of 10% with an exposure at 24 hpf to 1000 μg l(-1) of 11-ketotestosterone or to 2000 μg l(-1) of Fadrozole. Feminization of XY embryos was more efficient and induced up to 91% sex reversal with an exposure to 2000 μg l(-1) of 17α-ethynylestradiol. Interestingly, similar treatments failed to reverse YY fish to females, suggesting either that a sex determinant linked to the Y chromosome prevents the female pathway when present in two copies, or that a gene present on the X chromosome is needed for the development of a female phenotype. © 2014 Wiley Periodicals, Inc.

  10. The Effects of Synthetic Estrogen Exposure on the Sexually Dimorphic Liver Transcriptome of the Sex-Role-Reversed Gulf Pipefish.

    Directory of Open Access Journals (Sweden)

    Emily Rose

    Full Text Available Species exhibiting sex-role reversal provide an unusual perspective on the evolution of sex roles and sex differences. However, the proximate effects of sex-role reversal are largely unknown. Endocrine disruptors provide an experimental mechanism to address hormonal regulation of sexually dimorphic gene expression in sex-role-reversed taxa. Here, we investigate gene expression patterns in the liver of the sex-role-reversed Gulf pipefish, because the liver is known to be sexually dimorphic and estrogen-regulated in species with conventional sex roles. Using next-generation RNA-sequencing technology (RNA-seq, we detected sexually dimorphic hepatic gene expression patterns, with a total of 482 differentially expressed genes between the sexes in Gulf pipefish. Two-thirds of these genes were over-expressed in females, and the sex-specific transcriptomes of this sex-role-reversed pipefish's liver were superficially similar to those of fishes with conventional sex-roles. We exposed females, pregnant males, and non-pregnant males to 17α-ethinylestradiol (EE2 at ecologically relevant concentrations of 5ng/L and compared gene expression patterns in the livers of exposed fish to control fish. Several genes that were up-regulated in EE2-exposed males relative to control males were also found to be female-biased in control animals. These genes included several of the classic estrogen biomarkers, such as vitellogenin, choriogenin, and zona pellucida. Thus, estrogen exposure induced feminization of the male liver transcriptome in a sex-role-reversed pipefish. These results suggest that the ancestral state of estrogen-regulated female reproductive physiology has been retained in all sex-role-reversed vertebrates thus far studied, despite substantial evolution of the hormonal regulation of ornamentation and mating behavior in these interesting taxa.

  11. Incorporating peer support during in vivo exposure to reverse dropout from prolonged exposure therapy for posttraumatic stress disorder: Clinical outcomes.

    Science.gov (United States)

    Hernandez-Tejada, Melba A; Hamski, Stephanie; Sánchez-Carracedo, David

    2017-01-01

    Objective Prolonged exposure is characterized by reported dropout rates ranging from 25% to 40%. This premature attrition is also observed in other evidence-based treatments for posttraumatic stress disorder. While home-based telehealth delivery of prolonged exposure resolves logistical barriers to care such as travel time and cost, dropout appears unaffected. A previous study on dropouts from prolonged exposure delivered via telehealth found that Veterans, particularly those receiving care via telehealth, reported problems with in vivo exposure and that having a peer to offer support during in vivo exposure assignments might have prevented their attrition from treatment. Methods The present pilot study treatment was designed in a manner consistent with the aforementioned Veteran suggestions, specifically to involve peers offering verbal support and encouragement during in vivo exposure homework. Such a treatment modification might be particularly useful for those receiving care via telehealth, given increased difficulties with exposure reported when this treatment delivery modality is used. It was hypothesized that dropouts would agree to reengage in treatment with a peer and would subsequently evince improvement in posttraumatic stress disorder and depression scores as a result of this treatment reengagement. Results Of 82 dropouts from prolonged exposure, 29 reentered treatment when offered peer support during exposure (12 in telehealth and 17 in person). Conclusion Treatment reentry was effective insofar as indices of both posttraumatic stress disorder and depression were significantly reduced in both telehealth and in person groups, indicating that using peers in this way may be an effective means by which to return Veterans to care, and ultimately reduce symptomatology.

  12. A Reverse Genetics Platform That Spans the Zika Virus Family Tree.

    Science.gov (United States)

    Widman, Douglas G; Young, Ellen; Yount, Boyd L; Plante, Kenneth S; Gallichotte, Emily N; Carbaugh, Derek L; Peck, Kayla M; Plante, Jessica; Swanstrom, Jesica; Heise, Mark T; Lazear, Helen M; Baric, Ralph S

    2017-03-07

    Zika virus (ZIKV), a mosquito-borne flavivirus discovered in 1947, has only recently caused large outbreaks and emerged as a significant human pathogen. In 2015, ZIKV was detected in Brazil, and the resulting epidemic has spread throughout the Western Hemisphere. Severe complications from ZIKV infection include neurological disorders such as Guillain-Barré syndrome in adults and a variety of fetal abnormalities, including microcephaly, blindness, placental insufficiency, and fetal demise. There is an urgent need for tools and reagents to study the pathogenesis of epidemic ZIKV and for testing vaccines and antivirals. Using a reverse genetics platform, we generated six ZIKV infectious clones and derivative viruses representing diverse temporal and geographic origins. These include three versions of MR766, the prototype 1947 strain (with and without a glycosylation site in the envelope protein), and H/PF/2013, a 2013 human isolate from French Polynesia representative of the virus introduced to Brazil. In the course of synthesizing a clone of a circulating Brazilian strain, phylogenetic studies identified two distinct ZIKV clades in Brazil. We reconstructed viable clones of strains SPH2015 and BeH819015, representing ancestral members of each clade. We assessed recombinant virus replication, binding to monoclonal antibodies, and virulence in mice. This panel of molecular clones and recombinant virus isolates will enable targeted studies of viral determinants of pathogenesis, adaptation, and evolution, as well as the rational attenuation of contemporary outbreak strains to facilitate the design of vaccines and therapeutics. IMPORTANCE Viral emergence is a poorly understood process as evidenced by the sudden emergence of Zika virus in Latin America and the Caribbean. Malleable reagents that both predate and span an expanding epidemic are key to understanding the virologic determinants that regulate pathogenesis and transmission. We have generated representative c

  13. Generation of an external guide sequence library for a reverse genetic screen in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Yin Changxin

    2009-05-01

    Full Text Available Abstract Background A method for inhibiting the expression of particular genes using external guide sequences (EGSs has been developed in bacteria, mammalian cells and maize cells. Results To examine whether EGS technology can be used to down-regulate gene expression in Caenorhabditis elegans (C. elegans, we generated EGS-Ngfp-lacZ and EGS-Mtgfp that are targeted against Ngfp-lacZ and Mtgfp mRNA, respectively. These EGSs were introduced, both separately and together, into the C. elegans strain PD4251, which contains Ngfp-lacZ and Mtgfp. Consequently, the expression levels of Ngfp-lacZ and Mtgfp were affected by EGS-Ngfp-lacZ and EGS-Mtgfp, respectively. We further generated an EGS library that contains a randomized antisense domain of tRNA-derived EGS ("3/4 EGS". Examination of the composition of the EGS library showed that there was no obvious bias in the cloning of certain EGSs. A subset of EGSs was randomly chosen for screening in the C. elegans strain N2. About 6% of these EGSs induced abnormal phenotypes such as P0 slow postembryonic growth, P0 larval arrest, P0 larval lethality and P0 sterility. Of these, EGS-35 and EGS-83 caused the greatest phenotype changes, and their target mRNAs were identified as ZK858.7 mRNA and Lin-13 mRNA, respectively. Conclusion EGS technology can be used to down-regulate gene expression in C. elegans. The EGS library is a research tool for reverse genetic screening in C. elegans. These observations are potentially of great importance to further our understanding and use of C. elegans genomics.

  14. Generation of an external guide sequence library for a reverse genetic screen in Caenorhabditis elegans.

    Science.gov (United States)

    Yan, Qitao; Zhao, Rui; Zheng, Wenlin; Yin, Changxin; Zhang, Bao; Ma, Wenli

    2009-05-20

    A method for inhibiting the expression of particular genes using external guide sequences (EGSs) has been developed in bacteria, mammalian cells and maize cells. To examine whether EGS technology can be used to down-regulate gene expression in Caenorhabditis elegans (C. elegans), we generated EGS-Ngfp-lacZ and EGS-Mtgfp that are targeted against Ngfp-lacZ and Mtgfp mRNA, respectively. These EGSs were introduced, both separately and together, into the C. elegans strain PD4251, which contains Ngfp-lacZ and Mtgfp. Consequently, the expression levels of Ngfp-lacZ and Mtgfp were affected by EGS-Ngfp-lacZ and EGS-Mtgfp, respectively. We further generated an EGS library that contains a randomized antisense domain of tRNA-derived EGS ("3/4 EGS"). Examination of the composition of the EGS library showed that there was no obvious bias in the cloning of certain EGSs. A subset of EGSs was randomly chosen for screening in the C. elegans strain N2. About 6% of these EGSs induced abnormal phenotypes such as P0 slow postembryonic growth, P0 larval arrest, P0 larval lethality and P0 sterility. Of these, EGS-35 and EGS-83 caused the greatest phenotype changes, and their target mRNAs were identified as ZK858.7 mRNA and Lin-13 mRNA, respectively. EGS technology can be used to down-regulate gene expression in C. elegans. The EGS library is a research tool for reverse genetic screening in C. elegans. These observations are potentially of great importance to further our understanding and use of C. elegans genomics.

  15. Generation of High-Yielding Influenza A Viruses in African Green Monkey Kidney (Vero) Cells by Reverse Genetics

    OpenAIRE

    Ozaki, Hiroichi; Govorkova, Elena A.; Li, Chenghong; Xiong, Xiaoping; Webster, Robert G.; Webby, Richard J.

    2004-01-01

    Influenza A viruses are the cause of annual epidemics of human disease with occasional outbreaks of pandemic proportions. The zoonotic nature of the disease and the vast viral reservoirs in the aquatic birds of the world mean that influenza will not easily be eradicated and that vaccines will continue to be needed. Recent technological advances in reverse genetics methods and limitations of the conventional production of vaccines by using eggs have led to a push to develop cell-based strategi...

  16. Combat Exposure Severity as a Moderator of Genetic and Environmental Liability to Posttraumatic Stress Disorder

    Science.gov (United States)

    Wolf, Erika J.; Mitchell, Karen S.; Koenen, Karestan C.; Miller, Mark W.

    2014-01-01

    Background Twin studies of veterans and adults suggest that approximately 30–46% of the variance in posttraumatic stress disorder (PTSD) is attributable to genetic factors. The remaining variance is attributable to the non-shared environment, which, by definition, includes combat exposure. This study used a gene by measured environment twin design to examine if the effect of genetic and environmental factors that contribute to the etiology PTSD were dependent on level of combat exposure. Methods The sample was drawn from the Vietnam Era Twin Registry and included 620 male-male twin pairs who served in the U.S. Military in South East Asia during the Vietnam War era. Analyses were based on data from a clinical diagnostic interview of lifetime PTSD symptoms and a self-report measure of combat exposure. Results Biometric modeling revealed that the effect of genetic and non-shared environment factors on PTSD varied as a function of level of combat exposure such that the association between these factors and PTSD was stronger at higher levels of combat exposure. Conclusions Combat exposure may act as a catalyst that augments the impact of hereditary and environmental contributions to PTSD. Individuals with the greatest exposure to combat trauma were at increased risk for PTSD as a function of both genetic and other environmental factors. Additional work is needed to determine the biological and environmental mechanisms driving these associations. PMID:24001428

  17. Brief Daily Exposures to Asian Females Reverses Perceptual Narrowing for Asian Faces in Caucasian Infants

    Science.gov (United States)

    Anzures, Gizelle; Wheeler, Andrea; Quinn, Paul C.; Pascalis, Olivier; Slater, Alan M.; Heron-Delaney, Michelle; Tanaka, James W.; Lee, Kang

    2012-01-01

    Perceptual narrowing in the visual, auditory, and multisensory domains has its developmental origins during infancy. The current study shows that experimentally induced experience can reverse the effects of perceptual narrowing on infants' visual recognition memory of other-race faces. Caucasian 8- to 10-month-olds who could not discriminate…

  18. Post-partum testosterone administration partially reverses the effects of perinatal cadmium exposure on sexual behavior in rats

    OpenAIRE

    Couto-Moraes, Renato; Felício, Luciano Freitas; Oliveira, Claudio Alvarenga de; Bernardi, Maria Martha

    2012-01-01

    This study investigated the effects of perinatal cadmium exposure on sexual behavior, organ weight, and testosterone levels in adult rats. We examined whether immediate postpartum testosterone administration is able to reverse the toxic effects of the metal. Forty pregnant Wistar rats were divided into three groups: 1) control, 2) 10 mg kg-1 cadmium chloride per day, and 3) 20 mg kg-1 cadmium chloride per day. These dams were treated on gestational days 18 and 21 and from lactation 1 to 7. Im...

  19. Media Exposure and Genetic Literacy Skills to Evaluate Angelina Jolie's Decision for Prophylactic Mastectomy.

    Science.gov (United States)

    Abrams, Leah R; Koehly, Laura M; Hooker, Gillian W; Paquin, Ryan S; Capella, Joseph N; McBride, Colleen M

    2016-01-01

    To examine public preparedness to evaluate and respond to Angelina Jolie's well-publicized decision to have a prophylactic mastectomy. A consumer panel (n = 1,008) completed an online survey in November 2013, reporting exposure to Jolie's story, confidence applying genomic knowledge to evaluate her decision, and ability to interpret provided genetic risk information (genetic literacy skills). Linear and logistic regressions tested mediating/moderating models of these factors in association with opinions regarding mastectomies. Confidence with genomics was associated with increased genetic literacy skills and increased media exposure, with a significant interaction between the two. Confidence was also associated with favoring mastectomies for women with BRCA mutations, mediating the relationship with media exposure. Respondents were more likely to form opinions about mastectomies if they had high genetic literacy skills. These findings suggest that having higher genetic literacy skills may increase the public's ability to form opinions about clinical applications of genomic discovery. However, repeated media exposure to high-profile stories may artificially inflate confidence among those with low genetic literacy. © 2016 S. Karger AG, Basel.

  20. Post-partum testosterone administration does not reverse the effects of perinatal exposure to cadmium on rat offspring development.

    Science.gov (United States)

    Couto-Moraes, R; Felicio, L F; Bernardi, M M

    2010-04-01

    This study investigated the effects of perinatal cadmium exposure on physical and reflexologic development of pup rats. It was examined if the immediate postpartum testosterone administration was able to reverse the toxic effects of the metal. Forty Wistar pregnant rats were divided into three groups: control and 10 and 20 mg kg(-1) per day of cadmium chloride. These dams were treated from gestational days 18 to 21, and until the 7th lactation day. Immediately after birth, half of the offspring from the experimental and control groups received 50 microL of testosterone 0.2% i.p. The maternal body weight gain, food and water consumption were measured during the treatment period. In pups, the body weight, body length, physical landmarks, reflex development and the general activity were assessed. Results showed that: only 20 mg kg(-1) cadmium induced maternal toxicity; pup body weight and body weight gain were reduced in all experimental groups; only the cadmium-exposed offspring not treated with testosterone treatment showed a reduction in body length and body length gain; cadmium highest dose reduced the anogenital index in pups and delayed physical and reflexes development; and cadmium effects on the offspring, except in body length gain, were not reversed by testosterone. The results indicate that perinatal maternal exposure to cadmium promoted changes in the development of male rat offspring, reprogramming the pup's development. Testosterone administration was not able to reverse the cadmium effects, even on those parameters more directly related to the androgenic system as the testis descent and anogenital distance delays. (c) 2009 John Wiley & Sons, Ltd.

  1. Expanding the Lotus japonicus reverse genetics toolbox – Development of LORE1 retrotransposon mutagenesis and artificial miRNA-mediated silencing

    DEFF Research Database (Denmark)

    Urbanski, Dorian Fabian

    2011-01-01

    . The protocols developed in the current project are now the cornerstone of a new LORE1 reverse genetics resource characterized by efficient mutant line generation and accurate mutation annotation. In parallel, artificial microRNAs (amiRNAs) were designed based on both Arabidopsis and Lotus backbones......Currently, the most common approach to studying Lotus japonicus (Lotus) genes is forward genetics in which a gene responsible for the studied phenotype is identified through map-based cloning. In reverse genetics, the activity of a gene of interest is modified to discover its mutant phenotype....... Prior to this project, the only reverse genetics resource available in Lotus was the TILLING resource. In an attempt to advance Lotus genetic studies, present study is focused on the development of two additional resources. The first is based on insertional mutagenesis and the second on harnessing post...

  2. Reversible loss of reproductive fitness in zebrafish on chronic alcohol exposure.

    Science.gov (United States)

    Dewari, Pooran Singh; Ajani, Funmilola; Kushawah, Gopal; Kumar, Damera Santhosh; Mishra, Rakesh K

    2016-02-01

    Alcoholism is one of the most prevalent diseases in society and causes significant health and social problems. Alcohol consumption by pregnant women is reported to cause adverse effects on the physical and psychological growth of the fetus. However, the direct effect of chronic alcohol consumption on reproductive fitness has not been tested. In recent years, the zebrafish (Danio rerio) has emerged as a versatile model system to study the effects of alcohol on behavior and embryonic development. We utilized the zebrafish model system to address the effect of chronic alcohol exposure (0.5% alcohol in the holding tank for 9 weeks) on reproductive capacity. We found a dramatic decrease in fecundity, measured by counting the number of eggs laid, when at least one of the parents is subject to chronic alcohol exposure. Interestingly, a 9-week alcohol withdrawal program completely restored the reproductive capacity of the treated subjects. In agreement with observations on fecundity, the chronic alcohol exposure leads to increased anxiety, as measured by the novel-tank diving assay. Conversely, the withdrawal program diminished heightened anxiety in alcohol-exposed subjects. Our results highlight the adverse effects of chronic alcohol exposure on the reproductive capacity of both males and females, and underscore the utility of the zebrafish model system to understand the biology of chronic alcoholism. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Reversing Implicit Gender Stereotype Activation as a Function of Exposure to Traditional Gender Roles

    NARCIS (Netherlands)

    de Lemus, Soledad; Spears, Russell; Bukowski, Marcin; Moya, Miguel; Lupianez, Juan

    2013-01-01

    We examined the influence of exposure to traditional gender roles on the activation of gender stereotypes in Spanish women. An associative procedure was used to expose participants to stereotypical vs. counterstereotypical gender roles, and a word categorization task with stereotypically feminine

  4. Reversing the mere exposure effect in spider fearfuls: Preliminary evidence of sensitization

    NARCIS (Netherlands)

    Becker, E.S.; Rinck, M.

    2016-01-01

    A mere exposure effect (MEE) is said to occur when individuals' liking of a suboptimally and repeatedly presented stimulus increases compared to never-presented stimuli, while they are unable to indicate which stimuli were previously presented and which were not. In two experiments, we used the MEE

  5. Genetic susceptibility loci, pesticide exposure and prostate cancer risk.

    Directory of Open Access Journals (Sweden)

    Stella Koutros

    Full Text Available Uncovering SNP (single nucleotide polymorphisms-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs and 95% confidence intervals (CIs. Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1 SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44-8.15 (P-interaction= 0.003. Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41 (P-interaction= 0.006. In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.

  6. Toxicant Exposure and Bioaccumulation: A Common and Potentially Reversible Cause of Cognitive Dysfunction and Dementia

    Directory of Open Access Journals (Sweden)

    Stephen J. Genuis

    2015-01-01

    Full Text Available Juxtaposed alongside the ongoing rise in the incidence and prevalence of dementia, is the surge of recent research confirming widespread exposure and bioaccumulation of chemical toxicants. Evidence from sources such as the Centers for Disease Control reveals that most people have accrued varying degrees of assorted toxic pollutants including heavy metals, flame retardants, and pesticide residues within their bodies. It has been well established that many of these toxicants have neurodegenerative as well as neurodevelopmental impact as a result of various pathophysiologic mechanisms including neuronal mitochondrial toxicity and disruption of neurotransmitter regulation. Elimination of stockpiled toxicants from the body may diminish adverse toxicant impact on human biology and allow restoration of normal physiological function. Incorporating a review of medical literature on toxicant exposure and dementia with a case history of a lead-exposed individual diagnosed with dementia, this paper will discuss a much overlooked and potentially widespread cause of declining brain function and dementia.

  7. Accelerated habit formation following amphetamine exposure is reversed by D1, but enhanced by D2, receptor antagonists

    Directory of Open Access Journals (Sweden)

    Andrew John Dudley Nelson

    2013-05-01

    Full Text Available Repeated exposure to the psychostimulant amphetamine has been shown to disrupt goal-directed instrumental actions and promote the early and abnormal development of goal-insensitive habitual responding (Nelson and Killcross, 2006. To investigate the neuropharmacological specificity of this effect as well as restore goal-directed responding in animals with pre-training amphetamine exposure, animals were treated with the non-selective dopamine antagonist α-flupenthixol, the selective D1 antagonist SCH 23390 or the selective D2 antagonist eticlopride, prior to instrumental training (3 sessions. Subsequently, the reinforcer was paired with LiCL-induced gastric-malaise and animals were given a test of goal-sensitivity both in extinction and reacquisition. The effect of these dopaminergic antagonists on the sensitivity of lever press performance to outcome devaluation was assessed in animals with pre-training exposure to amphetamine (Experiments 1a-1c or in non-sensitized animals (Experiment 2. Both α-flupenthixol and SCH23390 reversed accelerated habit formation following amphetamine sensitization. However, eticlopride appeared to enhance this effect and render instrumental performance compulsive as these animals were unable to inhibit responding both in extinction and reacquisition, even though a consumption test confirmed they had acquired an aversion to the reinforcer. These findings demonstrate that amphetamine induced-disruption of goal-directed behaviour is mediated by activity at distinct dopamine receptor subtypes and may represent a putative model of the neurochemical processes involved in the loss of voluntary control over behaviour.

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

    Energy Technology Data Exchange (ETDEWEB)

    Albariño, César G., E-mail: calbarino@cdc.gov; Wiggleton Guerrero, Lisa; Lo, Michael K.; Nichol, Stuart T.; Towner, Jonathan S.

    2015-10-15

    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 usefulness 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.

  9. XX sex reversal, palmoplantar keratoderma, and predisposition to squamous cell carcinoma: genetic analysis in one family.

    Science.gov (United States)

    Radi, Orietta; Parma, Pietro; Imbeaud, Sandrine; Nasca, Maria Rita; Uccellatore, Filippo; Maraschio, Paola; Tiepolo, Luciano; Micali, Giuseppe; Camerino, Giovanna

    2005-10-15

    We describe a large inbred Sicilian family that includes four 46, XX (SRY-) brothers. Palmoplantar hyperkeratosis (PPK) and an associated predisposition to squamous cell carcinoma (SCC) of the skin, segregates as a recessive trait within the family. Interestingly, all the PPK-affected members of the family are phenotypic males (46,XY or 46,XX) while seven XX sibs are healthy phenotypic females with no signs of PPK. We propose that homozygosity for a single mutational event, possibly including contiguous genes, may cause PPK/SCC in both XY or XX individuals and sex reversal in XX individuals. The family is informative for linkage analysis for the PPK trait and allows linkage exclusion for the sex reversal trait. Here we show that 15 loci involved in PPK etiology, skin differentiation, function or malignancy, and nine loci involved in sex determination/differentiation are not implicated in the phenotype of this family.

  10. [Current problems of estimation of genetic risk of human exposure to radiation].

    Science.gov (United States)

    Shevchenko, V A

    2000-01-01

    The methodology of assessing the genetic risk of radiation exposure is based on the concept of "hitting the target" in development of which N.V. Timofeeff-Ressovsky has played and important role. To predict genetic risk posed by irradiation, the UN Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) has worked out direct and indirect methods of assessment, extrapolational, integral and populational criteria of risk analysis that together permit calculating the risk from human exposure on the basis of data obtained for mice. Laboratory mice are the main objects in studying radiation mutagenesis due to the fact that the data on the frequency of radiation-induced human mutations are rather scarce. The method of doubling dose based on the determination of a dose doubling the level of natural mutational process in humans is the main one used to predict the genetic risk. The evolution of views about the genetics risk of human exposure to radiation for last 40 years is considered. Till 1972 the main model for assessing the genetic risk was the "human/mouse" model (the use of data on the spontaneous human variability and data on the frequency of induced mutations in mice). In the period form 1972 till 1994 the "mouse/mouse" model was intensively elaborated in many laboratories. This model was also used in this period by UNSCEAR experts to analyze the genetic risk from human irradiation. Recent achievements associated with the study of the molecular nature of many hereditary human diseases as well as the criticism of number fundamental principles of the "mouse/mouse" model for estimating the genetic risk on a new basis. The estimates of risk for the different classes of genetic diseases have been obtained using the doubling-dose method. The estimate of doubling dose used in the calculations is 1 Gy for low dose/chronic low-LET radiation conditions.

  11. Genetic Diversity Influences the Response of the Brain to Developmental Lead Exposure

    Science.gov (United States)

    Schneider, Jay S.; Talsania, Keyur; Mettil, William; Anderson, David W.

    2014-01-01

    Although extrinsic factors, such as nutritional status, and some intrinsic genetic factors may modify susceptibility to developmental lead (Pb) poisoning, no studies have specifically examined the influence of genetic background on outcomes from Pb exposure. In this study, we used gene microarray profiling to identify Pb-responsive genes in rats of different genetic backgrounds, including inbred (Fischer 344 (F344)) and outbred (Long Evans (LE), Sprague Dawley (SD)) strains, to investigate the role that genetic variation may play in influencing outcomes from developmental Pb exposure. Male and female animals received either perinatal (gestation through lactation) or postnatal (birth through weaning) exposure to Pb in food (0, 250, or 750 ppm). RNA was extracted from the hippocampus at day 55 and hybridized to Affymetrix Rat Gene 1.0 ST Arrays. There were significant strain-specific effects of Pb on the hippocampal transcriptome with 978 transcripts differentially expressed in LE rats across all experimental groups, 269 transcripts differentially expressed in F344 rats, and only 179 transcripts differentially expressed in SD rats. These results were not due to strain-related differences in brain accumulation of Pb. Further, no genes were consistently differentially regulated in all experimental conditions. There was no set of “Pb toxicity” genes that are a molecular signature for Pb neurotoxicity that transcended sex, exposure condition, and strain. These results demonstrate the influence that strain and genetic background play in modifying the brain's response to developmental Pb exposure and may have relevance for better understanding the molecular underpinnings of the lack of a neurobehavioral signature in childhood Pb poisoning. PMID:24913800

  12. Enhancing exposure to genetics and genomics through an innovative medical school curriculum.

    Science.gov (United States)

    Dhar, Shweta U; Alford, Raye L; Nelson, Elizabeth A; Potocki, Lorraine

    2012-01-01

    Physicians entering medical practice in the 21st century will require more than a basic understanding of human genetics because of rapid progress in the field of genetics and genomics. The current undergraduate medical curriculum at most institutions is not adequate to prepare medical students for these challenges. Enhancing exposure to genetics throughout the medical school curriculum should help prepare the next generation of physicians to use genetic and genomic information for optimal patient care. We have introduced a Genetics Track Curriculum to the undergraduate medical curriculum at Baylor College of Medicine. This track runs in parallel to the existing 4-year curriculum and includes didactic sessions, small group discussions, longitudinal clinical experiences, clinical and laboratory rotations, community outreach, and scholarly projects related to genetics. It also provides the students a means to network and discuss topics and career paths in medical genetics. We have developed a novel curriculum that enhances genomic education for medical students with the ultimate goal of enabling our graduates to deliver more effective and personalized medical care. We believe that the Genetics Track Curriculum at Baylor College of Medicine can serve as a prototype for other medical schools across the country and abroad.

  13. Rat reverse genetics : generation and characterization of chemically induced rat mutants

    NARCIS (Netherlands)

    van Boxtel, R.

    2010-01-01

    The use of animal models has been crucial for studying the function of genetic elements in the human genome. Embryonic stem (ES) cell-based homologous recombination (HR) has proven a very efficient technique for gene manipulation. However, this technique is not (yet) available for all model

  14. L-Carnitine reverses maternal cigarette smoke exposure-induced renal oxidative stress and mitochondrial dysfunction in mouse offspring.

    Science.gov (United States)

    Nguyen, Long T; Stangenberg, Stefanie; Chen, Hui; Al-Odat, Ibrahim; Chan, Yik L; Gosnell, Martin E; Anwer, Ayad G; Goldys, Ewa M; Pollock, Carol A; Saad, Sonia

    2015-04-01

    Maternal smoking is associated with metabolic disorders, renal underdevelopment, and a predisposition to chronic kidney disease in offspring, yet the underlying mechanisms are unclear. By exposing female Balb/c mice to cigarette smoke for 6 wk premating and during gestation and lactation, we showed that maternal smoke exposure induced glucose intolerance, renal underdevelopment, inflammation, and albuminuria in male offspring. This was associated with increased renal oxidative stress and mitochondrial dysfunction at birth and in adulthood. Importantly, we demonstrated that dietary supplementation of l-carnitine, an amino acid shown to increase antioxidant defenses and mitochondrial function in numerous diseases, in smoke-exposed mothers during pregnancy and lactation significantly reversed the detrimental maternal impacts on kidney pathology in these male offspring. It increased SOD2 and glutathione peroxidase 1, reduced ROS accumulation, and normalized levels of mitochondrial preprotein translocases of the outer membrane, and oxidative phosphorylation complexes I-V in the kidneys of mouse progeny after intrauterine cigarette smoke exposure. These findings support the hypothesis that oxidative stress and mitochondrial dysfunction are closely linked to the adverse effects of maternal smoking on male offspring renal pathology. The results of our study suggest that l-carnitine administration in cigarette smoke-exposed mothers mitigates these deleterious renal consequences. Copyright © 2015 the American Physiological Society.

  15. Long-term exposure to MST-312 leads to telomerase reverse transcriptase overexpression in MCF-7 breast cancer cells.

    Science.gov (United States)

    Morais, Karollyne S; Guimarãesb, Ana Flávia R; Ramos, Doralina A R; Silva, Fábio P; de Oliveira, Diêgo M

    2017-08-01

    Telomerase is an enzyme responsible for telomere maintenance in almost all human cancer cells, but generally not expressed in somatic ones. Therefore, antitelomerase therapy is a potentially revolutionary therapeutic strategy, and the antitumor activity of telomerase inhibitors (TI) has been studied extensively recently, mainly for breast cancer. However, the effects expected from treatment with TI will appear only after many cell divisions, but the effects of this long-term approach are unknown. In this work, the consequences of 3120 h exposure of human breast cancer cells to TI MST-312 were investigated. MCF-7 cells were treated with MST-312 at a subtoxic concentration for a long time, and then cell morphology, viability, senescence, and proliferation were analyzed by phase-contrast microscopy, MTT assay, β-galactosidase test, and the trypan blue exclusion assay, respectively. Also, chromosomal stability was evaluated by classical cytogenetic analysis. The average length of telomeres and telomerase reverse transcriptase expression were accessed by real-time PCR and real-time RT-PCR, respectively. The MST-312 showed cytotoxic action and promoted telomere erosion, senescence, and chromosome aberrations, as expected, but in a small proportion. Nevertheless, the proliferation rate of the culture was not affected. As the main effect, the chronic exposure led to cell adaptation by overexpression of telomerase in response to the inhibitor, which is a potential cause of therapeutic failure and may be associated with a poor prognosis. In conclusion, despite the high therapeutic potential of TIs such as MST-312, the molecular outcomes of long-term exposure of tumors on these drugs have to be evaluated when considering their clinical application, especially for breast cancer treatment.

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

    OpenAIRE

    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 re...

  17. Evolved resistance to colistin and its loss due to genetic reversion in Pseudomonas aeruginosa

    OpenAIRE

    Ji-Young Lee; Young Kyoung Park; Eun Seon Chung; In Young Na; Kwan Soo Ko

    2016-01-01

    The increased reliance on colistin for treating multidrug-resistant Gram-negative bacterial infections has resulted in the emergence of colistin-resistant Pseudomonas aeruginosa. We attempted to identify genetic contributors to colistin resistance in vitro evolved isogenic colistin-resistant and -susceptible strains of two P. aeruginosa lineages (P5 and P155). Their evolutionary paths to acquisition and loss of colistin resistance were also tracked. Comparative genomic analysis revealed 13 an...

  18. The reverse cholesterol transport pathway improves understanding of genetic networks for fat deposition and muscle growth in beef cattle.

    Directory of Open Access Journals (Sweden)

    Tyler F Daniels

    Full Text Available In the present study, thirteen genes involved in the reverse cholesterol transport (RCT pathway were investigated for their associations with three fat depositions, eight fatty acid compositions and two growth-related phenotypes in a Wagyu x Limousin reference population, including 6 F(1 bulls, 113 F(1 dams, and 246 F(2 progeny. A total of 37 amplicons were used to screen single nucleotide polymorphisms (SNPs on 6 F(1 bulls. Among 36 SNPs detected in 11 of these 13 genes, 19 were selected for genotyping by the Sequenom assay design on all F(2 progeny. Single-marker analysis revealed seven SNPs in ATP binding cassette A1, apolipoproteins A1, B and E, phospholipid transfer protein and paraoxinase 1 genes significantly associated with nine phenotypes (P<0.05. Previously, we reported genetic networks associated with 19 complex phenotypes based on a total of 138 genetic polymorphisms derived from 71 known functional genes. Therefore, after Bonferroni correction, these significant (adjusted P<0.05 and suggestive (adjusted P<0.10 associations were then used to identify genetic networks related to the RCT pathway. Multiple-marker analysis suggested possible genetic networks involving the RCT pathway for kidney-pelvic-heart fat percentage, rib-eye area, and subcutaneous fat depth phenotypes with markers derived from paraoxinase 1, apolipoproteins A1 and E, respectively. The present study confirmed that genes involved in cholesterol homeostasis are useful targets for investigating obesity in humans as well as for improving meat quality phenotypes in a livestock production.

  19. The molecular genetics of sex determination and sex reversal in mammals.

    Science.gov (United States)

    Quinn, Alexander; Koopman, Peter

    2012-10-01

    The process of sex determination in mammals normally unfolds in three distinct stages: (1) establishment of chromosomal sex at fertilization (XX or XY); (2) commitment to the appropriate pathway of gonadal differentiation with respect to chromosomal sex, through the action (or absence) of the Y chromosome gene SRY; and (3) correct development of secondary sexual characteristics, including internal and external genitalia, in accordance with gonadal sex. At any of these three steps, the process of sex determination can go awry, leading to disorders of sexual development. In this article, we review the typical mechanism and process of mammalian sex determination, with an emphasis on the well-characterized mouse and human models. We also consider aberrant mammalian sex determination, focusing on examples of sex reversal stemming from gene defects. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  20. Reverse genetic engineering of the human rhinovirus serotype 16 genome to introduce an antibody-detectable tag.

    Science.gov (United States)

    Walker, Erin J; Jensen, Lora M; Ghildyal, Reena

    2015-01-01

    The ability to accurately detect viral proteins during infection is essential for virology research, and the lack of specific antibodies can make this detection difficult. Reverse genetic engineering of virus genomes to alter the wild-type genome is a powerful technique to introduce a detectable tag onto a viral protein. Here we outline a method to incorporate an influenza hemagglutinin epitope tag onto the 2A protease of HRV16. The method uses site-directed mutagenesis PCR to introduce the sequence for the HA antigen onto either the C or N termini of 2A protease while keeping the relevant internal cleavage sites intact. The new viral product is then cloned into a wild-type HRV16 plasmid and transfected into Ohio Hela cells to produce recombinant virus.

  1. Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer's disease mouse model.

    Science.gov (United States)

    Zhang, Yongfang; Kurup, Pradeep; Xu, Jian; Carty, Nikisha; Fernandez, Stephanie M; Nygaard, Haakon B; Pittenger, Christopher; Greengard, Paul; Strittmatter, Stephen M; Nairn, Angus C; Lombroso, Paul J

    2010-11-02

    Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disorder. Early in the pathophysiology of AD, synaptic function is disrupted by soluble Aβ oligomers, possibly through Aβ-mediated internalization of NMDA receptors. Striatal-enriched phosphatase (STEP) is a tyrosine phosphatase that regulates the internalization of NMDA receptors. Recent work shows that STEP is elevated in the prefrontal cortex of human AD patients and in animal models of AD. Here, we use genetic manipulations to reduce STEP activity in a triple transgenic AD mouse model and show that a decrease in STEP levels reverses cognitive and cellular deficits observed in these mice. Our results suggest that STEP inhibitors may prove therapeutic for this devastating disorder.

  2. Genetic Modification of the Penicillin G Acylase Surface To Improve Its Reversible Immobilization on Ionic Exchangers▿

    Science.gov (United States)

    Montes, Tamara; Grazú, Valeria; López-Gallego, Fernando; Hermoso, Juan A.; García, Jose L.; Manso, Isabel; Galán, Beatriz; González, Ramón; Fernández-Lafuente, Roberto; Guisán, José M.

    2007-01-01

    A new mutant of the industrial enzyme penicillin G acylase (PGA) from Escherichia coli has been designed to improve its reversible immobilization on anionic exchangers (DEAE- or polyethyleneimine [PEI]-coated agarose) by assembling eight new glutamic residues distributed homogeneously through the enzyme surface via site-directed mutagenesis. The mutant PGA is produced and processed in vivo as is the native enzyme. Moreover, it has a similar specific activity to and shows the same pH activity profile as native PGA; however, its isoelectric point decreased from 6.4 to 4.3. Although the new enzyme is adsorbed on both supports, the adsorption was even stronger when supports were coated with PEI, allowing us to improve the enzyme stability in organic cosolvents. The use of restrictive conditions during the enzyme adsorption on anionic exchangers (pH 5 and high ionic strength) permitted us to still further increase the strength of adsorption and the enzyme stability in the presence of organic solvents, suggesting that these conditions allow the penetration of the enzyme inside the polymeric beds, thus becoming fully covered with the polymer. After the enzyme inactivation, it can be desorbed to reuse the support. The possibility to improve the immobilization properties on an enzyme by site-directed mutagenesis of its surface opens a promising new scenario for enzyme engineering. PMID:17098917

  3. Physiology and genetic traits of reverse osmosis membrane biofilms: a case study with Pseudomonas aeruginosa.

    Science.gov (United States)

    Herzberg, Moshe; Elimelech, Menachem

    2008-02-01

    Biofilm formation of Pseudomonas aeruginosa on the surface of a reverse osmosis (RO) membrane was studied using a synthetic wastewater medium to simulate conditions relevant to reclamation of secondary wastewater effluent. P. aeruginosa biofilm physiology and spatial activity were analyzed following growth on the membrane using a short-life green fluorescent protein derivative expressed in a growth-dependent manner. As a consequence of the limiting carbon source prevailing in the suspended culture of the RO unit, a higher distribution of active cells was observed in the biofilm close to the membrane surface, likely due to the higher nutrient levels induced by concentration polarization effects. The faster growth of the RO-sessile cells compared to the planktonic cells in the RO unit was reflected by the transcriptome of the two cultures analyzed with DNA microarrays. In contrast to the findings recently reported in gene expression studies of P. aeruginosa biofilms, in the RO system, genes related to stress, adaptation, chemotaxis and resistance to antibacterial agents were induced in the planktonic cells. In agreement with the findings of previous P. aeruginosa biofilm studies, motility- and attachment-related genes were repressed in the RO P. aeruginosa biofilm. Supported by the microarray data, an increase in both motility and chemotaxis phenotypes was observed in the suspended cells. The increase in nutrient concentration in close proximity to the membrane is suggested to enhance biofouling by chemotaxis response of the suspended cells and their swimming toward the membrane surface.

  4. Inflammatory changes in the airways of mice caused by cigarette smoke exposure are only partially reversed after smoking cessation

    Directory of Open Access Journals (Sweden)

    Kraneveld Aletta D

    2010-07-01

    Full Text Available Abstract Background Tobacco smoking irritates and damages the respiratory tract and contributes to a higher risk of developing lung emphysema. At present, smoking cessation is the only effective treatment for reducing the progression of lung emphysema, however, there is hardly anything known about the effects of smoking cessation on cytokine and chemokine levels in the airways. To the best of our knowledge, this is the first reported in vivo study in which cytokine profiles were determined after cessation of cigarette smoke exposure. Methods The severity of airway remodeling and inflammation was studied by analyzing alveolar enlargement, heart hypertrophy, inflammatory cells in the bronchoalveolar lavage fluid (BALF and lung tissue and by determining the cytokine and chemokine profiles in the BALF of A/J mice exposed to cigarette smoke for 20 weeks and 8 weeks after smoking cessation. Results The alveolar enlargement and right ventricle heart hypertrophy found in smoke-exposed mice remained unchanged after smoking cessation. Although the neutrophilic inflammation in the BALF of cigarette smoke-exposed animals was reduced after smoking cessation, a sustained inflammation in the lung tissue was observed. The elevated cytokine (IL-1α and TNF-α and chemokine (CCL2 and CCL3 levels in the BALF of smoke-exposed mice returned to basal levels after smoking cessation, while the increased IL-12 levels did not return to its basal level. The cigarette smoke-enhanced VEGF levels did not significantly change after smoking cessation. Moreover, IL-10 levels were reduced in the BALF of smoke-exposed mice and these levels were still significantly decreased after smoking cessation compared to the control animals. Conclusion The inflammatory changes in the airways caused by cigarette smoke exposure were only partially reversed after smoking cessation. Although smoking cessation should be the first step in reducing the progression of lung emphysema, additional

  5. Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse.

    Directory of Open Access Journals (Sweden)

    Tia DiTommaso

    2014-10-01

    Full Text Available The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP. A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1, while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1. The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.

  6. Pathogenicity study in sheep using reverse-genetics-based reassortant bluetongue viruses.

    Science.gov (United States)

    Celma, Cristina C; Bhattacharya, Bishnupriya; Eschbaumer, Michael; Wernike, Kerstin; Beer, Martin; Roy, Polly

    2014-11-07

    Bluetongue (BT) disease, caused by the non-enveloped bluetongue virus (BTV) belonging to the Reoviridae family, is an economically important disease that affects a wide range of wild and domestic ruminants. Currently, 26 different serotypes of BTV are recognized in the world, of which BTV-8 has been found to exhibit one of the most virulent manifestations of BT disease in livestock. In recent years incursions of BTV-8 in Europe have resulted in significant morbidity and mortality not only in sheep but also in cattle. The molecular and genetic basis of BTV-8 pathogenesis is not known. To understand the genetic basis of BTV-8 pathogenicity, we generated reassortant viruses by replacing the 3 most variable genes, S2, S6 and S10 of a recent isolate of BTV-8, in different combinations into the backbone of an attenuated strain of BTV-1. The growth profiles of these reassortant viruses were then analyzed in two different ovine cell lines derived from different organs, kidney and thymus. Distinct patterns for each reassortant virus in these two cell lines were observed. To determine the pathogenicity of these reassortant viruses, groups of BTV-susceptible sheep were infected with each of these viruses. The data suggested that the clinical manifestations of these two different serotypes, BTV-1 and BTV-8, were slightly distinct and BTV-1, when comprising all 3 genome segments of BTV-8, behaved differently to BTV-1. Our results also suggested that the molecular basis of BT disease is highly complex. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Exposure to polymers reverses inhibition of pulmonary surfactant by serum, meconium, or cholesterol in the captive bubble surfactometer.

    Science.gov (United States)

    López-Rodríguez, Elena; Ospina, Olga Lucía; Echaide, Mercedes; Taeusch, H William; Pérez-Gil, Jesús

    2012-10-03

    Dysfunction of pulmonary surfactant in the lungs is associated with respiratory pathologies such as acute respiratory distress syndrome or meconium aspiration syndrome. Serum, cholesterol, and meconium have been described as inhibitory agents of surfactant's interfacial activity once these substances appear in alveolar spaces during lung injury and inflammation. The deleterious action of these agents has been only partly evaluated under physiologically relevant conditions. We have optimized a protocol to assess surfactant inhibition by serum, cholesterol, or meconium in the captive bubble surfactometer. Specific measures of surface activity before and after native surfactant was exposed to inhibitors included i), film formation, ii), readsorption of material from surface-associated reservoirs, and iii), interfacial film dynamics during compression-expansion cycling. Results show that serum creates a steric barrier that impedes surfactant reaching the interface. A mechanical perturbation of this barrier allows native surfactant to compete efficiently with serum to form a highly surface-active film. Exposure of native surfactant to cholesterol or meconium, on the other hand, modifies the compressibility of surfactant films though optimal compressibility properties recover on repetitive compression-expansion cycling. Addition of polymers like dextran or hyaluronic acid to surfactant fully reverses inhibition by serum. These polymers also prevent surfactant inhibition by cholesterol or meconium, suggesting that the protective action of polymers goes beyond the mere enhancement of interfacial adsorption as described by depletion force theories. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  8. Reverse osmosis membrane composition, structure and performance modification by bisulphite, iron(III), bromide and chlorite exposure.

    Science.gov (United States)

    Ferrer, O; Gibert, O; Cortina, J L

    2016-10-15

    Reverse osmosis (RO) membrane exposure to bisulphite, chlorite, bromide and iron(III) was assessed in terms of membrane composition, structure and performance. Membrane composition was determined by Rutherford backscattering spectrometry (RBS) and membrane performance was assessed by water and chloride permeation, using a modified version of the solution-diffusion model. Iron(III) dosage in presence of bisulphite led to an autooxidation of the latter, probably generating free radicals which damaged the membrane. It comprised a significant raise in chloride passage (chloride permeation coefficient increased 5.3-5.1 fold compared to the virgin membrane under the conditions studied) rapidly. No major differences in terms of water permeability and membrane composition were observed. Nevertheless, an increase in the size of the network pores, and a raise in the fraction of aggregate pores of the polyamide (PA) layer were identified, but no amide bond cleavage was observed. These structural changes were therefore, in accordance with the transport properties observed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Elevated Human Telomerase Reverse Transcriptase Gene Expression in Blood Cells Associated with Chronic Arsenic Exposure in Inner Mongolia, China

    Science.gov (United States)

    Mo, Jinyao; Xia, Yajuan; Ning, Zhixiong; Wade, Timothy J.; Mumford, Judy L.

    2009-01-01

    Background Arsenic exposure is associated with human cancer. Telomerase-containing human telomerase reverse transcriptase (hTERT) can extend telomeres of chromosomes, delay senescence, and promote cell proliferation leading to tumorigenesis. Objective The goal of this study was to investigate the effects of As on hTERT mRNA expression in humans and in vitro. Method A total of 324 Inner Mongolia residents who have been exposed to As via drinking water participated in this study. Water and toenail samples were collected and analyzed for As. Blood samples were quantified for hTERT mRNA expression using real-time polymerase chain reaction. The hTERT mRNA levels were linked to water and nail As concentrations and skin hyperkeratosis. Human epidermal keratinocytes were treated with arsenite to assess effects on cell viability and hTERT expression in vitro. Results hTERT mRNA expression levels were significantly associated with As concentrations of water (p insults by As and may also indicate that As may function as a tumor promoter in carcinogenesis in humans. PMID:19337508

  10. Determination of appropriate exposure angles for the reverse water's view using a head phantom

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Min Su; Lee, Keun Ohk [Dept. of Radiology, Soonchunhyang University Hospital, Bucheon (Korea, Republic of); Choi, Jae Ho [Dept. of Radiological Technology, Ansan University, Ansan (Korea, Republic of); Jung, Jae Hong [Dept. of Biomedical Engineering, College of Medicine, The Catholic University, Seoul (Korea, Republic of)

    2017-06-15

    Early diagnosis for upper facial trauma is difficult by using the standard Water's view (S-Water's) in general radiograph due to overlapping of anatomical structures, the uncertainty of patient positioning, and specific patients with obese, pediatric, old, or high-risk. The purpose of this study was to analyze appropriate exposure angles through a comparison of two different protocols (S-Water's vs. reverse Water's view (R-Water's)) by using a head phantom. A head phantom and general radiograph with 75 kVp, 400 mA, 45 ms 18 mAs, and SID 100 cm. Images of R-Water's were obtained by different angles in the range of 0 degree to 50 degrees, which adjusted an angle at 1 degree interval in supine position. Survey elements were developed and three observers were evaluated with four elements including the maxillary sinus, zygomatic arch, petrous ridge, and image distortion. Statistical significant analysis were used the Krippendorff's alpha and Fleiss' kappa. The intra-class correlation (ICC) coefficient for three observers were high with maxillary, 0.957 (0.903, 0.995); zygomatic arch, 0.939 (0.866, 0.987); petrous ridge, 0.972 (0.897, 1.000); and image distortion, 0.949 (0.830, 1.000). The high-quality image (HI) and perfect agreement (PA) for acquired exposure angles were high in range of the maxillary sinus (36 degrees – 44 degrees), zygomatic arch (33 degrees – 40 degrees), petrous ridge (32 degrees – 50 degrees), and image distortion (44 degrees– 50 degrees). Consequently, an appropriate exposure angles for the R-Water's view in the supine position for patients with facial trauma are in the from 36 degrees to 40 degrees in this phantom study. The results of this study will be helpful for the rapid diagnosis of facial fractures by simple radiography.

  11. A Hypomethylated population of Brassica rapa for forward and reverse Epi-genetics

    Directory of Open Access Journals (Sweden)

    Amoah Stephen

    2012-10-01

    decreased oil content, as well as decreased erucic acid and corresponding increases in linoleic and/or palmitic acid. Each 5-AzaC-treated line represents a unique combination of hypomethylated epialleles. Conclusions The approach and populations developed are available for forward and reverse screening of epiallelic variation and subsequent functional and inheritance studies. The generation of stochastically hypomethylated populations has utility in epiallele discovery for a wide range of crop plants, and has considerable potential as an intervention strategy for crop improvement.

  12. A single-plasmid reverse genetics system for the rescue of non-segmented negative-strand RNA viruses from cloned full-length cDNA

    NARCIS (Netherlands)

    Peeters, Ben; Leeuw, de Olav

    2017-01-01

    Reverse genetics systems for non-segmented negative-strand RNA viruses rely on co-transfection of a plasmid containing the full-length viral cDNA and helper plasmids encoding essential viral replication proteins. Here, a system is presented in which virus can be rescued from a single plasmid

  13. A Drosophila model for toxicogenomics: Genetic variation in susceptibility to heavy metal exposure.

    Directory of Open Access Journals (Sweden)

    Shanshan Zhou

    2017-07-01

    Full Text Available The genetic factors that give rise to variation in susceptibility to environmental toxins remain largely unexplored. Studies on genetic variation in susceptibility to environmental toxins are challenging in human populations, due to the variety of clinical symptoms and difficulty in determining which symptoms causally result from toxic exposure; uncontrolled environments, often with exposure to multiple toxicants; and difficulty in relating phenotypic effect size to toxic dose, especially when symptoms become manifest with a substantial time lag. Drosophila melanogaster is a powerful model that enables genome-wide studies for the identification of allelic variants that contribute to variation in susceptibility to environmental toxins, since the genetic background, environmental rearing conditions and toxic exposure can be precisely controlled. Here, we used extreme QTL mapping in an outbred population derived from the D. melanogaster Genetic Reference Panel to identify alleles associated with resistance to lead and/or cadmium, two ubiquitous environmental toxins that present serious health risks. We identified single nucleotide polymorphisms (SNPs associated with variation in resistance to both heavy metals as well as SNPs associated with resistance specific to each of them. The effects of these SNPs were largely sex-specific. We applied mutational and RNAi analyses to 33 candidate genes and functionally validated 28 of them. We constructed networks of candidate genes as blueprints for orthologous networks of human genes. The latter not only provided functional contexts for known human targets of heavy metal toxicity, but also implicated novel candidate susceptibility genes. These studies validate Drosophila as a translational toxicogenomics gene discovery system.

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

    Science.gov (United States)

    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.

  15. Development of a reverse genetics system for respiratory syncytial virus long strain and an immunogenicity study of the recombinant virus.

