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Sample records for anguillarum genetic response

  1. Stress response and virulence in Vibrio anguillarum

    OpenAIRE

    Weber, Barbara

    2010-01-01

    Bacteria use quorum sensing, a cell to cell signaling mechanism mediated by small molecules that are produced by specific signal molecule synthases, to regulate gene expression in response to population density. In Vibrio anguillarum, the quorum-sensing phosphorelay channels information from three hybrid sensor kinases VanN, VanQ, CqsS that sense signal molecules produced by the synthases VanM, VanS and CqsA, onto the phosphotransferase VanU, to regulate activity of the response regulator Van...

  2. Elucidation of the Vibrio anguillarum genetic response to the potential fish probiont Pseudomonas fluorescens AH2, using RNA-arbitrarily primed PCR

    DEFF Research Database (Denmark)

    Holmstrøm, Kim; Gram, Lone

    2003-01-01

    or another V. anguillarum siderophore. On the pJM1 plasmid of V anguillarum serotype O1, a pseudogene designated open reading frame E (ORF E) that contains a frameshift mutation was previously identified. The gene homologous to vibE identified in this study, interestingly, also has significant homology...... to ORF E on the amino acid level and does not possess the frameshift mutation. Thus, the chromosomally encoded vibE homologue could fulfil the role of the inactive plasmid-encoded ORF E pseudogene. Addition of Fe3+ to the system eliminated the growth arrest, and the genes homologous to rpoS and vibE were...

  3. Proteomic and metabolomic responses in hepatopancreas of Mytilus galloprovincialis challenged by Micrococcus luteus and Vibrio anguillarum.

    Science.gov (United States)

    Wu, Huifeng; Ji, Chenglong; Wei, Lei; Zhao, Jianmin; Lu, Hongjian

    2013-12-06

    The outbreak of pathogens can induce diseases and lead to massive mortalities of aquaculture animals including fish, mollusk and shrimp. In this work, the responses induced by Micrococcus luteus and Vibrio anguillarum were investigated in hepatopancreas of mussel Mytilus galloprovincialis using proteomics and metabolomics. Metabolic biomarkers demonstrated that M. luteus and V. anguillarum injections could induce osmotic stress and disturbance in energy metabolism. And the uniquely and more markedly altered metabolic biomarkers (glutamine, succinate, aspartate, glucose, ATP, homarine and tyrosine) indicated that V. anguillarum could cause more severe disturbances in osmotic regulation and energy metabolism. The differentially altered proteins meant that M. luteus and V. anguillarum induced different effects in mussels. However, the common proteomic biomarkers, arginine kinase and small heat shock protein, demonstrated that these two bacteria induced similar effects including oxidative stress and disturbance in energy metabolism in M. galloprovincialis. In addition, some metabolic biomarkers, ATP and glutamine, were confirmed by related proteins including arginine kinase, ATP synthase, nucleoside diphosphate kinase and glutamine synthetase in bacteria-challenged mussels. This study demonstrated that proteomics and metabolomics could provide an insightful view into the effects of environmental pathogens to the marine mussel M. galloprovincialis. The outbreak of pathogens can lead to diseases and massive mortalities of aquaculture animals including fish, mollusk and shrimp. The mussel M. galloprovincialis distributes widely along the Bohai coast and is popularly consumed as delicious seafood by local residents. This bivalve has become one of the important species in marine aquaculture industry in China. Therefore a study on pathogen-induced effects is necessary. In the present study, an integrated metabolomic and proteomic approach was used to elucidate the

  4. Genetic Variability of the Heme Uptake System among Different Strains of the Fish Pathogen Vibrio anguillarum: Identification of a New Heme Receptor

    Science.gov (United States)

    Mouriño, Susana; Rodríguez-Ares, Isabel; Osorio, Carlos R.; Lemos, Manuel L.

    2005-01-01

    The ability to utilize heme compounds as iron sources was investigated in Vibrio anguillarum strains belonging to serotypes O1 to O10. All strains, regardless of their serotype or isolation origin could utilize hemin and hemoglobin as sole iron sources. Similarly, all of the isolates could bind hemin and Congo red, and this binding was mediated by cell envelope proteins. PCR and Southern hybridization were used to assay the occurrence of heme transport genes huvABCD, which have been previously described in serotype O1. Of 23 strains studied, two serotype O3 isolates proved negative for all huvABCD genes, whereas nine strains included in serotypes O2, O3, O4, O6, O7, and O10 tested negative for the outer membrane heme receptor gene huvA. A gene coding for a novel outer membrane heme receptor was cloned and characterized in a V. anguillarum serotype O3 strain lacking huvA. The new heme receptor, named HuvS, showed significant similarity to other outer membrane heme receptors described in Vibrionaceae, but little homology (39%) to HuvA. This heme receptor was present in 9 out of 11 of the V. anguillarum strains that tested negative for HuvA. Furthermore, complementation experiments demonstrated that HuvS could substitute for the HuvA function in Escherichia coli and V. anguillarum mutants. The huvS and huvA sequences alignment, as well as the analysis of their respective upstream and downstream DNA sequences, suggest that horizontal transfer and recombination might be responsible for generating this genetic diversity. PMID:16332832

  5. 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

    Introduction: The fish pathogen Vibrio anguillarum is a major problem in aquaculture causing Vibriosis. Bacteria of the Roseobacter clade can antagonize pathogenic vibrios in cultures in live feed such as microalgae, rotifers and Artemia, as well as in fish larvae. Therefore, roseobacters could...

  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

    unaffected, supporting the application of TDA-producing roseobacters as probiotics in aquaculture. It is important to limit the use of antibiotics in our food production, to reduce the risk of bacteria developing antibiotic resistance. We showed previously that marine bacteria of the Roseobacter clade can......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...... potential side effects of long-term exposure of the pathogen to the probionts or any compounds they produce. Here we exposed the fish pathogen Vibrio anguillarum to TDA for several hundred generations in an adaptive evolution experiment. No tolerance or resistance arose during the 90 days of exposure...

  7. MHC polymorphism and disease resistance to vibrio anguillarum in 8 families of half-smooth tongue sole (Cynoglossus semilaevis

    Directory of Open Access Journals (Sweden)

    Liu Yan-hong

    2011-09-01

    Full Text Available Abstract Background Genes in the major histocompatibility complex (MHC have a critical role in both the innate and adaptive immune responses because of their involvement in presenting foreign peptides to T cells. However, the nature has remained largely unknown. Results We examined the genetic variation in MHC class IIB in half-smooth tongue sole (Cynoglossus semilaevis after challenge with vibrio anguillarum. Two thousand and four hundred fry from 12 half-smooth tongue sole families were challenged with Vibrio anguillarum. To determine any association between alleles and resistance or susceptibility to V. anguillarum, 160 individuals from four high-resistance (HR, 73.27% mortality families were selected for MHC IIB exon2 gene sequence analysis. The MHC IIB exon2 genes of tongue sole displayed a high level of polymorphism and were discovered at least four loci. Meanwhile, the dN/dS [the ratio of non-synonymous (dN substitutions to synonymous (dS substitutions] in the peptide-binding region (PBR was higher than that in the non-peptide-binding region (non-PBR. Eighty-eight alleles were discovered among 160 individuals, and 13 out of 88 alleles were used to analyze the distribution pattern between the resistant and susceptible families. Certain alleles presented in HR and LR with a different frequency, while other alleles were discovered in only the HR or LR families, not both. Five alleles, Cyse-DBB*6501, Cyse-DBB*4002, Cyse-DBB*6102, Cyse-DBB*5601 and Cyse-DBB*2801, were found to be associated with susceptibility to V. anguillarum with a frequency of 1.25%, 1.25%, 1.25%, 1.25% and 2.5% in the HR families, and 35%, 33.75%, 27.5%, 16.25%, 15% in the LR families (p Cyse-DBB*3301, Cyse-DBB*4701, Cyse-DBB*6801 and Cyse-DBB*5901, were found to be associated with resistance to V. anguillarum, with a frequency of 13.75%, 11.25%, 11.25%, 8.75% in the HR families and 1.25%, 1.25%, 1.25%, 1.25% and 1.25% in the LR families (p Conclusions Elucidation of the

  8. Vibriophages and Their Interactions with the Fish Pathogen Vibrio anguillarum

    DEFF Research Database (Denmark)

    Tan, Demeng; Gram, Lone; Middelboe, Mathias

    2014-01-01

    Vibrio anguillarum is an important pathogen in aquaculture, responsible for the disease vibriosis in many fish and invertebrate species. Disease control by antibiotics is a concern due to potential development and spread of antibiotic resistance. The use of bacteriophages to control the pathogen...... patterns of the individual host isolates, key phenotypic properties related to phage susceptibility are distributed worldwide and maintained in the global Vibrio community for decades. The phage susceptibility pattern of the isolates did not show any relation to the physiological relationships obtained...... from Biolog GN2 profiles, demonstrating that similar phage susceptibility patterns occur across broad phylogenetic and physiological differences in Vibrio strains. Subsequent culture experiments with two phages and two V. anguillarum hosts demonstrated an initial strong lytic potential of the phages...

  9. Molecular characterization and expression analysis of Lily-type lectin ( SmLTL) in turbot Scophthalmus maximus, and its response to Vibrio anguillarum

    Science.gov (United States)

    Xia, Dandan; Ma, Aijun; Huang, Zhihui; Shang, Xiaomei; Cui, Wenxiao; Yang, Zhi; Qu, Jiangbo

    2018-03-01

    A full-length lily-type lectin ( SmLTL) was identified from turbot ( Scophthalmus maximus) in this study. By searching database for protein identification and function prediction, SmLTL were confirmed. The full-length cDNA of SmLTL is composed of 569 bp and contains a 339 bp ORF that encodes 112 amino acid residues. The SmLTL peptide is characterized by a specific β-prism architecture and contains three mannose binding sites in a three-fold internal repeat between amino acids 30-99; two of the repeats share the classical mannose binding domain (QxDxNxVxY) while the third binding site was similar to other fish-specific binding motifs (TxTxGxRxV). The primary, secondary, and tertiary structures of SmLTL were predicted and analyzed, indicating that the SmLTL protein was hydrophilic, contained 5.36% α-helices, 39.29% extended strands, 16.07% β-folds, and 39.29% random coils, and three β-folds. Quantitative realtime polymerase chain reaction (qPCR) analysis revealed that the SmLTL mRNA was abundantly expressed in skin, gill, and intestine. Low levels of SmLTL expression were observed in other tissues. The expression of SmLTL in gill, skin and intestine increased at mRNA level after stimulation of Vibrio anguillarum, our results suggest that SmLTL serve as the first line of defence against microbial infections and play a pivotal role in the innate mucosal immune system. The current study indicates that SmLTL is a member of the lilytype lectin family and the information reported here will provide an important foundation for future research on the role of this protein.

  10. Bacteriophage interactions with Vibrio anguillarum and the potential for phage therapy in marine aquaculture

    DEFF Research Database (Denmark)

    Rørbo, Nanna Iben

    is widespread in the Vibrio community which underscore the lysogenic phages influence on bacterial evolution and functional properties. Highly genetically similar Vibrio phages, termed H20-like prophages, were isolated across large geographical scales being present both as freeliving phages and as prophages...... in V. anguillarum genomes. The H20-like phages’ widespread presence suggests a mutualistic interaction which selects for co-existence with V. anguillarum. In aquaculture, especially the larvae and fry are vulnerable to pathogens, and they are not susceptible to alternatives to antibiotics, e...

  11. The Roles of Heat Shock Proteins 70 and 90 in Exopalaemon carinicauda After WSSV and Vibrio anguillarum Challenges

    Science.gov (United States)

    Li, Jitao; Li, Jian; Duan, Yafei; Chen, Ping; Liu, Ping

    2018-04-01

    Heat shock proteins (HSPs), such as HSP70 and HSP90, are a suite of highly conserved proteins produced in all cellular organisms when they are exposed to stresses. In aquatic animals, they have been proved to play important roles in response to environmental pollutants and particularly in the non-specific immune responses to pathogen infections. In the present study, the expression profiles of HSP70 and HSP90 genes in hemocytes and hepatopancreas from the ridgetail white prawn Exopalaemon carinicauda infected with WSSV and Vibrio anguillarum were detected using reverse transcription polymerase chain reaction (RT-PCR). After WSSV challenge, the expression level of HSP 70 gene transcripts in the hemocytes and hepatopancreas increased to peak level at 6 h and 48 h, respectively. HSP90 gene transcripts in hemocytes and hepatopancreas were up-regulated significantly at 12 h and 6 h, respectively. During V. anguillarum challenge, the mRNA content of HSP70 gene in hemocytes and hepatopancreas increased significantly at 12 h and 6 h post-infection, respectively. The expression level of HSP90 gene both in hemocytes and hepatopancreas were up-regulated in the first 3 h. The expression patterns of HSP70 and HSP90 genes in hemocytes and hepatopancreas showed temporal and spatial differences after challenged with WSSV and V. anguillarum. The results suggested that HSPs might be involved in immune responses to pathogens challenge in E. carinicauda.

  12. Gel shift analysis of the empA promoter region in Vibrio anguillarum

    Directory of Open Access Journals (Sweden)

    Denkin Steven M

    2004-10-01

    . anguillarum NB10 cells contain a protein that binds to a 50 bp oligomer containing the empA promoter-lux box-like region. NB10 cells express empA during stationary phase in all growth conditions. The DNA binding protein is not present in M93Sm extracts. M93Sm cells express protease activity only when incubated at high cell density in fish gastrointestinal mucus. The gel shift observed with NB10 cells is not due to VanT binding. The data also suggest that the DNA binding protein is responsible for the less restrictive expression of empA in NB10 compared to M93Sm.

  13. Complete genome sequence of Vibrio anguillarum phage CHOED successfully used for phage therapy in aquaculture

    DEFF Research Database (Denmark)

    Romero, Jaime; Higuera, Gastón; Gajardo, Felipe

    2014-01-01

    Vibrio anguillarum phage CHOED was isolated from Chilean mussels. It is a virulent phage showing effective inhibition of V. anguillarum. CHOED has potential in phage therapy, because it can protect fish from vibriosis in fish farms. Here, we announce the completely sequenced genome of V....... anguillarum phage CHOED....

  14. Production of acylated homoserine lactones by different serotypes of Vibrio anguillarum both in culture and during infection of rainbow trout

    DEFF Research Database (Denmark)

    Buch, C.; Sigh, J.; Nielsen, J.

    2003-01-01

    Onehundred and forty-eight out of onehundred and fifty strains of Vibrio anguillarum isolated from vibriosis in Danish marine aquaculture produced bacterial communication signals, acylated homoserine lactones, eliciting a response in the Agrobacterium tumefaciens (pZLR4) monitoring system. One...... strain, a serotype O4, induced a strong response in the Chromobacterium violaceum (CV026) monitoring system. Profiles of AHLs determined by TLC separation revealed the presence of at least four AHLs and a compound similar to N-3-oxo-decanoyl homoserine lactone (3-oxo-C10-HSL) was present in all strains...

  15. Exploring the Effect of Phage Therapy in Preventing Vibrio anguillarum Infections in Cod and Turbot Larvae

    DEFF Research Database (Denmark)

    Rørbo, Nanna; Rønneseth, Anita; Kalatzis, Panos G.

    2018-01-01

    The aquaculture industry is suffering from losses associated with bacterial infections by opportunistic pathogens. Vibrio anguillarum is one of the most important pathogens, causing vibriosis in fish and shellfish cultures leading to high mortalities and economic losses. Bacterial resistance to a...... KVP40, demonstrating that the phage could also reduce mortality imposed by the background population of pathogens. Overall, phage-mediated reduction in mortality of cod and turbot larvae in experimental challenge assays with V. anguillarum pathogens suggested that application of broad...

  16. Vibriophages differentially influence biofilm formation by Vibrio anguillarum strains

    DEFF Research Database (Denmark)

    Tan, Demeng; Dahl, Amalie; Middelboe, Mathias

    2015-01-01

    different effects on the biofilm development. Addition of phage ΦH20 to strain BA35 showed efficient control of biofilm formation and density of free-living cells. The interactions between BA35 and ΦH20 were thus characterized by a strong phage control of the phage-sensitive population and subsequent...... against phage infection. By the formation of biofilms, strain PF430-3 created spatial refuges that protected the host from phage infection and allowed coexistence between phage-sensitive cells and lytic phage KVP40. Together, the results demonstrate highly variable phage protection mechanisms in two......-living and surface-associated growth conditions. In this study, we explored in vitro phage-host interactions in two different strains of V. anguillarum (BA35 and PF430-3) during growth in microcolonies, biofilms, and free-living cells. Two vibriophages, ΦH20 (Siphoviridae) and KVP40 (Myoviridae), had completely...

  17. Zebrafish (Danio rerio) as a model to visualize infection dynamics of Vibrio anguillarum following intraperitoneal injection and bath exposure

    DEFF Research Database (Denmark)

    Schmidt, Jacob Günther; Korbut, Rozalia; Ohtani, Maki

    2017-01-01

    , for which the vaccines are targeted. The zebrafish is by now a well established practical vertebrate model species due in part to its size and ease of maintenance and genetic manipulation. Here we use zebrafish as a model to visualize and compare the development of infection of Vibrio anguillarum......Vaccine development is important for sustainable fish farming and novel vaccines need to be efficacy tested before release to the market. Challenge of fish with the pathogen towards which the vaccine has been produced can be conducted either by external exposure though bathing or cohabitation...... on and in the fish following injection or bathing. Injection of 103 bacteria per fish resulted in approximately 50% mortality by day 4 post-injection. Similar mortality levels were reached in the other group by bathing in 1.25 × 109 bacteria for 1 min. The spreading of bacteria was followed for the first 24 h after...

  18. Defense systems in developing Artemia franciscana nauplii and their modulation by probiotic bacteria offer protection against a Vibrio anguillarum challenge.

    Science.gov (United States)

    Giarma, Eleni; Amanetidou, Eleni; Toufexi, Alexia; Touraki, Maria

    2017-07-01

    The alterations of immune responses of Artemia franciscana nauplii as a function of culture time and after a challenge with the pathogen Vibrio anguillarum were studied. The effect of the administration of the probiotic bacteria Bacillus subtilis, Lactobacillus plantarum and Lactococcus lactis either alone or in combination with the pathogen was evaluated. The activity of the antioxidant enzymes superoxide dismutase (SOD), Glutathione reductase (GRed), Glutathione transferase (GST) and Phenoloxidase (PO) presented a significant increase as a function of culture time, appeared elevated following probiotic administration and were depleted 48 h following the experimental challenge. Lipid peroxidation reached peak levels at 48 h of culture, when nauplii start feeding and returned to lower values at 144 h, remaining however significantly higher than control (P probiotics significantly reduced lipid peroxidation in comparison with the corresponding control, while challenge with the pathogen resulted in its threefold increase. Survival of nauplii remained high throughout culture and was either increased or remained at control levels following the administration of the probiotics. The challenge with the pathogen resulted in a significantly decreased survival of 15.3% for the positive control, while in the probiotic treated series survival values were not significantly different from the negative control (P > 0.05). Following a combined administration of each probiotic and the pathogen the activities of all enzymes tested were significantly lower (P probiotic). Lipid peroxidation was significantly lower in the probiotic treated series in comparison to the positive control (P probiotics B. subtilis, L. plantarum and L. lactis protect Artemia against a V. anguillarum challenge by enhancing its immune responses thus contributing to reduced oxidative damage and increased survival. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Monitoring adaptive genetic responses to environmental change

    DEFF Research Database (Denmark)

    Hansen, M.M.; Olivieri, I.; Waller, D.M.

    2012-01-01

    Widespread environmental changes including climate change, selective harvesting and landscape alterations now greatly affect selection regimes for most organisms. How animals and plants can adapt to these altered environments via contemporary evolution is thus of strong interest. We discuss how...... for selection and establishing clear links between genetic and environmental change. We then review a few exemplary studies that explore adaptive responses to climate change in Drosophila, selective responses to hunting and fishing, and contemporary evolution in Daphnia using resurrected resting eggs. We...

  20. Determining Vaccination Frequency in Farmed Rainbow Trout Using Vibrio anguillarum O1 Specific Serum Antibody Measurements

    DEFF Research Database (Denmark)

    Holten-Andersen, Lars; Dalsgaard, Inger; Nylén, Jørgen

    2012-01-01

    Background Despite vaccination with a commercial vaccine with a documented protective effect against Vibrio anguillarum O1 disease outbreaks caused by this bacterium have been registered among rainbow trout at Danish fish farms. The present study examined specific serum antibody levels as a valid...

  1. The phosphotransferase VanU represses expression of four qrr genes antagonizing VanO-mediated quorum-sensing regulation in Vibrio anguillarum.

    Science.gov (United States)

    Weber, Barbara; Lindell, Kristoffer; El Qaidi, Samir; Hjerde, Erik; Willassen, Nils-Peder; Milton, Debra L

    2011-12-01

    Vibrio anguillarum utilizes quorum sensing to regulate stress responses required for survival in the aquatic environment. Like other Vibrio species, V. anguillarum contains the gene qrr1, which encodes the ancestral quorum regulatory RNA Qrr1, and phosphorelay quorum-sensing systems that modulate the expression of small regulatory RNAs (sRNAs) that destabilize mRNA encoding the transcriptional regulator VanT. In this study, three additional Qrr sRNAs were identified. All four sRNAs were positively regulated by σ(54) and the σ(54)-dependent response regulator VanO, and showed a redundant activity. The Qrr sRNAs, together with the RNA chaperone Hfq, destabilized vanT mRNA and modulated expression of VanT-regulated genes. Unexpectedly, expression of all four qrr genes peaked at high cell density, and exogenously added N-acylhomoserine lactone molecules induced expression of the qrr genes at low cell density. The phosphotransferase VanU, which phosphorylates and activates VanO, repressed expression of the Qrr sRNAs and stabilized vanT mRNA. A model is presented proposing that VanU acts as a branch point, aiding cross-regulation between two independent phosphorelay systems that activate or repress expression of the Qrr sRNAs, giving flexibility and precision in modulating VanT expression and inducing a quorum-sensing response to stresses found in a constantly changing aquatic environment.

  2. RpoS induces expression of the Vibrio anguillarum quorum-sensing regulator VanT.

    Science.gov (United States)

    Weber, Barbara; Croxatto, Antony; Chen, Chang; Milton, Debra L

    2008-03-01

    In vibrios, regulation of the Vibrio harveyi-like LuxR transcriptional activators occurs post-transcriptionally via small regulatory RNAs (sRNAs) that destabilize the luxR mRNA at a low cell population, eliminating expression of LuxR. Expression of the sRNAs is modulated by the vibrio quorum-sensing phosphorelay systems. However, vanT mRNA, which encodes a LuxR homologue in Vibrio anguillarum, is abundant at low and high cell density, indicating that VanT expression may be regulated via additional mechanisms. In this study, Western analyses showed that VanT was expressed throughout growth with a peak of expression during late exponential growth. VanO induced partial destabilization of vanT mRNA via activation of at least one Qrr sRNA. Interestingly, the sigma factor RpoS significantly stabilized vanT mRNA and induced VanT expression during late exponential growth. This induction was in part due to RpoS repressing expression of Hfq, an RNA chaperone. RpoS is not part of the quorum-sensing regulatory cascade since RpoS did not regulate expression or activity of VanO, and RpoS was not regulated by VanO or VanT. VanT and RpoS were needed for survival following UV irradiation and for pigment and metalloprotease production, suggesting that RpoS works with the quorum-sensing systems to modulate expression of VanT, which regulates survival and stress responses.

  3. Protective efficacy of six immunogenic recombinant proteins of Vibrio anguillarum and evaluation them as vaccine candidate for flounder (Paralichthys olivaceus).

    Science.gov (United States)

    Xing, Jing; Xu, Hongsen; Wang, Yang; Tang, Xiaoqian; Sheng, Xiuzhen; Zhan, Wenbin

    2017-06-01

    Vibrio anguillarum is a severe bacterium that causes terminal haemorrhagic septicaemia in freshwater and marine fish. Virulence-associated proteins play an important role in bacterial pathogenicity and could be applied for immunoprophylaxis. In this study, six antigenic proteins from V. anguillarum were selected and the immune protective efficacy of their recombinant proteins was investigated. VirA, CheR, FlaC, OmpK, OmpR and Hsp33 were recombinantly produced and the reactions of recombinant proteins to flounder-anti-V. anguillarum antibodies (fV-ab) were detected, respectively. Then the recombinant proteins were injected to fish, after immunization, the percentages of surface membrane immunoglobulin-positive (sIg+) cell in lymphocytes, total antibodies, antibodies against V. anguillarum, antibodies against recombinant proteins and relative percent survival (RPS) were analyzed, respectively. The results showed that all the recombinant proteins could react to fV-ab, proliferate sIg + cells in lymphocytes and induce production of total antibodies, specific antibodies against V. anguillarum or the recombinant proteins; the RPS of rVirA, rCheR, rFlaC, rOmpK, rOmpR and rHsp33 against V. anguillarum was 70.27%, 27.03%, 16.22%, 62.16%, 45.95% and 81.08%, respectively. The results revealed that rHsp33, rVirA and rOmpK have good protections against V. anguillarum and could be vaccine candidates against V. anguillarum. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Effect of multiple infections with white spot syndrome virus and Vibrio anguillarum on Pacific white shrimp Litopenaeus vannamei (L.): mortality and viral replication.

    Science.gov (United States)

    Jang, I K; Qiao, G; Kim, S-K

    2014-10-01

    Multiple infections are commonly found in practical shrimp culture and may cause more serious consequences than infections by one pathogen only. Therefore, this study was conducted to evaluate the effect of multiple infections with white spot syndrome virus (WSSV) and Vibrio anguillarum on Pacific white shrimp Litopenaeus vannamei (L.), mortality, WSSV replication in vivo and host immune response. In the WSSV single-infection group (WSSV load, 2 × 10(2) copies μL(-1)), mean cumulative mortality was 29.2%. In the V. anguillarum single-infection group, cumulative mortality was 12.5% when shrimp were challenged by 10(5) CFU mL(-1) of bacteria. In the co- and super-infection groups, 37.5% and 50% cumulative mortalities, respectively, were observed at a lower bacterial concentration of 10(3) CFU mL(-1), suggesting that shrimp with multiple infections died earlier and more frequently than singly infected shrimp. WSSV load after injection was tracked over time by TaqMan quantitative PCR. WSSV load increased more rapidly in the multiple-infection groups than in the single-infection group. Additionally, mRNA expression of the genes encoding prophenoloxidase 1 and 2, which are closely involved in innate immunity in shrimp, was down-regulated more extensively in multiple-infection groups than in single-infection groups, as indicated by quantitative reverse-transcription PCR. © 2013 John Wiley & Sons Ltd.

  5. Molecular cloning of the recA analog from the marine fish pathogen Vibrio anguillarum 775

    International Nuclear Information System (INIS)

    Singer, J.T.

    1989-01-01

    The recA analog from Vibrio anguillarum 775 was isolated by complementation of recA mutations in Escherichia coli, and its protein product was identified. The recA analog promoted recombination between two partially deleted lactose operons, stimulated both spontaneous and mitomycin C-induced phage production in RecA- lambda lysogens, and restored near wild-type levels of resistance to UV radiation and methyl methanesulfonate

  6. Inhibition of Vibrio anguillarum by Pseudomonas fluorescens AH2, a possible probiotic treatment of fish

    DEFF Research Database (Denmark)

    Gram, Lone; Melchiorsen, Jette; Spanggaard, Bettina

    1999-01-01

    To study the possible use of probiotics in fish farming, we evaluated the in vitro and in vivo antagonism of antibacterial strain Pseudomonas fluorescens strain AH2 against the fish- pathogenic bacterium Vibrio anguillarum. As iron is important in virulence and bacterial interactions, the effect....... fluorescens AH2 inhibited the growth of V. anguillarum during coculture, independently of the iron concentration, when the initial count of the antagonist was 100 to 1,000 times greater that of the fish pathogen. These in vitro results were successfully repeated in vivo. A probiotic effect in vivo was tested...... by exposing rainbow trout (Oncorynchus mykiss Walbaum) to P. fluorescens AH2 at a density of 10(5) CFU/ml for 5 days before a challenge with V. anguillarum at 10(4) to 10(5) CFU/ml for 1 h. Some fish were also exposed to P. fluorescens AH2 at 10(7) CFU/ml during the 1-h infection. The combined probiotic...

  7. Quorum sensing determines the choice of antiphage defense strategy in Vibrio anguillarum

    DEFF Research Database (Denmark)

    Tan, Demeng; Svenningsen, Sine Lo; Middelboe, Mathias

    2015-01-01

    of the outcome of phage-bacterial encounters in the fish pathogen Vibrio anguillarum is bacterial cell-cell communication, known as quorum sensing. Specifically, V. anguillarum PF430-3 cells locked in the low-cell-density state (ΔvanT mutant) express high levels of the phage receptor OmpK, resulting in a high...... susceptibility to phage KVP40, but achieve protection from infection by enhanced biofilm formation. By contrast, cells locked in the high-cell-density state (ΔvanΟ mutant) are almost completely unsusceptible due to quorum-sensing-mediated downregulation of OmpK expression. The phenotypes of the two quorum......-sensing mutant strains are accurately reflected in the behavior of wild-type V. anguillarum, which (i) displays increased OmpK expression in aggregated cells compared to free-living variants in the same culture, (ii) displays a clear inverse correlation between ompK mRNA levels and the concentration of N...

  8. Colonization of fish skin is vital for Vibrio anguillarum to cause disease.

    Science.gov (United States)

    Weber, Barbara; Chen, Chang; Milton, Debra L

    2010-02-01

    Vibrio anguillarum causes a fatal haemorrhagic septicaemia in marine fish. During initial stages of infection, host surfaces are colonized; however, few virulence factors required for colonization of the host are identified. In this study, in vivo bioluminescent imaging was used to analyse directly the colonization of the whole rainbow trout animal by V. anguillarum. The wild type rapidly colonized both the skin and the intestines by 24 h; however, the bacterial numbers on the skin were significantly higher than in the intestines indicating that skin colonization may be important for disease to occur. Mutants defective for the anguibactin iron uptake system, exopolysaccharide transport, or Hfq, an RNA chaperone, were attenuated for virulence, did not colonize the skin, and penetrated skin mucus less efficiently than the wild type. These mutants, however, did colonize the intestines and were as resistant to 2% bile salts as is the wild type. Moreover, exopolysaccharide mutants were significantly more sensitive to lysozyme and antimicrobial peptides, while the Hfq and anguibactin mutants were sensitive to lysozyme compared with the wild type. Vibrio anguillarum encodes several mechanisms to protect against antimicrobial components of skin mucus enabling an amazingly abundant growth on the skin enhancing its disease opportunities. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

  9. Genetic analysis of Myanmar Vigna species in responses to salt ...

    African Journals Online (AJOL)

    Genetic analysis of Myanmar Vigna species in responses to salt stress at the ... of reduction was highly dependent on different genotypes and salinity levels. ... the mechanism of salt tolerance and for the provision of genetic resources for ...

  10. Genetic influence demonstrated for MEG-recorded somatosensory evoked responses

    NARCIS (Netherlands)

    van 't Ent, D.; van Soelen, I.L.C.; Stam, K.J.; de Geus, E.J.C.; Boomsma, D.I.

    2010-01-01

    We tested for a genetic influence on magnetoencephalogram (MEG)-recorded somatosensory evoked fields (SEFs) in 20 monozygotic (MZ) and 14 dizygotic (DZ) twin pairs. Previous electroencephalogram (EEG) studies that demonstrated a genetic contribution to evoked responses generally focused on

  11. Exploration of Phage-Host Interactions in Fish Pathogen Vibrio anguillarum and Anti-Phage Defense Strategies

    DEFF Research Database (Denmark)

    Tan, Demeng

    The disease vibriosis is caused by the bacterial pathogen Vibrio anguillarum and results in large losses in aquaculture both in Denmark and around the world. Antibiotics have been widely used in antimicrobial prophylaxis and treatment of vibriosis. Recently, numerous multidrug-resistant strains...... of V. anguillarum have been isolated, indicating that antibiotic use has to be restricted and alternatives have to be developed. Lytic phages have been demonstrated to play an essential role in preventing bacterial infection. However, phages are also known to play a critical role in the evolution...... of bacterial pathogenicity development. Therefore, successful application of phage therapy in the treatment of vibriosis requires a detailed understanding of phage-host interactions, especially with regards to anti-phage defense mechanisms in the host. Part I. As a first approach, 24 V. anguillarum and 13...

  12. Genetic polymorphisms and lipid response to dietary changes in humans

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Ordovas, J.M.; Ramos-Galluzzi, J.; Katan, M.B.

    2001-01-01

    Previous studies on the effects of genetic polymorphisms on the serum cholesterol response to dietary treatments were often inconsistent and frequently involved small numbers of subjects. We studied the effect of 10 genetic polymorphisms on the responses of serum cholesterol to saturated and trans

  13. Pathogenicity of Vibrio anguillarum serogroup O1 strains compared to plasmids, outer membrane protein profiles and siderophore production

    DEFF Research Database (Denmark)

    Pedersen, K.; Gram, Lone; Austin, D.A.

    1997-01-01

    The virulence of 18 strains of Vibrio anguillarum serogroup 01 was compared to plasmid content, expression of siderophores and outer membrane proteins. All strains, irrespective of plasmid content, produced siderophores and inducible outer membrane proteins under iron-limited conditions. Only str...

  14. Development of a two-step, non-probed multiplex real-time PCR for surveilling Vibrio anguillarum in seawater

    Science.gov (United States)

    Vibrio anguillarum is an aggressive and halophilic bacterial pathogen commonly found in seawater. Its presence in aquaculture facilities causes significant morbidity and mortality among aquaculture species primarily from hemorrhaging of the body and skin of the infected fish that eventually leads t...

  15. Oral administration of formalin killed Vibrio anguillarum cells improves growth and protection against challenge with Vibrio harveyi in banana shrimp.

    Science.gov (United States)

    Patil, P K; Gopal, C; Panigrahi, A; Rajababu, D; Pillai, S M

    2014-03-01

    Larval rearing in hatcheries and highly intensive grow-out culture practices followed in shrimp production systems favour the growth of potential pathogenic bacterial loads. This study reports the efficacy of formalin-killed vibrio bacterin on growth, survival and protection to challenge with virulent Vibrio harveyi and Vibrio anguillarum in juveniles of banana shrimp Fenneropenaeus merguiensis. Postlarvae 15 (0·24 ± 0·01 g) were administered orally in different concentrations of bacterial preparation (0, 10(6) , 10(8) , 10(10) and 10(12 ) CFU kg(-1) feed) for a period of 6 weeks. Physicochemical and microbial quality of water in larval rearing tanks, and growth and survival of the postlarvae were monitored at regular intervals, and body composition was estimated at the end of the experiment. Shrimps were challenged with V. harveyi and V. anguillarum, and cumulative mortality was calculated. The group receiving 10(8)  CFU kg(-1) feed showed highest average weight gain (162·66 ± 22·94 mg) and survival (90·33 ± 4·5%) and lowest cumulative mortality following the challenge with V. anguillarum (26%) and V. harveyi (36·67%). The results of the study suggest that formalized vibrio administered orally to F. merguiensis postlarvae could induce both homologous and heterologous protection against V. anguillarum and V. harveyi. 'Vaccination' of shrimp postlarvae at hatcheries would help in preventing the losses due to vibriosis and the most susceptible stages of shrimp development. The study demonstrates the cross-protection offered by the oral feeding of formalin-killed Vibrio anguillarum against pathogenic V. harveyi challenge at the early developmental stages of banana shrimp, Fenneropenaeus merguiensis. © 2013 The Society for Applied Microbiology.

  16. Genetics Home Reference: biotin-thiamine-responsive basal ganglia disease

    Science.gov (United States)

    ... BTBGD thiamine metabolism dysfunction syndrome 2 thiamine-responsive encephalopathy thiamine transporter-2 deficiency THMD2 Related Information How ... genetic testing? What is precision medicine? What is newborn screening? New Pages LMNA-related congenital muscular dystrophy ...

  17. Identification of immunogenic proteins and evaluation of four recombinant proteins as potential vaccine antigens from Vibrio anguillarum in flounder (Paralichthys olivaceus).

    Science.gov (United States)

    Xing, Jing; Xu, Hongsen; Wang, Yang; Tang, Xiaoqian; Sheng, Xiuzhen; Zhan, Wenbin

    2017-05-31

    Vibrio anguillarum is a severe bacterial pathogen that can infect a wide range of fish species. Identification of immunogenic proteins and development of vaccine are essential for disease prevention. In this study, immunogenic proteins were screened and identified from V. anguillarum, and then protective efficacy of the immunogenic proteins was evaluated. Immunogenic proteins in V. anguillarum whole cell were detected by Western blotting (WB) using immunized flounder (Paralichthys olivaceus) serum, and then identified by Mass spectrometry (MS). The recombinant proteins of four identified immunogenic proteins were produced and immunized to fish, and then percentages of surface membrane immunoglobulin-positive (sIg+) cells in peripheral blood lymphocytes (PBL), total antibodies, antibodies against V. anguillarum, antibodies against recombinant proteins and relative percent survival (RPS) were measured, respectively. The results showed that five immunogenic proteins, VAA, Groel, OmpU, PteF and SpK, were identified; their recombinant proteins, rOmpU, rGroel, rSpK and rVAA, could induce the proliferation of sIg+ cells in PBL and production of total antibodies, antibodies against V. anguillarum and antibodies against the recombinant proteins; their protection against V. anguillarum showed 64.86%, 72.97%, 21.62% and 78.38% RPS, respectively. The results revealed that the immunoproteomic technique using fish anti-V. anguillarum serum provided an efficient way to screen the immunogenic protein for vaccine antigen. Moreover, the rVAA, rGroel and rOmpU had potential to be vaccine candidates against V. anguillarum infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Ocean acidification genetics - Genetics and genomics of response to ocean acidification

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — We are applying a variety of genetic tools to assess the response of our ocean resources to ocean acidification, including gene expression techniques, identification...

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

    Science.gov (United States)

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

    2011-01-01

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

  20. Profiling of acylated homoserine lactones of Vibrio anguillarum in vitro and in vivo: influence of growth conditions and serotype

    DEFF Research Database (Denmark)

    Buchholtz, Chrstiane; Nielsen, Kristian Fog; L. Milton, Debra

    2006-01-01

    Vibrio anguillarum produces several interlinked acylated homoserine lactone (AHL) signal molecules which may Vibrio anguillarum produces several interlinked acylated homoserine lactone (AHL) signal molecules which may influence expression of its virulence factors such as exoprotease production...... concentration) has little influence on the AHL-profile. Most strains produced N-(3-oxodecanoyl)-l-homoserine lactone (3-oxo-C10-HSL) and N-(3-hydroxy-hexanoyl)-l-homoserine lactone (3-hydroxy-C6-HSL) as the dominant molecules. Also, two spots with AHL activity appeared on TLC plates, which could...... not be identified as AHL structures. Trace amounts of N-(3-hydroxy-octanoyl)-l-homoserine lactone, N-(3-hydroxy-decanoyl)-l-homoserine lactone and N-(3-hydroxy-dodecanoyl)-l-homoserine lactone (3-hydroxy-C8-HSL, 3-hydroxy-C10-HSL and 3-oxo-C12-HSL, respectively) were also detected by HPLC-HRMS analysis from...

  1. Complete genome sequence of Vibrio anguillarum strain NB10, a virulent isolate from the Gulf of Bothnia.

    Science.gov (United States)

    Holm, Kåre Olav; Nilsson, Kristina; Hjerde, Erik; Willassen, Nils-Peder; Milton, Debra L

    2015-01-01

    Vibrio anguillarum causes a fatal hemorrhagic septicemia in marine fish that leads to great economical losses in aquaculture world-wide. Vibrio anguillarum strain NB10 serotype O1 is a Gram-negative, motile, curved rod-shaped bacterium, isolated from a diseased fish on the Swedish coast of the Gulf of Bothnia, and is slightly halophilic. Strain NB10 is a virulent isolate that readily colonizes fish skin and intestinal tissues. Here, the features of this bacterium are described and the annotation and analysis of its complete genome sequence is presented. The genome is 4,373,835 bp in size, consists of two circular chromosomes and one plasmid, and contains 3,783 protein-coding genes and 129 RNA genes.

  2. Mouse genetic approaches applied to the normal tissue radiation response

    International Nuclear Information System (INIS)

    Haston, Christina K.

    2012-01-01

    The varying responses of inbred mouse models to radiation exposure present a unique opportunity to dissect the genetic basis of radiation sensitivity and tissue injury. Such studies are complementary to human association studies as they permit both the analysis of clinical features of disease, and of specific variants associated with its presentation, in a controlled environment. Herein I review how animal models are studied to identify specific genetic variants influencing predisposition to radiation-induced traits. Among these radiation-induced responses are documented strain differences in repair of DNA damage and in extent of tissue injury (in the lung, skin, and intestine) which form the base for genetic investigations. For example, radiation-induced DNA damage is consistently greater in tissues from BALB/cJ mice, than the levels in C57BL/6J mice, suggesting there may be an inherent DNA damage level per strain. Regarding tissue injury, strain specific inflammatory and fibrotic phenotypes have been documented for principally, C57BL/6 C3H and A/J mice but a correlation among responses such that knowledge of the radiation injury in one tissue informs of the response in another is not evident. Strategies to identify genetic differences contributing to a trait based on inbred strain differences, which include linkage analysis and the evaluation of recombinant congenic (RC) strains, are presented, with a focus on the lung response to irradiation which is the only radiation-induced tissue injury mapped to date. Such approaches are needed to reveal genetic differences in susceptibility to radiation injury, and also to provide a context for the effects of specific genetic variation uncovered in anticipated clinical association studies. In summary, mouse models can be studied to uncover heritable variation predisposing to specific radiation responses, and such variations may point to pathways of importance to phenotype development in the clinic.

  3. Genetic responses against nitric oxide toxicity

    Directory of Open Access Journals (Sweden)

    B. Demple

    1999-11-01

    Full Text Available The threat of free radical damage is opposed by coordinated responses that modulate expression of sets of gene products. In mammalian cells, 12 proteins are induced by exposure to nitric oxide (NO levels that are sub-toxic but exceed the level needed to activate guanylate cyclase. Heme oxygenase 1 (HO-1 synthesis increases substantially, due to a 30- to 70-fold increase in the level of HO-1 mRNA. HO-1 induction is cGMP-independent and occurs mainly through increased mRNA stability, which therefore indicates a new NO-signaling pathway. HO-1 induction contributes to dramatically increased NO resistance and, together with the other inducible functions, constitutes an adaptive resistance pathway that also defends against oxidants such as H2O2. In E. coli, an oxidative stress response, the soxRS regulon, is activated by direct exposure of E. coli to NO, or by NO generated in murine macrophages after phagocytosis of the bacteria. This response is governed by the SoxR protein, a homodimeric transcription factor (17-kDa subunits containing [2Fe-2S] clusters essential for its activity. SoxR responds to superoxide stress through one-electron oxidation of the iron-sulfur centers, but such oxidation is not observed in reactions of NO with SoxR. Instead, NO nitrosylates the iron-sulfur centers of SoxR both in vitro and in intact cells, which yields a form of the protein with maximal transcriptional activity. Although nitrosylated SoxR is very stable in purified form, the spectroscopic signals for the nitrosylated iron-sulfur centers disappear rapidly in vivo, indicating an active process to reverse or eliminate them.

  4. Lipopolysaccharide O-antigen prevents phagocytosis of Vibrio anguillarum by rainbow trout (Oncorhynchus mykiss skin epithelial cells.

    Directory of Open Access Journals (Sweden)

    Kristoffer Lindell

    Full Text Available Colonization of host tissues is a first step taken by many pathogens during the initial stages of infection. Despite the impact of bacterial disease on wild and farmed fish, only a few direct studies have characterized bacterial factors required for colonization of fish tissues. In this study, using live-cell and confocal microscopy, rainbow trout skin epithelial cells, the main structural component of the skin epidermis, were demonstrated to phagocytize bacteria. Mutant analyses showed that the fish pathogen Vibrio anguillarum required the lipopolysaccharide O-antigen to evade phagocytosis and that O-antigen transport required the putative wzm-wzt-wbhA operon, which encodes two ABC polysaccharide transporter proteins and a methyltransferase. Pretreatment of the epithelial cells with mannose prevented phagocytosis of V. anguillarum suggesting that a mannose receptor is involved in the uptake process. In addition, the O-antigen transport mutants could not colonize the skin but they did colonize the intestines of rainbow trout. The O-antigen polysaccharides were also shown to aid resistance to the antimicrobial factors, lysozyme and polymyxin B. In summary, rainbow trout skin epithelial cells play a role in the fish innate immunity by clearing bacteria from the skin epidermis. In defense, V. anguillarum utilizes O-antigen polysaccharides to evade phagocytosis by the epithelial cells allowing it to colonize rapidly fish skin tissues.

  5. Lipopolysaccharide O-Antigen Prevents Phagocytosis of Vibrio anguillarum by Rainbow Trout (Oncorhynchus mykiss) Skin Epithelial Cells

    Science.gov (United States)

    Lindell, Kristoffer; Fahlgren, Anna; Hjerde, Erik; Willassen, Nils-Peder; Fällman, Maria; Milton, Debra L.

    2012-01-01

    Colonization of host tissues is a first step taken by many pathogens during the initial stages of infection. Despite the impact of bacterial disease on wild and farmed fish, only a few direct studies have characterized bacterial factors required for colonization of fish tissues. In this study, using live-cell and confocal microscopy, rainbow trout skin epithelial cells, the main structural component of the skin epidermis, were demonstrated to phagocytize bacteria. Mutant analyses showed that the fish pathogen Vibrio anguillarum required the lipopolysaccharide O-antigen to evade phagocytosis and that O-antigen transport required the putative wzm-wzt-wbhA operon, which encodes two ABC polysaccharide transporter proteins and a methyltransferase. Pretreatment of the epithelial cells with mannose prevented phagocytosis of V. anguillarum suggesting that a mannose receptor is involved in the uptake process. In addition, the O-antigen transport mutants could not colonize the skin but they did colonize the intestines of rainbow trout. The O-antigen polysaccharides were also shown to aid resistance to the antimicrobial factors, lysozyme and polymyxin B. In summary, rainbow trout skin epithelial cells play a role in the fish innate immunity by clearing bacteria from the skin epidermis. In defense, V. anguillarum utilizes O-antigen polysaccharides to evade phagocytosis by the epithelial cells allowing it to colonize rapidly fish skin tissues. PMID:22662189

  6. Genetic Testing Accounts of Autonomy, Responsibility and Blame

    DEFF Research Database (Denmark)

    Arribas-Ayllon, M.; Sarangi, Srikant; Clarke, Angus

    Advances in molecular genetics have led to the increasing availability of genetic testing for a variety of inherited disorders. While this new knowledge presents many obvious health benefits to prospective individuals and their families it also raises complex ethical and moral dilemmas for famili......, the assessment of competence and maturity, the ability to engage in shared decision-making through acts of disclosure and choice, are just some of the issues that are examined in detail....... as well as genetic professionals. This book explores the ways in which genetic testing generates not only probabilities of potential futures, but also enjoys new forms of social, individual and professional responsibility. Concerns about confidentiality and informed consent involving children...

  7. Genetics of growth habit and photoperiodic response to flowering ...

    Indian Academy of Sciences (India)

    2014-04-16

    Apr 16, 2014 ... 3Department of Agricultural Entomology, University of Agricultural Sciences, Gandhi Krishi Vignana Kendra,. Bangalore 560 065, India. [Keerthi C. M., Ramesh S., Byregowda M., Rao A. M., Rajendra Prasad B. S. and Vaijayanthi P. V. 2014 Genetics of growth habit and photoperiodic response to flowering ...

  8. Genetic and epigenetic control of plant heat responses

    Directory of Open Access Journals (Sweden)

    Junzhong eLiu

    2015-04-01

    Full Text Available Plants have evolved sophisticated genetic and epigenetic regulatory systems to respond quickly to unfavorable environmental conditions such as heat, cold, drought, and pathogen infections. In particular, heat greatly affects plant growth and development, immunity and circadian rhythm, and poses a serious threat to the global food supply. According to temperatures exposing, heat can be usually classified as warm ambient temperature (about 22-27℃, high temperature (27-30℃ and extremely high temperature (37-42℃, also known as heat stress for the model plant Arabidopsis thaliana. The genetic mechanisms of plant responses to heat have been well studied, mainly focusing on elevated ambient temperature-mediated morphological acclimation and acceleration of flowering, modulation of plant immunity and circadian clock by high temperatures, and thermotolerance to heat stress. Recently, great progress has been achieved on epigenetic regulation of heat responses, including DNA methylation, histone modifications, histone variants, ATP-dependent chromatin remodeling, histone chaperones, small RNAs, long non-coding RNAs and other undefined epigenetic mechanisms. These epigenetic modifications regulate the expression of heat-responsive genes and function to prevent heat-related damage. This review focuses on recent progresses regarding the genetic and epigenetic control of heat responses in plants, and pays more attention to the role of the major epigenetic mechanisms in plant heat responses. Further research perspectives are also discussed.

  9. A genetic dissection of the photophobic response of Paramecium tetraurelia.

    Science.gov (United States)

    Hinrichsen, Robert; Peters, Christian

    2013-05-01

    Paramecium tetraurelia displayed two behavioral responses upon the initiation of a light stimulus at 7 x 10(4) lux. The cells exhibited a photophobic response in the form of behavioral avoiding reactions, followed by an increase in forward swimming velocity that was significantly higher than prior to the light stimulus activation. It was determined that an intensity of approximately 6.5 x 10(3) lux was required to initiate a moderate avoidance behavioral response. Following the avoiding response, a gradual increase in speed occurred as the intensity increased, indicating that increased swimming speeds are dependent on the light intensity. Two mutants, pawnA and Dancer, were utilized since they affect known Ca(2+)-currents of the cell. The use of pawnA cells, which lack voltage-dependent Ca(2+) channel activity, showed that the two responses to light could be genetically separated, in that the cells showed no avoiding reactions, but did increase their swimming speed. The Dancer cells, which display exaggerated Ca(2+) channel activity, exhibited similar initial avoiding responses as the wild type cells, however did not increase their swimming speed as the intensity of the light was increased. This phenotype as replicated in wildtype cells that had been placed in 25 μM 8-Br-cGMP. These data demonstrate that the photophobic light response of Paramecium tetraurelia can be genetically dissected as a means of elucidating the molecular mechanisms of the light response. Copyright © 2013 Elsevier GmbH. All rights reserved.