    Science.gov (United States)

    Hu, Bing; Jiang, Jiawei; Zhan, Jianbo; Li, Guoming; Jiang, Yongzhong; Guan, Xuhua; Chen, Yuanding; Fang, Zhizheng

    2014-08-08

    Respiratory Syncytial Virus (RSV) is an important human respiratory pathogen, particularly of infants and older adults, and despite several decades of research and development, no licensed vaccine is available. Studies have confirmed that enhancement of RSV disease does not occur after inoculation with RSV live-attenuated vaccine candidates, making such vaccines preferable. In this paper, reverse genetics was used to construct two recombinant viruses, a recombinant Long strain (rLong) and rLong-∆G-EGFP; rLong-∆G-EGFP is a recombinant mutant in which G was replaced with the EGFP gene, based on the Long strain of RSV. Both rLong and rLong-∆G-EGFP were constructed successfully and recovered in Hep-2 cells, and autofluorescence was observed in rLong-∆G-EGFP-infected cells during consecutive passages. Titers of rLong and rLong-∆G-EGFP were ~100-fold lower than the parental strain. Although virulence was attenuated, high titers of neutralizing antibodies were induced in BALB/c mice after being inoculated with recombinant viruses in a three-dose schedule. Unexpectedly, the neutralizing antibody titer in rLong-∆G-EGFP-immunized recipients did not decline significantly compared with the rLong strain. Protective efficacy of recombinant viruses in lung tissue was up to 100%, and the serum neutralizing antibody levels could stabilize at 21 days with no significant fall post-challenge. Enzyme-linked immunospot (ELISPOT) assays showed that both recombinant viruses were capable of inducing CD8+ T cell immune responses, which are crucial for virus clearance, and that rLong stimulated a higher level of IFN-γ production by comparison. In terms of inducing a balanced immune response, rLong-∆G-EGFP elicited slightly higher levels of IgG2a antibodies and lower levels of IgG1/IgG2a than the rLong virus. This study suggested that immunization with rLong and rLong-∆G-EGFP were immunogenic and protected against RSV infection in the lower respiratory tract of BALB/c mice

  16. [Engineering by reverse genetics and characterization of the new reassortant influenza virus strain H5N1].

    Science.gov (United States)

    Zeberezhnyĭ, A D; Grebennikova, T V; Vorkunova, G K; Yuzhakov, A G; Kostina, L V; Norkina, S N; Aliper, T I; Nepoklonov, E A; Lvov, D K

    2014-01-01

    Reverse genetics was applied to engineering of the reassortantvaccine candidate strain against highly pathogenic avian influenza viruses (HPAIVs) of the H5 subtype. The new strain recPR8-H5N1 contains the HA gene from the Russian HPAIV A/Kurgan/05/2005 (H5N1), the NA and internal genes from A/Puerto Rico/8/34 (H1N1). The strain recPR8-H5N1 demonstrated the antigenic specificity (H5), high proliferation rate in 12 days chicken embryos, and was lethal for the embryos in 36 hours. An inactivated emulsified vaccine based on the strain recPR8-H5N1 elicited high antibody titers and protected 6-week-old chickens from lethal challenge with the HPAIV A/Kurgan/05/2005 (H5N1) on day 21 after single immunization. Infection of non-vaccinated birds with the strain recPR8-H5N1 did not cause any pathology, and the virus was not detected using PCR in blood and cloacal swabs on day 7 p.i. Specific weak seroconversion caused by infection with the strain recPR8-H5N1 was detected on day 14 p.i. As a result, a new influenza virus strain was obtained with modified properties.

  17. Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans

    DEFF Research Database (Denmark)

    Sundelin, Elias; Gormsen, Lars Christian; Jensen, Jonas Brorson

    2017-01-01

    Metformin has been used successfully to treat type 2 diabetes for decades. However, the efficacy of the drug varies considerably from patient to patient and this may in part be due to its pharmacokinetic properties. The aim of this study was to examine if common polymorphisms in SLC22A1, encoding...... the transporter protein OCT1, affect the hepatic distribution of metformin in humans. We performed noninvasive 11C-metformin positron emission tomography (PET)/computed tomography (CT) to determine hepatic exposure in 12 subjects genotyped for variants in SLC22A1. Hepatic distribution of metformin...... was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin. Our data show that genetic polymorphisms in transporter proteins cause variation in hepatic exposure to metformin, and it demonstrates...

  18. Combat exposure severity as a moderator of genetic and environmental liability to post-traumatic stress disorder.

    Science.gov (United States)

    Wolf, E J; Mitchell, K S; Koenen, K C; Miller, M W

    2014-05-01

    Twin studies of veterans and adults suggest that approximately 30-46% of the variance in post-traumatic stress disorder (PTSD) is attributable to genetic factors. The remaining variance is attributable to the non-shared environment, which, by definition, includes combat exposure. This study used a gene by measured environment twin design to determine whether the effects of genetic and environmental factors that contribute to the etiology of PTSD are dependent on the level of combat exposure. The sample was drawn from the Vietnam Era Twin Registry (VETR) and included 620 male-male twin pairs who served in the US Military in South East Asia during the Vietnam War era. Analyses were based on data from a clinical diagnostic interview of lifetime PTSD symptoms and a self-report measure of combat exposure. Biometric modeling revealed that the effects of genetic and non-shared environment factors on PTSD varied as a function of level of combat exposure such that the association between these factors and PTSD was stronger at higher levels of combat exposure. Combat exposure may act as a catalyst that augments the impact of hereditary and environmental contributions to PTSD. Individuals with the greatest exposure to combat trauma were at increased risk for PTSD as a function of both genetic and environmental factors. Additional work is needed to determine the biological and environmental mechanisms driving these associations.

  19. [Methylmercury exposure in the general population; toxicokinetics; differences by gender, nutritional and genetic factors].

    Science.gov (United States)

    González-Estecha, Montserrat; Bodas-Pinedo, Andrés; Guillén-Pérez, José Jesús; Rubio-Herrera, Miguel Ángel; Ordóñez-Iriarte, José M; Trasobares-Iglesias, Elena M; Martell-Claros, Nieves; Martínez-Álvarez, Jesús Román; Farré-Rovira, Rosaura; Herráiz-Martínez, Miguel Ángel; Martínez-Astorquiza, Txantón; Calvo-Manuel, Elpidio; Sáinz-Martín, María; Bretón-Lesmes, Irene; Prieto-Menchero, Santiago; Llorente-Ballesteros, M Teresa; Martínez-García, M José; Salas-Salvadó, Jordi; Bermejo-Barrera, Pilar; García-Donaire, José Antonio; Cuadrado-Cenzual, M Ángeles; Gallardo-Pino, Carmen; Moreno-Rojas, Rafael; Arroyo-Fernández, Manuel; Calle-Pascual, Alfonso

    2014-11-01

    Mercury is an environmental toxicant that causes numerous adverse effects on human health and natural ecosystems. The factors that determine the existance of adverse effects, as well as their severity are, among others: the chemical form of mercury (elemental, inorganic, organic), dosis, age, period of exposure, pathways of exposure and environmental, nutritional and genetic factors. In the aquatic cycle of mercury, once it has been deposited, it is transformed into methylmercury due to the action of certain sulphate-reducing bacteria, which bioaccumulates in the aquatic organisms and moves into the food chain. The methylmercury content of large, long-lived fish such as swordfish, shark, tuna or marlin, is higher. Methylmercury binds to protein in fish and is therefore not eliminated by cleaning or cooking the fish. Fetuses and small children are more vulnerable to the neurotoxic effects of methylmercury from the consumption of contaminated fish. Methylmercury is absorbed in the gastrointestinal tract and crosses the blood-brain barrier and the placenta. The intake of certain dietary components such as polyunsaturated fatty acids, selenium, fiber, thiol compounds, certain phytochemicals and other nutrients can modify methylmercury bioaccesibility and its toxicity. Apart from environmental factors, genetic factors can influence mercury toxicity and explain part of the individual vulnerability. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  20. Oxidative Stress-Related Genetic Variants May Modify Associations of Phthalate Exposures with Asthma

    Directory of Open Access Journals (Sweden)

    I-Jen Wang

    2017-02-01

    Full Text Available Background: Phthalate exposure may increase the risk of asthma. Little is known about whether oxidative-stress related genes may alter this association. First, this motivated us to investigate whether genetic polymorphisms of the oxidative-stress related genes glutathione S-transferase Mu 1 (GSTM1, glutathione S-transferase pi 1 (GSTP1, superoxide dismutase 2 (SOD2, catalase (CAT, myeloperoxidase (MPO, and EPHX1 in children are associated with phthalate urine concentrations. Second, we addressed the question whether these genes may affect the influence of phthalates on asthma. Methods: In a case-control study composed of 126 asthmatic children and 327 controls, urine phthalate metabolites (monoethyl phthalate (MEP, monobutyl phthalate (MBP, monobenzyl phthalate (MBzP, and mono(2-ethyl-5-hydroxyhexylphthalate (MEHHP were measured by UPLC-MS/MS at age 3. Genetic variants were analyzed by TaqMan assay. Information on asthma and environmental exposures was also collected. Analyses of variance and logistic regressions were performed. Results: Urine MEHHP levels were associated with asthma (adjusted OR 1.33, 95% CI (1.11–1.60. Children with the GSTP1 (rs1695 AA and SOD2 (rs5746136 TT genotypes had higher MEHHP levels as compared to GG and CC types, respectively. Since only SOD2 TT genotype was significantly associated with asthma (adjusted OR (95% CI: 2.78 (1.54–5.02, we estimated whether SOD2 variants modify the association of MEHHP levels and asthma. As MEHHP concentrations were dependent on GSTP1 and SOD2, but the assessment of interaction requires independent variables, we estimated MEHHP residuals and assessed their interaction, showing that the OR for SOD2 TT was further elevated to 3.32 (1.75–6.32 when the residuals of MEHHP were high. Conclusions: Urine phthalate metabolite concentrations are associated with oxidative-stress related genetic variants. Genetic variants of SOD2, considered to be reflect oxidative stress metabolisms, might

  1. Human Cytokine Genetic Variants Associated With HBsAg Reverse Seroconversion in Rituximab-Treated Non-Hodgkin Lymphoma Patients.

    Science.gov (United States)

    Hsiao, Liang-Tsai; Wang, Hao-Yuan; Yang, Ching-Fen; Chiou, Tzeon-Jye; Gau, Jyh-Pyng; Yu, Yuan-Bin; Liu, Hsiao-Ling; Chang, Wen-Chun; Chen, Po-Min; Tzeng, Cheng-Hwai; Chan, Yu-Jiun; Yang, Muh-Hwa; Liu, Jin-Hwang; Huang, Yi-Hsiang

    2016-03-01

    Hepatitis B virus (HBV) reactivation has been noted in HBV surface antigen (HBsAg)-seronegative patients with CD20 B-cell non-Hodgkin lymphoma (NHL) undergoing rituximab treatment. Clinically, hepatitis flares are usually associated with the reappearance of HBsAg (reverse seroconversion of HBsAg, HBV-RS). It is unclear whether human genetic factors are related to rituximab-associated HBV reactivation. Unvaccinated HBsAg-seronegative adults (n = 104) with CD20 NHL who had received rituximab-containing therapy without anti-HBV prophylaxis were enrolled. Eighty-nine candidate single nucleotide polymorphisms (SNPs) of 49 human cytokine genes were chosen and were analyzed using the iPLEX technique. Competing risk regression was used to identify the factors associated with HBV-RS. Participants had a median age of 66.1 years and 56.7% were male (n = 59). The anti-HBs and anti-HBc positivity rates were 82.4% and 94.1%, respectively, among patients for whom data were available (approximately 81%). A mean of 7.14 cycles of rituximab therapy were administered, and a total of 14 (13.4%) patients developed HBV-RS. Nine SNPs showed significant differences in frequency between patients with or without HBV-RS: CD40 rs1883832, IL4 rs2243248 and rs2243263, IL13 rs1295686, IL18 rs243908, IL20 rs1518108, and TNFSF13B rs12428930 and rs12583006. Multivariate analysis showed that ≥6 cycles of rituximab therapy, IL18 rs243908, and the IL4 haplotype rs2243248∼rs2243263 were independently associated with HBV-RS. The IL4 haplotype rs2243248∼rs2243263 was significantly associated with HBV-RS regardless of anti-HBs status. Polymorphisms in human cytokine genes impact the risk of rituximab-associated HBV-RS.

  2. Ontogenic and morphological study of gonadal formation in genetically-modified sex reversal XY(POS) mice.

    Science.gov (United States)

    Umemura, Yuria; Miyamoto, Ryosuke; Hashimoto, Rie; Kinoshita, Kyoko; Omotehara, Takuya; Nagahara, Daichi; Hirano, Tetsushi; Kubota, Naoto; Minami, Kiichi; Yanai, Shogo; Masuda, Natsumi; Yuasa, Hideto; Mantani, Youhei; Matsuo, Eiko; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2016-01-01

    Mammalian sexual fate is determined by the presence or absence of sex determining region of the Y chromosome (Sry) in the "bipotential" gonads. Recent studies have demonstrated that both male and female sexual development are induced by distinct and active genetic pathways. Breeding the Y chromosome from Mus m. domesticus poschiavinus (POS) strains into C57BL/6J (B6J) mice (B6J-XY(POS)) has been shown to induce sex reversal (75%: bilateral ovary, 25%: true hermaphrodites). However, our B6N-XY(POS) mice, which were generated by backcrossing of B6J-XY(POS) on an inbred B6N-XX, develop as males (36%: bilateral testis with fertility as well as bilateral ovary (34%), and the remainder develop as true hermaphrodites. Here, we investigated in detail the expressions of essential sex-related genes and histological features in B6N-XY(POS) mice from the fetal period to adulthood. The onsets of both Sry and SRY-box 9 (Sox9) expressions as determined spatiotemporally by whole-mount immunohistochemistry in the B6N-XY(POS) gonads occurred 2-3 tail somites later than those in B6N-XY(B6) gonads, but earlier than those in B6J-XY(POS), respectively. It is possible that such a small difference in timing of the Sry expression underlies testicular development in our B6N-XY(POS). Our study is the first to histologically show the expression and ectopic localization of a female-related gene in the XY(POS) testes and a male-related gene in the XY(POS) ovaries. The results from these and previous experiments indicate that the interplay between genome variants, epigenetics and developmental gene regulation is crucial for testis development.

  3. A systemic gene silencing method suitable for high throughput, reverse genetic analyses of gene function in fern gametophytes

    Directory of Open Access Journals (Sweden)

    Tanurdzic Milos

    2004-04-01

    Full Text Available Abstract Background Ceratopteris richardii is a useful experimental system for studying gametophyte development and sexual reproduction in plants. However, few tools for cloning mutant genes or disrupting gene function exist for this species. The feasibility of systemic gene silencing as a reverse genetics tool was examined in this study. Results Several DNA constructs targeting a Ceratopteris protoporphyrin IX magnesium chelatase (CrChlI gene that is required for chlorophyll biosynthesis were each introduced into young gametophytes by biolistic delivery. Their transient expression in individual cells resulted in a colorless cell phenotype that affected most cells of the mature gametophyte, including the meristem and gametangia. The colorless phenotype was associated with a 7-fold decrease in the abundance of the endogenous transcript. While a construct designed to promote the transient expression of a CrChlI double stranded, potentially hairpin-forming RNA was found to be the most efficient in systemically silencing the endogenous gene, a plasmid containing the CrChlI cDNA insert alone was sufficient to induce silencing. Bombarded, colorless hermaphroditic gametophytes produced colorless embryos following self-fertilization, demonstrating that the silencing signal could be transmitted through gametogenesis and fertilization. Bombardment of young gametophytes with constructs targeting the Ceratopteris filamentous temperature sensitive (CrFtsZ and uroporphyrin dehydrogenase (CrUrod genes also produced the expected mutant phenotypes. Conclusion A method that induces the systemic silencing of target genes in the Ceratopteris gametophyte is described. It provides a simple, inexpensive and rapid means to test the functions of genes involved in gametophyte development, especially those involved in cellular processes common to all plants.

  4. The Effects of Synthetic Estrogen Exposure on the Sexually Dimorphic Liver Transcriptome of the Sex-Role-Reversed Gulf Pipefish

    National Research Council Canada - National Science Library

    Rose, Emily; Flanagan, Sarah P; Jones, Adam G

    2015-01-01

    .... Here, we investigate gene expression patterns in the liver of the sex-role-reversed Gulf pipefish, because the liver is known to be sexually dimorphic and estrogen-regulated in species with conventional sex roles...

  5. Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures

    Science.gov (United States)

    Galanter, Joshua M; Gignoux, Christopher R; Oh, Sam S; Torgerson, Dara; Pino-Yanes, Maria; Thakur, Neeta; Eng, Celeste; Hu, Donglei; Huntsman, Scott; Farber, Harold J; Avila, Pedro C; Brigino-Buenaventura, Emerita; LeNoir, Michael A; Meade, Kelly; Serebrisky, Denise; Rodríguez-Cintrón, William; Kumar, Rajesh; Rodríguez-Santana, Jose R; Seibold, Max A; Borrell, Luisa N; Burchard, Esteban G; Zaitlen, Noah

    2017-01-01

    Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10-64) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation. DOI: http://dx.doi.org/10.7554/eLife.20532.001 PMID:28044981

  6. Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms.

    Science.gov (United States)

    Figueroa, Jonine D; Koutros, Stella; Colt, Joanne S; Kogevinas, Manolis; Garcia-Closas, Montserrat; Real, Francisco X; Friesen, Melissa C; Baris, Dalsu; Stewart, Patricia; Schwenn, Molly; Johnson, Alison; Karagas, Margaret R; Armenti, Karla R; Moore, Lee E; Schned, Alan; Lenz, Petra; Prokunina-Olsson, Ludmila; Banday, A Rouf; Paquin, Ashley; Ylaya, Kris; Chung, Joon-Yong; Hewitt, Stephen M; Nickerson, Michael L; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Malats, Núria; Fraumeni, Joseph F; Chanock, Stephen J; Chatterjee, Nilanjan; Rothman, Nathaniel; Silverman, Debra T

    2015-11-01

    Few studies have demonstrated gene/environment interactions in cancer research. Using data on high-risk occupations for 2258 case patients and 2410 control patients from two bladder cancer studies, we observed that three of 16 known or candidate bladder cancer susceptibility variants displayed statistically significant and consistent evidence of additive interactions; specifically, the GSTM1 deletion polymorphism (P interaction ≤ .001), rs11892031 (UGT1A, P interaction = .01), and rs798766 (TMEM129-TACC3-FGFR3, P interaction = .03). There was limited evidence for multiplicative interactions. When we examined detailed data on a prevalent occupational exposure associated with increased bladder cancer risk, straight metalworking fluids, we also observed statistically significant additive interaction for rs798766 (TMEM129-TACC3-FGFR3, P interaction = .02), with the interaction more apparent in patients with tumors positive for FGFR3 expression. All statistical tests were two-sided. The interaction we observed for rs798766 (TMEM129-TACC3-FGFR3) with specific exposure to straight metalworking fluids illustrates the value of integrating germline genetic variation, environmental exposures, and tumor marker data to provide insight into the mechanisms of bladder carcinogenesis. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. Genetic susceptibility to viral exposure may increase the risk of cerebral palsy.

    Science.gov (United States)

    Djukic, Michael; Gibson, Catherine S; Maclennan, Alastair H; Goldwater, Paul N; Haan, Eric A; McMichael, Gai; Priest, Kevin; Dekker, Gustaaf A; Hague, William M; Chan, Annabelle; Rudzki, Zbigniew; VAN Essen, Phillipa; Khong, T Yee; Morton, Mark R; Ranieri, Enzo; Scott, Heather; Tapp, Heather; Casey, Graeme

    2009-06-01

    Cytokine polymorphisms may alter the fetal inflammatory response, increasing susceptibility to cerebral palsy (CP). This study investigates associations between selected inflammatory mediator and cytokine gene polymorphisms (Toll-like receptor-4 (TLR-4) Asp299Gly, interleukin-6 G-174C and interleukin-4 C-589T) and CP from 443 CP infants and 883 control infants. Results were correlated with viral nucleic acids in the same samples. At all gestational ages (GA), TLR-4 was associated with a decreased risk of developing CP (homozygous/heterozygous odds ratio (OR) 0.70, 95% confidence interval (CI) 0.50-0.98) and interleukin (IL)-6 was associated with an increased risk of developing hemiplegia (OR 1.38, 95% CI 1.05-1.83). For infants born 32-36 weeks GA, there was a tenfold increase in the risk of quadriplegic CP with homozygous/heterozygous IL-6 (OR 10.42, 95% CI 1.34-80.82). Viral exposure in combination with IL-4 in preterm infants was associated with a fourfold increased risk of quadriplegia (homozygous/heterozygous OR 4.25, 95% CI 1.21-14.95). In very preterm infants, the absence of detectable viral exposure in combination with IL-4 decreased the risk of developing CP (homozygous/heterozygous OR 0.31, 95% CI 0.13-0.76). Polymorphisms in TLR-4 may be associated with a decreased risk of CP. Polymorphisms in IL-6 or IL-4 may act as susceptibility genes, in the presence of viral exposure, for the development of hemiplegic and quadriplegic CP. These associations require confirmation but they suggest a hypothesis for CP causation due to double jeopardy from neurotropic viral exposure and genetic susceptibility to infection.

  8. Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children.

    Science.gov (United States)

    De Leonibus, C; Chatelain, P; Knight, C; Clayton, P; Stevens, A

    2016-11-01

    The response to growth hormone in humans is dependent on phenotypic, genetic and environmental factors. The present study in children with growth hormone deficiency (GHD) collected worldwide characterised gene-environment interactions on growth response to recombinant human growth hormone (r-hGH). Growth responses in children are linked to latitude, and we found that a correlate of latitude, summer daylight exposure (SDE), was a key environmental factor related to growth response to r-hGH. In turn growth response was determined by an interaction between both SDE and genes known to affect growth response to r-hGH. In addition, analysis of associated networks of gene expression implicated a role for circadian clock pathways and specifically the developmental transcription factor NANOG. This work provides the first observation of gene-environment interactions in children treated with r-hGH.

  9. RNAi-based reverse genetics in the chelicerate model Tetranychus urticae: A comparative analysis of five methods for gene silencing.

    Directory of Open Access Journals (Sweden)

    Takeshi Suzuki

    Full Text Available RNA interference (RNAi can be used for the protection against agricultural pests through the silencing of genes required for pest fitness. To assess the potential of RNAi approaches in the two-spotted spider mite, Tetranychus urticae, we compared 5 methods for the delivery of double-stranded RNA (dsRNA. These methods include mite feeding on either (i leaves floating on a dsRNA solution, (ii dsRNA-expressing plants, (iii artificial diet supplemented with dsRNA, or (iv dsRNA-coated leaves, and (v mite soaking in a dsRNA solution. In all cases, the gene targeted for method validation was the Vacuolar-type H+-ATPase (TuVATPase, encoding a constitutively expressed ATP-driven proton pump located in the membrane. Down-regulation of TuVATPase increased mortality and/or reduced fecundity in all methods, but with variable efficiency. The most efficient methods for dsRNA delivery were direct soaking of mites in the dsRNA solution and mite feeding on dsRNA-coated leaves that mimics dsRNA application as a sprayable pesticide. Both resulted in a dark-body phenotype not observed in mites treated with a control dsRNA. Although with lower efficiency, dsRNA designed for TuVATPase silencing and expressed in transgenic Arabidopsis plants impacted the fitness of mites feeding on these plants. RNAi may thus be a valuable strategy to control spider mite populations, either as a sprayable pesticide or through transgenic crops. This comparative methodological study focusing on the induction of RNAi-based gene silencing in T. urticae paves the way for reverse genetics approaches in this model chelicerate system and prepares large-scale systematic RNAi screens as a first step towards the development of specific RNA-based pesticides. Such alternative molecules may help control spider mites that cause significant damages to crops and ornamental plant species, as well as other chelicerates detrimental to agriculture and health.

  10. RNAi-based reverse genetics in the chelicerate model Tetranychus urticae: A comparative analysis of five methods for gene silencing.

    Science.gov (United States)

    Suzuki, Takeshi; Nunes, Maria Andreia; España, María Urizarna; Namin, Hooman Hosseinzadeh; Jin, Pengyu; Bensoussan, Nicolas; Zhurov, Vladimir; Rahman, Tawhid; De Clercq, Rebecca; Hilson, Pierre; Grbic, Vojislava; Grbic, Miodrag

    2017-01-01

    RNA interference (RNAi) can be used for the protection against agricultural pests through the silencing of genes required for pest fitness. To assess the potential of RNAi approaches in the two-spotted spider mite, Tetranychus urticae, we compared 5 methods for the delivery of double-stranded RNA (dsRNA). These methods include mite feeding on either (i) leaves floating on a dsRNA solution, (ii) dsRNA-expressing plants, (iii) artificial diet supplemented with dsRNA, or (iv) dsRNA-coated leaves, and (v) mite soaking in a dsRNA solution. In all cases, the gene targeted for method validation was the Vacuolar-type H+-ATPase (TuVATPase), encoding a constitutively expressed ATP-driven proton pump located in the membrane. Down-regulation of TuVATPase increased mortality and/or reduced fecundity in all methods, but with variable efficiency. The most efficient methods for dsRNA delivery were direct soaking of mites in the dsRNA solution and mite feeding on dsRNA-coated leaves that mimics dsRNA application as a sprayable pesticide. Both resulted in a dark-body phenotype not observed in mites treated with a control dsRNA. Although with lower efficiency, dsRNA designed for TuVATPase silencing and expressed in transgenic Arabidopsis plants impacted the fitness of mites feeding on these plants. RNAi may thus be a valuable strategy to control spider mite populations, either as a sprayable pesticide or through transgenic crops. This comparative methodological study focusing on the induction of RNAi-based gene silencing in T. urticae paves the way for reverse genetics approaches in this model chelicerate system and prepares large-scale systematic RNAi screens as a first step towards the development of specific RNA-based pesticides. Such alternative molecules may help control spider mites that cause significant damages to crops and ornamental plant species, as well as other chelicerates detrimental to agriculture and health.

  11. RNAi-based reverse genetics in the chelicerate model Tetranychus urticae: A comparative analysis of five methods for gene silencing

    Science.gov (United States)

    Namin, Hooman Hosseinzadeh; Jin, Pengyu; Bensoussan, Nicolas; Zhurov, Vladimir; Rahman, Tawhid; De Clercq, Rebecca; Hilson, Pierre; Grbic, Miodrag

    2017-01-01

    RNA interference (RNAi) can be used for the protection against agricultural pests through the silencing of genes required for pest fitness. To assess the potential of RNAi approaches in the two-spotted spider mite, Tetranychus urticae, we compared 5 methods for the delivery of double-stranded RNA (dsRNA). These methods include mite feeding on either (i) leaves floating on a dsRNA solution, (ii) dsRNA-expressing plants, (iii) artificial diet supplemented with dsRNA, or (iv) dsRNA-coated leaves, and (v) mite soaking in a dsRNA solution. In all cases, the gene targeted for method validation was the Vacuolar-type H+-ATPase (TuVATPase), encoding a constitutively expressed ATP-driven proton pump located in the membrane. Down-regulation of TuVATPase increased mortality and/or reduced fecundity in all methods, but with variable efficiency. The most efficient methods for dsRNA delivery were direct soaking of mites in the dsRNA solution and mite feeding on dsRNA-coated leaves that mimics dsRNA application as a sprayable pesticide. Both resulted in a dark-body phenotype not observed in mites treated with a control dsRNA. Although with lower efficiency, dsRNA designed for TuVATPase silencing and expressed in transgenic Arabidopsis plants impacted the fitness of mites feeding on these plants. RNAi may thus be a valuable strategy to control spider mite populations, either as a sprayable pesticide or through transgenic crops. This comparative methodological study focusing on the induction of RNAi-based gene silencing in T. urticae paves the way for reverse genetics approaches in this model chelicerate system and prepares large-scale systematic RNAi screens as a first step towards the development of specific RNA-based pesticides. Such alternative molecules may help control spider mites that cause significant damages to crops and ornamental plant species, as well as other chelicerates detrimental to agriculture and health. PMID:28704448

  12. Effects of perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on spatial and visual reversal learning in rats.

    Science.gov (United States)

    Widholm, John J; Seo, Byung Woun; Strupp, Barbara J; Seegal, Richard F; Schantz, Susan L

    2003-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that has been shown to alter spatial and visual learning following developmental exposure. The current study examined the effects of gestational and lactational exposure to TCDD on spatial and visual discrimination/reversal learning (spatial and visual RL) in rats using two-lever operant testing chambers. Pregnant Sprague-Dawley rats (10 per dose) received either 0 or 0.1 microg/kg TCDD per orem in corn oil from gestational day (GD) 10 to GD 16. One male and one female from each litter were tested beginning at 100 days of age. For spatial RL, animals were reinforced for pressing the lever associated with the correct spatial location (either left or right). For visual RL, the animals were reinforced for pressing the lever associated with the correct visual stimulus (either the illuminated or nonilluminated cuelight). After reaching 85% correct for two consecutive days, the opposite spatial location or visual cue was reinforced. Five reversals were conducted for spatial RL, and two reversals for visual RL. For spatial RL, there were no differences between the TCDD-exposed and control rats in total number of errors committed. However, an in-depth analysis of errors in four different phases of the learning process revealed that TCDD-exposed rats made more errors early in learning when they were just beginning to learn the new reinforcement contingencies. The importance of this increase in errors during the initial stage of learning is unclear, given that there was no increase in overall errors to criterion. For visual RL, there was a reduction in errors on original learning (OL) for TCDD-exposed males, while TCDD-exposed females exhibited a reduction in errors on the second reversal. Subsequent response pattern analyses revealed that the facilitation in performance was due to a more rapid transition through the early phase of learning. Why males were improved on OL and females were not

  13. Impact of exposure to mosquito transmission-blocking antibodies on Plasmodium falciparum population genetic structure.

    Science.gov (United States)

    Sandeu, Maurice M; Abate, Luc; Tchioffo, Majoline T; Bayibéki, Albert N; Awono-Ambéné, Parfait H; Nsango, Sandrine E; Chesnais, Cédric B; Dinglasan, Rhoel R; de Meeûs, Thierry; Morlais, Isabelle

    2016-11-01

    Progress in malaria control has led to a significant reduction of the malaria burden. Interventions that interrupt transmission are now needed to achieve the elimination goal. Transmission-blocking vaccines (TBV) that aim to prevent mosquito infections represent promising tools and several vaccine candidates targeting different stages of the parasite's lifecycle are currently under development. A mosquito-midgut antigen, the anopheline alanyl aminopeptidase (AnAPN1) is one of the lead TBV candidates; antibodies against AnAPN1 prevent ookinete invasion. In this study, we explored the transmission dynamics of Plasmodium falciparum in mosquitoes fed with anti-AnAPN1 monoclonal antibodies (mAbs) vs. untreated controls, and investigated whether the parasite genetic content affects or is affected by antibody treatment. Exposure to anti-AnAPN1 mAbs was efficient at blocking parasite transmission and the effect was dose-dependent. Genetic analysis revealed a significant sib-mating within P. falciparum infra-populations infecting one host, as measured by the strong correlation between Wright's FIS and multiplicity of infection. Treatments also resulted in significant decrease in FIS as a by-product of drop in infra-population genetic diversity and concomitant increase of apparent panmictic genotyping proportions. Genetic differentiation analyses indicated that mosquitoes fed on a same donor randomly sampled blood-circulating gametocytes. We did not detect trace of selection, as the genetic differentiation between different donors did not decrease with increasing mAb concentration and was not significant between treatments for each gametocyte donor. Thus, there is apparently no specific genotype associated with the loss of diversity under mAb treatment. Finally, the anti-AnAPN1 mAbs were effective at reducing mosquito infection and a vaccine aiming at eliciting anti-AnAPN1 mAbs has a strong potential to decrease the burden of malaria in transmission-blocking interventions

  14. Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans.

    Science.gov (United States)

    Sundelin, Eio; Gormsen, L C; Jensen, J B; Vendelbo, M H; Jakobsen, S; Munk, O L; Christensen, Mmh; Brøsen, K; Frøkiaer, J; Jessen, N

    2017-11-01

    Metformin has been used successfully to treat type 2 diabetes for decades. However, the efficacy of the drug varies considerably from patient to patient and this may in part be due to its pharmacokinetic properties. The aim of this study was to examine if common polymorphisms in SLC22A1, encoding the transporter protein OCT1, affect the hepatic distribution of metformin in humans. We performed noninvasive 11 C-metformin positron emission tomography (PET)/computed tomography (CT) to determine hepatic exposure in 12 subjects genotyped for variants in SLC22A1. Hepatic distribution of metformin was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin. Our data show that genetic polymorphisms in transporter proteins cause variation in hepatic exposure to metformin, and it demonstrates the application of novel imaging techniques to investigate pharmacogenetic properties in humans. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  15. Consequences for Protaphorura armata (Collembola: Onychiuridae) following exposure to genetically modified Bacillus thuringiensis (Bt) maize and non-Bt maize

    DEFF Research Database (Denmark)

    Heckmann, L.-H.; Griffiths, B. S.; Caul, S.

    2006-01-01

    Studies on the effect of genetically modified Bacillus thuringiensis (Bt) crops on true soil dwelling non-target arthropods are scarce. The objective of this study was to assess the influence of a 4-week exposure to two Bt maize varieties (Cry1Ab) Cascade and MEB307 on the collembolan Protaphorura...

  16. The reverse cholesterol transport pathway improves understanding of genetic networks for fat deposition and muscle growth in beef cattle

    Science.gov (United States)

    In the present study, thirteen genes involved in the reverse cholesterol transport (RCT) pathway were investigated for their associations with three fat depositions, eight fatty acid compositions and two growth-related phenotypes in a Wagyu x Limousin reference population, including 6 F1 bulls, 113 ...

  17. The effect of chemical warfare on respiratory symptoms, pulmonary function tests and their reversibility 23-25 years after exposure.

    Science.gov (United States)

    Boskabady, Mrteza; Boskabady, Mohammad Hossein; Zabihi, Narges Amel; Boskabady, Marzie

    2015-01-01

    Pulmonary complications due to mustard gas exposure range from no effect to severe bronchial stenosis. Pulmonary function tests (PFTs) and respiratory symptoms in chemical war victims were studied 23-25 years after exposure to sulfur mustard (SM). Respiratory symptoms were evaluated in a sample of 142 chemical war victims and 120 control subjects with similar age from the general population using a questionnaire including questions on respiratory symptoms in the past year. PFT values were also measured in chemical war victims before and 15 min after the inhalation of 200 µg salbutamol and baseline PFT in controls. All chemical war victims (100%) reported respiratory symptoms. Wheezing (66.19%), cough (64.78%), and chest tightness (54.4%) were the most common symptoms and only 15.5% of chemical war victims reported sputum (p war victims had wheeze in chest examination, which were significantly higher than control group (p war victims than that in control subjects (p war victims, 23-25 years after exposure to chemical warfare have higher frequencies and severity of respiratory symptoms. PFT values were also significantly reduced among chemical war victims, which showed reversibility due to the inhalation of 200 µg salbutamol. © The Author(s) 2012.

  18. A strategy for the identification of new abiotic stress determinants in Arabidopsis using web-based data mining and reverse genetics.

    Science.gov (United States)

    Azevedo, Herlânder; Silva-Correia, Joana; Oliveira, Juliana; Laranjeira, Sara; Barbeta, Cátia; Amorim-Silva, Vitor; Botella, Miguel A; Lino-Neto, Teresa; Tavares, Rui M

    2011-12-01

    Since the sequencing of the Arabidopsis thaliana genome in 2000, plant researchers have faced the complex challenge of assigning function to thousands of genes. Functional discovery by in silico prediction or homology search resolved a significant number of genes, but only a minor part has been experimentally validated. Arabidopsis entry into the post-genomic era signified a massive increase in high-throughput approaches to functional discovery, which have since become available through publicly-available web-based resources. The present work focuses on an easy and straightforward strategy that couples data-mining to reverse genetics principles, to allow for the identification of new abiotic stress determinant genes. The strategy explores systematic microarray-based transcriptomics experiments, involving Arabidopsis abiotic stress responses. An overview of the most significant resources and databases for functional discovery in Arabidopsis is presented. The successful application of the outlined strategy is illustrated by the identification of a new abiotic stress determinant gene, HRR, which displays a heat-stress-related phenotype after a loss-of-function reverse genetics approach.

  19. Detection of genetically modified crops using multiplex asymmetric polymerase chain reaction and asymmetric hyperbranched rolling circle amplification coupled with reverse dot blot.

    Science.gov (United States)

    Wang, Xiumin; Teng, Da; Guan, Qingfeng; Tian, Fang; Wang, Jianhua

    2015-04-15

    To meet the ever-increasing demand for detection of genetically modified crops (GMCs), low-cost, high-throughput and high-accuracy detection assays are needed. The new multiplex asymmetric polymerase chain reaction and asymmetric hyper-branched rolling circle amplification coupled with reverse dot blot (RDB) systems were developed to detect GMCs. Thirteen oligonucleotide probes were designed to identify endogenous targets (Lec1, Hmg and Sad1), event-specific targets (RRS-5C, RRS-3C, Bt176-3C and MON810-3C), screening targets (35S promoter and NOS terminator), and control targets (18S and PLX). Optimised conditions were as follows: tailed hybridization probes (1-2 pmol/l) were immobilized on a membrane by baking for 2h, and a 10:1 ratio of forward to reverse primers was used. The detection limits were 0.1 μg/l of 2% RRS and 0.5 ng/l of DNA from genetically modified (GM) soybean. These results indicate that the RDB assay could be used to detect multiplex target genes of GMCs rapidly and inexpensively. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Activation and Reversal of Lipotoxicity in PC12 and Rat Cortical Cells Following Exposure to Palmitic Acid

    Science.gov (United States)

    Almaguel, Frankis G.; Liu, Jo-Wen; Pacheco, Fabio J.; Casiano, Carlos A.; De Leon, Marino

    2009-01-01

    Lipotoxicity involves a series of pathological cellular responses after exposure to elevated levels of fatty acids. This process may be detrimental to normal cellular homeostasis and cell viability. The present study shows that nerve growth factor-differentiated PC12 cells (NGFDPC12) and rat cortical cells (RCC) exposed to high levels of palmitic acid (PA) exhibit significant lipotoxicity and death linked to an “augmented state of cellular oxidative stress” (ASCOS). The ASCOS response includes generation of reactive oxygen species (ROS), alterations in the mitochondrial transmembrane potential, and increase in the mRNA levels of key cell death/survival regulatory genes. The observed cell death was apoptotic based on nuclear morphology, caspase-3 activation, and cleavage of lamin B and PARP. Quantitative real-time PCR measurements showed that cells undergoing lipotoxicity exhibited an increase in the expression of the mRNAs encoding the cell death-associated proteins BNIP3 and FAS receptor. Cotreatment of NGFDPC12 and RCC cells undergoing lipotoxicity with docosahexaenoic acid (DHA) and bovine serum albumin (BSA) significantly reduced cell death within the first 2 hr following the initial exposure to PA. The data suggest that lipotoxicity in NGFDPC12 and cortical neurons triggers a strong cell death apoptotic response. Results with NGFDPC12 cells suggest a linkage between induction of ASCOS and the apoptotic process and exhibit a temporal window that is sensitive to DHA and BSA interventions. PMID:18951473

  1. Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan

    Directory of Open Access Journals (Sweden)

    Ling-I Hsu

    2015-01-01

    Full Text Available Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1, reactive oxygen species (ROS related metabolic genes (NQO1, EPHX1, and HO-1, and DNA repair genes (XRCC1, XPD, hOGG1, and ATM together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR and 95% confidence interval (CI using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01–8.83; OR = 2.04, 95% CI = 0.99–4.27; OR = 1.74, 95% CI = 1.00–3.02, resp.. However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated.

  2. Effects of Lead Exposure and Genetic Polymorphisms on ALAD and GPx Activities in Brazilian Battery Workers.

    Science.gov (United States)

    da Cunha Martins, Airton; Mazzaron Barcelos, Gustavo Rafael; Jacob Ferreira, Anna Laura Bechara; de Souza, Marilesia Ferreira; de Syllos Cólus, Ilce Mara; Antunes, Lusânia Maria Greggi; Bastos Paoliello, Monica Maria; Adeyemi, Joseph A; Barbosa, Fernando

    2015-01-01

    Lead (Pb) is a toxic metal that is widely used by metallurgical industries such as car battery recycling. Exposure to the metal may modify the redox status of the cells and consequently result in changes in activities of important enzymes such as delta-aminolevulinic acid dehydratase (ALAD) and glutathione peroxidase (GPx). Similarly, genetic polymorphisms may modulate the activities of enzymes related to detoxification processes of the metal and may modify Pb body burden. Therefore, the aims of the present study were (i) to evaluate the correlation between blood lead levels (BLL) and activities of the enzymes ALAD and GPx, and (ii) to determine whether activities of these enzymes may be influenced by polymorphisms in ALAD and GPx genes in Brazilian automotive battery workers chronically exposed to Pb, as well as the effects of these polymorphisms on BLL. Our study included 257 participants; BLL were determined by inductively couple plasma-mass spectrometry (ICP-MS), and the activities of the enzymes ALAD and GPx were quantified spectrophotometrically; and genotyping of ALAD (rs1800435) and GPx-1 (rs1800668) polymorphisms was performed by TaqMan assays (real-time polymerase chain reaction, RT-PCR). Significant negative correlations were found between BLL and ALAD activity. Subjects who carried at least one polymorphic allele for ALAD gene displayed markedly lower ALAD activities, while no significant effect was observed regarding GPx-1 polymorphism and activity of the same enzyme. Further, ALAD and GPx-1 polymorphisms exerted no marked influence on BLL. Taken together, our results showed that BLL affected ALAD but not GPx activities, and these were not modulated by polymorphisms in ALAD and GPx gene. Further, the rs1800435 SNP showed a tendency to modulate ALAD activity, while the rs1800668 SNP did not modulate GPx activity in Brazilian automotive battery workers exposed to Pb.

  3. IMPACT OF GENETIC POLYMORPHISMS AND GENE–ENVIRONMENT INTERACTIONS ASSESING HEALTH EFFECTS OF ENVIRONMENTAL AND OCCUPATIONAL EXPOSURE TO LEAD

    Directory of Open Access Journals (Sweden)

    Natalia Pawlas

    2010-12-01

    Full Text Available Health effects of exposure to xenobiotics, e.g. lead, differ between individuals. They are mainly influenced by xenobiotics’ concentration, however genetic polymorphisms may play a role in the interindividual variation. There is a number of reports indicating the influence of polymorphisms in the genes of δ-aminolevulinic acid dehydratase (ALAD, the vitamin D receptor (VDR, endothelial nitric oxide synthase (eNOS on blood lead concentration in lead-exposed workers and environmentally exposed children.

  4. The Arabidopsis Plant Intracellular Ras-group LRR (PIRL Family and the Value of Reverse Genetic Analysis for Identifying Genes that Function in Gametophyte Development

    Directory of Open Access Journals (Sweden)

    Nancy R. Forsthoefel

    2013-08-01

    Full Text Available Arabidopsis thaliana has proven a powerful system for developmental genetics, but identification of gametophytic genes with developmental mutants can be complicated by factors such as gametophyte-lethality, functional redundancy, or poor penetrance. These issues are exemplified by the Plant Intracellular Ras-group LRR (PIRL genes, a family of nine genes encoding a class of leucine-rich repeat proteins structurally related to animal and fungal LRR proteins involved in developmental signaling. Previous analysis of T-DNA insertion mutants showed that two of these genes, PIRL1 and PIRL9, have an essential function in pollen formation but are functionally redundant. Here, we present evidence implicating three more PIRLs in gametophyte development. Scanning electron microscopy revealed that disruption of either PIRL2 or PIRL3 results in a low frequency of pollen morphological abnormalities. In addition, molecular analysis of putative pirl6 insertion mutants indicated that knockout alleles of this gene are not represented in current Arabidopsis mutant populations, suggesting gametophyte lethality may hinder mutant recovery. Consistent with this, available microarray and RNA-seq data have documented strongest PIRL6 expression in developing pollen. Taken together, these results now implicate five PIRLs in gametophyte development. Systematic reverse genetic analysis of this novel LRR family has therefore identified gametophytically active genes that otherwise would likely be missed by forward genetic screens.

  5. Exposure and genetics increase risk of beryllium sensitisation and chronic beryllium disease in the nuclear weapons industry.

    Science.gov (United States)

    Van Dyke, Michael V; Martyny, John W; Mroz, Margaret M; Silveira, Lori J; Strand, Matt; Cragle, Donna L; Tankersley, William G; Wells, Susan M; Newman, Lee S; Maier, Lisa A

    2011-11-01

    Beryllium sensitisation (BeS) and chronic beryllium disease (CBD) are caused by exposure to beryllium with susceptibility affected by at least one well-studied genetic host factor, a glutamic acid residue at position 69 (E69) of the HLA-DPβ chain (DPβE69). However, the nature of the relationship between exposure and carriage of the DPβE69 genotype has not been well studied. The goal of this study was to determine the relationship between DPβE69 and exposure in BeS and CBD. Current and former workers (n=181) from a US nuclear weapons production facility, the Y-12 National Security Complex (Oak Ridge, Tennessee, USA), were enrolled in a case-control study including 35 individuals with BeS and 19 with CBD. HLA-DPB1 genotypes were determined by PCR-SSP. Beryllium exposures were assessed through worker interviews and industrial hygiene assessment of work tasks. After removing the confounding effect of potential beryllium exposure at another facility, multivariate models showed a sixfold (OR 6.06, 95% CI 1.96 to 18.7) increased odds for BeS and CBD combined among DPβE69 carriers and a fourfold (OR 3.98, 95% CI 1.43 to 11.0) increased odds for those exposed over an assigned lifetime-weighted average exposure of 0.1 μg/m(3). Those with both risk factors had higher increased odds (OR 24.1, 95% CI 4.77 to 122). DPβE69 carriage and high exposure to beryllium appear to contribute individually to the development of BeS and CBD. Among workers at a beryllium-using facility, the magnitude of risk associated with either elevated beryllium exposure or carriage of DPβE69 alone appears to be similar.

  6. Exposure and genetics increase risk of beryllium sensitisation and chronic beryllium disease in the nuclear weapons industry

    Energy Technology Data Exchange (ETDEWEB)

    Van Dyke, M. V. [National Jewish Health, Denver, CO (United States). Hollis Lab.; Colorado State Univ., Fort Collins, CO (United States); Martyny, John W. [National Jewish Health, Denver, CO (United States). Hollis Lab.; Colorado State Univ., Fort Collins, CO (United States); Univ. of Colorado Denver School of Medicine and Colorado School of Public Health, Denver, CO (United States); Mroz, M. M. [National Jewish Health, Denver, CO (United States). Hollis Lab.; Silveira, L. J. [National Jewish Health, Denver, CO (United States). Hollis Lab.; Strand, M. [National Jewish Health, Denver, CO (United States). Hollis Lab.; Cragle, D. L. [Oak Ridge Associated Univ., Oak Ridge, TN (United States); Tankersley, W. G. [Oak Ridge Associated Univ., Oak Ridge, TN (United States); Wells, S. M. [Oak Ridge Associated Univ., Oak Ridge, TN (United States); Newman, L. S. [Univ. of Colorado Denver School of Medicine and Colorado School of Public Health, Denver, CO (United States); Maier, L. A. [National Jewish Health, Denver, CO (United States). Hollis Lab.; Univ. of Colorado Denver School of Medicine and Colorado School of Public Health, Denver, CO (United States)

    2011-04-02

    Beryllium sensitisation (BeS) and chronic beryllium disease (CBD) are caused by exposure to beryllium with susceptibility affected by at least one well-studied genetic host factor, a glutamic acid residue at position 69 (E69) of the HLA-DPb chain (DPbE69). However, the nature of the relationship between exposure and carriage of the DPbE69 genotype has not been well studied. The goal of this study was to determine the relationship between DP{beta}E69 and exposure in BeS and CBD. Current and former workers (n=181) from a US nuclear weapons production facility, the Y-12 National Security Complex (Oak Ridge, Tennessee, USA), were enrolled in a case-control study including 35 individuals with BeS and 19 with CBD. HLA-DPB1 genotypes were determined by PCR-SSP. Beryllium exposures were assessed through worker interviews and industrial hygiene assessment of work tasks. After removing the confounding effect of potential beryllium exposure at another facility, multivariate models showed a sixfold (OR 6.06, 95% CI 1.96 to 18.7) increased odds for BeS and CBD combined among DP{beta}E69 carriers and a fourfold (OR 3.98, 95% CI 1.43 to 11.0) increased odds for those exposed over an assigned lifetime-weighted average exposure of 0.1 {micro}g/m{sup 3}. Those with both risk factors had higher increased odds (OR 24.1, 95% CI 4.77 to 122). DP{beta}E69 carriage and high exposure to beryllium appear to contribute individually to the development of BeS and CBD. Among workers at a beryllium-using facility, the magnitude of risk associated with either elevated beryllium exposure or carriage of DP{beta}E69 alone appears to be similar.

  7. An extensive cocktail approach for rapid risk assessment of in vitro CYP450 direct reversible inhibition by xenobiotic exposure.

    Science.gov (United States)

    Spaggiari, Dany; Daali, Youssef; Rudaz, Serge

    2016-07-01

    Acute exposure to environmental factors strongly affects the metabolic activity of cytochrome P450 (P450). As a consequence, the risk of interaction could be increased, modifying the clinical outcomes of a medication. Because toxic agents cannot be administered to humans for ethical reasons, in vitro approaches are therefore essential to evaluate their impact on P450 activities. In this work, an extensive cocktail mixture was developed and validated for in vitro P450 inhibition studies using human liver microsomes (HLM). The cocktail comprised eleven P450-specific probe substrates to simultaneously assess the activities of the following isoforms: 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2J2 and subfamily 3A. The high selectivity and sensitivity of the developed UHPLC-MS/MS method were critical for the success of this methodology, whose main advantages are: (i) the use of eleven probe substrates with minimized interactions, (ii) a low HLM concentration, (iii) fast incubation (5min) and (iv) the use of metabolic ratios as microsomal P450 activities markers. This cocktail approach was successfully validated by comparing the obtained IC50 values for model inhibitors with those generated with the conventional single probe methods. Accordingly, reliable inhibition values could be generated 10-fold faster using a 10-fold smaller amount of HLM compared to individual assays. This approach was applied to assess the P450 inhibition potential of widespread insecticides, namely, chlorpyrifos, fenitrothion, methylparathion and profenofos. In all cases, P450 2B6 was the most affected with IC50 values in the nanomolar range. For the first time, mixtures of these four insecticides incubated at low concentrations showed a cumulative inhibitory in vitro effect on P450 2B6. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model

    Science.gov (United States)

    Zhang, Yongfang; Kurup, Pradeep; Xu, Jian; Carty, Nikisha; Fernandez, Stephanie M.; Nygaard, Haakon B.; Pittenger, Christopher; Greengard, Paul; Strittmatter, Stephen M.; Nairn, Angus C.; Lombroso, Paul J.

    2010-01-01

    Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disorder. Early in the pathophysiology of AD, synaptic function is disrupted by soluble Aβ oligomers, possibly through Aβ-mediated internalization of NMDA receptors. Striatal-enriched phosphatase (STEP) is a tyrosine phosphatase that regulates the internalization of NMDA receptors. Recent work shows that STEP is elevated in the prefrontal cortex of human AD patients and in animal models of AD. Here, we use genetic manipulations to reduce STEP activity in a triple transgenic AD mouse model and show that a decrease in STEP levels reverses cognitive and cellular deficits observed in these mice. Our results suggest that STEP inhibitors may prove therapeutic for this devastating disorder. PMID:20956308

  9. 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

    Science.gov (United States)

    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

  10. Development and characterization of a reverse genetic system for studying dengue virus serotype 3 strain variation and neutralization.

    Directory of Open Access Journals (Sweden)

    William B Messer

    Full Text Available Dengue viruses (DENV are enveloped single-stranded positive-sense RNA viruses transmitted by Aedes spp. mosquitoes. There are four genetically distinct serotypes designated DENV-1 through DENV-4, each further subdivided into distinct genotypes. The dengue scientific community has long contended that infection with one serotype confers lifelong protection against subsequent infection with the same serotype, irrespective of virus genotype. However this hypothesis is under increased scrutiny and the role of DENV genotypic variation in protection from repeated infection is less certain. As dengue vaccine trials move increasingly into field-testing, there is an urgent need to develop tools to better define the role of genotypic variation in DENV infection and immunity. To better understand genotypic variation in DENV-3 neutralization and protection, we designed and constructed a panel of isogenic, recombinant DENV-3 infectious clones, each expressing an envelope glycoprotein from a different DENV-3 genotype; Philippines 1982 (genotype I, Thailand 1995 (genotype II, Sri Lanka 1989 and Cuba 2002 (genotype III and Puerto Rico 1977 (genotype IV. We used the panel to explore how natural envelope variation influences DENV-polyclonal serum interactions. When the recombinant viruses were tested in neutralization assays using immune sera from primary DENV infections, neutralization titers varied by as much as ∼19-fold, depending on the expressed envelope glycoprotein. The observed variability in neutralization titers suggests that relatively few residue changes in the E glycoprotein may have significant effects on DENV specific humoral immunity and influence antibody mediated protection or disease enhancement in the setting of both natural infection and vaccination. These genotypic differences are also likely to be important in temporal and spatial microevolution of DENV-3 in the background of heterotypic neutralization. The recombinant and synthetic tools

  11. Radiation exposure in the remote period after the Chernobyl accident caused oxidative stress and genetic effects in Scots pine populations

    Science.gov (United States)

    Volkova, Polina Yu.; Geras'Kin, Stanislav A.; Kazakova, Elizaveta A.

    2017-02-01

    Even 30 years after the Chernobyl accident, biological effects of irradiation are observed in the chronically exposed Scots pine populations. Chronic radiation exposure at dose rates above 50 mGy•yr-1 caused oxidative stress and led to the increase of antioxidants concentrations in these populations. Genetic variability was examined for 6 enzymes and 14 enzymatic loci of 6 Scots pine populations. Dose rates over 10 mGy•yr-1 caused the increased frequency of mutations and changes in genetic structure of Scots pine populations. However, the same dose rates had no effect on enzymatic activities. The results indicate that even relatively low dose rates of radiation can be considered as an ecological factor which should be taken into account for ecological management and radiation protection of biota species.

  12. Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study.

    Directory of Open Access Journals (Sweden)

    Ning Ding

    Full Text Available Cumulative exposure to lead is associated with cardiovascular outcomes. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD, hemochromatosis (HFE, heme oxygenase-1 (HMOX1, vitamin D receptor (VDR, glutathione S-transferase (GST supergene family (GSTP1, GSTT1, GSTM1, apolipoprotein E (APOE,angiotensin II receptor-1 (AGTR1 and angiotensinogen (AGT genes, are believed to alter toxicokinetics and/or toxicodynamics of lead.We assessed possible effect modification by genetic polymorphisms in ALAD, HFE, HMOX1, VDR, GSTP1, GSTT1, GSTM1, APOE, AGTR1 and AGT individually and as the genetic risk score (GRS on the association between cumulative lead exposure and incident coronary heart disease (CHD events.We used K-shell-X-ray fluorescence to measure bone lead levels. GRS was calculated on the basis of 22 lead-related loci. We constructed Cox proportional hazard models to compute adjusted hazard ratios (HRs and 95% confidence intervals (CIs for incident CHD. We applied inverse probability weighting to account for potential selection bias due to recruitment into the bone lead sub-study.Significant effect modification was found by VDR, HMOX1, GSTP1, APOE, and AGT genetic polymorphisms when evaluated individually. Further, the bone lead-CHD associations became larger as GRS increases. After adjusting for potential confounders, a HR of CHD was 2.27 (95%CI: 1.50-3.42 with 2-fold increase in patella lead levels, among participants in the top tertile of GRS. We also detected an increasing trend in HRs across tertiles of GRS (p-trend = 0.0063.Our findings suggest that lead-related loci as a whole may play an important role in susceptibility to lead-related CHD risk. These findings need to be validated in a separate cohort containing bone lead, lead-related genetic loci and incident CHD data.

  13. Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1

    Directory of Open Access Journals (Sweden)

    Sordillo Joanne E

    2011-12-01

    Full Text Available Abstract Background Polymorphisms in the endotoxin-mediated TLR4 pathway genes have been associated with asthma and atopy. We aimed to examine how genetic polymorphisms in innate immunity pathways interact with endotoxin to influence asthma risk in children. Methods In a previous analysis of 372 children from the Boston Home Allergens and the Connecticut Childhood Asthma studies, 7 SNPs in 6 genes (CARD15, TGFB1, LY96, ACAA1, DEFB1 and IFNG involved in innate immune pathways were associated with asthma, and 5 SNPs in 3 genes (CD80, STAT4, IRAK2 were associated with eczema. We tested these SNPs for interaction with early life endotoxin exposure (n = 291, in models for asthma and eczema by age 6. Results We found a significant interaction between endotoxin and a SNP (rs156265 in ACAA1 (p = 0.0013 for interaction. Increased endotoxin exposure (by quartile showed protective effects for asthma in individuals with at least one copy of the minor allele (OR = 0.39 per quartile increase in endotoxin, 95% CI 0.15 to 1.01. Endotoxin exposure did not reduce the risk of asthma in children homozygous for the major allele. Conclusion Our findings suggest that protective effects of endotoxin exposure on asthma may vary depending upon the presence or absence of a polymorphism in ACAA1.

  14. Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Cheng-Chia [Institute of Oral Science, Chung Shan Medical University, Taichung, Taiwan (China); School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Chang, Yu-Chao, E-mail: cyc@csmu.edu.tw [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China)

    2013-02-01

    Cigarette smoking is one of the major risk factors in the development and further progression of tumorigenesis, including oral squamous cell carcinoma (OSCC). Recent studies suggest that interplay cancer stem-like cells (CSCs) and epithelial−mesenchymal transdifferentiation (EMT) properties are responsible for the tumor maintenance and metastasis in OSCC. The aim of the present study was to investigate the effects of long-term exposure with nicotine, a major component in cigarette, on CSCs and EMT characteristics. The possible reversal regulators were further explored in nicotine-induced CSCs and EMT properties in human oral epithelial (OE) cells. Long-term exposure with nicotine was demonstrated to up-regulate ALDH1 population in normal gingival and primary OSCC OE cells dose-dependently. Moreover, long-term nicotine treatment was found to enhance the self-renewal sphere-forming ability and stemness gene signatures expression and EMT regulators in OE cells. The migration/cell invasiveness/anchorage independent growth and in vivo tumor growth by nude mice xenotransplantation assay was enhanced in long-term nicotine-stimulated OE cells. Knockdown of Snail in long-term nicotine-treated OE cells was found to reduce their CSCs properties. Therapeutic delivery of Si-Snail significantly blocked the xenograft tumorigenesis of long-term nicotine-treated OSCC cells and largely significantly improved the recipient survival. The present study demonstrated that the enrichment of CSCs coupled EMT property in oral epithelial cells induced by nicotine is critical for the development of OSCC tumorigenesis. Targeting Snail might offer a new strategy for the treatment of OSCC patients with smoking habit. -- Highlights: ► Sustained nicotine treatment induced CSCs properties of oral epithelial cells. ► Long-term nicotine treatment enhance EMT properties of oral epithelial cells. ► Long-term nicotine exposure increased tumorigenicity of oral epithelial cells. ► Si

  15. Sociability impairments in Genetic Absence Epilepsy Rats from Strasbourg: Reversal by the T-type calcium channel antagonist Z944.

    Science.gov (United States)

    Henbid, Mark T; Marks, Wendie N; Collins, Madeline J; Cain, Stuart M; Snutch, Terrance P; Howland, John G

    2017-10-01

    Childhood absence epilepsy (CAE) is associated with interictal co-morbid symptoms including abnormalities in social behaviour. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a model of CAE that exhibits physiological and behavioural alterations characteristic of the human disorder. However, it is unknown if GAERS display the social deficits often observed in CAE. Sociability in rodents is thought to be mediated by neural circuits densely populated with T-type calcium channels and GAERS contain a missense mutation in the Cav3.2 T-type calcium channel gene. Thus, the objective of this study was to examine the effects of the clinical stage pan-T-type calcium channel blocker, Z944, on sociability behaviour in male and female GAERS and non-epileptic control (NEC) animals. Female GAERS showed reduced sociability in a three-chamber sociability task whereas male GAERS, male NECs, and female NECs all showed a preference for the chamber containing a stranger rat. In drug trials, pre-treatment with 5mg/kg of Z944 normalized sociability in female GAERS. In contrast, female NECs showed impaired sociability following Z944 treatment. Dose-dependent decreases in locomotor activity were noted following Z944 treatment in both strains. Treatment with 10mg/kg of Z944 altered exploration such that only 8 of the 16 rats tested explored both sides of the testing chamber. In those that explored the chamber, significant preference for the stranger rat was observed in GAERS but not NECs. Overall, the data suggest that T-type calcium channels are critical in regulating sociability in both GAERS and NEC animals. Future research should focus on T-type calcium channels in the treatment of sociability deficits observed in disorders such as CAE. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Reverse Logistics

    OpenAIRE

    Kulikova, Olga

    2016-01-01

    This thesis was focused on the analysis of the concept of reverse logistics and actual reverse processes which are implemented in mining industry and finding solutions for the optimization of reverse logistics in this sphere. The objective of this paper was the assessment of the development of reverse logistics in mining industry on the example of potash production. The theoretical part was based on reverse logistics and mining waste related literature and provided foundations for further...

  17. A reverse genetics system for the Great Lakes strain of viral hemorrhagic septicemia virus: the NV gene is required for pathogenicity

    Science.gov (United States)

    Ammayappan, Arun; Kurath, Gael; Thompson, Tarin M.; Vakharia, Vikram N.

    2011-01-01

    Viral hemorrhagic septicemia virus (VHSV), belonging to the genus Novirhabdovirus in the family of Rhabdoviridae, causes a highly contagious disease of fresh and saltwater fish worldwide. Recently, a novel genotype of VHSV, designated IVb, has invaded the Great Lakes in North America, causing large-scale epidemics in wild fish. An efficient reverse genetics system was developed to generate a recombinant VHSV of genotype IVb from cloned cDNA. The recombinant VHSV (rVHSV) was comparable to the parental wild-type strain both in vitro and in vivo, causing high mortality in yellow perch (Perca flavescens). A modified recombinant VHSV was generated in which the NV gene was substituted with an enhanced green fluorescent protein gene (rVHSV-ΔNV-EGFP), and another recombinant was made by inserting the EGFP gene into the full-length viral clone between the P and M genes (rVHSV-EGFP). The in vitro replication kinetics of rVHSV-EGFP was similar to rVHSV; however, the rVHSV-ΔNV-EGFP grew 2 logs lower. In yellow perch challenges, wtVHSV and rVHSV induced 82-100% cumulative per cent mortality (CPM), respectively, whereas rVHSV-EGFP produced 62% CPM and rVHSV-ΔNV-EGFP caused only 15% CPM. No reversion of mutation was detected in the recovered viruses and the recombinant viruses stably maintained the foreign gene after several passages. These results indicate that the NV gene of VHSV is not essential for viral replication in vitro and in vivo, but it plays an important role in viral replication efficiency and pathogenicity. This system will facilitate studies of VHSV replication, virulence, and production of viral vectored vaccines.

  18. Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome

    Energy Technology Data Exchange (ETDEWEB)

    Snijders, Antoine M.; Langley, Sasha A.; Kim, Young-Mo; Brislawn, Colin J.; Noecker, Cecilia; Zink, Erika M.; Fansler, Sarah J.; Casey, Cameron P.; Miller, Darla R.; Huang, Yurong; Karpen, Gary H.; Celniker, Susan E.; Brown, James B.; Borenstein, Elhanan; Jansson, Janet K.; Metz, Thomas O.; Mao, Jian-Hua

    2016-11-28

    Although the gut microbiome plays important roles in host physiology, health and disease1, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut.We used the genetically diverse Collaborative Cross mouse system2 to discover that early life history impacts themicrobiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes in the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity.

  19. Genetics

    Science.gov (United States)

    ... Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... mother and medications). These include: Asthma Cancer Coronary heart disease Diabetes Hypertension Stroke MITOCHONDRIAL DNA-LINKED DISORDERS Mitochondria ...

  20. Metal allergy--a review on exposures, penetration, genetics, prevalence, and clinical implications

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Menné, Torkil

    2010-01-01

    The prevalence of metal allergy is high in the general population, and it is estimated that up to 17% of women and 3% of men are allergic to nickel and that 1-3% are allergic to cobalt and chromium. Among dermatitis patients, the prevalence of metal allergy is even higher. Metal allergy is mainly...... an environmental disorder although null mutations in the filaggrin gene complex were recently found to be associated with nickel allergy and dermatitis. Environmental metal exposures include jewelry, buttons, clothing fasteners, dental restorations, mobile phones, and leather. Although consumer exposure...... is responsible for most cases of metal allergy, the importance of occupational metal exposure remains present and should always be taken into consideration when one interprets allergic patch test reactions to metals. Traditionally, nickel, cobalt, and chromium have been the most important contact allergens...

  1. Epi-genetics modifications induced by a depleted uranium exposure in the zebra fish

    Energy Technology Data Exchange (ETDEWEB)

    Gombeau, K.; Pereira, S.; Adam-Guillermin, C. [IRSN/PRP-ENV/SERIS/LECO (France); Bourdineaud, J.P. [UMR CNRS 5805 EPOC (France); Ravanat, J.L. [INAC/Scib UMR E3 CEA-UJF (France)

    2014-07-01

    The work presented here integrates in the general framework of assessment of effects of chronic exposure to low doses of radionuclides. This evaluation necessarily involves the study of the mechanisms of toxic action at the cellular or subcellular level, in order to better understand the processes of propagation of effects to the level of the populations or ecosystems. As such, the question of the mechanisms underlying the trans-generational effects and the adaptive capacity of organisms is central, both in humans and in animal species. Epigenetic refer to changes in gene function that do not involve changes in DNA sequence, and which are transmitted in a hereditary manner by mitosis or meiosis. The latter plays a key role in these trans-generational effects. Among these changes, DNA-methylation is one of the most studied epigenetic parameters. This work is part of a PhD, included in the European COMET project (Euratom 7. Framework Program), and focuses on epigenetic modifications induced in zebra fish after a chronic exposure to radionuclides. Male and female fishes were exposed to 2 and 20 μg.L{sup -1} of depleted uranium for 24 days. After 7 and 24 days of exposure, brain, gonads, and eyes were collected in order to study changes in DNA methylation. In addition, genotoxicity was measured by the γH2AX assay. The overall changes in DNA methylation were studied by AFLP-MS and HPLC-MS, in order to know if the exposure to depleted uranium changes the global status of DNA methylation. We have found a decrease in the global level of methylation in the eyes of males after 24 days of exposure, the diminution being much more important and significant at the higher concentration of exposure (11.79 ± 3.62 against 52.43 ± 3.01 for controls) This study will be refined by analyzing the methylation of specific regions of the genome, because it represent the sequences of genes involved in major physiological functions and that may be subject to variations in the methylation

  2. Biochemical and genetic alterations in the freshwater neotropical fish Prochilodus lineatus after acute exposure to Microcystis aeruginosa

    Directory of Open Access Journals (Sweden)

    Cylene Zambrozi Garcia

    Full Text Available Microcystins are secondary metabolites produced by different species of cyanobacteria, such as Microcystis aeruginosa (MA. In this study, the biochemical and genetic effects of lyophilized MA were evaluated in the neotropical fish Prochilodus lineatus exposed to 1 or 2 mg L-1 lyophilized MA (treated group or only water (control group in static toxicity tests for 24 and 96 h. The gills and liver were used in the analysis of biotransformation enzymes and antioxidant defenses, blood and gill cells in genetic analysis and in brain and muscle it was determined the activity of acetylcholinesterase (AChE. The results showed the biotransformation pathway activation due to the increase in hepatic CYP1A and in branchial and hepatic glutathione S-transferase (GST. The antioxidant defense proved to be greatly affected by MA exposure leading to changes, both in gills and liver, in the activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, glutathione reductase (GR and in the content of tripeptide glutathione (GSH. Lipid peroxidation was not detected, but damage to DNA molecule was observed in blood cells. In conclusion, it can be state the lyophilized MA is able to promote changes in the biochemical and genetic parameters of P. lineatus.

  3. Molecular Imprint of Exposure to Naturally Occurring Genetic Variants of Human Cytomegalovirus on the T cell Repertoire

    Science.gov (United States)

    Smith, Corey; Gras, Stephanie; Brennan, Rebekah M.; Bird, Nicola L.; Valkenburg, Sophie A.; Twist, Kelly-Anne; Burrows, Jacqueline M.; Miles, John J.; Chambers, Daniel; Bell, Scott; Campbell, Scott; Kedzierska, Katherine; Burrows, Scott R.; Rossjohn, Jamie; Khanna, Rajiv

    2014-02-01

    Exposure to naturally occurring variants of herpesviruses in clinical settings can have a dramatic impact on anti-viral immunity. Here we have evaluated the molecular imprint of variant peptide-MHC complexes on the T-cell repertoire during human cytomegalovirus (CMV) infection and demonstrate that primary co-infection with genetic variants of CMV was coincident with development of strain-specific T-cell immunity followed by emergence of cross-reactive virus-specific T-cells. Cross-reactive CMV-specific T cells exhibited a highly conserved public T cell repertoire, while T cells directed towards specific genetic variants displayed oligoclonal repertoires, unique to each individual. T cell recognition foot-print and pMHC-I structural analyses revealed that the cross-reactive T cells accommodate alterations in the pMHC complex with a broader foot-print focussing on the core of the peptide epitope. These findings provide novel molecular insight into how infection with naturally occurring genetic variants of persistent human herpesviruses imprints on the evolution of the anti-viral T-cell repertoire.

  4. Sex reversal of brook trout (Salvelinus fontinalis) by 17α-methyltestosterone exposure: A serial experimental approach to determine optimal timing and delivery regimes.

    Science.gov (United States)

    Fatima, Shafaq; Adams, Mark; Wilkinson, Ryan

    2016-12-01

    Commercial culture of Brook trout (Salvelinus fontinalis) in Tasmania was partly abandoned due to sexual maturation of male fish early on during the estuarine rearing phase. Maturation adversely affects body mass, flesh quality and immunocompetency effectively. Sex reversal techniques such as the in-feed addition of a synthetic androgen have proven difficult to adapt in brook trout. An appropriate timing, duration and delivery vehicle for administration of 17α-methyltestosterone (MT) to produce phenotypic males (neomales) from genotypically female brook trout required further investigation. In this study, groups of brook trout eggs (n=1000) maintained at 9.5±0.15-10±0.14°C, were immersed in MT (400μgL -1 ) for four hours on two alternate days (two immersions/group) staggered over a two week period surrounding the hatch of embryos (control groups excluded). The groups were then split and half received MT-supplemented feed for 60days and the other a standard diet. Following an 11 month on-growing period sex phenotypes were determined by gross & histological gonad morphology. The highest proportion of male phenotypes (75%) was found in fish immersed six and four days pre-hatch and subsequently fed a normal diet. Fish fed a MT supplemented diet and immersed in MT showed significantly higher proportions of sterile fish. These data indicate that a pre-hatch immersion-only regime (4-6days pre-hatch at 9.5°C) should be pursued as a target for optimization studies to further refine the effective concentration and duration of exposure to MT for the successful production of neo-male brook trout. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima–media thickness in Bangladesh

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Fen [Department of Population Health, New York University School of Medicine, New York, NY (United States); Department of Environmental Medicine, New York University School of Medicine, New York, NY (United States); Jasmine, Farzana; Kibriya, Muhammad G. [Department of Health Studies, The University of Chicago, Chicago, IL (United States); The University of Chicago Comprehensive Cancer Center, Chicago, IL (United States); Liu, Mengling; Cheng, Xin [Department of Population Health, New York University School of Medicine, New York, NY (United States); Department of Environmental Medicine, New York University School of Medicine, New York, NY (United States); Parvez, Faruque [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, NY (United States); Paul-Brutus, Rachelle [Department of Health Studies, The University of Chicago, Chicago, IL (United States); The University of Chicago Comprehensive Cancer Center, Chicago, IL (United States); Islam, Tariqul; Paul, Rina Rani; Sarwar, Golam; Ahmed, Alauddin [U-Chicago Research Bangladesh, Ltd., Dhaka (Bangladesh); Jiang, Jieying [Department of Population Health, New York University School of Medicine, New York, NY (United States); Department of Environmental Medicine, New York University School of Medicine, New York, NY (United States); Islam, Tariqul [U-Chicago Research Bangladesh, Ltd., Dhaka (Bangladesh); Slavkovich, Vesna [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, NY (United States); Rundek, Tatjana [Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL (United States); Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL (United States); Demmer, Ryan T.; Desvarieux, Moise [Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, NY (United States); and others

    2014-05-01

    Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima–media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = − 5.1 μm, 95% CI = − 31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = − 3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings. - Highlights: • Nine SNPs had a nominally significant interaction with well-water arsenic in cIMT. • Three SNPs in AS3MT showed nominally significant interactions with urinary arsenic. • cIMT was much higher among subjects with higher arsenic exposure and AS3MT

  6. Optimization of influenza A vaccine virus by reverse genetic using chimeric HA and NA genes with an extended PR8 backbone.

    Science.gov (United States)

    Medina, Julie; Boukhebza, Houda; De Saint Jean, Amélie; Sodoyer, Régis; Legastelois, Isabelle; Moste, Catherine

    2015-08-20

    The yield of influenza antigen production may significantly vary between vaccine strains; for example the A/California/07/09 (H1N1)-X179A vaccine virus, prepared during 2009 influenza pandemic, presented a low antigen yield in eggs compared to other seasonal H1N1 reassortants. In this study a bi-chimeric virus expressing HA and NA genes with A/Puerto Rico/8/34 (H1N1) (PR8) and X179A domains was rescued by reverse genetics using a mixture of Vero/CHOK1 cell lines (Medina et al. [7]). The bi-chimeric virus obtained demonstrated to yield much larger amounts of HA than X179A in eggs as measured by single-radial-immunodiffusion (SRID), the reference method to quantify HA protein in influenza vaccine. Such kind of optimized virus using PR8 backbone derived chimeric glycoproteins could be used as improved seed viruses for vaccine production. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Metal allergy--a review on exposures, penetration, genetics, prevalence, and clinical implications

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Menné, Torkil

    2010-01-01

    by the absence of regulation. The prevalence of chromium allergy is increasing in the United States, Singapore, and Denmark among dermatitis patients. This increase is significantly associated with leather exposure in Denmark. Metal allergy may result in allergic contact dermatitis and systemic allergic (contact......) dermatitis. Furthermore, metal allergy has been associated with device failure following insertion of intracoronary stents, hip and knee prostheses, as well as other implants. This area is in need of more research....

  8. The Molecular Epidemiology of Breast Cancer: Risk from Environmental Exposures and Genetic Susceptibility.

    Science.gov (United States)

    1996-10-01

    significantly associated with any of the exposure variables under investigation. DDE was weakly positively related to quetelet index (r=O. 14). A somewhat...stronger positive association with quetelet index was observed for congener 118 (r=0.20). Inverse associations with quetelet index were found for...lactation and quetelet index) and upon observed associations with the outcome variables in previous analyses. Some of the organochlorines under

  9. Metal allergy--a review on exposures, penetration, genetics, prevalence, and clinical implications.

    Science.gov (United States)

    Thyssen, Jacob P; Menné, Torkil

    2010-02-15

    The prevalence of metal allergy is high in the general population, and it is estimated that up to 17% of women and 3% of men are allergic to nickel and that 1-3% are allergic to cobalt and chromium. Among dermatitis patients, the prevalence of metal allergy is even higher. Metal allergy is mainly an environmental disorder although null mutations in the filaggrin gene complex were recently found to be associated with nickel allergy and dermatitis. Environmental metal exposures include jewelry, buttons, clothing fasteners, dental restorations, mobile phones, and leather. Although consumer exposure is responsible for most cases of metal allergy, the importance of occupational metal exposure remains present and should always be taken into consideration when one interprets allergic patch test reactions to metals. Traditionally, nickel, cobalt, and chromium have been the most important contact allergens. However, recently, gold and palladium have drawn much attention as the prevalence of contact allergy to these metals is high. Palladium allergy is mainly a result of cross-sensitization to nickel, whereas gold allergy is rarely clinically relevant when one takes its high prevalence into account. The epidemiology of metal allergy has recently changed in Europe as nickel allergy among ear-pierced Danish women has decreased following regulatory intervention on nickel release from consumer products. In the United States, the prevalence of nickel allergy is still increasing, which may be explained by the absence of regulation. The prevalence of chromium allergy is increasing in the United States, Singapore, and Denmark among dermatitis patients. This increase is significantly associated with leather exposure in Denmark. Metal allergy may result in allergic contact dermatitis and systemic allergic (contact) dermatitis. Furthermore, metal allergy has been associated with device failure following insertion of intracoronary stents, hip and knee prostheses, as well as other

  10. Genetic susceptibility to breast cancer risk associated with inorganic arsenic exposure.

    Science.gov (United States)

    Gamboa-Loira, Brenda; Cebrián, Mariano E; Salinas-Rodríguez, Aarón; López-Carrillo, Lizbeth

    2017-12-01

    To evaluate whether the association between breast cancer (BC) and inorganic arsenic (iAs) exposure is modulated by selected polymorphisms in iAs metabolism. A population based case-control (1016/1028) study was conducted in Northern Mexico. Urinary arsenic metabolites were measured by High Performance Liquid Chromatography. Metabolites percentages and methylation ratios, were estimated. Genotypes of selected polymorphisms were determined by allelic discrimination. The interaction between polymorphisms and iAs metabolites percentages and methylation ratios on BC was assessed with unconditional logistic regression models. A significant interaction (p=0.002) between MTR c.2756A>G polymorphism and percentage dimethylarsinic acid (DMA) on BC was found; BC risk related with %DMA was lower in AG+GG carriers than in AA carriers. No other significant interactions were found. MTR c.2756A>G polymorphism may confer protection for BC associated with iAs exposure. Further research is warranted to elucidate the potential involvement of other polymorphisms in iAs-related BC. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Reverse genetics in complex multigene operons by co-transformation of the plastid genome and its application to the open reading frame previously designated psbN.

    Science.gov (United States)

    Krech, Katharina; Fu, Han-Yi; Thiele, Wolfram; Ruf, Stephanie; Schöttler, Mark A; Bock, Ralph

    2013-09-01

    Reverse genetics approaches have contributed enormously to the elucidation of gene functions in plastid genomes and the determination of structure-function relationships in chloroplast multiprotein complexes. Gene knock-outs are usually performed by disrupting the reading frame of interest with a selectable marker cassette. Site-directed mutagenesis is done by placing the marker into the adjacent intergenic spacer and relying on co-integration of the desired mutation by homologous recombination. These strategies are not applicable to genes residing in large multigene operons or other gene-dense genomic regions, because insertion of the marker cassette into an operon-internal gene or into the nearest intergenic spacer is likely to interfere with expression of adjacent genes in the operon or disrupt cis-elements for the expression of neighboring genes and operons. Here we have explored the possibility of using a co-transformation strategy to mutate a small gene of unknown function (psbN) that is embedded in a complex multigene operon. Although inactivation of psbN resulted in strong impairment of photosynthesis, homoplasmic knock-out lines were readily recovered by co-transformation with a selectable marker integrating >38 kb away from the targeted psbN. Our results suggest co-transformation as a suitable strategy for the functional analysis of plastid genes and operons, which allows the recovery of unselected homoplasmic mutants even if the introduced mutations entail a significant selective disadvantage. Moreover, our data provide evidence for involvement of the psbN gene product in the biogenesis of both photosystem I and photosystem II. We therefore propose to rename the gene product 'photosystem biogenesis factor 1' and the gene pbf1. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  12. Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine.

    Science.gov (United States)

    Jimenez-Guardeño, Jose M; Regla-Nava, Jose A; Nieto-Torres, Jose L; DeDiego, Marta L; Castaño-Rodriguez, Carlos; Fernandez-Delgado, Raul; Perlman, Stanley; Enjuanes, Luis

    2015-10-01

    A SARS-CoV lacking the full-length E gene (SARS-CoV-∆E) was attenuated and an effective vaccine. Here, we show that this mutant virus regained fitness after serial passages in cell culture or in vivo, resulting in the partial duplication of the membrane gene or in the insertion of a new sequence in gene 8a, respectively. The chimeric proteins generated in cell culture increased virus fitness in vitro but remained attenuated in mice. In contrast, during SARS-CoV-∆E passage in mice, the virus incorporated a mutated variant of 8a protein, resulting in reversion to a virulent phenotype. When the full-length E protein was deleted or its PDZ-binding motif (PBM) was mutated, the revertant viruses either incorporated a novel chimeric protein with a PBM or restored the sequence of the PBM on the E protein, respectively. Similarly, after passage in mice, SARS-CoV-∆E protein 8a mutated, to now encode a PBM, and also regained virulence. These data indicated that the virus requires a PBM on a transmembrane protein to compensate for removal of this motif from the E protein. To increase the genetic stability of the vaccine candidate, we introduced small attenuating deletions in E gene that did not affect the endogenous PBM, preventing the incorporation of novel chimeric proteins in the virus genome. In addition, to increase vaccine biosafety, we introduced additional attenuating mutations into the nsp1 protein. Deletions in the carboxy-terminal region of nsp1 protein led to higher host interferon responses and virus attenuation. Recombinant viruses including attenuating mutations in E and nsp1 genes maintained their attenuation after passage in vitro and in vivo. Further, these viruses fully protected mice against challenge with the lethal parental virus, and are therefore safe and stable vaccine candidates for protection against SARS-CoV.

  13. Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine

    Science.gov (United States)

    Nieto-Torres, Jose L.; DeDiego, Marta L.; Castaño-Rodriguez, Carlos; Fernandez-Delgado, Raul; Perlman, Stanley; Enjuanes, Luis

    2015-01-01

    A SARS-CoV lacking the full-length E gene (SARS-CoV-∆E) was attenuated and an effective vaccine. Here, we show that this mutant virus regained fitness after serial passages in cell culture or in vivo, resulting in the partial duplication of the membrane gene or in the insertion of a new sequence in gene 8a, respectively. The chimeric proteins generated in cell culture increased virus fitness in vitro but remained attenuated in mice. In contrast, during SARS-CoV-∆E passage in mice, the virus incorporated a mutated variant of 8a protein, resulting in reversion to a virulent phenotype. When the full-length E protein was deleted or its PDZ-binding motif (PBM) was mutated, the revertant viruses either incorporated a novel chimeric protein with a PBM or restored the sequence of the PBM on the E protein, respectively. Similarly, after passage in mice, SARS-CoV-∆E protein 8a mutated, to now encode a PBM, and also regained virulence. These data indicated that the virus requires a PBM on a transmembrane protein to compensate for removal of this motif from the E protein. To increase the genetic stability of the vaccine candidate, we introduced small attenuating deletions in E gene that did not affect the endogenous PBM, preventing the incorporation of novel chimeric proteins in the virus genome. In addition, to increase vaccine biosafety, we introduced additional attenuating mutations into the nsp1 protein. Deletions in the carboxy-terminal region of nsp1 protein led to higher host interferon responses and virus attenuation. Recombinant viruses including attenuating mutations in E and nsp1 genes maintained their attenuation after passage in vitro and in vivo. Further, these viruses fully protected mice against challenge with the lethal parental virus, and are therefore safe and stable vaccine candidates for protection against SARS-CoV. PMID:26513244

  14. Estimating the risks of cancer mortality and genetic defects resulting from exposures to low levels of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Buhl, T.E.; Hansen, W.R.

    1984-05-01

    Estimators for calculating the risk of cancer and genetic disorders induced by exposure to ionizing radiation have been recommended by the US National Academy of Sciences Committee on the Biological Effects of Ionizing Radiations, the UN Scientific Committee on the Effects of Atomic Radiation, and the International Committee on Radiological Protection. These groups have also considered the risks of somatic effects other than cancer. The US National Council on Radiation Protection and Measurements has discussed risk estimate procedures for radiation-induced health effects. The recommendations of these national and international advisory committees are summarized and compared in this report. Based on this review, two procedures for risk estimation are presented for use in radiological assessments performed by the US Department of Energy under the National Environmental Policy Act of 1969 (NEPA). In the first procedure, age- and sex-averaged risk estimators calculated with US average demographic statistics would be used with estimates of radiation dose to calculate the projected risk of cancer and genetic disorders that would result from the operation being reviewed under NEPA. If more site-specific risk estimators are needed, and the demographic information is available, a second procedure is described that would involve direct calculation of the risk estimators using recommended risk-rate factors. The computer program REPCAL has been written to perform this calculation and is described in this report. 25 references, 16 tables.

  15. Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada.

    Science.gov (United States)

    Aris, Aziz; Leblanc, Samuel

    2011-05-01

    Pesticides associated to genetically modified foods (PAGMF), are engineered to tolerate herbicides such as glyphosate (GLYP) and gluphosinate (GLUF) or insecticides such as the bacterial toxin bacillus thuringiensis (Bt). The aim of this study was to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels of GLYP and its metabolite aminomethyl phosphoric acid (AMPA), GLUF and its metabolite 3-methylphosphinicopropionic acid (3-MPPA) and Cry1Ab protein (a Bt toxin) in Eastern Townships of Quebec, Canada. Blood of thirty pregnant women (PW) and thirty-nine nonpregnant women (NPW) were studied. Serum GLYP and GLUF were detected in NPW and not detected in PW. Serum 3-MPPA and CryAb1 toxin were detected in PW, their fetuses and NPW. This is the first study to reveal the presence of circulating PAGMF in women with and without pregnancy, paving the way for a new field in reproductive toxicology including nutrition and utero-placental toxicities. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Establishment of Vero cell RNA polymerase I-driven reverse genetics for Influenza A virus and its application for pandemic (H1N1) 2009 influenza virus vaccine production.

    Science.gov (United States)

    Song, Min-Suk; Baek, Yun Hee; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Park, Su-Jin; Kim, Eun-Ha; Lim, Gyo-Jin; Choi, Young-Ki

    2013-06-01

    The constant threat of newly emerging influenza viruses with pandemic potential requires the need for prompt vaccine production. Here, we utilized the Vero cell polymerase I (PolI) promoter, rather than the commonly used human PolI promoter, in an established reverse-genetics system to rescue viable influenza viruses in Vero cells, an approved cell line for human vaccine production. The Vero PolI promoter was more efficient in Vero cells and demonstrated enhanced transcription levels and virus rescue rates commensurate with that of the human RNA PolI promoter in 293T cells. These results appeared to be associated with more efficient generation of A(H1N1)pdm09- and H5N1-derived vaccine seed viruses in Vero cells, whilst the rescue rates in 293T cells were comparable. Our study provides an alternative means for improving vaccine preparation by using a novel reverse-genetics system for generating influenza A viruses.

  17. Children's exposure to environmental pollutants and biomarkers of genetic damage. I. Overview and critical issues

    DEFF Research Database (Denmark)

    Neri, Monica; Bonassi, Stefano; Knudsen, Lisbeth E

    2005-01-01

    In the last decade, molecular epidemiological studies have provided new perspectives on studying environmental risks in pediatric populations, based on the growing understanding that children may be more susceptible to toxicants than adults. Protecting children's health is a social priority...... biomarker results into intervention strategies and for integrating them with environmental monitoring and health data, (iv) optimal ways to obtain consent and provide information to children and/or their parents participating in the studies and (v) techniques for the effective communication with policy...... makers and the public. Critical issues in children's environmental research discussed in this paper include specific needs of study design, exposure assessment, sample collection and ethics. Special consideration is given to the autonomy of the child in giving consent, the details and nature...

  18. The Effects of Synthetic Estrogen Exposure on the Sexually Dimorphic Liver Transcriptome of the Sex-Role-Reversed Gulf Pipefish: e0139401

    National Research Council Canada - National Science Library

    Emily Rose; Sarah P Flanagan; Adam G Jones

    2015-01-01

    .... Here, we investigate gene expression patterns in the liver of the sex-role-reversed Gulf pipefish, because the liver is known to be sexually dimorphic and estrogen-regulated in species with conventional sex roles...

  19. Efficient reverse genetics reveals genetic determinants of budding and fusogenic differences between Nipah and Hendra viruses and enables real-time monitoring of viral spread in small animal models of henipavirus infection.

    Science.gov (United States)

    Yun, Tatyana; Park, Arnold; Hill, Terence E; Pernet, Olivier; Beaty, Shannon M; Juelich, Terry L; Smith, Jennifer K; Zhang, Lihong; Wang, Yao E; Vigant, Frederic; Gao, Junling; Wu, Ping; Lee, Benhur; Freiberg, Alexander N

    2015-01-15

    Nipah virus (NiV) and Hendra virus (HeV) are closely related henipaviruses of the Paramyxovirinae. Spillover from their fruit bat reservoirs can cause severe disease in humans and livestock. Despite their high sequence similarity, NiV and HeV exhibit apparent differences in receptor and tissue tropism, envelope-mediated fusogenicity, replicative fitness, and other pathophysiologic manifestations. To investigate the molecular basis for these differences, we first established a highly efficient reverse genetics system that increased rescue titers by ≥3 log units, which offset the difficulty of generating multiple recombinants under constraining biosafety level 4 (BSL-4) conditions. We then replaced, singly and in combination, the matrix (M), fusion (F), and attachment glycoprotein (G) genes in mCherry-expressing recombinant NiV (rNiV) with their HeV counterparts. These chimeric but isogenic rNiVs replicated well in primary human endothelial and neuronal cells, indicating efficient heterotypic complementation. The determinants of budding efficiency, fusogenicity, and replicative fitness were dissociable: HeV-M budded more efficiently than NiV-M, accounting for the higher replicative titers of HeV-M-bearing chimeras at early times, while the enhanced fusogenicity of NiV-G-bearing chimeras did not correlate with increased replicative fitness. Furthermore, to facilitate spatiotemporal studies on henipavirus pathogenesis, we generated a firefly luciferase-expressing NiV and monitored virus replication and spread in infected interferon alpha/beta receptor knockout mice via bioluminescence imaging. While intraperitoneal inoculation resulted in neuroinvasion following systemic spread and replication in the respiratory tract, intranasal inoculation resulted in confined spread to regions corresponding to olfactory bulbs and salivary glands before subsequent neuroinvasion. This optimized henipavirus reverse genetics system will facilitate future investigations into the

  20. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

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

  1. Genetics Home Reference: nephronophthisis

    Science.gov (United States)

    ... with nephronophthisis have additional features, which can include liver fibrosis, heart abnormalities, or mirror image reversal of the ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (13 links) Genetic Testing Registry: ...

  2. Sex Reversal in Birds.

    Science.gov (United States)

    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.

  3. Reverse logistics

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); S.D.P. Flapper; R. Dekker (Rommert)

    2002-01-01

    textabstractThis paper gives an overview of scientific literature that describes and discusses cases of reverse logistics activities in practice. Over sixty case studies are considered. Based on these studies we are able to indicate critical factors for the practice of reverse logistics. In

  4. Genetic Deletion of Neuronal PPARγ Enhances the Emotional Response to Acute Stress and Exacerbates Anxiety: An Effect Reversed by Rescue of Amygdala PPARγ Function.

    Science.gov (United States)

    Domi, Esi; Uhrig, Stefanie; Soverchia, Laura; Spanagel, Rainer; Hansson, Anita C; Barbier, Estelle; Heilig, Markus; Ciccocioppo, Roberto; Ubaldi, Massimo

    2016-12-14

    PPARγ is one of the three isoforms of the Peroxisome Proliferator-Activated Receptors (PPARs). PPARγ is activated by thiazolidinediones such as pioglitazone and is targeted to treat insulin resistance. PPARγ is densely expressed in brain areas involved in regulation of motivational and emotional processes. Here, we investigated the role of PPARγ in the brain and explored its role in anxiety and stress responses in mice. The results show that stimulation of PPARγ by pioglitazone did not affect basal anxiety, but fully prevented the anxiogenic effect of acute stress. Using mice with genetic ablation of neuronal PPARγ (PPARγNestinCre), we demonstrated that a lack of receptors, specifically in neurons, exacerbated basal anxiety and enhanced stress sensitivity. The administration of GW9662, a selective PPARγ antagonist, elicited a marked anxiogenic response in PPARγ wild-type (WT), but not in PPARγNestinCre knock-out (KO) mice. Using c-Fos immunohistochemistry, we observed that acute stress exposure resulted in a different pattern of neuronal activation in the amygdala (AMY) and the hippocampus (HIPP) of PPARγNestinCre KO mice compared with WT mice. No differences were found between WT and KO mice in hypothalamic regions responsible for hormonal response to stress or in blood corticosterone levels. Microinjection of pioglitazone into the AMY, but not into the HIPP, abolished the anxiogenic response elicited by acute stress. Results also showed that, in both regions, PPARγ colocalizes with GABAergic cells. These findings demonstrate that neuronal PPARγ is involved the regulation of the stress response and that the AMY is a key substrate for the anxiolytic effect of PPARγ. Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) is a classical target for antidiabetic therapies with thiazolidinedione compounds. PPARγ agonists such as rosiglitazone and pioglitazone are in clinical use for the treatment of insulin resistance. PPARγ has recently attracted

  5. Utility of a multiplex reverse transcriptasepolymerase chain reaction assay (HemaVision in the evaluation of genetic abnormalities in Korean children with acute leukemia: a single institution study

    Directory of Open Access Journals (Sweden)

    Hye-Jin kim

    2013-06-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; In children with acute leukemia, bone marrow genetic abnormalities (GA have prognostic significance, and may be the basis for minimal residual disease monitoring. Since April 2007, we have used a multiplex reverse transcriptase-polymerase chain reaction tool (HemaVision to detect of GA. &lt;b&gt;Methods:&lt;/b&gt; In this study, we reviewed the results of HemaVision screening in 270 children with acute leukemia, newly diagnosed at The Catholic University of Korea from April 2007 to December 2011, and compared the results with those of fluorescence in situ hybridization (FISH, and G-band karyotyping. &lt;b&gt;Results:&lt;/b&gt; Among the 270 children (153 males, 117 females, 187 acute lymphoblastic leukemia and 74 acute myeloid leukemia patients were identified. Overall, GA was detected in 230 patients (85.2%. HemaVision, FISH, and G-band karyotyping identified GA in 125 (46.3%, 126 (46.7%, and 215 patients (79.6%, respectively. TEL-AML1 (20.9%, 39/187 and AML1-ETO (27%, 20/74 were the most common GA in ALL and AML, respectively. Overall sensitivity of HemaVision was 98.4%, with false-negative results in 2 instances: 1 each for TEL-AML1 and MLL-AF4 . An aggregate of diseasesspecific FISH showed 100% sensitivity in detection of GA covered by HemaVision for actual probes utilized. G-band karyotype revealed GA other than those covered by HemaVison screening in 133 patients (49.3%. Except for hyperdiplody and hypodiploidy, recurrent GA as defined by the World Health Organizationthat were not screened by HemaVision, were absent in the karyotype. &lt;b&gt;Conclusion:&lt;/b&gt; HemaVision, supported by an aggregate of FISH tests for important translocations, may allow for accurate diagnosis of GA in Korean children with acute leukemia.

  6. Comparison of occupational exposure assessment methods in a case-control study of lead, genetic susceptibility and risk of adult brain tumors

    Science.gov (United States)

    Bhatti, Parveen; Stewart, Patricia A.; Linet, Martha S.; Blair, Aaron; Inskip, Peter D.; Rajaraman, Preetha

    2013-01-01

    Objectives There is great interest in evaluating gene-environment interactions with chemical exposures, but exposure assessment poses a unique challenge in case-control studies. Expert assessment of detailed work history data is usually considered the best approach, but it is a laborious and time-consuming process. We set out to determine if a less intensive method of exposure assessment (a job exposure matrix [JEM]) would produce similar results to a previous analysis that found evidence of effect modification between expert assessed-lead exposure and risk of brain tumors by a single nucleotide polymorphism in the ALAD gene (rs1800435). Methods We used data from a study of 355 patients with glioma, 151 patients with meningioma and 505 controls. Logistic regression models were used to examine associations between brain tumor risk and lead exposure and effect modification by genotype. We evaluated Cohen’s kappa, sensitivity and specificity for the JEM compared to the expert-assessed exposure metrics. Results Although effect estimates were imprecise and driven by a small number of cases, we found evidence of effect modification between lead exposure and ALAD genotype when using expert- but not JEM-derived lead exposure estimates. Kappa values indicated only modest agreement (exposure metrics, with the JEM indicating high specificity (~0.9) but poor sensitivity (~0.5). Disagreement between the two methods was generally due to having additional information in the detailed work history. Conclusion These results provide preliminary evidence suggesting that high quality exposure data are likely to improve the ability to detect genetic effect modification. PMID:20798009

  7. Reverse Osmosis

    Indian Academy of Sciences (India)

    ment of Civil Engineering and is presently the. Chairman of Center for. Sustainable Technologies,. Indian Institute of Science,. Bangalore. His research areas include, unsaturated soil behaviour, hazardous waste management, water quality and remediation of contaminated water. Keywords. Osmosis, reverse osmosis,.

  8. Reverse Osmosis

    Indian Academy of Sciences (India)

    and is an Associate Faculty at Center for Sustainable. Technologies, Indian. Institute of Science,. Bangalore. His research areas include, unsaturated soil behaviour, hazardous waste management, water quality and remediation of contaminated water. Keywords. Osmosis, reverse osmosis, desalinatiion, seawater, water.

  9. Reverse Osmosis

    Indian Academy of Sciences (India)

    /fulltext/reso/012/05/0037-0040. Keywords. Osmosis; reverse osmosis; desalinatiion; seawater; water purification. Author Affiliations. Sudhakar M Rao1. Department of Civil Engineering, Indian Institute of Science, Bangalore 560012, India.

  10. Reversible Sterilization

    Science.gov (United States)

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  11. In-utero exposure to maternal smoking is not linked to tobacco use in adulthood after controlling for genetic and family influences: a Swedish sibling study.

    Science.gov (United States)

    Rydell, Mina; Granath, Fredrik; Cnattingius, Sven; Magnusson, Cecilia; Galanti, Maria Rosaria

    2014-07-01

    Previous studies have linked maternal smoking during pregnancy with regular tobacco use in offspring, but findings are not consistent and confounding from genetic and environmental factors have not fully been taken into account. A comparison between siblings discordant for prenatal smoking exposure adjusts for confounding by shared familial (i.e., genetic and environmental) factors. We investigated the association between prenatal exposure to maternal smoking during pregnancy and the risk of regular smoking or snus (Swedish moist smokeless tobacco) use in young adult offspring, using a population based matched cohort study. The cohort consisted of 1,538 randomly sampled same-sex sibling pairs, discordant for maternal smoking during pregnancy, 19-27 years old, participating in a survey conducted in Sweden 2010-2011. Lifetime and current history of tobacco use was self-reported in the survey, and information about maternal smoking during pregnancy was retrieved from the Medical Birth Register. Conditional logistic regression and stratified Cox proportional hazards regression were used to calculate odds ratios, hazard ratios, and corresponding 95% confidence intervals. Analyses of exposure-discordant siblings did not reveal significant associations between prenatal exposure to maternal smoking and lifetime or current daily tobacco use, intensity of use, or time to onset of daily tobacco use. These findings suggest that the previously reported higher risks of tobacco use in offspring of mothers who smoked during pregnancy, compared with offspring of non-smoking mothers, were likely due to confounding from genetic or environmental factors.

  12. Genetic toxicity evaluation of 1,1,1,2,3,3,3- heptatfluoropropane. Volume 1. Results of salmonella typhimurium histidine reversion assay (ames assay). Final report, March-December 1994

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, A.D.

    1995-01-01

    Under subcontract to ManTech Environmental Technology, Incorporated, Uenesys Research, Incorporated tested 1,1,12,3,3,3- heptafluoropropane (HFC-227ea) using Billups-Rothenberg exposure chambers for the exposure chamber modification of the Salmonella typhimurium histidine (his) reversion mutagenesis system (the Ames test), a microbial assay that measures his his+ reversion induced by chemicals that cause base changes or frameshift mutations i the genome of this organism. Testing was conducted using five Salmonella strains, with and without metabolic activation. HFC-227ea was tested in a preliminary test and in a mutagenesis assay. HFC-227ea was tested to toxic levels in the mutagenesis assay, but a sufficient number of nontoxic concentrations were tested to determine if HFC-227ea were capable of inducing a dose-related mutagenic response, and the positive control responses were consistent with historical data from the laboratory, and no evidence of a mutagenic response was obtained in any strain without or with activation. Therefore, HFC-227ea was negative in the Salmonella typhimurium histidine reversion mutagenesis test in the presence and absence of metabolic activation.

  13. Neuritin reverses deficits in murine novel object associative recognition memory caused by exposure to extremely low-frequency (50 Hz) electromagnetic fields

    Science.gov (United States)

    Zhao, Qian-Ru; Lu, Jun-Mei; Yao, Jin-Jing; Zhang, Zheng-Yu; Ling, Chen; Mei, Yan-Ai

    2015-01-01

    Animal studies have shown that electromagnetic field exposure may interfere with the activity of brain cells, thereby generating behavioral and cognitive disturbances. However, the underlying mechanisms and possible preventions are still unknown. In this study, we used a mouse model to examine the effects of exposure to extremely low-frequency (50 Hz) electromagnetic fields (ELF MFs) on a recognition memory task and morphological changes of hippocampal neurons. The data showed that ELF MFs exposure (1 mT, 12 h/day) induced a time-dependent deficit in novel object associative recognition memory and also decreased hippocampal dendritic spine density. This effect was observed without corresponding changes in spontaneous locomotor activity and was transient, which has only been seen after exposing mice to ELF MFs for 7-10 days. The over-expression of hippocampal neuritin, an activity-dependent neurotrophic factor, using an adeno-associated virus (AAV) vector significantly increased the neuritin level and dendritic spine density. This increase was paralleled with ELF MFs exposure-induced deficits in recognition memory and reductions of dendritic spine density. Collectively, our study provides evidence for the association between ELF MFs exposure, impairment of recognition memory, and resulting changes in hippocampal dendritic spine density. Neuritin prevented this ELF MFs-exposure-induced effect by increasing the hippocampal spine density. PMID:26138388

  14. Reversible long-term changes in auditory processing in mature auditory cortex in the absence of hearing loss induced by passive, moderate-level sound exposure.

    Science.gov (United States)

    Pienkowski, Martin; Eggermont, Jos J

    2012-01-01

    It has become increasingly clear that even occasional exposure to loud sounds in occupational or recreational settings can cause irreversible damage to the hair cells of the cochlea and the auditory nerve fibers, even if the resulting partial loss of hearing sensitivity, usually accompanied by tinnitus, disappears within hours or days of the exposure. Such exposure may explain at least some cases of poor speech intelligibility in noise in the face of a normal or near-normal audiogram. Recent findings from our laboratory suggest that long-term changes to auditory brain function-potentially leading to problems with speech intelligibility-can be effected by persistent, passive exposure to more moderate levels of noise (in the 70 dB SPL range) in the apparent absence of damage to the auditory periphery (as reflected in normal distortion product otoacoustic emissions and auditory brainstem responses). Specifically, passive exposure of adult cats to moderate levels of band-pass-filtered noise, or to band-limited ensembles of dense, random tone pips, can lead to a profound decrease of neural activity in the auditory cortex roughly in the exposure frequency range, and to an increase of activity outside that range. This can progress to an apparent reorganization of the cortical tonotopic map, which is reminiscent of the reorganization resulting from hearing loss restricted to a part of the hearing frequency range, although again, no hearing loss was apparent after our moderate-level sound exposure. Here, we review this work focusing specifically on the potential hearing problems that may arise despite a normally functioning auditory periphery.