  10. Plant genetic and molecular responses to water deficit

    Directory of Open Access Journals (Sweden)

    Silvio Salvi

    2011-02-01

    Full Text Available Plant productivity is severely affected by unfavourable environmental conditions (biotic and abiotic stresses. Among others, water deficit is the plant stress condition which mostly limits the quality and the quantity of plant products. Tolerance to water deficit is a polygenic trait strictly dependent on the coordinated expression of a large set of genes coding for proteins directly involved in stress-induced protection/repair mechanisms (dehydrins, chaperonins, enzymes for the synthesis of osmoprotectants and detoxifying compounds, and others as well as genes involved in transducing the stress signal and regulating gene expression (transcription factors, kinases, phosphatases. Recently, research activities in the field evolved from the study of single genes directly involved in cellular stress tolerance (functional genes to the identification and characterization of key regulatory genes involved in stress perception and transduction and able to rapidly and efficiently activate the complex gene network involved in the response to stress. The complexity of the events occurring in response to stress have been recently approached by genomics tools; in fact the analysis of transcriptome, proteome and metabolome of a plant tissue/cell in response to stress already allowed to have a global view of the cellular and molecular events occurring in response to water deficit, by the identification of genes activated and co-regulated by the stress conditions and the characterization of new signalling pathways. Moreover the recent application of forward and reverse genetic approaches, trough mutant collection development, screening and characterization, is giving a tremendous impulse to the identification of gene functions with key role in stress tolerance. The integration of data obtained by high-throughput genomic approaches, by means of powerful informatic tools, is allowing nowadays to rapidly identify of major genes/QTLs involved in stress tolerance

  11. Influence of chlorine on the susceptibility of striped bass (Morone saxatilis) to Vibrio anguillarum

    Energy Technology Data Exchange (ETDEWEB)

    Hetrick, F M; Hall, Jr, L W; Wolski, S; Graves, W C; Roberson, B S

    1984-09-01

    The subtle effects that low levels of pollutants have on fish populations are probably more important than the effects of large spills, since the effects are less likely to be obvious and the source more difficult to detect in time to save the environment. An experiment was carried out to determine if exposure of striped bass to sublethal concentrations of chlorine affected their susceptibility to bacterial infection. Exposure of striped bass for 96 h to sublethal concentrations of total residual chlorine (TRC) (0.05-0.23 mg/L) did not increase their susceptibility to infection with the bacterial pathogen Vibrio anguillarum. Variables examined were TRC concentrations, length of exposure to chlorine, and the order of exposure to chlorine and the pathogen. Mortalities in the groups exposed to both chlorine and pathogen were not significantly different from those seen in groups receiving the bacteria only. Smaller fish are more susceptible than larger fish, and the LD50 is markedly affected by the ambient temperature in that fewer bacteria are needed to kill fish at lower temperatures. One contributing factor to this increased resistance of fish at higher water temperatures appears to be related to their immune status. 29 references, 5 tables.

  12. Host genetic variation influences gene expression response to rhinovirus infection.

    Directory of Open Access Journals (Sweden)

    Minal Çalışkan

    2015-04-01

    Full Text Available Rhinovirus (RV is the most prevalent human respiratory virus and is responsible for at least half of all common colds. RV infections may result in a broad spectrum of effects that range from asymptomatic infections to severe lower respiratory illnesses. The basis for inter-individual variation in the response to RV infection is not well understood. In this study, we explored whether host genetic variation is associated with variation in gene expression response to RV infections between individuals. To do so, we obtained genome-wide genotype and gene expression data in uninfected and RV-infected peripheral blood mononuclear cells (PBMCs from 98 individuals. We mapped local and distant genetic variation that is associated with inter-individual differences in gene expression levels (eQTLs in both uninfected and RV-infected cells. We focused specifically on response eQTLs (reQTLs, namely, genetic associations with inter-individual variation in gene expression response to RV infection. We identified local reQTLs for 38 genes, including genes with known functions in viral response (UBA7, OAS1, IRF5 and genes that have been associated with immune and RV-related diseases (e.g., ITGA2, MSR1, GSTM3. The putative regulatory regions of genes with reQTLs were enriched for binding sites of virus-activated STAT2, highlighting the role of condition-specific transcription factors in genotype-by-environment interactions. Overall, we suggest that the 38 loci associated with inter-individual variation in gene expression response to RV-infection represent promising candidates for affecting immune and RV-related respiratory diseases.

  13. Host genetic variation influences gene expression response to rhinovirus infection.

    Science.gov (United States)

    Çalışkan, Minal; Baker, Samuel W; Gilad, Yoav; Ober, Carole

    2015-04-01

    Rhinovirus (RV) is the most prevalent human respiratory virus and is responsible for at least half of all common colds. RV infections may result in a broad spectrum of effects that range from asymptomatic infections to severe lower respiratory illnesses. The basis for inter-individual variation in the response to RV infection is not well understood. In this study, we explored whether host genetic variation is associated with variation in gene expression response to RV infections between individuals. To do so, we obtained genome-wide genotype and gene expression data in uninfected and RV-infected peripheral blood mononuclear cells (PBMCs) from 98 individuals. We mapped local and distant genetic variation that is associated with inter-individual differences in gene expression levels (eQTLs) in both uninfected and RV-infected cells. We focused specifically on response eQTLs (reQTLs), namely, genetic associations with inter-individual variation in gene expression response to RV infection. We identified local reQTLs for 38 genes, including genes with known functions in viral response (UBA7, OAS1, IRF5) and genes that have been associated with immune and RV-related diseases (e.g., ITGA2, MSR1, GSTM3). The putative regulatory regions of genes with reQTLs were enriched for binding sites of virus-activated STAT2, highlighting the role of condition-specific transcription factors in genotype-by-environment interactions. Overall, we suggest that the 38 loci associated with inter-individual variation in gene expression response to RV-infection represent promising candidates for affecting immune and RV-related respiratory diseases.

  14. Phaeobacter gallaeciensis Reduces Vibrio anguillarum in Cultures of Microalgae and Rotifers, and Prevents Vibriosis in Cod Larvae

    Science.gov (United States)

    D’Alvise, Paul W.; Lillebø, Siril; Prol-Garcia, Maria J.; Wergeland, Heidrun I.; Nielsen, Kristian F.; Bergh, Øivind; Gram, Lone

    2012-01-01

    Phaeobacter gallaeciensis can antagonize fish-pathogenic bacteria in vitro, and the purpose of this study was to evaluate the organism as a probiont for marine fish larvae and their feed cultures. An in vivo mechanism of action of the antagonistic probiotic bacterium is suggested using a non-antagonistic mutant. P. gallaeciensis was readily established in axenic cultures of the two microalgae Tetraselmis suecica and Nannochloropsis oculata, and of the rotifer Brachionus plicatilis. P. gallaeciensis reached densities of 107 cfu/ml and did not adversely affect growth of algae or rotifers. Vibrio anguillarum was significantly reduced by wild-type P. gallaeciensis, when introduced into these cultures. A P. gallaeciensis mutant that did not produce the antibacterial compound tropodithietic acid (TDA) did not reduce V. anguillarum numbers, suggesting that production of the antibacterial compound is important for the antagonistic properties of P. gallaeciensis. The ability of P. gallaeciensis to protect fish larvae from vibriosis was determined in a bath challenge experiment using a multidish system with 1 larva per well. Unchallenged larvae reached 40% accumulated mortality which increased to 100% when infected with V. anguillarum. P. gallaeciensis reduced the mortality of challenged cod larvae (Gadus morhua) to 10%, significantly below the levels of both the challenged and the unchallenged larvae. The TDA mutant reduced mortality of the cod larvae in some of the replicates, although to a much lesser extent than the wild type. It is concluded that P. gallaeciensis is a promising probiont in marine larviculture and that TDA production likely contributes to its probiotic effect. PMID:22928051

  15. Phaeobacter gallaeciensis reduces Vibrio anguillarum in cultures of microalgae and rotifers, and prevents vibriosis in cod larvae.

    Directory of Open Access Journals (Sweden)

    Paul W D'Alvise

    Full Text Available Phaeobacter gallaeciensis can antagonize fish-pathogenic bacteria in vitro, and the purpose of this study was to evaluate the organism as a probiont for marine fish larvae and their feed cultures. An in vivo mechanism of action of the antagonistic probiotic bacterium is suggested using a non-antagonistic mutant. P. gallaeciensis was readily established in axenic cultures of the two microalgae Tetraselmis suecica and Nannochloropsis oculata, and of the rotifer Brachionus plicatilis. P. gallaeciensis reached densities of 10(7 cfu/ml and did not adversely affect growth of algae or rotifers. Vibrio anguillarum was significantly reduced by wild-type P. gallaeciensis, when introduced into these cultures. A P. gallaeciensis mutant that did not produce the antibacterial compound tropodithietic acid (TDA did not reduce V. anguillarum numbers, suggesting that production of the antibacterial compound is important for the antagonistic properties of P. gallaeciensis. The ability of P. gallaeciensis to protect fish larvae from vibriosis was determined in a bath challenge experiment using a multidish system with 1 larva per well. Unchallenged larvae reached 40% accumulated mortality which increased to 100% when infected with V. anguillarum. P. gallaeciensis reduced the mortality of challenged cod larvae (Gadus morhua to 10%, significantly below the levels of both the challenged and the unchallenged larvae. The TDA mutant reduced mortality of the cod larvae in some of the replicates, although to a much lesser extent than the wild type. It is concluded that P. gallaeciensis is a promising probiont in marine larviculture and that TDA production likely contributes to its probiotic effect.

  16. Isocitrate dehydrogenase mutation in Vibrio anguillarum results in virulence attenuation and immunoprotection in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Mou, Xiangyu; Spinard, Edward J; Hillman, Shelby L; Nelson, David R

    2017-11-14

    Vibrio anguillarum is an extracellular bacterial pathogen that is a causative agent of vibriosis in finfish and crustaceans with mortality rates ranging from 30% to 100%. Mutations in central metabolism (glycolysis and the TCA cycle) of intracellular pathogens often result in attenuated virulence due to depletion of required metabolic intermediates; however, it was not known whether mutations in central metabolism would affect virulence in an extracellular pathogen such as V. anguillarum. Seven central metabolism mutants were created and characterized with regard to growth in minimal and complex media, expression of virulence genes, and virulence in juvenile rainbow trout (Oncorhynchus mykiss). Only the isocitrate dehydrogenase (icd) mutant was attenuated in virulence against rainbow trout challenged by either intraperitoneal injection or immersion. Further, the icd mutant was shown to be immunoprotective against wild type V. anguillarum infection. There was no significant decrease in the expression of the three hemolysin genes detected by qRT-PCR. Additionally, only the icd mutant exhibited a significantly decreased growth yield in complex media. Growth yield was directly related to the abundance of glutamate. A strain with a restored wild type icd gene was created and shown to restore growth to a wild type cell density in complex media and pathogenicity in rainbow trout. The data strongly suggest that a decreased growth yield, resulting from the inability to synthesize α-ketoglutarate, caused the attenuation despite normal levels of expression of virulence genes. Therefore, the ability of an extracellular pathogen to cause disease is dependent upon the availability of host-supplied nutrients for growth. Additionally, a live vaccine strain could be created from an icd deletion strain.

  17. Genetic Influences on Response to Alcohol and Response to Pharmacotherapies for Alcoholism

    Science.gov (United States)

    Enoch, Mary-Anne

    2014-01-01

    Although very many individuals drink alcohol at safe levels, a significant proportion escalates their consumption with addiction as the end result. Alcoholism is a common, moderately heritable, psychiatric disorder that is accompanied by considerable morbidity and mortality. Variation in clinical presentation suggests inter-individual variation in mechanisms of vulnerability including genetic risk factors. The development of addiction is likely to involve numerous functional genetic variants of small effects. The first part of this review will focus on genetic factors underlying inter-individual variability in response to alcohol consumption, including variants in alcohol metabolizing genes that produce an aversive response (the flushing syndrome) and variants that predict the level of subjective and physiological response to alcohol. The second part of this review will report on genetic variants that identify subgroups of alcoholics who are more likely to respond to pharmacotherapy to reduce levels of drinking or maintain abstinence. Genetic analyses of the level of response to alcohol, particularly of the functional OPRM1 A118G polymorphism and 5′ and 3′ functional polymorphisms in SLC6A4, are beginning to provide insights into the etiology of alcoholism and also genotype-stratified subgroup responses to naltrexone and SSRIs / ondansetron respectively. Because of large inter-ethnic variation in allele frequencies, the relevance of these functional polymorphisms will vary between ethnic groups. However there are relatively few published studies in this field, particularly with large sample sizes in pharmacogenetic studies, therefore it is premature to draw any conclusions at this stage. PMID:24220019

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

    Lifescience Database Archive (English)

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

  19. Impact of genetic polymorphisms on clinical response to antithrombotics

    Directory of Open Access Journals (Sweden)

    Kena J Lanham

    2010-06-01

    Full Text Available Kena J Lanham1,2, Julie H Oestreich3, Steven P Dunn1,2, Steven R Steinhubl41Pharmacy Services, UK HealthCare, University of Kentucky, Lexington, Kentucky, USA; 2Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA; 3Department of Pharmacy Practice, College of Pharmacy, University of Nebraska, Omaha, Nebraska, USA; 4The Medicines Company, Zurich, Switzerland and The Geisinger Clinic, Danville, Pennsylvania, USAAbstract: Antithrombotic therapy, including anticoagulants as well as antiplatelet drugs, is an important component in the treatment of cardiovascular disease. Variability in response to such medications, of which pharmacogenetic response is a major source, can decrease or enhance the benefits expected. This review is a comprehensive assessment of the literature published to date on the effects of genetic polymorphisms on the actions of a variety of antithrombotic medications, including warfarin, clopidogrel, prasugrel, and aspirin. Literature evaluating surrogate markers in addition to the impact of pharmacogenetics on clinical outcomes has been reviewed. The results of the studies are conflicting as to what degree pharmacogenetics will affect medication management in cardiovascular disease. Additional research is necessary to discover, characterize, and prospectively evaluate genetic and non-genetic factors that impact antithrombotic treatment in order to maximize the effectiveness and limit the harmful effects of these valuable agents.Keywords: aspirin, warfarin, clopidogrel, prasugrel, pharmacogenetic, antithrombotic, antiplatelet

  20. Genetic predictors of response to antidepressants in the GENDEP project

    DEFF Research Database (Denmark)

    Uher, Rudolf; Huezo-Diaz, Patricia; Perroud, Nader

    2009-01-01

    -reuptake-inhibiting and norepinephrine-reuptake-inhibiting antidepressants. A total of 116 single nucleotide polymorphisms in 10 candidate genes were genotyped in 760 adult patients with moderate-to-severe depression, treated with escitalopram (a serotonin reuptake inhibitor) or nortriptyline (a norepinephrine reuptake inhibitor......) for 12 weeks in an open-label part-randomized multicenter study. The effect of genetic variants on change in depressive symptoms was evaluated using mixed linear models. Several variants in a serotonin receptor gene (HTR2A) predicted response to escitalopram with one marker (rs9316233) explaining 1...... to the serotonin-reuptake-inhibiting escitalopram, genes encoding proteins in norepinephrine signaling influencing response to the norepinephrine-reuptake-inhibiting nortriptyline and a common pathway gene influencing response to both antidepressants. The single marker associations explained only a small...

  1. A genetically encoded biosensor for visualising hypoxia responses in vivo

    Directory of Open Access Journals (Sweden)

    Tvisha Misra

    2017-02-01

    Full Text Available Cells experience different oxygen concentrations depending on location, organismal developmental stage, and physiological or pathological conditions. Responses to reduced oxygen levels (hypoxia rely on the conserved hypoxia-inducible factor 1 (HIF-1. Understanding the developmental and tissue-specific responses to changing oxygen levels has been limited by the lack of adequate tools for monitoring HIF-1 in vivo. To visualise and analyse HIF-1 dynamics in Drosophila, we used a hypoxia biosensor consisting of GFP fused to the oxygen-dependent degradation domain (ODD of the HIF-1 homologue Sima. GFP-ODD responds to changing oxygen levels and to genetic manipulations of the hypoxia pathway, reflecting oxygen-dependent regulation of HIF-1 at the single-cell level. Ratiometric imaging of GFP-ODD and a red-fluorescent reference protein reveals tissue-specific differences in the cellular hypoxic status at ambient normoxia. Strikingly, cells in the larval brain show distinct hypoxic states that correlate with the distribution and relative densities of respiratory tubes. We present a set of genetic and image analysis tools that enable new approaches to map hypoxic microenvironments, to probe effects of perturbations on hypoxic signalling, and to identify new regulators of the hypoxia response.

  2. Disruption of Cell-to-Cell Signaling Does Not Abolish the Antagonism of Phaeobacter gallaeciensis toward the Fish Pathogen Vibrio anguillarum in Algal Systems

    DEFF Research Database (Denmark)

    Prol García, María Jesús; D'Alvise, Paul; Gram, Lone

    2013-01-01

    Quorum sensing (QS) regulates Phaeobacter gallaeciensis antagonism in broth systems; however, we demonstrate here that QS is not important for antagonism in algal cultures. QS mutants reduced Vibrio anguillarum to the same extent as the wild type. Consequently, a combination of probiotic Phaeobac...... Phaeobacter and QS inhibitors is a feasible strategy for aquaculture disease control....

  3. Genetic analysis of superovulatory response of Holstein cows in Canada.

    Science.gov (United States)

    Jaton, C; Koeck, A; Sargolzaei, M; Malchiodi, F; Price, C A; Schenkel, F S; Miglior, F

    2016-05-01

    Superovulation of dairy cattle is frequently used in Canada. The cost of this protocol is high, and so is the variability of the outcome. Knowing the superovulatory potential of a donor cow could influence the breeder's decision to superovulate it or not. The main objective of this study was to perform a genetic analysis for superovulatory response of Holstein cows in Canada using data recorded by Holstein Canada, and to investigate if these data could be used for genetic evaluation. Data contained the total number of embryos and the number of viable embryos from every successful flushing performed across Canada. After editing, 137,446 records of superovulation performed between 1992 and 2014 were analyzed. A univariate repeatability animal model analysis was performed for both total number of embryos and number of viable embryos. Because both data and residuals did not follow a normal distribution, records were subject to either logarithmic or Anscombe transformation. Using logarithmic transformation, heritability estimates (SE) of 0.15 (0.01) and 0.14 (0.01) were found for total number of embryos and number of viable embryos, respectively. Using Anscombe transformation, heritability estimates (SE) of 0.17 (0.01) and 0.14 (0.01) were found for total number of embryos and number of viable embryos, respectively. The genetic correlation between the 2 traits was estimated at 0.97 using logarithmic transformation and 0.95 using Anscombe transformation. Breeding values were estimated for 54,463 cows, and 3,513 sires. Only estimated breeding values of sires having a reliability higher than 40% were considered for estimated breeding values correlations with other routinely evaluated traits. The results showed that selection for a higher response to superovulation would lead to a slight decrease in milk production, but an improvement for functional traits, including all reproduction traits. In all cases, the estimated correlations are either low or modest. We conclude that

  4. Isolation and characterization of pathogenic Listonella anguillarum of diseased half-smooth tongue sole ( Cynoglossus semilaevis Günther)

    Science.gov (United States)

    Tang, Xiaoqian; Zhou, Li; Zhan, Wenbin

    2008-08-01

    Studies were conducted to determine the cause of the acute mortality of half-smooth tongue sole Cynoglossus semilaevis Günther juveniles in a fish farm in Jimo, Shandong Province, China, in June 2006. Gross signs of the diseased tongue sole included several petechiae and ecchymoses on the body and fin necrosis and hemorrhagic lesion at the base of the fin. Bacteria were isolated from kidney, liver and hemorrhagic lesions of the diseased tongue sole. Among14 strains, SJ060621 was proved to be highly virulent to juvenile tongue sole with LD50 value of antibiotics tested, SJ060621 was sensitive to gentamicin and nitrofurantoin. It was identified as Listonella anguillarum with conventional plate and tube tests in combination with API 20E analysis. 16S rRNA gene and partial HSP60 gene sequenceing analysis revealed that the strain was highly homologous with L. anguillarum. Examination of the infected musculature by electron microscopy indicated numerous bacteria and lots of macrophages containing phagocytosed bacteria. Histopathological investigations revealed severe necrotic degenerative changes in the infected organs. Indirect immunofluorescence assay (IFA) was employed to detect the location of occurrence of bacteria, and bacteria were found in aggregations in the inflammatory areas in musculature.

  5. Dataset on genetic and physiological adults׳ responses to social distress.

    Science.gov (United States)

    Bonassi, Andrea; Ghilardi, Tommaso; Truzzi, Anna; Cataldo, Ilaria; Azhari, Atiqah; Setoh, Peipei; Shinohara, Kazuyuki; Esposito, Gianluca

    2017-08-01

    Both expectations towards interactions with conspecifics, and genetic predispositions, affect adults׳ social behaviors. However, the underlying mechanisms remain largely unknown. Here, we report data to investigate the interaction between genetic factors, (oxytocin receptor (OXTR) and serotonin transporter (5-HTTLPR) polymorphisms), and adult interactional patterns in shaping physiological responses to social distress. During the presentation of distress vocalizations (cries of human female, infants and bonobos) we assessed participants׳ ( N = 42 males) heart rate (HR) and peripheral nose temperature, which index state of arousal and readiness to action. Self-reported questionnaires were used to evaluate participants' interactional patterns towards peers (Attachment Style Questionnaire, Feeney et al., 1994[1]), and the quality of bond with intimate partners (Experiences in Close Relationships Scale, Fraley et al., 2000 [2]). To assess participants׳ genetic predispositions, the OXTR gene (regions rs53576, and rs2254298) and the 5-HTTLPR gene (region SLC6A4) were genotyped. The data set is made publicly available to enable critical or extended analyzes.

  6. Dataset on genetic and physiological adults׳ responses to social distress

    Directory of Open Access Journals (Sweden)

    Andrea Bonassi

    2017-08-01

    Full Text Available Both expectations towards interactions with conspecifics, and genetic predispositions, affect adults׳ social behaviors. However, the underlying mechanisms remain largely unknown. Here, we report data to investigate the interaction between genetic factors, (oxytocin receptor (OXTR and serotonin transporter (5-HTTLPR polymorphisms, and adult interactional patterns in shaping physiological responses to social distress. During the presentation of distress vocalizations (cries of human female, infants and bonobos we assessed participants׳ (N = 42 males heart rate (HR and peripheral nose temperature, which index state of arousal and readiness to action. Self-reported questionnaires were used to evaluate participants’ interactional patterns towards peers (Attachment Style Questionnaire, Feeney et al., 1994 [1], and the quality of bond with intimate partners (Experiences in Close Relationships Scale, Fraley et al., 2000 [2]. To assess participants׳ genetic predispositions, the OXTR gene (regions rs53576, and rs2254298 and the 5-HTTLPR gene (region SLC6A4 were genotyped. The data set is made publicly available to enable critical or extended analyzes.

  7. VanT, a homologue of Vibrio harveyi LuxR, regulates serine, metalloprotease, pigment, and biofilm production in Vibrio anguillarum.

    Science.gov (United States)

    Croxatto, Antony; Chalker, Victoria J; Lauritz, Johan; Jass, Jana; Hardman, Andrea; Williams, Paul; Cámara, Miguel; Milton, Debra L

    2002-03-01

    Vibrio anguillarum possesses at least two N-acylhomoserine lactone (AHL) quorum-sensing circuits, one of which is related to the luxMN system of Vibrio harveyi. In this study, we have cloned an additional gene of this circuit, vanT, encoding a V. harveyi LuxR-like transcriptional regulator. A V. anguillarum Delta vanT null mutation resulted in a significant decrease in total protease activity due to loss of expression of the metalloprotease EmpA, but no changes in either AHL production or virulence. Additional genes positively regulated by VanT were identified from a plasmid-based gene library fused to a promoterless lacZ. Three lacZ fusions (serA::lacZ, hpdA-hgdA::lacZ, and sat-vps73::lacZ) were identified which exhibited decreased expression in the Delta vanT strain. SerA is similar to 3-phosphoglycerate dehydrogenases and catalyzes the first step in the serine-glycine biosynthesis pathway. HgdA has identity with homogentisate dioxygenases, and HpdA is homologous to 4-hydroxyphenylpyruvate dioxygenases (HPPDs) involved in pigment production. V. anguillarum strains require an active VanT to produce high levels of an L-tyrosine-induced brown color via HPPD, suggesting that VanT controls pigment production. Vps73 and Sat are related to Vibrio cholerae proteins encoded within a DNA locus required for biofilm formation. A V. anguillarum Delta vanT mutant and a mutant carrying a polar mutation in the sat-vps73 DNA locus were shown to produce defective biofilms. Hence, a new member of the V. harveyi LuxR transcriptional activator family has been characterized in V. anguillarum that positively regulates serine, metalloprotease, pigment, and biofilm production.

  8. Rapid genetic restoration of a keystone species exhibiting delayed demographic response

    Science.gov (United States)

    Genetic founder effects are often expected when animals colonize restored habitat in fragmented landscapes, but empirical data on genetic responses to restoration are limited. We examined the genetic response of banner-tailed kangaroo rats (Dipodomys spectabilis) to landscape-scale grassland restor...

  9. Integration of population genetic structure and plant response to climate change: sustaining genetic resources through evaluation of projected threats

    Science.gov (United States)

    Bryce A. Richardson; Marcus V. Warwell; Mee-Sook Kim; Ned B. Klopfenstein; Geral I. McDonald

    2010-01-01

    To assess threats or predict responses to disturbances, or both, it is essential to recognize and characterize the population structures of forest species in relation to changing environments. Appropriate management of these genetic resources in the future will require (1) understanding the existing genetic diversity/variation and population structure of forest trees...

  10. Genetic analysis of the SOS response of Escherichia coli

    International Nuclear Information System (INIS)

    Mount, D.W.; Wertman, K.F.; Ennis, D.G.; Peterson, K.R.; Fisher, B.L.; Lyons, G.

    1983-01-01

    In the SOS response, a large number of E. coli genes having different functions are derepressed when the cellular DNA is damaged. This derepression occurs through inactivation of a repressor, the product of the lexA gene, by a protease activity of the recA gene product. The protease is thought to be activated in response to changes in DNA metabolism which follow the damage. After the SOS functions have acted, the protease activity declines and repression is again established. Because the DNA sequence of both lexA and recA have been determined, it is possible to induce many mutations in their regulatory and structural regions in order to analyze further the control of the SOS response. We are studying the effects of mutations in both the lexA and recA regulatory regions, and mutations which affect the protease activity or the sensitivity of repressor to the protease. Finally, we are using genetic methods to analyze a newly identified requirement for recA protein, induced mutagenesis in cells lacking repressor. 16 references, 3 figures

  11. 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.

  12. Evaluation of Optimum Genetic Contribution Theory to Control Inbreeding While Maximizing Genetic Response

    Directory of Open Access Journals (Sweden)

    S.-H. Oh

    2012-03-01

    Full Text Available Inbreeding is the mating of relatives that produce progeny having more homozygous alleles than non-inbred animals. Inbreeding increases numbers of recessive alleles, which is often associated with decreased performance known as inbreeding depression. The magnitude of inbreeding depression depends on the level of inbreeding in the animal. Level of inbreeding is expressed by the inbreeding coefficient. One breeding goal in livestock is uniform productivity while maintaining acceptable inbreeding levels, especially keeping inbreeding less than 20%. However, in closed herds without the introduction of new genetic sources high levels of inbreeding over time are unavoidable. One method that increases selection response and minimizes inbreeding is selection of individuals by weighting estimated breeding values with average relationships among individuals. Optimum genetic contribution theory (OGC uses relationships among individuals as weighting factors. The algorithm is as follows: i Identify the individual having the best EBV; ii Calculate average relationships ( r j ¯ between selected and candidates; iii Select the individual having the best EBV adjusted for average relationships using the weighting factor k, E B V * = E B V j ( 1 - k r j ¯ . iv Repeat process until the number of individuals selected equals number required. The objective of this study was to compare simulated results based on OGC selection under different conditions over 30 generations. Individuals (n = 110 were generated for the base population with pseudo random numbers of N~ (0, 3, ten were assumed male, and the remainder female. Each male was mated to ten females, and every female was assumed to have 5 progeny resulting in 500 individuals in the following generation. Results showed the OGC algorithm effectively controlled inbreeding and maintained consistent increases in selection response. Difference in breeding values between selection with OGC algorithm and by EBV only was 8

  13. Ecological Genetics of Vernalization Response in Bromus tectorum L. (Poaceae)

    Science.gov (United States)

    MEYER, SUSAN E.; NELSON, DAVID L.; CARLSON, STEPHANIE L.

    2004-01-01

    • Background and Aims Bromus tectorum (cheatgrass or downy brome) is an exotic annual grass that is dominant over large areas of former shrubland in western North America. To flower in time for seed production in early summer, B. tectorum plants generally require vernalization at winter temperatures, either as imbibed seeds or as established seedlings. • Methods Variation in response to increasing periods of vernalization as seeds or seedlings for progeny of ten full‐sib families from each of four B. tectorum populations from contrasting habitats was studied. • Key Results As vernalization was increased from 0 to 10 weeks, the proportion of plants flowering within 20 weeks increased, weeks to initiation of flowering decreased, and seed yield per plant increased, regardless of whether plants were vernalized as seeds or seedlings. Most of the variation was accounted for by differences among populations. Plants of the warm desert population flowered promptly even without vernalization, while those of the cold desert, foothill and montane populations showed incremental changes in response variables as a function of vernalization period. Populations differed in among‐family variance, with the warm desert population generally showing the least variance and the cold desert population the most. Variation among populations and among families within populations decreased as vernalization period increased, whereas the non‐genetic component of variance showed no such pattern. • Conclusions Variation in vernalization response was found to be adaptively significant and apparently represents the result of contrasting selection regimes on a range of founder genotypes. PMID:15087300

  14. Behavioral genetics and criminal responsibility at the courtroom.

    Science.gov (United States)

    Tatarelli, Roberto; Del Casale, Antonio; Tatarelli, Caterina; Serata, Daniele; Rapinesi, Chiara; Sani, Gabriele; Kotzalidis, Georgios D; Girardi, Paolo

    2014-04-01

    Several questions arise from the recent use of behavioral genetic research data in the courtroom. Ethical issues concerning the influence of biological factors on human free will, must be considered when specific gene patterns are advocated to constrain court's judgment, especially regarding violent crimes. Aggression genetics studies are both difficult to interpret and inconsistent, hence, in the absence of a psychiatric diagnosis, genetic data are currently difficult to prioritize in the courtroom. The judge's probabilistic considerations in formulating a sentence must take into account causality, and the latter cannot be currently ensured by genetic data. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Exposing College Students to Exercise: The Training Interventions and Genetics of Exercise Response (TIGER) Study

    Science.gov (United States)

    Sailors, Mary H.; Jackson, Andrew S.; McFarlin, Brian K.; Turpin, Ian; Ellis, Kenneth J.; Foreyt, John P.; Hoelscher, Deanna M.; Bray, Molly S.

    2010-01-01

    Objective: The Training Interventions and Genetics of Exercise Response (TIGER) study is an exercise program designed to introduce sedentary college students to regular physical activity and to identify genetic factors that influence response to exercise. Participants: A multiracial/ethnic cohort (N = 1,567; 39% male), age 18 to 35 years,…

  16. Systematic review genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Sørensen, Signe Bek; Nielsen, J V; Bo Bojesen, Anders

    2016-01-01

    BACKGROUND: Personalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient. AIM......2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers...... in an explorative analysis. CONCLUSIONS: There are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms...

  17. Exploring genetic responsibility for the self, family and kin in the case of hereditary raised cholesterol.

    Science.gov (United States)

    Weiner, Kate

    2011-06-01

    This paper explores the notion of genetic responsibility, i.e. the responsibility to know and manage one's own genome for oneself and the sake of others, focusing particularly on responsibilities to family and kin. It also considers wider ideas about the emergence of new forms of biological subjectivities with which the concept of genetic responsibility is associated. The paper draws on a UK-based study concerned with lay constructions of familial hypercholesterolaemia (FH), a treatable inherited form of high cholesterol, which involved qualitative interviews with 31 people with the condition recruited through a specialist outpatient clinic. The paper is an attempt to open out discussions about the significance of genetic responsibility and biological subjectivity. I argue that in this study, FH was not associated with a notable family narrative of illness or a strongly defined specific disease community, and no clear sense emerged of obligations to kin or others derived through genetic risks or genetic connections. While responsibilities concerned with the welfare of oneself and one's existing offspring were enunciated, obligations to other potential or actual kin, e.g. to tell and encourage kin to manage their risks, were much less clearly defined. Drawing on these findings, I start to address questions about the pervasiveness of genetic responsibility and genetic identity and the contexts in which they might be significant. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Genetics Home Reference: thiamine-responsive megaloblastic anemia syndrome

    Science.gov (United States)

    ... Thiamine-responsive megaloblastic anemia syndrome Thiamine-responsive megaloblastic anemia syndrome Printable PDF Open All Close All Enable ... the expand/collapse boxes. Description Thiamine-responsive megaloblastic anemia syndrome is a rare condition characterized by hearing ...

  19. Researcher responsibilities and genetic counseling for pure-bred dog populations.

    Science.gov (United States)

    Bell, Jerold S

    2011-08-01

    Breeders of dogs have ethical responsibilities regarding the testing and management of genetic disease. Molecular genetics researchers have their own responsibilities, highlighted in this article. Laboratories offering commercial genetic testing should have proper sample identification and quality control, official test result certificates, clear explanations of test results and reasonably priced testing fees. Providing test results to a publicly-accessible genetic health registry allows breeders and the public to search for health-tested parents to reduce the risk of producing or purchasing affected offspring. Counseling on the testing and elimination of defective genes must consider the effects of genetic selection on the population. Recommendations to breed quality carriers to normal-testing dogs and replacing them with quality normal-testing offspring will help to preserve breeding lines and breed genetic diversity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Genetic erosion impedes adaptive responses to stressful environments

    NARCIS (Netherlands)

    Bijlsma, R.; Loeschcke, Volker

    Biodiversity is increasingly subjected to human-induced changes of the environment. To persist, populations continually have to adapt to these often stressful changes including pollution and climate change. Genetic erosion in small populations, owing to fragmentation of natural habitats, is expected

  1. Genetic evolution, plasticity, and bet-hedging as adaptive responses to temporally autocorrelated fluctuating selection: A quantitative genetic model.

    Science.gov (United States)

    Tufto, Jarle

    2015-08-01

    Adaptive responses to autocorrelated environmental fluctuations through evolution in mean reaction norm elevation and slope and an independent component of the phenotypic variance are analyzed using a quantitative genetic model. Analytic approximations expressing the mutual dependencies between all three response modes are derived and solved for the joint evolutionary outcome. Both genetic evolution in reaction norm elevation and plasticity are favored by slow temporal fluctuations, with plasticity, in the absence of microenvironmental variability, being the dominant evolutionary outcome for reasonable parameter values. For fast fluctuations, tracking of the optimal phenotype through genetic evolution and plasticity is limited. If residual fluctuations in the optimal phenotype are large and stabilizing selection is strong, selection then acts to increase the phenotypic variance (bet-hedging adaptive). Otherwise, canalizing selection occurs. If the phenotypic variance increases with plasticity through the effect of microenvironmental variability, this shifts the joint evolutionary balance away from plasticity in favor of genetic evolution. If microenvironmental deviations experienced by each individual at the time of development and selection are correlated, however, more plasticity evolves. The adaptive significance of evolutionary fluctuations in plasticity and the phenotypic variance, transient evolution, and the validity of the analytic approximations are investigated using simulations. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  2. Heritability of brain activity related to response inhibition: a longitudinal genetic study in adolescent twins

    Science.gov (United States)

    Anokhin, Andrey P.; Golosheykin, Simon; Grant, Julia D.; Heath, Andrew C.

    2017-01-01

    The ability to inhibit prepotent but context- or goal-inappropriate responses is essential for adaptive self-regulation of behavior. Deficits in response inhibition, a key component of impulsivity, have been implicated as a core dysfunction in a range of neuropsychiatric disorders such as ADHD and addictions. Identification of genetically transmitted variation in the neural underpinnings of response inhibition can help to elucidate etiological pathways to these disorders and establish the links between genes, brain, and behavior. However, little is known about genetic influences on the neural mechanisms of response inhibition during adolescence, a developmental period characterized by weak self-regulation of behavior. Here we investigated heritability of ERPs elicited in a Go/No-Go task in a large sample of adolescent twins assessed longitudinally at ages 12, 14, and 16. Genetic analyses showed significant heritability of inhibition-related frontal N2 and P3 components at all three ages, with 50 to 60% of inter-individual variability being attributable to genetic factors. These genetic influences included both common genetic factors active at different ages and novel genetic influences emerging during development. Finally, individual differences in the rate of developmental changes from age 12 to age 16 were significantly influenced by genetic factors. In conclusion, the present study provides the first evidence for genetic influences on neural correlates of response inhibition during adolescence and suggests that ERPs elicited in the Go/No-Go task can serve as intermediate neurophysiological phenotypes (endophenotypes) for the study of disinhibition and impulse control disorders. PMID:28300615

  3. Race, Genetic Ancestry and Response to Antidepressant Treatment for Major Depression

    Science.gov (United States)

    Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

    2013-01-01

    The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials. PMID:23827886

  4. Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli.

    Science.gov (United States)

    Gat-Viks, Irit; Chevrier, Nicolas; Wilentzik, Roni; Eisenhaure, Thomas; Raychowdhury, Raktima; Steuerman, Yael; Shalek, Alex K; Hacohen, Nir; Amit, Ido; Regev, Aviv

    2013-04-01

    Individual genetic variation affects gene responsiveness to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness quantitative trait loci or reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant responds as an activator of the antiviral response; using RNA interference, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli.

  5. Dissecting genetic architecture of startle response in Drosophila melanogaster using multi-omics information.

    Science.gov (United States)

    Xue, Angli; Wang, Hongcheng; Zhu, Jun

    2017-09-28

    Startle behavior is important for survival, and abnormal startle responses are related to several neurological diseases. Drosophila melanogaster provides a powerful system to investigate the genetic underpinnings of variation in startle behavior. Since mechanically induced, startle responses and environmental conditions can be readily quantified and precisely controlled. The 156 wild-derived fully sequenced lines of the Drosophila Genetic Reference Panel (DGRP) were used to identify SNPs and transcripts associated with variation in startle behavior. The results validated highly significant effects of 33 quantitative trait SNPs (QTSs) and 81 quantitative trait transcripts (QTTs) directly associated with phenotypic variation of startle response. We also detected QTT variation controlled by 20 QTSs (tQTSs) and 73 transcripts (tQTTs). Association mapping based on genomic and transcriptomic data enabled us to construct a complex genetic network that underlies variation in startle behavior. Based on principles of evolutionary conservation, human orthologous genes could be superimposed on this network. This study provided both genetic and biological insights into the variation of startle response behavior of Drosophila melanogaster, and highlighted the importance of genetic network to understand the genetic architecture of complex traits.

  6. HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS

    NARCIS (Netherlands)

    Roberts, Susanna; Keers, Robert; Lester, Kathryn J.; Coleman, Jonathan R. I.; Breen, Gerome; Arendt, Kristian; Blatter-Meunier, Judith; Cooper, Peter; Creswell, Cathy; Fjermestad, Krister; Havik, Odd E.; Herren, Chantal; Hogendoorn, Sanne M.; Hudson, Jennifer L.; Krause, Karen; Lyneham, Heidi J.; Morris, Talia; Nauta, Maaike; Rapee, Ronald M.; Rey, Yasmin; Schneider, Silvia; Schneider, Sophie C.; Silverman, Wendy K.; Thastum, Mikael; Thirlwall, Kerstin; Waite, Polly; Eley, Thalia C.; Wong, Chloe C. Y.

    2015-01-01

    Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive

  7. Genetic dissection of the maize (Zea mays L.) MAMP response

    Science.gov (United States)

    Microbe-associated molecular patterns (MAMPs) are highly conserved molecules commonly found in microbes which can be recognized by plant pattern recognition receptors (PRRs). Recognition triggers a suite of responses including production of reactive oxygen species (ROS) and nitric oxide (NO) and ex...

  8. Genetic variations in non-specific immune response to ...

    African Journals Online (AJOL)

    Non-specific immune response in three strains of Heterobranchus bidorsalis challenged with the bacterium Aeromonas hydrophilia was evaluated. The study was undertaken in three strains of H. bidorsalis from different ecological zones in Nigeria and the percentage cumulative mortality was lowest and significantly ...

  9. Genetic variation of response to water deficit in parental genotypes ...

    African Journals Online (AJOL)

    dgomi

    In this study, we investigated morphological and photosynthetic responses to water deficit in parental genotypes of M. ... for adaptation to water deficit in legumes is a prerequisite for any research aiming to improve legume yields. ...... tolerant genotypes in rainfed lowland rice. Field Crop. Res. 99:48-58. Rouached A, Slama I, ...

  10. Role of population genetics in guiding ecological responses to climate.

    Science.gov (United States)

    Rehfeldt, Gerald E; Leites, Laura P; Joyce, Dennis G; Weiskittel, Aaron R

    2018-02-01

    Population responses to climate were assessed using 3-7 years height growth data gathered for 266 populations growing in 12 common gardens established in the 1980s as part of five disparate studies of Pinus contorta var. latifolia. Responses are interpreted according to three concepts: the ecological optimum, the climate where a population is competitively exclusive and in which, therefore, it occurs naturally; the physiological optimum, the climate where a population grows best but is most often competitively excluded; and growth potential, the innate capacity for growth at the physiological optimum. Statistical analyses identified winter cold, measured by the square root of negative degree-days calculated from the daily minimum temperature (MINDD0 1/2 ), as the climatic effect most closely related to population growth potential; the colder the winter inhabited by a population, the lower its growth potential, a relationship presumably molded by natural selection. By splitting the data into groups based on population MINDD0 1/2 and using a function suited to skewed normal distributions, regressions were developed for predicting growth from the distance in climate space (MINDD0 1/2 ) populations had been transferred from their native location to a planting site. The regressions were skewed, showing that the ecological optimum of most populations is colder than the physiological optimum and that the discrepancy between the two increases as the ecological optimum becomes colder. Response to climate change is dependent on innate growth potential and the discrepancy between the two optima and, therefore, is population-specific, developing out of genotype-environment interactions. Response to warming in the short-term can be either positive or negative, but long term responses will be negative for all populations, with the timing of the demise dependent on the amount of skew. The results pertain to physiological modeling, species distribution models, and climate

  11. Genetic architecture of a hormonal response to gene knockdown in honey bees.

    Science.gov (United States)

    Ihle, Kate E; Rueppell, Olav; Huang, Zachary Y; Wang, Ying; Fondrk, M Kim; Page, Robert E; Amdam, Gro V

    2015-01-01

    Variation in endocrine signaling is proposed to underlie the evolution and regulation of social life histories, but the genetic architecture of endocrine signaling is still poorly understood. An excellent example of a hormonally influenced set of social traits is found in the honey bee (Apis mellifera): a dynamic and mutually suppressive relationship between juvenile hormone (JH) and the yolk precursor protein vitellogenin (Vg) regulates behavioral maturation and foraging of workers. Several other traits cosegregate with these behavioral phenotypes, comprising the pollen hoarding syndrome (PHS) one of the best-described animal behavioral syndromes. Genotype differences in responsiveness of JH to Vg are a potential mechanistic basis for the PHS. Here, we reduced Vg expression via RNA interference in progeny from a backcross between 2 selected lines of honey bees that differ in JH responsiveness to Vg reduction and measured JH response and ovary size, which represents another key aspect of the PHS. Genetic mapping based on restriction site-associated DNA tag sequencing identified suggestive quantitative trait loci (QTL) for ovary size and JH responsiveness. We confirmed genetic effects on both traits near many QTL that had been identified previously for their effect on various PHS traits. Thus, our results support a role for endocrine control of complex traits at a genetic level. Furthermore, this first example of a genetic map of a hormonal response to gene knockdown in a social insect helps to refine the genetic understanding of complex behaviors and the physiology that may underlie behavioral control in general. © The American Genetic Association. 2015.

  12. Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer.

    Science.gov (United States)

    Janjigian, Yelena Y; Sanchez-Vega, Francisco; Jonsson, Philip; Chatila, Walid K; Hechtman, Jaclyn F; Ku, Geoffrey Y; Riches, Jamie C; Tuvy, Yaelle; Kundra, Ritika; Bouvier, Nancy; Vakiani, Efsevia; Gao, Jianjiong; Heins, Zachary J; Gross, Benjamin E; Kelsen, David P; Zhang, Liying; Strong, Vivian E; Schattner, Mark; Gerdes, Hans; Coit, Daniel G; Bains, Manjit; Stadler, Zsofia K; Rusch, Valerie W; Jones, David R; Molena, Daniela; Shia, Jinru; Robson, Mark E; Capanu, Marinela; Middha, Sumit; Zehir, Ahmet; Hyman, David M; Scaltriti, Maurizio; Ladanyi, Marc; Rosen, Neal; Ilson, David H; Berger, Michael F; Tang, Laura; Taylor, Barry S; Solit, David B; Schultz, Nikolaus

    2018-01-01

    The incidence of esophagogastric cancer is rapidly rising, but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of patients with metastatic esophagogastric cancer. There was no association between homologous recombination deficiency defects and response to platinum-based chemotherapy. Patients with microsatellite instability-high tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy. The single Epstein-Barr virus-positive patient achieved a durable, complete response to immunotherapy. The level of ERBB2 amplification as determined by sequencing was predictive of trastuzumab benefit. Selection for a tumor subclone lacking ERBB2 amplification, deletion of ERBB2 exon 16, and comutations in the receptor tyrosine kinase, RAS, and PI3K pathways were associated with intrinsic and/or acquired trastuzumab resistance. Prospective genomic profiling can identify patients most likely to derive durable benefit to immunotherapy and trastuzumab and guide strategies to overcome drug resistance. Significance: Clinical application of multiplex sequencing can identify biomarkers of treatment response to contemporary systemic therapies in metastatic esophagogastric cancer. This large prospective analysis sheds light on the biological complexity and the dynamic nature of therapeutic resistance in metastatic esophagogastric cancers. Cancer Discov; 8(1); 49-58. ©2017 AACR. See related commentary by Sundar and Tan, p. 14 See related article by Pectasides et al., p. 37 This article is highlighted in the In This Issue feature, p. 1 . ©2017 American Association for Cancer Research.

  13. Genetic influences on phase synchrony of brain oscillations supporting response inhibition.

    Science.gov (United States)

    Müller, Viktor; Anokhin, Andrey P; Lindenberger, Ulman

    2017-05-01

    Phase synchronization of neuronal oscillations is a fundamental mechanism underlying cognitive processing and behavior, including context-dependent response production and inhibition. Abnormalities in neural synchrony can lead to abnormal information processing and contribute to cognitive and behavioral deficits in neuropsychiatric disorders. However, little is known about genetic and environmental contributions to individual differences in cortical oscillatory dynamics underlying response inhibition. This study examined heritability of event-related phase synchronization of brain oscillations in 302 young female twins including 94 MZ and 57 DZ pairs performing a cued Go/No-Go version of the Continuous Performance Test (CPT). We used the Phase Locking Index (PLI) to assess inter-trial phase clustering (synchrony) in several frequency bands in two time intervals after stimulus onset (0-300 and 301-600ms). Response inhibition (i.e., successful response suppression in No-Go trials) was characterized by a transient increase in phase synchronization of delta- and theta-band oscillations in the fronto-central midline region. Genetic analysis showed significant heritability of the phase locking measures related to response inhibition, with 30 to 49% of inter-individual variability being accounted for by genetic factors. This is the first study providing evidence for heritability of task-related neural synchrony. The present results suggest that PLI can serve as an indicator of genetically transmitted individual differences in neural substrates of response inhibition. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Diet enriched with mushroom Phellinus linteus extract enhances the growth, innate immune response, and disease resistance of kelp grouper, Epinephelus bruneus against vibriosis.

    Science.gov (United States)

    Harikrishnan, Ramasamy; Balasundaram, Chellam; Heo, Moon-Soo

    2011-01-01

    The effect of diet supplemented with Phellinus linteus fed for 30 days was investigated in grouper Epinephelus bruneus challenged with Vibrio anguillarum, Vibrio harveyi, Vibrio alginolyticus, and Vibrio carchariae; infected and treated fish had a significantly higher percent weight gain and feed efficiency. In groups fed with enriched diet and challenged with V. anguillarum and V. harveyi the mortality rate declined with a consequent rise in survival rate than with other pathogens. On the other hand, in groups fed with P. linteus enriched diet and challenged with V. anguillarum, V. harveyi, and V. alginolyticus the cellular and humoral immune responses, such as the alternative complement activity (ACH(50)), serum lysozyme activity, phagocytic activity (PA), phagocytic index (PI) significantly higher than in the control group. The respiratory bursts (RB), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were found significantly enhanced when the groups fed with enriched diet against V. anguillarum and V. harveyi. The results reveal that kelp grouper fed for 30 days with P. linteus enriched diet had higher cellular and humoral immune response and disease protection from vibriosis than the group fed on basal diet with the protection linked to stimulation of immune system. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Effects of Behavioral Genetic Evidence on Perceptions of Criminal Responsibility and Appropriate Punishment

    Science.gov (United States)

    Appelbaum, Paul S.; Scurich, Nicholas; Raad, Raymond

    2015-01-01

    Demonstrations of a link between genetic variants and criminal behavior have stimulated increasing use of genetic evidence to reduce perceptions of defendants’ responsibility for criminal behavior and to mitigate punishment. However, because only limited data exist regarding the impact of such evidence on decision makers and the public at large, we recruited a representative sample of the U.S. adult population (n=960) for a web-based survey. Participants were presented with descriptions of three legal cases and were asked to: determine the length of incarceration for a convicted murderer; adjudicate an insanity defense; and decide whether a defendant should receive the death penalty. A fully crossed, between-participants, factorial design was used, varying the type of evidence (none, genetic, neuroimaging, both), heinousness of the crime, and past criminal record, with sentence or verdict as the primary outcome. Also assessed were participants’ apprehension of the defendant, belief in free will, political ideology, and genetic knowledge. Across all three cases, genetic evidence had no significant effects on outcomes. Neuroimaging data showed an inconsistent effect in one of the two cases in which it was introduced. In contrast, heinousness of the offense and past criminal record were strongly related to participants’ decisions. Moreover, participants’ beliefs about the controllability of criminal behavior and political orientations were significantly associated with their choices. Our findings suggest that neither hopes that genetic evidence will modify judgments of culpability and punishment nor fears about the impact of genetic evidence on decision makers are likely to come to fruition. PMID:26240516

  16. Effects of Behavioral Genetic Evidence on Perceptions of Criminal Responsibility and Appropriate Punishment.

    Science.gov (United States)

    Appelbaum, Paul S; Scurich, Nicholas; Raad, Raymond

    2015-05-01

    Demonstrations of a link between genetic variants and criminal behavior have stimulated increasing use of genetic evidence to reduce perceptions of defendants' responsibility for criminal behavior and to mitigate punishment. However, because only limited data exist regarding the impact of such evidence on decision makers and the public at large, we recruited a representative sample of the U.S. adult population (n=960) for a web-based survey. Participants were presented with descriptions of three legal cases and were asked to: determine the length of incarceration for a convicted murderer; adjudicate an insanity defense; and decide whether a defendant should receive the death penalty. A fully crossed, between-participants, factorial design was used, varying the type of evidence (none, genetic, neuroimaging, both), heinousness of the crime, and past criminal record, with sentence or verdict as the primary outcome. Also assessed were participants' apprehension of the defendant, belief in free will, political ideology, and genetic knowledge. Across all three cases, genetic evidence had no significant effects on outcomes. Neuroimaging data showed an inconsistent effect in one of the two cases in which it was introduced. In contrast, heinousness of the offense and past criminal record were strongly related to participants' decisions. Moreover, participants' beliefs about the controllability of criminal behavior and political orientations were significantly associated with their choices. Our findings suggest that neither hopes that genetic evidence will modify judgments of culpability and punishment nor fears about the impact of genetic evidence on decision makers are likely to come to fruition.