  15. Study on association between genetic polymorphisms of haem oxygenase-1, tumour necrosis factor, cadmium exposure and malaria pathogenicity and severity

    Directory of Open Access Journals (Sweden)

    Ruangweerayut Ronnatrai

    2010-09-01

    Full Text Available Abstract Background Malaria is the most important public health problems in tropical and sub-tropical countries. Haem oxygenase (HO enzyme and the pro-inflammatory cytokine tumour necrosis factor (TNF have been proposed as one of the factors that may play significant role in pathogenicity/severity of malaria infection. HO is the enzyme of the microsomal haem degradation pathway that yields biliverdin, carbon monoxide, and iron. In this study, the association between malaria disease pathogenicity/severity and (GTn repeat polymorphism in the promoter region of the inducible HO-1 including the effect of cadmium exposure (potent inducer of HO-1 transcription as well as polymorphism of TNF were investigated. Methods Blood samples were collected from 329 cases non-severe malaria with acute uncomplicated Plasmodium falciparum malaria (UM and 80 cases with Plasmodium vivax malaria (VM, and 77 cases with severe or cerebral malaria (SM for analysis of genetic polymorphisms of HO-1 and TNF and cadmium levels. These patients consisted of 123 (25.3% Thai, 243 (50.0% Burmese and 120 (24.7% Karen who were present at Mae Sot General Hospital, Mae Sot, Tak Province, Thailand. Results The number of (GTn repeats of the HO-1 gene in all patients varied between 16 and 39 and categorized to short (S, medium (M and long (L GTn repeats. The genotype of (GTn repeat of HO-1 was found to be significantly different among the three ethnic groups of patients. Significantly higher frequency of S/L genotype was found in Burmese compared with Thai patients, while significantly lower frequencies of S/S and M/L but higher frequency of M/M genotype was observed in Burmese compared with Karen patients. No significant association between HO-1 and TNF polymorphisms including the inducing effect of cadmium and malaria pathogenicity/severity was observed. Conclusions Difference in the expression of HO-1 genotype in different ethnic groups may contribute to different severity of malaria

  16. Fetal exposure to maternal inflammation does not affect postnatal development of genetically-driven ileitis and colitis.

    Directory of Open Access Journals (Sweden)

    Jana Hemmerling

    Full Text Available BACKGROUND: Chronic inflammatory disorders have been increasing in incidence over the past decades following geographical patterns of industrialization. Fetal exposure to maternal inflammation may alter organ functions and the offspring's disease risk. We studied the development of genetically-driven ileitis and colitis in response to maternal inflammation using mouse models. METHODS: Disease susceptible (TnfΔARE/+ and IL10-/- and disease-free (Tnf+/+ and IL10-/+ offspring were raised in inflamed and non-inflamed dams. Ileal, caecal and colonic pathology was evaluated in the offspring at 8 or 12 weeks of age. Ly6G-positive cells in inflamed sections from the distal ileum and distal colon were analysed by immunofluorescence microscopy. Gene expression of pro-inflammatory cytokines was measured in whole tissue specimens by quantitative PCR. Microarray analyses were performed on laser microdissected intestinal epithelium. Caecal bacterial communities were assessed by Illumina sequencing of 16S rRNA amplicons. RESULTS: Disease severity, the number of infiltrated neutrophils as well as Tnf and Il12p40 mRNA expression were independent of maternal inflammation in the offspring of mouse models for ileitis (TnfΔARE/+ and colitis (IL10-/-. Although TNF-driven maternal inflammation regulated 2,174 (wild type and 3,345 (TnfΔARE/+ genes in the fetal epithelium, prenatal gene expression patterns were completely overwritten after birth. In addition, co-housing experiments revealed no change in phylogenetic diversity of the offspring's caecal microbiota in response to maternal inflammation. This is independent of the offspring's genotype before and after the onset of tissue pathology. CONCLUSIONS: Disease risk and activity in mouse models of chronic ileitis and colitis was independent of the fetal exposure to maternal inflammation. Likewise, maternal inflammation did not alter the diversity and composition of offspring's caecal microbiota, clearly

  17. Predicting alcohol consumption in adolescence from alcohol-specific and general externalizing genetic risk factors, key environmental exposures and their interaction.

    Science.gov (United States)

    Kendler, K S; Gardner, C; Dick, D M

    2011-07-01

    Alcohol consumption is influenced by specific genetic risk factors for alcohol use disorders (AUDs), non-specific genetic risk factors for externalizing behaviors and various environmental experiences. We have limited knowledge of how these risk factors inter-relate through development. Retrospective assessments in 1796 adult male twins using a life history calendar of key environmental exposures and alcohol consumption from early adolescence to mid-adulthood. Analysis by linear mixed models. The importance of non-specific genetic risk factors on maximal alcohol consumption rose rapidly in early to mid-adolescence, peaked at ages 15-17 years and then declined slowly. Alcohol-specific genetic risk factors increased slowly in influence through mid-adulthood. We detected robust evidence for environmental moderation of genetic effects on alcohol consumption that was more pronounced in early and mid-adolescence than in later periods. Alcohol availability, peer deviance and low prosocial behaviors showing the strongest moderation effects. More interactions with environmental risk factors were seen for the non-specific externalizing disorder risk than for specific genetic risk for AUDs. The impact of specific and non-specific genetic influences on alcohol consumption have different development trajectories. Genetic effects on alcohol use are more pronounced when social constraints are minimized (e.g. low prosocial behaviors or parental monitoring) or when the environment permits easy access to alcohol and/or encourages its use (e.g. high alcohol availability or peer deviance). Gene-environment interactions influencing alcohol intake may be more robust at younger ages, indicating greater plasticity of genetic influences early in the development of drinking patterns.

  18. Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jansen-van der Weide, Marijke C. [University Medical Center Groningen, University of Groningen, Department of Radiology, Hanzeplein 1, PO Box 30.001, Groningen (Netherlands); University Medical Center Groningen, University of Groningen, Department of Epidemiology, Groningen (Netherlands); Greuter, Marcel J.W.; Pijnappel, Ruud M. [University Medical Center Groningen, University of Groningen, Department of Radiology, Hanzeplein 1, PO Box 30.001, Groningen (Netherlands); Jansen, Liesbeth [University Medical Center Groningen, University of Groningen, Department of Surgery, Groningen (Netherlands); Oosterwijk, Jan C. [University Medical Center Groningen, University of Groningen, Department of Clinical Genetics, Groningen (Netherlands); Bock, Geertruida H. de [University Medical Center Groningen, University of Groningen, Department of Epidemiology, Groningen (Netherlands)

    2010-11-15

    Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the question of how low-dose radiation exposure affects breast cancer risk among high-risk women. A systematic search was conducted for articles addressing breast cancer, mammography screening, radiation and high-risk women. Effects of low-dose radiation on breast cancer risk were presented in terms of pooled odds ratios (OR). Of 127 articles found, 7 were selected for the meta-analysis. Pooled OR revealed an increased risk of breast cancer among high-risk women due to low-dose radiation exposure (OR = 1.3, 95% CI: 0.9- 1.8). Exposure before age 20 (OR = 2.0, 95% CI: 1.3-3.1) or a mean of {>=}5 exposures (OR = 1.8, 95% CI: 1.1-3.0) was significantly associated with a higher radiation-induced breast cancer risk. Low-dose radiation increases breast cancer risk among high-risk women. When using low-dose radiation among high-risk women, a careful approach is needed, by means of reducing repeated exposure, avoidance of exposure at a younger age and using non-ionising screening techniques. (orig.)

  19. Reverse mortgages.

    Science.gov (United States)

    Farnesi, D

    1995-09-01

    Elders and their families are often caught in a financial bind when it comes to paying for much-needed home care services. Reverse mortgages may offer a solution to elderly home care clients who own their homes but have a limited income with which to maintain their independence.

  20. Reversible Computing

    Science.gov (United States)

    1980-02-01

    will have been introduced. 9. Reversible celular autemata We shall assume the reader to have some familiarity with the concept of cel- lular...10003 Mr. Kin B. Thcmpson 1 copy Technical Director Information Systems Divisia.i Naval Research Laboratory (OP-91T) Technical Information Division

  1. Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task.

    Directory of Open Access Journals (Sweden)

    Simon R O Nilsson

    Full Text Available Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS-, in a T- or Y-maze configuration. This was followed by three conditions; (1 Full reversal, where contingencies reversed; (2 Perseverance, where the previous CS+ became CS- and the previous CS- was replaced by a novel CS+; (3 Learned non-reward, where the previous CS- became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss

  2. Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task.

    Science.gov (United States)

    Nilsson, Simon R O; Somerville, Elizabeth M; Clifton, Peter G

    2013-01-01

    Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR) function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg) in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS-), in a T- or Y-maze configuration. This was followed by three conditions; (1) Full reversal, where contingencies reversed; (2) Perseverance, where the previous CS+ became CS- and the previous CS- was replaced by a novel CS+; (3) Learned non-reward, where the previous CS- became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss on the

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

    Science.gov (United States)

    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...

  4. Sun exposure, vitamin D receptor genetic variants, and risk of breast cancer in the Agricultural Health Study.

    Science.gov (United States)

    Engel, Lawrence S; Satagopan, Jaya; Sima, Camelia S; Orlow, Irene; Mujumdar, Urvi; Coble, Joseph; Roy, Pampa; Yoo, Sarah; Sandler, Dale P; Alavanja, Michael C

    2014-02-01

    Epidemiologic evidence suggests a negative relation between sunlight exposure and breast cancer risk. The hypothesized mechanism is sunlight-induced cutaneous synthesis of vitamin D. Our goal was to examine sun exposure and its interaction with vitamin D receptor (VDR) gene variants on breast cancer risk. We examined sun exposure and breast cancer incidence among 31,021 private pesticide applicators' wives, including 578 cases, enrolled in the prospective Agricultural Health Study cohort and followed 8.6 years on average. We estimated interactions between sun exposure, VDR variants, and breast cancer in a nested case-control study comprising 293 cases and 586 matched controls. Information on sun exposure was obtained by questionnaire at cohort enrollment. Relative risks were estimated using Cox proportional hazards regression for the cohort data and conditional logistic regression for the nested case-control data. We observed a small decrease in breast cancer risk in association with usual sun exposure of ≥ 1 hr/day (versus sun exposure may be associated with reduced risk of breast cancer, but we did not find clear evidence of modification by VDR variants. Larger studies are warranted, particularly among populations in whom low levels of usual sun exposure can be more precisely characterized.

  5. Effects of Chronic Interpersonal Stress Exposure on Depressive Symptoms are Moderated by Genetic Variation at IL6 and IL1β in Youth

    Science.gov (United States)

    Tartter, Margaret; Hammen, Constance; Bower, Julienne E.; Brennan, Patricia A.; Cole, Steven

    2015-01-01

    Aims Close to one third of patients with major depression show increases in pro-inflammatory cytokines, which are in turn associated with risk for inflammatory disease. Genetic variants that enhance immune reactivity may thus enhance inflammatory and depressive reactions to stress. The aim of the present study was to investigate a trio of functional SNPs in the promoter regions of IL6 (-174G>C, rs1800795), IL1β (-511C>T, rs16944), and TNF (-308G>A, rs1800629) as moderators of the relationship between chronic stress exposure and elevations in depressive symptoms. Methods Participants were 444 Australian youth (mean age = 20.12) whose exposure to chronic stress in the past 6 months was assessed using the semi-structured UCLA Life Stress Interview, and who completed the Beck Depression Inventory II at ages 15 and 20. Between ages 22 and 25, all participants in the selected sample provided blood samples for genotyping. Results In line with a hypothesized moderation effect, -174G allele carriers at IL6 had fewer depressive symptoms following interpersonal stress, relative to C/C homozygotes with equal interpersonal stress exposure. However, IL6 genotype did not moderate the effects of non-interpersonal stress exposure (i.e., financial, work and health-related difficulties) on depression. Also in line with hypotheses, the -511C allele in IL1β, previously associated with higher IL-1β expression, was associated with more severe depression following chronic interpersonal stress exposure, relative to T/T homozygotes. Again, the moderating effect was specific to interpersonal stressors and did not generalize to non-interpersonal stress. TNF was not a moderator of the effects of either interpersonal or non-interpersonal stress on later depression outcomes. Conclusion Findings were consistent with the hypothesis that pro-inflammatory genetic variation increases the risk of stress-induced depression. The present results provide evidence of a genetic mechanism contributing to

  6. Effects of chronic interpersonal stress exposure on depressive symptoms are moderated by genetic variation at IL6 and IL1β in youth.

    Science.gov (United States)

    Tartter, Margaret; Hammen, Constance; Bower, Julienne E; Brennan, Patricia A; Cole, Steven

    2015-05-01

    Close to one third of patients with major depression show increases in pro-inflammatory cytokines, which are in turn associated with risk for inflammatory disease. Genetic variants that enhance immune reactivity may thus enhance inflammatory and depressive reactions to stress. The aim of the present study was to investigate a trio of functional SNPs in the promoter regions of IL6 (-174G>C, rs1800795), IL1β (-511C>T, rs16944), and TNF (-308G>A, rs1800629) as moderators of the relationship between chronic stress exposure and elevations in depressive symptoms. Participants were 444 Australian youth (mean age=20.12) whose exposure to chronic stress in the past 6months was assessed using the semi-structured UCLA Life Stress Interview, and who completed the Beck Depression Inventory II at ages 15 and 20. Between ages 22 and 25, all participants in the selected sample provided blood samples for genotyping. In line with a hypothesized moderation effect, -174G allele carriers at IL6 had fewer depressive symptoms following interpersonal stress, relative to C/C homozygotes with equal interpersonal stress exposure. However, IL6 genotype did not moderate the effects of non-interpersonal stress exposure (i.e., financial, work and health-related difficulties) on depression. Also in line with hypotheses, the -511C allele in IL1β, previously associated with higher IL-1β expression, was associated with more severe depression following chronic interpersonal stress exposure, relative to T/T homozygotes. Again, the moderating effect was specific to interpersonal stressors and did not generalize to non-interpersonal stress. TNF was not a moderator of the effects of either interpersonal or non-interpersonal stress on later depression outcomes. Findings were consistent with the hypothesis that pro-inflammatory genetic variation increases the risk of stress-induced depression. The present results provide evidence of a genetic mechanism contributing to individual differences in

  7. Is Hypospadias Associated with Prenatal Exposure to Endocrine Disruptors? A French Collaborative Controlled Study of a Cohort of 300 Consecutive Children Without Genetic Defect.

    Science.gov (United States)

    Kalfa, Nicolas; Paris, Françoise; Philibert, Pascal; Orsini, Mattea; Broussous, Sylvie; Fauconnet-Servant, Nadège; Audran, Françoise; Gaspari, Laura; Lehors, Hélène; Haddad, Myriam; Guys, Jean-Michel; Reynaud, Rachel; Alessandrini, Pierre; Merrot, Thierry; Wagner, Kathy; Kurzenne, Jean-Yves; Bastiani, Florence; Bréaud, Jean; Valla, Jean-Stéphane; Lacombe, Gérard Morisson; Dobremez, Eric; Zahhaf, Amel; Daures, Jean-Pierre; Sultan, Charles

    2015-12-01

    Numerous studies have focused on the association between endocrine-disrupting chemicals (EDCs) and hypospadias. Phenotype variability, the absence of representative comparison groups and concomitant genetic testing prevent any definitive conclusions. To identify the role of occupational and environmental exposures to EDCs in nongenetic isolated hypospadias. A total of 408 consecutive children with isolated hypospadias and 302 normal boys were prospectively included (2009-2014) in a multi-institutional study in the south of France, the area of the country with the highest prevalence of hypospadias surgery. In patients without AR, SRD5A2, and MAMLD1 mutations, parental occupational and professional exposures to EDCs were evaluated based on European questionnaire QLK4-1999-01422 and a validated job-exposure matrix for EDCs. Environmental exposure was estimated using the zip code, the type of surrounding hazards, and distance from these hazards. Multivariate analysis was performed. Fetal exposure to EDCs around the window of genital differentiation was more frequent in the case of hypospadias (40.00% vs 17.55%, odds ratio 3.13, 95% confidence interval 2.11-4.65). The substances were paints/solvents/adhesives (16.0%), detergents (11.0%), pesticides (9.0%), cosmetics (5.6%), and industrial chemicals (4.0%). Jobs with exposure were more frequent in mothers of hypospadiac boys (19.73% vs 10.26%, p=0.0019), especially cleaners, hairdressers, beauticians, and laboratory workers. Paternal job exposure was more frequent in the cases of hypospadias (40.13% vs 27.48%, p=0.02). Industrial areas, incinerators, and waste areas were more frequent within a 3-km radius for mothers of hypospadiac boys (13.29% vs. 6.64%, phypospadias through occupational and environmental exposure during fetal life. The association of various types of exposures may increase this risk. Our multi-institutional study showed that parental professional, occupational, and environmental exposures to chemical

  8. PT-Flax (phenotyping and TILLinG of flax): development of a flax (Linum usitatissimum L.) mutant population and TILLinG platform for forward and reverse genetics.

    Science.gov (United States)

    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

  9. Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants.

    Directory of Open Access Journals (Sweden)

    Maria Sellitto

    Full Text Available Celiac disease (CD is a unique autoimmune disorder in which the genetic factors (DQ2/DQ8 and the environmental trigger (gluten are known and necessary but not sufficient for its development. Other environmental components contributing to CD are poorly understood. Studies suggest that aspects of gluten intake might influence the risk of CD occurrence and timing of its onset, i.e., the amount and quality of ingested gluten, together with the pattern of infant feeding and the age at which gluten is introduced in the diet. In this study, we hypothesize that the intestinal microbiota as a whole rather than specific infections dictates the switch from tolerance to immune response in genetically susceptible individuals. Using a sample of infants genetically at risk of CD, we characterized the longitudinal changes in the microbial communities that colonize infants from birth to 24 months and the impact of two patterns of gluten introduction (early vs. late on the gut microbiota and metabolome, and the switch from gluten tolerance to immune response, including onset of CD autoimmunity. We show that infants genetically susceptible to CD who are exposed to gluten early mount an immune response against gluten and develop CD autoimmunity more frequently than at-risk infants in which gluten exposure is delayed until 12 months of age. The data, while derived from a relatively small number of subjects, suggest differences between the developing microbiota of infants with genetic predisposition for CD and the microbiota from infants with a non-selected genetic background, with an overall lack of bacteria of the phylum Bacteriodetes along with a high abundance of Firmicutes and microbiota that do not resemble that of adults even at 2 years of age. Furthermore, metabolomics analysis reveals potential biomarkers for the prediction of CD. This study constitutes a definite proof-of-principle that these combined genomic and metabolomic approaches will be key to

  10. Environmental Exposures, Genetic Polymorphisms and p53 Mutational Spectra in a Case-Control Study of Breast Cancer

    National Research Council Canada - National Science Library

    Shields, eter

    1999-01-01

    .... Other genetic analyses are completed for MEH3, MEH4, CYP2D6, GSTMl, GST-T and CYP1A1. We have been validating a p53 mutational spectra detection technology using the Affymetrix gene chip array...

  11. Monitoring the Short-Term Response to Salt Exposure of Two Genetically Distinct Phragmites australis Clones with Different Salinity Tolerance Levels

    DEFF Research Database (Denmark)

    Achenbach, Luciana; Brix, Hans

    2014-01-01

    in the 15-minute experiment. The Greeny-type also recovered after the 70-minute exposure, but not the Land-type. We conclude that the response to osmotic stress is genotype-dependent and that the salt-tolerant clone possesses very efficient signaling pathways to detect changes in the soil water potential......Aims: Two genetically distinct clones of Phragmites australis were used to investigate the immediate response induced by osmotic stress. The study aimed at elucidating if the response time, the inhibition rate and the recovery from salinity stress vary between these two genotypes. The experimental...... salt concentrations (20 and 40 parts per thousand salinity). Important findings: The osmotic stress induced stomata closure and reduction of Pmax and E for both clones. The clone-specific responses as measured through physiological parameters were negatively correlated with exposure time and salt...

  12. Hypospadias in a male (78,XY; SRY-positive) dog and sex reversal female (78,XX; SRY-negative) dogs: clinical, histological and genetic studies.

    Science.gov (United States)

    Switonski, M; Payan-Carreira, R; Bartz, M; Nowacka-Woszuk, J; Szczerbal, I; Colaço, B; Pires, M A; Ochota, M; Nizanski, W

    2012-01-01

    Hypospadias is rarely reported in dogs. In this study we pre-sent 2 novel cases of this disorder of sexual development and, in addition, a case of hereditary sex reversal in a female with an enlarged clitoris. The first case was a male Moscow watchdog with a normal karyotype (78,XY) and the presence of the SRY gene. In this dog, perineal hypospadias, bilateral inguinal cryptorchidism and testes were observed. The second case, representing the Cocker spaniel breed, had a small penis with a hypospadic orifice of the urethra, bilateral cryptorchidism, testis and a rudimentary gonad inside an ovarian bursa, a normal female karyotype (78,XX) and a lack of the SRY gene. This animal was classified as a compound sex reversal (78,XX, SRY-negative) with the hypospadias syndrome. The third case was a Cocker spaniel female with an enlarged clitoris and internally located ovotestes. Cytogenetic and molecular analyses revealed a normal female karyotype (78,XX) and a lack of the SRY gene, while histology of the gonads showed an ovotesticular structure. This case was classified as a typical hereditary sex reversal syndrome (78,XX, SRY-negative). Molecular studies were focused on coding sequences of the SRY gene (case 1) and 2 candidates for monogenic hypospadias, namely MAMLD1 (mastermind-like domain containing 1) and SRD5A2 (steroid-5-alpha-reductase, alpha polypeptide 2). Sequencing of the entire SRY gene, including 5'- and 3'-flanking regions, did not reveal any mutation. The entire coding sequence of MAMLD1 and SRD5A2 was analyzed in all the intersexes, as well as in 4 phenotypically normal control dogs (3 females and 1 male). In MAMLD1 2 SNPs, including 1 missense substitution in exon 1 (c.128A>G, Asp43Ser), were identified, whereas in SRD5A2 7 polymorphisms, including 1 missense SNP (c.358G>A, Ala120Thr), were found. None of the identified polymorphisms cosegregated with the intersexual phenotype, thus, we cannot confirm that hypospadias may be associated with polymorphism

  13. Biological monitoring the exposure to polycyclic aromatic hydrocarbons of coke oven workers in relation to smoking and genetic polymorphisms for GSTM1 and GSTT1

    Energy Technology Data Exchange (ETDEWEB)

    Joost H.M. van Delft; Marie-Jose S.T. Steenwinkel; Jeff G. van Asten; Nico de Vogel; Truus C.D.M. Bruijntjes-Rozier; Ton Schouten; Patricia Cramers; Lou Maas; Marcel H. van Herwijnen; Frederik-Jan van Schooten; Piet M.J. Hopmans [TNO Nutrition and Food Research Institute (Netherlands). Toxicology Division

    2001-07-01

    Occupational exposure to polycyclic aromatic hydrocarbons (PAH) increases the risk of developing lung cancer. Human exposure is often demonstrated by increased internal levels of PAH metabolites and of markers for early biological effects, like DNA adducts and cytogenetic aberrations. This study aimed to assess whether the current exposure to PAH of coke oven workers in a Dutch plant induced biological effects, and to determine if these effects are influenced by tobacco smoking and by genetic polymorphisms for the glutathione S-transferase genes GSTM1 and GSTT1. Urinary 1-hydroxypyrene (1-OHpyr) levels were used to monitor the internal dose, while the internal effective dose was assessed by monitoring PAH-DNA adducts, DNA strand breaks (Comet assay), sister-chromatid exchanges (SCE) and cells with a high frequency of SCE (HFC) in lymphocytes together with micronuclei (MN) in exfoliated urothelial cells. Occupational exposure to PAH resulted in statistically significant increased 1-OHpyr levels, but it did not cause a significant induction of SCE, HFC, MN, DNA strand breaks or DNA adducts. Smoking caused a significant increase of 1-OHpyr, SCE, HFC and DNA adducts, but not of MN or DNA strand breaks. Following correction for the smoking-related effects, no occupational induction of the effect biomarkers could be discerned. Multi-variate analysis did not show a significant influence of GSTM1 and GSTT1 polymorphisms on any biomarker. Also no significant interactions were observed between the various biomarkers.

  14. Exposure to Drinking Water Trihalomethanes and Their Association with Low Birth Weight and Small for Gestational Age in Genetically Susceptible Women

    Directory of Open Access Journals (Sweden)

    Mark J. Nieuwenhuijsen

    2012-12-01

    Full Text Available Little is known about genetic susceptibility to individual trihalomethanes (THM in relation to adverse pregnancy outcomes. We conducted a nested case-control study of 682 pregnant women in Kaunas (Lithuania and, using individual information on drinking water, ingestion, showering and bathing, and uptake factors of THMs in blood, estimated an internal THM dose. We used logistic regression to evaluate the relationship between internal THM dose, birth outcomes and individual and joint (modifying effects of metabolic gene polymorphisms. THM exposure during entire pregnancy and specific trimesters slightly increased low birth weight (LBW risk. When considering both THM exposure and maternal genotypes, the largest associations were found for third trimester among total THM (TTHM and chloroform-exposed women with the GSTM1–0 genotype (OR: 4.37; 95% CI: 1.36–14.08 and OR: 5.06; 95% CI: 1.50–17.05, respectively. A test of interaction between internal THM dose and GSTM1–0 genotype suggested a modifying effect of exposure to chloroform and bromodichloromethane on LBW risk. However, the effect on small for gestational age (SGA was not statistically significant. These data suggest that THM internal dose may affect foetal growth and that maternal GSTM1 genotype modifies the THM exposure effects on LBW.

  15. Exposure to drinking water trihalomethanes and their association with low birth weight and small for gestational age in genetically susceptible women.

    Science.gov (United States)

    Danileviciute, Asta; Grazuleviciene, Regina; Vencloviene, Jone; Paulauskas, Algimantas; Nieuwenhuijsen, Mark J

    2012-12-06

    Little is known about genetic susceptibility to individual trihalomethanes (THM) in relation to adverse pregnancy outcomes. We conducted a nested case-control study of 682 pregnant women in Kaunas (Lithuania) and, using individual information on drinking water, ingestion, showering and bathing, and uptake factors of THMs in blood, estimated an internal THM dose. We used logistic regression to evaluate the relationship between internal THM dose, birth outcomes and individual and joint (modifying) effects of metabolic gene polymorphisms. THM exposure during entire pregnancy and specific trimesters slightly increased low birth weight (LBW) risk. When considering both THM exposure and maternal genotypes, the largest associations were found for third trimester among total THM (TTHM) and chloroform-exposed women with the GSTM1-0 genotype (OR: 4.37; 95% CI: 1.36-14.08 and OR: 5.06; 95% CI: 1.50-17.05, respectively). A test of interaction between internal THM dose and GSTM1-0 genotype suggested a modifying effect of exposure to chloroform and bromodichloromethane on LBW risk. However, the effect on small for gestational age (SGA) was not statistically significant. These data suggest that THM internal dose may affect foetal growth and that maternal GSTM1 genotype modifies the THM exposure effects on LBW.

  16. Sex determination and sex reversal.

    Science.gov (United States)

    Camerino, Giovanna; Parma, Pietro; Radi, Orietta; Valentini, Stella

    2006-06-01

    Sex determination in mammals is based on a genetic cascade that controls the fate of the gonads. Gonads will then direct the establishment of phenotypic sex through the production of hormones. Different types of sex reversal are expected to occur if mutations disrupt one of the three steps of gonadal differentiation: formation of the gonadal primordia, sex determination, and testis or ovary development.

  17. A simian-human immunodeficiency virus carrying the rt gene from Chinese CRF01_AE strain of HIV is sensitive to nucleoside reverse transcriptase inhibitors and has a highly genetic stability in vivo.

    Science.gov (United States)

    Wang, Wei; Yao, Nan; Ju, Bin; Dong, Zhihui; Cong, Zhe; Jiang, Hong; Qin, Chuan; Wei, Qiang

    2014-06-01

    Human immunodeficiency virus (HIV)-1 subtype CRF01_AE is one of the major HIV-1 subtypes that dominate the global epidemic. However, its drug resistance, associated mutations, and viral fitness have not been systemically studied, because available chimeric simian-HIVs (SHIVs) usually express the HIV-1 reverse transcriptase (rt) gene of subtype B HIV-1, which is different from subtype CRF01_AE HIV-1. In this study, a recombinant plasmid, pRT-SHIV/AE, was constructed to generate a chimeric RT-SHIV/AE by replacing the rt gene of simian immunodeficiency virus (SIVmac239) with the counterpart of Chinese HIV-1 subtype CRF01_AE. The infectivity, replication capacity, co-receptor tropism, drug sensitivity, and genetic stability of RT-SHIV/AE were characterized. The new chimeric RT-SHIV/AE effectively infected and replicated in human T cell line and rhesus peripheral blood mononuclear cells (rhPBMC). The rt gene of RT-SHIV/AE lacked the common mutation (T215I) associated with drug resistance. RT-SHIV-AE retained infectivity and immunogenicity, similar to that of its counterpart RT-SHIV/TC virus following intravenous inoculation in Chinese rhesus macaque. RT-SHIV-AE was more sensitive to nucleoside reverse transcriptase inhibitors (NRTIs) than the RT-SHIV/TC. RT-SHIV/AE was genetically stable in Chinese rhesus macaque. The new chimeric RT-SHIV/AE may be a valuable tool for evaluating the efficacy of the rt-based antiviral drugs against the subtype CRF01_AE HIV-1. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  18. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... in different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved...

  19. Modelling individual space?time exposure opportunities: A novel approach to unravelling the genetic or environment disease causation debate

    DEFF Research Database (Denmark)

    Sabel, Clive E; Boyle, Paul; Raab, Gillian

    2009-01-01

    The aetiology of Amyotrophic Lateral Sclerosis (ALS) is uncertain. While around 10% is assumed to be inherited, the relative influence of genetic versus physical or social environmental factors (or some combination of the two) has yet to be determined. A previous study identified significant...... clustering of ALS at the time of birth in south-east Finland and this could support either a genetic or an environmental hypothesis. We know that south-east Finland is an environmentally degraded area, but the population in this region may also be genetically susceptible to this condition. We therefore...... extend this research by comparing the lifetime residential histories of 1000 ALS cases and 1000 controls matched by birth date, sex and municipality of birth. By focusing on those who originated in the south-east, and comparing the subsequent residential mobility of these two groups, we test whether...

  20. Math anxiety and exposure to statistics in messages about genetically modified foods: effects of numeracy, math self-efficacy, and form of presentation.

    Science.gov (United States)

    Silk, Kami J; Parrott, Roxanne L

    2014-01-01

    Health risks are often communicated to the lay public in statistical formats even though low math skills, or innumeracy, have been found to be prevalent among lay individuals. Although numeracy has been a topic of much research investigation, the role of math self-efficacy and math anxiety on health and risk communication processing has received scant attention from health communication researchers. To advance theoretical and applied understanding regarding health message processing, the authors consider the role of math anxiety, including the effects of math self-efficacy, numeracy, and form of presenting statistics on math anxiety, and the potential effects for comprehension, yielding, and behavioral intentions. The authors also examine math anxiety in a health risk context through an evaluation of the effects of exposure to a message about genetically modified foods on levels of math anxiety. Participants (N = 323) were randomly assigned to read a message that varied the presentation of statistical evidence about potential risks associated with genetically modified foods. Findings reveal that exposure increased levels of math anxiety, with increases in math anxiety limiting yielding. Moreover, math anxiety impaired comprehension but was mediated by perceivers' math confidence and skills. Last, math anxiety facilitated behavioral intentions. Participants who received a text-based message with percentages were more likely to yield than participants who received either a bar graph with percentages or a combined form. Implications are discussed as they relate to math competence and its role in processing health and risk messages.

  1. Continuous Exposure Of Vibrio Anguillarum To Tropodithietic Acid: Genetic Changes And Influence On Virulence

    DEFF Research Database (Denmark)

    Rasmussen, Bastian Barker; D'Alvise, Paul; Grotkjær, Torben

    2015-01-01

    be promising as probiotics in fish rearing. Production of the antibacterial compound tropodithietic acid (TDA) by roseobacters is key in the antagonism of vibrios. However, the effects of continuous exposure to TDA on V. anguillarum remain unknown. The purpose of this study was to investigate how prolonged TDA...... exposure affects V. anguillarum focusing on the development of resistance towards TDA and changes in virulence.Methods: Seven lineages of V. anguillarum were exposed to increasing TDA concentrations over 300-400 generations and were subsequently genome sequenced. Virulence of the lineages is currently...... motor switch protein. However, mutations in this gene were observed in non-exposed controls as well.Conclusions: In conclusion, TDA resistance does not appear to develop, and the virulence genes of V. anguillarum are unaffected by TDA exposure, supporting the application of TDA-producing roseobacters...

  2. Genetic risk for violent behavior and environmental exposure to disadvantage and violent crime: the case for gene-environment interaction.

    Science.gov (United States)

    Barnes, J C; Jacobs, Bruce A

    2013-01-01

    Despite mounds of evidence to suggest that neighborhood structural factors predict violent behavior, almost no attention has been given to how these influences work synergistically (i.e., interact) with an individual's genetic propensity toward violent behavior. Indeed, two streams of research have, heretofore, flowed independently of one another. On one hand, criminologists have underscored the importance of neighborhood context in the etiology of violence. On the other hand, behavioral geneticists have argued that individual-level genetic propensities are important for understanding violence. The current study seeks to integrate these two compatible frameworks by exploring gene-environment interactions (GxE). Two GxEs were examined and supported by the data (i.e., the National Longitudinal Study of Adolescent Health). Using a scale of genetic risk based on three dopamine genes, the analysis revealed that genetic risk had a greater influence on violent behavior when the individual was also exposed to neighborhood disadvantage or when the individual was exposed to higher violent crime rates. The relevance of these findings for criminological theorizing was considered.

  3. High sensitive RNA detection by one-step RT-PCR using the genetically engineered variant of DNA polymerase with reverse transcriptase activity from hyperthermophilies.

    Science.gov (United States)

    Okano, Hiroyuki; Baba, Misato; Kawato, Katsuhiro; Hidese, Ryota; Yanagihara, Itaru; Kojima, Kenji; Takita, Teisuke; Fujiwara, Shinsuke; Yasukawa, Kiyoshi

    2017-10-31

    One-step RT-PCR has not been widely used even though some thermostable DNA polymerases with reverse transcriptase (RT) activity were developed from bacterial and archaeal polymerases, which is owing to low cDNA synthesis activity from RNA. In the present study, we developed highly-sensitive one-step RT-PCR using the single variant of family A DNA polymerase with RT activity, K4pol L329A (L329A), from the hyperthermophilic bacterium Thermotoga petrophila K4 or the 16-tuple variant of family B DNA polymerase with RT activity, RTX, from the hyperthermophilic archaeon Thermococcus kodakarensis. Optimization of reaction condition revealed that the activities for cDNA synthesis and PCR of K4pol L329A and RTX were highly affected by the concentrations of MgCl 2 and Mn(OCOCH 3 ) 2 as well as those of K4pol L329A or RTX. Under the optimized condition, 300 copies/μl of target RNA in 10 μl reaction volumes were successfully detected by the one-step RT-PCR with K4pol L329A or RTX, which was almost equally sensitive enough compared with the current RT-PCR condition using retroviral RT and thermostable DNA polymerase. Considering that K4pol L329A and RTX are stable even at 90-100°C, our results suggest that the one-step RT-PCR with K4pol L329A or RTX is more advantageous than the current one. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  4. Reverse genetic characterization of two paralogous acetoacetyl CoA thiolase genes in Arabidopsis reveals their importance in plant growth and development

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Huanan; Song, Zhihong; Nikolau, Basil J.

    2012-03-31

    Acetoacetyl CoA thiolase (AACT, EC 2.3.1.9) catalyzes the condensation of two acetyl CoA molecules to form acetoacetyl CoA. Two AACT‐encoding genes, At5g47720 (AACT1) and At5g48230 (AACT2), were functionally identified in the Arabidopsis genome by direct enzymological assays and functional expression in yeast. Promoter::GUS fusion experiments indicated that AACT1 is primarily expressed in the vascular system and AACT2 is highly expressed in root tips, young leaves, top stems and anthers. Characterization of T‐DNA insertion mutant alleles at each AACT locus established that AACT2 function is required for embryogenesis and for normal male gamete transmission. In contrast, plants lacking AACT1 function are completely viable and show no apparent growth phenotypes, indicating that AACT1 is functionally redundant with respect to AACT2 function. RNAi lines that express reduced levels of AACT2 show pleiotropic phenotypes, including reduced apical dominance, elongated life span and flowering duration, sterility, dwarfing, reduced seed yield and shorter root length. Microscopic analysis reveals that the reduced stature is caused by a reduction in cell size and fewer cells, and male sterility is caused by loss of the pollen coat and premature degeneration of the tapetal cells. Biochemical analyses established that the roots of AACT2 RNAi plants show quantitative and qualitative alterations in phytosterol profiles. These phenotypes and biochemical alterations are reversed when AACT2 RNAi plants are grown in the presence of mevalonate, which is consistent with the role of AACT2 in generating the bulk of the acetoacetyl CoA precursor required for the cytosol‐localized, mevalonate‐derived isoprenoid biosynthetic pathway.

  5. Genetic variation as a modifier of association between therapeutic exposure and subsequent malignant neoplasms in cancer survivors.

    Science.gov (United States)

    Bhatia, Smita

    2015-03-01

    Subsequent malignant neoplasms (SMNs) are associated with significant morbidity and are a major cause of premature mortality among cancer survivors. Several large studies have demonstrated a strong association between the radiation and/or chemotherapy used to treat primary cancer and the risk of developing SMNs. However, for any given therapeutic exposure, the risk of developing an SMN varies between individuals. Genomic variation can potentially modify the association between therapeutic exposures and SMN risk and may explain the observed interindividual variability. In this review, the author provides a brief overview of the current knowledge regarding the role of genomic variation in the development of therapy-related SMNs and discusses the methodological challenges in undertaking an endeavor to develop a deeper understanding of the molecular underpinnings of therapy-related SMNs, such as an appropriate study design, the identification of an adequately sized study population together with a reliable plan for collecting and maintaining high-quality DNA, clinical validation of the phenotype, and the selection of an appropriate approach or platform for genotyping. Understanding the factors that can modify the risk of treatment-related SMNs is critical to developing targeted intervention strategies and optimizing risk-based health care for cancer survivors. © 2014 American Cancer Society.

  6. Vibrio anguillarum Is Genetically and Phenotypically Unaffected by Long-Term Continuous Exposure to the Antibacterial Compound Tropodithietic Acid

    DEFF Research Database (Denmark)

    Rasmussen, Bastian Barker; Grotkjær, Torben; D'Alvise, Paul

    2016-01-01

    -pathogenic vibrios in fish larvae and live feed cultures for fish larvae. The antibacterial compound tropodithietic acid (TDA), an antiporter that disrupts the proton motive force, is key in the antibacterial activity of several roseobacters. Introducing probiotics on a larger scale requires understanding of any......, and whole-genome sequencing of TDA-exposed lineages and clones revealed few mutational changes, compared to lineages grown without TDA. Amino acid-changing mutations were found in two to six different genes per clone; however, no mutations appeared unique to the TDA-exposed lineages or clones. None...... prevent or reduce bacterial diseases in fish larvae, acting as probiotics. Roseobacters produce the antimicrobial compound tropodithietic acid (TDA), and we were concerned regarding whether long-term exposure to this compound could induce resistance or affect the disease-causing ability of the fish...

  7. Mitochondrial genetic background modifies the relationship between traffic-related air pollution exposure and systemic biomarkers of inflammation.

    Directory of Open Access Journals (Sweden)

    Sharine Wittkopp

    Full Text Available BACKGROUND: Mitochondria are the main source of reactive oxygen species (ROS. Human mitochondrial haplogroups are linked to differences in ROS production and oxidative-stress induced inflammation that may influence disease pathogenesis, including coronary artery disease (CAD. We previously showed that traffic-related air pollutants were associated with biomarkers of systemic inflammation in a cohort panel of subjects with CAD in the Los Angeles air basin. OBJECTIVE: We tested whether air pollutant exposure-associated inflammation was stronger in mitochondrial haplogroup H than U (high versus low ROS production in this panel (38 subjects and 417 observations. METHODS: Inflammation biomarkers were measured weekly in each subject (≤ 12 weeks, including interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, C-reactive protein, interleukin-6 soluble receptor and tumor necrosis factor-soluble receptor II. We determined haplogroup by restriction fragment length polymorphism analysis. Air pollutants included nitrogen oxides (NOx, carbon monoxide (CO, organic carbon, elemental and black carbon (EC, BC; and particulate matter mass, three size fractions (<0.25 µm, 0.25-2.5 µm, and 2.5-10 µm in aerodynamic diameter. Particulate matter extracts were analyzed for organic compounds, including polycyclic aromatic hydrocarbons (PAH, and in vitro oxidative potential of aqueous extracts. Associations between exposures and biomarkers, stratified by haplogroup, were analyzed by mixed-effects models. RESULTS: IL-6 and TNF-α were associated with traffic-related air pollutants (BC, CO, NOx and PAH, and with mass and oxidative potential of quasi-ultrafine particles <0.25 µm. These associations were stronger for haplogroup H than haplogroup U. CONCLUSIONS: Results suggest that mitochondrial haplogroup U is a novel protective factor for air pollution-related systemic inflammation in this small group of subjects.

  8. Association Between Myopia, Ultraviolet B Radiation Exposure, Serum Vitamin D Concentrations, and Genetic Polymorphisms in Vitamin D Metabolic Pathways in a Multicountry European Study.

    Science.gov (United States)

    Williams, Katie M; Bentham, Graham C G; Young, Ian S; McGinty, Ann; McKay, Gareth J; Hogg, Ruth; Hammond, Christopher J; Chakravarthy, Usha; Rahu, Mati; Seland, Johan; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Fletcher, Astrid E

    2017-01-01

    Myopia is becoming increasingly common globally and is associated with potentially sight-threatening complications. Spending time outdoors is protective, but the mechanism underlying this association is poorly understood. To examine the association of myopia with ultraviolet B radiation (UVB; directly associated with time outdoors and sunlight exposure), serum vitamin D concentrations, and vitamin D pathway genetic variants, adjusting for years in education. A cross-sectional, population-based random sample of participants 65 years and older was chosen from 6 study centers from the European Eye Study between November 6, 2000, to November 15, 2002. Of 4187 participants, 4166 attended an eye examination including refraction, gave a blood sample, and were interviewed by trained fieldworkers using a structured questionnaire. Myopia was defined as a mean spherical equivalent of -0.75 diopters or less. Exclusion criteria included aphakia, pseudophakia, late age-related macular degeneration, and vision impairment due to cataract, resulting in 371 participants with myopia and 2797 without. Exposure to UVB estimated by combining meteorological and questionnaire data at different ages, single-nucleotide polymorphisms in vitamin D metabolic pathway genes, serum vitamin D3 concentrations, and years of education. Odds ratios (ORs) of UVB, serum vitamin D3 concentrations, vitamin D single-nucleotide polymorphisms, and myopia estimated from logistic regression. Of the included 3168 participants, the mean (SD) age was 72.4 (5) years, and 1456 (46.0%) were male. An SD increase in UVB exposure at age 14 to 19 years (OR, 0.81; 95% CI, 0.71-0.92) and 20 to 39 years (OR, 0.7; 95% CI, 0.62-0.93) was associated with a reduced adjusted OR of myopia; those in the highest tertile of years of education had twice the OR of myopia (OR, 2.08; 95% CI, 1.41-3.06). No independent associations between myopia and serum vitamin D3 concentrations nor variants in genes associated with vitamin D

  9. Ozone exposure, vitamin C intake, and genetic susceptibility of asthmatic children in Mexico City: a cohort study

    Directory of Open Access Journals (Sweden)

    Moreno-Macías Hortensia

    2013-02-01

    Full Text Available Abstract Background We previously reported that asthmatic children with GSTM1 null genotype may be more susceptible to the acute effect of ozone on the small airways and might benefit from antioxidant supplementation. This study aims to assess the acute effect of ozone on lung function (FEF25-75 in asthmatic children according to dietary intake of vitamin C and the number of putative risk alleles in three antioxidant genes: GSTM1, GSTP1 (rs1695, and NQO1 (rs1800566. Methods 257 asthmatic children from two cohort studies conducted in Mexico City were included. Stratified linear mixed models with random intercepts and random slopes on ozone were used. Potential confounding by ethnicity was assessed. Analyses were conducted under single gene and genotype score approaches. Results The change in FEF25-75 per interquartile range (60 ppb of ozone in persistent asthmatic children with low vitamin C intake and GSTM1 null was −91.2 ml/s (p = 0.06. Persistent asthmatic children with 4 to 6 risk alleles and low vitamin C intake showed an average decrement in FEF25-75 of 97.2 ml/s per 60 ppb of ozone (p = 0.03. In contrast in children with 1 to 3 risk alleles, acute effects of ozone on FEF25-75 did not differ by vitamin C intake. Conclusions Our results provide further evidence that asthmatic children predicted to have compromised antioxidant defense by virtue of genetic susceptibility combined with deficient antioxidant intake may be at increased risk of adverse effects of ozone on pulmonary function.

  10. The fitness consequences of environmental sex reversal in fish: a quantitative review.

    Science.gov (United States)

    Senior, Alistair McNair; Nat Lim, Jiahui; Nakagawa, Shinichi

    2012-11-01

    Environmental sex reversal (ESR) occurs when environmental factors overpower genetic sex-determining factors. The phenomenon of ESR is observed widely in teleost species, where it can be induced by exposing developing fish to endocrine disrupting chemicals (EDCs). EDC-induced ESR has been exploited by the aquaculture industry, while ecological and evolutionary models are also beginning to elucidate the potential roles that sex-reversed individuals play in influencing population dynamics. However, how EDC exposure affects individual fitness remains relatively unknown. To date, many experimental studies have induced sex reversal in fish and measured fitness-as indicated by related traits such as size, survival and gonadal somatic index (GSI), but the reported results vary. Here, we meta-analytically combine the results of 78 studies of induced ESR to gain insight into the fitness of sex-reversed individuals. Overall, our results suggest that the fitness of fish exposed to EDCs is reduced at the time of exposure, with exposed individuals having a smaller size and likely a smaller GSI. Given a period of non-exposure, fish treated with EDCs can regain a size equal to those not exposed, although GSI remains compromised. Interestingly, survival does not appear to be affected by EDC treatment. The published reports that comprise our dataset are, however, based on captive fish and the general small size resulting from exposure is likely to lead to reduced survival in the wild. Additionally, reduced fitness-related parameters are likely to be due to exposure to EDCs rather than ESR itself. We suggest that theoretical models of ESR should account for the fitness-related effects that we report. Whilst we are able to shed light on the physical fitness of EDC-exposed fish, the behaviour of such individuals remains largely untested and should be the focus of future experimental manipulation. © 2012 The Authors. Biological Reviews © 2012 Cambridge Philosophical Society.

  11. Managing Reverse Logistics or Reversing Logistics Management?

    OpenAIRE

    Brito, Marisa

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse logistics. The thesis brings insights on reverse logistics decision-making and it lays down theoretical principles for reverse logistics as a research field.In particular it puts together a framework ...

  12. Genetics Home Reference: hyperprolinemia

    Science.gov (United States)

    ... converting it to the amino acid glutamate. The conversion between proline and glutamate, and the reverse reaction ... Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related ...

  13. Effect modification by vitamin D receptor genetic polymorphisms in the association between cumulative lead exposure and pulse pressure: a longitudinal study.

    Science.gov (United States)

    Jhun, Min A; Hu, Howard; Schwartz, Joel; Weisskopf, Marc G; Nie, Linda H; Sparrow, David; Vokonas, Pantel S; Park, Sung Kyun

    2015-01-13

    Although the association between lead and cardiovascular disease is well established, potential mechanisms are still poorly understood. Calcium metabolism plays a role in lead toxicity and thus, vitamin D receptor (VDR) polymorphisms have been suggested to modulate the association between lead and health outcomes. We investigated effect modification by VDR genetic polymorphisms in the association between cumulative lead exposure and pulse pressure, a marker of arterial stiffness. We examined 727 participants (3,100 observations from follow-ups from 1991 to 2011) from the Normative Aging Study (NAS), a longitudinal study of aging. Tibia and patella bone lead levels were measured using K-x-ray fluorescence. Four single nucleotide polymorphisms (SNPs) in the VDR gene, Bsm1, Taq1, Apa1, and Fok1, were genotyped. Linear mixed effects models with random intercepts were implemented to take into account repeated measurements. Adjusting for potential confounders, pulse pressure was 2.5 mmHg (95% CI: 0.4-4.7) and 1.9 mmHg (95% CI: 0.1-3.8) greater per interquartile range (IQR) increase in tibia lead (15 μg/g) and patella lead (20 μg/g), respectively, in those with at least one minor frequency allele in Bsm1 compared with those with major frequency allele homozygotes. The observed interaction effect between bone lead and the Bsm1 genotype persists over time during the follow-up. Similar results were observed in effect modification by Taq1. This study suggests that subjects with the minor frequency alleles of VDR Bsm1 or Taq1 may be more susceptible to cumulative lead exposure-related elevated pulse pressure.

  14. Genetic variation in Glutathione S-Transferase Omega-1, Arsenic Methyltransferase and Methylene-tetrahydrofolate Reductase, arsenic exposure and bladder cancer: a case–control study

    Directory of Open Access Journals (Sweden)

    Beebe-Dimmer Jennifer L

    2012-06-01

    Full Text Available Abstract Background Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer. Methods Single nucleotide polymorphisms (SNPs in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a case–control study in Southeastern Michigan and exposed to low to moderate ( Results While no single SNP in As3MT was significantly associated with bladder cancer overall, several SNPs were associated with bladder cancer among those exposed to higher arsenic levels. Individuals with one or more copies of the C allele in rs11191439 (the Met287Thr polymorphism had an elevated risk of bladder cancer (OR = 1.17; 95% CI = 1.04-1.32 per 1 μg/L increase in average exposure. However, no association was observed between average arsenic exposure and bladder cancer among TT homozygotes in the same SNP. Bladder cancer cases were also 60% less likely to be homozygotes for the A allele in rs1476413 in MTHFR compared to controls (OR = 0.40; 95% CI = 0.18-0.88. Conclusions Variation in As3MT and MTHFR is associated with bladder cancer among those exposed to relatively low concentrations of inorganic arsenic. Further investigation is warranted to confirm these findings.

  15. Managing Reverse Logistics or Reversing Logistics Management?

    NARCIS (Netherlands)

    M.P. de Brito (Marisa)

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse

  16. Reversible Thermoset Adhesives

    Science.gov (United States)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  17. Genetic GIScience

    DEFF Research Database (Denmark)

    Jacquez, Geoffrey; Sabel, Clive E; Shi, Chen

    2015-01-01

    The exposome, defined as the totality of an individual's exposures over the life course, is a seminal concept in the environmental health sciences. Although inherently geographic, the exposome as yet is unfamiliar to many geographers. This article proposes a place-based synthesis, genetic...... geographic information science (genetic GIScience), that is founded on the exposome, genome+, and behavome. It provides an improved understanding of human health in relation to biology (the genome+), environmental exposures (the exposome), and their social, societal, and behavioral determinants (the behavome......). Genetic GIScience poses three key needs: first, a mathematical foundation for emergent theory; second, process-based models that bridge biological and geographic scales; third, biologically plausible estimates of space?time disease lags. Compartmental models are a possible solution; this article develops...

  18. Forward and reverse mutagenesis in C. elegans.

    Science.gov (United States)

    Kutscher, Lena M; Shaham, Shai

    2014-01-17

    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.

  19. Reverse logistics - a framework

    OpenAIRE

    Brito, Marisa; Dekker, Rommert

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of products, processes and actors. In addition we provide a decision framework for Reverse Logistics and we present it according to long, medium and short term decisions, i.e. strategic-tactic-operational decis...

  20. Reverse logistics - a framework

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); R. Dekker (Rommert)

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of

  1. Factors predisposing to coma and delirium: fentanyl and midazolam exposure; CYP3A5, ABCB1, and ABCG2 genetic polymorphisms; and inflammatory factors.

    Science.gov (United States)

    Skrobik, Yoanna; Leger, Caroline; Cossette, Mariève; Michaud, Veronique; Turgeon, Jacques

    2013-04-01

    Delirium and sedative-induced coma are described as incremental manifestations of cerebral dysfunction. Both may be associated with sedative or opiate doses and pharmacokinetic or pharmacogenetic variables, such as drug plasma levels (exposure), drug metabolism, and/or their transport across the blood-brain barrier. To compare biological and drug treatment characteristics in patients with coma and/or delirium while in the ICU. In 99 patients receiving IV fentanyl, midazolam, or both, we evaluated drug doses, covariates likely to influence drug effects (age, body mass index, and renal and hepatic dysfunction); delirium risk factors; concomitant administration of CYP3A and P-glycoprotein substrates/inhibitors; ABCB1, ABCG2, and CYP3A5 genetic polymorphisms; and fentanyl and midazolam plasma levels. Delirium and coma were evaluated daily. In patients with only coma (n=15), only delirium (n=7), and neither ever (n=14), we measured plasma levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-1RA, IL-6, IL-8, IL-10, IL-17,macrophage inflammatory protein-1β, and monocyte chemotactic protein-1. Time to first coma was associated with fentanyl and midazolam doses (p=0.03 and p=0.01, respectively). The number of days in coma was associated with the number of days of coadministration of CYP3A inhibitors (r=0.30; p=0.006). Plasma levels of fentanyl were higher in patients with clinical coma (3.7±4.7 vs. 2.0±1.8 ng/mL, p=0.0001) as were midazolam plasma levels (1050±2232 vs. 168±249 ng/mL, p=0.0001). Delirium occurrence was unrelated to midazolam administration, cumulative doses, or serum levels. Days with delirium were associated with days of coadministration of P-glycoprotein inhibitor (r=0.35; p=0.0004). Delirious patients had higher levels of the inflammatory mediator IL-6 than comatose patients (129.3 vs. 35.0 pg/mL, p=0.05). Coma is associated with fentanyl and midazolam exposure; delirium is unrelated to midazolam and may be linked to inflammatory status

  2. Genetic Aspects of Epilepsy

    African Journals Online (AJOL)

    mine the advisability of marriage, rather than genetic considerations, in view of the low penetrance of the gene. S. Air. Med. J., 48, 603 (1974). My delight in the field of genetics, so far from being an amiable foible, springs from what I call the. Paradox of Reversibility. This implies that once the origin of a pathological condition ...

  3. Increased rodenticide exposure rate and risk of toxicosis in barn owls (Tyto alba) from southwestern Canada and linkage with demographic but not genetic factors.

    Science.gov (United States)

    Huang, Andrew C; Elliott, John E; Hindmarch, Sofi; Lee, Sandi L; Maisonneuve, France; Bowes, Victoria; Cheng, Kimberly M; Martin, Kathy

    2016-08-01

    Among many anthropogenic drivers of population decline, continual rapid urbanization and industrialization pose major challenges for the survival of wildlife species. Barn owls (Tyto alba) in southwestern British Columbia (BC) face a multitude of threats ranging from habitat fragmentation to vehicle strikes. They are also at risk from secondary poisoning of second-generation anticoagulant rodenticides (SGARs), a suite of toxic compounds which at high doses results in a depletion of blood clotting factors leading to internal bleeding and death. Here, using long-term data (N = 119) for the hepatic residue levels of SGAR, we assessed the risk of toxicosis from SGAR for the BC barn owl population over the past two decades. We also investigated whether sensitivity to SGAR is associated with genetic factors, namely Single Nucleotide Polymorphisms (SNPs) found in the CYP2C45 gene of barn owls. We found that residue concentration for total SGAR was significantly higher in 2006-2013 (141 ng/g) relative to 1992-2003 (57 ng/g). The proportion of owls exposed to multiple SGAR types was also significantly higher in 2006-2013. Those measures accordingly translate directly into an increase in toxicosis risk level. We also detected demographic differences, where adult females showed on average lower concentration of total SGAR (64 ng/g) when compared to adult males (106 ng/g). Juveniles were overall more likely to show signs of toxicosis than adults (33.3 and 6.9 %, respectively), and those symptoms were positively predicted by SGAR concentrations. We found no evidence that SNPs in the CYP2C45 gene of barn owls were associated with intraspecific variation in SGAR sensitivity. We recommend several preventative measures be taken to minimize wildlife exposure to SGAR.

  4. Biological monitoring the exposure to polycyclic aromatic hydrocarbons of coke oven workers in relation to smoking and genetic polymorphisms for GSTM1 GSTT1

    NARCIS (Netherlands)

    Delft, J.H.M. van; Steenwinkel, M.-J.S.T.; Asten, J.G. van; Vogel, N. de; Bruijntjes-Rozier, T.C.D.M.; Schouten, T.; Cramers, P.; Maas, L.; Herwijnen, M.H. van; Schooten, F.-J. van; Hopmans, P.M.J.

    2001-01-01

    Occupational exposure to polycyclic aromatic hydrocarbons (PAH) increases the risk of developing lung cancer. Human exposure is often demonstrated by increased internal levels of PAH metabolites and of markers for early biological effects, like DNA adducts and cytogenetic aberrations. Objective:

  5. Sex-specific characterization and evaluation of the Alzheimer's disease genetic risk factor sorl1 in zebrafish during aging and in the adult brain following a 100 ppb embryonic lead exposure.

    Science.gov (United States)

    Lee, Jinyoung; Peterson, Samuel M; Freeman, Jennifer L

    2017-04-01

    Developmental lead (Pb) exposure is suggested in laboratory studies to be a trigger for neurodegenerative diseases such as Alzheimer's disease (AD). Sortilin-related receptor, L (DLR class) A repeats-containing (SORL1) is a recently identified AD genetic risk factor. SORL1 has limited characterization in vertebrate models in comparison to other AD genetic risk factors. To characterize SORL1 further, protein sequence homology between humans, mice and zebrafish was analyzed and showed conservation of functional repeats and domain orientation. Next, spatial expression of sorl1 in zebrafish larvae was completed and diffuse expression in neural tissue that was not restricted to the brain was observed. Influences of sex and age on quantitative expression of sorl1 in the brain of adult zebrafish were then assessed. Sex-specific alteration of sorl1 expression transpired during the aging process in females. The zebrafish was then utilized to investigate the impacts of a 100 ppb embryonic Pb exposure on sorl1 expression and other known AD genetic risk factors. Sex-specific quantitative gene expression analysis was completed with adult zebrafish brain to compare those developmentally exposed to Pb or a control treatment, but no significant difference in sorl1 expression or other AD genetic risk factors was observed. Overall, this study provided characterization of sorl1 with changes in brain expression during aging being female-specific. This finding is in agreement with females being more prone to the onset of AD, but analysis of additional AD genetic risk factors is needed to facilitate our understanding of the impact of a 100 ppb embryonic Pb exposure. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Genetic Restoration of the Florida Panther

    National Research Council Canada - National Science Library

    Warren E. Johnson; David P. Onorato; Melody E. Roelke; E. Darrell Land; Mark Cunningham; Robert C. Belden; Roy McBride; Deborah Jansen; Mark Lotz; David Shindle; JoGayle Howard; David E. Wildt; Linda M. Penfold; Jeffrey A. Hostetler; Madan K. Oli; Stephen J. O’Brien

    2010-01-01

    .... In 1995, conservation managers translocated eight female pumas ( P. c. stanleyana ) from Texas to increase depleted genetic diversity, improve population numbers, and reverse indications of inbreeding depression...

  7. Introduction to reversible computing

    CERN Document Server

    Perumalla, Kalyan S

    2013-01-01

    Few books comprehensively cover the software and programming aspects of reversible computing. Filling this gap, Introduction to Reversible Computing offers an expanded view of the field that includes the traditional energy-motivated hardware viewpoint as well as the emerging application-motivated software approach. Collecting scattered knowledge into one coherent account, the book provides a compendium of both classical and recently developed results on reversible computing. It explores up-and-coming theories, techniques, and tools for the application of rever

  8. Reversal of resistance to pyriproxyfen in the Q biotype of Bemisia tabaci (Hemiptera: Aleyrodidae).

    Science.gov (United States)

    Wilson, Margaret; Moshitzky, Pnina; Laor, Einat; Ghanim, Murad; Horowitz, A Rami; Morin, Shai

    2007-08-01

    Pyriproxyfen, a juvenile hormone (JH) mimic, is a biorational insecticide that disrupts insect development. It is one of the principal insecticides being used to control Bemisia tabaci (Gennadius) on cotton, and has many environmentally positive attributes that make it compatible with integrated pest management (IPM) programs. In Israel, a high level of resistance to pyriproxyfen has been observed in several isolated regions. Here, tests were conducted to establish whether temporal refuges from exposure to pyriproxyfen could be useful for restoring the effectiveness of the compound. Resistance was found to decrease by a factor of 8 when exposure to pyriproxyfen was ceased for 13 generations. Reversal of resistance was accompanied with increased biotic fitness of the revertant colony. By incorporating experimental estimates of nymph survival, sex ratio, fecundity, egg hatching rate and developmental time, the seasonal cost per generation for resistant insects was estimated to be 25%. A genetic simulation model, optimized by empirical data from bioassays, predicted fitness cost per generation of 19% for resistant homozygous (RR) females and hemizygous (R) males, and produced rates of reversal similar to the experimental results. The model also predicted that, even after 5 years ( approximately 55 generations) without pyriproxyfen treatments, the frequency of the resistance allele (R) will still remain high (0.02). It is therefore concluded, on the basis of experimental and modeling results, that the effectiveness of temporal refuges for reversing development of resistance to pyriproxyfen in B. tabaci may be limited. Copyright (c) 2007 Society of Chemical Industry

  9. Reverse Core Engine with Thrust Reverser

    Science.gov (United States)

    Suciu, Gabriel L. (Inventor); Chandler, Jesse M. (Inventor)

    2017-01-01

    An engine system has a gas generator, a bi-fi wall surrounding at least a portion of the gas generator, a casing surrounding a fan, and the casing having first and second thrust reverser doors which in a deployed position abut each other and the bi-fi wall.

  10. Myocardial reverse remodeling.

    Science.gov (United States)

    Hellawell, Jennifer L; Margulies, Kenneth B

    2012-06-01

    Despite an extensive literature defining the mechanisms and significance of pathological myocardial remodeling, there has been no comprehensive review of the inverse process, often labeled reverse remodeling. Accordingly, the goal of this review is to overview the varied settings in which clinically significant reverse remodeling has been well documented. When available, we reviewed relevant randomized, controlled clinical trials, and meta-analyses with sufficient cardiac imaging data to permit conclusions about reverse remodeling. When these types of studies were not available, relevant case-control studies and case series that employed appropriate methodology were reviewed. Regression of pathological myocardial hypertrophy, chamber shape distortions, and dysfunction occurs in a wide variety of settings. Although reverse remodeling occurs spontaneously in some etiologies of myocardial dysfunction and failure, remodeling is more commonly observed in response to medical, device-based, or surgical therapies, including β-blockers, revascularization, cardiac resynchronization therapy, and valve surgery. Indeed, reverse remodeling following pathophysiologically targeted interventions helps validate that the targeted mechanisms are propelling and/or sustaining pathological remodeling. The diverse clinical settings in which reverse remodeling has been observed demonstrates that myocardial remodeling is bidirectional and occurs across the full spectrum of myocardial disease severity, duration, and etiology. Observations in several settings suggest that recovered hearts are not truly normal despite parallel improvements at organ, tissue, and cellular level. Nevertheless, the link between reverse remodeling and improved outcomes should inspire further research to better understand the mechanisms responsible for both reverse remodeling and persistent deviations from normalcy. © 2010 Blackwell Publishing Ltd.

  11. Extremely low frequency electromagnetic field exposure causes cognitive impairment associated with alteration of the glutamate level, MAPK pathway activation and decreased CREB phosphorylation in mice hippocampus: reversal by procyanidins extracted from the lotus seedpod.

    Science.gov (United States)

    Duan, Yuqing; Wang, Zhigao; Zhang, Haihui; He, Yuanqing; Fan, Rong; Cheng, Yanxiang; Sun, Guibo; Sun, Xiaobo

    2014-09-01

    Lotus seedpod procyanidins (LSPCs) could effectively prevent learning and memory damage and oxidative damage caused by extremely low frequency electromagnetic field (ELF-EMF) exposure. However, LSPCs protect neurons from ELF-EMF-induced damage by mechanisms currently not clear. An excessive release of glutamate is considered to be one of the molecular mechanisms of neuronal damage in several neurological diseases. In this study we determined whether the ELF-EMF (50 Hz, 8 mT, 28 days) exposure induced alterations of glutamate release in mice hippocampus and explored the possible mechanism, and if LSPC treatment normalized its alterations. The results showed that ELF-EMF exposure induced the increased contents of glutamate, GABA, excessively activated NMDA receptors, increasing the number of NMDA receptor 2B (NR2B) and intracellular Ca(2+) concentration [Ca(2+)]i in hippocampus. In addition, ELF-EMF exposure decreased the ERK1/2 and CREB phosphorylation, which suggested that the Ca(2+) influx induced by the ELF-EMF exposure stimulated activity of the ERK, in turn, influences the expression of downstream proteins in this signaling pathway. Besides, ELF-EMF exposure also increased JNK1/2 phosphorylation through the activated ASK1, which plays a pivotal role in hippocampal neuronal cell death. However, oral administration of LSPCs (especially 60 and 90 mg kg(-1)) markedly improved expressions of p-CREB, p-ERK1/2 and p-JNK1/2, accompanied by decreased levels of glutamate, GABA, [Ca(2+)]i and NR2B. Thus, the results from the present study suggest that p-ERK1/2, p-JNK1/2, [Ca(2+)]i and p-CREB expression normalized, possibly via a NMDA receptor-channel through the changes of GABA, glutamate and NR2B, which might be responsible for the neuroprotective or memory enhancing effects of LSPCs.

  12. Genotype and toxicity relationships among Hyalella azteca: I. Acute exposure to metals or low pH

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Y.; Guttman, S.I.; Oris, J.T.; Bailer, A.J.

    2000-05-01

    Comparative genotype and toxin interactions at three polymorphic enzyme loci were examined in a laboratory population of amphipods (Hyalella azteca) during acute exposure to cadmium, zinc, copper, lead, or low pH. Significant toxin-genotype interactions were observed using logistic regression to model mortality in ten of 15 analyses. Both stressor-specific and nonspecific modes of selection were observed. In general, low pH selected for different genotypes than those selected by metals, especially zinc. Different modes of selection were also observed when amphipods were exposed to different metals. These results suggest that exposure to low pH would significantly reduce the ability of H. azteca to survive subsequent contamination by metals; exposure to stressors in the reverse order would also compromise a population's chance of survival. A genetic distance analysis showed that the magnitude of genetic differentiation consistently increased among survivors compared with that of the initial populations. These increases in genetic divergence estimates suggest that acute exposure to metals or low pH may have an evolutionarily significant impact on the species. They also suggest that both genotype frequency and genetic distance measures (based on allozyme data) may be used as bioindicators for environmental monitoring programs. Validation of such bioindicators requires an understanding of the population's genetic background, genetic structure, and history.

  13. Direct oral anticoagulant reversal

    DEFF Research Database (Denmark)

    Dzeshka, Mikhail S; Pastori, Daniele; Lip, Gregory Y H

    2017-01-01

    to manage bleeding depending on severity, with a particular focus on specific reversal agents, are discussed. Expert commentary: Due to short half-life of NOACs compared to warfarin, discontinuation of drug, mechanical compression, and volume substitution are considered to be sufficient measures in most...... of bleeding cases. In case of life-threatening bleeding or urgent surgery, hemostasis can be achieved with non-specific reversal agents (prothrombin complex concentrates) in patients treated with factor Xa inhibitor until specific antidotes (andexanet α and ciraparantag) will receive approval. Thus far......, idarucizumab has been the only reversal agent approved for dabigatran....

  14. Cigarette smoke-induced effects on bone marrow B-cell subsets and CD4+:CD8+ T-cell ratios are reversed by smoking cessation: influence of bone mass on immune cell response to and recovery from smoke exposure.

    Science.gov (United States)

    Fusby, Jenny S; Kassmeier, Michele D; Palmer, Victoria L; Perry, Greg A; Anderson, Dirk K; Hackfort, Bryan T; Alvarez, Gwen K; Cullen, Diane M; Akhter, Mohammed P; Swanson, Patrick C

    2010-08-01

    Cigarette smoking adversely affects the immune system, and is a risk factor for developing osteoporosis. How smoking contributes to osteoporosis is unclear, but since lymphocytes help maintain bone homeostasis and lymphocyte depletion results in bone loss, one potential mechanism for how smoke exposure promotes osteoporosis is by reducing bone marrow lymphocytes. Since the risk for developing osteoporosis is reportedly greater in smokers with polymorphisms in LRP5, a gene involved in canonical Wnt signaling that regulates bone metabolism, smoking-induced effects on lymphocytes may be influenced by Lrp5 functionality. To test these possibilities, we examined how the duration and cessation of cigarette smoke exposure affects lymphocyte distribution and function in normal mice and mice predisposed to low or high bone mass due to disruption or mutation of Lrp5. We find that, independent of genotype, mice exposed to cigarette smoke for 3-12 weeks showed a significant reduction in bone marrow B220(+)CD43(-) B cells and splenic transitional T1 B cells, and exhibited a splenic CD4(+):CD8(+) T-cell ratio that was skewed toward CD8(+) T cells. Smoke exposure had little or no effect on other lymphocyte subsets or on lymphocyte function ex vivo. Interestingly, these differences were no longer apparent after 6 weeks without smoke exposure, except in mice with high bone mass where bone marrow B220(+)CD43(-) B cells failed to fully recover. These data provide the first evidence that smoke exposure reduces bone marrow B cells, providing a plausible mechanism for how smoking contributes to osteoporosis.

  15. An algebra of reversible computation.

    Science.gov (United States)

    Wang, Yong

    2016-01-01

    We design an axiomatization for reversible computation called reversible ACP (RACP). It has four extendible modules: basic reversible processes algebra, algebra of reversible communicating processes, recursion and abstraction. Just like process algebra ACP in classical computing, RACP can be treated as an axiomatization foundation for reversible computation.

  16. Reversible flowchart languages and the structured reversible program theorem

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    Many irreversible computation models have reversible counterparts, but these are poorly understood at present. We introduce reversible flowcharts with an assertion operator and show that any reversible flowchart can be simulated by a structured reversible flowchart using only three control flow o...... justification for low-level machine code for reversible microprocessors as well as high-level block-structured reversible languages. We give examples for both such languages and illustrate them with a lossless encoder for permutations given by Dijkstra....

  17. Tubal Ligation Reversal

    Science.gov (United States)

    ... and other factors. Success rates may be as high as 80 percent or as low as near 40 percent depending on your circumstances. Tubal ligation reversal is abdominal surgery, which carries a risk of infection, bleeding and ...

  18. Sex reversal in vertebrates

    OpenAIRE

    2016-01-01

    This special topic issue of Sexual Development gives an overview of sex reversal in vertebrates, from fishes naturally changing their sex, to rodents escaping the mammalian SRY-determining system. It offers eight up-to-date reviews on specific subjects in sex reversal, considering fishes, amphibians, reptiles, birds, marsupials, and placental mammals, including humans. The broad scope of represented animals makes this ideal for students and researchers, especially those interested in the...

  19. PROCESSING REVERSE LOGISTICS INVENTORIES

    OpenAIRE

    Bajor, Ivona; Novačko, Luka; Ogrizović, Dario

    2014-01-01

    Developed logistics systems have organized reverse logistics flows and are continuously analyzing product returns, tending to detect patterns in oscillations of returning products in certain time periods. Inventory management in reverse logistics systems depends on different criteria, regarding goods categories, formed contracts between subjects of supply chains, uncertainty in manufacturer’s quantities of DOA (dead on arrival) products, etc. The developing logistics systems, such as the Croa...

  20. Early sorafenib-induced toxicity is associated with drug exposure and UGTIA9 genetic polymorphism in patients with solid tumors: a preliminary study.

    Directory of Open Access Journals (Sweden)

    Pascaline Boudou-Rouquette

    Full Text Available BACKGROUND: Identifying predictive biomarkers of drug response is of key importance to improve therapy management and drug selection in cancer therapy. To date, the influence of drug exposure and pharmacogenetic variants on sorafenib-induced toxicity remains poorly documented. The aim of this pharmacokinetic/pharmacodynamic (PK/PD study was to investigate the relationship between early toxicity and drug exposure or pharmacogenetic variants in unselected adult outpatients treated with single-agent sorafenib for advanced solid tumors. METHODS: Toxicity was recorded in 54 patients on days 15 and 30 after treatment initiation and sorafenib exposure was assessed in 51 patients. The influence of polymorphisms in CYP3A5, UGT1A9, ABCB1 and ABCG2 was examined in relation to sorafenib exposure and toxicity. Clinical characteristics, drug exposure and pharmacogenetic variants were tested univariately for association with toxicities. Candidate variables with p<0.1 were analyzed in a multivariate analysis. RESULTS: Gender was the sole parameter independently associated with sorafenib exposure (p = 0.0008. Multivariate analysis showed that increased cumulated sorafenib (AUC(cum was independently associated with any grade ≥ 3 toxicity (p = 0.037; UGT1A9 polymorphism (rs17868320 with grade ≥ 2 diarrhea (p = 0.015 and female gender with grade ≥ 2 hand-foot skin reaction (p = 0.018. Using ROC curve, the threshold AUC(cum value of 3,161 mg/L.h was associated with the highest risk to develop any grade ≥ 3 toxicity (p = 0.018. CONCLUSION: In this preliminary study, increased cumulated drug exposure and UGT1A9 polymorphism (rs17868320 identified patients at high risk for early sorafenib-induced severe toxicity. Further PK/PD studies on larger population are warranted to confirm these preliminary results.

  1. Exposure to maternal obesogenic diet worsens some but not all pre-cancer phenotypes in a murine genetic model of prostate cancer.

    Directory of Open Access Journals (Sweden)

    Theresa Okeyo-Owuor

    Full Text Available Prostate cancer research has been predominantly focused on adult exposures and risk factors. However, because the prostate develops during gestation and early life, exposure to external factors, such as obesity, during development could affect the prostate cancer progression in adults. Our previous work demonstrated that exposure to a high fat/high sugar (HF/HS diet during gestation and until weaning stimulated prostate hyperplasia and altered the Pten/Akt pathway in adult mice fed a normal diet after weaning. Here, we asked whether maternal exposure to HF/HS would worsen prostate phenotypes in mice lacking Pten, a widely accepted driver of prostate cancer. We found that, at six weeks of age, both Chow (control-and HF/HS-exposed Pten knockout mice showed evidence of murine PIN that included ducts with central comedo necrosis but that the HF/HS exposure did not influence murine PIN progression. The Pten knockout mice exposed to HF/HS in utero had significantly more mitotic cells than Pten knockouts exposed to Chow diet. In the Pten null background, the maternal HF/HS diet enhanced proliferation but did not have an additive effect on Akt activation. We observed neuroendocrine differentiation in Pten knockout mice, a phenotype that had not been previously described in this model.

  2. Children's exposure to environmental pollutants and biomarkers of genetic damage. II. Results of a comprehensive literature search and meta-analysis

    DEFF Research Database (Denmark)

    Neri, Monica; Ugolini, Donatella; Bonassi, Stefano

    2005-01-01

    aberrations (CA) and micronuclei (MN) but not sister chromatid exchanges (SCE) were found consistently increased in children exposed to environmental pollutants. Meta-analysis of the studies reporting SCE in cord blood showed similar levels of SCE in exposed and in non-exposed newborns. Exposure to airborne......-DNA adducts were found in fetal than in maternal tissue, suggesting a specific susceptibility of the fetus to this class of ubiquitous environmental pollutants. According to these findings, future research and biomonitoring programs on children would greatly benefit from the inclusion of selected biomarkers...... pollutants, soil and drinking water contaminants, mostly increased CA and, to a lesser extent, MN levels in children. The effect of exposure to airborne urban pollutants was consistently reported by field studies measuring DNA, albumin and hemoglobin adducts. Prenatal (in utero) and postnatal exposure...

  3. Reversible Communicating Processes

    Directory of Open Access Journals (Sweden)

    Geoffrey Brown

    2016-02-01

    Full Text Available Reversible distributed programs have the ability to abort unproductive computation paths and backtrack, while unwinding communication that occurred in the aborted paths. While it is natural to assume that reversibility implies full state recovery (as with traditional roll-back recovery protocols, an interesting alternative is to separate backtracking from local state recovery. For example, such a model could be used to create complex transactions out of nested compensable transactions where a programmer-supplied compensation defines the work required to "unwind" a transaction. Reversible distributed computing has received considerable theoretical attention, but little reduction to practice; the few published implementations of languages supporting reversibility depend upon a high degree of central control. The objective of this paper is to demonstrate that a practical reversible distributed language can be efficiently implemented in a fully distributed manner. We discuss such a language, supporting CSP-style synchronous communication, embedded in Scala. While this language provided the motivation for the work described in this paper, our focus is upon the distributed implementation. In particular, we demonstrate that a "high-level" semantic model can be implemented using a simple point-to-point protocol.

  4. Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition : a meta-analysis

    NARCIS (Netherlands)

    Jansen-van der Weide, Marijke C.; Greuter, Marcel J. W.; Jansen, Liesbeth; Oosterwijk, Jan C.; Pijnappel, Ruud M.; de Bock, Geertruida H.

    2010-01-01

    Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the

  5. MPA-capped CdTe quantum dots exposure causes neurotoxic effects in nematode Caenorhabditis elegans by affecting the transporters and receptors of glutamate, serotonin and dopamine at the genetic level, or by increasing ROS, or both

    Science.gov (United States)

    Wu, Tianshu; He, Keyu; Zhan, Qinglin; Ang, Shengjun; Ying, Jiali; Zhang, Shihan; Zhang, Ting; Xue, Yuying; Tang, Meng

    2015-12-01

    As quantum dots (QDs) are widely used in biomedical applications, the number of studies focusing on their biological properties is increasing. While several studies have attempted to evaluate the toxicity of QDs towards neural cells, the in vivo toxic effects on the nervous system and the molecular mechanisms are unclear. The aim of the present study was to investigate the neurotoxic effects and the underlying mechanisms of water-soluble cadmium telluride (CdTe) QDs capped with 3-mercaptopropionic acid (MPA) in Caenorhabditis elegans (C. elegans). Our results showed that exposure to MPA-capped CdTe QDs induced behavioral defects, including alterations to body bending, head thrashing, pharyngeal pumping and defecation intervals, as well as impaired learning and memory behavior plasticity, based on chemotaxis or thermotaxis, in a dose-, time- and size-dependent manner. Further investigations suggested that MPA-capped CdTe QDs exposure inhibited the transporters and receptors of glutamate, serotonin and dopamine in C. elegans at the genetic level within 24 h, while opposite results were observed after 72 h. Additionally, excessive reactive oxygen species (ROS) generation was observed in the CdTe QD-treated worms, which confirmed the common nanotoxicity mechanism of oxidative stress damage, and might overcome the increased gene expression of neurotransmitter transporters and receptors in C. elegans induced by long-term QD exposure, resulting in more severe behavioral impairments.

  6. Reversed extension flow

    DEFF Research Database (Denmark)

    Nielsen, Jens Kromann; Rasmussen, Henrik K.

    2008-01-01

    Afilament stretching rheometer (FSR) was used for measuring the start-up of uni-axial elongational flow followed by reversed bi-axial flow, both with a constant elongational rate. A narrow molecular mass distribution linear polystyrene with a molecular weight of 145 kg / mole wis subjected...... to the start-up of elongation for three Hencky strain units and subsequently the reversed flow. The integral molecular stress function formulation within the 'interchain pressure' concept agrees with the experiments. In the experiments the Hencky strain at which the str~ss becomes zero (the recovery strain...

  7. Sex reversal assessments reveal different vulnerability to endocrine disruption between deeply diverged anuran lineages

    Science.gov (United States)

    Tamschick, Stephanie; Rozenblut-Kościsty, Beata; Ogielska, Maria; Lehmann, Andreas; Lymberakis, Petros; Hoffmann, Frauke; Lutz, Ilka; Kloas, Werner; Stöck, Matthias

    2016-01-01

    Multiple anthropogenic stressors cause worldwide amphibian declines. Among several poorly investigated causes is global pollution of aquatic ecosystems with endocrine disrupting compounds (EDCs). These substances interfere with the endocrine system and can affect the sexual development of vertebrates including amphibians. We test the susceptibility to an environmentally relevant contraceptive, the artificial estrogen 17α-ethinylestradiol (EE2), simultaneously in three deeply divergent systematic anuran families, a model-species, Xenopus laevis (Pipidae), and two non-models, Hyla arborea (Hylidae) and Bufo viridis (Bufonidae). Our new approach combines synchronized tadpole exposure to three EE2-concentrations (50, 500, 5,000 ng/L) in a flow-through-system and pioneers genetic and histological sexing of metamorphs in non-model anurans for EDC-studies. This novel methodology reveals striking quantitative differences in genetic-male-to-phenotypic-female sex reversal in non-model vs. model species. Our findings qualify molecular sexing in EDC-analyses as requirement to identify sex reversals and state-of-the-art approaches as mandatory to detect species-specific vulnerabilities to EDCs in amphibians. PMID:27029458

  8. Sex reversal assessments reveal different vulnerability to endocrine disruption between deeply diverged anuran lineages.

    Science.gov (United States)

    Tamschick, Stephanie; Rozenblut-Kościsty, Beata; Ogielska, Maria; Lehmann, Andreas; Lymberakis, Petros; Hoffmann, Frauke; Lutz, Ilka; Kloas, Werner; Stöck, Matthias

    2016-03-31

    Multiple anthropogenic stressors cause worldwide amphibian declines. Among several poorly investigated causes is global pollution of aquatic ecosystems with endocrine disrupting compounds (EDCs). These substances interfere with the endocrine system and can affect the sexual development of vertebrates including amphibians. We test the susceptibility to an environmentally relevant contraceptive, the artificial estrogen 17α-ethinylestradiol (EE2), simultaneously in three deeply divergent systematic anuran families, a model-species, Xenopus laevis (Pipidae), and two non-models, Hyla arborea (Hylidae) and Bufo viridis (Bufonidae). Our new approach combines synchronized tadpole exposure to three EE2-concentrations (50, 500, 5,000 ng/L) in a flow-through-system and pioneers genetic and histological sexing of metamorphs in non-model anurans for EDC-studies. This novel methodology reveals striking quantitative differences in genetic-male-to-phenotypic-female sex reversal in non-model vs. model species. Our findings qualify molecular sexing in EDC-analyses as requirement to identify sex reversals and state-of-the-art approaches as mandatory to detect species-specific vulnerabilities to EDCs in amphibians.

  9. Reversing Discrimination: A Perspective

    Science.gov (United States)

    Pati, Gopal; Reilly, Charles W.

    1977-01-01

    Examines the debate over affirmative action and reverse discrimination, and discusses how and why the present dilemma has developed. Suggests that organizations can best address the problem through an honest, in-depth analysis of their organizational structure and management practices. (JG)

  10. Elastomers with Reversible Nanoporosity

    DEFF Research Database (Denmark)

    Szewczykowski, Piotr Przemyslaw; Andersen, K.; Schulte, Lars

    2009-01-01

    nanostructure and displays liquid-filled cavities. Upon several cycles of swelling and drying the cavities open and close in a reversible fashion. When exposed to a nonsolvent, the material remains collapsed. This discriminating behavior of liquid-material interaction holds potential for the use...

  11. Engineering Encounters: Reverse Engineering

    Science.gov (United States)

    McGowan, Veronica Cassone; Ventura, Marcia; Bell, Philip

    2017-01-01

    This column presents ideas and techniques to enhance your science teaching. This month's issue shares information on how students' everyday experiences can support science learning through engineering design. In this article, the authors outline a reverse-engineering model of instruction and describe one example of how it looked in our fifth-grade…

  12. REVERSE SUPPLY CHAIN

    Directory of Open Access Journals (Sweden)

    Tomasz DOMAGAŁA

    2013-10-01

    Full Text Available The paper focuses on the presentation of the reverse supply chain, of which the role in the modern business grows along with the increasing number of environmental regulations and possibilities of reducing an operating cost. The paper also describes main problems in developing the profitable chain and possibilities to take an action in order to overcome them.

  13. Time reversal communication system

    Science.gov (United States)

    Candy, James V.; Meyer, Alan W.

    2008-12-02

    A system of transmitting a signal through a channel medium comprises digitizing the signal, time-reversing the digitized signal, and transmitting the signal through the channel medium. The channel medium may be air, earth, water, tissue, metal, and/or non-metal.

  14. Modeling risk and uncertainty in designing reverse logistics problem

    OpenAIRE

    Aida Nazari Gooran; Hamed Rafiei; Masoud Rabani

    2018-01-01

    Increasing attention to environmental problems and social responsibility lead to appear reverse logistic (RL) issues in designing supply chain which, in most recently, has received considerable attention from both academicians and practitioners. In this paper, a multi-product reverse logistic network design model is developed; then a hybrid method including Chance-constrained programming, Genetic algorithm and Monte Carlo simulation, are proposed to solve the developed model. The proposed mod...

  15. The behavioural consequences of sex reversal in dragons

    Science.gov (United States)

    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.

  16. Arsenic removal in drinking water by reverse osmosis

    OpenAIRE

    Ahmad, Md. Fayej

    2012-01-01

    Arsenic is widely distributed in nature in the air, water and soil. Acute and chronic arsenic exposure by drinking water has been reported in many countries, especially Argentina, Bangladesh, India, Mexico, Mongolia, Thailand and Taiwan. There are many techniques used to remove arsenic from drinking water. Among them reverse osmosis is widely used. Therefore the purpose of this study is to find the conditions favorable for removal of arsenic from drinking water by using reverse osmosis ...

  17. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics. Michael R. Rose. Articles written in Journal of Genetics. Volume 82 Issue 3 December 2003 pp 133-145. The devil in the details of life-history evolution: instability and reversal of genetic correlations during selection on Drosophila development · Adam K. Chippindale Anh L. Ngo Michael ...

  18. Posterior reversible encephalopathy syndrome.

    Science.gov (United States)

    Fischer, Marlene; Schmutzhard, Erich

    2017-08-01

    The posterior reversible encephalopathy syndrome (PRES) is a neurological disorder of (sub)acute onset characterized by varied neurological symptoms, which may include headache, impaired visual acuity or visual field deficits, disorders of consciousness, confusion, seizures, and focal neurological deficits. In a majority of patients the clinical presentation includes elevated arterial blood pressure up to hypertensive emergencies. Neuroimaging, in particular magnetic resonance imaging, frequently shows a distinctive parieto-occipital pattern with a symmetric distribution of changes reflecting vasogenic edema. PRES frequently develops in the context of cytotoxic medication, (pre)eclampsia, sepsis, renal disease or autoimmune disorders. The treatment is symptomatic and is determined by the underlying condition. The overall prognosis is favorable, since clinical symptoms as well as imaging lesions are reversible in most patients. However, neurological sequelae including long-term epilepsy may persist in individual cases.

  19. Reversible dysphasia and statins.

    Science.gov (United States)

    Davies, Gordon Robert Wyndham

    2012-04-01

    This paper presents a case of reversible dysphasia occurring in a patient prescribed atorvastatin in combination with indapamide. A milder dysphasia recurred with the prescription of rosuvastatin and was documented on clinical examination. This resolved following cessation of rosuvastatin. The case highlights both a need for a wider understanding of potential drug interactions through the CYP 450 system and for an increased awareness, questioning and reporting of drug side-effects.

  20. Reversible multi-head finite automata characterize reversible logarithmic space

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock

    2012-01-01

    Deterministic and non-deterministic multi-head finite automata are known to characterize the deterministic and non- deterministic logarithmic space complexity classes, respectively. Recently, Morita introduced reversible multi-head finite automata (RMFAs), and posed the question of whether RMFAs...... characterize reversible logarithmic space as well. Here, we resolve the question affirmatively, by exhibiting a clean RMFA simulation of logarithmic space reversible Turing machines. Indirectly, this also proves that reversible and deterministic multi-head finite automata recognize the same languages....

  1. Resistance of renal cell carcinoma to sorafenib is mediated by potentially reversible gene expression.

    Directory of Open Access Journals (Sweden)

    Liang Zhang

    Full Text Available PURPOSE: Resistance to antiangiogenic therapy is an important clinical problem. We examined whether resistance occurs at least in part via reversible, physiologic changes in the tumor, or results solely from stable genetic changes in resistant tumor cells. EXPERIMENTAL DESIGN: Mice bearing two human RCC xenografts were treated with sorafenib until they acquired resistance. Resistant 786-O cells were harvested and reimplanted into naïve mice. Mice bearing resistant A498 cells were subjected to a 1 week treatment break. Sorafenib was then again administered to both sets of mice. Tumor growth patterns, gene expression, viability, blood vessel density, and perfusion were serially assessed in treated vs control mice. RESULTS: Despite prior resistance, reimplanted 786-O tumors maintained their ability to stabilize on sorafenib in sequential reimplantation steps. A transcriptome profile of the tumors revealed that the gene expression profile of tumors upon reimplantation reapproximated that of the untreated tumors and was distinct from tumors exhibiting resistance to sorafenib. In A498 tumors, revascularization was noted with resistance and cessation of sorafenib therapy and tumor perfusion was reduced and tumor cell necrosis enhanced with re-exposure to sorafenib. CONCLUSIONS: In two RCC cell lines, resistance to sorafenib appears to be reversible. These results support the hypothesis that resistance to VEGF pathway therapy is not solely the result of a permanent genetic change in the tumor or selection of resistant clones, but rather is due to a great extent to reversible changes that likely occur in the tumor and/or its microenvironment.

  2. Exposure Forecaster

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Exposure Forecaster Database (ExpoCastDB) is EPA's database for aggregating chemical exposure information and can be used to help with chemical exposure...

  3. Forward chemical genetic screening.

    Science.gov (United States)

    Choi, Hyunmo; Kim, Jun-Young; Chang, Young Tae; Nam, Hong Gil

    2014-01-01

    Chemical genetics utilizes small molecules to perturb biological processes. Unlike conventional genetics methods, which involve the alteration of genetic information mostly with lasting effects, chemical genetics allows temporary and reversible alterations of biological processes. Furthermore, it enables the alteration of biological processes in a dose-dependent manner, providing an advantage over conventional genetics. In the present chapter, the general procedures of forward chemical genetic screening are described. Forward chemical genetic screening can be performed in three steps. The first step involves the identification of small molecules that induce phenotypic or physiological changes in a biological system from a chemical library. In the second step, cellular targets that interact with the isolated chemical, which are mostly proteins, are identified. Although several methods can be applied in the second step, the most common one is affinity pull-down assay using a target protein that binds to the isolated compound. However, affinity pull-down of a target protein is a formidable barrier in forward chemical genetics. We introduced a tagged chemical library approach that significantly facilitates the identification of target proteins. The third step consists of the validation of the target protein, which should include the assessment of target specificity. This step is critical because small molecules often show pleiotropic effects due to low specificity. The specificity test may include a competition assay using cold competitors and a genetic study using mutants or transgenic lines modified for the cellular target.

  4. Genetic polymorphisms in XRCC1, OGG1, APE1 and XRCC3 DNA repair genes, ionizing radiation exposure and chromosomal DNA damage in interventional cardiologists

    Energy Technology Data Exchange (ETDEWEB)

    Andreassi, Maria Grazia, E-mail: andreas@ifc.cnr.it [CNR Institute of Clinical Physiology, National Research Council, Pisa (Italy); Foffa, Ilenia [CNR Institute of Clinical Physiology, National Research Council, Pisa (Italy); Sant' Anna School of Advanced Studies, Pisa (Italy); Manfredi, Samantha; Botto, Nicoletta [CNR Institute of Clinical Physiology, National Research Council, Pisa (Italy); Cioppa, Angelo [Clinica Cardiologica ' Montevergine' , Mercogliano (Italy); Picano, Eugenio [CNR Institute of Clinical Physiology, National Research Council, Pisa (Italy); Clinica Cardiologica ' Montevergine' , Mercogliano (Italy)

    2009-06-18

    Interventional cardiologists working in high-volume cardiac catheterization laboratory are exposed to significant occupational radiation risks. Common single-nucleotide polymorphisms (SNPs) in DNA repair genes are thought to modify the effects of low-dose radiation exposure on DNA damage, the main initiating event in the development of cancer and hereditary disease. The aim of this study was to determine the relationship between XRCC1 (Arg194Trp and Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu) and XRCC3 (Thr241Met) SNPs and chromosomal DNA damage. We enrolled 77 subjects: 40 interventional cardiologists (27 male, 41.3 {+-} 9.4 years and 13 female, 37.8 {+-} 8.4 years) and 37 clinical cardiologists (26 male, 39.4 {+-} 9.5 years and 11 female, 35.0 {+-} 9.8 years) without radiation exposure as the control group. Micronucleus (MN) assay was performed as biomarker of chromosomal DNA damage and an early predictor of cancer. MN frequency was significantly higher in interventional cardiologists than in clinical physicians (19.7 {+-} 7.8 per mille vs. 13.5 {+-} 6.3 per mille , p = 0.0003). Within the exposed group, individuals carrying a XRCC3 Met241 allele had higher frequency than homozygous XRCC3 Thr241 (21.2 {+-} 7.8 per mille vs. 16.6 {+-} 7.1 per mille , p = 0.03). Individuals with two or more risk alleles showed a higher MN frequency when compared to subjects with one or no risk allele (18.4 {+-} 6.6 per mille vs. 14.4 {+-} 6.1 per mille , p = 0.02). An interactive effect was found between smoking, exposure >10 years and the presence of the two or more risk alleles on the MN frequency (F = 6.3, p = 0.02). XRCC3 241Met alleles, particularly in combination with multiple risk alleles of DNA repair genes, contribute to chromosomal DNA damage levels in interventional cardiologists.

  5. Vibrio anguillarum Is Genetically and Phenotypically Unaffected by Long-Term Continuous Exposure to the Antibacterial Compound Tropodithietic Acid

    DEFF Research Database (Denmark)

    Rasmussen, Bastian Barker; Grotkjær, Torben; D'Alvise, Paul

    2016-01-01

    prevent or reduce bacterial diseases in fish larvae, acting as probiotics. Roseobacters produce the antimicrobial compound tropodithietic acid (TDA), and we were concerned regarding whether long-term exposure to this compound could induce resistance or affect the disease-causing ability of the fish......Minimizing the use of antibiotics in the food production chain is essential for limiting the development and spread of antibiotic-resistant bacteria. One alternative intervention strategy is the use of probiotic bacteria, and bacteria of the marine Roseobacter clade are capable of antagonizing fish......-pathogenic vibrios in fish larvae and live feed cultures for fish larvae. The antibacterial compound tropodithietic acid (TDA), an antiporter that disrupts the proton motive force, is key in the antibacterial activity of several roseobacters. Introducing probiotics on a larger scale requires understanding of any...

  6. Geomagnetic Field During a Reversal

    Science.gov (United States)

    Heirtzler, J. R.

    2003-01-01

    It has frequently been suggested that only the geomagnetic dipole, rather than higher order poles, reverse during a geomagnetic field reversal. Under this assumption the geomagnetic field strength has been calculated for the surface of the Earth for various steps of the reversal process. Even without an eminent a reversal of the field, extrapolation of the present secular change (although problematic) shows that the field strength may become zero in some geographic areas within a few hundred years.

  7. Phenotypic Plasticity, Epigenetic or Genetic Modifications in Relation to the Duration of Cd-Exposure within a Microevolution Time Range in the Beet Armyworm.

    Directory of Open Access Journals (Sweden)

    Maria Augustyniak

    Full Text Available In the case of the pests inhabiting metal polluted or fields where the use of pesticides is common, a natural selection of resistant individuals can occur. This may pose serious problems for humans, agriculture, as well as the economies of many countries. In this study, the hypothesis that multigenerational (120 generations exposure to cadmium of a beet armyworm population could be a selecting factor toward a more efficient DNA protection was verified. The hemocytes of individuals from two culture strains (control and Cd-exposed were treated with H2O2 (a DNA-damaging agent or PBS (reference. The level of DNA damage was assessed using the Comet assay immediately and 5, 15 and 30 min. after the treatment. The immediate result of the contact with H2O2 was that the level of DNA damage in the hemocytes of the insects from both strains increased significantly. However, in the cells of the Cd-exposed individuals, the level of DNA damage decreased over time, while in the cells from the control insects it remained at the same level with no evidence of repair. These results suggest that efficient defense mechanisms may exist in the cells of insects that have prolonged contact with cadmium. Some evolutionary and trade-off aspects of the phenomenon are discussed. In a wider context, comparing the results obtained in the laboratory with field studies may be beneficial for understanding basic mechanisms of the resistance of an organism. To summarize, the high potential for the repair of DNA damage that was observed in the insects from the cadmium strain may confirm the hypothesis that multigenerational exposure to that metal may possibly contribute to the selection of insects that have a wider tolerance to oxidative stress. However, our investigations of polymorphism using AFLP did not reveal differences between the two main insect strains.

  8. Reversible brazing process

    Science.gov (United States)

    Pierce, Jim D.; Stephens, John J.; Walker, Charles A.

    1999-01-01

    A method of reversibly brazing surfaces together. An interface is affixed to each surface. The interfaces can be affixed by processes such as mechanical joining, welding, or brazing. The two interfaces are then brazed together using a brazing process that does not defeat the surface to interface joint. Interfaces of materials such as Ni-200 can be affixed to metallic surfaces by welding or by brazing with a first braze alloy. The Ni-200 interfaces can then be brazed together using a second braze alloy. The second braze alloy can be chosen so that it minimally alters the properties of the interfaces to allow multiple braze, heat and disassemble, rebraze cycles.

  9. Reversibly Bistable Flexible Electronics

    KAUST Repository

    Alfaraj, Nasir

    2015-05-01

    Introducing the notion of transformational silicon electronics has paved the way for integrating various applications with silicon-based, modern, high-performance electronic circuits that are mechanically flexible and optically semitransparent. While maintaining large-scale production and prototyping rapidity, this flexible and translucent scheme demonstrates the potential to transform conventionally stiff electronic devices into thin and foldable ones without compromising long-term performance and reliability. In this work, we report on the fabrication and characterization of reversibly bistable flexible electronic switches that utilize flexible n-channel metal-oxide-semiconductor field-effect transistors. The transistors are fabricated initially on rigid (100) silicon substrates before they are peeled off. They can be used to control flexible batches of light-emitting diodes, demonstrating both the relative ease of scaling at minimum cost and maximum reliability and the feasibility of integration. The peeled-off silicon fabric is about 25 µm thick. The fabricated devices are transferred to a reversibly bistable flexible platform through which, for example, a flexible smartphone can be wrapped around a user’s wrist and can also be set back to its original mechanical position. Buckling and cyclic bending of such host platforms brings a completely new dimension to the development of flexible electronics, especially rollable displays.

  10. Fundamentals of reversible flowchart languages

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2016-01-01

    Abstract This paper presents the fundamentals of reversible flowcharts. They are intended to naturally represent the structure and control flow of reversible (imperative) programming languages in a simple computation model, in the same way classical flowcharts do for conventional languages...... flowcharts are both expressive and robust: reversible flowcharts can simulate irreversible ones, by adapting reversibilization techniques to the flowchart model. Thus, reversible flowcharts are r-Turing-complete, meaning that they can compute exactly all injective computable functions. Furthermore......, structured reversible flowcharts are as expressive as unstructured ones, as shown by a reversible version of the classic Structured Program Theorem. We illustrate how reversible flowcharts can be concretized with two example programming languages, complete with syntax and semantics: a low-level unstructured...

  11. Genetics Home Reference: ichthyosis with confetti

    Science.gov (United States)

    ... AJ, Bree A, Milstone LM, Lifton RP. Mitotic recombination in patients with ichthyosis causes reversion of dominant ... 36-9. Review. Citation on PubMed More from Genetics Home Reference Bulletins Rare Disease Day 2018 Darwin ...

  12. Reversible posterior leukoencephalopathy syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ja; Yu, Won Jong; Ahn, Kook Jin; Jung, So Lyung; Lee, Yeon Soo; Kim, Ji Chang; Kang, Si Won [The Catholic Univ. of Korea, Taejon (Korea, Republic of); Song, Chang Joon [Chungnam National Univ. School of Medicine, Cheonju (Korea, Republic of); Song, Soon-Young; Koo, Ja Hong [Kwandong Univ. College of Medicine, Myungji Hospital, Seoul (Korea, Republic of); Kim, Man Deuk [College of Medicine Pochon CHA Univ., Seoul (Korea, Republic of)

    2001-10-01

    To review reversible posterior leukoencephalopathy syndrome. We reviewed 22 patients (M:F=3:19; age, 17-46 years) with the characteristic clinical and imaging features of reversible posterior leukoencephalopathy syndrome. All underwent brain MRI, and in three cases both CT and MRI were performed. In one, MRA was obtained, and in eleven, follow-up MR images were obtained. We evaluated the causes of this syndrome, its clinical manifestations, and MR findings including the locations of lesions, the presence or absence of contrast enhancement, and the changes seen at follow-up MRI. Of the 22 patients, 13 had eclampsia (six during pregnancy and seven during puerperium). Four were receiving immunosuppressive therapy (three, cyclosporine ; one, FK 506). Four suffered renal failure and one had complicated migraine. The clinical manifestations included headache (n=12), visual disturbance (n=13), seizure (n=15), focal neurologic sign (n=3), and altered mental status (n=2). Fifteen patients had hypertension and the others normotension. MRI revealed that lesions were bilateral (n=20) or unilateral (n=2). In all patients the lesion was found in the cortical and subcortical areas of the parieto-occipital lobes ; other locations were the basal ganglia (n=9), posterior temporal lobe (n=8), frontal lobe (n=5), cerebellum (n=5), pons (n=2), and thalamus (n=1). All lesions were of high signal intensity on T2-weighted images, and of iso to low intensity on T1-weighted images. One was combined with acute hematoma in the left basal ganglia. In eight of 11 patients who underwent postcontrast T1-weighted MRI, there was no definite enhancement ; in one, enhancement was mild, and in tow, patchy. CT studies showed low attenuation, and MRA revealed mild vasospasm. The symptoms of all patients improved. Follow-up MRI in nine of 11 patients depicted complete resolution of the lesions ; in two, small infarctions remained but the extent of the lesions had decreased. Reversible posterior

  13. Genetics Home Reference: mycosis fungoides

    Science.gov (United States)

    ... other factors, such as environmental exposure or certain bacterial or viral infections, are involved in the development of mycosis fungoides . However, the influence of genetic and environmental factors on the development of this ...

  14. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    McMordie Stoughton, Kate; Duan, Xiaoli; Wendel, Emily M.

    2013-08-26

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). ¬The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.¬

  15. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-08-01

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.

  16. Sex Reversal in Amphibians.

    Science.gov (United States)

    Flament, Stéphane

    2016-01-01

    Amphibians have been widely used to study developmental biology due to the fact that embryo development takes place independently of the maternal organism and that observations and experimental approaches are easy. Some amphibians like Xenopus became model organisms in this field. In the first part of this article, the differentiation of the gonads in amphibians and the mechanisms governing this process are reviewed. In the second part, the state of the art about sex reversal, which can be induced by steroid hormones in general and by temperature in some species, is presented. Also information about pollutants found in the environment that could interfere with the development of the amphibian reproductive apparatus or with their reproductive physiology is given. Such compounds could play a part in the amphibian decline, since in the wild, many amphibians are endangered species. © 2016 S. Karger AG, Basel.