  17. Integrating environmental and genetic effects to predict responses of tree populations to climate.

    Science.gov (United States)

    Wang, Tongli; O'Neill, Gregory A; Aitken, Sally N

    2010-01-01

    Climate is a major environmental factor affecting the phenotype of trees and is also a critical agent of natural selection that has molded among-population genetic variation. Population response functions describe the environmental effect of planting site climates on the performance of a single population, whereas transfer functions describe among-population genetic variation molded by natural selection for climate. Although these approaches are widely used to predict the responses of trees to climate change, both have limitations. We present a novel approach that integrates both genetic and environmental effects into a single "universal response function" (URF) to better predict the influence of climate on phenotypes. Using a large lodgepole pine (Pinus contorta Dougl. ex Loud.) field transplant experiment composed of 140 populations planted on 62 sites to demonstrate the methodology, we show that the URF makes full use of data from provenance trials to: (1) improve predictions of climate change impacts on phenotypes; (2) reduce the size and cost of future provenance trials without compromising predictive power; (3) more fully exploit existing, less comprehensive provenance tests; (4) quantify and compare environmental and genetic effects of climate on population performance; and (5) predict the performance of any population growing in any climate. Finally, we discuss how the last attribute allows the URF to be used as a mechanistic model to predict population and species ranges for the future and to guide assisted migration of seed for reforestation, restoration, or afforestation and genetic conservation in a changing climate.

  18. Validation study of genetic biomarkers of response to TNF inhibitors in rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Rosario Lopez-Rodriguez

    Full Text Available Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA, given their variable response to TNF inhibitors (TNFi. However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi.

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

    Science.gov (United States)

    Sankar, Pamela L; Cho, Mildred K

    2015-01-01

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

  20. Voicing the lifeworld: Parental accounts of responsibility in genetic consultations for polycystic kidney disease

    DEFF Research Database (Denmark)

    Clarke, Angus; Sarangi, Srikant; Verrier-Jones, Kate

    2011-01-01

    decision making, parents nevertheless account for their actions and decisions in an attempt to display parental responsibility. In this paper we explore the accounting practices of parents in genetic consultations, focusing on how they articulate their responsibility with regard to testing their at......When parents, who are carriers of or are affected by a genetic disorder, make decisions about the health risks faced by their children, there may be multiple factors to consider. These may include the medical benefits, the parents’ own experiences of learning about their genetic status...... suggest that (i) parents tend to foreground their practical ‘lifeworld’ considerations to justify their decisional actions; and (ii) there is considerable variation in the ways in which parents respond to information and advice offered by the professionals. The affected parent often presents...

  1. Parallel responses of species and genetic diversities of Indonesian butterflies to disturbance in tropical rainforests

    NARCIS (Netherlands)

    Fauvelot, C.Y.; Cleary, D.F.R.; Menken, S.B.J.

    2007-01-01

    Cécile Fauvelot1,2, Daniel F.R Cleary2,3, and Steph B.J Menken2. Parallel responses of species and genetic diversities of Indonesian butterflies to disturbance in tropical rainforests. 1Environmental Science, University of Bologna at Ravenna, Via S. Alberto 163, I-48100 Ravenna, Italia; 2Institute

  2. Genetics of animal temperament: aggressive behaviour at mixing is genetically associated with the response to handling in pigs.

    Science.gov (United States)

    D'Eath, R B; Roehe, R; Turner, S P; Ison, S H; Farish, M; Jack, M C; Lawrence, A B

    2009-11-01

    Aggression when pigs are mixed into new social groups has negative impacts on welfare and production. Aggressive behaviour is moderately heritable and could be reduced by genetic selection. The possible wider impacts of selection for reduced aggressiveness on handling traits and activity in the home pen were investigated using 1663 male and female pedigree pigs (898 purebred Yorkshire and 765 Yorkshire × Landrace). Aggressive behaviour was observed over 24 h after pigs were mixed at 10 weeks of age into groups balanced for unfamiliarity and weight. Aggression was highly heritable (duration of involvement in reciprocal fighting h2 = 0.47 ± 0.03, and duration of delivering one-sided aggression h2 = 0.34 ± 0.03). Three weeks after mixing, home pen inactivity (indicated by the frequency of lying) was observed over 24 h. Inactivity was weakly heritable (h2 = 0.05 ± 0.01) but showed no significant genetic association with aggression. Pigs' behaviour during handling by humans was assessed on entry to, whilst inside and on exit from a weigh crate at both mixing and end of test at 22 weeks. Pigs were generally easy to handle, moving easily into and out of the crate. Scores indicating 'very difficult to move' were rare. Handling scores at weighing were weakly heritable (h2 = 0.03 to 0.17), and moderately correlated across the two weighings (rg = 0.28 to 0.76). Aggressive behaviour at mixing was genetically associated with handling at the end of test weighing: pigs that fought and delivered one-sided aggression had handling scores indicating more active behaviour at weighing (e.g. moving quickly into the crate v. fighting rg = 0.41 ± 0.05 and v. bullying rg = 0.60 ± 0.04). Also, there was a genetic association between receiving one-side aggression at mixing and producing high-pitched vocalisations in the weigh crate (rg = 0.78 ± 0.08). Correlated behavioural responses occurring across different challenging situations (e.g. social mixing and human handling) have been

  3. Identity recognition in response to different levels of genetic relatedness in commercial soya bean

    Science.gov (United States)

    Van Acker, Rene; Rajcan, Istvan; Swanton, Clarence J.

    2017-01-01

    Identity recognition systems allow plants to tailor competitive phenotypes in response to the genetic relatedness of neighbours. There is limited evidence for the existence of recognition systems in crop species and whether they operate at a level that would allow for identification of different degrees of relatedness. Here, we test the responses of commercial soya bean cultivars to neighbours of varying genetic relatedness consisting of other commercial cultivars (intraspecific), its wild progenitor Glycine soja, and another leguminous species Phaseolus vulgaris (interspecific). We found, for the first time to our knowledge, that a commercial soya bean cultivar, OAC Wallace, showed identity recognition responses to neighbours at different levels of genetic relatedness. OAC Wallace showed no response when grown with other commercial soya bean cultivars (intra-specific neighbours), showed increased allocation to leaves compared with stems with wild soya beans (highly related wild progenitor species), and increased allocation to leaves compared with stems and roots with white beans (interspecific neighbours). Wild soya bean also responded to identity recognition but these responses involved changes in biomass allocation towards stems instead of leaves suggesting that identity recognition responses are species-specific and consistent with the ecology of the species. In conclusion, elucidating identity recognition in crops may provide further knowledge into mechanisms of crop competition and the relationship between crop density and yield. PMID:28280587

  4. Plasticity and genetic adaptation mediate amphibian and reptile responses to climate change

    Science.gov (United States)

    Urban, Mark C; Richardson, Jonathan L; Freidenfelds, Nicole A

    2014-01-01

    Phenotypic plasticity and genetic adaptation are predicted to mitigate some of the negative biotic consequences of climate change. Here, we evaluate evidence for plastic and evolutionary responses to climate variation in amphibians and reptiles via a literature review and meta-analysis. We included studies that either document phenotypic changes through time or space. Plasticity had a clear and ubiquitous role in promoting phenotypic changes in response to climate variation. For adaptive evolution, we found no direct evidence for evolution of amphibians or reptiles in response to climate change over time. However, we found many studies that documented adaptive responses to climate along spatial gradients. Plasticity provided a mixture of adaptive and maladaptive responses to climate change, highlighting that plasticity frequently, but not always, could ameliorate climate change. Based on our review, we advocate for more experiments that survey genetic changes through time in response to climate change. Overall, plastic and genetic variation in amphibians and reptiles could buffer some of the formidable threats from climate change, but large uncertainties remain owing to limited data. PMID:24454550

  5. Genetic variation in the response of the weed Ruellia nudiflora (Acanthaceae) to arbuscular mycorrhizal fungi.

    Science.gov (United States)

    Ramos-Zapata, José Alberto; Campos-Navarrete, María José; Parra-Tabla, Víctor; Abdala-Roberts, Luis; Navarro-Alberto, Jorge

    2010-04-01

    The main goal of this work was to test for plant genetic variation in the phenotypic plasticity response of the weed Ruellia nudiflora to arbuscular mycorrhizal (AM) fungi inoculation. We collected plants in the field, kept them under homogeneous conditions inside a nursery, and then collected seeds from these parent plants to generate five inbred lines (i.e., genetic families). Half of the plants of each inbred line were inoculated with AM fungi while the other half were not (controls); a fully crossed experimental design was then used to test for the effects of treatment (with or without AM fungi inoculation) and inbred line (genetic family). For each plant, we recorded the number of leaves produced and the number of days it survived during a 2-month period. Results showed a strong positive treatment effect (plastic response to AM fungi inoculation) for leaf production and survival. Moreover, in terms of survival, the treatment effect differed between genetic families (significant genetic family by treatment interaction). These findings indicate that the positive effect of AM fungi on plant survival (and potentially also growth) differs across plant genotypes and that such condition may contribute to R. nudiflora's capacity to colonize new environments.

  6. When the topic is you: genetic counselor responses to prenatal patients' requests for self-disclosure.

    Science.gov (United States)

    Balcom, Jessica R; Veach, Patricia McCarthy; Bemmels, Heather; Redlinger-Grosse, Krista; LeRoy, Bonnie S

    2013-06-01

    A limited amount of research indicates patient requests play a major role in genetic counselors' self-disclosure decisions and that disclosure and non-disclosure responses to patient requests may differentially affect genetic counseling processes. Studies further suggest patient requests may be more common in prenatal settings, particularly when counselors are pregnant. Empirical evidence is limited however, concerning the nature of patient requests. This study explored genetic counselors' experiences of prenatal patients' requests for self-disclosure. Four major research questions were: (1) What types of questions do prenatal patients ask that invite self-disclosure?; (2) Do pregnant genetic counselors have unique experiences with prenatal patient disclosure requests?; (3) How do genetic counselors typically respond to disclosure requests?; and (4) What strategies are effective and ineffective in responding to disclosure requests? One hundred seventy-six genetic counselors completed an online survey and 40 also participated in telephone interviews. Inductive analysis of 21 interviews revealed patient questions vary, although questions about counselor demographics are most common, and patients are more likely to ask pregnant counselors questions about their personal pregnancy decisions. Participants reported greater discomfort with self-disclosure requests during pregnancy, yet also disclosing more frequently during pregnancy. Counselor responses included personal self-disclosure, professional self-disclosure, redirection, and declining to disclose. Factors perceived as influencing disclosure included: topic, patient motivations, timing of request, quality of counseling relationship, patient characteristics, and ethical/legal responsibilities. Disclosure practices changed over time for most counselors. Additional findings, practice implications, and research recommendations are discussed.

  7. Testing for a genetic response to sexual selection in a wild Drosophila population.

    Science.gov (United States)

    Gosden, T P; Thomson, J R; Blows, M W; Schaul, A; Chenoweth, S F

    2016-06-01

    In accordance with the consensus that sexual selection is responsible for the rapid evolution of display traits on macroevolutionary scales, microevolutionary studies suggest sexual selection is a widespread and often strong form of directional selection in nature. However, empirical evidence for the contemporary evolution of sexually selected traits via sexual rather than natural selection remains weak. In this study, we used a novel application of quantitative genetic breeding designs to test for a genetic response to sexual selection on eight chemical display traits from a field population of the fly, Drosophila serrata. Using our quantitative genetic approach, we were able to detect a genetically based difference in means between groups of males descended from fathers who had either successfully sired offspring or were randomly collected from the same wild population for one of these display traits, the diene (Z,Z)-5,9-C27 : 2 . Our experimental results, in combination with previous laboratory studies on this system, suggest that both natural and sexual selection may be influencing the evolutionary trajectories of these traits in nature, limiting the capacity for a contemporary evolutionary response. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  8. [SOS response of DNA repair and genetic cell instability under hypoxic conditions].

    Science.gov (United States)

    Vasil'eva, S V; Strel'tsova, D A

    2011-01-01

    The SOS DNA repair pathway is induced in E. coli as a multifunctional cell response to a wide variety of signals: UV, X or gamma-irradiation, mitomycin C or nalidixic acid treatment, thymine starvation, etc. Triggering of the system can be used as a general and early sign of DNA damage. Additionally, the SOS-response is known to be an "error-prone" DNA repair pathway and one of the sources of genetic instability. Hypoxic conditions are established to be the major factor of genetic instability as well. In this paper we for the first time studied the SOS DNA repair response under hypoxic conditions induced by the well known aerobic SOS-inducers. The SOS DNA repair response was examined as a reaction of E. coli PQ37 [sfiA::lacZ] cells to UVC, NO-donating agents and 4NQO. Here we provide evidence that those agents were able to induce the SOS DNA repair response in E. coli at anaerobic growth conditions. The process does not depend on the transcriptional activity of the universal protein of E. col anaerobic growth Fnr [4Fe-4S]2+ or can not be referred to as an indicator of genetic instability in hypoxic conditions.

  9. The effects of genetic polymorphism on treatment response of recombinant human growth hormone.

    Science.gov (United States)

    Chen, Shi; You, Hanxiao; Pan, Hui; Zhu, Huijuan; Yang, Hongbo; Gong, Fengying; Wang, Linjie; Jiang, Yu; Yan, Chengsheng

    2017-12-06

    Recombinant human growth hormone (rhGH) has been widely used in clinical treatment of growth hormone deficiency (GHD) or non GHD since 1985 and technology have achieved a great development in different long-acting formulations. Although the mathematical models for predicting the growth hormone response could help clinicians get to an individual personalized growth dose, many patients just can't reach the target height and the growth hormone responses differed.Genetic polymorphisms may play a role in the varies of individual responses in this treatment process.This article gives an overview of the genetic polymorphisms research of growth hormone in recent years, in order to give some potential suggestion and guide for the dose titration during treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Plant responses to UV and blue light: biochemical and genetic approaches

    International Nuclear Information System (INIS)

    Jenkins, G.I.; Christie, J.M.; Fuglevand, G.; Long, J.C.; Jackson, J.A.

    1995-01-01

    UV and blue light control many aspects of plant growth and development. It is evident that several different photoreceptors mediate responses to UV and blue light, and there are reports of the functional and biochemical characterisation of a putative photoreceptor for phototropism and of the functional and molecular characterisation of the CRY1 photoreceptor, encoded by the Arabidopsis HY4 gene. The CRY1 photoreceptor mediates extension growth and gene expression responses to UV-A/blue light presumably through different or branching signal transduction pathways. Progress has been made in cell physiological and biochemical studies of UV/blue light signal transduction, but much remains to be done to relate candidate UV/blue signal transduction events to particular photoreceptors and responses. The application of a genetic approach in Arabidopsis has been responsible for many advances in understanding UV/blue responses, but further UV-B, UV-A and blue light response mutants need to be isolated. (author)

  11. Genetics

    International Nuclear Information System (INIS)

    Hubitschek, H.E.

    1975-01-01

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

  12. Genetic Influences on Physiological and Subjective Responses to an Aerobic Exercise Session among Sedentary Adults

    International Nuclear Information System (INIS)

    Karoly, H. C.; Stevens, C.; Harlaar, N.; Hutchison, K. E.; Bryan, A. D.; Magnan, R. E.

    2012-01-01

    To determine whether genetic variants suggested by the literature to be associated with physiology and fitness phenotypes predicted differential physiological and subjective responses to a bout of aerobic exercise among inactive but otherwise healthy adults. Method. Participants completed a 30-minute submaximal aerobic exercise session. Measures of physiological and subjective responding were taken before, during, and after exercise. 14 single nucleotide polymorphisms (SNPs) that have been previously associated with various exercise phenotypes were tested for associations with physiological and subjective response to exercise phenotypes. Results. We found that two SNPs in the FTO gene (rs8044769 and rs3751812) were related to positive affect change during exercise. Two SNPs in the CREB1 gene (rs2253206 and 2360969) were related to change in temperature during exercise and with maximal oxygen capacity (VO 2 max). The SLIT2 SNP rs1379659 and the FAM5C SNP rs1935881 were associated with norepinephrine change during exercise. Finally, the OPRM1 SNP rs1799971 was related to changes in norepinephrine, lactate, and rate of perceived exertion (RPE) during exercise. Conclusion. Genetic factors influence both physiological and subjective responses to exercise. A better understanding of genetic factors underlying physiological and subjective responses to aerobic exercise has implications for development and potential tailoring of exercise interventions.

  13. Genetic polymorphism and immune response to tuberculosis in indigenous populations: a brief review

    Directory of Open Access Journals (Sweden)

    Renata Maronna Praça Longhi

    Full Text Available We systematically reviewed studies of the immune response to tuberculosis and the genetic polymorphisms associated with Th1-or Th2-mediated cytokine expression in indigenous populations. A bibliographic search was performed on the Medline and ISI databases and included studies published between January 1980 and October 2011. The search terms were tuberculosis, American Indians, Amerindian, indigenous, Indians, native people, aboriginal, immun*, host immune, immune response, cytokine*, polymorphism*, and gene. Regardless of their design, studies that evaluated immunoglobulin, cytokine levels and genetic polymorphisms that altered cytokine expression were included. Thirteen studies met the inclusion criteria. The majority of studies were performed in Latin America, and five investigated the Warao ethnic group of Venezuela. Most of the investigations indirectly evaluated the immune response. Higher anergy to the tuberculin skin test, higher IgG4 and IgM levels, higher IL-5 production and lower TNF-a, IL-12p40 and IFN-I production were found in the indigenous populations. The studies also reported a predominantly Th2-type response in these populations and a possibly higher susceptibility to tuberculosis. A better understanding of the relevant genetic polymorphisms and their role in immune regulation would help to clarify the immunogenetic mechanisms of TB infection in these populations. This information would be useful for identifying new treatments and preventing infection and progression to active disease.

  14. Genetics and genomics of susceptibility and immune response to necrotic enteritis in chicken: a review.

    Science.gov (United States)

    Zahoor, Imran; Ghayas, Abdul; Basheer, Atia

    2018-02-01

    Global poultry production is facing many challenges and is currently under pressure due to the presence of several diseases like Necrotic Enteritis (NE). It is estimated that NE-caused global economic losses has increased from 2 billion to 6 billion US$ in 2015 because it is not easy to diagnose and control disease at the earlier stage of occurrence. Additionally, ban on the in-feed antibiotics and some other genetic and non-genetic predisposing factors affect the occurrence of the disease. Though the incidence of the disease can be reduced by minimizing the predisposing factors and through immunization of birds but there is no single remedy to control the disease. Therefore, we suggest that there is need to find out the genetic variants that could help to select the birds resistant to NE. The current review details the pertinent features about the genetic and genomics of susceptibility and immune response of birds to Necrotic Enteritis. We report here the list of candidate gene reported for their involvement with the susceptibility and/or resistance to the disease. However, most of these genes are involved in immune-related functions. For better understanding of the role of Clostridium perfringens and its toxins in the pathogenesis of disease there is need to unveil the association between any specific genetic variation and clinical status of NE. However, the presence of substantial genetic variations among different breeds/strains of chicken shows that it is possible to develop broiler strain with genetic resistant against NE. It would help in the cost-effective and sustainable production of safe broiler meat.

  15. 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...

  16. Genetic variation in the cellular response of Daphnia magna (Crustacea: Cladocera) to its bacterial parasite.

    Science.gov (United States)

    Auld, Stuart K J R; Scholefield, Jennifer A; Little, Tom J

    2010-11-07

    Linking measures of immune function with infection, and ultimately, host and parasite fitness is a major goal in the field of ecological immunology. In this study, we tested for the presence and timing of a cellular immune response in the crustacean Daphnia magna following exposure to its sterilizing endoparasite Pasteuria ramosa. We found that D. magna possesses two cell types circulating in the haemolymph: a spherical one, which we call a granulocyte and an irregular-shaped amoeboid cell first described by Metchnikoff over 125 years ago. Daphnia magna mounts a strong cellular response (of the amoeboid cells) just a few hours after parasite exposure. We further tested for, and found, considerable genetic variation for the magnitude of this cellular response. These data fostered a heuristic model of resistance in this naturally coevolving host-parasite interaction. Specifically, the strongest cellular responses were found in the most susceptible hosts, indicating resistance is not always borne from a response that destroys invading parasites, but rather stems from mechanisms that prevent their initial entry. Thus, D. magna may have a two-stage defence--a genetically determined barrier to parasite establishment and a cellular response once establishment has begun.

  17. Genetic and pharmacokinetic determinants of response to transdermal nicotine in white, black, and Asian nonsmokers.

    Science.gov (United States)

    Dempsey, D A; St Helen, G; Jacob, P; Tyndale, R F; Benowitz, N L

    2013-12-01

    The aim of the study was to examine genetic, pharmacokinetic, and demographic factors that influence sensitivity to nicotine in never-smokers. Sixty never-smokers, balanced for gender and race (white, black, and Asian), wore 7-mg nicotine skin patches for up to 8 h. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, encoding the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in nine subjects and was strongly associated with rate of increase and peak concentrations of plasma nicotine. Toxicity and subjective and cardiovascular effects of nicotine were associated with the presence of reduced-function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. This study has implications for understanding individual differences in responses to nicotine medications, particularly when they are used for treating medical conditions in nonsmokers, and possibly in vulnerability to developing nicotine dependence.

  18. Probing genetic control of swine responses to PRRSV infection: current progress of the PRRS host genetics consortium

    Directory of Open Access Journals (Sweden)

    Lunney Joan K

    2011-06-01

    Full Text Available Abstract Background Understanding the role of host genetics in resistance to porcine reproductive and respiratory syndrome virus (PRRSV infection, and the effects of PRRS on pig health and related growth, are goals of the PRRS Host Genetics Consortium (PHGC. Methods The project uses a nursery pig model to assess pig resistance/susceptibility to primary PRRSV infection. To date, 6 groups of 200 crossbred pigs from high health farms were donated by commercial sources. After acclimation, the pigs were infected with PRRSV in a biosecure facility and followed for 42 days post infection (dpi. Blood samples were collected at 0, 4, 7, 10, 14, 21, 28, 35 and 42 dpi for serum and whole blood RNA gene expression analyses; weekly weights were recorded for growth traits. All data have been entered into the PHGC relational database. Genomic DNAs from all PHGC1-6 pigs were prepared and genotyped with the Porcine SNP60 SNPchip. Results Results have affirmed that all challenged pigs become PRRSV infected with peak viremia being observed between 4-21 dpi. Multivariate statistical analyses of viral load and weight data have identified PHGC pigs in different virus/weight categories. Sera are now being compared for factors involved in recovery from infection, including speed of response and levels of immune cytokines. Genome-wide association studies (GWAS are underway to identify genes and chromosomal locations that identify PRRS resistant/susceptible pigs and pigs able to maintain growth while infected with PRRSV. Conclusions Overall, the PHGC project will enable researchers to discover and verify important genotypes and phenotypes that predict resistance/susceptibility to PRRSV infection. The availability of PHGC samples provides a unique opportunity to continue to develop deeper phenotypes on every PRRSV infected pig.

  19. Preliminary evidence for genetic overlap between body mass index and striatal reward response.

    Science.gov (United States)

    Lancaster, T M; Ihssen, I; Brindley, L M; Linden, D E

    2018-01-10

    The reward-processing network is implicated in the aetiology of obesity. Several lines of evidence suggest obesity-linked genetic risk loci (such as DRD2 and FTO) may influence individual variation in body mass index (BMI) through neuropsychological processes reflected in alterations in activation of the striatum during reward processing. However, no study has tested the broader hypotheses that (a) the relationship between BMI and reward-related brain activation (measured through the blood oxygenation-dependent (BOLD) signal) may be observed in a large population study and (b) the overall genetic architecture of these phenotypes overlap, an assumption critical for the progression of imaging genetic studies in obesity research. Using data from the Human Connectome Project (N = 1055 healthy, young individuals: average BMI = 26.4), we first establish a phenotypic relationship between BMI and ventral striatal (VS) BOLD during the processing of rewarding (monetary) stimuli (β = 0.44, P = 0.013), accounting for potential confounds. BMI and VS BOLD were both significantly influenced by additive genetic factors (H2r = 0.57; 0.12, respectively). Further decomposition of this variance suggested that the relationship was driven by shared genetic (ρ g  = 0.47, P = 0.011), but not environmental (ρ E  = -0.07, P = 0.29) factors. To validate the assumption of genetic pleiotropy between BMI and VS BOLD, we further show that polygenic risk for higher BMI is also associated with increased VS BOLD response to appetitive stimuli (calorically high food images), in an independent sample (N = 81; P FWE-ROI  < 0.005). Together, these observations suggest that the genetic factors link risk to obesity to alterations within key nodes of the brain's reward circuity. These observations provide a basis for future work exploring the mechanistic role of genetic loci that confer risk for obesity using the imaging genetics approach.

  20. Genetic Components of Root Architecture Remodeling in Response to Salt Stress

    KAUST Repository

    Julkowska, Magdalena; Koevoets, Iko Tamar; Mol, Selena; Hoefsloot, Huub CJ; Feron, Richard; Tester, Mark A.; Keurentjes, Joost J.B.; Korte, Arthur; Haring, Michel A; de Boer, Gert-Jan; Testerink, Christa

    2017-01-01

    Salinity of the soil is highly detrimental to plant growth. Plants respond by a redistribution of root mass between main and lateral roots, yet the genetic machinery underlying this process is still largely unknown. Here, we describe the natural variation among 347 Arabidopsis thaliana accessions in root system architecture (RSA) and identify the traits with highest natural variation in their response to salt. Salt-induced changes in RSA were associated with 100 genetic loci using genome-wide association studies (GWAS). Two candidate loci associated with lateral root development were validated and further investigated. Changes in CYP79B2 expression in salt stress positively correlated with lateral root development in accessions, and cyp79b2 cyp79b3 double mutants developed fewer and shorter lateral roots under salt stress, but not in control conditions. By contrast, high HKT1 expression in the root repressed lateral root development, which could be partially rescued by addition of potassium. The collected data and Multi-Variate analysis of multiple RSA traits, available through the Salt_NV_Root App, capture root responses to salinity. Together, our results provide a better understanding of effective RSA remodeling responses, and the genetic components involved, for plant performance in stress conditions.

  1. Genetic Components of Root Architecture Remodeling in Response to Salt Stress

    KAUST Repository

    Julkowska, Magdalena

    2017-11-07

    Salinity of the soil is highly detrimental to plant growth. Plants respond by a redistribution of root mass between main and lateral roots, yet the genetic machinery underlying this process is still largely unknown. Here, we describe the natural variation among 347 Arabidopsis thaliana accessions in root system architecture (RSA) and identify the traits with highest natural variation in their response to salt. Salt-induced changes in RSA were associated with 100 genetic loci using genome-wide association studies (GWAS). Two candidate loci associated with lateral root development were validated and further investigated. Changes in CYP79B2 expression in salt stress positively correlated with lateral root development in accessions, and cyp79b2 cyp79b3 double mutants developed fewer and shorter lateral roots under salt stress, but not in control conditions. By contrast, high HKT1 expression in the root repressed lateral root development, which could be partially rescued by addition of potassium. The collected data and Multi-Variate analysis of multiple RSA traits, available through the Salt_NV_Root App, capture root responses to salinity. Together, our results provide a better understanding of effective RSA remodeling responses, and the genetic components involved, for plant performance in stress conditions.

  2. Nutrigenetics: links between genetic background and response to Mediterranean-type diets.

    Science.gov (United States)

    Lairon, Denis; Defoort, Catherine; Martin, Jean-Charles; Amiot-Carlin, Marie-Jo; Gastaldi, Marguerite; Planells, Richard

    2009-09-01

    It has been substantiated that the onset of most major diseases (CVD, diabetes, obesity, cancers, etc.) is modulated by the interaction between genetic traits (susceptibility) and environmental factors, especially diet. We aim to report more specific observations relating the effects of Mediterranean-type diets on cardiovascular risk factors and the genetic background of subjects. In the first part, general concepts about nutrigenetics are briefly presented. Human genome has, overall, only marginally changed since its origin but it is thought that minor changes (polymorphisms) of common genes that occurred during evolution are now widespread in human populations, and can alter metabolic pathways and response to diets. In the second part, we report the data obtained during the Medi-RIVAGE intervention study performed in the South-East of France. Data obtained in 169 subjects at moderate cardiovascular risk after a 3-month dietary intervention indicate that some of the twenty-three single nucleotide polymorphisms (SNP) studied exhibit interactions with diets regarding changes of particular parameters after 3-month regimens. Detailed examples are presented, such as interactions between SNP in genes coding for microsomial transfer protein (MTTP) or intestinal fatty acid binding protein (FABP2) and triglyceride, LDL-cholesterol or Framigham score lowering in responses to Mediterranean-type diets. The data provided add further evidence of the interaction between particular SNP and metabolic responses to diets. Finally, improvement in dietary recommendations by taking into account known genetic variability has been discussed.

  3. Genetic analysis of human traits in vitro: drug response and gene expression in lymphoblastoid cell lines.

    Directory of Open Access Journals (Sweden)

    Edwin Choy

    2008-11-01

    Full Text Available Lymphoblastoid cell lines (LCLs, originally collected as renewable sources of DNA, are now being used as a model system to study genotype-phenotype relationships in human cells, including searches for QTLs influencing levels of individual mRNAs and responses to drugs and radiation. In the course of attempting to map genes for drug response using 269 LCLs from the International HapMap Project, we evaluated the extent to which biological noise and non-genetic confounders contribute to trait variability in LCLs. While drug responses could be technically well measured on a given day, we observed significant day-to-day variability and substantial correlation to non-genetic confounders, such as baseline growth rates and metabolic state in culture. After correcting for these confounders, we were unable to detect any QTLs with genome-wide significance for drug response. A much higher proportion of variance in mRNA levels may be attributed to non-genetic factors (intra-individual variance--i.e., biological noise, levels of the EBV virus used to transform the cells, ATP levels than to detectable eQTLs. Finally, in an attempt to improve power, we focused analysis on those genes that had both detectable eQTLs and correlation to drug response; we were unable to detect evidence that eQTL SNPs are convincingly associated with drug response in the model. While LCLs are a promising model for pharmacogenetic experiments, biological noise and in vitro artifacts may reduce power and have the potential to create spurious association due to confounding.

  4. Genetic dissection of acute ethanol responsive gene networks in prefrontal cortex: functional and mechanistic implications.

    Directory of Open Access Journals (Sweden)

    Aaron R Wolen

    Full Text Available Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed the first systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens, and ventral midbrain across a highly diverse family of 27 isogenic mouse strains (BXD panel before and after treatment with ethanol.Acute ethanol altered the expression of ~2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted with a powerful graph theoretical method that efficiently summarized ethanol's effects. These networks correlated with acute behavioral responses to ethanol and other drugs of abuse. As predicted, networks were heavily populated by genes controlling synaptic transmission and neuroplasticity. Several of the most densely interconnected network hubs, including Kcnma1 and Gsk3β, are known to influence behavioral or physiological responses to ethanol, validating our overall approach. Other major hub genes like Grm3, Pten and Nrg3 represent novel targets of ethanol effects. Networks were under strong genetic control by variants that we mapped to a small number of chromosomal loci. Using a novel combination of genetic, bioinformatic and network-based approaches, we identified high priority cis-regulatory candidate genes, including Scn1b, Gria1, Sncb and Nell2.The ethanol-responsive gene networks identified here represent a previously uncharacterized intermediate phenotype between DNA variation and ethanol sensitivity in mice. Networks involved in synaptic transmission were strongly regulated by ethanol and could contribute to behavioral plasticity seen with chronic ethanol. Our novel finding that hub genes and a small number of loci exert major influence over the ethanol

  5. Artificial Selection Response due to Polygenic Adaptation from a Multilocus, Multiallelic Genetic Architecture.

    Science.gov (United States)

    Zan, Yanjun; Sheng, Zheya; Lillie, Mette; Rönnegård, Lars; Honaker, Christa F; Siegel, Paul B; Carlborg, Örjan

    2017-10-01

    The ability of a population to adapt to changes in their living conditions, whether in nature or captivity, often depends on polymorphisms in multiple genes across the genome. In-depth studies of such polygenic adaptations are difficult in natural populations, but can be approached using the resources provided by artificial selection experiments. Here, we dissect the genetic mechanisms involved in long-term selection responses of the Virginia chicken lines, populations that after 40 generations of divergent selection for 56-day body weight display a 9-fold difference in the selected trait. In the F15 generation of an intercross between the divergent lines, 20 loci explained >60% of the additive genetic variance for the selected trait. We focused particularly on fine-mapping seven major QTL that replicated in this population and found that only two fine-mapped to single, bi-allelic loci; the other five contained linked loci, multiple alleles or were epistatic. This detailed dissection of the polygenic adaptations in the Virginia lines provides a deeper understanding of the range of different genome-wide mechanisms that have been involved in these long-term selection responses. The results illustrate that the genetic architecture of a highly polygenic trait can involve a broad range of genetic mechanisms, and that this can be the case even in a small population bred from founders with limited genetic diversity. © 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.

  6. Genetic Dissection of Anopheles gambiae Gut Epithelial Responses to Serratia marcescens

    Science.gov (United States)

    Stathopoulos, Stavros; Neafsey, Daniel E.; Lawniczak, Mara K. N.; Muskavitch, Marc A. T.; Christophides, George K.

    2014-01-01

    Genetic variation in the mosquito Anopheles gambiae profoundly influences its ability to transmit malaria. Mosquito gut bacteria are shown to influence the outcome of infections with Plasmodium parasites and are also thought to exert a strong drive on genetic variation through natural selection; however, a link between antibacterial effects and genetic variation is yet to emerge. Here, we combined SNP genotyping and expression profiling with phenotypic analyses of candidate genes by RNAi-mediated silencing and 454 pyrosequencing to investigate this intricate biological system. We identified 138 An. gambiae genes to be genetically associated with the outcome of Serratia marcescens infection, including the peptidoglycan recognition receptor PGRPLC that triggers activation of the antibacterial IMD/REL2 pathway and the epidermal growth factor receptor EGFR. Silencing of three genes encoding type III fibronectin domain proteins (FN3Ds) increased the Serratia load and altered the gut microbiota composition in favor of Enterobacteriaceae. These data suggest that natural genetic variation in immune-related genes can shape the bacterial population structure of the mosquito gut with high specificity. Importantly, FN3D2 encodes a homolog of the hypervariable pattern recognition receptor Dscam, suggesting that pathogen-specific recognition may involve a broader family of immune factors. Additionally, we showed that silencing the gene encoding the gustatory receptor Gr9 that is also associated with the Serratia infection phenotype drastically increased Serratia levels. The Gr9 antibacterial activity appears to be related to mosquito feeding behavior and to mostly rely on changes of neuropeptide F expression, together suggesting a behavioral immune response following Serratia infection. Our findings reveal that the mosquito response to oral Serratia infection comprises both an epithelial and a behavioral immune component. PMID:24603764

  7. System Response Analysis and Model Order Reduction, Using Conventional Method, Bond Graph Technique and Genetic Programming

    Directory of Open Access Journals (Sweden)

    Lubna Moin

    2009-04-01

    Full Text Available This research paper basically explores and compares the different modeling and analysis techniques and than it also explores the model order reduction approach and significance. The traditional modeling and simulation techniques for dynamic systems are generally adequate for single-domain systems only, but the Bond Graph technique provides new strategies for reliable solutions of multi-domain system. They are also used for analyzing linear and non linear dynamic production system, artificial intelligence, image processing, robotics and industrial automation. This paper describes a unique technique of generating the Genetic design from the tree structured transfer function obtained from Bond Graph. This research work combines bond graphs for model representation with Genetic programming for exploring different ideas on design space tree structured transfer function result from replacing typical bond graph element with their impedance equivalent specifying impedance lows for Bond Graph multiport. This tree structured form thus obtained from Bond Graph is applied for generating the Genetic Tree. Application studies will identify key issues and importance for advancing this approach towards becoming on effective and efficient design tool for synthesizing design for Electrical system. In the first phase, the system is modeled using Bond Graph technique. Its system response and transfer function with conventional and Bond Graph method is analyzed and then a approach towards model order reduction is observed. The suggested algorithm and other known modern model order reduction techniques are applied to a 11th order high pass filter [1], with different approach. The model order reduction technique developed in this paper has least reduction errors and secondly the final model retains structural information. The system response and the stability analysis of the system transfer function taken by conventional and by Bond Graph method is compared and

  8. Shared genetic influences among childhood shyness, social competences, and cortical responses to emotions.

    Science.gov (United States)

    Battaglia, Marco; Michelini, Giorgia; Pezzica, Elettra; Ogliari, Anna; Fagnani, Corrado; Stazi, Maria-Antonietta; Bertoletti, Eleonora; Scaini, Simona

    2017-08-01

    Visual event-related potentials (ERPs) evoked by facial expressions are useful to map socioemotional responses among shy children and to predict transition into social phobia. We investigated the sources of covariation among childhood shyness, social competences, and ERPs to other children's happy, neutral, and angry expressions. Electrophysiological and twin analyses examined the phenotypic and etiological association among an index of childhood shyness, an index of social competences, and ERP responses to facial expressions in 200 twins (mean age=9.23years). Multivariate twin analyses showed that the covariation among shyness, social competences, and a composite of a frontal late negative component occurring around 200-400ms in response to happy, neutral, and angry expressions could be entirely explained by shared genetic factors. A coherent causal structure links childhood shyness, social competences, and the cortical responses to facial emotions. A common genetic substrate can explain the interrelatedness of individual differences for childhood shyness, social competences, and some associated electrophysiological responses to socioemotional signals. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Genetic variation in the endocannabinoid system and response to Cognitive Behavior Therapy for child anxiety disorders

    Science.gov (United States)

    Coleman, Jonathan R. I.; Roberts, Susanna; Keers, Robert; Breen, Gerome; Bögels, Susan; Creswell, Cathy; Hudson, Jennifer L.; McKinnon, Anna; Nauta, Maaike; Rapee, Ronald M.; Schneider, Silvia; Silverman, Wendy K.; Thastum, Mikael; Waite, Polly; Wergeland, Gro Janne H.; Eley, Thalia C.

    2016-01-01

    Extinction learning is an important mechanism in the successful psychological treatment of anxiety. Individual differences in response and relapse following Cognitive Behavior Therapy may in part be explained by variability in the ease with which fears are extinguished or the vulnerability of these fears to re‐emerge. Given the role of the endocannabinoid system in fear extinction, this study investigates whether genetic variation in the endocannabinoid system explains individual differences in response to CBT. Children (N = 1,309) with a primary anxiety disorder diagnosis were recruited. We investigated the relationship between variation in the CNR1, CNR2, and FAAH genes and change in primary anxiety disorder severity between pre‐ and post‐treatment and during the follow‐up period in the full sample and a subset with fear‐based anxiety disorder diagnoses. Change in symptom severity during active treatment was nominally associated (P < 0.05) with two SNPs. During the follow‐up period, five SNPs were nominally associated with a poorer treatment response (rs806365 [CNR1]; rs2501431 [CNR2]; rs2070956 [CNR2]; rs7769940 [CNR1]; rs2209172 [FAAH]) and one with a more favorable response (rs6928813 [CNR1]). Within the fear‐based subset, the effect of rs806365 survived multiple testing corrections (P < 0.0016). We found very limited evidence for an association between variants in endocannabinoid system genes and treatment response once multiple testing corrections were applied. Larger, more homogenous cohorts are needed to allow the identification of variants of small but statistically significant effect and to estimate effect sizes for these variants with greater precision in order to determine their potential clinical utility. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID:27346075

  10. Good and bad protons: genetic aspects of acidity stress responses in plants.

    Science.gov (United States)

    Shavrukov, Yuri; Hirai, Yoshihiko

    2016-01-01

    Physiological aspects of acidity stress in plants (synonymous with H(+) rhizotoxicity or low-pH stress) have long been a focus of research, in particular with respect to acidic soils where aluminium and H(+) rhizotoxicities often co-occur. However, toxic H(+) and Al(3+) elicit different response mechanisms in plants, and it is important to consider their effects separately. The primary aim of this review was to provide the current state of knowledge regarding the genetics of the specific reactions to low-pH stress in growing plants. A comparison of the results gleaned from quantitative trait loci analysis and global transcriptome profiling of plants in response to high proton concentrations revealed a two-stage genetic response: (i) in the short-term, proton pump H(+)-ATPases present the first barrier in root cells, allocating an excess of H(+) into either the apoplast or vacuole; the ensuing defence signaling system involves auxin, salicylic acid, and methyl jasmonate, which subsequently initiate expression of STOP and DREB transcription factors as well as chaperone ROF; (2) the long-term response includes other genes, such as alternative oxidase and type II NAD(P)H dehydrogenase, which act to detoxify dangerous reactive oxygen species in mitochondria, and help plants better manage the stress. A range of transporter genes including those for nitrate (NTR1), malate (ALMT1), and heavy metals are often up-regulated by H(+) rhizotoxicity. Expansins, cell-wall-related genes, the γ-aminobutyric acid shunt and biochemical pH-stat genes also reflect changes in cell metabolism and biochemistry in acidic conditions. However, the genetics underlying the acidity stress response of plants is complicated and only fragmentally understood. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  11. Drug-induced and genetic alterations in stress-responsive systems: Implications for specific addictive diseases.

    Science.gov (United States)

    Zhou, Yan; Proudnikov, Dmitri; Yuferov, Vadim; Kreek, Mary Jeanne

    2010-02-16

    From the earliest work in our laboratory, we hypothesized, and with studies conducted in both clinical research and animal models, we have shown that drugs of abuse, administered or self-administered, on a chronic basis, profoundly alter stress-responsive systems. Alterations of expression of specific genes involved in stress responsivity, with increases or decreases in mRNA levels, receptor, and neuropeptide levels, and resultant changes in hormone levels, have been documented to occur after chronic intermittent exposure to heroin, morphine, other opiates, cocaine, other stimulants, and alcohol in animal models and in human molecular genetics. The best studied of the stress-responsive systems in humans and mammalian species in general is undoubtedly the HPA axis. In addition, there are stress-responsive systems in other parts in the brain itself, and some of these include components of the HPA axis, such as CRF and CRF receptors, along with POMC gene and gene products. Several other stress-responsive systems are known to influence the HPA axis, such as the vasopressin-vasopressin receptor system. Orexin-hypocretin, acting at its receptors, may effect changes which suggest that it should be properly categorized as a stress-responsive system. However, less is known about the interactions and connectivity of some of these different neuropeptide and receptor systems, and in particular, about the possible connectivity of fast-acting (e.g., glutamate and GABA) and slow-acting (including dopamine, serotonin, and norepinephrine) neurotransmitters with each of these stress-responsive components and the resultant impact, especially in the setting of chronic exposure to drugs of abuse. Several of these stress-responsive systems and components, primarily based on our laboratory-based and human molecular genetics research of addictive diseases, will be briefly discussed in this review. Copyright 2009 Elsevier B.V. All rights reserved.

  12. Genetic architecture of wild soybean (Glycine soja) response to soybean cyst nematode (Heterodera glycines).

    Science.gov (United States)

    Zhang, Hengyou; Song, Qijian; Griffin, Joshua D; Song, Bao-Hua

    2017-12-01

    The soybean cyst nematode (SCN) is one of the most destructive pathogens of soybean plants worldwide. Host-plant resistance is an environmentally friendly method to mitigate SCN damage. To date, the resistant soybean cultivars harbor limited genetic variation, and some are losing resistance. Thus, a better understanding of the genetic mechanisms of the SCN resistance, as well as developing diverse resistant soybean cultivars, is urgently needed. In this study, a genome-wide association study (GWAS) was conducted using 1032 wild soybean (Glycine soja) accessions with over 42,000 single-nucleotide polymorphisms (SNPs) to understand the genetic architecture of G. soja resistance to SCN race 1. Ten SNPs were significantly associated with the response to race 1. Three SNPs on chromosome 18 were localized within the previously identified quantitative trait loci (QTLs), and two of which were localized within a strong linkage disequilibrium block encompassing a nucleotide-binding (NB)-ARC disease resistance gene (Glyma.18G102600). Genes encoding methyltransferases, the calcium-dependent signaling protein, the leucine-rich repeat kinase family protein, and the NB-ARC disease resistance protein, were identified as promising candidate genes. The identified SNPs and candidate genes can not only shed light on the molecular mechanisms underlying SCN resistance, but also can facilitate soybean improvement employing wild genetic resources.

  13. Genetic predispositions and parental bonding interact to shape adults’ physiological responses to social distress

    Science.gov (United States)

    Esposito, Gianluca; Truzzi, Anna; Setoh, Peipei; Putnick, Diane L.; Shinohara, Kazuyuki; Bornstein, Marc H.

    2018-01-01

    Parental bonding and oxytocin receptor (OXTR) gene genotype each influences social abilities in adulthood. Here, we hypothesized an interaction between the two – environmental experience (parental bonding history) and genetic factors (OXTR gene genotype) – in shaping adults’ social sensitivity (physiological response to distress). We assessed heart rate and peripheral temperature (tip of the nose) in 42 male adults during presentation of distress vocalizations (distress cries belonging to female human infants and adults as well as bonobo). The two physiological responses index, respectively, state of arousal and readiness to action. Participants’ parental bonding in childhood was assessed through the self-report Parental Bonding Instrument. To assess participants’ genetic predispositions, buccal mucosa cell samples were collected, and region rs2254298 of the oxytocin receptor gene was analyzed: previous OXTR gene findings point to associations between the G allele and better sociality (protective factor) and the A allele and poorer sociality (risk factor). We found a gene * environment interaction for susceptibility to social distress: Participants with a genetic risk factor (A carriers) with a history of high paternal overprotection showed higher heart rate increase than those without this risk factor (G/G genotype) to social distress. Also, a significant effect of the interaction between paternal care and genotype on nose temperature changes was found. This susceptibility appears to represent an indirect pathway through which genes and experiences interact to shape mature social sensitivity in males. PMID:27343933

  14. Genetic and Genomic Response to Selection for Food Consumption in Drosophila melanogaster

    Science.gov (United States)

    Garlapow, Megan E.; Everett, Logan J.; Zhou, Shanshan; Gearhart, Alexander W.; Fay, Kairsten A.; Huang, Wen; Morozova, Tatiana V.; Arya, Gunjan H.; Turlapati, Lavanya; Armour, Genevieve St.; Hussain, Yasmeen N.; McAdams, Sarah E.; Fochler, Sophia; Mackay, Trudy F. C.

    2016-01-01

    Food consumption is an essential component of animal fitness; however, excessive food intake in humans increases risk for many diseases. The roles of neuroendocrine feedback loops, food sensing modalities, and physiological state in regulating food intake are well understood, but not the genetic basis underlying variation in food consumption. Here, we applied ten generations of artificial selection for high and low food consumption in replicate populations of Drosophila melanogaster. The phenotypic response to selection was highly asymmetric, with significant responses only for increased food consumption and minimal correlated responses in body mass and composition. We assessed the molecular correlates of selection responses by DNA and RNA sequencing of the selection lines. The high and low selection lines had variants with significantly divergent allele frequencies within or near 2,081 genes and 3,526 differentially expressed genes in one or both sexes. A total of 519 genes were both genetically divergent and differentially expressed between the divergent selection lines. We performed functional analyses of the effects of RNAi suppression of gene expression and induced mutations for 27 of these candidate genes that have human orthologs and the strongest statistical support, and confirmed that 25 (93%) affected the mean and/or variance of food consumption. PMID:27704301

  15. Regulation of the Th1 immune response : the role of IL-23 and the influence of genetic variations

    NARCIS (Netherlands)

    Wetering, Diederik van de

    2010-01-01

    Part 1: The role of IL-23 in inducing IFN-g production and in the initiation of a Th1 response. Part 2: Genetic variations in the type-1 cytokine pathway. Part 3: Treatment options for a genetic deficiency in the type-1 cytokine pathway

  16. Estimating host genetic effects on susceptibility and infectivity to infectious diseases and their contribution to response to selection

    NARCIS (Netherlands)

    Anche, M.T.

    2016-01-01

    Mahlet Teka Anche. (2016). Estimating host genetic effects on susceptibility and infectivity to infectious diseases and their contribution to response to selection. PhD thesis, Wageningen University, the Netherlands

    Genetic approaches aiming to reduce the prevalence of an infection in a

  17. Genetic and environmental contributions to pro-social attitudes: a twin study of social responsibility.

    Science.gov (United States)

    Rushton, J Philippe

    2004-12-22

    Although 51 twin and adoption studies have been performed on the genetic architecture of antisocial behaviour, only four previous studies have examined a genetic contribution to pro-social behaviour. Earlier work by the author with the University of London Institute of Psychiatry Adult Twin Register found that genes contributed approximately half of the variance to measures of self-report altruism, empathy, nurturance and aggression, including acts of violence. The present study extends those results by using a 22-item Social Responsibility Questionnaire with 174 pairs of monozygotic twins and 148 pairs of dizygotic twins. Forty-two per cent of the reliable variance was due to the twins' genes, 23% to the twins' common environment and the remainder to the twins' non-shared environment.

  18. Genetic and epigenetic features in radiation sensitivity. Part I: Cell signalling in radiation response

    International Nuclear Information System (INIS)

    Bourguignon, Michel H.; Gisone, Pablo A.; Perez, Maria R.; Michelin, Severino; Dubner, Diana; Giorgio, Marina di; Carosella, Edgardo D.

    2005-01-01

    Recent progress especially in the field of gene identification and expression has attracted greater attention to genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. It has been proposed that the occurrence and severity of the adverse reactions to radiation therapy are also influenced by such genetic susceptibility. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation offering a better likelihood of cure for malignant tumours. This paper, the first of two parts, reviews the main mechanisms involved in cell response to ionising radiation. DNA repair machinery and cell signalling pathways are considered and their role in radiosensitivity is analysed. The implication of non-targeted and delayed effects in radiosensitivity is also discussed. (orig.)