  17. A reversible processor architecture and its reversible logic design

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Axelsen, Holger Bock; Glück, Robert

    2012-01-01

    an architecture with an ISA that is expressive enough to serve as the target for a compiler from a high-level structured reversible programming language. All-in-all, this paper demonstrates that the design of a complete reversible computing architecture is possible and can serve as the core of a programmable......We describe the design of a purely reversible computing architecture, Bob, and its instruction set, BobISA. The special features of the design include a simple, yet expressive, locally-invertible instruction set, and fully reversible control logic and address calculation. We have designed...

  18. Functional reversion to identify controlling genes in multigenic responses: analysis of floral abortion

    National Research Council Canada - National Science Library

    John S. Boyer; John E. McLaughlin

    .... Identifying the controlling genes has proven difficult. However, in a few instances, it has been possible to reverse the phenotype by physiological or biochemical means without altering the genetics of the organism...

  19. Genetics Home Reference: 46,XX testicular disorder of sex development

    Science.gov (United States)

    ... area? Other Names for This Condition 46,XX sex reversal XX male syndrome XX sex reversal Related Information How are genetic conditions and genes ... 1 link) PubMed OMIM (1 link) 46,XX SEX REVERSAL 1 MedGen (1 link) 46,XX testicular disorder ...

  20. Defining the Polar Field Reversal

    Science.gov (United States)

    Upton, Lisa; Hathaway, David H.

    2013-01-01

    The polar fields on the Sun are directly related to solar cycle variability. Recently there has been interest in studying an important characteristic of the polar fields: the timing of the polar field reversals. However this characteristic has been poorly defined, mostly due to the limitations of early observations. In the past, the reversals have been calculated by averaging the flux above some latitude (i.e. 55deg or 75deg). Alternatively, the reversal could be defined by the time in which the previous polarity is completely canceled and replaced by the new polarity at 90de, precisely at the pole. We will use a surface flux transport model to illustrate the differences in the timing of the polar field reversal based on each of these definitions and propose standardization in the definition of the polar field reversal. The ability to predict the timing of the polar field reversal using a surface flux transport model will also be discussed.

  1. Bladder Cancer and Genetic Mutations.

    Science.gov (United States)

    Zhang, Xiaoying; Zhang, Yangde

    2015-09-01

    The most common type of urinary bladder cancer is called as transitional cell carcinoma. The major risk factors for bladder cancer are environmental, tobacco smoking, exposure to toxic industrial chemicals and gases, bladder inflammation due to microbial and parasitic infections, as well as some adverse side-effects of medications. The genetic mutations in some chromosomal genes, such as FGFR3, RB1, HRAS, TP53, TSC1, and others, occur which form tumors in the urinary bladder. These genes play an important role in the regulation of cell division which prevents cells from dividing too quickly. The changes in the genes of human chromosome 9 are usually responsible for tumor in bladder cancer, but the genetic mutation of chromosome 22 can also result in bladder cancer. The identification of p53 gene mutation has been studied at NIH, Washington, DC, USA, in urine samples of bladder cancer patients. The invasive bladder cancers were determined for the presence of gene mutations on p53 suppressor gene. The 18 different bladder tumors were evaluated, and 11 (61 %) had genetic mutations of p53 gene. The bladder cancer studies have suggested that 70 % of bladder cancers involve a specific mutation in a particular gene, namely telomerase reverse transcriptase (TERT) gene. The TERT gene is involved in DNA protection, cellular aging processes, and cancer. The Urothelial carcinomas of the bladder have been described in Atlas of genetics and cytogenetics in oncology and hematology. HRAS is a proto-oncogene and has potential to cause cancer in several organs including the bladder. The TSC1 c. 1907 1908 del (E636fs) mutation in bladder cancer suggests that the location of the mutation is Exon 15 with frequency of TSC1 mutation of 11.7 %. The recent findings of BAP1 mutations have shown that it contributes to BRCA pathway alterations in bladder cancer. The discoveries of more gene mutations and new biomarkers and polymerase chain reaction bioassays for gene mutations in bladder

  2. Reversing Neurodevelopmental Disorders in Adults

    National Research Council Canada - National Science Library

    Ehninger, Dan; Li, Weidong; Fox, Kevin; Stryker, Michael P; Silva, Alcino J

    2008-01-01

    .... Surprisingly, a number of recent animal model studies of neurodevelopmental disorders demonstrate that reversing the underlying molecular deficits can result in substantial improvements in function...

  3. Initiation of HIV Reverse Transcription

    Directory of Open Access Journals (Sweden)

    Roland Marquet

    2010-01-01

    Full Text Available Reverse transcription of retroviral genomes into double stranded DNA is a key event for viral replication. The very first stage of HIV reverse transcription, the initiation step, involves viral and cellular partners that are selectively packaged into the viral particle, leading to an RNA/protein complex with very specific structural and functional features, some of which being, in the case of HIV-1, linked to particular isolates. Recent understanding of the tight spatio-temporal regulation of reverse transcription and its importance for viral infectivity further points toward reverse transcription and potentially its initiation step as an important drug target.

  4. 49 CFR 230.89 - Reverse gear.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Reverse gear. 230.89 Section 230.89 Transportation... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants... quadrant. Proper counterbalance shall be provided for the valve gear. (b) Air-operated power reverse gear...

  5. Medical genetics

    Energy Technology Data Exchange (ETDEWEB)

    Jorde, L.B.; Carey, J.C.; White, R.L.

    1995-10-01

    This book on the subject of medical genetics is a textbook aimed at a very broad audience: principally, medical students, nursing students, graduate, and undergraduate students. The book is actually a primer of general genetics as applied to humans and provides a well-balanced introduction to the scientific and clinical basis of human genetics. The twelve chapters include: Introduction, Basic Cell Biology, Genetic Variation, Autosomal Dominant and Recessive Inheritance, Sex-linked and Mitochondrial Inheritance, Clinical Cytogenetics, Gene Mapping, Immunogenetics, Cancer Genetics, Multifactorial Inheritance and Common Disease, Genetic Screening, Genetic Diagnosis and Gene Therapy, and Clinical Genetics and Genetic Counseling.

  6. Genetic algorithms

    Science.gov (United States)

    Wang, Lui; Bayer, Steven E.

    1991-01-01

    Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.

  7. [Posterior reversible encephalopathy syndrome].

    Science.gov (United States)

    Fischer, M; Schmutzhard, E

    2016-06-01

    Posterior reversible encephalopathy syndrome refers to a neurological disorder characterized by headache, disorders of consciousness, visual disturbances, epileptic seizures, and subcortical vasogenic edema. About two thirds of patients develop neurological symptoms, which are associated with blood pressure fluctuations. One hypothesis is that hypertensive episodes cause autoregulatory failure, and values above the upper limit of cerebral autoregulation result in a breakthrough followed by hyperperfusion and blood-brain barrier dysfunction. In another hypothesis, endothelial dysfunction triggered by numerous factors including preeclampsia, immunosuppressive agents, chemotherapeutics, sepsis, or autoimmune disorders is thought to be the key pathomechanism. Endo- or exogenic toxic agents including pharmacological substances, cytokines, or bacterial toxins are supposed to trigger endothelial activation and dysfunction resulting in the release of vasoconstrictors, pro-inflammatory mediators, and vascular leakage. Diagnosis is usually based on clinical and neuroimaging findings that frequently show a bilateral, symmetric, and parietooccipital pattern. However, the diagnosis can often only be confirmed during the course of disease after excluding important differential diagnoses. Currently, there is no specific treatment available. Lowering of arterial blood pressure and eliminating the underlying cause usually leads to an improvement of clinical and neuroradiological findings. Admission to a critical care unit is required in about 40 % of patients due to complicating conditions including status epilepticus, cerebral vasoconstriction, ischemia, or intracerebral hemorrhage. Prognosis is favorable; in the majority of patients neurological deficits and imaging findings resolve completely.

  8. Mechanics of reversible unzipping

    Science.gov (United States)

    Maddalena, F.; Percivale, D.; Puglisi, G.; Truskinovsky, L.

    2009-07-01

    We study the mechanics of a reversible decohesion (unzipping) of an elastic layer subjected to quasi-static end-point loading. At the micro level the system is simulated by an elastic chain of particles interacting with a rigid foundation through breakable springs. Such system can be viewed as prototypical for the description of a wide range of phenomena from peeling of polymeric tapes, to rolling of cells, working of Gecko’s fibrillar structures and denaturation of DNA. We construct a rigorous continuum limit of the discrete model which captures both stable and metastable configurations and present a detailed parametric study of the interplay between elastic and cohesive interactions. We show that the model reproduces the experimentally observed abrupt transition from an incremental evolution of the adhesion front to a sudden complete decohesion of a macroscopic segment of the adhesion layer. As the microscopic parameters vary the macroscopic response changes from quasi-ductile to quasi-brittle, with corresponding decrease in the size of the adhesion hysteresis. At the micro-scale this corresponds to a transition from a ‘localized’ to a ‘diffuse’ structure of the decohesion front (domain wall). We obtain an explicit expression for the critical debonding threshold in the limit when the internal length scales are much smaller than the size of the system. The achieved parametric control of the microscopic mechanism can be used in the design of new biological inspired adhesion devices and machines.

  9. Time Reversal Violation

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, H; /SLAC

    2009-01-27

    This talk briefly reviews three types of time-asymmetry in physics, which I classify as universal, macroscopic and microscopic. Most of the talk is focused on the latter, namely the violation of T-reversal invariance in particle physics theories. In sum tests of microscopic T-invariance, or observations of its violation, are limited by the fact that, while we can measure many processes, only in very few cases can we construct a matched pair of process and inverse process and observe it with sufficient sensitivity to make a test. In both the cases discussed here we can achieve an observable T violation making use of flavor tagging, and in the second case also using the quantum properties of an antisymmetric coherent state of two B mesons to construct a CP-tag. Both these tagging properties depend only on very general properties of the flavor and/or CP quantum numbers and so provide model independent tests for T-invariance violations. The microscopic laws of physics are very close to T-symmetric. There are small effects that give CP- and T-violating processes in three-generation-probing weak decays. Where a T-violating observable can be constructed we see the relationships between T-violation and CP-violation expected in a CPT conserving theory. These microscopic effects are unrelated to the 'arrow of time' that is defined by increasing entropy, or in the time direction defined by the expansion of our Universe.

  10. Inherited XX sex reversal originating from wild medaka populations.

    Science.gov (United States)

    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.

  11. Genetic Counseling

    Science.gov (United States)

    Genetic counseling provides information and support to people who have, or may be at risk for, genetic disorders. A ... meets with you to discuss genetic risks. The counseling may be for yourself or a family member. ...

  12. Genetic Counseling

    Science.gov (United States)

    ... been added to your dashboard . KEY POINTS Genetic counseling helps you understand how genes, birth defects and medical ... in your area. What is genetic counseling? Genetic counseling helps you understand how genes , birth defects and other ...

  13. REVERSE LOGISTICS IN GLOBALIZATION ASPECTS

    OpenAIRE

    Janusz Grabara; Iwona Grabara

    2008-01-01

    This paper presents issues connected with adaptation of modern solutions of reverse logisticsmanagement in enterprise to the concept of sustainable development promoted by the European Union.Nowadays more and more businesses are looking to grow their reverse logistics capabilities in global market.

  14. Enzymatic reactions in reversed micelles

    NARCIS (Netherlands)

    Hilhorst, M.H.

    1984-01-01

    It has been recognised that enzymes in reversed micelles have potential for application in chemical synthesis. Before these expectations will be realised many problems must be overcome. This thesis deals with some of them.
    In Chapter 1 the present knowledge about reversed micelles and

  15. Enzyme recovery using reversed micelles

    NARCIS (Netherlands)

    Dekker, M.

    1990-01-01

    The objective of this study was to develop a liquid-liquid extraction process for the recovery of extracellular enzymes. The potentials of reaching this goal by using reversed micelles in an organic solvent have been investigated.

    Reversed micelles are aggregates of surfactant

  16. MODELS OF PROJECT REVERSE ENGINEERING

    Directory of Open Access Journals (Sweden)

    Віктор Володимирович ІВАНОВ

    2017-03-01

    Full Text Available Reverse engineering decided important scientific and technical problems of increasing the cost of the existing technical product by transforming it into a product with other features or design. Search ideas of the new application of existing products on the base of heuristic analysis were created. The concept of reverse engineering and its division into three types: conceptual, aggregate and complete was expanded. The use of heuristic methods for reverse engineering concept was showed. The modification model of Reverse engineering based on the model of РМВОК was developed. Our model includes two new phases: identification and transformation. At the identification phase, technical control is made. At the transformation phase, search heuristic idea of the new applied existing technical product was made. The model of execution phase that included heuristic methods, metrological equipment, and CAD/CAM/CAE program complex was created. The model that connected economic indicators of reverse engineering project was developed.

  17. Reversible gates and circuits descriptions

    Science.gov (United States)

    Gracki, Krzystof

    2017-08-01

    This paper presents basic methods of reversible circuit description. To design reversible circuit a set of gates has to be chosen. Most popular libraries are composed of three types of gates so called CNT gates (Control, NOT and Toffoli). The gate indexing method presented in this paper is based on the CNT gates set. It introduces a uniform indexing of the gates used during synthesis process of reversible circuits. The paper is organized as follows. Section 1 recalls basic concepts of reversible logic. In Section 2 and 3 a graphical representation of the reversible gates and circuits is described. Section 4 describes proposed uniform NCT gates indexing. The presented gate indexing method provides gate numbering scheme independent of lines number of the designed circuit. The solution for a circuit consisting of smaller number of lines is a subset of solution for a larger circuit.

  18. Fatal Hyperammonemic Brain Injury from Valproic Acid Exposure

    Directory of Open Access Journals (Sweden)

    Danny Bega

    2012-12-01

    Full Text Available Background: Hyperammonemia is known to cause neuronal injury, and can result from valproic acid exposure. Prompt reduction of elevated ammonia levels may prevent permanent neurological injury. We report a case of fatal hyperammonemic brain injury in a woman exposed to valproic acid. Case: A 38-year-old woman with schizoaffective disorder and recent increase in valproic acid dosage presented with somnolence and confusion and rapidly progressed to obtundation. Brain MRI showed diffuse bilateral restricted diffusion in nearly the entire cerebral cortex. She had normal liver function tests but serum ammonia level was severely elevated at 288 µmol/l. Genetic testing showed no mutation in urea cycle enzymes. Despite successful elimination of ammonia with hemodialysis she developed fatal cerebral edema. Conclusion: Cerebral edema secondary to hyperammonemia is potentially reversible if recognized early. Ammonia excretion can be facilitated by initiation of hemodialysis and administration of scavenging agents (sodium phenylacetate and sodium benzoate. Severe hyperammonemia can result from valproic acid exposure even in the absence of hepatotoxicity or inborn errors of metabolism. It is important to check serum ammonia in any patient with encephalopathy who has had recent valproic acid exposure.

  19. Adolescent cocaine exposure simplifies orbitofrontal cortical dendritic arbors

    Directory of Open Access Journals (Sweden)

    Lauren M DePoy

    2014-10-01

    Full Text Available Cocaine and amphetamine remodel dendritic spines within discrete cortico-limbic brain structures including the orbitofrontal cortex (oPFC. Whether dendrite structure is similarly affected, and whether pre-existing cellular characteristics influence behavioral vulnerabilities to drugs of abuse, remain unclear. Animal models provide an ideal venue to address these issues because neurobehavioral phenotypes can be defined both before, and following, drug exposure. We exposed mice to cocaine from postnatal days 31-35, corresponding to early adolescence, using a dosing protocol that causes impairments in an instrumental reversal task in adulthood. We then imaged and reconstructed excitatory neurons in deep-layer oPFC. Prior cocaine exposure shortened and simplified arbors, particularly in the basal region. Next, we imaged and reconstructed orbital neurons in a developmental-genetic model of cocaine vulnerability – the p190rhogap+/- mouse. p190RhoGAP is an actin cytoskeleton regulatory protein that stabilizes dendrites and dendritic spines, and p190rhogap+/- mice develop rapid and robust locomotor activation in response to cocaine. Despite this, oPFC dendritic arbors were intact in drug-naïve p190rhogap+/- mice. Together, these findings provide evidence that adolescent cocaine exposure has long-term effects on dendrite structure in the oPFC, and they suggest that cocaine-induced modifications in dendrite structure may contribute to the behavioral effects of cocaine more so than pre-existing structural abnormalities in this cell population.

  20. Reversible Surface Properties of Polybenzoxazine/Silica Nanocomposites Thin Films

    Directory of Open Access Journals (Sweden)

    Wei-Chen Su

    2013-01-01

    Full Text Available We report the reversible surface properties (hydrophilicity, hydrophobicity of a polybenzoxazine (PBZ thin film through simple application of alternating UV illumination and thermal treatment. The fraction of intermolecularly hydrogen bonded O–H⋯O=C units in the PBZ film increased after UV exposure, inducing a hydrophilic surface; the surface recovered its hydrophobicity after heating, due to greater O–H⋯N intramolecular hydrogen bonding. Taking advantage of these phenomena, we prepared a PBZ/silica nanocomposite coating through two simple steps; this material exhibited reversible transitions from superhydrophobicity to superhydrophilicity upon sequential UV irradiation and thermal treatment.

  1. Effects of the Interactions between Dust Exposure and Genetic Polymorphisms in Nalp3, Caspase-1, and IL-1β on the Risk of Silicosis: A Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Shaofan Weng

    Full Text Available To evaluate the effects of the interactions between polymorphisms in Nalp3, caspase-1, and interleukin(IL-1β genes and occupational dust exposure on the risk of silicosis.We conducted a population-based case-control study in a large iron mine in China. Between January 2006 and December 2009, we identified 179 patients with silicosis to evaluate as cases and 201 individuals without silicosis to evaluate as controls. We estimated cumulative dust exposure (CDE for all subjects and we genotyped polymorphisms in Nalp3, caspase-1, and IL-1β genes. We estimated odds ratios(ORs, 95% confidence intervals(95%CIs, and p-values using logistic regression models adjusted for selected confounders.After adjusting for age, smoking status, and CDE, subjects with the CT genotype of Ex4-849C>T in Nalp3 and the GA genotype of Ex2+37G>A in caspase-1 had increased risks of silicosis (adjusted ORs[95%CIs] = 2.40 [1.12-5.12] and 3.62 [1.63-8.02], respectively. Among subjects younger than 70 years old, those with the CC genotype of IVS8-7652A>C in Nalp3 had a lower risk of silicosis than those with other genotypes (adjusted OR[95%CI] = 0.24[0.06-0.88]. Among subjects aged 70 years and older, those with the CT genotype of Ex4-849C>T in Nalp3 and those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs [95%CI] = 2.52[1.04-6.12] and 5.19[1.88-14.35], respectively. Among subjects with CDE greater than 120 mg/m3×year and among smokers, those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs[95%CIs] = 26.37[3.35-207.39] and 3.47[1.40-8.64], respectively.Genetic polymorphisms in Nalp3 and caspase-1 may be associated with individual susceptibility to silicosis, especially when the polymorphisms interact with age, CDE, or smoking status.

  2. Effects of the Interactions between Dust Exposure and Genetic Polymorphisms in Nalp3, Caspase-1, and IL-1β on the Risk of Silicosis: A Case-Control Study.

    Science.gov (United States)

    Weng, Shaofan; Wang, Lihua; Rong, Yi; Liu, Yuewei; Wang, Xin; Guan, Hongyu; Chen, Weihong

    2015-01-01

    To evaluate the effects of the interactions between polymorphisms in Nalp3, caspase-1, and interleukin(IL)-1β genes and occupational dust exposure on the risk of silicosis. We conducted a population-based case-control study in a large iron mine in China. Between January 2006 and December 2009, we identified 179 patients with silicosis to evaluate as cases and 201 individuals without silicosis to evaluate as controls. We estimated cumulative dust exposure (CDE) for all subjects and we genotyped polymorphisms in Nalp3, caspase-1, and IL-1β genes. We estimated odds ratios(ORs), 95% confidence intervals(95%CIs), and p-values using logistic regression models adjusted for selected confounders. After adjusting for age, smoking status, and CDE, subjects with the CT genotype of Ex4-849C>T in Nalp3 and the GA genotype of Ex2+37G>A in caspase-1 had increased risks of silicosis (adjusted ORs[95%CIs] = 2.40 [1.12-5.12] and 3.62 [1.63-8.02], respectively). Among subjects younger than 70 years old, those with the CC genotype of IVS8-7652A>C in Nalp3 had a lower risk of silicosis than those with other genotypes (adjusted OR[95%CI] = 0.24[0.06-0.88]). Among subjects aged 70 years and older, those with the CT genotype of Ex4-849C>T in Nalp3 and those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs [95%CI] = 2.52[1.04-6.12] and 5.19[1.88-14.35], respectively). Among subjects with CDE greater than 120 mg/m3×year and among smokers, those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs[95%CIs] = 26.37[3.35-207.39] and 3.47[1.40-8.64], respectively). Genetic polymorphisms in Nalp3 and caspase-1 may be associated with individual susceptibility to silicosis, especially when the polymorphisms interact with age, CDE, or smoking status.

  3. Reversible simulation of irreversible computation

    Science.gov (United States)

    Li, Ming; Tromp, John; Vitányi, Paul

    1998-09-01

    Computer computations are generally irreversible while the laws of physics are reversible. This mismatch is penalized by among other things generating excess thermic entropy in the computation. Computing performance has improved to the extent that efficiency degrades unless all algorithms are executed reversibly, for example by a universal reversible simulation of irreversible computations. All known reversible simulations are either space hungry or time hungry. The leanest method was proposed by Bennett and can be analyzed using a simple ‘reversible’ pebble game. The reachable reversible simulation instantaneous descriptions (pebble configurations) of such pebble games are characterized completely. As a corollary we obtain the reversible simulation by Bennett and, moreover, show that it is a space-optimal pebble game. We also introduce irreversible steps and give a theorem on the tradeoff between the number of allowed irreversible steps and the memory gain in the pebble game. In this resource-bounded setting the limited erasing needs to be performed at precise instants during the simulation. The reversible simulation can be modified so that it is applicable also when the simulated computation time is unknown.

  4. Supercritical fluid reverse micelle separation

    Science.gov (United States)

    Fulton, J.L.; Smith, R.D.

    1993-11-30

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

  5. A high-throughput Arabidopsis reverse genetics system.

    Science.gov (United States)

    Sessions, Allen; Burke, Ellen; Presting, Gernot; Aux, George; McElver, John; Patton, David; Dietrich, Bob; Ho, Patrick; Bacwaden, Johana; Ko, Cynthia; Clarke, Joseph D; Cotton, David; Bullis, David; Snell, Jennifer; Miguel, Trini; Hutchison, Don; Kimmerly, Bill; Mitzel, Theresa; Katagiri, Fumiaki; Glazebrook, Jane; Law, Marc; Goff, Stephen A

    2002-12-01

    A collection of Arabidopsis lines with T-DNA insertions in known sites was generated to increase the efficiency of functional genomics. A high-throughput modified thermal asymmetric interlaced (TAIL)-PCR protocol was developed and used to amplify DNA fragments flanking the T-DNA left borders from approximately 100000 transformed lines. A total of 85108 TAIL-PCR products from 52964 T-DNA lines were sequenced and compared with the Arabidopsis genome to determine the positions of T-DNAs in each line. Predicted T-DNA insertion sites, when mapped, showed a bias against predicted coding sequences. Predicted insertion mutations in genes of interest can be identified using Arabidopsis Gene Index name searches or by BLAST (Basic Local Alignment Search Tool) search. Insertions can be confirmed by simple PCR assays on individual lines. Predicted insertions were confirmed in 257 of 340 lines tested (76%). This resource has been named SAIL (Syngenta Arabidopsis Insertion Library) and is available to the scientific community at www.tmri.org.

  6. Forward and reverse genetics: The LORE1 retrotransposon insertion mutants

    DEFF Research Database (Denmark)

    Fukai, Eigo; Malolepszy, Anna; Sandal, Niels Nørgaard

    2014-01-01

    The endogenous Lotus retrotransposon 1 (LORE1) transposes in the germ line of Lotus japonicus plants that carry an active element. This feature of LORE1 has been exploited for generation of a large non-transgenic insertion mutant population, where insertions have been annotated using next......-generation sequencing approaches. The LORE1 mutant lines are freely available and can be ordered online. Endogenous retrotransposons are also active in many other plant species. Based on the methods developed for LORE1 mutagenesis, it should be simple to establish similar systems in other species, once an appropriate...

  7. Reverse engineering large-scale genetic networks: synthetic versus ...

    Indian Academy of Sciences (India)

    School of Computer Engineering and Science, Shanghai University, 149 Yanchang Road, Zhabei District, Shanghai 200072, People's Republic of China; Institute of Systems Biology, Shanghai University, 99 Shangda Road, Baoshan District, Shanghai 200072, People's Republic of China; Academy of Mathematics and ...

  8. Reverse engineering large-scale genetic networks: synthetic versus ...

    Indian Academy of Sciences (India)

    2010-04-19

    Apr 19, 2010 ... 1School of Computer Engineering and Science, Shanghai University, 149 Yanchang Road, Zhabei District,. Shanghai 200072 ... plex biological system by efficient computer modelling tools. Such tools are gaining ..... combining both assessment approaches, we are likely to ob- tain a more reliable picture ...

  9. A Framework for Reverse Logistics

    OpenAIRE

    Brito, Marisa; Dekker, Rommert

    2003-01-01

    textabstractReverse Logistics has been stretching out worldwide, involving all the layers of supply chains in various industry sectors. While some actors in the chain have been forced to take products back, others have pro-actively done so, attracted by the value in used products One way or the other, Reverse Logistics has become a key competence in modern supply chains. In this paper, we present a content analysis of reverse logistics issues. To do so, we propose a content framework focusing...

  10. Short-Term Stock Price Reversals May Be Reversed

    Directory of Open Access Journals (Sweden)

    Andrey Kudryavtsev

    2012-12-01

    Full Text Available In present study, I explore intraday behavior of stock prices. In particular, I try to shed light onthe dynamics of stock price reversals and namely, on the short-term character the latter maypossess. For each of the stocks currently making up the Dow Jones Industrial Index, I calculateintraday upside and downside volatility measures, following Becker et al. (2008 and Klossner etal. (2012, as a proxy for reversed overreactions to good and bad news, respectively. I documentthat for all the stocks in the sample, mean daily returns following the days when a stock’supside volatility measure was higher or equal to its downside volatility measure are higher thanfollowing the days when the opposite relationship held, indicating that stock prices display ashort-run ‘reversals of reversals’ behavior following corrected, or reversed, overreactions tonews. Furthermore, I construct seven different portfolios built upon the idea of daily adjustinga long position in the stocks that according to ‘reversals of reversals’ behavior are expectedto yield high daily returns, and a short position in the stocks, whose daily returns are expectedto be low. All the portfolios yield significantly positive returns, providing an evidence for thepractical applicability of the ‘reversals of reversals’ pattern in stock prices.

  11. Metaheuristic analysis in reverse logistics of waste

    Energy Technology Data Exchange (ETDEWEB)

    Serrano Elena, A.

    2016-07-01

    This paper focuses in the use of search metaheuristic techniques on a dynamic and deterministic model to analyze and solve cost optimization problems and location in reverse logistics, within the field of municipal waste management of Málaga (Spain). In this work we have selected two metaheuristic techniques having relevance in present research, to test the validity of the proposed approach: an important technique for its international presence as is the Genetic Algorithm (GA) and another interesting technique that works with swarm intelligence as is the Particles Swarm Optimization (PSO). These metaheuristic techniques will be used to solve cost optimization problems and location of MSW recovery facilities (transfer centers and treatment plants). (Author)

  12. Network Reverse Engineering Approach in Synthetic Biology

    Science.gov (United States)

    Zhang, Haoqian; Liu, Ao; Lu, Yuheng; Sheng, Ying; Wu, Qianzhu; Yin, Zhenzhen; Chen, Yiwei; Liu, Zairan; Pan, Heng; Ouyang, Qi

    2013-12-01

    Synthetic biology is a new branch of interdisciplinary science that has been developed in recent years. The main purpose of synthetic biology is to apply successful principles that have been developed in electronic and chemical engineering to develop basic biological functional modules, and through rational design, develop man-made biological systems that have predicted useful functions. Here, we discuss an important principle in rational design of functional biological circuits: the reverse engineering design. We will use a research project that was conducted at Peking University for the International Genetic Engineering Machine Competition (iGEM) to illustrate the principle: synthesis a cell which has a semi-log dose-response to the environment. Through this work we try to demonstrate the potential application of network engineering in synthetic biology.

  13. Reverse Knowledge Transfer in MNEs

    DEFF Research Database (Denmark)

    Mudambi, Ram; Piscitello, Lucia; Rabbiosi, Larissa

    2014-01-01

    a positive correlation with the extent of reverse knowledge transfers to the parent MNE. Relying on the headquarters-subsidiary view of the MNE, we argue that, beyond a point, increasing subsidiary innovativeness will be associated with lower reverse knowledge transfers. Further, we argue...... that this relationship is sensitive to the subsidiary entry mode. Using data from a sample of 293 Italian subsidiaries, we find strong support for our hypotheses. In particular, our results confirm that the effect of subsidiary innovativeness on reverse knowledge transfers displays an inverted-U shape......, and that the curvilinearity is greater for greenfield entries relative to acquisition entries. The U-shaped relationship between subsidiary innovativeness and reverse knowledge transfers, as well as the sensitivity of this result to entry mode are important new findings in the literature on the role of subsidiaries...

  14. Designing the Reverse Supply Chain

    DEFF Research Database (Denmark)

    Gobbi, Chiara

    2011-01-01

    for the reverse supply chain. Design/methodology/approach – In order to identify the relevance of the Fisher model, the model needs to be recast in terms of PRV, which, in this context, is considered the independent variable in the reverse logistics arena. Products defined as innovative in Fisher's taxonomy......Purpose – The purpose of this paper is to explore the impact of the product residual value (PRV) and the loss of value over time of returned products in the reverse supply chain configuration. It also examines whether or not the distinction of Fisher's functional and innovative products holds...... correspond to disposed products with high residual value, whereas functional products correspond to disposed products with low residual value. Furthermore, the PRV and the speed at which returned products lose their value are considered in order to determine the configuration of the reverse supply chain...

  15. CONCEPTUAL ISSUES REGARDING REVERSE LOGISTICS

    National Research Council Canada - National Science Library

    Ioana Olariu

    2014-01-01

    ... of reverse logistics in companies. Many firms attracted by the value available in the flow, have proactively participated in handling returned products at the end of their usefulness or from other parts of the product life cycle...

  16. A Typology of Reverse Innovation

    DEFF Research Database (Denmark)

    von Zedtwitz, Max; Corsi, Simone; Søberg, Peder Veng

    2015-01-01

    Reverse innovation commonly refers to an innovation initially launched in a developing country and later introduced to an advanced country. Adopting a linear innovation model with the four sequential phases of concept ideation, product development, primary target market introduction, and subsequent...... secondary market introduction, this study expands the espoused definition of reverse innovation beyond its market-introduction focus with reversals in the flow of innovation in the ideation and product development phases. Recognizing that each phase can take place in different geographical locations...... taking place in an emerging country. This analytical framework allows recasting of current research at the intersection between innovation and international business. Of the 10 reverse innovation flows, six are new and have not been covered in the literature to date. The study addresses questions...

  17. Towards a reversible functional language

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2012-01-01

    We identify concepts of reversibility for a functional language by means of a set of semantic rules with specific properties. These properties include injectivity along with local backward determinism, an important operational property for an efficient reversible language. We define a concise...... reversible first-order functional language in which access to the backward semantics is provided to the programmer by inverse function calls. Reversibility guarantees that in this language a backward run (inverse interpretation) is as fast as the corresponding forward run itself. By adopting a symmetric...... first-match policy for case expressions, we can write overlapping patterns in case branches, as is customary in ordinary functional languages, and also in leaf expressions, unlike existing inverse interpreter methods, which enables concise programs. In patterns, the use of a duplication...

  18. Laparoscopic reversal of Hartmann's procedure

    DEFF Research Database (Denmark)

    Svenningsen, Peter Olsen; Bulut, Orhan; Jess, Per

    2010-01-01

    A change in procedure from open to laparoscopic reversal of Hartmann's colostomy was implemented at our department between May 2005 and December 2008. The aim of the study was to investigate if this change was beneficial for the patients.......A change in procedure from open to laparoscopic reversal of Hartmann's colostomy was implemented at our department between May 2005 and December 2008. The aim of the study was to investigate if this change was beneficial for the patients....

  19. Deterministic chaos in geomagnetic reversals

    Science.gov (United States)

    Sidorovskaia, N.; Richter, C.; Rypina, I.

    2013-12-01

    In a recent publication Gissinger (Eur. Phys. J. B 85,137, 2012) proposed a new deterministic chaos model for the generation of the Earth's magnetic field and an explanation of the observed statistics of geomagnetic pole reversal occurrences. The new model is described by a system of three coupled non-linear differential equations limited to quadratic terms. If such a low degree of freedom system is adequate for the description of Earth's geomagnetic dynamo, it has to reflect in statistics and non-linear dynamic characteristics of the temporal interval between geomagnetic reversals. We present the results of the extended statistical analysis of the 2012 compilation of magnetic reversal data spanning the last 170 m.yr. We calculate the Grassberger-Procaccia correlation dimension in the context of a single-variable dataset of waiting times between measured geomagnetic reversals in paleomagnetic records to predict the complexity of the underlying geomagnetic dynamo system. First, we inspect if the time series of geomagnetic reversals has the same or a different correlation dimension than a random time series with the same number of points. This allows us to determine whether geomagnetic reversals are indistinguishable from a stochastic process, or are described by a chaotic rather than stochastic process. Next, higher-dimensional vectors are constructed from the time series of geomagnetic reversals, and correlation dimension is calculated for these higher-dimensional vectors to find out if the correlation dimension has a convergence limit as we increase the vector space dimension. If the convergence limit is revealed from the experimental dataset, then the geomagnetic reversals are chaotic rather than stochastic and are described by a system with limited number of degrees of freedom determined by the correlation dimension. If one expects to describe the geomagnetic dynamo by a low-order system of non-linear differential equations, the system should have a low

  20. Hybrid Algorithms for Fuzzy Reverse Supply Chain Network Design

    Directory of Open Access Journals (Sweden)

    Z. H. Che

    2014-01-01

    Full Text Available 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.

  1. Hybrid Algorithms for Fuzzy Reverse Supply Chain Network Design

    Science.gov (United States)

    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

  2. Hybrid algorithms for fuzzy reverse supply chain network design.

    Science.gov (United States)

    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.

  3. Sex Reversal in Non-Human Placental Mammals.

    Science.gov (United States)

    Parma, Pietro; Veyrunes, Frédéric; Pailhoux, Eric

    2016-01-01

    Gonads are very peculiar organs given their bipotential competence. Indeed, early differentiating genital ridges evolve into either of 2 very distinct organs: the testis or the ovary. Accumulating evidence now demonstrates that both genetic pathways must repress the other in order for the organs to differentiate properly, meaning that if this repression is disrupted or attenuated, the other pathway may completely or partially be expressed, leading to disorders of sex development. Among these disorders are the cases of XY male-to-female and XX female-to-male sex reversals as well as true hermaphrodites, in which there is a discrepancy between the chromosomal and gonadal sex. Here, we review known cases of XY and XX sex reversals described in mammals, focusing mostly on domestic animals where sex reversal pathologies occur and on wild species in which deviations from the usual XX/XY system have been documented. © 2016 S. Karger AG, Basel.

  4. Garbage collection for reversible functional languages

    DEFF Research Database (Denmark)

    Mogensen, Torben Ægidius

    2015-01-01

    Reversible languages are programming languages where all programs can run both forwards and backwards. Reversible functional languages have been proposed that use symmetric pattern matching and data construction. To be reversible, these languages require linearity: Every variable must be used...

  5. Genetic screens in Caenorhabditis elegans models for neurodegenerative diseases

    NARCIS (Netherlands)

    Alvarenga Fernandes Sin, Olga; Michels, Helen; Nollen, Ellen A. A.

    2014-01-01

    Caenorhabditis elegans comprises unique features that make it an attractive model organism in diverse fields of biology. Genetic screens are powerful to identify genes and C. elegans can be customized to forward or reverse genetic screens and to establish gene function. These genetic screens can be

  6. Reversal and Relapse of Hypogonadotropic Hypogonadism: Resilience and Fragility of the Reproductive Neuroendocrine System

    Science.gov (United States)

    Sidhoum, Valerie F.; Chan, Yee-Ming; Lippincott, Margaret F.; Balasubramanian, Ravikumar; Quinton, Richard; Plummer, Lacey; Dwyer, Andrew; Pitteloud, Nelly; Hayes, Frances J.; Hall, Janet E.; Martin, Kathryn A.; Boepple, Paul A.

    2014-01-01

    Context: A subset of patients diagnosed with idiopathic hypogonadotropic hypogonadism (IHH) later achieves activation of their hypothalamic-pituitary-gonadal axis with normalization of steroidogenesis and/or gametogenesis, a phenomenon termed reversal. Objective: The objective of this study was to determine the natural history of reversal and to identify associated phenotypes and genotypes. Design, Setting, and Subjects: This was a retrospective review of clinical, biochemical, and genetic features of patients with IHH evaluated at an academic medical center. Main Outcome Measures: History of spontaneous fertility, regular menses, testicular growth, or normalization of serum sex steroids, LH secretory profiles, brain imaging findings, and sequences of 14 genes associated with IHH were reviewed. Results: Of 308 patients with IHH, 44 underwent reversal. Time-to-event analysis estimated a lifetime incidence of reversal of 22%. There were no differences in the rates of cryptorchidism, micropenis, or partial pubertal development in patients with reversal vs IHH patients without reversal. Fifteen patients with reversal (30%) had Kallmann syndrome (IHH and anosmia); one had undetectable olfactory bulbs on a brain magnetic resonance imaging scan. Subjects with reversal were enriched for mutations affecting neurokinin B signaling compared with a cohort of IHH patients without reversal (10% vs 3%, P = .044), had comparable frequencies of mutations in FGFR1, PROKR2, and GNRHR, and had no mutations in KAL1. Five men did not sustain their reversal and again developed hypogonadotropism. Conclusions: Reversal of IHH may be more widespread than previously appreciated and occurs across a broad range of genotypes and phenotypes. Enrichment for mutations that disrupt neurokinin B signaling in patients who reversed indicates that, despite the importance of this signaling pathway for normal pubertal timing, its function is dispensable later in life. The occurrence of reversal in a

  7. Environmental epigenetics in metal exposure

    Science.gov (United States)

    Martinez-Zamudio, Ricardo

    2011-01-01

    Although it is widely accepted that chronic exposure to arsenite, nickel, chromium and cadmium increases cancer incidence in individuals, the molecular mechanisms underlying their ability to transform cells remain largely unknown. Carcinogenic metals are typically weak mutagens, suggesting that genetic-based mechanisms may not be primarily responsible for metal-induced carcinogenesis. Growing evidence shows that environmental metal exposure involves changes in epigenetic marks, which may lead to a possible link between heritable changes in gene expression and disease susceptibility and development. Here, we review recent advances in the understanding of metal exposure affecting epigenetic marks and discuss establishment of heritable gene expression in metal-induced carcinogenesis. PMID:21610324

  8. HuR interacts with human immunodeficiency virus type 1 reverse transcriptase, and modulates reverse transcription in infected cells

    Directory of Open Access Journals (Sweden)

    Ennifar Eric

    2008-06-01

    Full Text Available Abstract 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.

  9. Genetic and perinatal effects of abused substances

    Energy Technology Data Exchange (ETDEWEB)

    Brande, M.C.; Zimmerman, A.M.

    1987-01-01

    This book provides an overview of the effects of several abused drugs, including opiates, cannabinoids, alcohol, nicotine, and cocaine, with special emphasis on the actions of these substances at the molecular and cellular levels. The first half deals with genetic effects, including molecular genetics, biochemical genetics, pharmacogenetics, cytogenetics, and genetic toxicity. The second half focuses on perinatal effects and covers: drug abuse during pregnancy; biochemical aspects of marihuana on male reproduction; and long-term behavioral and neuroendocrine effects of perinatal alcohol exposure.

  10. Acute stress impairs set-shifting but not reversal learning.

    Science.gov (United States)

    Butts, K A; Floresco, S B; Phillips, A G

    2013-09-01

    The ability to update and modify previously learned behavioral responses in a changing environment is essential for successful utilization of promising opportunities and for coping with adverse events. Valid models of cognitive flexibility that contribute to behavioral flexibility include set-shifting and reversal learning. One immediate effect of acute stress is the selective impairment of performance on higher-order cognitive control tasks mediated by the medial prefrontal cortex (mPFC) but not the hippocampus. Previous studies show that the mPFC is required for set-shifting but not for reversal learning, therefore the aim of the present experiment is to assess whether exposure to acute stress (15 min of mild tail-pinch stress) given immediately before testing on either a set-shifting or reversal learning tasks would impair performance selectively on the set-shifting task. An automated operant chamber-based task, confirmed that exposure to acute stress significantly disrupts set-shifting but has no effect on reversal learning. Rats exposed to an acute stressor require significantly more trials to reach criterion and make significantly more perseverative errors. Thus, these data reveal that an immediate effect of acute stress is to impair mPFC-dependent cognition selectively by disrupting the ability to inhibit the use of a previously relevant cognitive strategy. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Reverse degradation of nickel graphene junction by hydrogen annealing

    Directory of Open Access Journals (Sweden)

    Zhenjun Zhang

    2016-02-01

    Full Text Available Metal contacts are fundamental building components for graphene based electronic devices and their properties are greatly influenced by interface quality during device fabrication, leading to resistance variation. Here we show that nickel graphene junction degrades after air exposure, due to interfacial oxidation, thus creating a tunneling barrier. Most importantly, we demonstrate that hydrogen annealing at moderate temperature (300 0C is an effective technique to reverse the degradation.

  12. Reverse degradation of nickel graphene junction by hydrogen annealing

    CERN Document Server

    Zhang, Zhenjun; Agnihotri, Pratik; Lee, Ji Ung; Lloyd, Jim R

    2016-01-01

    Metal contacts are fundamental building components for graphene based electronic devices and their properties are greatly influenced by interface quality during device fabrication, leading to resistance variation. Here we show that nickel graphene junction degrades after air exposure, due to interfacial oxidation, thus creating a tunneling barrier. Most importantly, we demonstrate that hydrogen annealing at moderate temperature (300 0C) is an effective technique to reverse the degradation.

  13. Natural variation, an underexploited resource of genetic variation for plant genetics

    NARCIS (Netherlands)

    Alonso-Blanco, C.; Koornneef, M.

    2000-01-01

    The definition of gene functions requires the phenotypic characterization of genetic variants. Currently, such functional analysis of Arabidopsis genes is based largely on laboratory-induced mutants that are selected in forward and reverse genetic studies. An alternative complementary source of

  14. Basic reversal-learning capacity in flies suggests rudiments of complex cognition.

    Science.gov (United States)

    Foley, Brad R; Marjoram, Paul; Nuzhdin, Sergey V

    2017-01-01

    The most basic models of learning are reinforcement learning models (for instance, classical and operant conditioning) that posit a constant learning rate; however many animals change their learning rates with experience. This process is sometimes studied by reversing an existing association between cues and rewards, and measuring the rate of relearning. Augmented reversal-learning, where learning rates increase with practice, can be an important component of behavioral flexibility; and may provide insight into higher cognition. Previous studies of reversal-learning in Drosophila have not measured learning rates, but have tended to focus on measuring gross deficits in reversal-learning, as the ratio of two timepoints. These studies have uncovered a diversity of mechanisms underlying reversal-learning, but natural genetic variation in this trait has yet to be assessed. We conducted a reversal-learning regime on a diverse panel of Drosophila melanogaster genotypes. We found highly significant genetic variation in their baseline ability to learn. We also found that they have a consistent, and strong (1.3×), increase in their learning speed with reversal. We found no evidence, however, that there was genetic variation in their ability to increase their learning rates with experience. This may suggest that Drosophila have a hitherto unrecognized ability to integrate acquired information, and improve their decision making; but that their mechanisms for doing so are under strong constraints.

  15. Basic reversal-learning capacity in flies suggests rudiments of complex cognition.

    Directory of Open Access Journals (Sweden)

    Brad R Foley

    Full Text Available The most basic models of learning are reinforcement learning models (for instance, classical and operant conditioning that posit a constant learning rate; however many animals change their learning rates with experience. This process is sometimes studied by reversing an existing association between cues and rewards, and measuring the rate of relearning. Augmented reversal-learning, where learning rates increase with practice, can be an important component of behavioral flexibility; and may provide insight into higher cognition. Previous studies of reversal-learning in Drosophila have not measured learning rates, but have tended to focus on measuring gross deficits in reversal-learning, as the ratio of two timepoints. These studies have uncovered a diversity of mechanisms underlying reversal-learning, but natural genetic variation in this trait has yet to be assessed. We conducted a reversal-learning regime on a diverse panel of Drosophila melanogaster genotypes. We found highly significant genetic variation in their baseline ability to learn. We also found that they have a consistent, and strong (1.3×, increase in their learning speed with reversal. We found no evidence, however, that there was genetic variation in their ability to increase their learning rates with experience. This may suggest that Drosophila have a hitherto unrecognized ability to integrate acquired information, and improve their decision making; but that their mechanisms for doing so are under strong constraints.

  16. Single Locus Maintains Large Variation of Sex Reversal in Half-Smooth Tongue Sole (Cynoglossus semilaevis

    Directory of Open Access Journals (Sweden)

    Li Jiang

    2017-02-01

    Full Text Available Sex determination is a fundamental biological process for individual sex development and population sex ratios. However, for some species, the primary sex might be altered during development, and individuals can develop into the opposite sex. Sex reversal may happen in insects, reptiles, amphibians, and fishes. In half-smooth tongue sole (Cynoglossus semilaevis, some genetically female fish irreversibly reverse to pseudomales, resulting in higher costs in aquaculture owing to a lower growth rate of male fish during a 2-yr growth period. Here, we identified a locus with large controlling effect on sex reversal in the half-smooth tongue sole through genome-wide association study with high-density single nucleotide polymorphisms (SNPs. This SNP is located at the third intron of the F-box and leucine rich repeat protein 17 (FBXL17 gene on the Z chromosome, and it has two alleles, A and T. Genetic females with ZAW genotypes will never reverse into phenotypic males, but those with ZTW genotypes can sometimes undergo sex reversal. This SNP explains 82.7% of the genetic variation, or 58.4% of the phenotypic variation. Based on our results, a reproductive management program could be developed to improve the phenotypic female ratio in aquaculture, and elucidate the mechanism of sex reversal in half-smooth tongue sole. We expect that these findings will have a substantial impact on the population management in many harvested species where sex reversal occurs.

  17. Single Locus Maintains Large Variation of Sex Reversal in Half-Smooth Tongue Sole (Cynoglossus semilaevis).

    Science.gov (United States)

    Jiang, Li; Li, Hengde

    2017-02-09

    Sex determination is a fundamental biological process for individual sex development and population sex ratios. However, for some species, the primary sex might be altered during development, and individuals can develop into the opposite sex. Sex reversal may happen in insects, reptiles, amphibians, and fishes. In half-smooth tongue sole ( Cynoglossus semilaevis ), some genetically female fish irreversibly reverse to pseudomales, resulting in higher costs in aquaculture owing to a lower growth rate of male fish during a 2-yr growth period. Here, we identified a locus with large controlling effect on sex reversal in the half-smooth tongue sole through genome-wide association study with high-density single nucleotide polymorphisms (SNPs). This SNP is located at the third intron of the F-box and leucine rich repeat protein 17 ( FBXL17 ) gene on the Z chromosome, and it has two alleles, A and T. Genetic females with Z A W genotypes will never reverse into phenotypic males, but those with Z T W genotypes can sometimes undergo sex reversal. This SNP explains 82.7% of the genetic variation, or 58.4% of the phenotypic variation. Based on our results, a reproductive management program could be developed to improve the phenotypic female ratio in aquaculture, and elucidate the mechanism of sex reversal in half-smooth tongue sole. We expect that these findings will have a substantial impact on the population management in many harvested species where sex reversal occurs. Copyright © 2017 Jiang and Li.

  18. Vasectomy reversal: a clinical update

    Directory of Open Access Journals (Sweden)

    Abhishek P Patel

    2016-01-01

    Full Text Available Vasectomy is a safe and effective method of contraception used by 42-60 million men worldwide. Approximately 3%-6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage, or to alleviate the dreaded postvasectomy pain syndrome. Unlike vasectomy, vasectomy reversal is a much more technically challenging procedure that is performed only by a minority of urologists and places a larger financial strain on the patient since it is usually not covered by insurance. Interest in this procedure has increased since the operating microscope became available in the 1970s, which consequently led to improved patency and pregnancy rates following the procedure. In this clinical update, we discuss patient evaluation, variables that may influence reversal success rates, factors to consider in choosing to perform vasovasostomy versus vasoepididymostomy, and the usefulness of vasectomy reversal to alleviate postvasectomy pain syndrome. We also review the use of robotics for vasectomy reversal and other novel techniques and instrumentation that have emerged in recent years to aid in the success of this surgery.

  19. Genetic Disorders

    Science.gov (United States)

    ... This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from ... during your lifetime. There are three types of genetic disorders: Single-gene disorders, where a mutation affects ...

  20. Genetic Counseling

    Science.gov (United States)

    ... and their families. Clinical Geneticists Clinical geneticists are medical doctors with special training in genetics. In addition to educating families about genetic conditions, they perform clinical exams and order lab tests to diagnose the causes ...

  1. Genetic modification and genetic determinism

    Science.gov (United States)

    Resnik, David B; Vorhaus, Daniel B

    2006-01-01

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

  2. Genetic modification and genetic determinism.

    Science.gov (United States)

    Resnik, David B; Vorhaus, Daniel B

    2006-06-26

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  3. Imaging Genetics

    Science.gov (United States)

    Munoz, Karen E.; Hyde, Luke W.; Hariri, Ahmad R.

    2009-01-01

    Imaging genetics is an experimental strategy that integrates molecular genetics and neuroimaging technology to examine biological mechanisms that mediate differences in behavior and the risks for psychiatric disorder. The basic principles in imaging genetics and the development of the field are discussed.

  4. Reverse innovation in maternal health.

    Science.gov (United States)

    Firoz, Tabassum; Makanga, Prestige Tatenda; Nathan, Hannah L; Payne, Beth; Magee, Laura A

    2017-09-01

    Reverse innovation, defined as the flow of ideas from low- to high-income settings, is gaining traction in healthcare. With an increasing focus on value, investing in low-cost but effective and innovative solutions can be of mutual benefit to both high- and low-income countries. Reverse innovation has a role in addressing maternal health challenges in high-income countries by harnessing these innovative solutions for vulnerable populations especially in rural and remote regions. In this paper, we present three examples of 'reverse innovation' for maternal health: a low-cost, easy-to-use blood pressure device (CRADLE), a diagnostic algorithm (mini PIERS) and accompanying mobile app (PIERS on the Move), and a novel method for mapping maternal outcomes (MOM).