  19. Ecological genetics of Chinese rhesus macaque in response to mountain building: all things are not equal.

    Directory of Open Access Journals (Sweden)

    Shan-Jin Wu

    Full Text Available Pliocene uplifting of the Qinghai-Tibetan Plateau (QTP and Quaternary glaciation may have impacted the Asian biota more than any other events. Little is documented with respect to how the geological and climatological events influenced speciation as well as spatial and genetic structuring, especially in vertebrate endotherms. Macaca mulatta is the most widely distributed non-human primate. It may be the most suitable model to test hypotheses regarding the genetic consequences of orogenesis on an endotherm.Using a large dataset of maternally inherited mitochondrial DNA gene sequences and nuclear microsatellite DNA data, we discovered two maternal super-haplogroups exist, one in western China and the other in eastern China. M. mulatta formed around 2.31 Ma (1.51-3.15, 95%, and divergence of the two major matrilines was estimated at 1.15 Ma (0.78-1.55, 95%. The western super-haplogroup exhibits significant geographic structure. In contrast, the eastern super-haplogroup has far greater haplotypic variability with little structure based on analyses of six variable microsatellite loci using Structure and Geneland. Analysis using Migrate detected greater gene flow from WEST to EAST than vice versa. We did not detect signals of bottlenecking in most populations.Analyses of the nuclear and mitochondrial datasets obtained large differences in genetic patterns for M. mulatta. The difference likely reflects inheritance mechanisms of the maternally inherited mtDNA genome versus nuclear biparentally inherited STRs and male-mediated gene flow. Dramatic environmental changes may be responsible for shaping the matrilineal history of macaques. The timing of events, the formation of M. mulatta, and the divergence of the super-haplogroups, corresponds to both the uplifting of the QTP and Quaternary climatic oscillations. Orogenesis likely drove divergence of western populations in China, and Pleistocene glaciations are likely responsible for genetic structuring in

  20. Quantitative genetic analysis of responses to larval food limitation in a polyphenic butterfly indicates environment- and trait-specific effects

    NARCIS (Netherlands)

    Saastamoinen, M.; Brommer, J.E.; Brakefield, P.M.; Zwaan, B.J.

    2013-01-01

    Different components of heritability, including genetic variance (VG), are influenced by environmental conditions. Here, we assessed phenotypic responses of life-history traits to two different developmental conditions, temperature and food limitation. The former represents an environment that

  1. Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression Profile

    Directory of Open Access Journals (Sweden)

    Luz María Medrano

    2015-01-01

    Full Text Available Substantial proportion of Crohn’s disease (CD patients shows no response or a limited response to treatment with infliximab (IFX and to identify biomarkers of response would be of great clinical and economic benefit. The expression profile of five genes (S100A8-S100A9, G0S2, TNFAIP6, and IL11 reportedly predicted response to IFX and we aimed at investigating their etiologic role through genetic association analysis. Patients with active CD (350 who received at least three induction doses of IFX were included and classified according to IFX response. A tagging strategy was used to select genetic polymorphisms that cover the variability present in the chromosomal regions encoding the identified genes with altered expression. Following genotyping, differences between responders and nonresponders to IFX were observed in haplotypes of the studied regions: S100A8-S100A9 (rs11205276*G/rs3014866*C/rs724781*C/rs3006488*A; P=0.05; G0S2 (rs4844486*A/rs1473683*T; P=0.15; TNFAIP6 (rs11677200*C/rs2342910*A/rs3755480*G/rs10432475*A; P=0.10; and IL11 (rs1126760*C/rs1042506*G; P=0.07. These differences were amplified in patients with colonic and ileocolonic location for all but the TNFAIP6 haplotype, which evidenced significant difference in ileal CD patients. Our results support the role of the reported expression signature as predictive of anti-TNF outcome in CD patients and suggest an etiological role of those top-five genes in the IFX response pathway.

  2. Genetic and demographic responses of mosquitofish (Gambusia holbrooki) populations exposed to mercury for multiple generations

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    Tatara, C.P.; Mulvey, M.; Newman, M.C.

    1999-12-01

    Genetic and demographic responses of mosquitofish were examined after multiple generations of exposure to mercury. Previous studies of acute lethal exposures of mosquitofish to either mercury or arsenic demonstrated a consistent correlation between time to death and genotype at the glucosephosphate isomerase-2 (Gpi-2) locus. A mesocosm study involving mosquitofish populations exposed to mercury for 111 d showed significant female sexual selection and fecundity selection at the Gpi-2 locus. Here the mesocosm study was extended to populations exposed to mercury for several (approx. four) generations. After 2 years, control and mercury-exposed populations met Hardy-Weinberg expectations and showed no evidence of genetic bottlenecks. The mean number of heterozygous loci did not differ significantly between the mercury-exposed and control populations. Significant differences in allele frequencies at the Gpi-2 locus were observed between the mercury-exposed and control populations. Relative to the initial and control allele frequencies, the GPI-2{sup 100} allele frequency was lower, the Gpi-2{sup 66} allele frequency increased, but the Gpi-2{sup 38} allele frequency did not change in mercury-exposed populations. No significant differences were found in standard length, weight, sex ratio, or age class ratio between the control and mercury-exposed populations. Allele frequency changes at the Gpi-2 locus suggest population-level response to chronic mercury exposure. Changes in allele frequency may be useful as indicators of population response to contaminants, provided that the population in question is well understood.

  3. Epigenetic and genetic factors in the cellular response to radiations and DNA-damaging chemicals

    International Nuclear Information System (INIS)

    Williams, J.R.; D'Arpa, P.

    1981-01-01

    DNA-damaging agents are widely used as therapeutic tools for a variety of disease states. Many such agents are considered to produce detrimental side effects. Thus, it is important to evaluate both therapeutic efficacy and potential risk. DNA-damaging agents can be so evaluated by comparison to agents whose therapeutic benefit and potential hazards are better known. We propose a framework for such comparison, demonstrating that a simple transformation of cytotoxicity-dose response patterns permits a facile comparison of variation between cells exposed to a single DNA-damaging agent or to different cytotoxic agents. Further, by transforming data from experiments which compare responses of 2 cell populations to an effects ratio, different patterns for the changes in cytotoxicity produced by epigenetic and genetic factors were compared. Using these transformations, we found that there is a wide variation (a factor of 4) between laboratories for a single agent (UVC) and only a slightly larger variation (factor of 6) between normal cell response for different types of DNA-damaging agents (x-ray, UVC, alkylating agents, crosslinking agents). Epigenetic factors such as repair and recovery appear to be a factor only at higher dose levels. Comparison in the cytotoxic effect of a spectrum of DNA-damaging agents in xeroderma pigmentosum, ataxia telangiectasia, and Fanconi's anemia cells indicates significantly different patterns, implying that the effect, and perhaps the nature, of these genetic conditions are quite different

  4. Association genetics and transcriptome analysis reveal a gibberellin-responsive pathway involved in regulating photosynthesis.

    Science.gov (United States)

    Xie, Jianbo; Tian, Jiaxing; Du, Qingzhang; Chen, Jinhui; Li, Ying; Yang, Xiaohui; Li, Bailian; Zhang, Deqiang

    2016-05-01

    Gibberellins (GAs) regulate a wide range of important processes in plant growth and development, including photosynthesis. However, the mechanism by which GAs regulate photosynthesis remains to be understood. Here, we used multi-gene association to investigate the effect of genes in the GA-responsive pathway, as constructed by RNA sequencing, on photosynthesis, growth, and wood property traits, in a population of 435 Populus tomentosa By analyzing changes in the transcriptome following GA treatment, we identified many key photosynthetic genes, in agreement with the observed increase in measurements of photosynthesis. Regulatory motif enrichment analysis revealed that 37 differentially expressed genes related to photosynthesis shared two essential GA-related cis-regulatory elements, the GA response element and the pyrimidine box. Thus, we constructed a GA-responsive pathway consisting of 47 genes involved in regulating photosynthesis, including GID1, RGA, GID2, MYBGa, and 37 photosynthetic differentially expressed genes. Single nucleotide polymorphism (SNP)-based association analysis showed that 142 SNPs, representing 40 candidate genes in this pathway, were significantly associated with photosynthesis, growth, and wood property traits. Epistasis analysis uncovered interactions between 310 SNP-SNP pairs from 37 genes in this pathway, revealing possible genetic interactions. Moreover, a structural gene-gene matrix based on a time-course of transcript abundances provided a better understanding of the multi-gene pathway affecting photosynthesis. The results imply a functional role for these genes in mediating photosynthesis, growth, and wood properties, demonstrating the potential of combining transcriptome-based regulatory pathway construction and genetic association approaches to detect the complex genetic networks underlying quantitative traits. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights

  5. HSP70 gene expression in Mytilus galloprovincialis hemocytes is triggered by moderate heat shock and Vibrio anguillarum, but not by V. splendidus or Micrococcus lysodeikticus.

    Science.gov (United States)

    Cellura, Cinzia; Toubiana, Mylène; Parrinello, Nicolo; Roch, Philippe

    2006-01-01

    Complete sequence of HSP70 cDNA from the mussel, Mytilus galloprovincialis was established before quantifying its expression following moderate heat shock or injection of heat-killed bacteria. HSP70 cDNA is comprised of 2378 bp including one ORF of 654 aa, with a predicted 70 bp 5'-UTR and a 343 bp 3'-UTR (GenBank, 18 Jan 05, AY861684). Alignment identity ranged from 89% for Crassostrea ariakensis to 72% for C. virginica. Curiously, HSP70 gene and cDNA sequences from M. galloprovincialis, deposited later (03 and 27 May), show only 73% identity with the present sequence. Meanwhile, characteristic motifs of the HSP70 family were located in conserved positions. Expression of HSP70 gene was quantified on circulating hemocyte mRNA using Q-PCR after RT using random hexaprimers. Housekeeping gene was 28S rRNA. Four stresses were applied: heat shock that consisted of immersing mussels for 90 min at 30 degrees C and returning them to 20 degrees C sea water, one injection of heat-killed Gram-negative bacteria, Vibrio splendidus LGP32, one injection of heat-killed Gram-negative bacteria Vibrio anguillarum, one injection of heat-killed Gram-positive bacteria Micrococcus lysodeikticus. We found no significant modification of 28S rRNA gene expression. Significant increase of 5.2 +/- 0.4 fold the ratio HSP70/28S rRNA was observed 6 h after heat shock and was maximum at 15 h (6.1 +/- 1.1), and still significant after 24 h (1.7 +/- 0.03). Similarly, injecting V. anguillarum resulted in a significant increase of 2.7 +/- 0.1 after 12 h. Expression was maximum after 48 h (5.2 +/- 0.05) and returned to baseline after 72 h. In contrast, injecting V. splendidus or M. lysodeikticus failed to significantly modulate HSP70 gene expression at least during the first 3 days post-injection. Consequently, mussel hemocytes appeared to discriminate between pathogenic and non-pathogenic Vibrios, as well as between Gram-negative and Gram-positive bacteria.

  6. The micropolitics of responsibility vis-à-vis autonomy: parental accounts of childhood genetic testing and (non)disclosure.

    Science.gov (United States)

    Arribas-Ayllon, Michael; Sarangi, Srikant; Clarke, Angus

    2008-03-01

    Genetic testing and (non)disclosure of genetic information present ethical and moral dilemmas for the management of parental responsibility vis-à-vis the child's autonomy. Ethical guidelines aimed at professionals currently seek to defer childhood testing where there is no clear medical or psychosocial benefit. This version of autonomy is derived from a bioethical paradigm which brackets the individual rights and capacities of the child. In this paper we focus on situated parental accounts of responsibility/autonomy to understand the complex forms of relational work -i.e. the micropolitics of balancing rights and responsibilities - involving a range of inherited genetic disorders. Interviews (n= 20) were conducted with parents whose genetic condition may have had consequences for their children. Using rhetorical discourse analysis, we show how parents draw upon a number of rhetorical/discoursal devices to produce accounts where genetic responsibility is actually or potentially transmitted to the child. We identify three kinds of accounting practice: (1) aligned responsibility; (2) deferred responsibility; and (3) misaligned responsibility. Each of these practices demonstrates how parents position themselves responsibly by foregrounding figures and events onto which the child's autonomy is selectively mapped. Rather than simple representations, we regard these accounts as complex moral performances that seek alignment with broader bioethical discourses.

  7. Genetic modulation of plasma NPY stress response is suppressed in substance abuse: association with clinical outcomes.

    Science.gov (United States)

    Xu, Ke; Hong, Kwangik Adam; Zhou, Zhifeng; Hauger, Richard L; Goldman, David; Sinha, Rajita

    2012-04-01

    Neuropeptide Y (NPY) is involved in stress regulation. Genetic variations predict plasma NPY and neural correlates of emotion and stress. We examined whether the functional NPY haplotype modulates stress-induced NPY and anxiety responses, and if plasma NPY stress responses are associated with substance dependence outcomes. Thirty-seven treatment-engaged, abstinent substance dependent (SD) patients and 28 healthy controls (HCs) characterized on NPY diplotypes (HH: high expression; HLLL: intermediate/low expression) were exposed to stress, alcohol/drug cues and neutral relaxing cues, using individualized guided imagery, in a 3-session laboratory experiment. Plasma NPY, heart rate and anxiety were assessed. Patients were prospectively followed for 90-days post-treatment to assess relapse outcomes. HH individuals showed significantly lower stress-induced NPY with greater heart rate and anxiety ratings, while the HLLL group showed the reverse pattern of NPY, anxiety and heart rate responses. This differential genetic modulation of NPY stress response was suppressed in the SD group, who showed no stress-related increases in NPY and higher heart rate and greater anxiety, regardless of diplotype. Lower NPY predicted subsequent higher number of days and greater amounts of post-treatment drug use. These preliminary findings are the first to document chronic drug abuse influences on NPY diplotype expression where NPY diplotype modulation of stress-related plasma NPY, heart rate and anxiety responses was absent in the substance abuse sample. The finding that lower stress-related NPY is predictive of greater relapse severity provides support for therapeutic development of neuropeptide Y targets in the treatment of substance use disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Chromosome 15q25.1 genetic markers associated with level of response to alcohol in humans.

    Science.gov (United States)

    Joslyn, Geoff; Brush, Gerry; Robertson, Margaret; Smith, Tom L; Kalmijn, Jelger; Schuckit, Marc; White, Raymond L

    2008-12-23

    As with other genetically complex common psychiatric and medical conditions, multiple genetic and environmental components contribute to alcohol use disorders (AUDs), which can confound attempts to identify genetic components. Intermediate phenotypes are often more closely correlated with underlying biology and have often proven invaluable in genetic studies. Level of response (LR) to alcohol is an intermediate phenotype for AUDs, and individuals with a low LR are at increased risk. A high rate of concurrent alcohol and nicotine use and dependence suggests that these conditions may share biochemical and genetic mechanisms. Genetic association studies indicate that a genetic locus, which includes the CHRNA5-CHRNA3-CHRNB4 gene cluster, plays a role in nicotine consumption and dependence. Genetic association with alcohol dependence was also recently shown. We show here that two of the markers from the nicotine studies also show an association (multiple testing corrected P a sample of 367 siblings. Additional markers in the region were analyzed and shown to be located in a 250-kb expanse of high linkage disequilibrium containing three additional genes. These findings indicate that LR intermediate phenotypes have utility in genetic approaches to AUDs and will prove valuable in the identification of other genetic loci conferring susceptibility to AUDs.

  9. Genetics of dwarfness in induced mutants of hexaploid triticale and its response to exogenous GA3

    International Nuclear Information System (INIS)

    Reddy, V.D.; Reddy, G.M.

    1991-01-01

    Genetics of dwarfism in two induced mutant (d 1 and d 2 ) of hexaploid triticale, DTS 330, revealed that this trait is governed by single recessive gene. Both d 1 and d 2 were allelic to each other and d 1 was dominant over d 2 . Both d 1 , d 2 and their F 1 showed no response to exogenous GA 3 , whereas, DTS 330, d 1 x DTS 330 and d 2 x DTS 330 were responsive. The endogenous levels of GA 3 were more in the dwarf mutants than control, suggesting that dwarfness in these may be due to a partial block in the GA utilizing mechanism, rather than a block in GA biosynthesis. (author). 5 refs., 2 tabs

  10. Detection of thermogenesis in rodents in response to anti-obesity drugs and genetic modification

    Directory of Open Access Journals (Sweden)

    Jonathan R S Arch

    2013-04-01

    Full Text Available Many compounds and genetic manipulations are claimed to confer resistance to obesity in rodents by raising energy expenditure. Examples taken from recent and older literature, demonstrate that such claims are often based on measurements of energy expenditure after body composition has changed and depend on comparisons of energy expenditure divided by body weight. This is misleading because white adipose tissue has less influence than lean tissue on energy expenditure. Application of this approach to human data would suggest that human obesity is usually due to a low metabolic rate, which is not an accepted view. Increased energy expenditure per animal is a surer way of demonstrating thermogenesis, but even then it is important to know whether this is due to altered body composition (repartitioning, or increased locomotor activity rather than thermogenesis per se. Regression analysis offers other approaches. The thermogenic response to some compounds has a rapid onset and so cannot be due to altered body composition. These compounds usually mimic or activate the sympathetic nervous system. Thermogenesis occurs in, but may not be confined to, brown adipose tissue. It should not be assumed that weight loss in response to these treatments is due to thermogenesis unless there is a sustained increase in 24-h energy expenditure. Thyroid hormones and fibroblast growth factor 21 also raise energy expenditure before they affect body composition. Some treatments and genetic modifications alter the diurnal rhythm of energy expenditure. It is important to establish whether this is due to altered locomotor activity or efficiency of locomotion. There are no good examples of compounds that do not affect short-term energy expenditure but have a delayed effect. How and under what conditions a genetic modification or compound increases energy expenditure influences the decision on whether to seek drugs for the target or take a candidate drug into clinical studies.

  11. Responses to recipient and donor B cells by genetically donor T cells from human haploidentical chimeras

    International Nuclear Information System (INIS)

    Schiff, S.; Sampson, H.; Buckley, R.

    1986-01-01

    Following administration of haploidentical stem cells to infants with severe combined immunodeficiency (SCID), mature T cells of donor karyotype appear later in the recipient without causing graft-versus-host disease. To investigate the effect of the host environment on the responsiveness of these genetically donor T cells, blood B and T lymphocytes from 6 SCID recipients, their parental donors and unrelated controls were purified by double SRBC rosetting. T cells were stimulated by irradiated B cells at a 1:1 ratio in 6 day cultures. Engrafted T cells of donor karyotype gave much smaller responses to irradiated genetically recipient B cells than did fresh donor T cells. Moreover, engrafted T cells of donor karyotype from two of the three SCIDs who are longest post-transplantation responded more vigorously (14,685 and 31,623 cpm) than fresh donor T cells (5141 and 22,709 cpm) to donor B cells. These data indicate that T lymphocytes which have matured from donor stem cells in the recipient microenvironment behave differently from those that have matured in the donor

  12. Genetics and Treatment Response in Parkinson's Disease: An Update on Pharmacogenetic Studies.

    Science.gov (United States)

    Politi, Cristina; Ciccacci, Cinzia; Novelli, Giuseppe; Borgiani, Paola

    2018-03-01

    Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by a progressive loss of dopamine neurons of the central nervous system. The disease determines a significant disability due to a combination of motor symptoms such as bradykinesia, rigidity and rest tremor and non-motor symptoms such as sleep disorders, hallucinations, psychosis and compulsive behaviors. The current therapies consist in combination of drugs acting to control only the symptoms of the illness by the replacement of the dopamine lost. Although patients generally receive benefits from this symptomatic pharmacological management, they also show great variability in drug response in terms of both efficacy and adverse effects. Pharmacogenetic studies highlighted that genetic factors play a relevant influence in this drug response variability. In this review, we tried to give an overview of the recent progresses in the pharmacogenetics of PD, reporting the major genetic factors identified as involved in the response to drugs and highlighting the potential use of some of these genomic variants in the clinical practice. Many genes have been investigated and several associations have been reported especially with adverse drug reactions. However, only polymorphisms in few genes, including DRD2, COMT and SLC6A3, have been confirmed as associated in different populations and in large cohorts. The identification of genomic biomarkers involved in drug response variability represents an important step in PD treatment, opening the prospective of more personalized therapies in order to identify, for each person, the better therapy in terms of efficacy and toxicity and to improve the PD patients' quality of life.

  13. Evaluation of Oxidative Stress Response Related Genetic Variants, Pro-oxidants, Antioxidants and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Nicole Lavender

    2015-09-01

    Full Text Available Background: Oxidative stress and detoxification mechanisms have been commonly studied in Prostate Cancer (PCa due to their function in the detoxification of potentially damaging reactive oxygen species (ROS and carcinogens. However, findings have been either inconsistent or inconclusive. These mixed findings may, in part, relate to failure to consider interactions among oxidative stress response related genetic variants along with pro- and antioxidant factors. Methods: We examined the effects of 33 genetic and 26 environmental oxidative stress and defense factors on PCa risk and disease aggressiveness among 2,286 men from the Cancer Genetic Markers of Susceptibility project (1,175 cases, 1,111 controls. Single and joint effects were analyzed using a comprehensive statistical approach involving logistic regression, multi-dimensionality reduction, and entropy graphs. Results: Inheritance of one CYP2C8 rs7909236 T or two SOD2 rs2758331 A alleles was linked to a 1.3- and 1.4-fold increase in risk of developing PCa, respectively (p-value = 0.006-0.013. Carriers of CYP1B1 rs1800440GG, CYP2C8 rs1058932TC and, NAT2 (rs1208GG, rs1390358CC, rs7832071TT genotypes were associated with a 1.3 to 2.2-fold increase in aggressive PCa [p-value = 0.04-0.001, FDR 0.088-0.939]. We observed a 23% reduction in aggressive disease linked to inheritance of one or more NAT2 rs4646247 A alleles (p = 0.04, FDR = 0.405. Only three NAT2 sequence variants remained significant after adjusting for multiple hypotheses testing, namely NAT2 rs1208, rs1390358, and rs7832071. Lastly, there were no significant gene-environment or gene-gene interactions associated with PCa outcomes. Conclusions: Variations in genes involved in oxidative stress and defense pathways may modify PCa. Our findings do not firmly support the role of oxidative stress genetic variants combined with lifestyle/environmental factors as modifiers of PCa and disease progression. However, additional multi

  14. The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose.

    Science.gov (United States)

    Auld, Stuart K J R; Edel, Kai H; Little, Tom J

    2012-10-01

    In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  15. Intergenerational Transmission of Risk for Social Inhibition: the Interplay between Parental Responsiveness and Genetic Influences

    Science.gov (United States)

    Natsuaki, Misaki N.; Leve, Leslie D.; Neiderhiser, Jenae M.; Shaw, Daniel S.; Scaramella, Laura V.; Ge, Xiaojia; Reiss, David

    2013-01-01

    To better understand mechanisms underlying the intergenerational transmission of social anxiety, we used a prospective adoption design to examine the roles of genetic influences (inferred from birth mothers’ social phobia) and rearing environment (adoptive mothers’ and fathers’ responsiveness) on the development of socially inhibited, anxious behaviors in children between 18 and 27 months of age. The sample consisted of 275 adoption-linked families, each including an adopted child, adoptive parents, and a birth mother. Results indicated that children whose birth mothers met criteria for the diagnosis of social phobia showed elevated levels of observed behavioral inhibition in a social situation at 27 months of age if their adoptive mothers provided less emotionally and verbally responsive rearing environments at 18 months of age. Conversely, in the context of higher levels of maternal responsiveness, children of birth mothers with a history of social phobia did not show elevated levels of behavioral inhibition. These findings on maternal responsiveness were replicated in a model predicting parent reports of child social anxiety. The findings are discussed in terms of genotype × environment interactions in the intergenerational transmission of social anxiety. PMID:23398764

  16. ATM directs DNA damage responses and proteostasis via genetically separable pathways.

    Science.gov (United States)

    Lee, Ji-Hoon; Mand, Michael R; Kao, Chung-Hsuan; Zhou, Yi; Ryu, Seung W; Richards, Alicia L; Coon, Joshua J; Paull, Tanya T

    2018-01-09

    The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated the activation of ATM by DNA damage from that by oxidative stress using separation-of-function mutations. We found that deficient activation of ATM by the Mre11-Rad50-Nbs1 complex and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage. In contrast, loss of oxidative activation of ATM had minimal effects on DNA damage-related outcomes but blocked ATM-mediated initiation of checkpoint responses after oxidative stress and resulted in deficiencies in mitochondrial function and autophagy. In addition, expression of a variant ATM incapable of activation by oxidative stress resulted in widespread protein aggregation. These results indicate a direct relationship between the mechanism of ATM activation and its effects on cellular metabolism and DNA damage responses in human cells and implicate ATM in the control of protein homeostasis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  17. Intergenerational transmission of risk for social inhibition: the interplay between parental responsiveness and genetic influences.

    Science.gov (United States)

    Natsuaki, Misaki N; Leve, Leslie D; Neiderhiser, Jenae M; Shaw, Daniel S; Scaramella, Laura V; Ge, Xiaojia; Reiss, David

    2013-02-01

    To better understand mechanisms underlying the intergenerational transmission of social anxiety, we used a prospective adoption design to examine the roles of genetic influences (inferred from birth mothers' social phobia) and rearing environment (adoptive mothers' and fathers' responsiveness) on the development of socially inhibited, anxious behaviors in children between 18 and 27 months of age. The sample consisted of 275 adoption-linked families, each including an adopted child, adoptive parents, and a birth mother. Results indicated that children whose birth mothers met criteria for the diagnosis of social phobia showed elevated levels of observed behavioral inhibition in a social situation at 27 months of age if their adoptive mothers provided less emotionally and verbally responsive rearing environments at 18 months of age. Conversely, in the context of higher levels of maternal responsiveness, children of birth mothers with a history of social phobia did not show elevated levels of behavioral inhibition. These findings on maternal responsiveness were replicated in a model predicting parent reports of child social anxiety. The findings are discussed in terms of gene-environment interactions in the intergenerational transmission of social anxiety.

  18. Aging, Genetic Variations, and Ethnopharmacology: Building Cultural Competence Through Awareness of Drug Responses in Ethnic Minority Elders.

    Science.gov (United States)

    Woods, Diana Lynn; Mentes, Janet C; Cadogan, Mary; Phillips, Linda R

    2017-01-01

    Unique drug responses that may result in adverse events are among the ethnocultural differences described by the Agency for Healthcare Research and Quality. These differences, often attributed to a lack of adherence on the part of the older adult, may be linked to genetic variations that influence drug responses in different ethnic groups. The paucity of research coupled with a lack of knowledge among health care providers compound the problem, contributing to further disparities, especially in this era of personalized medicine and pharmacogenomics. This article examines how age-related changes and genetic differences influence variations in drug responses among older adults in unique ethnocultural groups. The article starts with an overview of age-related changes and ethnopharmacology, moves to describing genetic differences that affect drug responses, with a focus on medications commonly prescribed for older adults, and ends with application of these issues to culturally congruent health care. © The Author(s) 2015.

  19. Determination of Critical Conditions for Puncturing Almonds Using Coupled Response Surface Methodology and Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Mahmood Mahmoodi-Eshkaftaki

    2013-01-01

    Full Text Available In this study, the effect of seed moisture content, probe diameter and loading velocity (puncture conditions on some mechanical properties of almond kernel and peeled almond kernel is considered to model a relationship between the puncture conditions and rupture energy. Furthermore, distribution of the mechanical properties is determined. The main objective is to determine the critical values of mechanical properties significant for peeling machines. The response surface methodology was used to find the relationship between the input parameters and the output responses, and the fitness function was applied to measure the optimal values using the genetic algorithm. Two-parameter Weibull function was used to describe the distribution of mechanical properties. Based on the Weibull parameter values, i.e. shape parameter (β and scale parameter (η calculated for each property, the mechanical distribution variations were completely described and it was confirmed that the mechanical properties are rule governed, which makes the Weibull function suitable for estimating their distributions. The energy model estimated using response surface methodology shows that the mechanical properties relate exponentially to the moisture, and polynomially to the loading velocity and probe diameter, which enabled successful estimation of the rupture energy (R²=0.94. The genetic algorithm calculated the critical values of seed moisture, probe diameter, and loading velocity to be 18.11 % on dry mass basis, 0.79 mm, and 0.15 mm/min, respectively, and optimum rupture energy of 1.97·10-³ J. These conditions were used for comparison with new samples, where the rupture energy was experimentally measured to be 2.68 and 2.21·10-³ J for kernel and peeled kernel, respectively, which was nearly in agreement with our model results.

  20. Mapping genetic variants associated with beta-adrenergic responses in inbred mice.

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    Micha Hersch

    Full Text Available β-blockers and β-agonists are primarily used to treat cardiovascular diseases. Inter-individual variability in response to both drug classes is well recognized, yet the identity and relative contribution of the genetic players involved are poorly understood. This work is the first genome-wide association study (GWAS addressing the values and susceptibility of cardiovascular-related traits to a selective β(1-blocker, Atenolol (ate, and a β-agonist, Isoproterenol (iso. The phenotypic dataset consisted of 27 highly heritable traits, each measured across 22 inbred mouse strains and four pharmacological conditions. The genotypic panel comprised 79922 informative SNPs of the mouse HapMap resource. Associations were mapped by Efficient Mixed Model Association (EMMA, a method that corrects for the population structure and genetic relatedness of the various strains. A total of 205 separate genome-wide scans were analyzed. The most significant hits include three candidate loci related to cardiac and body weight, three loci for electrocardiographic (ECG values, two loci for the susceptibility of atrial weight index to iso, four loci for the susceptibility of systolic blood pressure (SBP to perturbations of the β-adrenergic system, and one locus for the responsiveness of QTc (p<10(-8. An additional 60 loci were suggestive for one or the other of the 27 traits, while 46 others were suggestive for one or the other drug effects (p<10(-6. Most hits tagged unexpected regions, yet at least two loci for the susceptibility of SBP to β-adrenergic drugs pointed at members of the hypothalamic-pituitary-thyroid axis. Loci for cardiac-related traits were preferentially enriched in genes expressed in the heart, while 23% of the testable loci were replicated with datasets of the Mouse Phenome Database (MPD. Altogether these data and validation tests indicate that the mapped loci are relevant to the traits and responses studied.

  1. Genetic and environmental modulation of neurotrophic and anabolic stress response: Counterbalancing forces.

    Science.gov (United States)

    Taylor, Marcus K; Carpenter, Jennifer; Stone, Michael; Hernandez, Lisa M; Rauh, Mitchell J; Laurent, Heidemarie K; Granger, Douglas A

    2015-11-01

    The serotonin transporter genetic variant 5HTTLPR influences activation and feedback control of the hypothalamic-pituitary-adrenal axis, and has been shown to influence the effect of stressful life events on behavioral health. We recently reported that 5HTTLPR modulates cortisol response in healthy military men exposed to intense stress. Less is known of its combined effects with environmental factors in this context, or of its effect on neuroprotective stress responses. In this follow-up study, we examined the unique and combined effects of 5HTTLPR and prior trauma exposure on neuroprotective (salivary nerve growth factor [sNGF]), anabolic (dehydroepiandrosterone sulfate [DHEAS] and testosterone), and catabolic (cortisol) stress responses. Ninety-three healthy, active-duty military men were studied before, during, and 24h after a stressful 12-day survival course. Distinct and interactive effects of 5HTTLPR long allele carriage [L] versus homozygous short allele carriage [SS]) and prior trauma exposure (low versus high) were evaluated, after which a priori group comparisons were performed between hypothesized high resilience (L/low) and low resilience (SS/high) groups. For sNGF, L/low produced the greatest sNGF throughout stress exposure while SS/high demonstrated the smallest; L/high and SS/low bisected these two extremes and were nearly identical to each other (i.e., SS/high counterbalancing (additive) forces. Similar patterns were found for DHEAS. To our knowledge, this study is the first to report counterbalancing genetic and environmental effects on novel biomarkers related to resilience in humans exposed to real-world stress. These findings have profound implications for health, performance and training in high-stress occupational settings. Copyright © 2015. Published by Elsevier Inc.

  2. Growth condition dependency is the major cause of non-responsiveness upon genetic perturbation.

    Directory of Open Access Journals (Sweden)

    Saman Amini

    Full Text Available Investigating the role and interplay between individual proteins in biological processes is often performed by assessing the functional consequences of gene inactivation or removal. Depending on the sensitivity of the assay used for determining phenotype, between 66% (growth and 53% (gene expression of Saccharomyces cerevisiae gene deletion strains show no defect when analyzed under a single condition. Although it is well known that this non-responsive behavior is caused by different types of redundancy mechanisms or by growth condition/cell type dependency, it is not known what the relative contribution of these different causes is. Understanding the underlying causes of and their relative contribution to non-responsive behavior upon genetic perturbation is extremely important for designing efficient strategies aimed at elucidating gene function and unraveling complex cellular systems. Here, we provide a systematic classification of the underlying causes of and their relative contribution to non-responsive behavior upon gene deletion. The overall contribution of redundancy to non-responsive behavior is estimated at 29%, of which approximately 17% is due to homology-based redundancy and 12% is due to pathway-based redundancy. The major determinant of non-responsiveness is condition dependency (71%. For approximately 14% of protein complexes, just-in-time assembly can be put forward as a potential mechanistic explanation for how proteins can be regulated in a condition dependent manner. Taken together, the results underscore the large contribution of growth condition requirement to non-responsive behavior, which needs to be taken into account for strategies aimed at determining gene function. The classification provided here, can also be further harnessed in systematic analyses of complex cellular systems.

  3. Genetic loci involved in antibody response to Mycobacterium avium ssp. paratuberculosis in cattle.

    Directory of Open Access Journals (Sweden)

    Giulietta Minozzi

    Full Text Available BACKGROUND: Mycobacterium avium subsp. paratuberculosis (MAP causes chronic enteritis in a wide range of animal species. In cattle, MAP causes a chronic disease called Johne's disease, or paratuberculosis, that is not treatable and the efficacy of vaccine control is controversial. The clinical phase of the disease is characterised by diarrhoea, weight loss, drop in milk production and eventually death. Susceptibility to MAP infection is heritable with heritability estimates ranging from 0.06 to 0.10. There have been several studies over the last few years that have identified genetic loci putatively associated with MAP susceptibility, however, with the availability of genome-wide high density SNP maker panels it is now possible to carry out association studies that have higher precision. METHODOLOGY/PRINCIPAL FINDINGS: The objective of the current study was to localize genes having an impact on Johne's disease susceptibility using the latest bovine genome information and a high density SNP panel (Illumina BovineSNP50 BeadChip to perform a case/control, genome-wide association analysis. Samples from MAP case and negative controls were selected from field samples collected in 2007 and 2008 in the province of Lombardy, Italy. Cases were defined as animals serologically positive for MAP by ELISA. In total 966 samples were genotyped: 483 MAP ELISA positive and 483 ELISA negative. Samples were selected randomly among those collected from 119 farms which had at least one positive animal. CONCLUSION/SIGNIFICANCE: THE ANALYSIS OF THE GENOTYPE DATA IDENTIFIED SEVERAL CHROMOSOMAL REGIONS ASSOCIATED WITH DISEASE STATUS: a region on chromosome 12 with high significance (P<5x10(-6, while regions on chromosome 9, 11, and 12 had moderate significance (P<5x10(-5. These results provide evidence for genetic loci involved in the humoral response to MAP. Knowledge of genetic variations related to susceptibility will facilitate the incorporation of this information

  4. Genetic response in masseter muscle after orthognathic surgery in comparison with healthy controls - A Microarray study.

    Science.gov (United States)

    Marewski, Maya; Petto, Carola; Schneider, Matthias; Harzer, Winfried

    2017-04-01

    One third of adult patients with orthognathic surgery of a prognathic or retrognathic mandible show relapse. The sagittal split osteotomy of the mandible leads to a displacement of both parts up to 10 mm without any changes of muscle attachment. Changed mandible length needs adaptation of muscle capacity because of changed force to moment ratio. The aim of this Microarray study was to analyze the general genetic response of masseter muscle in patients with retrognathism or prognathism of the mandible six months after surgery in comparison with healthy untreated controls. We found in tissue samples from masseter muscle a reduction of different entities between patients and controls but less in retrognathic than in prognathic patients (274/429). The different entities to controls in prognathia were reduced from 1862 to 1749 but increased in retrognathia from 1070 to 1563. We have to consider that the total amount of different entities to the controls is higher in patients with prognathic mandible (7364) because of their strong genetic controlled development compared with that in patients with retrognathic mandible (4126), which is more environmentally influenced. It can be concluded that function follows form after surgical change with high inheritance. In retrognathic patients the adaptation could be delayed or the capacity of regeneration potential is not sufficient. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  5. Molecular responses of genetically modified maize to abiotic stresses as determined through proteomic and metabolomic analyses.

    Directory of Open Access Journals (Sweden)

    Rafael Fonseca Benevenuto

    Full Text Available Some genetically modified (GM plants have transgenes that confer tolerance to abiotic stressors. Meanwhile, other transgenes may interact with abiotic stressors, causing pleiotropic effects that will affect the plant physiology. Thus, physiological alteration might have an impact on the product safety. However, routine risk assessment (RA analyses do not evaluate the response of GM plants exposed to different environmental conditions. Therefore, we here present a proteome profile of herbicide-tolerant maize, including the levels of phytohormones and related compounds, compared to its near-isogenic non-GM variety under drought and herbicide stresses. Twenty differentially abundant proteins were detected between GM and non-GM hybrids under different water deficiency conditions and herbicide sprays. Pathway enrichment analysis showed that most of these proteins are assigned to energetic/carbohydrate metabolic processes. Among phytohormones and related compounds, different levels of ABA, CA, JA, MeJA and SA were detected in the maize varieties and stress conditions analysed. In pathway and proteome analyses, environment was found to be the major source of variation followed by the genetic transformation factor. Nonetheless, differences were detected in the levels of JA, MeJA and CA and in the abundance of 11 proteins when comparing the GM plant and its non-GM near-isogenic variety under the same environmental conditions. Thus, these findings do support molecular studies in GM plants Risk Assessment analyses.

  6. The key elements for genetic response in Finnish dairy cattle breeding

    Directory of Open Access Journals (Sweden)

    Jarmo Juga

    1998-01-01

    Full Text Available This paper reviews some key elements of Finnish animal breeding research contributing to the Finnish dairy cattle breeding programme and discusses the possibilities and problems in collecting data for genetic evaluation, prediction of breeding values both within and across countries, estimation of the economic value of important traits, and selection of bulls and cows. Economic values are calculated for fertility, udder health and production traits when one genetic standard deviation unit (gen. sd. is changed in each trait independently and the financial returns from selection response in the Finnish dairy cattle breeding programme are estimated. The following components were used to calculate the economic value of mastitis treatments: 1 cost of mastitis including discarded milk and treatment costs, 2 reduction in milk price due to higher somatic cell count, 3 replacement costs and 4 lower production level of the herd due to involuntary culling of cows because of udder problems. A high somatic cell count lowers the price of milk and eventually leads to involuntary culling. For treatments for fertility disorders the following costs were included: 1 treatment costs 2 higher replacement costs and 3 decreased milk production in the herd. Days open included the following costs: 1 extra insemination, 2 reduced annual milk yield and 3 fewer calves born. Animal breeding was found to be a very cost effective investment, yielding returns of FIM 876.9 per cow from one round of selection when the gene flow was followed for over 25 years in the Finnish dairy cattle breeding programme.

  7. Defining genes using "blueprint" versus "instruction" metaphors: effects for genetic determinism, response efficacy, and perceived control.

    Science.gov (United States)

    Parrott, Roxanne; Smith, Rachel A

    2014-01-01

    Evidence supports mixed attributions aligned with personal and/or clinical control and gene expression for health in this era of genomic science and health care. We consider variance in these attributions and possible relationships to individual mind sets associated with essentialist beliefs that genes determine health versus threat beliefs that genes increase susceptibility for disease and severity linked to gene-environment interactions. Further, we contribute to theory and empirical research to evaluate the use of metaphors to define genes. Participants (N = 324) read a message that varied the introduction by providing a definition of genes that used either an "instruction" metaphor or a "blueprint" metaphor. The "instruction" metaphor compared to the "blueprint" metaphor promoted stronger threat perceptions, which aligned with both belief in the response efficacy of genetic research for health and perceived behavioral control linked to genes and health. The "blueprint" metaphor compared to the "instruction" metaphor promoted stronger essentialist beliefs, which aligned with more intense positive regard for the efficacy of genetic research and human health. Implications for health communicators include societal effects aligned with stigma and discrimination that such findings portend.

  8. Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis.

    Science.gov (United States)

    Sieberts, Solveig K; Zhu, Fan; García-García, Javier; Stahl, Eli; Pratap, Abhishek; Pandey, Gaurav; Pappas, Dimitrios; Aguilar, Daniel; Anton, Bernat; Bonet, Jaume; Eksi, Ridvan; Fornés, Oriol; Guney, Emre; Li, Hongdong; Marín, Manuel Alejandro; Panwar, Bharat; Planas-Iglesias, Joan; Poglayen, Daniel; Cui, Jing; Falcao, Andre O; Suver, Christine; Hoff, Bruce; Balagurusamy, Venkat S K; Dillenberger, Donna; Neto, Elias Chaibub; Norman, Thea; Aittokallio, Tero; Ammad-Ud-Din, Muhammad; Azencott, Chloe-Agathe; Bellón, Víctor; Boeva, Valentina; Bunte, Kerstin; Chheda, Himanshu; Cheng, Lu; Corander, Jukka; Dumontier, Michel; Goldenberg, Anna; Gopalacharyulu, Peddinti; Hajiloo, Mohsen; Hidru, Daniel; Jaiswal, Alok; Kaski, Samuel; Khalfaoui, Beyrem; Khan, Suleiman Ali; Kramer, Eric R; Marttinen, Pekka; Mezlini, Aziz M; Molparia, Bhuvan; Pirinen, Matti; Saarela, Janna; Samwald, Matthias; Stoven, Véronique; Tang, Hao; Tang, Jing; Torkamani, Ali; Vert, Jean-Phillipe; Wang, Bo; Wang, Tao; Wennerberg, Krister; Wineinger, Nathan E; Xiao, Guanghua; Xie, Yang; Yeung, Rae; Zhan, Xiaowei; Zhao, Cheng; Greenberg, Jeff; Kremer, Joel; Michaud, Kaleb; Barton, Anne; Coenen, Marieke; Mariette, Xavier; Miceli, Corinne; Shadick, Nancy; Weinblatt, Michael; de Vries, Niek; Tak, Paul P; Gerlag, Danielle; Huizinga, Tom W J; Kurreeman, Fina; Allaart, Cornelia F; Louis Bridges, S; Criswell, Lindsey; Moreland, Larry; Klareskog, Lars; Saevarsdottir, Saedis; Padyukov, Leonid; Gregersen, Peter K; Friend, Stephen; Plenge, Robert; Stolovitzky, Gustavo; Oliva, Baldo; Guan, Yuanfang; Mangravite, Lara M; Bridges, S Louis; Criswell, Lindsey; Moreland, Larry; Klareskog, Lars; Saevarsdottir, Saedis; Padyukov, Leonid; Gregersen, Peter K; Friend, Stephen; Plenge, Robert; Stolovitzky, Gustavo; Oliva, Baldo; Guan, Yuanfang; Mangravite, Lara M

    2016-08-23

    Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h(2)=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.

  9. Genetic variants in the apoptosis gene BCL2L1 improve response to interferon-based treatment of hepatitis C virus genotype 3 infection

    DEFF Research Database (Denmark)

    Clausen, Louise Nygaard; Weis, Nina; Ladelund, Steen

    2015-01-01

    Genetic variation upstream of the apoptosis pathway has been associated with outcome of hepatitis C virus (HCV) infection. We investigated genetic polymorphisms in the intrinsic apoptosis pathway to assess their influence on sustained virological response (SVR) to pegylated interferon-α and ribav......Genetic variation upstream of the apoptosis pathway has been associated with outcome of hepatitis C virus (HCV) infection. We investigated genetic polymorphisms in the intrinsic apoptosis pathway to assess their influence on sustained virological response (SVR) to pegylated interferon...

  10. Strategies to Genetically Modulate Dendritic Cells to Potentiate Anti-Tumor Responses in Hematologic Malignancies

    Directory of Open Access Journals (Sweden)

    Annelisa M. Cornel

    2018-05-01

    Full Text Available Dendritic cell (DC vaccination has been investigated as a potential strategy to target hematologic malignancies, while generating sustained immunological responses to control potential future relapse. Nonetheless, few clinical trials have shown robust long-term efficacy. It has been suggested that a combination of surmountable shortcomings, such as selection of utilized DC subsets, DC loading and maturation strategies, as well as tumor-induced immunosuppression may be targeted to maximize anti-tumor responses of DC vaccines. Generation of DC from CD34+ hematopoietic stem and progenitor cells (HSPCs may provide potential in patients undergoing allogeneic HSPC transplantations for hematologic malignancies. CD34+ HSPC from the graft can be genetically modified to optimize antigen presentation and to provide sufficient T cell stimulatory signals. We here describe beneficial (gene-modifications that can be implemented in various processes in T cell activation by DC, among which major histocompatibility complex (MHC class I and MHC class II presentation, DC maturation and migration, cross-presentation, co-stimulation, and immunosuppression to improve anti-tumor responses.

  11. Application of response surface methodology (RSM) and genetic algorithm in minimizing warpage on side arm

    Science.gov (United States)

    Raimee, N. A.; Fathullah, M.; Shayfull, Z.; Nasir, S. M.; Hazwan, M. H. M.

    2017-09-01

    The plastic injection moulding process produces large numbers of parts of high quality with great accuracy and quickly. It has widely used for production of plastic part with various shapes and geometries. Side arm is one of the product using injection moulding to manufacture it. However, there are some difficulties in adjusting the parameter variables which are mould temperature, melt temperature, packing pressure, packing time and cooling time as there are warpage happen at the tip part of side arm. Therefore, the work reported herein is about minimizing warpage on side arm product by optimizing the process parameter using Response Surface Methodology (RSM) and with additional artificial intelligence (AI) method which is Genetic Algorithm (GA).

  12. Long-term response to genomic selection: effects of estimation method and reference population structure for different genetic architectures.

    Science.gov (United States)

    Bastiaansen, John W M; Coster, Albart; Calus, Mario P L; van Arendonk, Johan A M; Bovenhuis, Henk

    2012-01-24

    Genomic selection has become an important tool in the genetic improvement of animals and plants. The objective of this study was to investigate the impacts of breeding value estimation method, reference population structure, and trait genetic architecture, on long-term response to genomic selection without updating marker effects. Three methods were used to estimate genomic breeding values: a BLUP method with relationships estimated from genome-wide markers (GBLUP), a Bayesian method, and a partial least squares regression method (PLSR). A shallow (individuals from one generation) or deep reference population (individuals from five generations) was used with each method. The effects of the different selection approaches were compared under four different genetic architectures for the trait under selection. Selection was based on one of the three genomic breeding values, on pedigree BLUP breeding values, or performed at random. Selection continued for ten generations. Differences in long-term selection response were small. For a genetic architecture with a very small number of three to four quantitative trait loci (QTL), the Bayesian method achieved a response that was 0.05 to 0.1 genetic standard deviation higher than other methods in generation 10. For genetic architectures with approximately 30 to 300 QTL, PLSR (shallow reference) or GBLUP (deep reference) had an average advantage of 0.2 genetic standard deviation over the Bayesian method in generation 10. GBLUP resulted in 0.6% and 0.9% less inbreeding than PLSR and BM and on average a one third smaller reduction of genetic variance. Responses in early generations were greater with the shallow reference population while long-term response was not affected by reference population structure. The ranking of estimation methods was different with than without selection. Under selection, applying GBLUP led to lower inbreeding and a smaller reduction of genetic variance while a similar response to selection was

  13. What would you say? Genetic counseling graduate students' and counselors' hypothetical responses to patient requested self-disclosure.

    Science.gov (United States)

    Redlinger-Grosse, Krista; Veach, Patricia McCarthy; MacFarlane, Ian M

    2013-08-01

    Genetic counselor self-disclosure is a complex behavior that lacks extensive characterization. In particular, data are limited about genetic counselors' responses when patients ask them to self-disclose. Accordingly, this study investigated genetic counseling students' (n = 114) and practicing genetic counselors' (n = 123) responses to two hypothetical scenarios in which a female prenatal patient requests self-disclosure. Scenarios were identical except for a final patient question: "Have you ever had an amniocentesis?" or "What would you do if you were me?" Imagining themselves as the counselor, participants wrote a response for each scenario and then explained their response. Differences in disclosure frequency for students vs. counselors and disclosure question were assessed, and themes in participant responses and explanations were extracted via content and thematic analysis methods. Chi-square analyses indicated no significant differences in frequency of student versus counselor disclosure. Self-disclosure was significantly higher for, "Have you ever had an amniocentesis?" (78.5 %) than for, "What would you do if you were me?" (53.2 %) (p self-disclosures included personal, professional, and mixed disclosures. Prevalent explanations for disclosure and non-disclosure responses included: remain patient focused and support/empower the patient. Additional findings, practice and training implications, and research recommendations are presented.

  14. Genetic privacy.

    Science.gov (United States)

    Sankar, Pamela

    2003-01-01

    During the past 10 years, the number of genetic tests performed more than tripled, and public concern about genetic privacy emerged. The majority of states and the U.S. government have passed regulations protecting genetic information. However, research has shown that concerns about genetic privacy are disproportionate to known instances of information misuse. Beliefs in genetic determinacy explain some of the heightened concern about genetic privacy. Discussion of the debate over genetic testing within families illustrates the most recent response to genetic privacy concerns.

  15. Response of predatory mites to a herbivore-induced plant volatile: genetic variation for context-dependent behaviour.

    Science.gov (United States)

    Sznajder, Beata; Sabelis, Maurice W; Egas, Martijn

    2010-07-01

    Plants infested with herbivores release specific volatile compounds that are known to recruit natural enemies. The response of natural enemies to these volatiles may be either learned or genetically determined. We asked whether there is genetic variation in the response of the predatory mite Phytoseiulus persimilis to methyl salicylate (MeSa). MeSa is a volatile compound consistently produced by plants being attacked by the two-spotted spider mite, the prey of P. persimilis. We predicted that predators express genetically determined responses during long-distance migration where previously learned associations may have less value. Additionally, we asked whether these responses depend on odors from uninfested plants as a background to MeSa. To infer a genetic basis, we analyzed the variation in response to MeSa among iso-female lines of P. persimilis by using choice-tests that involved either (1) MeSa presented as a single compound or (2) MeSa with background-odor from uninfested lima bean plants. These tests were conducted for starved and satiated predators, i.e., two physiological states, one that approximates migration and another that mimics local patch exploration. We found variation among iso-female lines in the responses to MeSa, thus showing genetic variation for this behavior. The variation was more pronounced in the starved predators, thus indicating that P. persimilis relies on innate preferences when migrating. Background volatiles of uninfested plants changed the predators' responses to MeSa in a manner that depended on physiological state and iso-female line. Thus, it is possible to select for context-dependent behavioral responses of natural enemies to plant volatiles.