  5. MRI reveals reversible lesions resembling posterior reversible encephalopathy in porphyria

    Energy Technology Data Exchange (ETDEWEB)

    Celik, M. [Huesrev Gerede c, 128/4 Tesvikiye, 80690 Istanbul (Turkey); Department of Neurology, Sisli Etfal Education and Research Hospital, Sisli Etfal S., Sisli, Istanbul (Turkey); Forta, H.; Babacan, G. [Department of Neurology, Sisli Etfal Education and Research Hospital, Sisli Etfal S., Sisli, Istanbul (Turkey); Dalkilic, Tuerker [Department of Neurosurgery, Sisli Etfal Education and Research Hospital, Sisli Etfal S., Sisli, Istanbul (Turkey)

    2002-10-01

    We report a 20-year-old woman who had an attack of acute intermittent porphyria with seizures, hallucinations, autonomic and somatic neuropathy. T2-weighted MRI revealed multiple lesions which were no longer visible 3 months later. We suggest a similar mechanism to posterior reversible encephalopathy underlying cerebral symptoms in porphyria. (orig.)

  6. What do reversible programs compute?

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock; Glück, Robert

    2011-01-01

    are not strictly classically universal, but that they support another notion of universality; we call this RTM-universality. Thus, even though the RTMs are sub-universal in the classical sense, they are powerful enough as to include a self-interpreter. Lifting this to other computation models, we propose r...... be the starting point of a computational theory of reversible computing. We provide a novel semantics-based approach to such a theory, using reversible Turing machines (RTMs) as the underlying computation model. We show that the RTMs can compute exactly all injective, computable functions. We find that the RTMs...

  7. Reference counting for reversible languages

    DEFF Research Database (Denmark)

    Mogensen, Torben Ægidius

    2014-01-01

    Modern programming languages and operating systems use heap memory that allows allocation and deallocation of memory to be decoupled, so they don't follow a stack discipline. Axelsen and Glück have presented a reversible heap manager where allocation and deallocation are each other's logical...... inverses: Freeing a block of memory is done by running the allocation procedure backwards. Axelsen and Glück use this heap manager to sketch implementation of a simple reversible functional language where pattern matching a constructor is the inverse of construction, so pattern-matching implies...

  8. Stagnation point reverse flow combustor

    Science.gov (United States)

    Zinn, Ben T. (Inventor); Neumeier, Yedidia (Inventor); Seitzman, Jerry M. (Inventor); Jagoda, Jechiel (Inventor); Weksler, Yoav (Inventor)

    2008-01-01

    A method for combusting a combustible fuel includes providing a vessel having an opening near a proximate end and a closed distal end defining a combustion chamber. A combustible reactants mixture is presented into the combustion chamber. The combustible reactants mixture is ignited creating a flame and combustion products. The closed end of the combustion chamber is utilized for directing combustion products toward the opening of the combustion chamber creating a reverse flow of combustion products within the combustion chamber. The reverse flow of combustion products is intermixed with combustible reactants mixture to maintain the flame.

  9. Reversible Multiparty Sessions with Checkpoints

    Directory of Open Access Journals (Sweden)

    Mariangiola Dezani-Ciancaglini

    2016-08-01

    Full Text Available Reversible interactions model different scenarios, like biochemical systems and human as well as automatic negotiations. We abstract interactions via multiparty sessions enriched with named checkpoints. Computations can either go forward or roll back to some checkpoints, where possibly different choices may be taken. In this way communications can be undone and different conversations may be tried. Interactions are typed with global types, which control also rollbacks. Typeability of session participants in agreement with global types ensures session fidelity and progress of reversible communications.

  10. Reversible logic gate using adiabatic superconducting devices.

    Science.gov (United States)

    Takeuchi, N; Yamanashi, Y; Yoshikawa, N

    2014-09-15

    Reversible computing has been studied since Rolf Landauer advanced the argument that has come to be known as Landauer's principle. This principle states that there is no minimum energy dissipation for logic operations in reversible computing, because it is not accompanied by reductions in information entropy. However, until now, no practical reversible logic gates have been demonstrated. One of the problems is that reversible logic gates must be built by using extremely energy-efficient logic devices. Another difficulty is that reversible logic gates must be both logically and physically reversible. Here we propose the first practical reversible logic gate using adiabatic superconducting devices and experimentally demonstrate the logical and physical reversibility of the gate. Additionally, we estimate the energy dissipation of the gate, and discuss the minimum energy dissipation required for reversible logic operations. It is expected that the results of this study will enable reversible computing to move from the theoretical stage into practical usage.

  11. Interplay between cigarette smoking and pulmonary reverse lipid transport.

    Science.gov (United States)

    Jubinville, Éric; Talbot, Maude; Bérubé, Jean-Christophe; Hamel-Auger, Mélanie; Maranda-Robitaille, Michaël; Beaulieu, Marie-Josée; Aubin, Sophie; Paré, Marie-Ève; Kallend, David G; Arsenault, Benoit; Bossé, Yohan; Morissette, Mathieu C

    2017-09-01

    Reverse lipid transport is critical to maintain homeostasis. Smoking causes lipid accumulation in macrophages, therefore suggesting suboptimal reverse lipid transport mechanisms. In this study, we investigated the interplay between smoking and reverse lipid transport and the consequences on smoking-induced lung and peripheral alterations.To investigate the relationship between smoking and reverse lipid transport, we used a clinical lung gene expression dataset and a mouse model of cigarette smoke exposure. We also used ApoA-1(-/-) mice, with reduced reverse lipid transport capacity, and a recombinant ApoA-1 Milano/phospholipid complex (MDCO-216) to boost reverse lipid transport. Cellular and functional analyses were performed on the lungs and impact on body composition was also assessed.Smoking affects pulmonary expression of abca1, abcg1, apoe and scarb1 in both mice and humans, key genes involved in reverse lipid transport. In mice, the capacity of bronchoalveolar lavage fluid and serum to stimulate cholesterol efflux in macrophages was increased after a single exposure to cigarette smoke. ApoA-1(-/-) mice showed increased lung neutrophilia, larger macrophages and greater loss in lean mass in response to smoking, whereas treatment with MDCO-216 reduced the size of macrophages and increased the lean mass of mice exposed to cigarette smoke.Altogether, this study shows a functional interaction between smoking and reverse lipid transport, and opens new avenues for better understanding the link between metabolic and pulmonary diseases related to smoking. Copyright ©ERS 2017.

  12. CAPSULE REPORT: REVERSE OSMOSIS PROCESS

    Science.gov (United States)

    A failure analysis has been completed for the reverse osmosis (RO) process. The focus was on process failures that result in releases of liquids and vapors to the environment. The report includes the following: 1) A description of RO and coverage of the principles behind the proc...

  13. Reversibility of chronic airflow obstruction

    NARCIS (Netherlands)

    Postma, Dirkje Sjoukje

    1984-01-01

    This thesis deals with variations in airway diameter in patients with chronic, partly reversible airflow obstruction. The patients studied in this thesis have been addressed in the literature with terms as CAO, COPD, CNSLD. The confusion caused by combining patients in one descriptive term, e.g.

  14. Vasectomy reversal : a clinical update

    NARCIS (Netherlands)

    A.P. Patel (Abhishek); R.P. Smith (Ryan)

    2016-01-01

    textabstractVasectomy is a safe and effective method of contraception used by 42-60 million men worldwide. Approximately 3%-6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage,

  15. A Framework for Reverse Logistics

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); R. Dekker (Rommert)

    2003-01-01

    textabstractReverse Logistics has been stretching out worldwide, involving all the layers of supply chains in various industry sectors. While some actors in the chain have been forced to take products back, others have pro-actively done so, attracted by the value in used products One way or the

  16. Reversible blindness in fulminating preeclampsia

    African Journals Online (AJOL)

    blindness can be due to involvement of the occipital cortex or the retina. Although very alarming, this type of blindness is usually reversible following appropriate management of such patients. Here we present the case of a woman in whom fulminating preeclampsia was complicated by blindness. Fundoscopic findings were ...

  17. Reversible simulations of elastic collisions

    Energy Technology Data Exchange (ETDEWEB)

    Perumalla, Kalyan S.; Protopopescu, Vladimir A.

    2013-05-01

    Consider a system of N identical hard spherical particles moving in a d-dimensional box and undergoing elastic, possibly multi-particle, collisions. We develop a new algorithm that recovers the pre-collision state from the post-collision state of the system, across a series of consecutive collisions, \\textit{with essentially no memory overhead}. The challenge in achieving reversibility for an n-particle collision (where, in general, n<< N) arises from the presence of nd-d-1 degrees of freedom (arbitrary angles) during each collision, as well as from the complex geometrical constraints placed on the colliding particles. To reverse the collisions in a traditional simulation setting, all of the particular realizations of these degrees of freedom (angles) during the forward simulation must be tracked. This requires memory proportional to the number of collisions, which grows very fast with N and d, thereby severely limiting the \\textit{de facto} applicability of the scheme. This limitation is addressed here by first performing a pseudo-randomization of angles, which ensures determinism in the reverse path for any values of n and d. To address the more difficult problem of geometrical and dynamic constraints, a new approach is developed which correctly samples the constrained phase space. Upon combining the pseudo-randomization with correct phase space sampling, perfect reversibility of collisions is achieved, as illustrated for n<=3, d=2, and n=2, d=3. This result enables, for the first time, reversible simulations of elastic collisions with essentially zero memory accumulation. In principle, the approach presented here could be generalized to larger values of n, which would be of definite interest for molecular dynamics simulations at high densities.

  18. Network Mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways.

    Science.gov (United States)

    Burgess, Stephen; Daniel, Rhian M; Butterworth, Adam S; Thompson, Simon G

    2015-04-01

    Mendelian randomization uses genetic variants, assumed to be instrumental variables for a particular exposure, to estimate the causal effect of that exposure on an outcome. If the instrumental variable criteria are satisfied, the resulting estimator is consistent even in the presence of unmeasured confounding and reverse causation. We extend the Mendelian randomization paradigm to investigate more complex networks of relationships between variables, in particular where some of the effect of an exposure on the outcome may operate through an intermediate variable (a mediator). If instrumental variables for the exposure and mediator are available, direct and indirect effects of the exposure on the outcome can be estimated, for example using either a regression-based method or structural equation models. The direction of effect between the exposure and a possible mediator can also be assessed. Methods are illustrated in an applied example considering causal relationships between body mass index, C-reactive protein and uric acid. These estimators are consistent in the presence of unmeasured confounding if, in addition to the instrumental variable assumptions, the effects of both the exposure on the mediator and the mediator on the outcome are homogeneous across individuals and linear without interactions. Nevertheless, a simulation study demonstrates that even considerable heterogeneity in these effects does not lead to bias in the estimates. These methods can be used to estimate direct and indirect causal effects in a mediation setting, and have potential for the investigation of more complex networks between multiple interrelated exposures and disease outcomes. © The Author 2014. Published by Oxford University Press on behalf of the International Epidemiological Association.

  19. Single Locus Maintains Large Variation of Sex Reversal in Half-Smooth Tongue Sole (Cynoglossus semilaevis)

    OpenAIRE

    Jiang, Li; Li, Hengde

    2016-01-01

    Sex determination is a fundamental biological process for individual sex development and population sex ratios. However, for some species, the primary sex might be altered during development, and individuals can develop into the opposite sex. Sex reversal may happen in insects, reptiles, amphibians, and fishes. In half-smooth tongue sole (Cynoglossus semilaevis), some genetically female fish irreversibly reverse to pseudomales, resulting in higher costs in aquaculture owing to a lower growth ...

  20. Sex reversal and primary sex ratios in the common frog (Rana temporaria).

    Science.gov (United States)

    Alho, Jussi S; Matsuba, Chikako; Merilä, Juha

    2010-05-01

    Sex reversal has been suggested to have profound implications for the evolution of sex chromosomes and population dynamics in ectotherms. Occasional sex reversal of genetic males has been hypothesized to prevent the evolutionary decay of nonrecombining Y chromosomes caused by the accumulation of deleterious mutations. At the same time, sex reversals can have a negative effect on population growth rate. Here, we studied phenotypic and genotypic sex in the common frog (Rana temporaria) in a subarctic environment, where strongly female-biased sex ratios have raised the possibility of frequent sex reversals. We developed two novel sex-linked microsatellite markers for the species and used them with a third, existing marker and a Bayesian modelling approach to study the occurrence of sex reversal and to determine primary sex ratios in egg clutches. Our results show that a significant proportion (0.09, 95% credible interval: 0.04-0.18) of adults that were genetically female expressed the male phenotype, but there was no evidence of sex reversal of genetic males that is required for counteracting the degeneration of Y chromosome. The primary sex ratios were mostly equal, but three clutches consisted only of genetic females and three others had a significant female bias. Reproduction of the sex-reversed genetic females appears to create all-female clutches potentially skewing the population level adult sex-ratio consistent with field observations. However, based on a simulation model, such a bias is expected to be small and transient and thus does not fully explain the observed female-bias in the field.

  1. Calmodulin-mediated reversible immobilization of enzymes.

    Science.gov (United States)

    Daunert, Sylvia; Bachas, Leonidas G; Schauer-Vukasinovic, Vesna; Gregory, Kalvin J; Schrift, G; Deo, Sapna

    2007-07-01

    This work demonstrates the use of the protein calmodulin, CaM, as an affinity tag for the reversible immobilization of enzymes on surfaces. Our strategy takes advantage of the of the reversible, calcium-mediated binding of CaM to its ligand phenothiazine and of the ability to produce fusion proteins between CaM and a variety of enzymes to reversibly immobilize enzymes in an oriented fashion to different surfaces. Specifically, we employed two different enzymes, organophosphorus hydrolase (OPH) and beta-lactamase and two different solid supports, a silica surface and cellulose membrane modified by covalently attaching a phenothiazine ligand, to demonstrate the versatility of our immobilization method. Fusion proteins between CaM-OPH and CaM-beta-lactamase were prepared by using genetic engineering strategies to introduce the calmodulin tail at the N-terminus of each of the two enzymes. In the presence of Ca(2+), CaM adopts a conformation that favors interaction between hydrophobic pockets in CaM and phenothiazine, while in the presence of a Ca(2+)-chelating agent such as EGTA, the interaction between CaM and phenothiazine is disrupted, thus allowing for removal of the CaM-fusion protein from the surface under mild conditions. CaM also acts as a spacer molecule, orienting the enzyme away from the surface and toward the solution, which minimizes enzyme interactions with the immobilization surface. Since the method is based on the highly selective binding of CaM to its phenothiazine ligand, and this is covalently immobilized on the surface, the method does not suffer from ligand leaching nor from interference from other proteins present in the cell extract. An additional advantage lies in that the support can be regenerated by passing through EGTA, and then reused for the immobilization of the same or, if desired, a different enzyme. Using a fusion protein approach for immobilization purposes avoids the use of harsh conditions in the immobilization and/or regeneration

  2. Genetic polymorphisms in catalase and CYP1B1 determine DNA adduct formation by bento(a)pyrene ex vivo

    NARCIS (Netherlands)

    Schults, Marten A.; Chiu, Roland K.; Nagle, Peter; Kleinjans, J C; van Schooten, Frederik Jan; Godschalk, Roger W.

    Genetic polymorphisms can partially explain the large inter-individual variation in DNA adduct levels following exposure to polycyclic aromatic hydrocarbons. Effects of genetic polymorphisms on DNA adduct formation are difficult to assess in human studies because exposure misclassification

  3. Genetic barcodes

    Science.gov (United States)

    Weier, Heinz -Ulrich G

    2015-08-04

    Herein are described multicolor FISH probe sets termed "genetic barcodes" targeting several cancer or disease-related loci to assess gene rearrangements and copy number changes in tumor cells. Two, three or more different fluorophores are used to detect the genetic barcode sections thus permitting unique labeling and multilocus analysis in individual cell nuclei. Gene specific barcodes can be generated and combined to provide both numerical and structural genetic information for these and other pertinent disease associated genes.

  4. Exposure Prophylaxis

    African Journals Online (AJOL)

    opsig

    have the potential for exposure to infectious material, for example blood ... body fluid; wound causing bleeding and produced by sharp instrument ... Full blood count. Liver function test. Renal function test. HIV screening. Pregnancy test if EFV is considered. Two weeks. Full blood count. Liver function test. Renal function test.

  5. Data-mining-based automated reverse engineering and defect discovery

    Science.gov (United States)

    Smith, James F., III; Nguyen, ThanhVu H.

    2005-03-01

    A data mining based procedure for automated reverse engineering and defect discovery has been developed. The data mining algorithm for reverse engineering uses a genetic program (GP) as a data mining function. A GP is an evolutionary algorithm that automatically evolves populations of computer programs or mathematical expressions, eventually selecting one that is optimal in the sense it maximizes a fitness function. The system to be reverse engineered is typically a sensor that may not be disassembled and for which there are no design documents. The sensor is used to create a database of input signals and output measurements. Rules about the likely design properties of the sensor are collected from experts. The rules are used to create a fitness function for the GP allowing GP based data mining. This procedure incorporates not only the experts" rules into the fitness function, but also the information in the database. The information extracted through this process is the internal design specifications of the sensor. These design properties can be used to create a fitness function for a genetic algorithm, which is in turn used to search for defects in the digital logic design. Significant theoretical and experimental results are provided.

  6. Sex hormones alter sex ratios in the Indian skipper frog, Euphlyctis cyanophlyctis: Determining sensitive stages for gonadal sex reversal.

    Science.gov (United States)

    Phuge, S K; Gramapurohit, N P

    2015-09-01

    In amphibians, although genetic factors are involved in sex determination, gonadal sex differentiation can be modified by exogenous steroid hormones suggesting a possible role of sex steroids in regulating the process. We studied the effect of testosterone propionate (TP) and estradiol-17β (E2) on gonadal differentiation and sex ratio at metamorphosis in the Indian skipper frog, Euphlyctis cyanophlyctis with undifferentiated type of gonadal differentiation. A series of experiments were carried out to determine the optimum dose and sensitive stages for gonadal sex reversal. Our results clearly indicate the importance of sex hormones in controlling gonadal differentiation of E. cyanophlyctis. Treatment of tadpoles with 10, 20, 40, and 80μg/L TP throughout larval period resulted in the development of 100% males at metamorphosis at all concentrations. Similarly, treatment of tadpoles with 40μg/L TP during ovarian and testicular differentiation resulted in the development of 90% males, 10% intersexes and 100% males respectively. Treatment of tadpoles with 10, 20, 40, and 80μg/L E2 throughout larval period likewise produced 100% females at all concentrations. Furthermore, exposure to 40μg/L E2 during ovarian and testicular differentiation produced 95% females, 5% intersexes and 91% females, 9% intersexes respectively. Both TP and E2 were also effective in advancing the stages of gonadal development. Present study shows the effectiveness of both T and E2 in inducing complete sex reversal in E. cyanophlyctis. Generally, exposure to E2 increased the larval period resulting in significantly larger females than control group while the larval period of control and TP treated groups was comparable. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Inhibition of Reverse Transcriptase Activity Increases Stability of the HIV-1 Core

    Science.gov (United States)

    Yang, Yang; Fricke, Thomas

    2013-01-01

    Previous studies showed that HIV-1 reverse transcription occurs during or before uncoating, linking mechanistically reverse transcription with uncoating. Here we show that inhibition of reverse transcriptase (RT) during HIV-1 infection by pharmacologic or genetic means increased the stability of the HIV-1 core during infection. Interestingly, HIV-1 particles with increased core stability were resistant to the core-destabilizing effects of rhesus TRIM5α (TRIM5αrh). Collectively, this work implies that the surface of the HIV-1 core is dynamic and changes upon the ongoing processes within the core. PMID:23077298

  8. A functional language for describing reversible logic

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal

    2012-01-01

    Reversible logic is a computational model where all gates are logically reversible and combined in circuits such that no values are lost or duplicated. This paper presents a novel functional language that is designed to describe only reversible logic circuits. The language includes high....... Reversibility of descriptions is guaranteed with a type system based on linear types. The language is applied to three examples of reversible computations (ALU, linear cosine transformation, and binary adder). The paper also outlines a design flow that ensures garbage- free translation to reversible logic...

  9. Reversible Watermarking Using Statistical Information

    Directory of Open Access Journals (Sweden)

    Kurugollu Fatih

    2010-01-01

    Full Text Available In most reversible watermarking methods, a compressed location map is exploited in order to ensure reversibility. Besides, in some methods, a header containing critical information is appended to the payload for the extraction and recovery process. Such schemes have a highly fragile nature; that is, changing a single bit in watermarked data may prohibit recovery of the original host as well as the embedded watermark. In this paper, we propose a new scheme in which utilizing a compressed location map is completely removed. In addition, the amount of auxiliary data is decreased by employing the adjacent pixels information. Therefore, in addition to quality improvement, independent authentication of different regions of a watermarked image is possible.

  10. Laparoscopic reversal of Hartmann's procedure

    DEFF Research Database (Denmark)

    Svenningsen, Peter Olsen; Bulut, Orhan; Jess, Per

    2010-01-01

    INTRODUCTION: A change in procedure from open to laparoscopic reversal of Hartmann's colostomy was implemented at our department between May 2005 and December 2008. The aim of the study was to investigate if this change was beneficial for the patients. MATERIAL AND METHODS: The medical records...... of all patients who underwent reversal of a colostomy after a primary Hartmann's procedure during the period May 2005 to December 2008 were reviewed retrospectively in a case-control study. RESULTS: A total of 43 patients were included. Twenty-one had a laparoscopic and 22 an open procedure. The two...... groups matched with regard to age, sex, American Society of Anestheologists (ASA) score, body mass index and indication for Hartmann's operation. A significantly longer operation time was found for laparoscopic than for open surgery (median 285 versus 158 minutes, p

  11. Reverse osmosis water purification system

    Science.gov (United States)

    Ahlstrom, H. G.; Hames, P. S.; Menninger, F. J.

    1986-01-01

    A reverse osmosis water purification system, which uses a programmable controller (PC) as the control system, was designed and built to maintain the cleanliness and level of water for various systems of a 64-m antenna. The installation operates with other equipment of the antenna at the Goldstone Deep Space Communication Complex. The reverse osmosis system was designed to be fully automatic; with the PC, many complex sequential and timed logic networks were easily implemented and are modified. The PC monitors water levels, pressures, flows, control panel requests, and set points on analog meters; with this information various processes are initiated, monitored, modified, halted, or eliminated as required by the equipment being supplied pure water.

  12. A Generalized Reverse Jacket Transform

    OpenAIRE

    Lee, Moon Ho; Rajan, Sundar B; Park, JY

    2001-01-01

    Generalization of the well-known Walsh-Hadamard transform (WHT), namely center-weighted Hadamard transform (CWHT) and complex reverse-jacket transform (CRJT) have been proposed and their fast implementation and simple index generation algorithms have recently been reported. These transforms are of size 2(r) x 2(r) for integral values or r, and defined in terms of binary radix representation of integers. In this paper, using appropriate mixed-radix representation of integers, we present a gene...

  13. Reversible Destruction of Dynamical Localization

    OpenAIRE

    Lignier, Hans; Chabé, Julien; Delande, Dominique; Garreau, Jean Claude; Szriftgiser, Pascal

    2005-01-01

    4 pages, 2 eps figures (color); Dynamical localization is a localization phenomenon taking place, for example, in the quantum periodically-driven kicked rotor. It is due to subtle quantum destructive interferences and is thus of intrinsic quantum origin. It has been shown that deviation from strict periodicity in the driving rapidly destroys dynamical localization. We report experimental results showing that this destruction is partially reversible when the deterministic perturbation that des...

  14. CONCEPTUAL ISSUES REGARDING REVERSE LOGISTICS

    Directory of Open Access Journals (Sweden)

    Ioana Olariu

    2013-12-01

    Full Text Available As the power of consumers is growing, the product return for customer service and customer retention has become a common practice in the competitive market, which propels the recent practice of reverse logistics in companies. Many firms attracted by the value available in the flow, have proactively participated in handling returned products at the end of their usefulness or from other parts of the product life cycle. Reverse logistics is the flow and management of products, packaging, components and information from the point of consumption to the point of origin. It is a collection of practices similar to those of supply chain management, but in the opposite direction, from downstream to upstream. It involves activities such as reuse, repair, remanufacture, refurbish, reclaim and recycle. For the conventional forward logistics systems, the flow starts upstream as raw materials, later as manufactured parts and components to be assembled and continues downstream to reach customers as final products to be disposed once they reach their economic or useful lives. In reverse logistics, the disposed products are pushed upstream to be repaired, remanufactured, refurbished, and disassembled into components to be reused or as raw material to be recycled for later use.

  15. Time order reversals and saccades.

    Science.gov (United States)

    Kresevic, Jesse L; Marinovic, Welber; Johnston, Alan; Arnold, Derek H

    2016-08-01

    Ballistic eye movements, or saccades, present a major challenge to the visual system. They generate a rapid blur of movement across the surface of the retinae that is rarely consciously seen, as awareness of input is suppressed around the time of a saccade. Saccades are also associated with a number of perceptual distortions. Here we are primarily interested in a saccade-induced illusory reversal of apparent temporal order. We examine the apparent order of transient targets presented around the time of saccades. In agreement with previous reports, we find evidence for an illusory reversal of apparent temporal order when the second of two targets is presented during a saccade - but this is only apparent for some observers. This contrasts with the apparent salience of targets presented during a saccade, which is suppressed for all observers. Our data suggest that separable processes might underlie saccadic suppressions of salience and saccade-induced reversals of apparent order. We suggest the latter arises when neural transients, normally used for timing judgments, are suppressed due to a saccade - but that this is an insufficient pre-condition. We therefore make the further suggestion, that the loss of a neural transient must be coupled with a specific inferential strategy, whereby some people assume that when they lack a clear impression of event timing, that event must have happened less recently than alternate events for which they have a clear impression of timing. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  16. Genetic modification and genetic determinism

    Directory of Open Access Journals (Sweden)

    Vorhaus Daniel B

    2006-06-01

    Full Text Available Abstract In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  17. Epigenetic modification and inheritance in sexual reversal of fish

    Science.gov (United States)

    Shao, Changwei; Li, Qiye; Chen, Songlin; Zhang, Pei; Lian, Jinmin; Hu, Qiaomu; Sun, Bing; Jin, Lijun; Liu, Shanshan; Wang, Zongji; Zhao, Hongmei; Jin, Zonghui; Liang, Zhuo; Li, Yangzhen; Zheng, Qiumei; Zhang, Yong; Wang, Jun; Zhang, Guojie

    2014-01-01

    Environmental sex determination (ESD) occurs in divergent, phylogenetically unrelated taxa, and in some species, co-occurs with genetic sex determination (GSD) mechanisms. Although epigenetic regulation in response to environmental effects has long been proposed to be associated with ESD, a systemic analysis on epigenetic regulation of ESD is still lacking. Using half-smooth tongue sole (Cynoglossus semilaevis) as a model—a marine fish that has both ZW chromosomal GSD and temperature-dependent ESD—we investigated the role of DNA methylation in transition from GSD to ESD. Comparative analysis of the gonadal DNA methylomes of pseudomale, female, and normal male fish revealed that genes in the sex determination pathways are the major targets of substantial methylation modification during sexual reversal. Methylation modification in pseudomales is globally inherited in their ZW offspring, which can naturally develop into pseudomales without temperature incubation. Transcriptome analysis revealed that dosage compensation occurs in a restricted, methylated cytosine enriched Z chromosomal region in pseudomale testes, achieving equal expression level in normal male testes. In contrast, female-specific W chromosomal genes are suppressed in pseudomales by methylation regulation. We conclude that epigenetic regulation plays multiple crucial roles in sexual reversal of tongue sole fish. We also offer the first clues on the mechanisms behind gene dosage balancing in an organism that undergoes sexual reversal. Finally, we suggest a causal link between the bias sex chromosome assortment in the offspring of a pseudomale family and the transgenerational epigenetic inheritance of sexual reversal in tongue sole fish. PMID:24487721

  18. Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation*

    Science.gov (United States)

    Kunchithapautham, Kannan; Atkinson, Carl; Rohrer, Bärbel

    2014-01-01

    Age-related macular degeneration (AMD) is a complex disease caused by genetic and environmental factors, including genetic variants in complement components and smoking. Smoke exposure leads to oxidative stress, complement activation, endoplasmic reticulum (ER) stress, and lipid dysregulation, which have all been proposed to be associated with AMD pathogenesis. Here we examine the effects of smoke exposure on the retinal pigment epithelium (RPE). Mice were exposed to cigarette smoke or filtered air for 6 months. RPE cells grown as stable monolayers were exposed to 5% cigarette smoke extract (CSE). Effects of smoke were determined by biochemical, molecular, and histological measures. Effects of the alternative pathway (AP) of complement and complement C3a anaphylatoxin receptor signaling were analyzed using knock-out mice or specific inhibitors. ER stress markers were elevated after smoke exposure in RPE of intact mice, which was eliminated in AP-deficient mice. To examine this relationship further, RPE monolayers were exposed to CSE. Short term smoke exposure resulted in production and release of complement C3, the generation of C3a, oxidative stress, complement activation on the cell membrane, and ER stress. Long term exposure to CSE resulted in lipid accumulation, and secretion. All measures were reversed by blocking C3a complement receptor (C3aR), alternative complement pathway signaling, and antioxidant therapy. Taken together, our results provide clear evidence that smoke exposure results in oxidative stress and complement activation via the AP, resulting in ER stress-mediated lipid accumulation, and further suggesting that oxidative stress and complement act synergistically in the pathogenesis of AMD. PMID:24711457

  19. Contribution of genetics to ecological restoration.

    Science.gov (United States)

    Mijangos, Jose Luis; Pacioni, Carlo; Spencer, Peter B S; Craig, Michael D

    2015-01-01

    Ecological restoration of degraded ecosystems has emerged as a critical tool in the fight to reverse and ameliorate the current loss of biodiversity and ecosystem services. Approaches derived from different genetic disciplines are extending the theoretical and applied frameworks on which ecological restoration is based. We performed a search of scientific articles and identified 160 articles that employed a genetic approach within a restoration context to shed light on the links between genetics and restoration. These articles were then classified on whether they examined association between genetics and fitness or the application of genetics in demographic studies, and on the way the studies informed restoration practice. Although genetic research in restoration is rapidly growing, we found that studies could make better use of the extensive toolbox developed by applied fields in genetics. Overall, 41% of reviewed studies used genetic information to evaluate or monitor restoration, and 59% provided genetic information to guide prerestoration decision-making processes. Reviewed studies suggest that restoration practitioners often overlook the importance of including genetic aspects within their restoration goals. Even though there is a genetic basis influencing the provision of ecosystem services, few studies explored this relationship. We provide a view of research gaps, future directions and challenges in the genetics of restoration. © 2014 John Wiley & Sons Ltd.

  20. Genetic Mapping

    Science.gov (United States)

    ... at NHGRI About About the Institute Budget and Financial Information Divisions Director's Page How to Contact Us Institute ... genome, has greatly advanced genetics research. The improved quality of genetic ... for Biotechnology Information (NCBI) [ncbi.nlm.nih.gov], as well as ...

  1. Genetic Engineering

    Science.gov (United States)

    Phillips, John

    1973-01-01

    Presents a review of genetic engineering, in which the genotypes of plants and animals (including human genotypes) may be manipulated for the benefit of the human species. Discusses associated problems and solutions and provides an extensive bibliography of literature relating to genetic engineering. (JR)

  2. Excessive state switching underlies reversal learning deficits in cocaine users.

    Science.gov (United States)

    Patzelt, Edward H; Kurth-Nelson, Zeb; Lim, Kelvin O; MacDonald, Angus W

    2014-01-01

    Markers of chronic cocaine exposure on neural mechanisms in animals and humans is of great interest. The probabilistic reversal-learning task may be an effective way to examine dysfunction associated with cocaine addiction. However the exact nature of the performance deficits observed in cocaine users has yet to be disambiguated. Data from a probabilistic reversal-learning task performed by 45 cocaine users and 41 controls was compared and fit to a Bayesian hidden Markov model (HMM). Cocaine users demonstrated the predicted performance deficit in achieving the reversal criterion relative to controls. The deficit appeared to be due to excessive switching behavior as evidenced by responsivity to false feedback and spontaneous switching. This decision-making behavior could be captured by a single parameter in an HMM and did not require an additional parameter to represent perseverative errors. Cocaine users are characterized by excessive switching behavior on the reversal-learning task. While there may be a compulsive component to behavior on this task, impulsive decision-making may be more relevant to observed impairment. This is important in building diagnostic tools to quantify the degree to which each type of dysfunction is present in individuals, and may play a role in developing treatments for those dysfunctions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. ECOLOGICAL AND EVOLUTIONARY APPLICATIONS FOR ENVIRONMENTAL SEX REVERSAL OF FISH.

    Science.gov (United States)

    Mcnair, Alistair; Lokman, P Mark; Closs, Gerard P; Nakagawa, Shinichi

    2015-03-01

    Environmental sex reversal (ESR), which results in a mismatch between genotypic and phenotypic sex, is well documented in numerous fish species and may be induced by chemical exposure. Historically, research involving piscine ESR has been carried out with a view to improving profitability in aquaculture or to elucidate the processes governing sex determination and sexual differentiation. However, recent studies in evolution and ecology suggest research on ESR now has much wider applications and ramifications. We begin with an overview of ESR in fish and a brief review of the traditional applications thereof. We then discuss ESR and its potential demographic consequences in wild populations. Theory even suggests sex-reversed fish may be purposefully released to manipulate population dynamics. We suggest new research directions that may prove fruitful in understanding how ESR at the individual level translates to population-level processes. In the latter portion of the review we focus on evolutionary applications of ESR. Sex-reversal studies from the aquaculture literature provide insight in to the evolvability of determinants of sexual phenotype. Additionally, induced sex reversal can provide information about the evolution of sex chromosomes and sex-linked traits. Recently, naturally occurring ESR has been implicated as a mechanism contributing to the evolution of sex chromosomes.

  4. Natural Compounds: Role in Reversal of Epigenetic Changes.

    Science.gov (United States)

    Aggarwal, Ruchi; Jha, Meenakshi; Shrivastava, Anju; Jha, Abhimanyu Kumar

    2015-08-01

    The hallmarks of carcinogenesis are characterized by alterations in the expression of multiple genes that occur via genetic and epigenetic alterations, leading to genome rearrangements and instability. The reversible process of epigenetic regulation, which includes changes in DNA methylation, histone modifications, and alteration in microRNA (miRNA) expression that alter phenotype without any change in the DNA sequence, is recognized as a key mechanism in cancer cell metabolism. Recent advancements in the rapidly evolving field of cancer epigenetics have shown the anticarcinogenic potential of natural compounds targeting epigenetic mechanism as a common molecular approach for cancer treatment. This review summarizes the potential of natural chemopreventive agents to reverse cancer-related epigenetic aberrations by regulating the activity of histone deacetylases, histone acetyltransferases, DNA methyltransferase I, and miRNAs. Furthermore, there is impetus for determining novel and effective chemopreventive strategies, either alone or in combination with other anticancer agents that exhibit similar properties, for improving the therapeutic aspects of cancer.

  5. Exposures series

    OpenAIRE

    Stimson, Blake

    2011-01-01

    Reaktion Books’ Exposures series, edited by Peter Hamilton and Mark Haworth-Booth, is comprised of 13 volumes and counting, each less than 200 pages with 80 high-quality illustrations in color and black and white. Currently available titles include Photography and Australia, Photography and Spirit, Photography and Cinema, Photography and Literature, Photography and Flight, Photography and Egypt, Photography and Science, Photography and Africa, Photography and Italy, Photography and the USA, P...

  6. Reversible logic gate using adiabatic superconducting devices

    National Research Council Canada - National Science Library

    Takeuchi, N; Yamanashi, Y; Yoshikawa, N

    2014-01-01

    .... However, until now, no practical reversible logic gates have been demonstrated. One of the problems is that reversible logic gates must be built by using extremely energy-efficient logic devices...

  7. SELECTED PROBLEMS OF REVERSE LOGISTICS IN POLAND

    OpenAIRE

    Agata Mesjasz-Lech

    2009-01-01

    This paper presents the essence of reverse logistics and directions of physical and information flows between logistic network partners. It also analyses effects of implementation of the principles of reverse logistics in Poland in the years 2004-2007

  8. Reversible logic gate using adiabatic superconducting devices

    OpenAIRE

    Takeuchi, N.; Y. Yamanashi; Yoshikawa, N.

    2014-01-01

    Reversible computing has been studied since Rolf Landauer advanced the argument that has come to be known as Landauer's principle. This principle states that there is no minimum energy dissipation for logic operations in reversible computing, because it is not accompanied by reductions in information entropy. However, until now, no practical reversible logic gates have been demonstrated. One of the problems is that reversible logic gates must be built by using extremely energy-efficient logic...

  9. Reverse Skyline Computation over Sliding Windows

    OpenAIRE

    Junchang Xin; Zhiqiong Wang; Mei Bai; Guoren Wang

    2015-01-01

    Reverse skyline queries have been used in many real-world applications such as business planning, market analysis, and environmental monitoring. In this paper, we investigated how to efficiently evaluate continuous reverse skyline queries over sliding windows. We first theoretically analyzed the inherent properties of reverse skyline on data streams and proposed a novel pruning technique to reduce the number of data points preserved for processing continuous reverse skyline queries. Then, an ...

  10. Magnetic reversals from planetary dynamo waves

    DEFF Research Database (Denmark)

    Sheyko, Andrey; Finlay, Chris; Jackson, Andrew

    2016-01-01

    A striking feature of many natural dynamos is their ability to undergo polarity reversals. The best documented example is Earth's magnetic field, which has reversed hundreds of times during its history. The origin of geomagnetic polarity reversals lies in a magnetohydrodynamic process that takes ...... to kinematic dynamo waves. Because our results are relevant in a regime of low viscosity and high magnetic diffusivity, and with geophysically appropriate boundary conditions, this form of dynamo wave may also be involved in geomagnetic reversals....

  11. Managing reverse exchanges in service supply chains

    OpenAIRE

    Kumar, V.; Amorim, M.; Bhattacharya, A; Garza, J.

    2016-01-01

    Purpose\\ud \\ud This study aims to address the management of reverse flows in the context of service supply chains. The study builds on the characteristics of services production reported in literature to: identify diverse types of reverse flows in services supply chains; discuss key issues associated to the management of reverse service flows; and suggest directions for research for developing the knowledge for management of reverse flows in service contexts.\\ud \\ud Design/Methodology/Approac...

  12. Environmental enrichment reverses memory impairment induced by toluene in mice.

    Science.gov (United States)

    Montes, Sergio; Solís-Guillén, Rocío Del Carmen; García-Jácome, David; Páez-Martínez, Nayeli

    2017-05-01

    Toluene is the main component of a variety of inhalants that are used for intoxication purposes. Alterations in memory have been reported in inhalant users; however, it is unclear whether these impairments could be reversed, and the mechanisms involved in the putative recovery. Therefore, the main purpose of this study was to model the deleterious effects of toluene on memory in mice and to evaluate the effect of environmental enrichment on that response. In the second part of the study, the concentrations of glutamate and GABA, following chronic toluene exposure and after environmental enrichment treatment, were evaluated. Adolescent mice were exposed to either a single or repeated schedule of toluene administration and their responses to object recognition were analyzed. An independent group of mice was repeatedly exposed to toluene and then housed either under environmental enrichment or standard conditions for four weeks. At the end of the housing period, the rodents' performance in object recognition test, as well as the concentrations of neurotransmitters, were analyzed. The results showed that toluene caused memory impairment in mice that received a single or repeated solvent exposure. Remarkably, environmental enrichment could reverse memory deficits induced by repeated administration of toluene. Cessation of toluene exposure in mice in standard housing did not produce that response. The glutamate and GABA tissue contents were not involved in the effects of toluene or environmental enrichment of memory. Copyright © 2017. Published by Elsevier Inc.

  13. Sunflower genetic, genomic and ecological resources.

    Science.gov (United States)

    Kane, Nolan C; Burke, John M; Marek, Laura; Seiler, Gerald; Vear, Felicity; Baute, Gregory; Knapp, Steven J; Vincourt, Patrick; Rieseberg, Loren H

    2013-01-01

    Long a major focus of genetic research and breeding, sunflowers (Helianthus) are emerging as an increasingly important experimental system for ecological and evolutionary studies. Here, we review the various attributes of wild and domesticated sunflowers that make them valuable for ecological experimentation and describe the numerous publicly available resources that have enabled rapid advances in ecological and evolutionary genetics. Resources include seed collections available from germplasm centres at the USDA and INRA, genomic and EST sequences, mapping populations, genetic markers, genetic and physical maps and other forward- and reverse-genetic tools. We also discuss some of the key evolutionary, genetic and ecological questions being addressed in sunflowers, as well as gaps in our knowledge and promising areas for future research. © 2012 Blackwell Publishing Ltd.

  14. Dynamic Reverse Code Generation for Backward Execution

    DEFF Research Database (Denmark)

    Lee, Jooyong

    2007-01-01

    . In this paper, we present a method to generate reverse code, so that backtracking can be performed by executing reverse code. The novelty of our work is that we generate reverse code on-the-fly, while running a debugger, which makes it possible to apply the method even to debugging multi-threaded programs....

  15. THEORETICAL FRAMES FOR DESIGNING REVERSE LOGISTICS PROCESSES

    OpenAIRE

    Janusz K. Grabara; Sebastian Kot

    2009-01-01

    Logistics processes of return flow became more and more important in present business practice. Because of better customer satisfaction, environmental and financial aspects many enterprises deal with reverse logistics performance. The paper is a literature review focused on the design principles of reverse logistics processes Keywords: reverse logistics, designing.

  16. Prefix reversals on binary and ternary strings

    NARCIS (Netherlands)

    Hurkens, C.A.J.; van Iersel, L.J.J.; Keijsper, J.C.M.; Kelk, S.M.; Stougie, L.; Tromp, J.T.

    2007-01-01

    Given a permutation $\\pi$, the application of prefix reversal $f^{(i)}$ to $\\pi$ reverses the order of the first $i$ elements of $\\pi$. The problem of sorting by prefix reversals (also known as pancake flipping), made famous by Gates and Papadimitriou (Discrete Math., 27 (1979), pp. 47–57), asks

  17. Cleaning Our World through Reverse Graffiti

    Science.gov (United States)

    Randazzo, Gabe; LaJevic, Lisa

    2013-01-01

    Over the last decade artists have begun to experiment with "reverse pollution" techniques, such as reverse graffiti, which focuses on cleaning environmental surfaces. Having recently been introduced to the works of Moose, the artist known for inventing the reverse graffiti technique, the authors decided to design a curriculum to increase…

  18. From Genetics to Genetic Algorithms

    Indian Academy of Sciences (India)

    The strings of artificial genetic systems are analogous to chromosomes. GENERAL I ARTICLE. GAs operate by combining the information present in different possible solutions for a given problem, in such a way that a better solution is obtained in future generations. Terminologies used in natural genetic systems (NGS) and.

  19. Remote Whispering Applying Time Reversal

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Brian Eric [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-07-16

    The purpose of this project was to explore the use of time reversal technologies as a means for communication to a targeted individual or location. The idea is to have the privacy of whispering in one’s ear, but to do this remotely from loudspeakers not located near the target. Applications of this work include communicating with hostages and survivors in rescue operations, communicating imaging and operational conditions in deep drilling operations, monitoring storage of spent nuclear fuel in storage casks without wires, or clandestine activities requiring signaling between specific points. This technology provides a solution in any application where wires and radio communications are not possible or not desired. It also may be configured to self calibrate on a regular basis to adjust for changing conditions. These communications allow two people to converse with one another in real time, converse in an inaudible frequency range or medium (i.e. using ultrasonic frequencies and/or sending vibrations through a structure), or send information for a system to interpret (even allowing remote control of a system using sound). The time reversal process allows one to focus energy to a specific location in space and to send a clean transmission of a selected signal only to that location. In order for the time reversal process to work, a calibration signal must be obtained. This signal may be obtained experimentally using an impulsive sound, a known chirp signal, or other known signals. It may also be determined from a numerical model of a known environment in which the focusing is desired or from passive listening over time to ambient noise.

  20. Multiple sclerosis genetics.

    Science.gov (United States)

    Canto, Ester; Oksenberg, Jorge R

    2018-01-01

    A broad scientific consensus has emerged linking multiple sclerosis (MS) risk to multiple independent and interacting DNA variants that are relatively frequent in the population and act in concert with environmental exposures. The multifactorial, polygenic model of heritability provided the rationale and impetus to pursue genome-wide association studies (GWAS), which have been highly successful in uncovering genetic variants influencing susceptibility. Over 200 loci have been firmly associated with MS susceptibility. The main association signal genome-wide maps to the major histocompatibility complex ( MHC) gene cluster in chromosome 6p21. This association has been observed across all populations studied. However, a significant proportion of MS heritability remains unexplained. Decoding the genetics of MS represents a long-standing and important research goal in this disease, as the demonstration of even modest functional genomic effects on risk or the course of MS is likely to reveal fundamental disease mechanisms and possibly yield new therapeutic opportunities.

  1. How to play Reverse Hex

    DEFF Research Database (Denmark)

    Toft, Bjarne; Hayward, Ryan B.; Henderson, Philip

    2012-01-01

    We present new results on how to play Reverse Hex, also known as Rex, or Misère Hex, on n × n boards. We give new proofs – and strengthened versions – of Lagarias and Sleator’s theorem (for n × n boards, each player can prolong the game until the board is full, so the first/second player can always......, we find second-player winning replies. Finally, in response to comments by Martin Gardner, for each n ≤ 5, we give a simple winning strategy for the n × n board....

  2. Controversial reversal of nuclear option

    Directory of Open Access Journals (Sweden)

    Mesarović Miodrag

    2002-01-01

    Full Text Available Nuclear option is in a unique position to restore its original role of the main source of energy with an increased attention paid to the security of electricity supply as well as regulatory changes affecting fossil fuels, particularly with due introduction of climate change prevention measures. Recent developments indicate the advantages of nuclear option over other possible options in terms of sustainable development. However, a large number of controversial issues on nuclear energy make its reversal less clear. These are discussed with particular attention paid to recent developments worldwide, including the World Summit on Sustainable Development held in September 2002 in Johannesburg, South Africa.

  3. Presbycusis: reversible with anesthesia drugs?

    Science.gov (United States)

    Kocher, Carl A

    2009-02-01

    Age-related hearing impairment, or presbycusis, is a degenerative condition not currently treatable by medication. It is therefore significant that the author, as a patient, experienced a reversal of high-frequency hearing loss during a 2-day period following abdominal surgery with general anesthesia. This report documents the surgery and the subsequent restoration of hearing, which was bilateral and is estimated to have exceeded 50dB at 4kHz. A possible role is noted for anesthetic agents such as lidocaine, propofol, or fentanyl. This experience may hold a clue for research toward the development of medical treatments for presbycusis.

  4. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    Science.gov (United States)

    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.

  5. Quantitative genetics of functional characters in Drosophila ...

    Indian Academy of Sciences (India)

    line-cross analysis; epistasis; dominance; adaptation; experimental evolution; reverse evolution; life-history evolution; quantitative genetics; Drosophila. ... set of five populations maintained for several hundred generations on a two-week discrete-generation life cycle and a set of five populations adapted to starvation stress.

  6. Understanding sex determination in the mouse: genetics ...

    Indian Academy of Sciences (India)

    sex determination; gonad development; organogenesis; mouse genetics; sex reversal; testis determination. ... One challenge now is to understand how controlled epigenomic changes effect the now familiar sexually dimorphic transcriptomic profiles of the male and female gonads, firstly during primary sex determination, but ...

  7. The art and design of genetic screens: maize

    Science.gov (United States)

    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...

  8. New Genetics

    Science.gov (United States)

    ... RNA, transcription, RNA splicing, translation, ribosomes, antibiotics, genetic diseases, gene chips. » more Chapter 2: RNA and DNA Revealed: New Roles, New Rules Covers microRNAs, RNAi, epigenetics, telomeres, mtDNA, recombinant DNA. » more Chapter 3: Life's ...

  9. Genetic Discrimination

    Science.gov (United States)

    Skip to main content Genetic Discrimination Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research News Features ...

  10. Exercise prescription to reverse frailty.

    Science.gov (United States)

    Bray, Nick W; Smart, Rowan R; Jakobi, Jennifer M; Jones, Gareth R

    2016-10-01

    Frailty is a clinical geriatric syndrome caused by physiological deficits across multiple systems. These deficits make it challenging to sustain homeostasis required for the demands of everyday life. Exercise is likely the best therapy to reverse frailty status. Literature to date suggests that pre-frail older adults, those with 1-2 deficits on the Cardiovascular Health Study-Frailty Phenotype (CHS-frailty phenotype), should exercise 2-3 times a week, for 45-60 min. Aerobic, resistance, flexibility, and balance training components should be incorporated but resistance and balance activities should be emphasized. On the other hand, frail (CHS-frailty phenotype ≥ 3 physical deficits) older adults should exercise 3 times per week, for 30-45 min for each session with an emphasis on aerobic training. During aerobic, balance, and flexibility training, both frail and pre-frail older adults should work at an intensity equivalent to a rating of perceived exertion of 3-4 ("somewhat hard") on the Borg CR10 scale. Resistance-training intensity should be based on a percentage of 1-repetition estimated maximum (1RM). Program onset should occur at 55% of 1RM (endurance) and progress to higher intensities of 80% of 1RM (strength) to maximize functional gains. Exercise is the medicine to reverse or mitigate frailty, preserve quality of life, and restore independent functioning in older adults at risk of frailty.

  11. Reverse Skyline Computation over Sliding Windows

    Directory of Open Access Journals (Sweden)

    Junchang Xin

    2015-01-01

    Full Text Available Reverse skyline queries have been used in many real-world applications such as business planning, market analysis, and environmental monitoring. In this paper, we investigated how to efficiently evaluate continuous reverse skyline queries over sliding windows. We first theoretically analyzed the inherent properties of reverse skyline on data streams and proposed a novel pruning technique to reduce the number of data points preserved for processing continuous reverse skyline queries. Then, an efficient approach, called Semidominance Based Reverse Skyline (SDRS, was proposed to process continuous reverse skyline queries. Moreover, an extension was also proposed to handle n-of-N and (n1,n2-of-N reverse skyline queries. Our extensive experimental studies have demonstrated the efficiency as well as effectiveness of the proposed approach with various experimental settings.

  12. Genetic counseling.

    Science.gov (United States)

    Pina-Neto, João Monteiro de

    2008-08-01

    The objective of this review of genetic counseling (GC) is to describe the current concepts and philosophical and ethical principles accepted by the great majority of countries and recommended by the World Health Organization, the stages of the process, its results and the psychological impact that a genetic disease has on a family. The concepts presented are based on an historical synthesis of the literature on GC since the 1930s until today, and the articles cited represent the most important research published which today provides the foundation for the theory and practice of GC. The modern definition of GC is a process of communication that deals with the human problems related with the occurrence of a genetic disease in a family. It is of fundamental importance that health professionals are aware of the psychological aspects triggered by genetic diseases and the ways in which these can be managed. In the field of human and medical genetics we are still living in a phase in which technical and scientific aspects predominate, with little emphasis on the study of emotional reactions and people's processes of adaptation to these diseases, which leads to clients having a low level of understanding of the events that have taken place, with negative consequences for family life and for society. The review concludes by discussing the need to refer families with genetic diseases for GC and the need for professionals working in this area to invest more in humanizing care and developing non-directive psychological GC techniques.

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

    Science.gov (United States)

    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.…

  14. Genetic and Epigenetic of Medullary Thyroid Cancer

    Science.gov (United States)

    Khatami, Fatemeh; Tavangar, Seyed Mohammad

    2017-11-11

    Medullary thyroid carcinoma (MTC) is an infrequent, calcitonin producing neuroendocrine tumor and initiates from the parafollicular C cells of the thyroid gland. Several genetic and epigenetic alterations are collaterally responsible for medullary thyroid carcinogenesis. In this review article, we shed light on all the genetic and epigenetic hallmarks of MTC. From the genetic perspective, RET, HRAS, and KRAS are the most important genes that are characterized in MTC. From the epigenetic perspective, Ras-association domain family member 1A, telomerase reverse transcriptase promoter methylations, overexpression of histone methyltransferases, EZH2 and SMYD3, and wide ranging increase and decrease in non-coding RNAs can be responsible for medullary thyroid carcinogenesis.

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

    Science.gov (United States)

    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.

  16. Sexing a sex-role-reversed species based on plumage: potential challenges in the red phalarope

    Directory of Open Access Journals (Sweden)

    Marie-Andrée Giroux

    2016-05-01

    Full Text Available Sex-role reversal, in which males care for offspring, can occur when mate competition is stronger between females than males. Secondary sex traits and mate attracting displays in sex-role-reversed species are usually more pronounced in females than in males. The red phalarope (Phalaropus fulicarius is a textbook example of a sex-role-reversed species. It is generally agreed that males are responsible for all incubation and parental care duties, whereas females typically desert males after having completed a clutch and may pair with new males to lay additional clutches. The breeding plumage of female red phalaropes is usually more brightly colored than male plumage, a reversed sexual dichromatism usually associated with sex-role reversal. Here, we confirm with PCR-based sexing that male red phalaropes can exhibit both the red body plumage typical of a female and the incubation behavior typical of a male. Our result, combined with previous observations of brightly colored red phalaropes incubating nests at the same arctic location (Igloolik Island, Nunavut, Canada, suggests that plumage dichromatism alone may not be sufficient to distinguish males from females in this breeding population of red phalaropes. This stresses the need for more systematic genetic sexing combined with standardized description of intersexual differences in red phalarope plumages. Determining whether such female-like plumage on males is a result of phenotypic plasticity or genetic variation could contribute to further understanding sex-role reversal strategies in the short Arctic summer.

  17. Human biological monitoring of occupational genotoxic exposures

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Sorsa, M

    1993-01-01

    .g. the quantitation of identified DNA-adducts or substance unspecific as is the measurement of DNA-repair. The sample material used for analysis must be well characterized and subject to uniform processing for comparison of the results. Confounding factors of smoking, age and sex must be well controlled......) occupational exposure limit value of styrene in ambient air. The consideration of ethical issues in human genetic monitoring is an important but often overlooked aspect. This includes the scientific and preventional relevance of performing a test on individuals, pre- and post study information of donors......Human biological monitoring is a valuable tool for exposure assessment in groups of persons occupationally exposed to genotoxic agents. If the monitoring activity covers genetic material the term genetic monitoring is used. The methods used for genetic monitoring are either substance specific, e...

  18. J. Genet. classic 17

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 83, No. 1, April 2004. 17. Page 2. J. Genet. classic. Journal of Genetics, Vol. 83, No. 1, April 2004. 18. Page 3. J. Genet. classic. Journal of Genetics, Vol. 83, No. 1, April 2004. 19. Page 4. J. Genet. classic. Journal of Genetics, Vol. 83, No. 1, April 2004. 20. Page 5. J. Genet. classic. Journal of ...

  19. J. Genet. classic 99

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 84, No. 2, August 2005. 99. Page 2. J. Genet. classic. Journal of Genetics, Vol. 84, No. 2, August 2005. 100. Page 3. J. Genet. classic. Journal of Genetics, Vol. 84, No. 2, August 2005. 101. Page 4. J. Genet. classic. Journal of Genetics, Vol. 84, No. 2, August 2005. 102. Page 5. J. Genet. classic.

  20. J. Genet. classic 37

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 84, No. 1, April 2005. 37. Page 2. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 38. Page 3. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 39. Page 4. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 40. Page 5. J. Genet. classic. Journal of ...

  1. J. Genet. classic 101

    Indian Academy of Sciences (India)

    Journal of Genetics, Vol. 85, No. 2, August 2006. 101. Page 2. J. Genet. classic. 102. Journal of Genetics, Vol. 85, No. 2, August 2006. Page 3. J. Genet. classic. Journal of Genetics, Vol. 85, No. 2, August 2006. 103. Page 4. J. Genet. classic. 104. Journal of Genetics, Vol. 85, No. 2, August 2006. Page 5. J. Genet. classic.

  2. J. Genet. classic 125

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 83, No. 2, August 2004. 125. Page 2. J. Genet. classic. Journal of Genetics, Vol. 83, No. 2, August 2004. 126. Page 3. J. Genet. classic. Journal of Genetics, Vol. 83, No. 2, August 2004. 127. Page 4. J. Genet. classic. Journal of Genetics, Vol. 83, No. 2, August 2004. 128. Page 5. J. Genet. classic.

  3. J. Genet. classic 17

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 84, No. 1, April 2005. 17. Page 2. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 18. Page 3. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 19. Page 4. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 20. Page 5. J. Genet. classic. Journal of ...

  4. Reversibly assembled cellular composite materials.

    Science.gov (United States)

    Cheung, Kenneth C; Gershenfeld, Neil

    2013-09-13

    We introduce composite materials made by reversibly assembling a three-dimensional lattice of mass-produced carbon fiber-reinforced polymer composite parts with integrated mechanical interlocking connections. The resulting cellular composite materials can respond as an elastic solid with an extremely large measured modulus for an ultralight material (12.3 megapascals at a density of 7.2 milligrams per cubic centimeter). These materials offer a hierarchical decomposition in modeling, with bulk properties that can be predicted from component measurements and deformation modes that can be determined by the placement of part types. Because site locations are locally constrained, structures can be produced in a relative assembly process that merges desirable features of fiber composites, cellular materials, and additive manufacturing.

  5. Reverse Flow Pressure Limiting Aperture.

    Science.gov (United States)

    Danilatos

    2000-01-01

    The reverse flow pressure limiting aperture is a device that creates and sustains a substantial gas pressure difference between two chambers connected via an aperture. The aperture is surrounded by an annular orifice leading to a third chamber. The third chamber is maintained at a relatively high pressure that forces gas to flow through the annular aperture into the first of said two chambers. The ensuing gas flow develops into a supersonic annular gas jet, the core of which is coaxial with the central aperture. A pumping action is created at the core of the jet and any gas molecules leaking through the aperture from the second chamber are entrained and forced into the first chamber, thus creating a substantial pressure difference between the first and second chamber.

  6. About Genetic Counselors

    Science.gov (United States)

    ... seeing a genetic counselor? Q. What is a genetic counselor? A. Genetic counselors are healthcare professionals with ... and serve as patient advocates. Q. What is genetic counseling? A. Genetic counseling is the process of ...

  7. [Process of HIV-1 reverse transcription and its detection by using PCR].

    Science.gov (United States)

    Yao, Wen-Xue; Wu, Ying-Liang; Guo, Ying

    2008-02-01

    Human immunodeficiency virus (HIV) is a retrovirus, belongs to Lentiviridae family. As long as viral genetic material entering into host cytoplasm, double-strand DNAs synthesis occurs which is catalyzed by reverse transcriptase (RT) with viral plus-strand RNA as template. This reverse transcription is a key link of HIV-1 life cycle and an important target for anti-HIV drug development. The process of reverse transcription can be divided into several steps: formation of minus-strand strong-stop DNA; the first translocation; initiation of plus-strand DNA synthesis; and, the second translocation and the completion of both strands. These steps can be detected individually by using polymerase chain reaction (PCR) according to the amplified products on the region of R/U5, U3, U5/PBS and the sequence between LTR and Gag. In this review, we summarize the principle for detecting stages of HIV-1 reverse transcription by using PCR.

  8. HIV integrase variability and genetic barrier in antiretroviral naïve and experienced patients

    Directory of Open Access Journals (Sweden)

    Comolli Giuditta

    2011-03-01

    Full Text Available Abstract Background HIV-1 integrase (IN variability in treatment naïve patients with different HIV-1 subtypes is a major issue. In fact, the effect of previous exposure to antiretrovirals other than IN inhibitors (INI on IN variability has not been satisfactorily defined. In addition, the genetic barrier for specific INI resistance mutations remains to be calculated. Methods IN variability was analyzed and compared with reverse transcriptase (RT and protease (PR variability in 41 treatment naïve and 54 RT inhibitor (RTI and protease inhibitor (PRI experienced patients from subjects infected with subtype B and non-B strains. In addition, four HIV-2 strains were analyzed in parallel. Frequency and distribution of IN mutations were compared between HAART-naïve and RTI/PI-experienced patients; the genetic barrier for 27 amino acid positions related to INI susceptibility was calculated as well. Results Primary mutations associated with resistance to INI were not detected in patients not previously treated with this class of drug. However, some secondary mutations which have been shown to contribute to INI resistance were found. Only limited differences in codon usage distribution between patient groups were found. HIV-2 strains from INI naïve patients showed the presence of both primary and secondary resistance mutations. Conclusion Exposure to antivirals other than INI does not seem to significantly influence the emergence of mutations implicated in INI resistance. HIV-2 strain might have reduced susceptibility to INI.

  9. Principles of a reversible programming language

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    features of the language include explicit post-condition assertions, direct access to an inverse semantics and the possibility of clean (i.e., garbage-free) computation of injective functions. We suggest the clean simulation of reversible Turing machines as a criterion for computing strength of reversible......The principles of reversible programming languages are explicated and illustrated with reference to the design of a high-level imperative language, Janus. The fundamental properties for such languages include backward as well as forward determinism and reversible updates of data. The unique design...... languages, and demonstrate this for Janus. We show the practicality of the language by implementation of a reversible fast Fourier transform. Our results indicate that the reversible programming paradigm has fundamental properties that are relevant to many different areas of computer science....

  10. Reversing cell polarity: evidence and hypothesis.

    Science.gov (United States)

    Kaiser, Dale; Yu, Rosa

    2005-04-01

    The long, rod-shaped cells of myxobacteria are polarized by their gliding engines. At the rear, A-engines push while pili pull the front end forward. An hypothesis is developed whereby both engines are partially dis-assembled, then re-assembled at the opposite pole when cells reverse their movement direction. Reversals are induced by an Mgl G-protein switch that controls engine polarity. The switch is driven by an oscillatory circuit of Frizzy proteins. In growing cells, the circuit gives rise to an occasional reversal that makes swarming possible. Then, as myxobacteria begin fruiting body development, a rising level of C-signal input drives the oscillator and changes the reversal pattern. Cells reverse regularly every eight minutes in traveling waves, the reversal period is then prolonged enabling cells to form streams that enlarge tiny random aggregates into fruiting bodies.

  11. Electrochemical deposition and characterization of zinc–nickel alloys deposited by direct and reverse current

    Directory of Open Access Journals (Sweden)

    JELENA B. BAJAT

    2005-12-01

    Full Text Available Zn–Ni alloys electrochemically deposited on steel under various deposition conditions were investigated. The alloys were deposited on a rotating disc electrode and on a steel panel from chloride solutions by direct and reverse current. The influence of reverse plating variables (cathodic and anodic current densities and their time duration on the composition, phase structure and corrosion properties were investigated. The chemical content and phase composition affect the anticorrosive properties of Zn–Ni alloys during exposure to a corrosive agent (3 % NaCl solution. It was shown that the Zn–Ni alloy electrodeposited by reverse current with a full period T = 1 s and r = 0.2 exhibits the best corrosion properties of all the investigated alloys deposited by reverse current.

  12. Induction of reverse development in two marine Hydrozoans.

    Science.gov (United States)

    Schmich, Jurgen; Kraus, Yulia; De Vito, Doris; Graziussi, Daria; Boero, Ferdinando; Piraino, Stefano

    2007-01-01

    Cnidarians are unique organisms in the animal kingdom because of their unequalled potential to undergo reverse development (RD). The life cycle of some species can temporarily shift ordinary, downstream development from zygote to adult into the opposite ontogenetic direction by back-transformation of some life stages. The potential for RD in cnidarians offers the possibility to investigate how integrative signalling networks operate to control directionality of ontogeny (reverse vs. normal development). Striking examples are found in some hydrozoans, where RD of medusa bud or liberated medusa stages leads to rejuvenation of the post-larval polyp stage. Artificial stress may determine ontogeny reversal. We describe here the results of experimental assays on artificial induction of RD by different chemical and physical inducers on two marine hydrozoans, Turritopsis dohrnii and Hydractinia carnea, showing a different potential for RD. A cascade of morphogenetic events occurs during RD by molecular mechanisms and cellular patterns recalling larval metamorphosis. For the first time, we show here that exposure to cesium chloride (CsCl), an inducer of larval metamorphosis, may also induce RD, highlighting similarities and differences between these two master ontogenetic processes in cnidarians.

  13. Gravity controlled anti-reverse rotation device

    Science.gov (United States)

    Dickinson, Robert J.; Wetherill, Todd M.

    1983-01-01

    A gravity assisted anti-reverse rotation device for preventing reverse rotation of pumps and the like. A horizontally mounted pawl is disposed to mesh with a fixed ratchet preventing reverse rotation when the pawl is advanced into intercourse with the ratchet by a vertically mounted lever having a lumped mass. Gravitation action on the lumped mass urges the pawl into mesh with the ratchet, while centrifugal force on the lumped mass during forward, allowed rotation retracts the pawl away from the ratchet.

  14. Reverse-symmetry waveguides: Theory and fabrication

    DEFF Research Database (Denmark)

    Horvath, R.; Lindvold, Lars René; Larsen, N.B.

    2002-01-01

    We present an extensive theoretical analysis of reverse-symmetry waveguides with special focus on their potential application as sensor components in aqueous media and demonstrate a novel method for fabrication of such waveguides. The principle of reverse symmetry is based on making the refractiv...... has the advantage of deeper penetration of the evanescent electromagnetic field into the cover medium, theoretically permitting higher sensitivity to analytes compared to traditional waveguide designs. We present calculated sensitivities and probing depths of conventional and reverse...

  15. Reverse Logistics - a review of case studies

    OpenAIRE

    Brito, Marisa; Dekker, Rommert; Flapper, S.D.P.

    2003-01-01

    textabstractProducts, components, materials and other equipment stream forward and back wards and back in their supply chains. Reverse Logistics deals with the processes associated with the reverse stream from users/owners to re-users. This paper provides a review and content analysis of scientific literature on reverse logistics case studies. Over sixty case studies are included. In addition, we give an overview of particular issues, which we link with propositions, unanswered questions and ...

  16. REVERSE LOGISTICS AND APPLICATION OF ARAS METHOD

    OpenAIRE

    Koc, Nesrin; Uysal, Fahriye

    2017-01-01

    Purpose-In recent years, product recovery, environmental awareness, efficient use ofresources and sustainability issues have gained importance. For this reason,the importance attached to reverse logistics activities of information andproducts towards the starting point of the final user is also increasing.Reverse logistics gives firms a competitive advantage and allows them to createan image of an environmentalist firm. In this context, the critical successfactors that influence reverse logis...

  17. Predictable management of cracked teeth with reversible pulpitis.

    Science.gov (United States)

    Abbott, P; Leow, N

    2009-12-01

    The aims of this study were to assess symptoms and signs caused by cracks in teeth and to assess a conservative management protocol. The symptoms and signs of 100 consecutive teeth that had reversible pulpitis associated with cracks were compared to findings from other reports. Teeth were managed with a conservative protocol which involved removal of cracks, caries and restorations, followed by placement of a sedative lining and interim restoration unless there were pulp exposures or insufficient tooth structure remaining. Teeth were monitored for pulp healing after three months and for up to five years. Eighty teeth did not require endodontic treatment. One tooth had an uncertain pulp status at review appointments. Fifteen teeth required endodontic treatment at the initial appointment because of carious pulp exposures (4 teeth), cracks extending into the pulp (2), and posts required (9). Four other teeth required endodontic treatment later following conservative pulp treatment due to continued pulpitis under the temporary restoration (1), pulpitis after core restoration (2), and pulp necrosis diagnosed at the review (1). Provided there is an accurate diagnosis of the pulp status and its cause, teeth with reversible pulpitis due to cracks can be treated conservatively without endodontic treatment in about 80 per cent of cases.

  18. Combining or Separating Forward and Reverse Logistics

    DEFF Research Database (Denmark)

    Herbert-Hansen, Zaza Nadja Lee; Larsen, Samuel; Nielsen, Anders

    2017-01-01

    Purpose – While forward logistics handles and manages the flow of goods downstream in the supply chain from suppliers to customers, reverse logistics (RL) manages the flow of returned goods upstream. A firm can combine reverse logistics with forward logistics, keep the flows separated, or choose......-research addresses intra-RL issues while the relationship between forward and reverse logistics is under-researched. This paper contributes to RL-theory by identifying the contextual factors that determine the most advantageous relationship between forward and reverse logistics, and proposes a novel decision making...

  19. Parallelization of Reversible Ripple-carry Adders

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Axelsen, Holger Bock

    2009-01-01

    {O}(m\\cdot k)$. The underlying mechanisms of the parallelization scheme are formally proven correct. We also show designs for garbage-less reversible comparison circuits. We compare the circuit costs of the resulting ripple-block carry adder with known optimized reversible ripple-carry adders in measures...... wherein $m$ parallel $k$-bit reversible ripple-carry adders are combined to form a reversible $mk$-bit \\emph{ripple-block carry adder} with logic depth $\\mathcal{O}(m+k)$ for a \\emph{minimal} logic depth $\\mathcal{O}(\\sqrt{mk})$, thus improving on the $mk$-bit ripple-carry adder logic depth $\\mathcal...

  20. In vitro responses of chicken macrophage-like monocytes following exposure to pathogenic and non-pathogenic E. coli ghosts loaded with a rational design of conserved genetic materials of influenza and Newcastle disease viruses.

    Science.gov (United States)

    Lagzian, Milad; Bassami, Mohammad Reza; Dehghani, Hesam

    2016-08-01

    Avian influenza virus (AIV) and Newcastle disease virus (NDV) are two important viral diseases in the poultry industry. Therefore, new disease-fighting strategies, especially effective genetic vaccination, are in high demand. Bacterial Ghost (BG) is a promising platform for delivering genetic materials to macrophages, cells that are among the first to encounter these viruses. However, there is no investigation on the immune response of these macrophage-targeted treatments. Here, we investigated the effect of genetic materials of AIV and NDV on the gene expression profile of important pro-inflammatory cytokines, a chemokine, a transcription factor, major histocompatibility complexes, and the viability of the chicken macrophage-like monocyte cells (CMM). Our genetic construct contained the external domain of matrix protein 2 and nucleoprotein gene of AIV, and immunodominant epitopes of fusion and hemagglutinin-neuraminidase proteins of NDV (hereinafter referred to as pAIV-Vax), delivered via the pathogenic and non-pathogenic BGs (Escherichia coli O78K80 and E. coli TOP10 respectively). The results demonstrated that both types of BGs were able to efficiently deliver the construct to the CMM, although the pathogenic strain derived BG was a significantly better stimulant and delivery vehicle. Both BGs were safe regarding LPS toxicity and did not induce any cell death. Furthermore, the loaded BGs were more powerful in modulating the pro-inflammatory cytokines' responses and antigen presentation systems in comparison to the unloaded BGs. Nitric oxide production of the BG-stimulated cells was also comparable to those challenged by the live bacteria. According to the results, the combination of pAIV-Vax construct and E. coli O78K80 BG is promising in inducing a considerable innate and adaptive immune response against AIV-NDV and perhaps the pathogenic E. coli, provided that the current combination be a potential candidate for in vivo testing regarding the development of an

  1. Reverse ethnopharmacology and drug discovery.

    Science.gov (United States)

    Leonti, Marco; Stafford, Gary I; Cero, Maja Dal; Cabras, Stefano; Castellanos, Maria Eugenia; Casu, Laura; Weckerle, Caroline S

    2017-02-23

    Ethnopharmacological investigations of traditional medicines have made significant contributions to plant-derived drugs, as well as the advancement of pharmacology. Drug discovery from medicinal flora is more complex than generally acknowledged because plants are applied for different therapeutic indications within and across cultures. Therefore we propose the concept of "reverse ethnopharmacology" and compare biomedical uses of plant taxa with their ethnomedicinal and popular uses and test the effect of these on the probability of finding biomedical and specifically anticancer drugs. For this analysis we use data on taxonomy and medical indications of plant derived biomedical drugs, clinical trial, and preclinical trial drug candidates published by Zhu et al. (2011) and compare their therapeutic indications with their ethnomedicinal and popular uses as reported in the NAPRALERT® database. Specifically, we test for increase or decrease of the probability of finding anticancer drugs based on ethnomedicinal and popular reports with Bayesian logistic regression analyses. Anticancer therapy resulted as the most frequent biomedicinal indication of the therapeutics derived from the 225 drug producing higher plant taxa and showed an association with ethnomedicinal and popular uses in women's medicine, which was also the most important popular use-category. Popular remedies for dysmenorrhoea, and uses as emmenagogues, abortifacients and contraceptives showed a positive effect on the probability of finding anticancer drugs. Another positive effect on the probability of discovering anticancer therapeutics was estimated for popular herbal drugs associated with the therapy of viral and bacterial infections, while the highest effect was found for popular remedies used to treat cancer symptoms. However, this latter effect seems to be influenced by the feedback loop and divulgence of biomedical knowledge on the popular level. We introduce the concept of reverse ethnopharmacology

  2. Effects of acute restraint stress on set-shifting and reversal learning in male rats.

    Science.gov (United States)

    Thai, Chester A; Zhang, Ying; Howland, John G

    2013-03-01

    Exposure to acute stress alters cognition; however, few studies have examined the effects of acute stress on executive functions such as behavioral flexibility. The goal of the present experiments was to determine the effects of acute periods of stress on two distinct forms of behavioral flexibility: set-shifting and reversal learning. Male Sprague-Dawley rats were trained and tested in an operant-chamber-based task. Some of the rats were exposed to acute restraint stress (30 min) immediately before either the set-shifting test day or the reversal learning test day. Acute stress had no effect on set-shifting, but it significantly facilitated reversal learning, as assessed by both trials to criterion and total errors. In a second experiment, the roles of glucocorticoid (GR) and mineralocorticoid receptors (MR) in the acute-stress-induced facilitation of reversal learning were examined. Systemic administration of the GR-selective antagonist RU38486 (10 mg/kg) or the MR-selective antagonist spironolactone (50 mg/kg) 30 min prior to acute stress failed to block the facilitation on reversal learning. The present results demonstrate a dissociable effect of acute stress on set-shifting and reversal learning and suggest that the facilitation of reversal learning by acute stress may be mediated by factors other than corticosterone.

  3. Genetic Recombination

    Science.gov (United States)

    Whitehouse, H. L. K.

    1973-01-01

    Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

  4. Genetic counseling

    Science.gov (United States)

    ... MF, eds. Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice . 7th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 30. Review Date 1/25/2016 Updated by: Chad Haldeman-Englert, MD, FACMG, Fullerton Genetics Center, Asheville, NC. Review provided by VeriMed Healthcare ...

  5. Genetic Romanticism

    DEFF Research Database (Denmark)

    Tupasela, Aaro

    2016-01-01

    The role that national epic poetry has played in romantic nationalism during the nineteenth and twentieth centuries is well documented. The role that the new genetics has played in such processes, however, is less well known and understood as a form of writing national narratives of origin...

  6. Male infertility and environmental exposure to lead and cadmium.

    Science.gov (United States)

    Benoff, S; Jacob, A; Hurley, I R

    2000-01-01

    Humans are exposed occupationally and environmentally to metal aerosols including lead (Pb2+) and cadmium (Cd2+). These toxicants accumulate in male reproductive organs. Epidemiological studies have been equivocal about effects of Pb2+ and Cd2+ on hormone concentrations, male fertility and sperm parameters. Comparison of Pb2+ and Cd2+ concentrations in fertile and infertile men are problematic. Problem areas include failure to control confounding variables, but genetic polymorphisms as in somatic diseases may modulate Pb2+ and Cd2+ damage. Multiple calcium (Ca2+) and potassium (K+) channel isoforms have been identified in human testes and spermatozoa. These Ca2+ and K+ channels are involved in early events of acrosome reactions. Ca2+ channel are susceptible to Cd2+ poisoning and K+ channels to Pb2+. These channels offer entry paths for metallic toxicants into mature spermatozoa. Ion channel polymorphisms may cause differential sensitivities to Cd2+ and Pb2+, explaining in part prospective blinded studies showing high Cd2+ in varicocele-related human infertility and high Pb2+ in unexplained infertility. In both forms of male infertility the ability to undergo an acrosome reaction decreases. Reverse transcriptase-polymerase chain reaction assays for Ca2+ and K+ channel isoforms may identify susceptibility subgroups with lower resistance to environmental exposures.

  7. Airway remodeling and its reversibility in equine asthma

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Lavoie

    2017-06-01

    Full Text Available Despite effective therapies for controlling its clinical manifestations, human asthma remains an incurable disease. It is now recognized that inflammation induced structural changes (remodeling of the airways are responsible for the progressive loss of lung function in asthmatic patients. However, the peripheral airways, where most of the remodeling occurs in severe asthmatic patients, cannot be safely sampled in humans, and therefore, little is known of the effects of current therapies at reversing the established asthmatic remodeling, especially those occurring in the peripheral airways. Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, experiments in which the disease is artificially induced have been shown to have limited translational potential for humans. To the contrary, horses naturally suffer from an asthma-like condition which shares marked similarities with human asthma making this model unique to investigate the kinetics, reversibility, as well as the physiological consequences of tissue remodeling (Bullone and Lavoie 2015. We reported an increased deposition of smooth muscle, collagen and elastic fibers in the peripheral airways of affected horses, which was correlated with the lung function (Herszberg et al., 2006; Setlakwe et al., 2014. The airway subepithelial collagen depositions were almost completely reversed with 6 to 12 months of treatment with either antigen avoidance or inhaled corticosteroids (ICS administration, and there was a modest (30% on average decrease in airway smooth muscle (Leclere et al., 2011. A recent study also found that ICS combined with long-acting ß2-agonists drugs (LABA and ICS monotherapy similarly induced a 30% decrease of the airway smooth muscle mass at 3 months (Buollone, 2017. However, only ICS/LABA and antigen avoidance decreased airway luminal neutrophilia. The findings indicate the enhance therapeutic effect of ICS

  8. FGFR2 mutation in 46,XY sex reversal with craniosynostosis.

    Science.gov (United States)

    Bagheri-Fam, Stefan; Ono, Makoto; Li, Li; Zhao, Liang; Ryan, Janelle; Lai, Raymond; Katsura, Yukako; Rossello, Fernando J; Koopman, Peter; Scherer, Gerd; Bartsch, Oliver; Eswarakumar, Jacob V P; Harley, Vincent R

    2015-12-01

    Patients with 46,XY gonadal dysgenesis (GD) exhibit genital anomalies, which range from hypospadias to complete male-to-female sex reversal. However, a molecular diagnosis is made in only 30% of cases. Heterozygous mutations in the human FGFR2 gene cause various craniosynostosis syndromes including Crouzon and Pfeiffer, but testicular defects were not reported. Here, we describe a patient whose features we would suggest represent a new FGFR2-related syndrome, craniosynostosis with XY male-to-female sex reversal or CSR. The craniosynostosis patient was chromosomally XY, but presented as a phenotypic female due to complete GD. DNA sequencing identified the FGFR2c heterozygous missense mutation, c.1025G>C (p.Cys342Ser). Substitution of Cys342 by Ser or other amino acids (Arg/Phe/Try/Tyr) has been previously reported in Crouzon and Pfeiffer syndrome. We show that the 'knock-in' Crouzon mouse model Fgfr2c(C342Y/C342Y) carrying a Cys342Tyr substitution displays XY gonadal sex reversal with variable expressivity. We also show that despite FGFR2c-Cys342Tyr being widely considered a gain-of-function mutation, Cys342Tyr substitution in the gonad leads to loss of function, as demonstrated by sex reversal in Fgfr2c(C342Y/-) mice carrying the knock-in allele on a null background. The rarity of our patient suggests the influence of modifier genes which exacerbated the testicular phenotype. Indeed, patient whole exome analysis revealed several potential modifiers expressed in Sertoli cells at the time of testis determination in mice. In summary, this study identifies the first FGFR2 mutation in a 46,XY GD patient. We conclude that, in certain rare genetic contexts, maintaining normal levels of FGFR2 signaling is important for human testis determination. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. J. Genet. classic 235

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 83, No. 3, December 2004. 235. Page 2. J. Genet. classic. Journal of Genetics, Vol. 83, No. 3, December 2004. 236. Page 3. J. Genet. classic. Journal of Genetics, Vol. 83, No. 3, December 2004. 237. Page 4. J. Genet. classic. Journal of Genetics, Vol. 83, No. 3, December 2004. 238. Page 5 ...

  10. Reverse Engineering Adverse Outcome Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  11. Reversible hypothyroidism and Whipple's disease

    Directory of Open Access Journals (Sweden)

    Tran Huy A

    2006-05-01

    Full Text Available Abstract Background The major cause of primary hypothyroidism is autoimmune mediated with progressive and permanent destruction of the thyroid gland resulting in life-long replacement therapy. Treatable and reversible hypothyroidism is unusual and here forth is such a case due to infection of the thyroid gland with Tropheryma whippleii, Whipple disease. Case presentation A 45 year-old female presented with symptoms and signs consistent with primary hypothyroidism, which was also confirmed biochemically. Her response to thyroxine replacement therapy was poor however, requiring a significantly elevated amount. Further investigation revealed the presence of Whipple's disease involving the gastrointestinal trace and possibly the thyroid gland. Her thyroxine requirement decreased drastically following appropriate antimicrobial therapy for Whipple's disease to the extent that it was ceased. Thyrotropin releasing hormone testing in the steady state suggested there was diminished thyroid reserve due to Whipple's disease. Conclusion This is the first ante-mortem case report studying the possible involvement of the thyroid gland by Whipple's disease. Despite the normalization of her thyroid function test biochemically after antibiotic therapy, there is diminished thyroid reserve thus requiring close and regular monitoring.

  12. Methylthioadenosine reverses brain autoimmune disease.

    Science.gov (United States)

    Moreno, Beatriz; Hevia, Henar; Santamaria, Monica; Sepulcre, Jorge; Muñoz, Javier; García-Trevijano, Elena R; Berasain, Carmen; Corrales, Fernando J; Avila, Matias A; Villoslada, Pablo

    2006-09-01

    To assess the immunomodulatory activity of methylthioadenosine (MTA) in rodent experimental autoimmune encephalomyelitis (EAE) and in patients with multiple sclerosis. We studied the effect of intraperitoneal MTA in the acute and chronic EAE model by quantifying clinical and histological scores and by performing immunohistochemistry stains of the brain. We studied the immunomodulatory effect of MTA in lymphocytes from EAE animals and in peripheral blood mononuclear cells from healthy control subjects and multiple sclerosis patients by assessing cell proliferation and cytokine gene expression, by real-time polymerase chain reaction, and by nuclear factor-kappaB modulation by Western blot. We found that MTA prevents acute EAE and, more importantly, reverses chronic-relapsing EAE. MTA treatment markedly inhibited brain inflammation and reduced brain damage. Administration of MTA suppressed T-cell activation in vivo and in vitro, likely through a blockade in T-cell signaling resulting in the prevention of inhibitor of kappa B (IkappaB-alpha) degradation and in the impaired activation transcription factor nuclear factor-kappaB. Indeed, MTA suppressed the production of proinflammatory genes and cytokines (interferon-gamma, tumor necrosis factor-alpha, and inducible nitric oxide synthase) and increased the production of antiinflammatory cytokines (interleukin-10). MTA has a remarkable immunomodulatory activity and may be beneficial for multiple sclerosis and other autoimmune diseases.

  13. Reversed shunting in CREST syndrome.

    Science.gov (United States)

    Kafes, Habibe; Sen, Fatih; Unal, Sefa; Acar, Burak; Ozeke, Ozcan

    2016-07-08

    The patent foramen ovale (PFO) is one of the most common congenital defects and may as well stand for "potential for opening" in addition to patent foramen ovale. Although patients are usually asymptomatic because the defect is flap-like and does not permit significant left-to-right shunting, the pathological conditions that result in cardiac rotation or higher than normal right atrial pressures can reverse the normal left atrial to right atrial pressure gradient and cause a right-to-left shunt through a PFO. Pulmonary complications of systemic sclerosis (SSc) are common, and are the leading cause of SSc-related death. The most common pulmonary manifestations of SSc are pulmonary hypertension (PAH), interstitial lung disease, and any combination thereof. Compared with the idiopathic form of PAH (IPAH), patients with SSc-associated PAH have a threefold increased risk of death and may receive a diagnosis late in the course of disease because of insidious onset and the high prevalence of cardiac, musculoskeletal, and pulmonary parenchymal comorbidities. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:390-391, 2016. © 2015 Wiley Periodicals, Inc.

  14. Environmental change, phenotypic plasticity, and genetic compensation.

    Science.gov (United States)

    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.

  15. J. Genet. classic 9

    Indian Academy of Sciences (India)

    Journal of Genetics, Vol. 88, No. 1, April 2009. 9. Page 2. J. Genet. classic. 10. Journal of Genetics, Vol. 88, No. 1, April 2009. Page 3. J. Genet. classic. Journal of Genetics, Vol. 88, No. 1, April 2009. 11. Page 4. J. Genet. classic. 12. Journal of Genetics, Vol. 88, No. 1, April 2009. Page 5. J. Genet. classic. Journal of Genetics ...

  16. Design of a Multiobjective Reverse Logistics Network Considering the Cost and Service Level

    Directory of Open Access Journals (Sweden)

    Shuang Li

    2012-01-01

    Full Text Available Reverse logistics, which is induced by various forms of used products and materials, has received growing attention throughout this decade. In a highly competitive environment, the service level is an important criterion for reverse logistics network design. However, most previous studies about product returns only focused on the total cost of the reverse logistics and neglected the service level. To help a manufacturer of electronic products provide quality postsale repair service for their consumer, this paper proposes a multiobjective reverse logistics network optimisation model that considers the objectives of the cost, the total tardiness of the cycle time, and the coverage of customer zones. The Nondominated Sorting Genetic Algorithm II (NSGA-II is employed for solving this multiobjective optimisation model. To evaluate the performance of NSGA-II, a genetic algorithm based on weighted sum approach and Multiobjective Simulated Annealing (MOSA are also applied. The performance of these three heuristic algorithms is compared using numerical examples. The computational results show that NSGA-II outperforms MOSA and the genetic algorithm based on weighted sum approach. Furthermore, the key parameters of the model are tested, and some conclusions are drawn.

  17. Multiple reversal olfactory learning in honeybees

    Directory of Open Access Journals (Sweden)

    Theo Mota

    2010-07-01

    Full Text Available In multiple reversal learning, animals trained to discriminate a reinforced from a non-reinforced stimulus are subjected to various, successive reversals of stimulus contingencies (e.g. A+ vs. B-, A- vs. B+, A+ vs. B-. This protocol is useful to determine whether or not animals learn to learn and solve successive discriminations faster (or with fewer errors with increasing reversal experience. Here we used the olfactory conditioning of proboscis extension reflex to study how honeybees Apis mellifera perform in a multiple reversal task. Our experiment contemplated four consecutive differential conditioning phases involving the same odors (A+ vs. B- to A- vs. B+ to A+ vs. B- to A- vs. B+. We show that bees in which the weight of reinforced or non-reinforced stimuli was similar mastered the multiple olfactory reversals. Bees which failed the task exhibited asymmetric responses to reinforced and non-reinforced stimuli, thus being unable to rapidly reverse stimulus contingencies. Efficient reversers did not improve their successive discriminations but rather tended to generalize their choice to both odors at the end of conditioning. As a consequence, both discrimination and reversal efficiency decreasedalong experimental phases. This result invalidates a learning-to-learn effect and indicates that bees do not only respond to the actual stimulus contingencies but rather combine these with an average of past experiences with the same stimuli.  

  18. Magnetic reversals from planetary dynamo waves.

    Science.gov (United States)

    Sheyko, Andrey; Finlay, Christopher C; Jackson, Andrew

    2016-11-24

    A striking feature of many natural dynamos is their ability to undergo polarity reversals. The best documented example is Earth's magnetic field, which has reversed hundreds of times during its history. The origin of geomagnetic polarity reversals lies in a magnetohydrodynamic process that takes place in Earth's core, but the precise mechanism is debated. The majority of numerical geodynamo simulations that exhibit reversals operate in a regime in which the viscosity of the fluid remains important, and in which the dynamo mechanism primarily involves stretching and twisting of field lines by columnar convection. Here we present an example of another class of reversing-geodynamo model, which operates in a regime of comparatively low viscosity and high magnetic diffusivity. This class does not fit into the paradigm of reversal regimes that are dictated by the value of the local Rossby number (the ratio of advection to Coriolis force). Instead, stretching of the magnetic field by a strong shear in the east-west flow near the imaginary cylinder just touching the inner core and parallel to the axis of rotation is crucial to the reversal mechanism in our models, which involves a process akin to kinematic dynamo waves. Because our results are relevant in a regime of low viscosity and high magnetic diffusivity, and with geophysically appropriate boundary conditions, this form of dynamo wave may also be involved in geomagnetic reversals.

  19. Reverse pitch fan with divided splitter

    Science.gov (United States)

    Smith, L. H., Jr. (Inventor)

    1977-01-01

    A guide vane arrangement is described for improving gas turbine performance in the reverse thrust mode. This flow straightening method produces low losses in the fluid entering a core engine during reverse thrust operations and allows large supercharging of the core engine during forward thrust.

  20. Reversal of laryngotracheal separation in paediatric patients.

    LENUS (Irish Health Repository)

    Young, Orla

    2012-02-01

    OBJECTIVE: Laryngotracheal separation (LTS) is an effective and reliable definitive treatment for intractable aspiration. A major advantage of this treatment for intractable aspiration is its\\' potential reversibility. Should the underlying disorder improve, a reversal of the procedure may be attempted. This has been successfully achieved in the adult population. To our knowledge, no previous cases have been reported of successful reversal of LTS in children. METHODS: A retrospective review from 2003 to 2010 identified four cases of intractable aspiration treated with LTS in our department. Two of these patients displayed objective evidence of sufficient recovery of their underlying aspiration to consider reversal. Patient selection for reversal was dependent upon successful oral intake for 9 months along with videofluoroscopic evidence of normal or minimally impaired swallow. RESULTS: Two children who were successfully treated for intractable aspiration with LTS demonstrated objective evidence of recovery sufficient to attempt reversal. Both children underwent successful surgical reversal of LTS using a cricotracheal resection with end-to-end anastamosis, similar to that used in treatment of subglottic stenosis. Both children can now tolerate oral diet and their speech and language development is in line with their overall developmental level. CONCLUSIONS: Laryngotracheal separation is an effective and reliable definitive treatment for intractable aspiration facilitating protection of the airway and allowing safe swallowing with unimpeded respiration, but with the major drawback of loss of phonation. To our knowledge, we document the first two cases of successful LTS reversal in children.

  1. Online Reverse Auctions for Procurement of Services

    NARCIS (Netherlands)

    U.L. Radkevitch (Uladzimir)

    2008-01-01

    textabstractOnline reverse auctions, in which a buyer seeks to select a supplier and suppliers compete for contracts by bidding online, revolutionized corporate procurement early this century. Shortly after they had been pioneered by General Electric, many companies rushed to adopt reverse auctions

  2. Reverse Galilean telescopic spectacles in unilateral aphakia.

    Science.gov (United States)

    Krefman, R A

    1981-09-01

    Minimizing aniseikonia in unilateral aphakia is often a difficult task. A case is presented in which a patient preferred a reverse Galilean telescopic spectacle of his own design to a contact lens. The design of the spectacles and the patient's visual performance with them are described. A reverse Galilean telescopic spectacle should not be excluded from the therapeutic alternatives in unilateral aphakia.

  3. Probabilistic Reversible Automata and Quantum Automata

    OpenAIRE

    Golovkins, Marats; Kravtsev, Maksim

    2002-01-01

    To study relationship between quantum finite automata and probabilistic finite automata, we introduce a notion of probabilistic reversible automata (PRA, or doubly stochastic automata). We find that there is a strong relationship between different possible models of PRA and corresponding models of quantum finite automata. We also propose a classification of reversible finite 1-way automata.

  4. Preference Reversals: Violations of Unidimensional Procedure Invariance

    NARCIS (Netherlands)

    P.F.M. Stalmeier (Peep); P.P. Wakker (Peter); Th.G.G. Bezembinder (Thom)

    1997-01-01

    textabstractPreference reversals have usually been explained by weighted additive models, in which different tasks give rise to different importance weights for the stimulus attributes, resulting in contradictory trade-offs. This article presents a preference reversal of a more extreme nature. Let

  5. Preference reversals: violations of unidimensional procedure invariance

    NARCIS (Netherlands)

    Wakker, P.P.; Stalmeijer, P.F.M.; Bezembinder, T.G.G.

    1997-01-01

    Preference reversals have usually been explained by weighted additive models, in which different tasks give rise to different importance weights for the stimulus attributes, resulting in contradictory tradeoffs. This article presents a preference reversal of a more extreme nature. Let (10, 5 Migr)

  6. Reversible logic gates on Physarum Polycephalum

    Energy Technology Data Exchange (ETDEWEB)

    Schumann, Andrew [University of Information Technology and Management, Sucharskiego 2, Rzeszow, 35-225 (Poland)

    2015-03-10

    In this paper, we consider possibilities how to implement asynchronous sequential logic gates and quantum-style reversible logic gates on Physarum polycephalum motions. We show that in asynchronous sequential logic gates we can erase information because of uncertainty in the direction of plasmodium propagation. Therefore quantum-style reversible logic gates are more preferable for designing logic circuits on Physarum polycephalum.

  7. Reverse Logistics - a review of case studies

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); R. Dekker (Rommert); S.D.P. Flapper

    2003-01-01

    textabstractProducts, components, materials and other equipment stream forward and back wards and back in their supply chains. Reverse Logistics deals with the processes associated with the reverse stream from users/owners to re-users. This paper provides a review and content analysis of scientific

  8. Experimental Investigation of Solar Powered Reverse Osmosis ...

    African Journals Online (AJOL)

    fire7-

    Pollution and over exploitation of groundwater aquifer and surface water have led to a decrease ... favoring for implementing solar photovoltaic (PV) reverse osmosis (RO) desalination technology. The fast development of solar energy, especially photovoltaic, ... Among desalination technologies, reverse osmosis is rapidly.

  9. Manual Colostomy Reversals Following Wide Colorectal Resections ...

    African Journals Online (AJOL)

    Manual Colostomy Reversals Following Wide Colorectal Resections at Poorly Equipped Surgical Facilities. EBFK Odimba, M Nthele, M Mbambiko. Abstract. Background: The decision for colostomy reversal is usually not easy and often reflects patient's desire, fully analyzed and agreed by the surgeon. The unavailability of ...

  10. Exposures to patients in Australian radiological practice

    Energy Technology Data Exchange (ETDEWEB)

    Paix, D. (South Australian Inst. of Tech., Adelaide)

    1983-11-01

    The findings of a 1980 Australian Radiation Laboratory study of genetic and bone-marrow doses to the population from medical, dental and chiropractic uses of ionising radiation are discussed. Attention is drawn to the large variability in patient exposure: maximum values were from five to eleven times greater than the means.

  11. Occupational exposure and risk of breast cancer

    OpenAIRE

    Fenga, Concettina

    2016-01-01

    Breast cancer is a multifactorial disease and the most commonly diagnosed cancer in women. Traditional risk factors for breast cancer include reproductive status, genetic mutations, family history and lifestyle. However, increasing evidence has identified an association between breast cancer and occupational factors, including environmental stimuli. Epidemiological and experimental studies demonstrated that ionizing and non-ionizing radiation exposure, night-shift work, pesticides, polycyclic...

  12. Designing Novel Quaternary Quantum Reversible Subtractor Circuits

    Science.gov (United States)

    Haghparast, Majid; Monfared, Asma Taheri

    2018-01-01

    Reversible logic synthesis is an important area of current research because of its ability to reduce energy dissipation. In recent years, multiple valued logic has received great attention due to its ability to reduce the width of the reversible circuit which is a main requirement in quantum technology. Subtractor circuits are between major components used in quantum computers. In this paper, we will discuss the design of a quaternary quantum reversible half subtractor circuit using quaternary 1-qudit, 2-qudit Muthukrishnan-Stroud and 3-qudit controlled gates and a 2-qudit Generalized quaternary gate. Then a design of a quaternary quantum reversible full subtractor circuit based on the quaternary half subtractor will be presenting. The designs shall then be evaluated in terms of quantum cost, constant input, garbage output, and hardware complexity. The proposed quaternary quantum reversible circuits are the first attempt in the designing of the aforementioned subtractor.

  13. Designing Novel Quaternary Quantum Reversible Subtractor Circuits

    Science.gov (United States)

    Haghparast, Majid; Monfared, Asma Taheri

    2017-10-01

    Reversible logic synthesis is an important area of current research because of its ability to reduce energy dissipation. In recent years, multiple valued logic has received great attention due to its ability to reduce the width of the reversible circuit which is a main requirement in quantum technology. Subtractor circuits are between major components used in quantum computers. In this paper, we will discuss the design of a quaternary quantum reversible half subtractor circuit using quaternary 1-qudit, 2-qudit Muthukrishnan-Stroud and 3-qudit controlled gates and a 2-qudit Generalized quaternary gate. Then a design of a quaternary quantum reversible full subtractor circuit based on the quaternary half subtractor will be presenting. The designs shall then be evaluated in terms of quantum cost, constant input, garbage output, and hardware complexity. The proposed quaternary quantum reversible circuits are the first attempt in the designing of the aforementioned subtractor.

  14. Optimized reversible binary-coded decimal adders

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Glück, Robert

    2008-01-01

    Abstract Babu and Chowdhury [H.M.H. Babu, A.R. Chowdhury, Design of a compact reversible binary coded decimal adder circuit, Journal of Systems Architecture 52 (5) (2006) 272-282] recently proposed, in this journal, a reversible adder for binary-coded decimals. This paper corrects and optimizes....... Keywords: Reversible logic circuit; Full-adder; Half-adder; Parallel adder; Binary-coded decimal; Application of reversible logic synthesis......) BCD addition, the circuit delay of 49 gates is significantly lower than is the number of bits used for the BCD representation. A complete set of reversible half- and full-adders for n-bit binary numbers and m-decimal BCD numbers is presented. The results show that special-purpose design pays off...

  15. Chemical genetics of Plasmodium falciparum

    Science.gov (United States)

    Guiguemde, W. Armand; Shelat, Anang A.; Bouck, David; Duffy, Sandra; Crowther, Gregory J.; Davis, Paul H.; Smithson, David C.; Connelly, Michele; Clark, Julie; Zhu, Fangyi; Jiménez-Díaz, María B; Martinez, María S; Wilson, Emily B.; Tripathi, Abhai K.; Gut, Jiri; Sharlow, Elizabeth R.; Bathurst, Ian; El Mazouni, Farah; Fowble, Joseph W; Forquer, Isaac; McGinley, Paula L; Castro, Steve; Angulo-Barturen, Iñigo; Ferrer, Santiago; Rosenthal, Philip J.; DeRisi, Joseph L; Sullivan, David J.; Lazo, John S.; Roos, David S.; Riscoe, Michael K.; Phillips, Margaret A.; Rathod, Pradipsinh K.; Van Voorhis, Wesley C.; Avery, Vicky M; Guy, R. Kiplin

    2010-01-01

    Malaria caused by Plasmodium falciparum is a catastrophic disease worldwide (880,000 deaths yearly). Vaccine development has proved difficult and resistance has emerged for most antimalarials. In order to discover new antimalarial chemotypes, we have employed a phenotypic forward chemical genetic approach to assay 309,474 chemicals. Here we disclose structures and biological activity of the entire library, many of which exhibited potent in vitro activity against drug resistant strains, and detailed profiling of 172 representative candidates. A reverse chemical genetic study identified 19 new inhibitors of 4 validated drug targets and 15 novel binders among 61 malarial proteins. Phylochemogenetic profiling in multiple organisms revealed similarities between Toxoplasma gondii and mammalian cell lines and dissimilarities between P. falciparum and related protozoans. One exemplar compound displayed efficacy in a murine model. Overall, our findings provide the scientific community with new starting points for malaria drug discovery. PMID:20485428

  16. [Autism: genetics].

    Science.gov (United States)

    Gupta, Abha R; State, Matthew W

    2006-05-01

    Autism is a strongly genetic disorder, with an estimated heritability of greater than 90%. A combination of phenotypic heterogeneity and the likely involvement of multiple interacting loci have hampered efforts at gene discovery. As a consequence, the genetic etiology of the spectrum of autism related disorders remains largely unknown. Over the past several years, the convergence of rapidly advancing genomic technologies, the completion of the human genome project, and increasingly successful collaborative efforts to increase the number of patients available for study have led to the first solid clues to the biological origins of these disorders. This paper will review the literature to date summarizing the results of linkage, cytogenetic, and candidate gene studies with a focus on recent progress. In addition, promising avenues for future research are considered.

  17. Reversion mutation in dark variants of luminous bacteria and its application in gene toxicant monitoring

    Science.gov (United States)

    Sun, Yaliang; Guo, Jianli

    2001-09-01

    The luminous intensity of dark variant separated form photobacterium phosphoreum is 1/10000 less than that of wild-type. Ethidium Bromide (EB), Mytomycin C(MC), 2-amino fluorine can all strongly induce reversion mutation for S1 within 24h and increase reversion ratio significantly. The results of experiments indicated that these revertants have stable genetic character and the mutation may take place at gene levels. The mutagenesis to S1 caused by EB, MC and 2-AF was detected and it may be a new rapid, simple and sensitive method of gene toxicant monitoring.

  18. Genetic Prediction.

    Science.gov (United States)

    Turkheimer, Eric

    2015-01-01

    The fundamental reason that the genetics of behavior has remained so controversial for so long is that the layer of theory between data and their interpretation is thicker and more opaque than in more established areas of science. The finding that variations in tiny snippets of DNA have small but detectable relations to variation in behavior surprises no one, at least no one who was paying attention to the twin studies. How such snippets of DNA are related to differences in behavior-known as the gene-to-behavior pathway-is the great theoretical problem of modern behavioral genetics. Given that intentional human breeding is a horrific prospect, what kind of technology might we want (or fear) out of human behavioral genetics? One possibility is a technology that could predict important behavioral characteristics of humans based on their genomes alone. A moment's thought suggests significant benefits and risks that might be associated with such a possibility, but for the moment, just consider how convincing it would be if on the day of a baby's birth we could make meaningful predictions about whether he or she would become a concert pianist or an alcoholic. This article will consider where we are right now as regards that possibility, using human height and intelligence as the primary examples. © 2015 The Hastings Center.

  19. Reversible machine code and its abstract processor architecture

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock; Glück, Robert; Yokoyama, Tetsuo

    2007-01-01

    A reversible abstract machine architecture and its reversible machine code are presented and formalized. For machine code to be reversible, both the underlying control logic and each instruction must be reversible. A general class of machine instruction sets was proven to be reversible, building ...... on our concept of reversible updates. The presentation is abstract and can serve as a guideline for a family of reversible processor designs. By example, we illustrate programming principles for the abstract machine architecture formalized in this paper....

  20. The Genetics of Fetal Alcohol Spectrum Disorders.

    Science.gov (United States)

    Eberhart, Johann K; Parnell, Scott E

    2016-06-01

    The term "fetal alcohol spectrum disorders" (FASD) defines the full range of ethanol (EtOH)-induced birth defects. Numerous variables influence the phenotypic outcomes of embryonic EtOH exposure. Among these variables, genetics appears to play an important role, yet our understanding of the genetic predisposition to FASD is still in its infancy. We review the current literature that relates to the genetics of FASD susceptibility and gene-EtOH interactions. Where possible, we comment on potential mechanisms of reported gene-EtOH interactions. Early indications of genetic sensitivity to FASD came from human and animal studies using twins or inbred strains, respectively. These analyses prompted searches for susceptibility loci involved in EtOH metabolism and analyses of candidate loci, based on phenotypes observed in FASD. More recently, genetic screens in animal models have provided an additional insight into the genetics of FASD. Understanding FASD requires that we understand the many factors influencing phenotypic outcome following embryonic EtOH exposure. We are gaining ground on understanding some of the genetics behind FASD, yet much work remains to be carried out. Coordinated analyses using human patients and animal models are likely to be highly fruitful in uncovering the genetics behind FASD. Copyright © 2016 by the Research Society on Alcoholism.