  16. Evaluation of mature cow weight: genetic correlations with traits used in selection indices, correlated responses, and genetic trends in Nelore cattle.

    Science.gov (United States)

    Boligon, A A; Carvalheiro, R; Albuquerque, L G

    2013-01-01

    Genetic correlations of selection indices and the traits considered in these indices with mature weight (MW) of Nelore females and correlated responses were estimated to determine whether current selection practices will result in an undesired correlated response in MW. Genetic trends for weaning and yearling indices and MW were also estimated. Data from 612,244 Nelore animals born between 1984 and 2010, belonging to different beef cattle evaluation programs from Brazil and Paraguay, were used. The following traits were studied: weaning conformation (WC), weaning precocity (WP), weaning muscling (WM), yearling conformation (YC), yearling precocity (YP), yearling muscling (YM), weaning and yearling indices, BW gain from birth to weaning (BWG), postweaning BW gain (PWG), scrotal circumference (SC), and MW. The variance and covariance components were estimated by Bayesian inference in a multitrait analysis, including all traits in the same analysis, using a nonlinear (threshold) animal model for visual scores and a linear animal model for the other traits. The mean direct heritabilities were 0.21±0.007 (WC), 0.22±0.007 (WP), 0.20±0.007 (WM), 0.43±0.005 (YC), 0.40±0.005 (YP), 0.40±0.005 (YM), 0.17±0.003 (BWG), 0.21±0.004 (PWG), 0.32±0.001 (SC), and 0.44±0.018 (MW). The genetic correlations between MW and weaning and yearling indices were positive and of medium magnitude (0.30±0.01 and 0.31±0.01, respectively). The genetic changes in weaning index, yearling index, and MW, expressed as units of genetic SD per year, were 0.26, 0.27, and 0.01, respectively. The genetic trend for MW was nonsignificant, suggesting no negative correlated response. The selection practice based on the use of sires with high final index giving preference for those better ranked for yearling precocity and muscling than for conformation generates only a minimal correlated response in MW.

  17. Can Man Control His Biological Evolution? A Symposium on Genetic Engineering. Man's Responsibility to His Future

    Science.gov (United States)

    Hoagland, Hudson

    1972-01-01

    Biological evolution can be carried out in the laboratory. With new knowledge available in genetics, possibilities are raised that genetic characters can be transferred in the future to embryos according to a predetermined plan. (PS)

  18. Genetic effects of ELISA-based segregation for control of bacterial kidney disease in Chinook salmon (Oncorhynchus tshawytscha)

    Science.gov (United States)

    Hard, J.J.; Elliott, D.G.; Pascho, R.J.; Chase, D.M.; Park, L.K.; Winton, J.R.; Campton, D.E.

    2006-01-01

    We evaluated genetic variation in ability of Chinook salmon (Oncorhynchus tshawytscha) to resist two bacterial pathogens: Renibacterium salmoninarum, the agent of bacterial kidney disease (BKD), and Listonella anguillarum, an agent of vibriosis. After measuring R. salmoninarum antigen in 499 adults by enzyme-linked immunosorbent assay (ELISA), we mated each of 12 males with high or low antigen levels to two females with low to moderate levels and exposed subsets of their progeny to each pathogen separately. We found no correlation between R. salmoninarum antigen level in parents and survival of their progeny following pathogen exposure. We estimated high heritability for resistance to R. salmoninarum (survival h2 = 0.890 ?? 0.256 (mean ?? standard error)) independent of parental antigen level, but low heritability for resistance to L. anguillarum (h2 = 0.128 ?? 0.078). The genetic correlation between these survivals (rA = -0.204 ?? 0.309) was near zero. The genetic and phenotypic correlations between survival and antigen levels among surviving progeny exposed to R. salmoninarum were both negative (rA = -0.716 ?? 0.140; rP = -0.378 ?? 0.041), indicating that variation in antigen level is linked to survival. These results suggest that selective culling of female broodstock with high antigen titers, which is effective in controlling BKD in salmon hatcheries, will not affect resistance of their progeny. ?? 2006 NRC.

  19. Limiting Performance Analysis of Underwater Shock Isolation of a System with Biodynamic Response Using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Z. Zong

    2000-01-01

    Full Text Available Biodynamic response of shipboard crew to underwater shock is of a major concern to navies. An underwater shock can produce very high accelerations, resulting in severe human injuries aboard a battleship. Protection of human bodies from underwater shock is implemented by installing onboard isolators. In this paper, the optimal underwater shock isolation to protect human bodies is studied. A simple shock-structure-isolator-human interaction model is first constructed. The model incorporates the effect of fluid-structure interaction, biodynamic response of human body, isolator influence. Based on this model, the optimum shock isolation is then formulated. The performance index and restriction are defined. Thirdly, GA (genetic algorithm is employed to solve the formulated optimization problem. GA is a powerful evolutionary optimization scheme suitable for large-scale and multi-variable optimization problems that are otherwise hard to be solved by conventional methods. A brief introduction to GA is given in the paper. Finally, the method is applied to an example problem and the limiting performance characteristic is obtained.

  20. Genetics of PCOS: A systematic bioinformatics approach to unveil the proteins responsible for PCOS.

    Science.gov (United States)

    Panda, Pritam Kumar; Rane, Riya; Ravichandran, Rahul; Singh, Shrinkhla; Panchal, Hetalkumar

    2016-06-01

    Polycystic ovary syndrome (PCOS) is a hormonal imbalance in women, which causes problems during menstrual cycle and in pregnancy that sometimes results in fatality. Though the genetics of PCOS is not fully understood, early diagnosis and treatment can prevent long-term effects. In this study, we have studied the proteins involved in PCOS and the structural aspects of the proteins that are taken into consideration using computational tools. The proteins involved are modeled using Modeller 9v14 and Ab-initio programs. All the 43 proteins responsible for PCOS were subjected to phylogenetic analysis to identify the relatedness of the proteins. Further, microarray data analysis of PCOS datasets was analyzed that was downloaded from GEO datasets to find the significant protein-coding genes responsible for PCOS, which is an addition to the reported protein-coding genes. Various statistical analyses were done using R programming to get an insight into the structural aspects of PCOS that can be used as drug targets to treat PCOS and other related reproductive diseases.

  1. 'Faceness' and affectivity: evidence for genetic contributions to distinct components of electrocortical response to human faces.

    Science.gov (United States)

    Shannon, Robert W; Patrick, Christopher J; Venables, Noah C; He, Sheng

    2013-12-01

    The ability to recognize a variety of different human faces is undoubtedly one of the most important and impressive functions of the human perceptual system. Neuroimaging studies have revealed multiple brain regions (including the FFA, STS, OFA) and electrophysiological studies have identified differing brain event-related potential (ERP) components (e.g., N170, P200) possibly related to distinct types of face information processing. To evaluate the heritability of ERP components associated with face processing, including N170, P200, and LPP, we examined ERP responses to fearful and neutral face stimuli in monozygotic (MZ) and dizygotic (DZ) twins. Concordance levels for early brain response indices of face processing (N170, P200) were found to be stronger for MZ than DZ twins, providing evidence of a heritable basis to each. These findings support the idea that certain key neural mechanisms for face processing are genetically coded. Implications for understanding individual differences in recognition of facial identity and the emotional content of faces are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Investigating the toxicity, uptake, nanoparticle formation and genetic response of plants to gold.

    Directory of Open Access Journals (Sweden)

    Andrew F Taylor

    Full Text Available We have studied the physiological and genetic responses of Arabidopsis thaliana L. (Arabidopsis to gold. The root lengths of Arabidopsis seedlings grown on nutrient agar plates containing 100 mg/L gold were reduced by 75%. Oxidized gold was subsequently found in roots and shoots of these plants, but gold nanoparticles (reduced gold were only observed in the root tissues. We used a microarray-based study to monitor the expression of candidate genes involved in metal uptake and transport in Arabidopsis upon gold exposure. There was up-regulation of genes involved in plant stress response such as glutathione transferases, cytochromes P450, glucosyl transferases and peroxidases. In parallel, our data show the significant down-regulation of a discreet number of genes encoding proteins involved in the transport of copper, cadmium, iron and nickel ions, along with aquaporins, which bind to gold. We used Medicago sativa L. (alfalfa to study nanoparticle uptake from hydroponic culture using ionic gold as a non-nanoparticle control and concluded that nanoparticles between 5 and 100 nm in diameter are not directly accumulated by plants. Gold nanoparticles were only observed in plants exposed to ionic gold in solution. Together, we believe our results imply that gold is taken up by the plant predominantly as an ionic form, and that plants respond to gold exposure by up-regulating genes for plant stress and down-regulating specific metal transporters to reduce gold uptake.

  3. From brute luck to option luck? On genetics, justice, and moral responsibility in reproduction.

    Science.gov (United States)

    Denier, Yvonne

    2010-04-01

    The structure of our ethical experience depends, crucially, on a fundamental distinction between what we are responsible for doing or deciding and what is given to us. As such, the boundary between chance and choice is the spine of our conventional morality, and any serious shift in that boundary is thoroughly dislocating. Against this background, I analyze the way in which techniques of prenatal genetic diagnosis (PGD) pose such a fundamental challenge to our conventional ideas of justice and moral responsibility. After a short description of the situation, I first examine the influential luck egalitarian theory of justice, which is based on the distinction between choice and luck or, more specifically, between option luck and brute luck, and the way in which it would approach PGD (section II), followed by an analysis of the conceptual incoherencies (in section III) and moral problems (in section IV) that come with such an approach. Put shortly, the case of PGD shows that the luck egalitarian approach fails to express equal respect for the individual choices of people. The paradox of the matter is that by overemphasizing the fact of choice as such, without regard for the social framework in which they are being made, or for the fundamental and existential nature of particular choices-like choosing to have children and not to undergo PGD or not to abort a handicapped fetus-such choices actually become impossible.

  4. Investigating the Toxicity, Uptake, Nanoparticle Formation and Genetic Response of Plants to Gold

    Science.gov (United States)

    Taylor, Andrew F.; Rylott, Elizabeth L.; Anderson, Christopher W. N.; Bruce, Neil C.

    2014-01-01

    We have studied the physiological and genetic responses of Arabidopsis thaliana L. (Arabidopsis) to gold. The root lengths of Arabidopsis seedlings grown on nutrient agar plates containing 100 mg/L gold were reduced by 75%. Oxidized gold was subsequently found in roots and shoots of these plants, but gold nanoparticles (reduced gold) were only observed in the root tissues. We used a microarray-based study to monitor the expression of candidate genes involved in metal uptake and transport in Arabidopsis upon gold exposure. There was up-regulation of genes involved in plant stress response such as glutathione transferases, cytochromes P450, glucosyl transferases and peroxidases. In parallel, our data show the significant down-regulation of a discreet number of genes encoding proteins involved in the transport of copper, cadmium, iron and nickel ions, along with aquaporins, which bind to gold. We used Medicago sativa L. (alfalfa) to study nanoparticle uptake from hydroponic culture using ionic gold as a non-nanoparticle control and concluded that nanoparticles between 5 and 100 nm in diameter are not directly accumulated by plants. Gold nanoparticles were only observed in plants exposed to ionic gold in solution. Together, we believe our results imply that gold is taken up by the plant predominantly as an ionic form, and that plants respond to gold exposure by up-regulating genes for plant stress and down-regulating specific metal transporters to reduce gold uptake. PMID:24736522

  5. Molecular genetics of growth hormone deficient children: correlation with auxology and response to first year of growth hormone therapy.

    Science.gov (United States)

    Khadilkar, Vaman; Phadke, Nikhil; Khatod, Kavita; Ekbote, Veena; Gupte, Supriya Phanse; Nadar, Ruchi; Khadilkar, Anuradha

    2017-05-24

    With the paucity of available literature correlating genetic mutation and response to treatment, we aimed to study the genetic makeup of children with growth hormone (GH) deficiency in Western India and correlate the mutation with auxology and response to GH treatment at end of 1 year. Fifty-three (31 boys and 22 girls) children with severe short stature (height for age z-score imaging (MRI) brain scan was done in all. Genetic mutations were tested for in GH1, GHRH, LHX3, LHX4 and PROP1, POU1F1 and HESX1 genes. Mean age at presentation was 9.7±5.1 years. Thirty-seven children (Group A) had no genetic mutation detected. Six children (Group B) had mutations in the GH releasing hormone receptor (GHRHR) gene, while eight children (Group C) had mutation in the GH1 gene. In two children, one each had a mutation in PROP1 and LHX3. There was no statistically significant difference in baseline height, weight and BMI for age z-score and height velocity for age z-score (HVZ). HVZ was significantly lower, post 1 year GH treatment in the group with homozygous GH1 deletion than in children with no genetic defect. Response to GH at the end of 1 year was poor in children with the homozygous GH1 deletion as compared to those with GHRHR mutation or without a known mutation.

  6. A Drosophila genetic model of nephrolithiasis: transcriptional changes in response to diet induced stone formation.

    Science.gov (United States)

    Chung, Vera Y; Turney, Benjamin W

    2017-11-28

    Urolithiasis is a significant healthcare issue but the pathophysiology of stone disease remains poorly understood. Drosophila Malpighian tubules were known to share similar physiological function to human renal tubules. We have used Drosophila as a genetic model to study the transcriptional response to stone formation secondary to dietary manipulation. Wild-type male flies were raised on standard medium supplemented with lithogenic agents: control, sodium oxalate (NaOx) and ethylene glycol (EG). At 2 weeks, Malpighian tubules were dissected under polarized microscope to visualize crystals. The parallel group was dissected for RNA extraction and subsequent next-generation RNA sequencing. Crystal formation was visualized in 20%(±2.2) of flies on control diet, 73%(±3.6) on NaOx diet and 84%(±2.2) on EG diet. Differentially expressed genes were identified in flies fed with NaOx and EG diet comparing with the control group. Fifty-eight genes were differentially expressed (FDR <0.05, p < 0.05) in NaOx diet and 20 genes in EG diet. The molecular function of differentially expressed genes were assessed. Among these, Nervana 3, Eaat1 (Excitatory amino acid transporter 1), CG7912, CG5404, CG3036 worked as ion transmembrane transporters, which were possibly involved in stone pathogenesis. We have shown that by dietary modification, stone formation can be manipulated and visualized in Drosophila Malpighian tubules. This genetic model could be potentially used to identify the candidate genes that influence stone risk hence providing more insight to the pathogenesis of human stone disease.

  7. Exploring the Role of Genetic Variability and Lifestyle in Oxidative Stress Response for Healthy Aging and Longevity

    Directory of Open Access Journals (Sweden)

    Giuseppe Passarino

    2013-08-01

    Full Text Available Oxidative stress is both the cause and consequence of impaired functional homeostasis characterizing human aging. The worsening efficiency of stress response with age represents a health risk and leads to the onset and accrual of major age-related diseases. In contrast, centenarians seem to have evolved conservative stress response mechanisms, probably derived from a combination of a diet rich in natural antioxidants, an active lifestyle and a favorable genetic background, particularly rich in genetic variants able to counteract the stress overload at the level of both nuclear and mitochondrial DNA. The integration of these factors could allow centenarians to maintain moderate levels of free radicals that exert beneficial signaling and modulator effects on cellular metabolism. Considering the hot debate on the efficacy of antioxidant supplementation in promoting healthy aging, in this review we gathered the existing information regarding genetic variability and lifestyle factors which potentially modulate the stress response at old age. Evidence reported here suggests that the integration of lifestyle factors (moderate physical activity and healthy nutrition and genetic background could shift the balance in favor of the antioxidant cellular machinery by activating appropriate defense mechanisms in response to exceeding external and internal stress levels, and thus possibly achieving the prospect of living a longer life.

  8. Classical genetic analyses of responses to nicotine and ethanol in crosses derived from long- and short-sleep mice.

    Science.gov (United States)

    de Fiebre, C M; Collins, A C

    1992-04-01

    A classical (Mendelian) genetic analysis of responses to ethanol and nicotine was conducted in crosses derived from mouse lines which were selectively bred for differential duration of loss of the righting response (sleep-time) after ethanol. Dose-response curves for these mice, the long- and short-sleep mouse lines, as well as the derived F1, F2 and backcross (F1 x long-sleep and F1 x short-sleep) generations were generated for several measures of nicotine and ethanol sensitivity. Ethanol sensitivity was assessed using the sleep-time measure. Nicotine sensitivity was tested using a battery of behavioral and physiological tests which included measures of seizure activity, respiration rate, acoustic startle response, Y-maze activities (both crossing and rearing activities), heart rate and body temperature. The inheritance of sensitivities to both of these agents appears to be polygenic and inheritance can be explained primarily by additive genetic effects with some epistasis. Sensitivity to the ethanol sleep-time measure was genetically correlated with sensitivity to both nicotine-induced hypothermia and seizures; the correlation was greater between sleep-time and hypothermia. These data indicate that there is overlap in the genetic regulation of sensitivity to both ethanol and nicotine as measured by some, but not all, tests.

  9. Numerical thermal analysis and optimization of multi-chip LED module using response surface methodology and genetic algorithm

    NARCIS (Netherlands)

    Tang, Hong Yu; Ye, Huai Yu; Chen, Xian Ping; Qian, Cheng; Fan, Xue Jun; Zhang, G.Q.

    2017-01-01

    In this paper, the heat transfer performance of the multi-chip (MC) LED module is investigated numerically by using a general analytical solution. The configuration of the module is optimized with genetic algorithm (GA) combined with a response surface methodology. The space between chips, the

  10. Temporal genetic stability in natural populations of the waterflea Daphnia magna in response to strong selection pressure.

    Science.gov (United States)

    Orsini, Luisa; Marshall, Hollie; Cuenca Cambronero, Maria; Chaturvedi, Anurag; Thomas, Kelley W; Pfrender, Michael E; Spanier, Katina I; De Meester, Luc

    2016-12-01

    Studies monitoring changes in genetic diversity and composition through time allow a unique understanding of evolutionary dynamics and persistence of natural populations. However, such studies are often limited to species with short generation times that can be propagated in the laboratory or few exceptional cases in the wild. Species that produce dormant stages provide powerful models for the reconstruction of evolutionary dynamics in the natural environment. A remaining open question is to what extent dormant egg banks are an unbiased representation of populations and hence of the species' evolutionary potential, especially in the presence of strong environmental selection. We address this key question using the water flea Daphnia magna, which produces dormant stages that accumulate in biological archives over time. We assess temporal genetic stability in three biological archives, previously used in resurrection ecology studies showing adaptive evolutionary responses to rapid environmental change. We show that neutral genetic diversity does not decline with the age of the population and it is maintained in the presence of strong selection. In addition, by comparing temporal genetic stability in hatched and unhatched populations from the same biological archive, we show that dormant egg banks can be consulted to obtain a reliable measure of genetic diversity over time, at least in the multidecadal time frame studied here. The stability of neutral genetic diversity through time is likely mediated by the buffering effect of the resting egg bank. © 2016 John Wiley & Sons Ltd.

  11. Response properties of the genetically encoded optical H2O2 sensor HyPer.

    Science.gov (United States)

    Weller, Jonathan; Kizina, Kathrin M; Can, Karolina; Bao, Guobin; Müller, Michael

    2014-11-01

    Reactive oxygen species mediate cellular signaling and neuropathologies. Hence, there is tremendous interest in monitoring (sub)cellular redox conditions. We evaluated the genetically engineered redox sensor HyPer in mouse hippocampal cell cultures. Two days after lipofection, neurons and glia showed sufficient expression levels, and H2O2 reversibly and dose-dependently increased the fluorescence ratio of cytosolic HyPer. Yet, repeated H2O2 treatment caused progressively declining responses, and with millimolar doses an apparent recovery started while H2O2 was still present. Although HyPer should be H2O2 specific, it seemingly responded also to other oxidants and altered cell-endogenous superoxide production. Control experiments with the SypHer pH sensor confirmed that the HyPer ratio responds to pH changes, decreasing with acidosis and increasing during alkalosis. Anoxia/reoxygenation evoked biphasic HyPer responses reporting apparent reduction/oxidation; replacing Cl(-) exerted only negligible effects. Mitochondria-targeted HyPer readily responded to H2O2-albeit less intensely than cytosolic HyPer. With ratiometric two-photon excitation, H2O2 increased the cytosolic HyPer ratio. Time-correlated fluorescence-lifetime imaging microscopy (FLIM) revealed a monoexponential decay of HyPer fluorescence, and H2O2 decreased fluorescence lifetimes. Dithiothreitol failed to further reduce HyPer or to induce reasonable FLIM and two-photon responses. By enabling dynamic recordings, HyPer is superior to synthetic redox-sensitive dyes. Its feasibility for two-photon excitation also enables studies in more complex preparations. Based on FLIM, quantitative analyses might be possible independent of switching excitation wavelengths. Yet, because of its pronounced pH sensitivity, adaptation to repeated oxidation, and insensitivity to reducing stimuli, HyPer responses have to be interpreted carefully. For reliable data, side-by-side pH monitoring with SypHer is essential. Copyright

  12. Genetic and physiological responses of three freshwater diatoms to realistic diuron exposures.

    Science.gov (United States)

    Moisset, S; Kim Tiam, S; Feurtet-Mazel, A; Morin, S; Delmas, F; Mazzella, N; Gonzalez, P

    2015-03-01

    This study examined the effects of diuron on strains of three major freshwater diatom species, Eolimna minima, Nitzschia palea and Planothidium lanceolatum. These species are frequently recorded in the Morcille River, where diuron runs off during phytosanitary treatments of the vineyards around. Here, there were three diatom exposure groups for each species: 0, 1 and 10 μg/L diuron during a 14-day laboratory assessment. Diuron water concentration, cell number, photosynthetic activity and gene expression were assessed at 6 h and 2, 7 and 14 days after contamination. Diuron exposure altered photosynthetic activity in that the optimal quantum yield of photosystem II (PSII) decreased between 40 and 50% and, for P. lanceolatum at 10 μg/L, there was complete inhibition. Genetic responses indicated diuron effects on both photosystem II and mitochondrial metabolism in all three species at both diuron exposure levels. Thus, analysis of the expression of psaA, d1, cox1, nad5 and 12s could be an early biomarker to detect pesticide pollution. Overall, this study revealed differences in diuron sensitivity among the three species: E. minima and N. palea appeared to be more tolerant than P. lanceolatum. These results suggest that the development of molecular tools, and more precisely of biomarkers, will aid in early assessment of contamination and water quality.

  13. Genetic evidence for the association between the early growth response 3 (EGR3 gene and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Rui Zhang

    Full Text Available Recently, two genome scan meta-analysis studies have found strong evidence for the association of loci on chromosome 8p with schizophrenia. The early growth response 3 (EGR3 gene located in chromosome 8p21.3 was also found to be involved in the etiology of schizophrenia. However, subsequent studies failed to replicate this finding. To investigate the genetic role of EGR3 in Chinese patients, we genotyped four SNPs (average interval ∼2.3 kb in the chromosome region of EGR3 in 470 Chinese schizophrenia patients and 480 healthy control subjects. The SNP rs35201266 (located in intron 1 of EGR3 showed significant differences between cases and controls in both genotype frequency distribution (P = 0.016 and allele frequency distribution (P = 0.009. Analysis of the haplotype rs35201266-rs3750192 provided significant evidence for association with schizophrenia (P = 0.0012; a significant difference was found for the common haplotype AG (P = 0.0005. Furthermore, significant associations were also found in several other two-, and three-SNP tests of haplotype analyses. The meta-analysis revealed a statistically significant association between rs35201266 and schizophrenia (P = 0.0001. In summary, our study supports the association of EGR3 with schizophrenia in our Han Chinese sample, and further functional exploration of the EGR3 gene will contribute to the molecular basis for the complex network underlying schizophrenia pathogenesis.

  14. Genetically encoded ratiometric fluorescent thermometer with wide range and rapid response.

    Directory of Open Access Journals (Sweden)

    Masahiro Nakano

    Full Text Available Temperature is a fundamental physical parameter that plays an important role in biological reactions and events. Although thermometers developed previously have been used to investigate several important phenomena, such as heterogeneous temperature distribution in a single living cell and heat generation in mitochondria, the development of a thermometer with a sensitivity over a wide temperature range and rapid response is still desired to quantify temperature change in not only homeotherms but also poikilotherms from the cellular level to in vivo. To overcome the weaknesses of the conventional thermometers, such as a limitation of applicable species and a low temporal resolution, owing to the narrow temperature range of sensitivity and the thermometry method, respectively, we developed a genetically encoded ratiometric fluorescent temperature indicator, gTEMP, by using two fluorescent proteins with different temperature sensitivities. Our thermometric method enabled a fast tracking of the temperature change with a time resolution of 50 ms. We used this method to observe the spatiotemporal temperature change between the cytoplasm and nucleus in cells, and quantified thermogenesis from the mitochondria matrix in a single living cell after stimulation with carbonyl cyanide 4-(trifluoromethoxyphenylhydrazone, which was an uncoupler of oxidative phosphorylation. Moreover, exploiting the wide temperature range of sensitivity from 5°C to 50°C of gTEMP, we monitored the temperature in a living medaka embryo for 15 hours and showed the feasibility of in vivo thermometry in various living species.

  15. Genetic dissection of host immune response in pneumonia development and progression.

    Science.gov (United States)

    Smelaya, Tamara V; Belopolskaya, Olesya B; Smirnova, Svetlana V; Kuzovlev, Artem N; Moroz, Viktor V; Golubev, Arkadiy M; Pabalan, Noel A; Salnikova, Lyubov E

    2016-10-11

    The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls). Experimental data were included in a series of 11 meta-analyses and eight subset analyses related to pneumonia susceptibility and outcome. TLR2 rs5743708 minor genotype appeared to be associated with CAP/Legionnaires' disease/pneumococcal disease. In CAP patients, the IL6 rs1800795-C allele was associated with severe sepsis/septic shock/severe systemic inflammatory response, while the IL10 rs1800896-A allele protected against the development of these critical conditions. To contribute to deciphering of the above results, we performed an in silico analysis and a qualitative synthesis of literature data addressing basal and stimulated genotype-specific expression level. This data together with database information on transcription factors' affinity changes caused by SNPs in putative promoter regions, the results of linkage disequilibrium analysis along with SNPs functional annotations supported assumptions about the complexity underlying the revealed associations.

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

    Directory of Open Access Journals (Sweden)

    Masa Tsuchiya

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

  17. Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D-Related Genetic Variants.

    Science.gov (United States)

    Moon, Rebecca J; Harvey, Nicholas C; Cooper, Cyrus; D'Angelo, Stefania; Curtis, Elizabeth M; Crozier, Sarah R; Barton, Sheila J; Robinson, Sian M; Godfrey, Keith M; Graham, Nikki J; Holloway, John W; Bishop, Nicholas J; Kennedy, Stephen; Papageorghiou, Aris T; Schoenmakers, Inez; Fraser, Robert; Gandhi, Saurabh V; Prentice, Ann; Inskip, Hazel M; Javaid, M Kassim

    2017-08-01

    Single-nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation. To determine whether SNPs in DHCR7, CYP2R1, CYP24A1, and GC are associated with the response to gestational cholecalciferol supplementation. Within-randomization group analysis of the Maternal Vitamin D Osteoporosis Study trial of antenatal cholecalciferol supplementation. Hospital antenatal clinics. In total, 682 women of white ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped. 1000 IU/d cholecalciferol from 14 weeks of gestation until delivery. 25(OH)D at randomization and 34 weeks of gestation were measured in a single batch (Liaison; Diasorin, Dartford, UK). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model [β represents the change in 25(OH)D per additional common allele]. Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [β = 3.1 nmol/L; 95% confidence interval (CI), 1.0 to 5.2 nmol/L; P D status following supplementation, whereas rs12785878 and rs6013897 (CYP24A1) were not. Genetic variation in DHCR7, which encodes 7-dehyrocholesterol reductase in the epidermal vitamin D biosynthesis pathway, appears to modify baseline 25(OH)D. In contrast, the response to antenatal cholecalciferol supplementation was associated with SNPs in CYP2R1, which may alter 25-hydroxylase activity, and GC, which may affect vitamin D binding protein synthesis or metabolite affinity. Copyright © 2017 Endocrine Society

  18. Response to A Different Vantage Point Commentary: Psychotherapeutic Genetic Counseling, Is it?

    Science.gov (United States)

    Biesecker, Barbara; Austin, Jehannine; Caleshu, Colleen

    2017-04-01

    Whether genetic counseling is a form of psychotherapy is open for debate. Early practicioners in genetic counseling described it as such, and this claim has been replicated in recent publications. This commentary is a rebuttal to the claim that genetic counseling is distinct from psychotherapty. We argue that it is a a form of psychoterapy that aims to help clients manage a health threat that affects their psychological wellbeing, paralleling the goals of psychotherapy.

  19. Response to A Different Vantage Point Commentary: Psychotherapeutic Genetic Counseling, Is it?

    Science.gov (United States)

    Austin, Jehannine; Caleshu, Colleen

    2016-01-01

    Whether genetic counseling is a form of psychotherapy is open for debate. Early practicioners in genetic counseling described it as such, and this claim has been replicated in recent publications. This commentary is a rebuttal to the claim that genetic counseling is distinct from psychotherapty. We argue that it is a a form of psychoterapy that aims to help clients manage a health threat that affects their psychological wellbeing, paralleling the goals of psychotherapy. PMID:27804046

  20. Analyses between Reproductive Behavior, Genetic Diversity and Pythium Responsiveness in Zingiber spp. Reveal an Adaptive Significance for Hemiclonality

    Science.gov (United States)

    Thomas, Geethu E.; Geetha, Kiran A.; Augustine, Lesly; Mamiyil, Sabu; Thomas, George

    2016-01-01

    Mode of reproduction is generally considered to have long-range evolutionary implications on population survival. Because sexual reproduction produces genetically diverse genotypes, this mode of reproduction is predicted to positively influence the success potential of offspring in evolutionary arms race with parasites (Red queen) whereas, without segregation and recombination, the obligate asexual multiplication may push a species into extinction due to the steady accumulation of deleterious mutations (Muller’s ratchet). However, the extent of linearity between reproductive strategies, genetic diversity and population fitness, and the contributions of different breeding strategies to population fitness are yet to be understood clearly. Genus Zingiber belonging to the pan-tropic family Zingiberaceae represents a good system to study contributions of different breeding behavior on genetic diversity and population fitness, as this genus comprises species with contrasting breeding systems. In this study, we analyzed breeding behavior, amplified fragment length polymorphism diversity and response to the soft-rot pathogen Pythium aphanidermatum in 18 natural populations of three wild Zingiber spp.: Z. neesanum, Z. nimmonii, and Z. zerumbet, together with the obligately asexual cultivated congener, ginger (Z. officinale). Ginger showed an exceptionally narrow genetic base, and adding to this, all the tested cultivars were uniformly susceptible to soft-rot. Concordant with the postulates of Muller’s ratchet, the background selection may be continuously pushing ginger into the ancestral state, rendering it inefficient in host-pathogen coevolution. Z. neesanum and Z. nimmonii populations were sexual and genetically diverse; however, contrary to Red Queen expectations, the populations were highly susceptible to soft-rot. Z. zerumbet showed a hemiclonal breeding behavior. The populations inhabiting forest understory were large and continuous, sexual and genetically

  1. Direct-to-consumer genetic testing: perceptions, problems, and policy responses.

    Science.gov (United States)

    Caulfield, Timothy; McGuire, Amy L

    2012-01-01

    Direct-to-consumer (DTC) genetic testing has attracted a great amount of attention from policy makers, the scientific community, professional groups, and the media. Although it is unclear what the public demand is for these services, there does appear to be public interest in personal genetic risk information. As a result, many commentators have raised a variety of social, ethical, and regulatory issues associated with this emerging industry, including privacy issues, ensuring that DTC companies provide accurate information about the risks and limitations of their services, the possible adverse impact of DTC genetic testing on healthcare systems, and concern about how individuals may interpret and react to genetic risk information.

  2. Genetic and Computational Approaches for Studying Plant Development and Abiotic Stress Responses Using Image-Based Phenotyping

    Science.gov (United States)

    Campbell, M. T.; Walia, H.; Grondin, A.; Knecht, A.

    2017-12-01

    The development of abiotic stress tolerant crops (i.e. drought, salinity, or heat stress) requires the discovery of DNA sequence variants associated with stress tolerance-related traits. However, many traits underlying adaptation to abiotic stress involve a suite of physiological pathways that may be induced at different times throughout the duration of stress. Conventional single-point phenotyping approaches fail to fully capture these temporal responses, and thus downstream genetic analysis may only identify a subset of the genetic variants that are important for adaptation to sub-optimal environments. Although genomic resources for crops have advanced tremendously, the collection of phenotypic data for morphological and physiological traits is laborious and remains a significant bottleneck in bridging the phenotype-genotype gap. In recent years, the availability of automated, image-based phenotyping platforms has provided researchers with an opportunity to collect morphological and physiological traits non-destructively in a highly controlled environment. Moreover, these platforms allow abiotic stress responses to be recorded throughout the duration of the experiment, and have facilitated the use of function-valued traits for genetic analyses in major crops. We will present our approaches for addressing abiotic stress tolerance in cereals. This talk will focus on novel open-source software to process and extract biological meaningful data from images generated from these phenomics platforms. In addition, we will discuss the statistical approaches to model longitudinal phenotypes and dissect the genetic basis of dynamic responses to these abiotic stresses throughout development.

  3. Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

    Science.gov (United States)

    Arloth, Janine; Bogdan, Ryan; Weber, Peter; Frishman, Goar; Menke, Andreas; Wagner, Klaus V.; Balsevich, Georgia; Schmidt, Mathias V.; Karbalai, Nazanin; Czamara, Darina; Altmann, Andre; Trümbach, Dietrich; Wurst, Wolfgang; Mehta, Divya; Uhr, Manfred; Klengel, Torsten; Erhardt, Angelika; Carey, Caitlin E.; Conley, Emily Drabant; Ripke, Stephan; Wray, Naomi R.; Lewis, Cathryn M.; Hamilton, Steven P.; Weissman, Myrna M.; Breen, Gerome; Byrne, Enda M.; Blackwood, Douglas H.R.; Boomsma, Dorret I.; Cichon, Sven; Heath, Andrew C.; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A.F.; Martin, Nicholas G.; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M.; Penninx, Brenda P.; Pergadia, Michele L.; Potash, James B.; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J.; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H.; Preisig, Martin; Smoller, Jordan W.; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E.; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R.; Bettecken, Thomas; Binder, Elisabeth B.; Breuer, René; Castro, Victor M.; Churchill, Susanne E.; Coryell, William H.; Craddock, Nick; Craig, Ian W.; Czamara, Darina; De Geus, Eco J.; Degenhardt, Franziska; Farmer, Anne E.; Fava, Maurizio; Frank, Josef; Gainer, Vivian S.; Gallagher, Patience J.; Gordon, Scott D.; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V.; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A.; Kohane, Isaac S.; Kohli, Martin A.; Korszun, Ania; Landen, Mikael; Lawson, William B.; Lewis, Glyn; MacIntyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Middleton, Lefkos; Montgomery, Grant M.; Murphy, Shawn N.; Nauck, Matthias; Nolen, Willem A.; Nyholt, Dale R.; O’Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A.; Schulz, Andrea; Schulze, Thomas G.; Shyn, Stanley I.; Sigurdsson, Engilbert; Slager, Susan L.; Smit, Johannes H.; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J.C.G.; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B.; Willemsen, Gonneke; Zitman, Frans G.; Neale, Benjamin; Daly, Mark; Levinson, Douglas F.; Sullivan, Patrick F.; Ruepp, Andreas; Müller-Myhsok, Bertram; Hariri, Ahmad R.; Binder, Elisabeth B.

    2015-01-01

    Summary Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain. Video Abstract PMID:26050039

  4. Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)

    Science.gov (United States)

    The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variants through a...

  5. Genetic correlations between behavioural responses and performance traits in laying hens

    Directory of Open Access Journals (Sweden)

    Iwona Rozempolska-Rucińska

    2017-12-01

    Full Text Available Objective The aim of the study was to evaluate genetic correlations between the behavioural profile and performance in laying hens as an indirect answer to the question whether the observed behavioural responses are associated with increased levels of stress in these birds. Methods The assessment of birds’ temperament was carried out using the novel objects test. The behavioural test was conducted in two successive generations comprising 9,483 Rhode Island White (RIW birds (approx. 4,700 individuals per generation and 4,326 Rhode Island Red (RIR birds (approx. 2,100 individuals per generation. Based on the recorded responses, the birds were divided into two groups: a fearful profile (1,418 RIW hens and 580 RIR hens and a brave/curious profile (8,065 RIW hens and 3,746 RIR hens. The birds were subjected to standard assessment of their performance traits, including SM, age at sexual maturity; ST, shell thickness; SG, egg specific gravity; EW, mean egg weight; IP, initial egg production; and HC, number of hatched chicks. The pedigree was three generations deep (including two behaviour-recorded generations. Estimation of the (covariance components was performed with the Gibbs sampling method, which accounts for the discrete character of the behavioural profile denotation. Results The analyses revealed negative correlations between the performance traits of the laying hens and the behavioural profile defined as fearful. In the group of fearful RIW birds, delayed sexual maturation (0.22 as well as a decrease in the initial egg production (−0.30, egg weight (−0.54, egg specific gravity (−0.331, shell thickness (−0.11, and the number of hatched chicks (−0.24 could be expected. These correlations were less pronounced in the RIR breed, in which the fearful birds exhibited a decline in hatchability (−0.37, egg specific gravity (−0.11, and the number of hatched chicks (−0.18. There were no correlations in the case of the other traits or

  6. GENetic and clinical Predictors Of treatment response in Depression: the GenPod randomised trial protocol

    Directory of Open Access Journals (Sweden)

    O'Donovan Michael

    2008-05-01

    Full Text Available Abstract Background The most effective pharmacological treatments for depression inhibit the transporters that reuptake serotonin (Selective Serotonin Reuptake Inhibitors – SSRIs and noradrenaline (Noradrenaline Reuptake Inhibitors – NaRIs into the presynaptic terminal. There is evidence to suggest that noradrenaline and serotonin enhancing drugs work through separate mechanisms to produce their clinical antidepressant action. Although most of the current evidence suggests there is little difference in overall efficacy between SSRIs and NaRIs, there are patients who respond to one class of compounds and not another. This suggests that treatment response could be predicted by genetic and/or clinical characteristics. Firstly, this study aims to investigate the influence of a polymorphism (SLC6A4 in the 5HT transporter in altering response to SSRI medication. Secondly, the study will investigate whether those with more severe depression have a better response to NaRIs than SSRIs. Methods/design The GenPod trial is a multi-centre randomised controlled trial. GPs referred patients aged between 18–74 years presenting with a new episode of depression, who did not have any medical contraindications to antidepressant medication and who had no history of psychosis or alcohol/substance abuse. Patients were interviewed to ascertain their suitability for the study. Eligible participants (with a primary diagnosis of depression according to ICD10 criteria and a Beck Depression Inventory (BDI score > 14 were randomised to receive one of two antidepressant treatments, either the SSRI Citalopram or the NaRI Reboxetine, stratified according to severity. The final number randomised to the trial was 601. Follow-up assessments took place at 2, 6 and 12 weeks following randomisation. Primary outcome was measured at 6 weeks by the BDI. Outcomes will be analysed on an intention-to-treat basis and will use multiple regression models to compare treatments

  7. Responsible genetic approach to stock restoration, sea ranching and stock enhancement of marine fishes and invertebrates

    DEFF Research Database (Denmark)

    Grant, W. Stewart; Jasper, James; Bekkevold, Dorte

    2017-01-01

    of marine fishes and invertebrates have been implemented with various outcomes. A review of the literature indicates that considerable effort has been directed toward culture technologies to maximize production, but scant attention has been given to genetic risks to wild populations. Genetic risks from...

  8. Genetic information: Special or not? Responses from focus groups with members of a health maintenance organization.

    Science.gov (United States)

    Diergaarde, Brenda; Bowen, Deborah J; Ludman, Evette J; Culver, Julie O; Press, Nancy; Burke, Wylie

    2007-03-15

    Genetic information is used increasingly in health care. Some experts have argued that genetic information is qualitatively different from other medical information and, therefore, raises unique social issues. This view, called "genetic exceptionalism," has importantly influenced recent policy efforts. Others have argued that genetic information is like other medical information and that treating it differently may actually result in unintended disparities. Little is known about how the general public views genetic information. To identify opinions about implications of genetic and other medical information among the general population, we conducted a series of focus groups in Seattle, WA. Participants were women and men between ages 18 and 74, living within 30 miles of Seattle and members of the Group Health Cooperative. A structured discussion guide was used to ensure coverage of all predetermined topics. Sessions lasted approximately 2 hr; were audio taped and transcribed. The transcripts formed the basis of the current analysis. Key findings included the theme that genetic information was much like other medical information and that all sensitive medical information should be well protected. Personal choice (i.e., the right to choose whether to know health risk information and to control who else knows) was reported to be of crucial importance. Participants had an understanding of the tensions involved in protecting privacy versus sharing medical information to help another person. These data may guide future research and policy concerning the use and protection of medical information, including genetic information. (c) 2007 Wiley-Liss, Inc.

  9. Prediction of breeding values and selection responses with genetic heterogeneity of environmental variance

    NARCIS (Netherlands)

    Mulder, H.A.; Bijma, P.; Hill, W.G.

    2007-01-01

    There is empirical evidence that genotypes differ not only in mean, but also in environmental variance of the traits they affect. Genetic heterogeneity of environmental variance may indicate genetic differences in environmental sensitivity. The aim of this study was to develop a general framework

  10. Parallel responses of species and genetic diversity to El Nino Southern Oscillation-induced environmental destruction

    NARCIS (Netherlands)

    Cleary, D.F.R.; Fauvelot, C.Y.; Genner, J.; Menken, S.B.J.; Mooers, A.O.

    2006-01-01

    Species diversity within communities and genetic diversity within species are two fundamental levels of biodiversity. Positive relationships between species richness and within-species genetic diversity have recently been documented across natural and semi-natural habitat islands, leading Vellend to

  11. The effects of stress and sex on selection, genetic covariance, and the evolutionary response.

    Science.gov (United States)

    Holman, L; Jacomb, F

    2017-10-01

    The capacity of a population to adapt to selection (evolvability) depends on whether the structure of genetic variation permits the evolution of fitter trait combinations. Selection, genetic variance and genetic covariance can change under environmental stress, and males and females are not genetically independent, yet the combined effects of stress and dioecy on evolvability are not well understood. Here, we estimate selection, genetic (co)variance and evolvability in both sexes of Tribolium castaneum flour beetles under stressful and benign conditions, using a half-sib breeding design. Although stress uncovered substantial latent heritability, stress also affected genetic covariance, such that evolvability remained low under stress. Sexual selection on males and natural selection on females favoured a similar phenotype, and there was positive intersex genetic covariance. Consequently, sexual selection on males augmented adaptation in females, and intralocus sexual conflict was weak or absent. This study highlights that increased heritability does not necessarily increase evolvability, suggests that selection can deplete genetic variance for multivariate trait combinations with strong effects on fitness, and tests the recent hypothesis that sexual conflict is weaker in stressful or novel environments. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  12. Genetic moderation of the association between regulatory focus and reward responsiveness: a proof-of-concept study.

    Science.gov (United States)

    Goetz, Elena L; Hariri, Ahmad R; Pizzagalli, Diego A; Strauman, Timothy J

    2013-02-01

    Recent studies implicate individual differences in regulatory focus as contributing to self-regulatory dysfunction, particularly not responding to positive outcomes. How such individual differences emerge, however, is unclear. We conducted a proof-of-concept study to examine the moderating effects of genetically driven variation in dopamine signaling, a key modulator of neural reward circuits, on the association between regulatory focus and reward cue responsiveness. Healthy Caucasians (N=59) completed a measure of chronic regulatory focus and a probabilistic reward task. A common functional genetic polymorphism impacting prefrontal dopamine signaling (COMT rs4680) was evaluated. Response bias, the participants' propensity to modulate behavior as a function of reward, was predicted by an interaction of regulatory focus and COMT genotype. Specifically, self-perceived success at achieving promotion goals predicted total response bias, but only for individuals with the COMT genotype (Val/Val) associated with relatively increased phasic dopamine signaling and cognitive flexibility. The combination of success in promotion goal pursuit and Val/Val genotype appears to facilitate responding to reward opportunities in the environment. This study is among the first to integrate an assessment of self-regulatory style with an examination of genetic variability that underlies responsiveness to positive outcomes in goal pursuit.

  13. A Case Study on Maximizing Aqua Feed Pellet Properties Using Response Surface Methodology and Genetic Algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Tumuluru, Jaya

    2013-01-10

    Aims: The present case study is on maximizing the aqua feed properties using response surface methodology and genetic algorithm. Study Design: Effect of extrusion process variables like screw speed, L/D ratio, barrel temperature, and feed moisture content were analyzed to maximize the aqua feed properties like water stability, true density, and expansion ratio. Place and Duration of Study: This study was carried out in the Department of Agricultural and Food Engineering, Indian Institute of Technology, Kharagpur, India. Methodology: A variable length single screw extruder was used in the study. The process variables selected were screw speed (rpm), length-to-diameter (L/D) ratio, barrel temperature (degrees C), and feed moisture content (%). The pelletized aqua feed was analyzed for physical properties like water stability (WS), true density (TD), and expansion ratio (ER). Extrusion experimental data was collected by based on central composite design. The experimental data was further analyzed using response surface methodology (RSM) and genetic algorithm (GA) for maximizing feed properties. Results: Regression equations developed for the experimental data has adequately described the effect of process variables on the physical properties with coefficient of determination values (R2) of > 0.95. RSM analysis indicated WS, ER, and TD were maximized at L/D ratio of 12-13, screw speed of 60-80 rpm, feed moisture content of 30-40%, and barrel temperature of = 80 degrees C for ER and TD and > 90 degrees C for WS. Based on GA analysis, a maxium WS of 98.10% was predicted at a screw speed of 96.71 rpm, L/D radio of 13.67, barrel temperature of 96.26 degrees C, and feed moisture content of 33.55%. Maximum ER and TD of 0.99 and 1346.9 kg/m3 was also predicted at screw speed of 60.37 and 90.24 rpm, L/D ratio of 12.18 and 13.52, barrel temperature of 68.50 and 64.88 degrees C, and medium feed moisture content of 33.61 and 38.36%. Conclusion: The present data analysis indicated

  14. Importin-13 genetic variation is associated with improved airway responsiveness in childhood asthma

    Directory of Open Access Journals (Sweden)

    Lasky-Su Jessica

    2009-07-01

    Full Text Available Abstract Background Glucocorticoid function is dependent on efficient translocation of the glucocorticoid receptor (GR from the cytoplasm to the nucleus of cells. Importin-13 (IPO13 is a nuclear transport receptor that mediates nuclear entry of GR. In airway epithelial cells, inhibition of IPO13 expression prevents nuclear entry of GR and abrogates anti-inflammatory effects of glucocorticoids. Impaired nuclear entry of GR has been documented in steroid-non-responsive asthmatics. We hypothesize that common IPO13 genetic variation influences the anti-inflammatory effects of inhaled corticosteroids for the treatment of asthma, as measured by change in methacholine airway hyperresponsiveness (AHR-PC20. Methods 10 polymorphisms were evaluated in 654 children with mild-to-moderate asthma participating in the Childhood Asthma Management Program (CAMP, a clinical trial of inhaled anti-inflammatory medications (budesonide and nedocromil. Population-based association tests with repeated measures of PC20 were performed using mixed models and confirmed using family-based tests of association. Results Among participants randomized to placebo or nedocromil, IPO13 polymorphisms were associated with improved PC20 (i.e. less AHR, with subjects harboring minor alleles demonstrating an average 1.51–2.17 fold increase in mean PC20 at 8-months post-randomization that persisted over four years of observation (p = 0.01–0.005. This improvement was similar to that among children treated with long-term inhaled corticosteroids. There was no additional improvement in PC20 by IPO13 variants among children treated with inhaled corticosteroids. Conclusion IPO13 variation is associated with improved AHR in asthmatic children. The degree of this improvement is similar to that observed with long-term inhaled corticosteroid treatment, suggesting that IPO13 variation may improve nuclear bioavailability of endogenous glucocorticoids.

  15. Environmental and genetic preconditioning for long-term anoxia responses requires AMPK in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Bobby L LaRue

    2011-02-01

    Full Text Available Preconditioning environments or therapeutics, to suppress the cellular damage associated with severe oxygen deprivation, is of interest to our understanding of diseases associated with oxygen deprivation. Wildtype C. elegans exposed to anoxia enter into a state of suspended animation in which energy-requiring processes reversibly arrest. C. elegans at all developmental stages survive 24-hours of anoxia exposure however, the ability of adult hermaphrodites to survive three days of anoxia significantly decreases. Mutations in the insulin-like signaling receptor (daf-2 and LIN-12/Notch (glp-1 lead to an enhanced long-term anoxia survival phenotype.In this study we show that the combined growth environment of 25°C and a diet of HT115 E. coli will precondition adult hermaphrodites to survive long-term anoxia; many of these survivors have normal movement after anoxia treatment. Animals fed the drug metformin, which induces a dietary-restriction like state in animals and activates AMPK in mammalian cell culture, have a higher survival rate when exposed to long-term anoxia. Mutations in genes encoding components of AMPK (aak-2, aakb-1, aakb-2, aakg-2 suppress the environmentally and genetically induced long-term anoxia survival phenotype. We further determine that there is a correlation between the animals that survive long-term anoxia and increased levels of carminic acid staining, which is a fluorescent dye that incorporates in with carbohydrates such as glycogen.We conclude that small changes in growth conditions such as increased temperature and food source can influence the physiology of the animal thus affecting the responses to stress such as anoxia. Furthermore, this supports the idea that metformin should be further investigated as a therapeutic tool for treatment of oxygen-deprived tissues. Finally, the capacity for an animal to survive long bouts of severe oxygen deprivation is likely dependent on specific subunits of the heterotrimeric

  16. Genetic dissection of the Arabidopsis spaceflight transcriptome: Are some responses dispensable for the physiological adaptation of plants to spaceflight?

    Directory of Open Access Journals (Sweden)

    Anna-Lisa Paul

    Full Text Available Experimentation on the International Space Station has reached the stage where repeated and nuanced transcriptome studies are beginning to illuminate the structural and metabolic differences between plants grown in space compared to plants on the Earth. Genes that are important in establishing the spaceflight responses are being identified, their roles in spaceflight physiological adaptation are increasingly understood, and the fact that different genotypes adapt differently is recognized. However, the basic question of whether these spaceflight responses are actually required for survival has yet to be posed, and the fundamental notion that spaceflight responses may be non-adaptive has yet to be explored. Therefore the experiments presented here were designed to ask if portions of the plant spaceflight response can be genetically removed without causing loss of spaceflight survival and without causing increased stress responses. The CARA experiment compared the spaceflight transcriptome responses in the root tips of two Arabidopsis ecotypes, Col-0 and WS, as well as that of a PhyD mutant of Col-0. When grown with the ambient light of the ISS, phyD plants displayed a significantly reduced spaceflight transcriptome response compared to Col-0, suggesting that altering the activity of a single gene can actually improve spaceflight adaptation by reducing the transcriptome cost of physiological adaptation. The WS genotype showed an even simpler spaceflight transcriptome response in the ambient light of the ISS, more broadly indicating that the plant genotype can be manipulated to reduce the cost of spaceflight adaptation, as measured by transcriptional response. These differential genotypic responses suggest that genetic manipulation could further reduce, or perhaps eliminate the metabolic cost of spaceflight adaptation. When plants were germinated and then left in the dark on the ISS, the WS genotype actually mounted a larger transcriptome response

  17. Methylphenidate and Atomoxetine-Responsive Prefrontal Cortical Genetic Overlaps in "Impulsive" SHR/NCrl and Wistar Rats.

    Science.gov (United States)

    Dela Peña, Ike; Dela Peña, Irene Joy; de la Peña, June Bryan; Kim, Hee Jin; Shin, Chan Young; Han, Doug Hyun; Kim, Bung-Nyun; Ryu, Jong Hoon; Cheong, Jae Hoon

    2017-09-01

    Impulsivity, the predisposition to act prematurely without foresight, is associated with a number of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). Identifying genetic underpinnings of impulsive behavior may help decipher the complex etiology and neurobiological factors of disorders marked by impulsivity. To identify potential genetic factors of impulsivity, we examined common differentially expressed genes (DEGs) in the prefrontal cortex (PFC) of adolescent SHR/NCrl and Wistar rats, which showed marked decrease in preference for the large but delayed reward, compared with WKY/NCrl rats, in the delay discounting task. Of these DEGs, we examined drug-responsive transcripts whose mRNA levels were altered following treatment (in SHR/NCrl and Wistar rats) with drugs that alleviate impulsivity, namely, the ADHD medications methylphenidate and atomoxetine. Prefrontal cortical genetic overlaps between SHR/NCrl and Wistar rats in comparison with WKY/NCrl included genes associated with transcription (e.g., Btg2, Fos, Nr4a2), synaptic plasticity (e.g., Arc, Homer2), and neuron apoptosis (Grik2, Nmnat1). Treatment with methylphenidate and/or atomoxetine increased choice of the large, delayed reward in SHR/NCrl and Wistar rats and changed, in varying degrees, mRNA levels of Nr4a2, Btg2, and Homer2, genes with previously described roles in neuropsychiatric disorders characterized by impulsivity. While further studies are required, we dissected potential genetic factors that may influence impulsivity by identifying genetic overlaps in the PFC of "impulsive" SHR/NCrl and Wistar rats. Notably, these are also drug-responsive transcripts which may be studied further as biomarkers to predict response to ADHD drugs, and as potential targets for the development of treatments to improve impulsivity.

  18. In Vitro Studies on Space Radiation-Induced Delayed Genetic Responses: Shielding Effects

    Science.gov (United States)

    Kadhim, Munira A.; Green, Lora M.; Gridley, Daila S.; Murray, Deborah K.; Tran, Da Thao; Andres, Melba; Pocock, Debbie; Macdonald, Denise; Goodhead, Dudley T.; Moyers, Michael F.

    2003-01-01

    normalized to physical dose, the monoenergetic proton field present inside the helmet-protected phantom produced equivalent biological responses, when compared to unshielded cells, as measured by the induction of delayed genetic effects in murine haematopoietic stem cells.

  19. Chemosensory responsiveness to ethanol and its individual sensory components in alcohol-preferring, -nonpreferring and genetically heterogeneous rats

    Science.gov (United States)

    Brasser, Susan M.; Silbaugh, Bryant C.; Ketchum, Myles J.; Olney, Jeffrey J.; Lemon, Christian H.

    2011-01-01

    Alcohol activates orosensory circuits that project to motivationally relevant limbic forebrain areas that control appetite, feeding and drinking. To date, limited data exists regarding the contribution of chemosensory-derived ethanol reinforcement to ethanol preference and consumption. Measures of taste reactivity to intra-orally infused ethanol have not found differences in initial orofacial responses to alcohol between alcohol-preferring (P) and – nonpreferring (NP) genetically selected rat lines. Yet, in voluntary intake tests P rats prefer highly-concentrated ethanol upon initial exposure, suggesting an early sensory-mediated attraction. Here, we directly compared self-initiated chemosensory responding for alcohol and prototypic sweet, bitter, and oral trigeminal stimuli among selectively bred P, NP, and non-selected Wistar (WI) outbred lines to determine whether differential sensory responsiveness to ethanol and its putative sensory components are phenotypically associated with genetically-influenced alcohol preference. Rats were tested for immediate short-term lick responses to alcohol (3–40%), sucrose (0.01–1 M), quinine (0.01–3 mM) and capsaicin (0.003–1 mM) in a brief-access assay designed to index orosensory-guided behavior. P rats exhibited elevated short-term lick responses to both alcohol and sucrose relative to NP and WI lines across a broad range of concentrations of each stimulus and in the absence of blood alcohol levels that would produce significant postabsorptive effects. There was no consistent relationship between genetically-mediated alcohol preference and orosensory avoidance of quinine or capsaicin. These data indicate that enhanced initial chemosensory attraction to ethanol and sweet stimuli are phenotypes associated with genetic alcohol preference and are considered within the framework of downstream activation of oral appetitive reward circuits. PMID:22129513

  20. Chemosensory responsiveness to ethanol and its individual sensory components in alcohol-preferring, alcohol-nonpreferring and genetically heterogeneous rats.

    Science.gov (United States)

    Brasser, Susan M; Silbaugh, Bryant C; Ketchum, Myles J; Olney, Jeffrey J; Lemon, Christian H

    2012-03-01

    Alcohol activates orosensory circuits that project to motivationally relevant limbic forebrain areas that control appetite, feeding and drinking. To date, limited data exists regarding the contribution of chemosensory-derived ethanol reinforcement to ethanol preference and consumption. Measures of taste reactivity to intra-orally infused ethanol have not found differences in initial orofacial responses to alcohol between alcohol-preferring (P) and alcohol-non-preferring (NP) genetically selected rat lines. Yet, in voluntary intake tests, P rats prefer highly concentrated ethanol upon initial exposure, suggesting an early sensory-mediated attraction. Here, we directly compared self-initiated chemosensory responding for alcohol and prototypic sweet, bitter and oral trigeminal stimuli among selectively bred P, NP and non-selected Wistar (WI) outbred lines to determine whether differential sensory responsiveness to ethanol and its putative sensory components are phenotypically associated with genetically influenced alcohol preference. Rats were tested for immediate short-term lick responses to alcohol (3-40%), sucrose (0.01-1 M), quinine (0.01-3 mM) and capsaicin (0.003-1 mM) in a brief-access assay designed to index orosensory-guided behavior. P rats exhibited elevated short-term lick responses to both alcohol and sucrose relative to NP and WI lines across a broad range of concentrations of each stimulus and in the absence of blood alcohol levels that would produce significant post-absorptive effects. There was no consistent relationship between genetically mediated alcohol preference and orosensory avoidance of quinine or capsaicin. These data indicate that enhanced initial chemosensory attraction to ethanol and sweet stimuli are phenotypes associated with genetic alcohol preference and are considered within the framework of downstream activation of oral appetitive reward circuits. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of

  1. Genetic Liability, Environment, and the Development of Fussiness in Toddlers: The Roles of Maternal Depression and Parental Responsiveness

    OpenAIRE

    Natsuaki, Misaki N.; Ge, Xiaojia; Leve, Leslie D.; Neiderhiser, Jenae M.; Shaw, Daniel S.; Conger, Rand D.; Scaramella, Laura V.; Reid, John B.; Reiss, David

    2010-01-01

    Using a longitudinal, prospective adoption design, this study examined the effects of the environment (adoptive parents’ depressive symptoms and responsiveness) and genetic liability of maternal depression (inferred by birth mothers’ major depressive disorder [MDD]) on the development of fussiness between 9 and 18 months of age in adopted children. The sample included 281 families linked through adoption, with each family including four individuals (i.e., adopted child, birth mother, adoptive...

  2. Geographical gradients in selection can reveal genetic constraints for evolutionary responses to ocean acidification.

    Science.gov (United States)

    Gaitán-Espitia, Juan Diego; Marshall, Dustin; Dupont, Sam; Bacigalupe, Leonardo D; Bodrossy, Levente; Hobday, Alistair J

    2017-02-01

    Geographical gradients in selection can shape different genetic architectures in natural populations, reflecting potential genetic constraints for adaptive evolution under climate change. Investigation of natural pH/pCO 2 variation in upwelling regions reveals different spatio-temporal patterns of natural selection, generating genetic and phenotypic clines in populations, and potentially leading to local adaptation, relevant to understanding effects of ocean acidification (OA). Strong directional selection, associated with intense and continuous upwellings, may have depleted genetic variation in populations within these upwelling regions, favouring increased tolerances to low pH but with an associated cost in other traits. In contrast, diversifying or weak directional selection in populations with seasonal upwellings or outside major upwelling regions may have resulted in higher genetic variances and the lack of genetic correlations among traits. Testing this hypothesis in geographical regions with similar environmental conditions to those predicted under climate change will build insights into how selection may act in the future and how populations may respond to stressors such as OA. © 2017 The Author(s).

  3. Genetic polymorphisms in 5-Fluorouracil-related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer.

    Science.gov (United States)

    Nelson, Bailey; Carter, Jane V; Eichenberger, Maurice R; Netz, Uri; Galandiuk, Susan

    2016-11-01

    Many patients with rectal cancer undergo preoperative neoadjuvant chemoradiation, with approximately 70% exhibiting pathologic downstaging in response to treatment. Currently, there is no accurate test to predict patients who are likely to be complete responders to therapy. 5-Fluorouracil is used regularly in the neoadjuvant treatment of rectal cancer. Genetic polymorphisms affect the activity of thymidylate synthase, an enzyme involved in 5-Fluorouracil metabolism, which may account for observed differences in response to neoadjuvant treatment between patients. Detection of genetic polymorphisms might identify patients who are likely to have a complete response to neoadjuvant therapy and perhaps allow them to avoid operation. DNA was isolated from whole blood taken from patients with newly diagnosed rectal cancer who received neoadjuvant therapy (n = 50). Response to therapy was calculated with a tumor regression score based on histology from the time of operation. Polymerase chain reaction was performed targeting the promoter region of thymidylate synthase. Polymerase chain reaction products were separated using electrophoresis to determine whether patients were homozygous for a double-tandem repeat (2R), a triple-tandem repeat (3R), or were heterozygous (2R/3R). A single nucleotide polymorphism, 3G or 3C, also may be present in the second repeat unit of the triple-tandem repeat allele. Restriction fragment length polymorphism assays were performed in patients with at least one 3R allele using HaeIII. Patients with at least 1 thymidylate synthase 3G allele were more likely to have a complete or partial pathologic response to 5-Fluorouracil neoadjuvant therapy (odds ratio 10.4; 95% confidence interval, 1.3-81.6; P = .01) than those without at least one 3G allele. Identification of rectal cancer patients with specific genetic polymorphisms in enzymes involved in 5-Fluorouracil metabolism seems to predict the likelihood of complete or partial pathologic response

  4. Direct-to-consumer advertising of predictive genetic tests: a health belief model based examination of consumer response.

    Science.gov (United States)

    Rollins, Brent L; Ramakrishnan, Shravanan; Perri, Matthew

    2014-01-01

    Direct-to-consumer (DTC) advertising of predictive genetic tests (PGTs) has added a new dimension to health advertising. This study used an online survey based on the health belief model framework to examine and more fully understand consumers' responses and behavioral intentions in response to a PGT DTC advertisement. Overall, consumers reported moderate intentions to talk with their doctor and seek more information about PGTs after advertisement exposure, though consumers did not seem ready to take the advertised test or engage in active information search. Those who perceived greater threat from the disease, however, had significantly greater behavioral intentions and information search behavior.

  5. Precision Oncology and Genetic Risk Information: Exploring Patients' Preferences and Responses

    Science.gov (United States)

    Dr. Jada Hamilton is an Assistant Member at Memorial Sloan Kettering Cancer Center, as well as an Assistant Attending Psychologist in the Behavioral Sciences Service, Department of Psychiatry and Behavioral Sciences and in the Clinical Genetics Service, Department of Medicine at Memorial Hospital in New York, New York.  She leads a program of research at the intersection of behavioral science, cancer prevention, and genomics, with the goal of translating advances in genetic and genomic medicine into improved cancer care that is of high quality, aligned with patient preferences, and ultimately improves public health.  Dr. Hamilton is also currently leading a study to assess how patients and their families respond to inherited risk information that is revealed as part of tumor sequencing (funded through a Mentored Research Scholar Grant from the American Cancer Society), as well as studies to evaluate alternative models for offering genetic counseling and testing to patients with cancer, and to examine the effects of novel breast cancer genetic risk feedback on patients’ decision-making, psychological, and behavioral outcomes. Prior to joining the faculty of Memorial Sloan Kettering, Dr. Hamilton received a BA in Genetics and Psychology from Ohio Wesleyan University (2004), an MA and PhD in Social and Health Psychology from Stony Brook University (2006, 2009), and an MPH from the Mailman School of Public Health at Columbia University (2010).  She also completed a postdoctoral fellowship as part of the National Cancer Institute’s Cancer Prevention Fellowship Program.

  6. Pro-inflammatory Cytokine Response and Genetic Diversity in Merozoite Surface Protein 2 of Plasmodium falciparum Isolates from Nigeria.

    Science.gov (United States)

    Ajibaye, Olusola; Osuntoki, Akinniyi A; Ebuehi, Albert Ot; Iwalokun, Bamidele A; Balogun, Emmanuel O; Egbuna, Kathleen N

    2017-01-01

    Polymorphisms in Plasmodium falciparum merozoite surface protein-2 ( msp -2) and associated parasite genetic diversity which varies between malaria-endemic regions remain a limitation in malaria vaccine development. Pro-inflammatory cytokines are important in immunity against malaria, understanding the influence of genetic diversity on cytokine response is important for effective vaccine design. P. falciparum isolates obtained from 300 Nigerians with uncomplicated falciparum malaria at Ijede General Hospital, Ijede (IJE), General Hospital Ajeromi, Ajeromi (AJE) and Saint Kizito Mission Hospital, Lekki, were genotyped by nested polymerase chain reaction of msp -2 block 3 while ELISA was used to determine the pro-inflammatory cytokine response to describe the genetic diversity of P. falciparum . Eighteen alleles were observed for msp -2 loci. Of the 195 isolates, 61 (31.0%) had only FC27-type alleles, 38 (19.7%) had only 3D7-type alleles, and 49.3% had multiple parasite lines with both alleles. Band sizes were 275-625 bp for FC27 and 150-425 bp for 3D7. Four alleles were observed from LEK, 2 (375-425 bp) and 2 (275-325 bp) of FC27-and 3D7-types, respectively; 12 alleles from AJE, 9 (275-625 bp) and 3 (325-425 bp) of FC27-types and 3D7-types, respectively; while IJE had a total of 12 alleles, 9 (275-625 bp) and 3 (325-425 bp) of FC27-types and 3D7-types, respectively. Mean multiplicity of infection (MOI) was 1.54. Heterozygosity ( H E ) ranged from 0.77 to 0.87 and was highest for IJE (0.87). Cytokine response was higher among 0.05) but with neither parasite density nor infection type. P. falciparum genetic diversity is extensive in Nigeria, protection via pro-inflammatory cytokines have little or no interplay with infection multiplicity.

  7. Differential response of rat strains to obesogenic diets underlines the importance of genetic makeup of an individual towards obesity.

    Science.gov (United States)

    Mn, Muralidhar; Smvk, Prasad; Battula, Kiran Kumar; Nv, Giridharan; Kalashikam, Rajender Rao

    2017-08-22

    Obesity, a multifactorial disorder, results from a chronic imbalance of energy intake vs. expenditure. Apart from excessive consumption of high calorie diet, genetic predisposition also seems to be equally important for the development of obesity. However, the role of genetic predisposition in the etiology of obesity has not been clearly delineated. The present study addresses this problem by selecting three rat strains (WNIN, F-344, SD) with different genetic backgrounds and exposing them to high calorie diets. Rat strains were fed HF, HS, and HFS diets and assessed for physical, metabolic, biochemical, inflammatory responses, and mRNA expression. Under these conditions: significant increase in body weight, visceral adiposity, oxidative stress and systemic pro-inflammatory status; the hallmarks of central obesity were noticed only in WNIN. Further, they developed altered glucose and lipid homeostasis by exhibiting insulin resistance, impaired glucose tolerance, dyslipidemia and fatty liver condition. The present study demonstrates that WNIN is more prone to develop obesity and associated co-morbidities under high calorie environment. It thus underlines the cumulative role of genetics (nature) and diet (nurture) towards the development of obesity, which is critical for understanding this epidemic and devising new strategies to control and manage this modern malady.

  8. Analyses between Reproductive Behaviour, Genetic Diversity and Pythium Responsiveness in Zingiber spp. reveal an adaptive significance for hemiclonality

    Directory of Open Access Journals (Sweden)

    Geethu Elizabath Thomas

    2016-12-01

    Full Text Available AbstractMode of reproduction is generally considered to have long-range evolutionary implications on population survival. Because sexual reproduction produces genetically diverse genotypes, this mode of reproduction is predicted to positively influence the success potential of offspring in evolutionary arms race with parasites (Red queen whereas, without segregation and recombination, the obligate asexual multiplication may push a species into extinction due to the steady accumulation of deleterious mutations (Muller’s ratchet. However, the extent of linearity between reproductive strategies, genetic diversity and population fitness, and the contributions of different breeding strategies to population fitness are yet to be understood clearly. Genus Zingiber belonging to the pan-tropic family Zingiberaceae represents a good system to study contributions of different breeding behaviour on genetic diversity and population fitness, as this genus comprises species with contrasting breeding systems. In this study, we analyzed breeding behaviour, amplified fragment length polymorphism (AFLP diversity and response to the soft-rot pathogen Pythium aphanidermatum in 18 natural populations of three wild Zingiber spp.: Z. neesanum, Z. nimmonii and Z. zerumbet, together with the obligately asexual cultivated congener, ginger (Z. officinale. Ginger showed an exceptionally narrow genetic base, and adding to this, all the tested cultivars were uniformly susceptible to soft-rot. Concordant with the postulates of Muller’s ratchet, the background selection may be continuously pushing ginger into the ancestral state, rendering it inefficient in host-pathogen coevolution. Z. neesanum and Z. nimmonii populations were sexual and genetically diverse; however, contrary to Red Queen expectations, the populations were highly susceptible to soft-rot. Z. zerumbet showed a hemiclonal breeding behaviour. The populations inhabiting forest understory were large and

  9. Perception, experience, and response to genetic discrimination in Huntington disease: the international RESPOND-HD study.

    Science.gov (United States)

    Erwin, Cheryl; Williams, Janet K; Juhl, Andrew R; Mengeling, Michelle; Mills, James A; Bombard, Yvonne; Hayden, Michael R; Quaid, Kimberly; Shoulson, Ira; Taylor, Sandra; Paulsen, Jane S

    2010-07-01

    Genetic discrimination-defined as the denial of rights, privileges, or opportunities or other adverse treatment based solely on genetic information (including family history)-is an important concern to patients, healthcare professionals, lawmakers, and family members at risk for carrying a deleterious gene. Data from the United States, Canada, and Australia were collected from 433 individuals at risk for Huntington disease (HD) who have tested either positive or negative for the gene that causes HD and family members of affected individuals who have a 50% risk for developing the disorder but remain untested. Across all three countries, a total of 46.2% of respondents report genetic discrimination or stigma based on either their family history of HD or genetic testing for the HD gene mutation. We report on the overall incidence of discrimination and stigma in the domains of insurance (25.9%), employment (6.5%), relationships (32.9%), and other transactions (4.6%) in the United States, Canada, and Australia combined. The incidence of self-reported discrimination is less than the overall worry about the risk of discrimination, which is more prevalent in each domain. Despite a relatively low rate of perceived genetic discrimination in the areas of health insurance and employment, compared to the perception of discrimination and stigma in personal relationships, the cumulative burden of genetic discrimination across all domains of experience represents a challenge to those at risk for HD. The effect of this cumulative burden on daily life decisions remains unknown. (c) 2010 Wiley-Liss, Inc.

  10. Consumers’ response to genetically modified ingredients in processed food in an emerging economy

    DEFF Research Database (Denmark)

    Yormirzoev, Mirzobobo; Teuber, Ramona

    2017-01-01

    Genetically modified (GM) foods are available in many countries including post–Soviet Union countries. However, empirical evidence on consumer acceptance for this region is scarce. In this study, we investigate consumers’ willingness to purchase a processed food containing GM ingredients. For thi......Genetically modified (GM) foods are available in many countries including post–Soviet Union countries. However, empirical evidence on consumer acceptance for this region is scarce. In this study, we investigate consumers’ willingness to purchase a processed food containing GM ingredients...

  11. A possibilistic approach for transient identification with 'don't know' response capability optimized by genetic algorithm

    International Nuclear Information System (INIS)

    Almeida, Jose Carlos S. de; Schirru, Roberto; Pereira, Claudio M.N.A.; Universidade Federal, Rio de Janeiro, RJ

    2002-01-01

    This work describes a possibilistic approach for transient identification based on the minimum centroids set method, proposed in previous work, optimized by genetic algorithm. The idea behind this method is to split the complex classification problem into small and simple ones, so that the performance in the classification can be increased. In order to accomplish that, a genetic algorithm is used to learn, from realistic simulated data, the optimized time partitions, which the robustness and correctness in the classification are maximized. The use of a possibilistic classification approach propitiates natural and consistent classification rules, leading naturally to a good heuristic to handle the 'don't know 'response, in case of unrecognized transient, which is fairly desirable in transient classification systems where safety is critical. Application of the proposed approach to a nuclear transient indentification problem reveals good capability of the genetic algorithm in learning optimized possibilistic classification rules for efficient diagnosis including 'don't know' response. Obtained results are shown and commented. (author)

  12. Selection for increased desiccation resistance in Drosophila melanogaster: Additive genetic control and correlated responses for other stresses

    International Nuclear Information System (INIS)

    Hoffmann, A.A.; Parsons, P.A.

    1989-01-01

    Previously we found that Drosophila melanogaster lines selected for increased desiccation resistance have lowered metabolic rate and behavioral activity levels, and show correlated responses for resistance to starvation and a toxic ethanol level. These results were consistent with a prediction that increased resistance to many environmental stresses may be genetically correlated because of a reduction in metabolic energy expenditure. Here we present experiments on the genetic basis of the selection response and extend the study of correlated responses to other stresses. The response to selection was not sex-specific and involved X-linked and autosomal genes acting additively. Activity differences contributed little to differences in desiccation resistance between selected and control lines. Selected lines had lower metabolic rates than controls in darkness when activity was inhibited. Adults from selected lines showed increased resistance to a heat shock, 60 Co-gamma-radiation, and acute ethanol and acetic acid stress. The desiccation, ethanol and starvation resistance of isofemale lines set up from the F2s of a cross between one of the selected and one of the control lines were correlated. Selected and control lines did not differ in ether-extractable lipid content or in resistance to acetone, ether or a cold shock

  13. Genetic variation of transgenerational plasticity of offspring germination in response to salinity stress and the seed transcriptome of Medicago truncatula.

    Science.gov (United States)

    Vu, Wendy T; Chang, Peter L; Moriuchi, Ken S; Friesen, Maren L

    2015-04-01

    Transgenerational plasticity provides phenotypic variation that contributes to adaptation. For plants, the timing of seed germination is critical for offspring survival in stressful environments, as germination timing can alter the environmental conditions a seedling experiences. Stored seed transcripts are important determinants of seed germination, but have not previously been linked with transgenerational plasticity of germination behavior. In this study we used RNAseq and growth chamber experiments of the model legume M. trucantula to test whether parental exposure to salinity stress influences the expression of stored seed transcripts and early offspring traits and test for genetic variation. We detected genotype-dependent parental environmental effects (transgenerational plasticity) on the expression levels of stored seed transcripts, seed size, and germination behavior of four M. truncatula genotypes. More than 50% of the transcripts detected in the mature, ungerminated seed transcriptome were annotated as regulating seed germination, some of which are involved in abiotic stress response and post-embryonic development. Some genotypes showed increased seed size in response to parental exposure to salinity stress, but no parental environmental influence on germination timing. In contrast, other genotypes showed no seed size differences across contrasting parental conditions but displayed transgenerational plasticity for germimation timing, with significantly delayed germination in saline conditions when parental plants were exposed to salinity. In genotypes that show significant transgenerational plastic germination response, we found significant coexpression networks derived from salt responsive transcripts involved in post-transcriptional regulation of the germination pathway. Consistent with the delayed germination response to saline conditions in these genotypes, we found genes associated with dormancy and up-regulation of abscisic acid (ABA). Our results

  14. Evaluation of the innate immune response of Angus heifers with genetic marker variation for intramuscular fat deposition following a lipopolysaccharide challenge

    Science.gov (United States)

    This study evaluated the effect of genetic selection for markers related to marbling deposition in Angus heifers on the immune response following a lipopolysaccharide (LPS) challenge. Fall-born heifers (n = 19; ~7 months of age, 274 +/- 24 kg) with genetic variation for marbling were utilized inclu...

  15. A genomic portrait of the genetic architecture and regulatory impact of microRNA expression in response to infection.

    Science.gov (United States)

    Siddle, Katherine J; Deschamps, Matthieu; Tailleux, Ludovic; Nédélec, Yohann; Pothlichet, Julien; Lugo-Villarino, Geanncarlo; Libri, Valentina; Gicquel, Brigitte; Neyrolles, Olivier; Laval, Guillaume; Patin, Etienne; Barreiro, Luis B; Quintana-Murci, Lluís

    2014-05-01

    MicroRNAs (miRNAs) are critical regulators of gene expression, and their role in a wide variety of biological processes, including host antimicrobial defense, is increasingly well described. Consistent with their diverse functional effects, miRNA expression is highly context dependent and shows marked changes upon cellular activation. However, the genetic control of miRNA expression in response to external stimuli and the impact of such perturbations on miRNA-mediated regulatory networks at the population level remain to be determined. Here we assessed changes in miRNA expression upon Mycobacterium tuberculosis infection and mapped expression quantitative trait loci (eQTL) in dendritic cells from a panel of healthy individuals. Genome-wide expression profiling revealed that ∼40% of miRNAs are differentially expressed upon infection. We find that the expression of 3% of miRNAs is controlled by proximate genetic factors, which are enriched in a promoter-specific histone modification associated with active transcription. Notably, we identify two infection-specific response eQTLs, for miR-326 and miR-1260, providing an initial assessment of the impact of genotype-environment interactions on miRNA molecular phenotypes. Furthermore, we show that infection coincides with a marked remodeling of the genome-wide relationships between miRNA and mRNA expression levels. This observation, supplemented by experimental data using the model of miR-29a, sheds light on the role of a set of miRNAs in cellular responses to infection. Collectively, this study increases our understanding of the genetic architecture of miRNA expression in response to infection, and highlights the wide-reaching impact of altering miRNA expression on the transcriptional landscape of a cell.

  16. The ecology and evolution of animal medication: genetically fixed response versus phenotypic plasticity.

    Science.gov (United States)

    Choisy, Marc; de Roode, Jacobus C

    2014-08-01

    Animal medication against parasites can occur either as a genetically fixed (constitutive) or phenotypically plastic (induced) behavior. Taking the tritrophic interaction between the monarch butterfly Danaus plexippus, its protozoan parasite Ophryocystis elektroscirrha, and its food plant Asclepias spp. as a test case, we develop a game-theory model to identify the epidemiological (parasite prevalence and virulence) and environmental (plant toxicity and abundance) conditions that predict the evolution of genetically fixed versus phenotypically plastic forms of medication. Our model shows that the relative benefits (the antiparasitic properties of medicinal food) and costs (side effects of medicine, the costs of searching for medicine, and the costs of plasticity itself) crucially determine whether medication is genetically fixed or phenotypically plastic. Our model suggests that animals evolve phenotypic plasticity when parasite risk (a combination of virulence and prevalence and thus a measure of the strength of parasite-mediated selection) is relatively low to moderately high and genetically fixed medication when parasite risk becomes very high. The latter occurs because at high parasite risk, the costs of plasticity are outweighed by the benefits of medication. Our model provides a simple and general framework to study the conditions that drive the evolution of alternative forms of animal medication.

  17. The genetic influences on oxycodone response characteristics in human experimental pain

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Sato, Hiroe; Nielsen, Lecia M

    2015-01-01

    Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic respon......; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone....

  18. Assessments of genetic diversity and anthracnose disease response among Zimbabwe sorghum germplasm.

    Science.gov (United States)

    The USDA-ARS National Plant Germplasm System maintains a Zimbabwe sorghum collection of 1,235 accessions from different provinces. This germplasm has not been extensively employed in U.S. breeding programs due to the lack of phenotypic and genetic characterization. Therefore, 68 accessions from th...

  19. Nature, nurture, and item response theory: a psychometric approach to behaviour genetics

    NARCIS (Netherlands)

    Schwabe, Inga

    2016-01-01

    This dissertation discusses a number of psychometric issues that require special attention in the analysis of genetically-informative data, such as data on twins. These include heterogeneous measurement error, scaling and scale transformation, and harmonization of phenotypes. It is shown how

  20. Genetic control of plasticity in root morphology and anatomy of rice in response to water deficit

    NARCIS (Netherlands)

    Kadam, Niteen N.; Tamilselvan, Anandhan; Lawas, Lovely M.F.; Quinones, Cherryl; Bahuguna, Rajeev N.; Thomson, Michael J.; Dingkuhn, Michael; Muthurajan, Raveendran; Struik, Paul C.; Yin, Xinyou; Jagadish, Krishna S.V.

    2017-01-01

    Elucidating the genetic control of rooting behavior under water-deficit stress is essential to breed climate-robust rice (Oryza sativa) cultivars. Using a diverse panel of 274 indica genotypes grown under control and water-deficit conditions during vegetative growth, we phenotyped 35 traits, mostly

  1. Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep☆

    Science.gov (United States)

    Banks, Gareth; Heise, Ines; Starbuck, Becky; Osborne, Tamzin; Wisby, Laura; Potter, Paul; Jackson, Ian J.; Foster, Russell G.; Peirson, Stuart N.; Nolan, Patrick M.

    2015-01-01

    The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. PMID:25179226

  2. Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep.

    Science.gov (United States)

    Banks, Gareth; Heise, Ines; Starbuck, Becky; Osborne, Tamzin; Wisby, Laura; Potter, Paul; Jackson, Ian J; Foster, Russell G; Peirson, Stuart N; Nolan, Patrick M

    2015-01-01

    The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Tuberous Sclerosis Complex in 29 Children: Clinical and Genetic Analysis and Facial Angiofibroma Responses to Topical Sirolimus.

    Science.gov (United States)

    Wang, Senfen; Liu, Yuanxiang; Wei, Jinghai; Zhang, Jian; Wang, Zhaoyang; Xu, Zigang

    2017-09-01

    Tuberous sclerosis complex (TSC) is a genetic disorder and facial angiofibromas are disfiguring facial lesions. The aim of this study was to analyze the clinical and genetic features of TSC and to assess the treatment of facial angiofibromas using topical sirolimus in Chinese children. Information was collected on 29 patients with TSC. Genetic analyses were performed in 12 children and their parents. Children were treated with 0.1% sirolimus ointment for 36 weeks. Clinical efficacy and plasma sirolimus concentrations were evaluated at baseline and 12, 24, and 36 weeks. Twenty-seven (93%) of the 29 patients had hypomelanotic macules and 15 (52%) had shagreen patch; 11 of the 12 (92%) who underwent genetic analysis had gene mutations in the TSC1 or TSC2 gene. Twenty-four children completed 36 weeks of treatment with topical sirolimus; facial angiofibromas were clinically undetectable in four (17%). The mean decrease in the Facial Angiofibroma Severity Index (FASI) score at 36 weeks was 47.6 ± 30.4%. There was no significant difference in the FASI score between weeks 24 and 36 (F = 1.00, p = 0.33). There was no detectable systemic absorption of sirolimus. Hypomelanotic macules are often the first sign of TSC. Genetic testing has a high detection rate in patients with a clinical diagnosis of TSC. Topical sirolimus appears to be both effective and well-tolerated as a treatment of facial angiofibromas in children with TSC. The response typically plateaus after 12 to 24 weeks of treatment. © 2017 Wiley Periodicals, Inc.

  4. Associations between self-referral and health behavior responses to genetic risk information.

    Science.gov (United States)

    Christensen, Kurt D; Roberts, J Scott; Zikmund-Fisher, Brian J; Kardia, Sharon Lr; McBride, Colleen M; Linnenbringer, Erin; Green, Robert C

    2015-01-01

    Studies examining whether genetic risk information about common, complex diseases can motivate individuals to improve health behaviors and advance planning have shown mixed results. Examining the influence of different study recruitment strategies may help reconcile inconsistencies. Secondary analyses were conducted on data from the REVEAL study, a series of randomized clinical trials examining the impact of genetic susceptibility testing for Alzheimer's disease (AD). We tested whether self-referred participants (SRPs) were more likely than actively recruited participants (ARPs) to report health behavior and advance planning changes after AD risk and APOE genotype disclosure. Of 795 participants with known recruitment status, 546 (69%) were self-referred and 249 (31%) had been actively recruited. SRPs were younger, less likely to identify as African American, had higher household incomes, and were more attentive to AD than ARPs (all P change to at least one health behavior 6 weeks and 12 months after genetic risk disclosure, nor in intentions to change at least one behavior in the future. However, interaction effects were observed where ε4-positive SRPs were more likely than ε4-negative SRPs to report changes specifically to mental activities (38% vs 19%, p change long-term care insurance among SRPs (20% vs 5%, p behavior changes than those who respond to genetic testing offers. These results demonstrate how the behavioral impact of genetic risk information may vary according to the models by which services are provided, and suggest that how participants are recruited into translational genomics research can influence findings. ClinicalTrials.gov NCT00089882 and NCT00462917.

  5. USING OF MOUSE MODEL TO ANALYZE IMMUNE RESPONSE TO INFECTIOUS PATHOGENS BY THE METHODS OF CLASSICAL GENETICS

    Directory of Open Access Journals (Sweden)

    A. Poltorak

    2011-01-01

    Full Text Available Abstract. Identification and studying of numerous functions of all genes of the human beings is one of the main objects of modern biological science. Due to high level of homology between mouse and human genomes the important role to reach above mentioned goal belongs to the mouse model which using in the classical genetics increase in connection with appearance of different inbred mouse lines. For instance, the differences in immune response to infectious pathogens in various mouse lines were used many times to determine immunologically competent genes. That is why the contribution of mouse model in understanding of the mechanisms of immune response to infectious pathogens is difficult to overestimate. In the current review some of the most successful and well known examples of mouse using in studies of anti-infectious response are described.

  6. Genetic control of eosinophilia in mice: gene(s) expressed in bone marrow-derived cells control high responsiveness

    International Nuclear Information System (INIS)

    Vadas, M.A.

    1982-01-01

    A heterogeneity in the capacity of strains of mice to mount eosinophilia is described. BALB/c and C3H are eosinophil high responder strains (EO-HR) and CBA and A/J are eosinophil low responder strains (EO-LR), judged by the response of blood eosinophils to Ascaris suum, and the response of blood, bone marrow, and spleen eosinophils to keyhole limpet hemocyanin given 2 days after 150 mg/kg cyclophosphamide. Some of the gene(s) for high responsiveness appear to be dominant because (EO-HR x EO-LR)F 1 mice were intermediate to high responders. This gene is expressed in bone marrow-derived cells because radiation chimeras of the type EO-HR→F 1 were high responders and EO-LR→F 1 were low responders. This description of a genetic control of eosinophilia in mice may be useful in understanding the role of this cell in parasite immunity and allergy

  7. Genetic responses induced in olive roots upon colonization by the biocontrol endophytic bacterium Pseudomonas fluorescens PICF7.

    Directory of Open Access Journals (Sweden)

    Elisabetta Schilirò

    Full Text Available Knowledge on the genetic basis underlying interactions between beneficial bacteria and woody plants is still very limited, and totally absent in the case of olive. We aimed to elucidate genetic responses taking place during the colonization of olive roots by the native endophyte Pseudomonas fluorescens PICF7, an effective biocontrol agent against Verticillium wilt of olive. Roots of olive plants grown under non-gnotobiotic conditions were collected at different time points after PICF7 inoculation. A Suppression Subtractive Hybridization cDNA library enriched in induced genes was generated. Quantitative real time PCR (qRT-PCR analysis validated the induction of selected olive genes. Computational analysis of 445 olive ESTs showed that plant defence and response to different stresses represented nearly 45% of genes induced in PICF7-colonized olive roots. Moreover, quantitative real-time PCR (qRT-PCR analysis confirmed induction of lipoxygenase, phenylpropanoid, terpenoids and plant hormones biosynthesis transcripts. Different classes of transcription factors (i.e., bHLH, WRKYs, GRAS1 were also induced. This work highlights for the first time the ability of an endophytic Pseudomonas spp. strain to mount a wide array of defence responses in an economically-relevant woody crop such as olive, helping to explain its biocontrol activity.

  8. Response to family selection and genetic parameters in Japanese quail selected for four week breast weight

    DEFF Research Database (Denmark)

    Khaldari, Majid; Yeganeh, Hassan Mehrabani; Pakdel, Abbas

    2011-01-01

    An experiment was conducted to investigate the effect of short-term selection for 4 week breast weight (4wk BRW), and to estimate genetic parameters of body weight, and carcass traits. A selection (S) line and control (C) line was randomly selected from a base population. Data were collected over...... was 0.35±0.06. There were a significant difference for BW, and carcass weights but not for carcass percent components between lines (Pcarcass and leg weights were 0.46, 0.41 and 0.47, and 13.2, 16.2, 4.4 %, respectively....... The genetic correlations of BRW with BW, carcass, leg, and back weights were 0.85, 0.88 and 0.72, respectively. Selection for 4 wk BRW improved feed conversion ratio (FCR) about 0.19 units over the selection period. Inbreeding caused an insignificant decline of the mean of some traits. Results from...

  9. Genetics of PCOS: A systematic bioinformatics approach to unveil the proteins responsible for PCOS

    OpenAIRE

    Panda, Pritam Kumar; Rane, Riya; Ravichandran, Rahul; Singh, Shrinkhla; Panchal, Hetalkumar

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a hormonal imbalance in women, which causes problems during menstrual cycle and in pregnancy that sometimes results in fatality. Though the genetics of PCOS is not fully understood, early diagnosis and treatment can prevent long-term effects. In this study, we have studied the proteins involved in PCOS and the structural aspects of the proteins that are taken into consideration using computational tools. The proteins involved are modeled using Modeller 9v14...

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

    OpenAIRE

    Sankar, Pamela L.; Cho, Mildred K.

    2015-01-01

    Recent experiments have been used to “edit” genomes of various plant, animal and other species, including humans, with unprecedented precision. Furthermore, editing Cas9 endonuclease gene with a gene encoding the desired guide RNA into an organism, adjacent to an altered gene, could create a “gene drive” that could spread a trait through an entire population of organisms. These experiments represent advances along a spectrum of technological abilities that genetic engineers have been working ...

  11. Quantitative Chemical-Genetic Interaction Map Connects Gene Alterations to Drug Responses | Office of Cancer Genomics

    Science.gov (United States)

    In a recent Cancer Discovery report, CTD2 researchers at the University of California in San Francisco developed a new quantitative chemical-genetic interaction mapping approach to evaluate drug sensitivity or resistance in isogenic cell lines. Performing a high-throughput screen with isogenic cell lines allowed the researchers to explore the impact of a panel of emerging and established drugs on cells overexpressing a single cancer-associated gene in isolation.

  12. Angry Responses to Infant Challenges: Parent, Marital, and Child Genetic Factors Associated with Harsh Parenting

    OpenAIRE

    Hajal, Nastassia J.; Neiderhiser, Jenae M.; Moore, Ginger A.; Leve, Leslie D.; Shaw, Daniel S.; Harold, Gordon T.; Scaramella, Laura V.; Ganiban, Jody M.; Reiss, David

    2015-01-01

    This study examined genetic and environmental influences on harsh parenting of 9-month-olds. We examined whether positive child-, parent-, and family-level characteristics were associated with harsh parenting in addition to negative characteristics. We were particularly interested in examining evocative gene-environment correlation (rGE) by testing the effect of birth parent temperament on adoptive parents’ harsh parenting. Additionally, we examined associations among adoptive parents’ own te...

  13. GENETIC CONTROL IN GUINEA PIGS OF IMMUNE RESPONSE TO CONJUGATES OF HAPTENS AND POLY-L-LYSINE.

    Science.gov (United States)

    LEVINE, B B; BENACERRAF, B

    1965-01-29

    Random-bred Hartley strain guinea pigs which do not respond immunologically to conjugates of hapten and poly-L-lysine mere mated with heterozygous guinea pigs which do. These responders were considered heterozygous for this trait since their mating resulted in at least one nonresponder offspring. Of 31 offspring from 10 breeding pairs (nonresponder x heterozygous responder) 14 were responders. There was no evidence that this trait is sex-linked. This finding confirms the view that, in guinea pigs, development of an immune response to the aforementioned conjugates is a genetically transmitted autosomal, unigenic Mendelian dominant trait.

  14. In search of genetic constraints limiting the evolution of egg size: direct and correlated responses to artificial selection on a prenatal maternal effector.

    Science.gov (United States)

    Pick, J L; Hutter, P; Tschirren, B

    2016-06-01

    Maternal effects are an important force in nature, but the evolutionary dynamics of the traits that cause them are not well understood. Egg size is known to be a key mediator of prenatal maternal effects with an established genetic basis. In contrast to theoretical expectations for fitness-related traits, there is a large amount of additive genetic variation in egg size observed in natural populations. One possible mechanism for the maintenance of this variation is through genetic constraints caused by a shared genetic basis among traits. Here we created replicated, divergent selection lines for maternal egg investment in Japanese quail (Coturnix japonica) to quantify the role of genetic constraints in the evolution of egg size. We found that egg size responds rapidly to selection, accompanied by a strong response in all egg components. Initially, we observed a correlated response in body size, but this response declined over time, showing that egg size and body size can evolve independently. Furthermore, no correlated response in fecundity (measured as the proportion of days on which a female laid an egg) was observed. However, the response to selection was asymmetrical, with egg size plateauing after one generation of selection in the high but not the low investment lines. We attribute this pattern to the presence of genetic asymmetries, caused by directional dominance or unequal allele frequencies. Such asymmetries may contribute to the evolutionary stasis in egg size observed in natural populations, despite a positive association between egg size and fitness.

  15. Dose response behaviour of water scarcity towards genetical and morphological traits in spring wheat

    International Nuclear Information System (INIS)

    Noorkha, I.R.; Tabasum, S.

    2015-01-01

    Combining ability was studied in a Line * Tester mating fashion in wheat (Tricticum aestivum L.). Significant differences were observed for all the yield and yield contributing traits. GCA and SCA components of variation were found significant for most of the traits. Under water stressed conditions among lines the genotype Kohistan-97 revealed significant GCA effects for all the traits except spike length. Among testers, the genotype V08172 showed significant effects for the traits spike length, 1000-grain weight and flag leaf area. Based on desirable SCA effects and mean performance the cross combinations Kohistan-97 * V08172, Chakwal-86 * Punjab-81, Fsd-2008 * Punjab-81, Sehar-2006 * V08172 and Chakwal-86 * V08172 behaved best combiner to tolerate the water stress. Results of genetic analysis offered over dominance type of gene action that remained unchanged with the change in water provision for the traits like 1000 grain weight and economic yield. Similarly additive gene action was observed for the trait plant height under both normal irrigation and water stress conditions. However the cumulative genetic effects to control the expression of yield and yield components was shifted due to the changed environments. The study was concluded that due to presence of additive variance, selection could be practiced in early generation whereas in the presence of recessiveness the selection may be delayed up to the later generations. Plant traits associated with water stress tolerance having high heritability and with additive gene action may be used as indirect selection criteria for early selection of water stress tolerant genotypes. The information generated as a result of this study on genetic analysis of important economic traits of wheat under contrasting water availability positions will be of great value to the wheat breeders to design future breeding programmes. (author)

  16. IN SITU COMPARISON OF TREE-RING RESPONSES TO CLIMATE AND POPULATION GENETICS: THE NEED TO CONTROL FOR LOCAL CLIMATE AND SITE VARIABLES

    Directory of Open Access Journals (Sweden)

    Johann Mathias Housset

    2016-10-01

    Full Text Available Tree species responses to climate change will be greatly influenced by their evolutionary potential and their phenotypic plasticity. Investigating tree-rings responses to climate and population genetics at the regional scale is therefore crucial in assessing the tree behaviour to climate change. This study combined in situ dendroclimatology and population genetics over a latitudinal gradient and compared the variations between the two at the intra- and inter-population levels. This approach was applied on the northern marginal populations of Thuja occidentalis (eastern white-cedar in the Canadian boreal forest. We aimed first to assess the radial growth variability (response functional trait within populations across the gradient and to compare it with the genetic diversity (microsatellites. Second, we investigated the variability in the growth response to climate at the regional scale through the radial growth-climate relationships, and tested its correlation with environmental variables and population genetic structure. Model selection based on the Akaike Information Criteria revealed that the growth synchronicity between pairs of trees of a population covariates with both the genetic diversity of this population and the amount of precipitation (inverse correlation, although these variables only explained a small fraction of the observed variance. At the regional scale, variance partitioning and partial redundancy analysis indicate that the growth response to climate was greatly modulated by stand environmental variables, suggesting predominant plastic variations in growth-response to climate. Combining in situ dendroclimatology and population genetics is a promising way to investigate species’ response capacity to climate change in natural stands. We stress the need to control for local climate and site conditions effects on dendroclimatic response to climate to avoid misleading conclusions regarding the associations with genetic variables.

  17. Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen Report.

    Directory of Open Access Journals (Sweden)

    Mirko Manchia

    Full Text Available The assessment of response to lithium maintenance treatment in bipolar disorder (BD is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen study.Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ] and reliability [intra-class correlation coefficient (ICC] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling.Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively, without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively. Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders.We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.

  18. Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report

    Science.gov (United States)

    Manchia, Mirko; Adli, Mazda; Akula, Nirmala; Ardau, Raffaella; Aubry, Jean-Michel; Backlund, Lena; Banzato, Claudio EM.; Baune, Bernhard T.; Bellivier, Frank; Bengesser, Susanne; Biernacka, Joanna M.; Brichant-Petitjean, Clara; Bui, Elise; Calkin, Cynthia V.; Cheng, Andrew Tai Ann; Chillotti, Caterina; Cichon, Sven; Clark, Scott; Czerski, Piotr M.; Dantas, Clarissa; Zompo, Maria Del; DePaulo, J. Raymond; Detera-Wadleigh, Sevilla D.; Etain, Bruno; Falkai, Peter; Frisén, Louise; Frye, Mark A.; Fullerton, Jan; Gard, Sébastien; Garnham, Julie; Goes, Fernando S.; Grof, Paul; Gruber, Oliver; Hashimoto, Ryota; Hauser, Joanna; Heilbronner, Urs; Hoban, Rebecca; Hou, Liping; Jamain, Stéphane; Kahn, Jean-Pierre; Kassem, Layla; Kato, Tadafumi; Kelsoe, John R.; Kittel-Schneider, Sarah; Kliwicki, Sebastian; Kuo, Po-Hsiu; Kusumi, Ichiro; Laje, Gonzalo; Lavebratt, Catharina; Leboyer, Marion; Leckband, Susan G.; López Jaramillo, Carlos A.; Maj, Mario; Malafosse, Alain; Martinsson, Lina; Masui, Takuya; Mitchell, Philip B.; Mondimore, Frank; Monteleone, Palmiero; Nallet, Audrey; Neuner, Maria; Novák, Tomás; O’Donovan, Claire; Ösby, Urban; Ozaki, Norio; Perlis, Roy H.; Pfennig, Andrea; Potash, James B.; Reich-Erkelenz, Daniela; Reif, Andreas; Reininghaus, Eva; Richardson, Sara; Rouleau, Guy A.; Rybakowski, Janusz K.; Schalling, Martin; Schofield, Peter R.; Schubert, Oliver K.; Schweizer, Barbara; Seemüller, Florian; Grigoroiu-Serbanescu, Maria; Severino, Giovanni; Seymour, Lisa R.; Slaney, Claire; Smoller, Jordan W.; Squassina, Alessio; Stamm, Thomas; Steele, Jo; Stopkova, Pavla; Tighe, Sarah K.; Tortorella, Alfonso; Turecki, Gustavo; Wray, Naomi R.; Wright, Adam; Zandi, Peter P.; Zilles, David; Bauer, Michael; Rietschel, Marcella; McMahon, Francis J.

    2013-01-01

    Objective The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the “Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder” scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study. PMID:23840348

  19. Genetic Variations in Pattern Recognition Receptor Loci Are Associated with Anti-TNF Response in Patients with Rheumatoid Arthritis.

    Directory of Open Access Journals (Sweden)

    Jacob Sode

    Full Text Available To determine whether genetic variation within genes related to the Toll-like receptor, inflammasome and interferon-γ pathways contributes to the differences in treatment response to tumour necrosis factor inhibitors (anti-TNF in patients with rheumatoid arthritis (RA.In a retrospective case-case study, we assessed 23 functional single nucleotide polymorphisms (SNPs in 15 genes. We included 538 anti-TNF naïve Danish RA patients from the nationwide DANBIO database. Multivariable logistic regression analyses were performed to detect associations (p-value<0.05 between genotypes and European League Against Rheumatism (EULAR treatment responses. False Discovery Rate corrections for multiple testing (q-value and stratified analyses were performed to investigate association with individual therapies and IgM-rheumatoid factor (RF status.Six of twenty successfully genotyped polymorphisms were nominally associated with EULAR treatment response. Three of these were in weak to moderate linkage disequilibrium with polymorphisms previously reported associated with anti-TNF treatment response. TLR5(rs5744174 variant allele carriers (odds ratio(OR = 1.7(1.1-2.5,p = 0.010,q = 0.46 and TLR1(rs4833095 homozygous variant carriers (OR = 2.8(1.1-7.4,p = 0.037,q = 0.46 had higher odds for a positive treatment response. NLRP3(rs10754558 variant allele carriers (odds ratio(OR = 0.6(0.4-1.0,p = 0.045,q = 0.46 were more likely to have a negative treatment response. The association in TLR5(rs5744174 remained significant after correction for multiple comparisons among patients negative for RF (OR = 6.2(2.4-16.3,p = 0.0002,q = 0.024. No other association withstood correction for multiple testing. Post hoc analyses showed that change in Patient Global score on a visual analogue scale (VAS and change in pain VAS were the main factors responsible for the association.We reproduced previously reported associations between genetic variation in the TLR10/1/6 gene cluster, TLR5

  20. Genetics of mechanisms controlling responses to two major pathogens in broiler and layer chickens

    DEFF Research Database (Denmark)

    Hamzic, Edin

    The objective of this thesis was to improve the understanding of molecular mechanisms controlling the response to two major pathogens, Eimeria maxima (coccidiosis) and infectious bronchitis virus (IBV), in broiler and layer chickens, respectively. Breeding for the improved response to the two...

  1. The TreadWheel: A Novel Apparatus to Measure Genetic Variation in Response to Gently Induced Exercise for Drosophila.

    Directory of Open Access Journals (Sweden)

    Sean Mendez

    Full Text Available Obesity is one of the dramatic health issues affecting developed and developing nations, and exercise is a well-established intervention strategy. While exercise-by-genotype interactions have been shown in humans, overall little is known. Using the natural negative geotaxis of Drosophila melanogaster, an important model organism for the study of genetic interactions, a novel exercise machine, the TreadWheel, can be used to shed light on this interaction. The mechanism for inducing exercise with the TreadWheel is inherently gentle, thus minimizing possible confounding effects of other stressors. Using this machine, we were able to assess large cohorts of adult flies from eight genetic lines for their response to exercise after one week of training. We measured their triglyceride, glycerol, protein, glycogen, glucose content, and body weight, as well as their climbing ability and feeding behavior in response to exercise. Exercised flies showed decreased stored triglycerides, glycogen, and body weight, and increased stored protein and climbing ability. In addition to demonstrating an overall effect of TreadWheel exercise on flies, we found significant interactions of exercise with genotype, sex, or genotype-by-sex effects for most of the measured phenotypes. We also observed interaction effects between exercise, genotype, and tissue (abdomen or thorax for metabolite profiles, and those differences can be partially linked to innate differences in the flies' persistence in maintaining activity during exercise bouts. In addition, we assessed gene expression levels for a panel of 13 genes known to be associated with respiratory fitness and found that many responded to exercise. With this study, we have established the TreadWheel as a useful tool to study the effect of exercise in flies, shown significant genotype-specific and sex-specific impacts of exercise, and have laid the ground work for more extensive studies of how genetics, sex, environment

  2. The TreadWheel: A Novel Apparatus to Measure Genetic Variation in Response to Gently Induced Exercise for Drosophila

    Science.gov (United States)

    Mendez, Sean; Watanabe, Louis; Hill, Rachel; Owens, Meredith; Moraczewski, Jason; Rowe, Glenn C.; Riddle, Nicole C.

    2016-01-01

    Obesity is one of the dramatic health issues affecting developed and developing nations, and exercise is a well-established intervention strategy. While exercise-by-genotype interactions have been shown in humans, overall little is known. Using the natural negative geotaxis of Drosophila melanogaster, an important model organism for the study of genetic interactions, a novel exercise machine, the TreadWheel, can be used to shed light on this interaction. The mechanism for inducing exercise with the TreadWheel is inherently gentle, thus minimizing possible confounding effects of other stressors. Using this machine, we were able to assess large cohorts of adult flies from eight genetic lines for their response to exercise after one week of training. We measured their triglyceride, glycerol, protein, glycogen, glucose content, and body weight, as well as their climbing ability and feeding behavior in response to exercise. Exercised flies showed decreased stored triglycerides, glycogen, and body weight, and increased stored protein and climbing ability. In addition to demonstrating an overall effect of TreadWheel exercise on flies, we found significant interactions of exercise with genotype, sex, or genotype-by-sex effects for most of the measured phenotypes. We also observed interaction effects between exercise, genotype, and tissue (abdomen or thorax) for metabolite profiles, and those differences can be partially linked to innate differences in the flies' persistence in maintaining activity during exercise bouts. In addition, we assessed gene expression levels for a panel of 13 genes known to be associated with respiratory fitness and found that many responded to exercise. With this study, we have established the TreadWheel as a useful tool to study the effect of exercise in flies, shown significant genotype-specific and sex-specific impacts of exercise, and have laid the ground work for more extensive studies of how genetics, sex, environment, and aging interact

  3. Genetic control of the humoral immune response to avian egg white lysozymes in the chicken

    International Nuclear Information System (INIS)

    Flanagan, M.P.

    1987-01-01

    Chickens from two closely related sublines, GHs-B6 and GHs-B13, differing serologically at the major histocompatibility complex, were significantly different in their humoral response to three avian egg white lysozymes. Specific antisera levels were measured by radioimmunoassay using 125 I-labeled lysozymes. Antibodies elicited in response to these lysozymes are assumed to be directed against sites on these lysozymes where their amino acid sequence differs from that of the recipient G. domesticus egg white lysozyme (HEL). GHs-B6 birds produced a high level of antibody in response to immunization of turkey (TEL), pheasant (PhL) and guinea hen (GHL) lysozymes. GHs-B13 birds produced no detectable antibody to TEL, were intermediate in their response to PhL and equaled the antibody production of GHs-B6 birds in response to GHL. Antisera to each lysozyme were examined for crossreactivity with all other lysozymes by use of a competitive binding assay

  4. Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    P.J. Basso

    2014-09-01

    Full Text Available Inflammatory bowel disease (IBD, which includes Crohn's disease (CD and ulcerative colitis (UC, is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.

  5. Model for fitting longitudinal traits subject to threshold response applied to genetic evaluation for heat tolerance

    Directory of Open Access Journals (Sweden)

    Misztal Ignacy

    2009-01-01

    Full Text Available Abstract A semi-parametric non-linear longitudinal hierarchical model is presented. The model assumes that individual variation exists both in the degree of the linear change of performance (slope beyond a particular threshold of the independent variable scale and in the magnitude of the threshold itself; these individual variations are attributed to genetic and environmental components. During implementation via a Bayesian MCMC approach, threshold levels were sampled using a Metropolis step because their fully conditional posterior distributions do not have a closed form. The model was tested by simulation following designs similar to previous studies on genetics of heat stress. Posterior means of parameters of interest, under all simulation scenarios, were close to their true values with the latter always being included in the uncertain regions, indicating an absence of bias. The proposed models provide flexible tools for studying genotype by environmental interaction as well as for fitting other longitudinal traits subject to abrupt changes in the performance at particular points on the independent variable scale.

  6. Estimates of genetic correlations and correlated responses to selection in cashew (Anacardium occidentale L.

    Directory of Open Access Journals (Sweden)

    Diógenes Manoel Pedroza de Azevedo

    1998-09-01

    Full Text Available The present study estimates variances and genetic and phenotypic correlations for five traits in 27 progenies of cashew trees (Anacardium occidentale L.. Data were obtained from a trial conducted in 1992 at Pacajus, Ceará, experimental station of Embrapa Agroindústria Tropical. The characters studied were plant height (PH, North-South and East-West canopy spreads (NSS, EWS, and primary and secondary branch numbers (PBN, SBN. All genetic and phenotypic correlations presented positive and significant values. Selection to increase or decrease the average of any one of the five characteristics of cashew plants in the progenies studied affected the average of the others. The 16-month-old canopy spread can be predicted from NSS or EWS since correlations between them were high. Correlations between PH and SBN were low, indicating that there is a good possibility of obtaining smaller plants without causing drastic reductions in SBN. PH and SBN showed, respectively, the lowest and highest genetic variance estimates relative to the corresponding population means.Neste trabalho são estimadas variâncias, correlações genéticas e fenotípicas e respostas correlacionadas, envolvendo cinco caracteres em 27 progênies de cajueiro (Anacardium occidentale L.. Os dados foram obtidos em Pacajus-CE, num ensaio conduzido no Campo Experimental da Embrapa Agroindústria Tropical, em l992. Os caracteres estudados foram altura de planta (PH, envergaduras norte-sul (NSS e leste-oeste (EWS e número de ramos primários (PBN e secundários (SBN. Todas as correlacões genéticas e fenotípicas obtidas foram positivas e significativas. A seleção para aumentar ou reduzir a média de qualquer um dos cinco caracteres estudados nas progênies de cajueiro afetou indiretamente a média dos outros quatro caracteres. A envergadura da copa aos 16 meses pode ser representada por NSS ou EWS, tendo em vista que a correlação entre elas foi elevada. As correlações envolvendo PH

  7. Effects of Diet and Genetics on Growth Performance of Pigs in Response to Repeated Exposure to Heat Stress

    Directory of Open Access Journals (Sweden)

    Wendy M. Rauw

    2017-10-01

    Full Text Available Heat stress (HS is one of the costliest issues in the U.S. pork industry. Aims of the present study were to determine the consequences of repeated exposure to HS on growth performance, and the effects of a high fiber diet, the genetic potential for high lean tissue accretion, and the genetic potential for residual feed intake (RFI on resilience to HS. Barrows (n = 97 from three genetic lines (commercial, high RFI, low RFI where subjected three times to a 4-day HS treatment (HS1, HS2, and HS3 which was preceded by a 9-day neutral (TN adaptation period (TN1 and alternated by 7-day periods of neutral temperatures (TN2, TN3, and TN4. Body weight gain (BWG, feed intake (FI, feed conversion efficiency (FCE, RFI, and the drop in BWG and FI between TN and HS were estimated for each period, and slaughter traits were measured at the end of TN4. Commercial pigs had lower FI when fed a high fiber diet compared to a regular diet (2.70 ± 0.08 vs. 2.96 ± 0.08 kg/d; P < 0.05, while no differences were found for BWG, RFI or FCE. HS reduced FI, BWG, and FCE, increased RFI, and resulted in leaner pigs that generate smaller carcasses at slaughter. In TN, commercial pigs grew faster than the low and high RFI pigs (1.22 ± 0.06 vs. 0.720 ± 0.05 and 0.657 ± 0.07; P < 0.001 but growth rates were not significantly different between the lines during HS. Growth rates for the low RFI and high RFI pigs were similar both during TN and during HS. Pigs of interest for genetic improvement are those that are able to maintain growth rates during HS. Our results show that response in growth to HS was repeatable over subsequent 4-d HS cycles, which suggests the potential for including this response in the breeding index. The best performing animals during HS are likely those that are not highly superior for growth in TN.

  8. Angry responses to infant challenges: parent, marital, and child genetic factors associated with harsh parenting.

    Science.gov (United States)

    Hajal, Nastassia; Neiderhiser, Jenae; Moore, Ginger; Leve, Leslie; Shaw, Daniel; Harold, Gordon; Scaramella, Laura; Ganiban, Jody; Reiss, David

    2015-01-01

    This study examined genetic and environmental influences on harsh parenting of adopted 9-month-olds (N = 503), with an emphasis on positive child-, parent-, and family-level characteristics. Evocative gene-environment correlation (rGE) was examined by testing the effect of both positive and negative indices of birth parent temperament on adoptive parents' harsh parenting. Adoptive fathers' harsh parenting was inversely related to birth mother positive temperament, indicating evocative rGE, as well as to marital quality. Adoptive parents' negative temperamental characteristics were related to hostile parenting for both fathers and mothers. Findings support the importance of enhancing positive family characteristics in addition to mitigating negative characteristics, as well as engaging multiple levels of the family system to prevent harsh parenting. © 2015 The Authors. Child Development © 2015 Society for Research in Child Development, Inc.

  9. Anti-TNF treatment response in rheumatoid arthritis patients is associated with genetic variation in the NLRP3-inflammasome

    DEFF Research Database (Denmark)

    Sode, Jacob; Vogel, Ulla; Bank, Steffen

    2014-01-01

    OBJECTIVE: Many patients with rheumatoid arthritis (RA) benefit from tumor necrosis factor-α blocking treatment (anti-TNF), but about one third do not respond. The objective of this study was to replicate and extend previously found associations between anti-TNF treatment response and genetic...... logistic regression analyses were performed to test associations between genotypes and treatment response at 3-6 months using the European League Against Rheumatism (EULAR) response criterion. American College of Rheumatology treatment response (ACR50) and relative change in 28-joint disease activity score.......36-0.98), p = 0.040, q = 0.76). Current smokers who carried the NLRP3(rs4612666) variant allele were less likely to benefit from anti-TNF treatment (OR = 0.24 (0.10-0.56), p = 0.001, q = 0.04). CONCLUSIONS: In a population of Danish RA patients, we confirm the NLRP3 gene as associated with EULAR anti...

  10. Genetic differences in transcript responses to low-dose ionizing radiation identify tissue functions associated with breast cancer susceptibility.

    Science.gov (United States)

    Snijders, Antoine M; Marchetti, Francesco; Bhatnagar, Sandhya; Duru, Nadire; Han, Ju; Hu, Zhi; Mao, Jian-Hua; Gray, Joe W; Wyrobek, Andrew J

    2012-01-01

    High dose ionizing radiation (IR) is a well-known risk factor for breast cancer but the health effects after low-dose (LD, differences in their sensitivity to radiation-induced mammary cancer (BALB/c and C57BL/6) for the purpose of identifying mechanisms of mammary cancer susceptibility. Unirradiated mammary and blood tissues of these strains differed significantly in baseline expressions of DNA repair, tumor suppressor, and stress response genes. LD exposures of 7.5 cGy (weekly for 4 weeks) did not induce detectable genomic instability in either strain. However, the mammary glands of the sensitive strain but not the resistant strain showed early transcriptional responses involving: (a) diminished immune response, (b) increased cellular stress, (c) altered TGFβ-signaling, and (d) inappropriate expression of developmental genes. One month after LD exposure, the two strains showed opposing responses in transcriptional signatures linked to proliferation, senescence, and microenvironment functions. We also discovered a pre-exposure expression signature in both blood and mammary tissues that is predictive for poor survival among human cancer patients (p = 0.0001), and a post-LD-exposure signature also predictive for poor patient survival (pidentify genetic features that predispose or protect individuals from LD-induced breast cancer.

  11. Genetic liability, environment, and the development of fussiness in toddlers: the roles of maternal depression and parental responsiveness.

    Science.gov (United States)

    Natsuaki, Misaki N; Ge, Xiaojia; Leve, Leslie D; Neiderhiser, Jenae M; Shaw, Daniel S; Conger, Rand D; Scaramella, Laura V; Reid, John B; Reiss, David

    2010-09-01

    Using a longitudinal, prospective adoption design, the authors of this study examined the effects of the environment (adoptive parents' depressive symptoms and responsiveness) and genetic liability of maternal depression (inferred by birth mothers' major depressive disorder [MDD]) on the development of fussiness in adopted children between 9 and 18 months old. The sample included 281 families linked through adoption, with each family including 4 individuals (i.e., adopted child, birth mother, adoptive father and mother). Results showed that adoptive mothers' depressive symptoms when their child was 9 months old were positively associated with child fussiness at 18 months. A significant interaction between birth mothers' MDD and adoptive mothers' responsiveness indicated that children of birth mothers with MDD showed higher levels of fussiness at 18 months when adoptive mothers had been less responsive to the children at 9 months. However, in the context of high levels of adoptive mothers' responsiveness, children of birth mothers with MDD did not show elevated fussiness at 18 months. Findings are discussed in terms of gene-environment interactions in the intergenerational risk transmission of depression.

  12. Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses.

    Science.gov (United States)

    Luo, Jie; Xu, Pei; Cao, Peijian; Wan, Hongjian; Lv, Xiaonan; Xu, Shengchun; Wang, Gangjun; Cook, Melloni N; Jones, Byron C; Lu, Lu; Wang, Xusheng

    2018-01-01

    Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE) but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1), down-regulation in NOE but rescue in RSE (pattern 2), up-regulation in both restraint stress followed by a saline injection (RSS) and NOE, and further amplification in RSE (pattern 3), and up-regulation in RSS but reduction in both NOE and RSE (pattern 4). We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs) to the 14 co-expression modules, including γ-aminobutyric acid receptor (GABA) signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses.

  13. Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses

    Directory of Open Access Journals (Sweden)

    Jie Luo

    2018-04-01

    Full Text Available Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1, down-regulation in NOE but rescue in RSE (pattern 2, up-regulation in both restraint stress followed by a saline injection (RSS and NOE, and further amplification in RSE (pattern 3, and up-regulation in RSS but reduction in both NOE and RSE (pattern 4. We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs to the 14 co-expression modules, including γ-aminobutyric acid receptor (GABA signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses.

  14. Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity.

    Directory of Open Access Journals (Sweden)

    Stephen R Doyle

    2017-07-01

    Full Text Available Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR and sub-optimal responder (SOR parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs, with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic

  15. Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

    Science.gov (United States)

    Nana-Djeunga, Hugues C.; Kengne-Ouafo, Jonas A.; Pion, Sébastien D. S.; Bopda, Jean; Kamgno, Joseph; Wanji, Samuel; Che, Hua; Kuesel, Annette C.; Walker, Martin; Basáñez, Maria-Gloria; Boakye, Daniel A.; Osei-Atweneboana, Mike Y.; Boussinesq, Michel; Prichard, Roger K.; Grant, Warwick N.

    2017-01-01

    Background Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana—exposed to more than a decade of regular ivermectin treatment—have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread. Methodology/Principal findings Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR. Conclusions/Significance This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different

  16. Genetic and clinical predictors of ovarian response in assisted reproductive technology

    Science.gov (United States)

    Wiweko, B.; Damayanti, I.; Suryandari, D.; Natadisastra, M.; Pratama, G.; Sumapraja, K.; Meutia, K.; Iffanolia, P.; Harzief, A. K.; Hestiantoro, A.

    2017-08-01

    Several factors are known to influence ovarian response to rFSH stimulation such as age, antral follicle count (AFC), and basal FSH level, Mutation of allele Ser680Asn in FSHR gene was responsible to ovarian resistance toward exogenous FSH. The aim of this study is to develop a prediction model of ovarian response to COS in IVF. This study was a prospective cohort study. One hundred and thirteen women undergoing their first cycle of IVF in Yasmin IVF Clinic Jakarta were recruited to this study. Clinical datas included were age, BMI, and AFC. Basal FSH and E2 as well as serum AMH was measured from peripheral blood taken at second day of cycle. Bsr-1 enzyme is used to identify the polymorphism in exon 10 position 680 with RFLP technique. Three genotype polymorphism, Asn/Asn (255 bp ribbon), Asn/Ser (97 bp and 158 bp), and Ser/Ser (97 bp, 158 bp, and 255 bp). AFC has the highest predictor for ovarian response with AUC 0.922 (CI 95% 0.833-1.000). AMH also showed high predicting value (AUC 0.843 CI 95% 0.663-1.000). The multivariate analysis revealed combination of AFC, AMH, age, and basal FSH is a good model for ovarian response prediction (AUC=0.97). No significant relation between Asn/Asn, Asn/Ser, or Ser/Ser genotype FSHR polymorphism with ovarian response (p = 0.866) and total dose of rRSH (p = 0.08). This study showed that model combination of AFC, AMH, patient’s age and basal FSH are very good to predict number of mature oocytes.

  17. Genetic parameters and expected responses to selection for components of feed efficiency in a Duroc pig line.

    Science.gov (United States)

    Sánchez, Juan P; Ragab, Mohamed; Quintanilla, Raquel; Rothschild, Max F; Piles, Miriam

    2017-12-01

    Improving feed efficiency ([Formula: see text]) is a key factor for any pig breeding company. Although this can be achieved by selection on an index of multi-trait best linear unbiased prediction of breeding values with optimal economic weights, considering deviations of feed intake from actual needs ([Formula: see text]) should be of value for further research on biological aspects of [Formula: see text]. Here, we present a random regression model that extends the classical definition of [Formula: see text] by including animal-specific needs in the model. Using this model, we explore the genetic determinism of several [Formula: see text] components: use of feed for growth ([Formula: see text]), use of feed for backfat deposition ([Formula: see text]), use of feed for maintenance ([Formula: see text]), and unspecific efficiency in the use of feed ([Formula: see text]). Expected response to alternative selection indexes involving different components is also studied. Based on goodness-of-fit to the available feed intake ([Formula: see text]) data, the model that assumes individual (genetic and permanent) variation in the use of feed for maintenance, [Formula: see text] and [Formula: see text] showed the best performance. Joint individual variation in feed allocation to maintenance, growth and backfat deposition comprised 37% of the individual variation of [Formula: see text]. The estimated heritabilities of [Formula: see text] using the model that accounts for animal-specific needs and the traditional [Formula: see text] model were 0.12 and 0.18, respectively. The estimated heritabilities for the regression coefficients were 0.44, 0.39 and 0.55 for [Formula: see text], [Formula: see text] and [Formula: see text], respectively. Estimates of genetic correlations of [Formula: see text] were positive with amount of feed used for [Formula: see text] and [Formula: see text] but negative for [Formula: see text]. Expected response in overall efficiency, reducing [Formula

  18. Distribution of the Most Common Genetic Variants Associated with a Variable Drug Response in the Population of the Republic of Macedonia

    Directory of Open Access Journals (Sweden)

    Nestorovska Kapedanovska A.

    2014-12-01

    Full Text Available Genetic variation in the regulation, expression and activity of genes coding for Phase I, Phase II drug metabolizing enzymes (DMEs and drug targets, can be defining factors for the variability in both the effectiveness and occurrence of drug therapy side effects. Information regarding the geographic structure and multi-ethnic distribution of clinically relevant genetic variations is becoming increasingly useful for improving drug therapy and explaining inter-individual and inter-ethnic differences in drug response.

  19. Contradictory genetic make-up of Dutch harbour porpoises: Response to van der Plas-Duivesteijn et al.

    Science.gov (United States)

    Kopps, Anna M.; Palsbøll, Per J.

    2016-02-01

    The assessment of the status of endangered species or populations typically draw generously on the plethora of population genetic software available to detect population genetic structuring. However, despite the many available analytical approaches, population genetic inference methods [of neutral genetic variation] essentially capture three basic processes; migration, random genetic drift and mutation. Consequently, different analytical approaches essentially capture the same basic process, and should yield consistent results.

  20. Leptin responsiveness to energy restriction: genetic variation in the leptin receptor gene

    NARCIS (Netherlands)

    Mars, M.; Rossum, van C.T.M.; Graaf, de C.; Hoebee, B.; Groot, de C.P.G.M.; Kok, F.J.

    2004-01-01

    Serum leptin concentrations are an important afferent signal in energy balance homeostasis. It has been speculated that the leptin responsiveness to energy restriction is affected by the functionality of the leptin receptor. The purpose of this analysis was to explore the effect of polymorphisms in

  1. Genetic immunization in the lung induces potent local and systemic immune responses

    NARCIS (Netherlands)

    Song, Kaimei; Bolton, Diane L.; Wilson, Robert L.; Camp, Jeremy V.; Bao, Saran; Mattapallil, Joseph J.; Herzenberg, Leonore A.; Herzenberg, Leonard A.; Andrews, Charla A.; Sadoff, Jerald C.; Goudsmit, Jaap; Pau, Maria Grazia; Seder, Robert A.; Kozlowski, Pamela A.; Nabel, Gary J.; Roederer, Mario; Rao, Srinivas S.

    2010-01-01

    Successful vaccination against respiratory infections requires elicitation of high levels of potent and durable humoral and cellular responses in the lower airways. To accomplish this goal, we used a fine aerosol that targets the entire lung surface through normal respiration to deliver

  2. Functional genetic polymorphisms and female reproductive disorders : Part I: polycystic ovary syndrome and ovarian response

    NARCIS (Netherlands)

    Simoni, M.; Tempfer, C. B.; Destenaves, B.; Fauser, B. C. J. M.

    2008-01-01

    BACKGROUND: The identification of polymorphisms associated with a disease can help to elucidate its pathogenesis, and this knowledge can be used to improve prognosis for women with a particular disorder, such as polycystic ovary syndrome ( PCOS). Since an altered response to ovarian stimulation is

  3. Neural and genetic underpinnings of response inhibition in adolescents with attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    van Rooij, Daan

    2015-01-01

    In the huidige thesis onderzoek ik de neurale en genetische onderbouwing van response inhibitie in een groot cohort van adolescenten met ADHD, hun onaangedane siblings en gezonde controles. Ieder van de vier onderzoekshoofdstukken beantwoord een aparte vraag hieromtrent. In het tweede hoofdstuk van

  4. Genetic predictors for the response to therapy in colorectal cancer cells

    NARCIS (Netherlands)

    de Bruijn, M.T.

    2011-01-01

    The general goal of this thesis is to create a better insight into the genes and signaling proteins that influence the response of colorectal cancer cells to MEK-targeted therapy and chemotherapy (5-FU and oxaliplatin). In chapter 2 of this thesis we set out to explore the mechanisms of resistance

  5. Influence of some exo nucleases in response to the induced genetic damage in Escherichia coli by alpha radiation

    International Nuclear Information System (INIS)

    Aguilar M, M.

    2005-01-01

    Within the strategies with those that E. coli counts to overcome to the genetic damage there is the SOS response, a group of genes that participate in repair and/or tolerance that it confers to the bacteria major opportunities of surviving. These genes are repressed and its only are expressed when it happens genetic damage. So that this system is activated it is necessary that DNA of a band exists and in this sense the double ruptures (RDB) its are not able to induce this response unless there is a previous processing. In stumps with defects in certain genes that have to do with repair of RDB (as recO, recJ and xonA) the activity of SOS is smaller than in a wild stump what suggests that these participate in the previous processes to the activation of the response. The ionizing radiation produce among other many lesions, RDB in greater or smaller proportion, depending on the ionization capacity. A parameter to evaluate this capacity is the lineal energy transfer (LET), defined as the average energy given by unit of distance travelled. In general the LET of the corpuscular radiations is a lot but high that of the electromagnetic one, for what produces bigger quantity of ionizations inside a restricted zone and it increases by this way the probability that RDB has been generated. This work has for object to infer the participation of xonA and recJ in this response and to evaluate the damage produced by ionizing radiation of different LET (alpha particles of different energies) in a stump with all the functional repair mechanisms. Its were considered two parameters: the survival and the activity of SOS evaluated by means of the chromo test. The results indicate that the activity of these exo nucleases is necessary for the repair of RDB as well as for the processing of lesions foresaw to the activation of SOS. As for the treatment with alphas of different energies is observed that so much the survival like the activity of SOS vary as the LET of the radiation changes

  6. Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP.

    Directory of Open Access Journals (Sweden)

    Caleb C Roth

    Full Text Available Nanosecond electrical pulse (nsEP exposure activates signaling pathways, produces oxidative stress, stimulates hormone secretion, causes cell swelling and induces apoptotic and necrotic death. The underlying biophysical connection(s between these diverse cellular reactions and nsEP has yet to be elucidated. Using global genetic analysis, we evaluated how two commonly studied cell types, U937 and Jurkat, respond to nsEP exposure. We hypothesized that by studying the genetic response of the cells following exposure, we would gain direct insight into the stresses experienced by the cell and in turn better understand the biophysical interaction taking place during the exposure. Using Ingenuity Systems software, we found genes associated with cell growth, movement and development to be significantly up-regulated in both cell types 4 h post exposure to nsEP. In agreement with our hypothesis, we also found that both cell lines exhibit significant biological changes consistent with mechanical stress induction. These results advance nsEP research by providing strong evidence that the interaction of nsEPs with cells involves mechanical stress.

  7. Changes of antioxidative enzymes in Impatiens walleriana L. shoots in response to genetic transformation

    Directory of Open Access Journals (Sweden)

    Milošević Snežana

    2015-01-01

    Full Text Available Impatiens walleriana L. shoots were inoculated with Agrobacterium rhizogenes A4M70GUS and the effects of genetic transformation on the catalase (CAT, superoxide dismutase (SOD and peroxidase (POX activities in wounded region of stems and unwounded leaves were evaluated 10, 24, 240 and 720 hours after inoculation. Following Agrobacterum infection activities of plant antioxidative enzymes changed in a time-dependent manner indicating that dynamic processes occurred during plant-Agrobacterium interaction, plant cell transformation and formation of hairy roots. Appearance of hairy roots on wound sites of shoots was observed ten days after inoculation with A. rhizogenes and the root induction frequency was 100%. Among selected hairy root lines significant differences in growth rate and biomass production were observed and an average 3-fold increase in biomass production was observed for the best growing hairy root line compared with the untransformed roots. PCR analysis showed presence of uidA, rolB, rolC and rolD genes in all analyzed I. walleriana L. hairy root lines, while amplification fragment of rolA gene was detected in 83.3% transformed lines. Efficient transformation protocol for I. walleriana L described in this work offer possibilities to generate hairy root cultures for in vitro propagation of plant viruses. [Projekat Ministarstva nauke Republike Srbije, br. TR-31019

  8. Genetic response to metabolic fluctuations: correlation between central carbon metabolism and DNA replication in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Szalewska-Pałasz Agnieszka

    2011-03-01

    Full Text Available Abstract Background Until now, the direct link between central carbon metabolism and DNA replication has been demonstrated only in Bacillus. subtilis. Therefore, we asked if this is a specific phenomenon, characteristic for this bacterium and perhaps for its close relatives, or a more general biological rule. Results We found that temperature-sensitivity of mutants in particular genes coding for replication proteins could be suppressed by deletions of certain genes coding for enzymes of the central carbon metabolism. Namely, the effects of dnaA46(ts mutation could be suppressed by dysfunction of pta or ackA, effects of dnaB(ts by dysfunction of pgi or pta, effects of dnaE486(ts by dysfunction of tktB, effects of dnaG(ts by dysfunction of gpmA, pta or ackA, and effects of dnaN159(ts by dysfunction of pta or ackA. The observed suppression effects were not caused by a decrease in bacterial growth rate. Conclusions The genetic correlation exists between central carbon metabolism and DNA replication in the model Gram-negative bacterium, E. coli. This link exists at the steps of initiation and elongation of DNA replication, indicating the important global correlation between metabolic status of the cell and the events leading to cell reproduction.

  9. RNA-Seq reveals complex genetic response to deepwater horizon oil release in Fundulus grandis

    Directory of Open Access Journals (Sweden)

    Garcia Tzintzuni I

    2012-09-01

    Full Text Available Abstract Background The release of oil resulting from the blowout of the Deepwater Horizon (DH drilling platform was one of the largest in history discharging more than 189 million gallons of oil and subject to widespread application of oil dispersants. This event impacted a wide range of ecological habitats with a complex mix of pollutants whose biological impact is still not yet fully understood. To better understand the effects on a vertebrate genome, we studied gene expression in the salt marsh minnow Fundulus grandis, which is local to the northern coast of the Gulf of Mexico and is a sister species of the ecotoxicological model Fundulus heteroclitus. To assess genomic changes, we quantified mRNA expression using high throughput sequencing technologies (RNA-Seq in F. grandis populations in the marshes and estuaries impacted by DH oil release. This application of RNA-Seq to a non-model, wild, and ecologically significant organism is an important evaluation of the technology to quickly assess similar events in the future. Results Our de novo assembly of RNA-Seq data produced a large set of sequences which included many duplicates and fragments. In many cases several of these could be associated with a common reference sequence using blast to query a reference database. This reduced the set of significant genes to 1,070 down-regulated and 1,251 up-regulated genes. These genes indicate a broad and complex genomic response to DH oil exposure including the expected AHR-mediated response and CYP genes. In addition a response to hypoxic conditions and an immune response are also indicated. Several genes in the choriogenin family were down-regulated in the exposed group; a response that is consistent with AH exposure. These analyses are in agreement with oligonucleotide-based microarray analyses, and describe only a subset of significant genes with aberrant regulation in the exposed set. Conclusion RNA-Seq may be successfully applied to feral and

  10. Warfarin resistance associated with genetic polymorphism of VKORC1: linking clinical response to molecular mechanism using computational modeling.

    Science.gov (United States)

    Lewis, Benjamin C; Nair, Pramod C; Heran, Subash S; Somogyi, Andrew A; Bowden, Jeffrey J; Doogue, Matthew P; Miners, John O

    2016-01-01

    The variable response to warfarin treatment often has a genetic basis. A protein homology model of human vitamin K epoxide reductase, subunit 1 (VKORC1), was generated to elucidate the mechanism of warfarin resistance observed in a patient with the Val66Met mutation. The VKORC1 homology model comprises four transmembrane (TM) helical domains and a half helical lid domain. Cys132 and Cys135, located in the N-terminal end of TM-4, are linked through a disulfide bond. Two distinct binding sites for warfarin were identified. Site-1, which binds vitamin K epoxide (KO) in a catalytically favorable orientation, shows higher affinity for S-warfarin compared with R-warfarin. Site-2, positioned in the domain occupied by the hydrophobic tail of KO, binds both warfarin enantiomers with similar affinity. Displacement of Arg37 occurs in the Val66Met mutant, blocking access of warfarin (but not KO) to Site-1, consistent with clinical observation of warfarin resistance.

  11. Optimisation of process parameters on thin shell part using response surface methodology (RSM) and genetic algorithm (GA)

    Science.gov (United States)

    Faiz, J. M.; Shayfull, Z.; Nasir, S. M.; Fathullah, M.; Hazwan, M. H. M.

    2017-09-01

    This study conducts the simulation on optimisation of injection moulding process parameters using Autodesk Moldflow Insight (AMI) software. This study has applied some process parameters which are melt temperature, mould temperature, packing pressure, and cooling time in order to analyse the warpage value of the part. Besides, a part has been selected to be studied which made of Polypropylene (PP). The combination of the process parameters is analysed using Analysis of Variance (ANOVA) and the optimised value is obtained using Response Surface Methodology (RSM). The RSM as well as Genetic Algorithm are applied in Design Expert software in order to minimise the warpage value. The outcome of this study shows that the warpage value improved by using RSM and GA.

  12. Optimal electricity dispatch on isolated mini-grids using a demand response strategy for thermal storage backup with genetic algorithms

    International Nuclear Information System (INIS)

    Neves, Diana; Silva, Carlos A.

    2015-01-01

    The present study uses the DHW (domestic hot water) electric backup from solar thermal systems to optimize the total electricity dispatch of an isolated mini-grid. The proposed approach estimates the hourly DHW load, and proposes and simulates different DR (demand response) strategies, from the supply side, to minimize the dispatch costs of an energy system. The case study consists on optimizing the electricity load, in a representative day with low solar radiation, in Corvo Island, Azores. The DHW backup is induced by three different demand patterns. The study compares different DR strategies: backup at demand (no strategy), pre-scheduled backup using two different imposed schedules, a strategy based on linear programming, and finally two strategies using genetic algorithms, with different formulations for DHW backup – one that assigns number of systems and another that assigns energy demand. It is concluded that pre-determined DR strategies may increase the generation costs, but DR strategies based on optimization algorithms are able to decrease generation costs. In particular, linear programming is the strategy that presents the lowest increase on dispatch costs, but the strategy based on genetic algorithms is the one that best minimizes both daily operation costs and total energy demand, of the system. - Highlights: • Integrated hourly model of DHW electric impact and electricity dispatch of isolated grid. • Proposal and comparison of different DR (demand response) strategies for DHW backup. • LP strategy presents 12% increase on total electric load, plus 5% on dispatch costs. • GA strategy presents 7% increase on total electric load, plus 8% on dispatch costs

  13. A genetic screen in Myxococcus xanthus identifies mutants that uncouple outer membrane exchange from a downstream cellular response.

    Science.gov (United States)

    Dey, Arup; Wall, Daniel

    2014-12-01

    Upon physical contact with sibling cells, myxobacteria transiently fuse their outer membranes (OMs) and exchange OM proteins and lipids. From previous work, TraA and TraB were identified to be essential factors for OM exchange (OME) in donor and recipient cells. To define the genetic complexity of OME, we carried out a comprehensive forward genetic screen. The screen was based on the observation that Myxococcus xanthus nonmotile cells, by a Tra-dependent mechanism, block swarm expansion of motile cells when mixed. Thus, mutants defective in OME or a downstream responsive pathway were readily identified as escape flares from mixed inocula seeded on agar. This screen was surprisingly powerful, as we found >50 mutants defective in OME. Importantly, all of the mutations mapped to the traAB operon, suggesting that there may be few, if any, proteins besides TraA and TraB directly required for OME. We also found a second and phenotypically different class of mutants that exhibited wild-type OME but were defective in a responsive pathway. This pathway is postulated to control inner membrane homeostasis by covalently attaching amino acids to phospholipids. The identified proteins are homologous to the Staphylococcus aureus MprF protein, which is involved in membrane adaptation and antibiotic resistance. Interestingly, we also found that a small number of nonmotile cells were sufficient to block the swarming behavior of a large gliding-proficient population. This result suggests that an OME-derived signal could be amplified from a few nonmotile producers to act on many responder cells. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  14. Leptin responsiveness to energy restriction: genetic variation in the leptin receptor gene.

    Science.gov (United States)

    Mars, Monica; van Rossum, Caroline T M; de Graaf, Cees; Hoebee, Barbara; De Groot, Lisette C P G M; Kok, Frans J

    2004-03-01

    Serum leptin concentrations are an important afferent signal in energy balance homeostasis. It has been speculated that the leptin responsiveness to energy restriction is affected by the functionality of the leptin receptor. The purpose of this analysis was to explore the effect of polymorphisms in the LEPR gene on the acute decline in leptin after 4 days of 65% energy restriction. Leptin concentrations of the study group (n = 44; all men) declined by 2.3 +/- 1.5 micro g/L [-39.4% (95% confidence interval: -43.6 to -34.9)]. Leptin responses did not statistically differ between noncarriers and carriers of three mutant variants of the polymorphisms: Lys109/Lys109 (-41.4%) vs. Arg109/+ (-37.0%) (p = 0.33); Gln223/Gln223 (-41.5%) vs. Arg223/+ (-37.8%) (p = 0.40); Lys656/Lys656 (-39.5%) vs. Asn656/+ (-39.3%) (p = 0.96). No effect of the assessed polymorphisms in the LEPR gene on the acute decline in leptin after energy restriction was observed. Power calculations are provided for future studies on the leptin responsiveness to energy restriction.

  15. Attached and planktonic Listeria monocytogenes global proteomic responses and associated influence of strain genetics and temperature.

    Science.gov (United States)

    Mata, Marcia M; da Silva, Wladimir P; Wilson, Richard; Lowe, Edwin; Bowman, John P

    2015-02-06

    Contamination of industrial and domestic food usage environments by the attachement of bacterial food-borne pathogen Listeria monocytogenes has public health and economic implications. Comprehensive proteomics experiments using label-free liquid chromatography/tandem mass spectrometry were used to compare the proteomes of two different L. monocytogenes strains (Siliken_1/2c and F2365_4b), which show very different capacities to attach to surfaces. Growth temperature and strain type were highly influential on the proteomes in both attached and planktonic cells. On the basis of the proteomic data, it is highly unlikely that specific surface proteins play a direct role in adherence to inanimate surfaces. Instead, strain-dependent responses related to cell envelope polymer biosynthesis and stress response regulation likely contribute to a different ability to attach and also to survive external stressors. Collectively, the divergent proteome-level responses observed define strain- and growth-temperature-dependent differences relevant to attachment efficacy, highlight relevant proteins involved in stress protection in attached cells, and suggest that strain differences and growth conditions are important in relation to environmental persistence.

  16. Systematic differences in the response of genetic variation to pedigree and genome-based selection methods.

    Science.gov (United States)

    Heidaritabar, M; Vereijken, A; Muir, W M; Meuwissen, T; Cheng, H; Megens, H-J; Groenen, M A M; Bastiaansen, J W M

    2014-12-01

    Genomic selection (GS) is a DNA-based method of selecting for quantitative traits in animal and plant breeding, and offers a potentially superior alternative to traditional breeding methods that rely on pedigree and phenotype information. Using a 60 K SNP chip with markers spaced throughout the entire chicken genome, we compared the impact of GS and traditional BLUP (best linear unbiased prediction) selection methods applied side-by-side in three different lines of egg-laying chickens. Differences were demonstrated between methods, both at the level and genomic distribution of allele frequency changes. In all three lines, the average allele frequency changes were larger with GS, 0.056 0.064 and 0.066, compared with BLUP, 0.044, 0.045 and 0.036 for lines B1, B2 and W1, respectively. With BLUP, 35 selected regions (empirical P selected regions were identified. Empirical thresholds for local allele frequency changes were determined from gene dropping, and differed considerably between GS (0.167-0.198) and BLUP (0.105-0.126). Between lines, the genomic regions with large changes in allele frequencies showed limited overlap. Our results show that GS applies selection pressure much more locally than BLUP, resulting in larger allele frequency changes. With these results, novel insights into the nature of selection on quantitative traits have been gained and important questions regarding the long-term impact of GS are raised. The rapid changes to a part of the genetic architecture, while another part may not be selected, at least in the short term, require careful consideration, especially when selection occurs before phenotypes are observed.

  17. Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism.

    Science.gov (United States)

    Vandell, Alexander G; Walker, Joseph; Brown, Karen S; Zhang, George; Lin, Min; Grosso, Michael A; Mercuri, Michele F

    2017-11-01

    The aim of this study was to investigate whether genetic variants can identify patients with venous thromboembolism (VTE) at an increased risk of bleeding with warfarin. Hokusai-venous thromboembolism (Hokusai VTE), a randomised, multinational, double-blind, non-inferiority trial, evaluated the safety and efficacy of edoxaban versus warfarin in patients with VTE initially treated with heparin. In this subanalysis of Hokusai VTE, patients genotyped for variants in CYP2C9 and VKORC1 genes were divided into three warfarin sensitivity types (normal, sensitive and highly sensitive) based on their genotypes. An exploratory analysis was also conducted comparing normal responders to pooled sensitive responders (ie, sensitive and highly sensitive responders). The analysis included 47.7% (3956/8292) of the patients in Hokusai VTE. Among 1978 patients randomised to warfarin, 63.0% (1247) were normal responders, 34.1% (675) were sensitive responders and 2.8% (56) were highly sensitive responders. Compared with normal responders, sensitive and highly sensitive responders had heparin therapy discontinued earlier (pwarfarin dose (pwarfarin (sensitive responders HR 1.38 [95% CI 1.11 to 1.71], p=0.0035; highly sensitive responders 1.79 [1.09 to 2.99]; p=0.0252). In this study, CYP2C9 and VKORC1 genotypes identified patients with VTE at increased bleeding risk with warfarin. NCT00986154. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Role of genetic polymorphisms in NFKB-mediated inflammatory pathways in response to primary chemoradiation therapy for rectal cancer.

    Science.gov (United States)

    Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

    2014-11-01

    To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Role of Genetic Polymorphisms in NFKB-Mediated Inflammatory Pathways in Response to Primary Chemoradiation Therapy for Rectal Cancer

    International Nuclear Information System (INIS)

    Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

    2014-01-01

    Purpose: To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Methods and Materials: Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. Results: The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Conclusions: Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment

  20. SIRT1 genetic variants associate with the metabolic response of Caucasians to a controlled lifestyle intervention – the TULIP Study

    Directory of Open Access Journals (Sweden)

    Stefan Norbert

    2008-11-01

    Full Text Available Abstract Background Sirtuin1 (SIRT1 regulates gene expression in distinct metabolic pathways and mediates beneficial effects of caloric restriction in animal models. In humans, SIRT1 genetic variants associate with fasting energy expenditure. To investigate the relevance of SIRT1 for human metabolism and caloric restriction, we analyzed SIRT1 genetic variants in respect to the outcome of a controlled lifestyle intervention in Caucasians at risk for type 2 diabetes. Methods A total of 1013 non-diabetic Caucasians from the Tuebingen Family Study (TUEF were genotyped for four tagging SIRT1 SNPs (rs730821, rs12413112, rs7069102, rs2273773 for cross-sectional association analyses with prediabetic traits. SNPs that associated with basal energy expenditure in the TUEF cohort were additionally analyzed in 196 individuals who underwent a controlled lifestyle intervention (Tuebingen Lifestyle Intervention Program; TULIP. Multivariate regressions analyses with adjustment for relevant covariates were performed to detect associations of SIRT1 variants with the changes in anthropometrics, weight, body fat or metabolic characteristics (blood glucose, insulin sensitivity, insulin secretion and liver fat, measured by magnetic resonance techniques after the 9-month follow-up test in the TULIP study. Results Minor allele (X/A carriers of rs12413112 (G/A had a significantly lower basal energy expenditure (p = 0.04 and an increased respiratory quotient (p = 0.02. This group (rs12413112: X/A was resistant against lifestyle-induced improvement of fasting plasma glucose (GG: -2.01%, X/A: 0.53%; p = 0.04, had less increase in insulin sensitivity (GG: 17.3%, X/A: 9.6%; p = 0.05 and an attenuated decline in liver fat (GG: -38.4%, X/A: -7.5%; p = 0.01. Conclusion SIRT1 plays a role for the individual lifestyle intervention response, possibly owing to decreased basal energy expenditure and a lower lipid-oxidation rate in rs12413112 X/A allele carriers. SIRT1 genetic

  1. Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Katherine E Tansey

    Full Text Available It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way.The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study. After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10(-8. No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10(-8 were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D, with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D.No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the

  2. Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

    Science.gov (United States)

    Tansey, Katherine E; Guipponi, Michel; Perroud, Nader; Bondolfi, Guido; Domenici, Enrico; Evans, David; Hall, Stephanie K; Hauser, Joanna; Henigsberg, Neven; Hu, Xiaolan; Jerman, Borut; Maier, Wolfgang; Mors, Ole; O'Donovan, Michael; Peters, Tim J; Placentino, Anna; Rietschel, Marcella; Souery, Daniel; Aitchison, Katherine J; Craig, Ian; Farmer, Anne; Wendland, Jens R; Malafosse, Alain; Holmans, Peter; Lewis, Glyn; Lewis, Cathryn M; Stensbøl, Tine Bryan; Kapur, Shitij; McGuffin, Peter; Uher, Rudolf

    2012-01-01

    It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way. The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance panalysis of NEWMEDS and another large sample (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D. No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the Editors' Summary.

  3. Molecular genetics of human immune responsiveness to Lolium perenne (rye) allergen, Lol p III.

    Science.gov (United States)

    Ansari, A A; Freidhoff, L R; Marsh, D G

    1989-01-01

    Lol p II and III are each about 11-kD protein allergens from the pollen of Lolium perenne (rye grass). We have found that human immune responses (IgE and IgG antibodies) to both proteins are significantly associated with HLA-DR3. In addition, the two proteins are cross-reactive with the antibodies in many human sera (about 84% human sera showed the cross-reactivity). We have determined greater than 90% of the amino acid sequences of the two proteins and found that they are at least 54% homologous. Berzofsky found that 75% of the 23 known T cell sites in various proteins had an amphipathic structure. Our analysis by the same method showed that both Lol p II and III have a major region of amphipathicity (at residues 61-67, Lol p III numbering) which might contain sites for binding to an Ia molecule and a T cell receptor. This region is identical between Lol p II and III, except for an Arg-Lys substitution, and could account, in part, for the DR3 association with responsiveness to both molecules. An interesting difference between the two proteins is that immune response to Lol p III is associated with DR5 (in addition to DR3), whereas no DR5 association is found in the case of Lol p II. One possibility is that Lol p III has an additional site which binds to the DR5 Ia molecule. Lol p III indeed has a second highly amphiphathic peptide, 24-30 (Lol p III 24 R P G D T L A 30), which is different and not amphipathic in Lol p II.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. A genetic network model of cellular responses to lithium treatment and cocaine abuse in bipolar disorder

    Directory of Open Access Journals (Sweden)

    Keller Benjamin J

    2010-11-01

    Full Text Available Abstract Background Lithium is an effective treatment for Bipolar Disorder (BD and significantly reduces suicide risk, though the molecular basis of lithium's effectiveness is not well understood. We seek to improve our understanding of this effectiveness by posing hypotheses based on new experimental data as well as published data, testing these hypotheses in silico, and posing new hypotheses for validation in future studies. We initially hypothesized a gene-by-environment interaction where lithium, acting as an environmental influence, impacts signal transduction pathways leading to differential expression of genes important in the etiology of BD mania. Results Using microarray and rt-QPCR assays, we identified candidate genes that are differentially expressed with lithium treatment. We used a systems biology approach to identify interactions among these candidate genes and develop a network of genes that interact with the differentially expressed candidates. Notably, we also identified cocaine as having a potential influence on the network, consistent with the observed high rate of comorbidity for BD and cocaine abuse. The resulting network represents a novel hypothesis on how multiple genetic influences on bipolar disorder are impacted by both lithium treatment and cocaine use. Testing this network for association with BD and related phenotypes, we find that it is significantly over-represented for genes that participate in signal transduction, consistent with our hypothesized-gene-by environment interaction. In addition, it models related pharmacogenomic, psychiatric, and chemical dependence phenotypes. Conclusions We offer a network model of gene-by-environment interaction associated with lithium's effectiveness in treating BD mania, as well as the observed high rate of comorbidity of BD and cocaine abuse. We identified drug targets within this network that represent immediate candidates for therapeutic drug testing. Posing novel

  5. The response to selection in Glycoside Hydrolase Family 13 structures: A comparative quantitative genetics approach.

    Directory of Open Access Journals (Sweden)

    Jose Sergio Hleap

    Full Text Available The Glycoside Hydrolase Family 13 (GH13 is both evolutionarily diverse and relevant to many industrial applications. Its members hydrolyze starch into smaller carbohydrates and members of the family have been bioengineered to improve catalytic function under industrial environments. We introduce a framework to analyze the response to selection of GH13 protein structures given some phylogenetic and simulated dynamic information. We find that the TIM-barrel (a conserved protein fold consisting of eight α-helices and eight parallel β-strands that alternate along the peptide backbone, common to all amylases is not selectable since it is under purifying selection. We also show a method to rank important residues with higher inferred response to selection. These residues can be altered to effect change in properties. In this work, we define fitness as inferred thermodynamic stability. We show that under the developed framework, residues 112Y, 122K, 124D, 125W, and 126P are good candidates to increase the stability of the truncated α-amylase protein from Geobacillus thermoleovorans (PDB code: 4E2O; α-1,4-glucan-4-glucanohydrolase; EC 3.2.1.1. Overall, this paper demonstrates the feasibility of a framework for the analysis of protein structures for any other fitness landscape.

  6. Molecular genetics of Turner syndrome: correlation with clinical phenotype and response to growth hormone therapy.

    Science.gov (United States)

    Tsezou, A; Hadjiathanasiou, C; Gourgiotis, D; Galla, A; Kavazarakis, E; Pasparaki, A; Kapsetaki, M; Sismani, C; Theodoridis, C; Patsalis, P C; Moschonas, N; Kitsiou, S

    1999-12-01

    To correlate the origin of the retained X in Turner syndrome with phenotype, pre-treatment height and response to recombinant human growth hormone (rhGH) therapy, systematic clinical assessment and molecular studies were carried out in 33 Greek children with Turner syndrome and their parents including 18 children with 45,X and 15 with X-mosaicism. Microsatellite markers on X chromosomes (DXS101 and DXS337) revealed that the intact X was paternal (Xp) in 15/30 and maternal (Xm) in 15/30 children, while 3/33 families were non-informative. No significant relationship was found between parental origin of the retained X and birth weight/length/gestational age, blepharoptosis, pterygium colli, webbed neck, low hairline, abnormal ears, lymphoedema, short 4th metacarpal, shield chest, widely spaced nipples, cubitus valgus, pigmented naevi, streak gonads, and cardiovascular/renal anomalies. With regard to the children's pre-treatment height, there was a significant correlation with maternal height and target height in both Xm and Xp groups. No differences were found between Xm and Xp groups and the improvement of growth velocity (GV) during the first and second year of rhGH administration, while for both groups GV significantly improved with rhGH by the end of the first and the second year. To our knowledge, this is the first attempt to correlate the parental origin of Turner syndrome with the response to rhGH therapy.

  7. Egr-1 induction provides a genetic response to food aversion in zebrafish

    Directory of Open Access Journals (Sweden)

    Brigitte eBoyer

    2013-05-01

    Full Text Available As soon as zebrafish larvae start eating, they exhibit a marked aversion for bitter and acidic substances, as revealed by a consumption assay, in which fluorescent Tetrahymena serve as a feeding basis, to which various stimuli can be added. Bitter and acidic substances elicited an increase in mRNA accumulation of the immediate-early response gene egr-1, as revealed by in situ hybridization. Conversely, chemostimulants that did not induce aversion did not induce egr-1 response. Maximum labelling was observed in cells located in the oropharyngeal cavity and on the gill rakers. Gustatory areas of the brain were also labelled. Interestingly, when bitter tastants were repeatedly associated with food reward, zebrafish juveniles learned to ingest food in the presence of the bitter compound. After habituation, the acquisition of acceptance for bitterness was accompanied by a loss of egr-1 labelling. Altogether, our data indicate that egr-1 participates specifically in food aversion. The existence of reward-coupled changes in taste sensitivity in humans suggests that our results are relevant to situations in humans.

  8. Genomancy: predicting tumour response to cancer therapy based on the oracle of genetics.

    Science.gov (United States)

    Williams, P D; Lee, J K; Theodorescu, D

    2009-01-01

    Cells are complex systems that regulate a multitude of biologic pathways involving a diverse array of molecules. Cancer can develop when these pathways become deregulated as a result of mutations in the genes coding for these proteins or of epigenetic changes that affect gene expression, or both1,2. The diversity and interconnectedness of these pathways and their molecular components implies that a variety of mutations may lead to tumorigenic cellular deregulation3-6. This variety, combined with the requirement to overcome multiple anticancer defence mechanisms7, contributes to the heterogeneous nature of cancer. Consequently, tumours with similar histology may vary in their underlying molecular circuitry8-10, with resultant differences in biologic behaviour, manifested in proliferation rate, invasiveness, metastatic potential, and unfortunately, response to cytotoxic therapy. Thus, cancer can be thought of as a family of related tumour subtypes, highlighting the need for individualized prediction both of disease progression and of treatment response, based on the molecular characteristics of the tumour.

  9. Egr-1 induction provides a genetic response to food aversion in zebrafish.

    Science.gov (United States)

    Boyer, Brigitte; Ernest, Sylvain; Rosa, Frédéric

    2013-01-01

    As soon as zebrafish larvae start eating, they exhibit a marked aversion for bitter and acidic substances, as revealed by a consumption assay, in which fluorescent Tetrahymena serve as a feeding basis, to which various stimuli can be added. Bitter and acidic substances elicited an increase in mRNA accumulation of the immediate-early response gene egr-1, as revealed by in situ hybridization. Conversely, chemostimulants that did not induce aversion did not induce egr-1 response. Maximum labeling was observed in cells located in the oropharyngeal cavity and on the gill rakers. Gustatory areas of the brain were also labeled. Interestingly, when bitter tastants were repeatedly associated with food reward, zebrafish juveniles learned to ingest food in the presence of the bitter compound. After habituation, the acquisition of acceptance for bitterness was accompanied by a loss of egr-1 labeling. Altogether, our data indicate that egr-1 participates specifically in food aversion. The existence of reward-coupled changes in taste sensitivity in humans suggests that our results are relevant to situations in humans.

  10. A Psycho-Genetic Study of Hedonic Responsiveness in Relation to “Food Addiction”

    Directory of Open Access Journals (Sweden)

    Caroline Davis

    2014-10-01

    Full Text Available While food addiction has no formally-recognized definition, it is typically operationalized according to the diagnostic principles established by the Yale Food Addiction Scale—an inventory based on the symptom criteria for substance dependence in the DSM-IV. Currently, there is little biologically-based research investigating the risk factors for food addiction. What does exist has focused almost exclusively on dopaminergic reward pathways in the brain. While brain opioid signaling has also been strongly implicated in the control of food intake, there is no research examining this neural circuitry in the association with food addiction. The purpose of the study was therefore to test a model predicting that a stronger activation potential of opioid circuitry-as indicated by the functional A118G marker of the mu-opioid receptor gene-would serve as an indirect risk factor for food addiction via a heightened hedonic responsiveness to palatable food. Results confirmed these relationships. In addition, our findings that the food-addiction group had significantly higher levels of hedonic responsiveness to food suggests that this bio-behavioral trait may foster a proneness to overeating, to episodes of binge eating, and ultimately to a compulsive and addictive pattern of food intake.

  11. Genetics and evolution of function-valued traits: understanding environmentally responsive phenotypes.

    Science.gov (United States)

    Stinchcombe, John R; Kirkpatrick, Mark

    2012-11-01

    Many central questions in ecology and evolutionary biology require characterizing phenotypes that change with time and environmental conditions. Such traits are inherently functions, and new 'function-valued' methods use the order, spacing, and functional nature of the data typically ignored by traditional univariate and multivariate analyses. These rapidly developing methods account for the continuous change in traits of interest in response to other variables, and are superior to traditional summary-based analyses for growth trajectories, morphological shapes, and environmentally sensitive phenotypes. Here, we explain how function-valued methods make flexible use of data and lead to new biological insights. These approaches frequently offer enhanced statistical power, a natural basis of interpretation, and are applicable to many existing data sets. We also illustrate applications of function-valued methods to address ecological, evolutionary, and behavioral hypotheses, and highlight future directions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Somatic cell genetics of uranium miners and plutonium workers. A biological dose-response indicator

    International Nuclear Information System (INIS)

    Brandom, W.F.; Bloom, A.D.; Bistline, R.W.; Saccomanno, G.

    1978-01-01

    Two populations of underground uranium miners and plutonium workers work in the state of Colorado, United States of America. We have explored the prevalence of structural chromosome aberrations in peripheral blood lymphocytes as a possible biological indicator of absorbed radiation late-effects in these populations. The uranium miners are divided into four exposure groups expressed in Working Level Months (WLM), the plutonium workers into six groups with estimated 239 Pu burdens expressed in nCi. Comparison of chromosome aberration frequency data between controls, miners, and plutonium workers demonstrate: (1) a cytogenetic response to occupational ionizing radiation at low estimated doses; and (2) an increasing monotonic dose-response in the prevalence of complex (all exchange) or total aberrations in all exposure groups in these populations. We also compared trends in the prevalence of aberrations per exposure unit (WLM and nCi) in each exposure subgroup for each population. In the uranium miners, the effects per WLM seem to decrease monotonically with increasing dose, whereas in the Pu workers the change per nCi appears abrupt, with all exposure groups over 1.3 nCi (minimum detectable level) having essentially similar rates. The calculations of aberrations per respective current maximum permissible dose (120 WLM and 40 nCi) for the two populations yield 4.8 X 10 -2 /100 cells for uranium miners and 90.6 X 10 -2 /100 cells for Pu workers. Factors which may have influenced this apparent 20-fold increase in the effectiveness of plutonium in the production of complex aberrations (9-fold increase in total aberrations) are discussed. (author)

  13. Forward genetic screens identify a role for the mitochondrial HER2 in E-2-hexenal responsiveness.

    Science.gov (United States)

    Scala, Alessandra; Mirabella, Rossana; Goedhart, Joachim; de Vries, Michel; Haring, Michel A; Schuurink, Robert C

    2017-11-01

    This work adds a new player, HER2, downstream of the perception of E-2-hexenal, a green leaf volatile, and shows that E-2-hexenal specifically changes the redox status of the mitochondria. It is widely accepted that plants produce and respond to green leaf volatiles (GLVs), but the molecular components involved in transducing their perception are largely unknown. The GLV E-2-hexenal inhibits root elongation in seedlings and, using this phenotype, we isolated E-2-hexenal response (her) Arabidopsis thaliana mutants. Using map-based cloning we positioned the her2 mutation to the At5g63620 locus, resulting in a phenylalanine instead of serine on position 223. Knockdown and overexpression lines of HER2 confirmed the role of HER2, which encodes an oxidoreductase, in the responsiveness to E-2-hexenal. Since E-2-hexenal is a reactive electrophile species, which are known to influence the redox status of cells, we utilized redox sensitive GFP2 (roGFP2) to determine the redox status of E-2-hexenal-treated root cells. Since the signal peptide of HER2 directed mCherry to the mitochondria, we targeted the expression of roGFP2 to this organelle besides the cytosol. E-2-hexenal specifically induced a change in the redox status in the mitochondria. We did not see a difference in the redox status in her2 compared to wild-type Arabidopsis. Still, the mitochondrial redox status did not change with Z-3-hexenol, another abundant GLV. These results indicate that HER2 is involved in transducing the perception of E-2-hexenal, which changes the redox status of the mitochondria.

  14. Genetic polymorphisms potentially associated with response to metformin in postmenopausal diabetics suffering and not suffering with cancer.

    Science.gov (United States)

    Berstein, Lev M; Iyevleva, Aglaya G; Vasilyev, Dmitry; Poroshina, Tatyana E; Imyanitov, Evgeny N

    2013-12-01

    Metformin is a well-known antidiabetic medication, which, besides diabetes, may be involved into modulation of other age-related pathologies, including cancer. The study concerns 12 gene polymorphisms divided into 2 groups consisting of 6 genes each. The first group was composed from so-called "standard" (S) polymorphisms, for which the connection with metabolic response to metformin is already established. The second group included polymorphisms of genes encoding proteins possibly connected with diabetes mellitus type 2 (DM2), impaired glucose tolerance or cancer and entitled here as "associated" (A). A total of 156 postmenopausal women (average age 60.7 ± 0.7) were included, 37 of them healthy, 64 with type DM2 and concurrent treatment-naïve cancer (mostly breast, endometrial or colorectal cancer), 32 with DM2 without cancer, and 23 with treatment-naïve cancer and normal glucose tolerance. The leading metformin response S-marker in combined group of DM2 patients was the CC variant of OCT1-R61C polymorphism of organic cation transporter protein 1 gene. In cancer patients without DM2, this position belonged to AC and AA genotypes of OCT1_rs622342 polymorphism. Among the A-polymorphisms, GA variant of sex hormone-binding globulin gene SHBG_D356N was less frequently observed in DM2 patients with or without cancer. Besides, in diabetics, the same polymorphic variant of SHBG as well as GC genotype of oxidized lipoprotein receptor OLR1_G501C and GG genotype of locus rs11065987 near BRAP gene were carried rather often in combination with "metformin-positive" variant of OCT1_R61C. In addition, carriers of OCT1_R61C and OCT1_rs622342 polymorphisms with potentially positive reaction to metformin had higher insulin resistance score (HOMA-IR) values. Received data lead to the conclusion that postmenopausal diabetics, both with and without cancer, differ in genetic stigmata of potential response to metformin less than they differ from cancer patients without DM2. As genetic

  15. Optimization of microwave-assisted drying of Jerusalem artichokes (Helianthus tuberosus L. by response surface methodology and genetic algorithm

    Directory of Open Access Journals (Sweden)

    E. KARACABEY

    2016-03-01

    Full Text Available The objective of the present study was to investigate microwave-assisted drying of Jerusalem artichoke tubers to determine the effects of the processing conditions. Drying time (DT and effectivemoisture diffusivity (EMD were determined to evaluate the drying process in terms of dehydration performance, whereas the rehydration ratio (RhR was considered as a significant quality index. A pretreatment of soaking in a NaCl solution was applied before all trials. The output power of the microwave oven, slice thickness and NaCl concentration of the pretreatment solution werethe three investigated parameters. The drying process was accelerated by altering the conditions while obtaining a higher quality product. For optimization of the drying process, response surface methodology (RSM and genetic algorithms (GA were used. Model adequacy was evaluated for each corresponding mathematical expression developed for interested responses by RSM. The residual of the model obtained by GA was compared to that of the RSM model. The GA was successful in high-performance prediction and produced results similar to those of RSM. The analysis and results of the present study show that both RSM and GA models can be used in cohesion to gain insight into the bioprocessing system.

  16. Genetic basis, nutritional challenges and adaptive responses in the prenatal origin of obesity and type-2 diabetes.

    Science.gov (United States)

    Gonzalez-Bulnes, Antonio; Ovilo, Cristina

    2012-03-01

    Obesity and type-2 diabetes are currently considered global pandemics. A large set of epidemiological evidences are addressing both the importance of a genetic predisposition -starting with the thrifty genotype hypothesis- and the determinant role of the maternal nutrition during pregnancy -starting with longitudinal studies of individuals born during the Dutch famine- on the adult onset of the disease. Compelling evidences suggest that both over- and undernutrition may modify the intrauterine environment of the conceptus and may alter the expression of its genome, predisposing to disease in the adult life. However, the most recent data indicate that the consequences of this phenomenon, termed as prenatal programming, are influenced both by timing, degree and duration of the challenge and by the adaptive response of the mother and the conceptus; thus, the information acquired by interventional studies modifying these parameters is becoming increasingly important. Obviously, interventional research in human beings is limited by ethical issues; hence, investigations need to be conducted on animal models, either rodents or large animals. This review summarizes the results of epidemiological human studies and translational animal research in unraveling the interaction between genome, nutritional status and adaptive response on the establishment of postnatal obesity, insulin resistance and type-2 diabetes. © 2012 Bentham Science Publishers

  17. Report of the First Community Consultation on the Responsible Collection and Use of Samples for Genetic Research, September 25-26, 2000

    Energy Technology Data Exchange (ETDEWEB)

    Greenberg, Judith H.

    2002-05-22

    The First Community Consultation on the Responsible Collection and Use of Samples for Genetic Research was held in Bethesda, Maryland, on September 25-26, 2000. The consultation was convened by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH). Approximately 120 individuals participated in the consultation, half from a broad range of communities and populations, and half from government. The participants shared their views and concerns about population- and community-based genetic research, expanding the focus of the meeting from the collection and use of blood or other tissue samples for genetic research to broader issues and concerns about the conduct of genetic research in general with populations and communities.

  18. Effects of vitamin nutrition on the immune response of hatchery-reared salmonids. Annual report, 1984

    International Nuclear Information System (INIS)

    Leith, D.; Holmes, J.; Kaattari, S.; Yui, M.; Jones, T.

    1985-09-01

    Results demonstrate that immunological assays. Lymphocytes from both of the major lymphoid organs (spleen and anterior kidney) produce significant in vitro antibody responses to the antigen, trinitrophenyl-lipopolysaccharide. These cells also demonstrate significant mitogenic stimulation (proliferation) in response to bacterial lipopolysaccharide, phytohemagglutinin, and to a novel mitogen, Vibrio anguillarum extract. As an assessment of cell-mediated immunity, we have found that lymphocytes are capable of responding in a mixed lymphocyte reaction as demonstrated by increased incorporation of tritiated thymidine. Results also indicate that phagocytosis can be quantified by the uptake of radioiodinated Renibacterium salmoninarum and that production of migration inhibition factor (MIF)-like activity can be induced in immunized animals. Polyclonal activation of chinook lymphocytes was elicited by both Vibrio anguillarum extract and E. coli lipopolysaccharide. Groups of spring chinook salmon were fed a formula diet containing five dietary levels of pyridoxine (15, 30, 60, 120, and 1500 mg/kg diet). Data collected on growth and feed efficiency in the first eighteen weeks show no significant difference between these formulations. 46 refs., 20 figs., 7 tabs

  19. From genetics to response to injury: vascular smooth muscle cells in aneurysms and dissections of the ascending aorta.

    Science.gov (United States)

    Michel, Jean-Baptiste; Jondeau, Guillaume; Milewicz, Dianna M

    2018-03-15

    Vascular smooth muscle cells (vSMCs) play a crucial role in both the pathogenesis of Aneurysms and Dissections of the ascending thoracic aorta (TAAD) in humans and in the associated adaptive compensatory responses, since thrombosis and inflammatory processes are absent in the majority of cases. Aneurysms and dissections share numerous characteristics, including aetiologies and histopathological alterations: vSMC disappearance, medial areas of mucoid degeneration, and extracellular matrix (ECM) breakdown. Three aetiologies predominate in TAAD in humans: (i) genetic causes in heritable familial forms, (ii) an association with bicuspid aortic valves, and (iii) a sporadic degenerative form linked to the aortic aging process. Genetic forms include mutations in vSMC genes encoding for molecules of the ECM or the TGF-β pathways, or participating in vSMC tone. On the other hand, aneurysms and dissections, whatever their aetiologies, are characterized by an increase in wall permeability leading to transmural advection of plasma proteins which could interact with vSMCs and ECM components. In this context, blood-borne plasminogen appears to play an important role, because its outward convection through the wall is increased in TAAD, and it could be converted to active plasmin at the vSMC membrane. Active plasmin can induce vSMC disappearance, proteolysis of adhesive proteins, activation of MMPs and release of TGF-β from its ECM storage sites. Conversely, vSMCs could respond to aneurysmal biomechanical and proteolytic injury by an epigenetic phenotypic switch, including constitutional overexpression and nuclear translocation of Smad2 and an increase in antiprotease and ECM protein synthesis. In contrast, such an epigenetic phenomenon is not observed in dissections. In this context, dysfunction of proteins involved in vSMC tone are interesting to study, particularly in interaction with plasma protein transport through the wall and TGF-β activation, to establish the

  20. Responses to the change in the environment in pairs of male rats genetically selected for activity level.

    Science.gov (United States)

    Franková, S; Tikal, K

    1989-12-01

    Laboratory Wistar strain rats were genetically selected for high (+A) and low (-A) activity level. In thirteen pairs of adult males of the 23rd filial generation reactions to changes in the external environment were studied. The animals were housed in breeding cages four each. Two parallel studies were conducted: in pairs simultaneously placed into a novel environment (NOV), empty cages of the same dimensions as the home cage (HC), in the second, behaviour of the second pair that remained in the HC, after removal of two cage-mates, was tested. Once a minute, for a period of one hour, the type of activity was recorded and noted whether it was an element effected in contact with the partner or without any contact. The animals +A and -A differed in the frequency of various types of activity and immobility, in the ratio between behavioural manifestations shown in or without contact as well as in the response to the type of modified environment. To changes in the situation, whether removed cage-mates from the HC or placed into NOV +A animals reacted with a high wave of environment exploration which gradually habituated. -A rats equally responded with exploration but on a lower level. In +rats we recorded more frequently exploration without contact with the partner in HC and NOV in comparison with -A, more frequent grooming, less immobility in contact and with no contact. Between +A partners there was a greater number of contacts in NOV than in HC whereas in the -A group the incidence of contact did not differ between HC and NOV. ANOVA revealed the influence of factors of genetics and environment and interaction in several behavioural categories. The simple and in time economical method demonstrated the possibility of use for the detection of differences between +A and -A lines even at relatively small changes in the external stimulatory situation.

  1. Brain network reorganization differs in response to stress in rats genetically predisposed to depression and stress-resilient rats.

    Science.gov (United States)

    Gass, N; Becker, R; Schwarz, A J; Weber-Fahr, W; Clemm von Hohenberg, C; Vollmayr, B; Sartorius, A

    2016-12-06

    Treatment-resistant depression (TRD) remains a pressing clinical problem. Optimizing treatment requires better definition of the specificity of the involved brain circuits. The rat strain bred for negative cognitive state (NC) represents a genetic animal model of TRD with high face, construct and predictive validity. Vice versa, the positive cognitive state (PC) strain represents a stress-resilient phenotype. Although NC rats show depressive-like behavior, some symptoms such as anhedonia require an external trigger, i.e. a stressful event, which is similar to humans when stressful event induces a depressive episode in genetically predisposed individuals (gene-environment interaction). We aimed to distinguish neurobiological predisposition from the depressogenic pathology at the level of brain-network reorganization. For this purpose, resting-state functional magnetic resonance imaging time series were acquired at 9.4 Tesla scanner in NC (N=11) and PC (N=7) rats before and after stressful event. We used a graph theory analytical approach to calculate the brain-network global and local properties. There was no difference in the global characteristics between the strains. At the local level, the response in the risk strain was characterized with an increased internodal role and reduced local clustering and efficiency of the anterior cingulate cortex (ACC) and prelimbic cortex compared to the stress-resilient strain. We suggest that the increased internodal role of these prefrontal regions could be due to the enhancement of some of their long-range connections, given their connectivity with the amygdala and other default-mode-like network hubs, which could create a bias to attend to negative information characteristic for depression.

  2. Insulin-like signaling (IIS) responses to temperature, genetic background, and growth variation in garter snakes with divergent life histories.

    Science.gov (United States)

    Reding, Dawn M; Addis, Elizabeth A; Palacios, Maria G; Schwartz, Tonia S; Bronikowski, Anne M

    2016-07-01

    The insulin/insulin-like signaling pathway (IIS) has been shown to mediate life history trade-offs in mammalian model organisms, but the function of this pathway in wild and non-mammalian organisms is understudied. Populations of western terrestrial garter snakes (Thamnophis elegans) around Eagle Lake, California, have evolved variation in growth and maturation rates, mortality senescence rates, and annual reproductive output that partition into two ecotypes: "fast-living" and "slow-living". Thus, genes associated with the IIS network are good candidates for investigating the mechanisms underlying ecological divergence in this system. We reared neonates from each ecotype for 1.5years under two thermal treatments. We then used qPCR to compare mRNA expression levels in three tissue types (brain, liver, skeletal muscle) for four genes (igf1, igf2, igf1r, igf2r), and we used radioimmunoassay to measure plasma IGF-1 and IGF-2 protein levels. Our results show that, in contrast to most mammalian model systems, igf2 mRNA and protein levels exceed those of igf1 and suggest an important role for igf2 in postnatal growth in reptiles. Thermal rearing treatment and recent growth had greater impacts on IGF levels than genetic background (i.e., ecotype), and the two ecotypes responded similarly. This suggests that observed ecotypic differences in field measures of IGFs may more strongly reflect plastic responses in different environments than evolutionary divergence. Future analyses of additional components of the IIS pathway and sequence divergence between the ecotypes will further illuminate how environmental and genetic factors influence the endocrine system and its role in mediating life history trade-offs. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Genetic dissection of photoperiod response based on GWAS of pre-anthesis phase duration in spring barley.

    Directory of Open Access Journals (Sweden)

    Ahmad M Alqudah

    Full Text Available Heading time is a complex trait, and natural variation in photoperiod responses is a major factor controlling time to heading, adaptation and grain yield. In barley, previous heading time studies have been mainly conducted under field conditions to measure total days to heading. We followed a novel approach and studied the natural variation of time to heading in a world-wide spring barley collection (218 accessions, comprising of 95 photoperiod-sensitive (Ppd-H1 and 123 accessions with reduced photoperiod sensitivity (ppd-H1 to long-day (LD through dissecting pre-anthesis development into four major stages and sub-phases. The study was conducted under greenhouse (GH conditions (LD; 16/8 h; ∼20/∼16°C day/night. Genotyping was performed using a genome-wide high density 9K single nucleotide polymorphisms (SNPs chip which assayed 7842 SNPs. We used the barley physical map to identify candidate genes underlying genome-wide association scans (GWAS. GWAS for pre-anthesis stages/sub-phases in each photoperiod group provided great power for partitioning genetic effects on floral initiation and heading time. In addition to major genes known to regulate heading time under field conditions, several novel QTL with medium to high effects, including new QTL having major effects on developmental stages/sub-phases were found to be associated in this study. For example, highly associated SNPs tagged the physical regions around HvCO1 (barley CONSTANS1 and BFL (BARLEY FLORICAULA/LEAFY genes. Based upon our GWAS analysis, we propose a new genetic network model for each photoperiod group, which includes several newly identified genes, such as several HvCO-like genes, belonging to different heading time pathways in barley.

  4. Genetic constraints in the induction of the immune response to Ehrlich ascites tumor in mice

    International Nuclear Information System (INIS)

    Marusic, M.; Perkins, E.H.

    1981-01-01

    A single injection of irradiated Ehrlich ascites tumor (EAT) cells induces immunity in normal mice but fails to do so in T-cell-deficient-thymectomized, lethally irradiated, bone marrow-reconstituted (TIR) mice. TIR mice injected with normal syngeneic T cells develop an immune response to EAT when injected with irradiated EAT cells and reject a subsequent tumor cell challenge. In the present studies allogeneic T cells were unable to protect against EAT in TIR recipients even if harvested from donors tolerant to the recipient's transplantation antigens and injected into the TIR mice tolerant to the transplantation antigens of the injected T cells. Tolerance was produced by establishing long-term radiation chimeras of the P → F 1 type. Semiallogeneic T cells also failed to afford protection against EAT in TIR recipients. Whereas tolerance to other parental-strain transplantation antigens did not reverse the inability of parental T cells (cells from P → F 1 chimeric donors) to protect against EAT in F 1 TIR mice, it did enable F 1 T cells to afford protection in P → F 1 TIR mice

  5. Association study between genetic monoaminergic polymorphisms and OCD response to clomipramine treatment

    Directory of Open Access Journals (Sweden)

    K Miguita

    2011-01-01

    Full Text Available In the present paper, we investigated the 5HTTLPR and STin2 polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4, the G861C polymorphism (rs6296 of the serotonin receptor 1D beta (HTR1B, the T102C (rs6113 and C516T (rs6305 polymorphisms of the serotonin receptor gene subtype 2A (HTR2A, the DAT UTR, DAT intron 8 and DAT intron 14 of the dopamine transporter gene (SLC6A3, the Val-158-Met (rs4680 polymorphism of the COMT and the silent mutation G1287A (rs5569 in the norepinephrine transporter gene (SLC6A2. We genotyped 41 obsessive-compulsive disorder (OCD outpatients, classified as good-responders (n=27 and poor-responders (n=14 to treatment with clomipramine according to the Yale Brown Obsessive-Compulsive Scale (YBOCS. Patients who achieved a reduction in symptoms of 40% or more in YBOCS after 14 weeks of treatment were considered good-responders. Genotypes and alleles distribution of the investigated polymorphisms were compared between both groups. We did not find association between the studied polymorphisms and clomipramine response in our sample.

  6. Genetic analysis of the electrophysiological response to salicin, a bitter substance, in a polyphagous strain of the silkworm Bombyx mori.

    Directory of Open Access Journals (Sweden)

    Tetsuya Iizuka

    Full Text Available Sawa-J is a polyphagous silkworm (Bombyx mori L. strain that eats various plant leaves that normal silkworms do not. The feeding preference behavior of Sawa-J is controlled by one major recessive gene(s on the polyphagous (pph locus, and several minor genes; moreover, its deterrent cells possess low sensitivity to some bitter substances including salicin. To clarify whether taste sensitivity is controlled by the pph locus, we conducted a genetic analysis of the electrophysiological characteristics of the taste response using the polyphagous strain Sawa-J·lem, in which pph is linked to the visible larval marker lemon (lem on the third chromosome, and the normal strain Daiankyo, in which the wild-type gene of pph (+(pph is marked with Zebra (Ze. Maxillary taste neurons of the two strains had similar dose-response relationships for sucrose, inositol, and strychnine nitrate, but the deterrent cell of Sawa-J·lem showed a remarkably low sensitivity to salicin. The F(1 generation of the two strains had characteristics similar to the Daiankyo strain, consistent with the idea that pph is recessive. In the BF(1 progeny between F(1 females and Sawa-J·lem males where no crossing-over occurs, the lem and Ze phenotypes corresponded to different electrophysiological reactions to 25 mM salicin, indicating that the gene responsible for taste sensitivity to salicin is located on the same chromosome as the lem and Ze genes. The normal and weak reactions to 25 mM salicin were segregated in crossover-type larvae of the BF(1 progeny produced by a reciprocal cross, and the recombination frequency agreed well with the theoretical ratio for the loci of lem, pph, and Ze on the standard linkage map. These results indicate that taste sensitivity to salicin is controlled by the gene(s on the pph locus.

  7. DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics.

    Science.gov (United States)

    de Rosa, Nicole; Rodriguez-Bigas, Miguel A; Chang, George J; Veerapong, Jula; Borras, Ester; Krishnan, Sunil; Bednarski, Brian; Messick, Craig A; Skibber, John M; Feig, Barry W; Lynch, Patrick M; Vilar, Eduardo; You, Y Nancy

    2016-09-01

    DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer. Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer-specific survival were calculated by the Kaplan-Meier method. The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer-specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies. dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions. © 2016 by American Society of Clinical Oncology.

  8. Host Genetics and Environment Drive Divergent Responses of Two Resource Sharing Gall-Formers on Norway Spruce: A Common Garden Analysis.

    Science.gov (United States)

    Axelsson, E Petter; Iason, Glenn R; Julkunen-Tiitto, Riitta; Whitham, Thomas G

    2015-01-01

    A central issue in the field of community genetics is the expectation that trait variation among genotypes play a defining role in structuring associated species and in forming community phenotypes. Quantifying the existence of such community phenotypes in two common garden environments also has important consequences for our understanding of gene-by-environment interactions at the community level. The existence of community phenotypes has not been evaluated in the crowns of boreal forest trees. In this study we address the influence of tree genetics on needle chemistry and genetic x environment interactions on two gall-inducing adelgid aphids (Adelges spp. and Sacchiphantes spp.) that share the same elongating bud/shoot niche. We examine the hypothesis that the canopies of different genotypes of Norway spruce (Picea abies L.) support different community phenotypes. Three patterns emerged. First, the two gallers show clear differences in their response to host genetics and environment. Whereas genetics significantly affected the abundance of Adelges spp. galls, Sacchiphantes spp. was predominately affected by the environment suggesting that the genetic influence is stronger in Adelges spp. Second, the among family variation in genetically controlled resistance was large, i.e. fullsib families differed as much as 10 fold in susceptibility towards Adelges spp. (0.57 to 6.2 galls/branch). Also, the distribution of chemical profiles was continuous, showing both overlap as well as examples of significant differences among fullsib families. Third, despite the predicted effects of host chemistry on galls, principal component analyses using 31 different phenolic substances showed only limited association with galls and a similarity test showed that trees with similar phenolic chemical characteristics, did not host more similar communities of gallers. Nonetheless, the large genetic variation in trait expression and clear differences in how community members respond to host

  9. Host Genetics and Environment Drive Divergent Responses of Two Resource Sharing Gall-Formers on Norway Spruce: A Common Garden Analysis.

    Directory of Open Access Journals (Sweden)

    E Petter Axelsson

    Full Text Available A central issue in the field of community genetics is the expectation that trait variation among genotypes play a defining role in structuring associated species and in forming community phenotypes. Quantifying the existence of such community phenotypes in two common garden environments also has important consequences for our understanding of gene-by-environment interactions at the community level. The existence of community phenotypes has not been evaluated in the crowns of boreal forest trees. In this study we address the influence of tree genetics on needle chemistry and genetic x environment interactions on two gall-inducing adelgid aphids (Adelges spp. and Sacchiphantes spp. that share the same elongating bud/shoot niche. We examine the hypothesis that the canopies of different genotypes of Norway spruce (Picea abies L. support different community phenotypes. Three patterns emerged. First, the two gallers show clear differences in their response to host genetics and environment. Whereas genetics significantly affected the abundance of Adelges spp. galls, Sacchiphantes spp. was predominately affected by the environment suggesting that the genetic influence is stronger in Adelges spp. Second, the among family variation in genetically controlled resistance was large, i.e. fullsib families differed as much as 10 fold in susceptibility towards Adelges spp. (0.57 to 6.2 galls/branch. Also, the distribution of chemical profiles was continuous, showing both overlap as well as examples of significant differences among fullsib families. Third, despite the predicted effects of host chemistry on galls, principal component analyses using 31 different phenolic substances showed only limited association with galls and a similarity test showed that trees with similar phenolic chemical characteristics, did not host more similar communities of gallers. Nonetheless, the large genetic variation in trait expression and clear differences in how community members

  10. Genetic variations of PIP4K2A confer vulnerability to poor antipsychotic response in severely ill schizophrenia patients.

    Directory of Open Access Journals (Sweden)

    Harpreet Kaur

    incomplete responders with low severity (OR = 4.09, 95%-CI = 2.09-8.02. Our findings provide strong evidence that diplotype ATTGCT/ATTGCT of PIP4K2A gene conferred approximately three-times higher incomplete responsiveness towards antipsychotics in severely ill patients. These results are consistent with the known role of phosphatidyl-inositol-signaling elements in antipsychotic action and outcome. Findings have implication for future molecular genetic studies as well as personalized medicine. However more work is warranted to elucidate underlying causal biological pathway.

  11. Epigenome-wide association study of triglyceride postprandial responses to high-fat dietary challenge in the Genetics of Lipid Lowering Drugs and Diet Network study

    Science.gov (United States)

    Postprandial lipemia (PPL), the increased plasma triglyceride (TG) concentration after consuming a high-fat meal, is an independent risk factor for cardiovascular disease (CVD). Individual responses to a meal high in fat vary greatly, depending on genetic and lifestyle factors. However, only a few ...

  12. Genetic ancestry in relation to the metabolic response to a U.S. versus traditional Mexican diet: a randomized crossover feeding trial among women of Mexican descent

    OpenAIRE

    Santiago-Torres, Margarita; De Dieu Tapsoba, Jean; Kratz, Mario; Lampe, Johanna W.; Breymeyer, Kara L.; Levy, Lisa; Song, Xiaoling; Villase?or, Adriana; Wang, Ching-Yun; Fejerman, Laura; Neuhouser, Marian L.; Carlson, Christopher S.

    2016-01-01

    Background Certain populations with a large proportion of Indigenous American (IA) genetic ancestry may be evolutionarily adapted to traditional diets high in legumes and complex carbohydrates, and may have a detrimental metabolic response to U.S. diets high in refined carbohydrates and added sugars. We tested whether IA ancestry modified the metabolic response to a U.S. versus traditional Mexican diet in a controlled dietary intervention. Methods First and second generation Mexican immigrant...

  13. The study to understand the genetics of the acute response to metformin and glipizide in humans (SUGAR-MGH: design of a pharmacogenetic resource for type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Geoffrey A Walford

    Full Text Available Genome-wide association studies have uncovered a large number of genetic variants associated with type 2 diabetes or related phenotypes. In many cases the causal gene or polymorphism has not been identified, and its impact on response to anti-hyperglycemic medications is unknown. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH, NCT01762046 is a novel resource of genetic and biochemical data following glipizide and metformin administration. We describe recruitment, enrollment, and phenotyping procedures and preliminary results for the first 668 of our planned 1,000 participants enriched for individuals at risk of requiring anti-diabetic therapy in the future.All individuals are challenged with 5 mg glipizide × 1; twice daily 500 mg metformin × 2 days; and 75-g oral glucose tolerance test following metformin. Genetic variants associated with glycemic traits and blood glucose, insulin, and other hormones at baseline and following each intervention are measured.Approximately 50% of the cohort is female and 30% belong to an ethnic minority group. Following glipizide administration, peak insulin occurred at 60 minutes and trough glucose at 120 minutes. Thirty percent of participants experienced non-severe symptomatic hypoglycemia and required rescue with oral glucose. Following metformin administration, fasting glucose and insulin were reduced. Common genetic variants were associated with fasting glucose levels.SUGAR-MGH represents a viable pharmacogenetic resource which, when completed, will serve to characterize genetic influences on pharmacological perturbations, and help establish the functional relevance of newly discovered genetic loci to therapy of type 2 diabetes.ClinicalTrials.gov NCT01762046.

  14. Genetic and Histopathological Responses to Cadmium Toxicity in Rabbit's Kidney and Liver: Protection by Ginger (Zingiber officinale).

    Science.gov (United States)

    Baiomy, Ahmed A; Mansour, Ahmed A

    2016-04-01

    This study aimed to examine the protective effects of ginger (G) on the genetic response induced by cadmium (Cd) and immunohistochemical expression of Caspase3 and MKI67 in the kidney and liver of rabbits. Male rabbits were divided into three groups; each group contains 10 animals: group (C) received basic diet and tap water for 12 weeks, the second group (Cd) received 200 mg/kg b.w CdCl2 in water for 12 weeks, group (Cd + G) was given 200 mg/kg b.w CdCl2 in water and 400 mg ginger/kg b.w in food for 12 weeks. Cd administration increased the activity of mRNA expression of the examined apoptotic (Caspase3), proliferation (MKI67), proto-oncogene (C-fos), and antioxidant (GST), while decreased the expression of anti-apoptotic (Bcl2). Ginger counteracted the effects of Cd in (Cd + G) group and downregulated the previously upregulated genes under Cd administration appeared in (Cd) group. The immunohistochemical expression of Caspase3 and MKI67 in the liver and kidney cells of the (C) group was shown very faint to negative reactions, strong staining in hepatocytes and the tubular epithelium in cadmium-treated group, while slight staining in some hepatocytes and tubular epithelium in co-administration with ginger in (Cd + G) group. In conclusion, ginger administration showed a protective effect against cadmium toxicity.

  15. The association between genetic polymorphisms of coproporphyrinogen oxidase and an atypical porphyrinogenic response to mercury exposure in humans

    International Nuclear Information System (INIS)

    Woods, James S.; Echeverria, Diana; Heyer, Nicholas J.; Simmonds, P. Lynne; Wilkerson, Jasmine; Farin, Federico M.

    2005-01-01

    Previous studies have demonstrated highly specific urinary porphyrin profile (UPP) changes in response to mercury (Hg) exposure in animals and human subjects and have defined the biochemical etiology of this effect as selective alteration of the heme pathway enzymes, uroporphyrinogen decarboxylase (UROD), and coproporphyrinogen oxidase (CPOX) by Hg in the kidney. Ongoing validation studies in a population of dental practitioners with low-level occupational Hg exposure have demonstrated the predicted UPP change among ∼85% of subjects. This study focused on the genetic etiology of an atypical porphyrinogenic response (APR) seen among the remaining 15% of Hg-exposed subjects, characterized by excess excretion of 4- and 5-carboxyl porphyrins and also of the atypical ketoisocoproporphyrin (KICP). Automated DNA-sequencing-based assays were developed to examine the 7 exons and flanking intron-exon boundaries of the CPOX gene. Among several polymorphisms identified, an A814C variant in exon 4 encoding a N272H substitution was found to be predominant among subjects with the APR. Studies suggest that this variant CPOX preferentially converts the upstream 5-carboxylporphyrin (5-CP) to KICP. By partially inhibiting the 5- to 4-decarboxylation step of UROD, Hg promotes 5-CP accumulation, accounting for e xcess KICP excretion and the APR in Hg-exposed subjects carrying the variant CPOX gene. This finding represents the first report of a polymorphism in a human gene that modifies the effect of Hg on a biological process. The APR might serve as a biomarker of both Hg exposure and susceptibility to Hg toxicity

  16. Exploring Genetic Variability at PI, GSK3, HPA, and Glutamatergic Pathways in Lithium Response: Association With IMPA2, INPP1, and GSK3B Genes.

    Science.gov (United States)

    Mitjans, Marina; Arias, Bárbara; Jiménez, Esther; Goikolea, Jose M; Sáiz, Pilar A; García-Portilla, M Paz; Burón, Patricia; Bobes, Julio; Vieta, Eduard; Benabarre, Antoni

    2015-10-01

    Lithium is considered the first-line treatment in bipolar disorder, although response could range from an excellent response to a complete lack of response. Response to lithium is a complex phenotype in which different factors, part of them genetics, are involved. In this sense, the aim of this study was to investigate the potential association of genetic variability at genes related to phosphoinositide, glycogen synthetase kinase-3 (GSK3), hypothalamic-pituitary-adrenal, and glutamatergic pathways with lithium response. A sample of 131 bipolar patients (99 type I, 32 type II) were grouped and compared according to their level of response: excellent responders (ER), partial responders (PR), and nonresponders (NR). Genotype and allele distributions of the rs669838 (IMPA2), rs909270 (INNP1), rs11921360 (GSK3B), and rs28522620 (GRIK2) polymorphisms significantly differed between ER, PR, and NR. When we compared the ER versus PR+NR, the logistic regression showed significant association for rs669838-C (IMPA2; P = 0.021), rs909270-G (INPP1; P = 0.009), and rs11921360-A (GSK3B; P = 0.004) with lithium nonresponse. Haplotype analysis showed significant association for the haplotypes rs3791809-rs4853694-rs909270 (INPP1) and rs1732170-rs11921360-rs334558 (GSK3B) and lithium response. Our study is in line with previous studies reporting association between genetic variability at these genes and lithium response, pointing to an effect of IMPA2, INPP1, and GSK3B genes to lithium response in bipolar disorder patients. Further studies with larger samples are warranted to assess the strength of the reported associations.

  17. Clinical and genetic predictors of response to narrowband ultraviolet B for the treatment of chronic plaque psoriasis.

    LENUS (Irish Health Repository)

    Ryan, C

    2012-02-01

    BACKGROUND: There is considerable variability in the number of exposures of narrowband ultraviolet B (NB-UVB) needed to clear psoriasis and in the duration of remission. OBJECTIVES: We assessed clinical parameters as predictors of the number of exposures needed to clear psoriasis and of the duration of remission. The influence of genetic polymorphisms of the vitamin D receptor (VDR) on treatment response was also evaluated. METHODS: This was a prospective study of 119 patients with chronic plaque psoriasis treated with NB-UVB until clearance was achieved. They were then followed for up to 1 year or until relapse occurred. The frequency of the Fok1, Apa1, Bsm1, Taq1 and rs4516035 polymorphisms of the VDR gene was assessed in 93 of the 119 patients. RESULTS: Of the 119 patients, 105 completed the course of phototherapy. Using an intention to treat analysis, 83% of the initial cohort (99 of 119 patients) achieved clearance, in a median of 26 exposures (interquartile range 19-35) with a median remission duration of 16 weeks (interquartile range 9-22). Factors significantly associated with a lower number of exposures to clearance included a lower baseline Psoriasis Area and Severity Index (P = 0.004), lower baseline Dermatology Life Quality Index (P = 0.047), female sex (P = 0.043), lower body weight (P = 0.008), and a higher number of previous courses of TL-01 (P = 0.005). The only clinical factor influencing remission duration was number of exposures (P = 0.0009), with a decreased remission duration in those who required a greater number of exposures to clear. The Taq1 VDR polymorphism (rs731236) also significantly predicted remission duration (P = 0.038). Patients homozygous for the C allele, which is associated with decreased activity of the VDR, had a shorter remission duration than those heterozygous for the allele (P = 0.026) and those homozygous for the T allele (P = 0.013). CONCLUSIONS: This study highlights the fact that both genetic and clinical parameters

  18. Association of Genetic Variants With Response to Anti-Vascular Endothelial Growth Factor Therapy in Age-Related Macular Degeneration.

    Science.gov (United States)

    Lorés-Motta, Laura; Riaz, Moeen; Grunin, Michelle; Corominas, Jordi; van Asten, Freekje; Pauper, Marc; Leenders, Mathieu; Richardson, Andrea J; Muether, Philipp; Cree, Angela J; Griffiths, Helen L; Pham, Connie; Belanger, Marie-Claude; Meester-Smoor, Magda A; Ali, Manir; Heid, Iris M; Fritsche, Lars G; Chakravarthy, Usha; Gale, Richard; McKibbin, Martin; Inglehearn, Chris F; Schlingemann, Reinier O; Omar, Amer; Chen, John; Koenekoop, Robert K; Fauser, Sascha; Guymer, Robyn H; Hoyng, Carel B; de Jong, Eiko K; Lotery, Andrew J; Mitchell, Paul; den Hollander, Anneke I; Baird, Paul N; Chowers, Itay

    2018-05-31

    Visual acuity (VA) outcomes differ considerably among patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs. Identification of pharmacogenetic associations may help clinicians understand the mechanisms underlying this variability as well as pave the way for personalized treatment in nAMD. To identify genetic factors associated with variability in the response to anti-VEGF therapy for patients with nAMD. In this multicenter genome-wide association study, 678 patients with nAMD with genome-wide genotyping data were included in the discovery phase; 1380 additional patients with nAMD were genotyped for selected common variants in the replication phase. All participants received 3 monthly injections of bevacizumab or ranibizumab. Clinical data were evaluated for inclusion/exclusion criteria from October 2014 to October 2015, followed by data analysis from October 2015 to February 2016. For replication cohort genotyping, clinical data collection and analysis (including meta-analysis) was performed from March 2016 to April 2017. Change in VA after the loading dose of 3 monthly anti-VEGF injections compared with baseline. Of the 2058 included patients, 1210 (58.8%) were women, and the mean (SD) age across all cohorts was 78 (7.4) years. Patients included in the discovery cohort and most of the patients in the replication cohorts were of European descent. The mean (SD) baseline VA was 51.3 (20.3) Early Treatment Diabetic Retinopathy Study (ETDRS) score letters, and the mean (SD) change in VA after the loading dose of 3 monthly injections was a gain of 5.1 (13.9) ETDRS score letters (ie, 1-line gain). Genome-wide single-variant analyses of common variants revealed 5 independent loci that reached a P value less than 10 × 10-5. After replication and meta-analysis of the lead variants, rs12138564 located in the CCT3 gene remained nominally associated with a better treatment outcome (ETDRS letter

  19. Immune and biochemical responses in skin differ between bovine hosts genetically susceptible and resistant to the cattle tick Rhipicephalus microplus.

    Science.gov (United States)

    Franzin, Alessandra Mara; Maruyama, Sandra Regina; Garcia, Gustavo Rocha; Oliveira, Rosane Pereira; Ribeiro, José Marcos Chaves; Bishop, Richard; Maia, Antônio Augusto Mendes; Moré, Daniela Dantas; Ferreira, Beatriz Rossetti; Santos, Isabel Kinney Ferreira de Miranda

    2017-01-31

    Ticks attach to and penetrate their hosts' skin and inactivate multiple components of host responses in order to acquire a blood meal. Infestation loads with the cattle tick, Rhipicephalus microplus, are heritable: some breeds carry high loads of reproductively successful ticks, whereas in others, few ticks feed and reproduce efficiently. In order to elucidate the mechanisms that result in the different outcomes of infestations with cattle ticks, we examined global gene expression and inflammation induced by tick bites in skins from one resistant and one susceptible breed of cattle that underwent primary infestations with larvae and nymphs of R. microplus. We also examined the expression profiles of genes encoding secreted tick proteins that mediate parasitism in larvae and nymphs feeding on these breeds. Functional analyses of differentially expressed genes in the skin suggest that allergic contact-like dermatitis develops with ensuing production of IL-6, CXCL-8 and CCL-2 and is sustained by HMGB1, ISG15 and PKR, leading to expression of pro-inflammatory chemokines and cytokines that recruit granulocytes and T lymphocytes. Importantly, this response is delayed in susceptible hosts. Histopathological analyses of infested skins showed inflammatory reactions surrounding tick cement cones that enable attachment in both breeds, but in genetically tick-resistant bovines they destabilized the cone. The transcription data provided insights into tick-mediated activation of basophils, which have previously been shown to be a key to host resistance in model systems. Skin from tick-susceptible bovines expressed more transcripts encoding enzymes that detoxify tissues. Interestingly, these enzymes also produce volatile odoriferous compounds and, accordingly, skin rubbings from tick-susceptible bovines attracted significantly more tick larvae than rubbings from resistant hosts. Moreover, transcripts encoding secreted modulatory molecules by the tick were significantly more

  20. Ubiquitin-conjugating enzyme E2-like gene associated to pathogen response in Concholepas concholepas: SNP identification and transcription expression.

    Science.gov (United States)

    Núñez-Acuña, Gustavo; Aguilar-Espinoza, Andrea; Chávez-Mardones, Jacqueline; Gallardo-Escárate, Cristian

    2012-10-01

    Ubiquitin-conjugated E2 enzyme (UBE2) is one of the main components of the proteasome degradation cascade. Previous studies have shown an increase of expression levels in individuals challenged to some pathogen organism such as virus and bacteria. The study was to characterize the immune response of UBE2 gene in the gastropod Concholepas concholepas through expression analysis and single nucleotide polymorphisms (SNP) discovery. Hence, UBE2 was identified from a cDNA library by 454 pyrosequencing, while SNP identification and validation were performed using De novo assembly and high resolution melting analysis. Challenge trials with Vibrio anguillarum was carried out to evaluate the relative transcript abundance of UBE2 gene from two to thirty-three hours post-treatment. The results showed a partial UBE2 sequence of 889 base pair (bp) with a partial coding region of 291 bp. SNP variation (A/C) was observed at the 546th position. Individuals challenged by V. anguillarum showed an overexpression of the UBE2 gene, the expression being significantly higher in homozygous individuals (AA) than (CC) or heterozygous individuals (A/C). This study contributes useful information relating to the UBE2 gene and its association with innate immune response in marine invertebrates. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Perception, experience, and response to genetic discrimination in Huntington's disease: the Australian results of The International RESPOND-HD study.

    Science.gov (United States)

    Goh, Anita M Y; Chiu, Edmond; Yastrubetskaya, Olga; Erwin, Cheryl; Williams, Janet K; Juhl, Andrew R; Paulsen, Jane S

    2013-02-01

    This study examines elements of genetic discrimination among an at-risk, clinically undiagnosed Huntington's disease (HD) population. Sixty at-risk individuals, either positive or negative for the HD genetic mutation, completed a survey regarding their experiences of genetic discrimination, adverse and unfair treatment, and knowledge about existing laws and policies surrounding genetic discrimination. Sixty eight percent of participants reported feeling "Great benefit" from knowing their genetic test results. Reported benefits of knowledge included planning for the future, making decisions, and many individuals found meaning in active participation in the HD community and in advocating for themselves or families at risk for HD. Many individuals found personal meaning and a sense of community from knowledge of this information and from the ability to participate in research. Despite these positive feelings toward gene testing, results demonstrated that 33% of participants perceived experiences of genetic discrimination, which occurred repeatedly and caused great self-reported distress. Significantly, more gene-positive respondents reported experiencing incidents of genetic discrimination, compared to gene-negative respondents. At least 58 separate incidents of discrimination were reported, the number of incidents ranged from 1 to 10, with 45% of individuals (9/20 respondents) indicating more than one event. Of the most significant events of discrimination, 58% were related to insurance, 21% to employment, 16% to transactions of daily life, and 5% to relationships. Results contribute toward validation of empirical data regarding genetic discrimination.

  2. Predicting evolutionary responses when genetic variance and selection covary with the environment: a large-scale Open Access Data approach

    NARCIS (Netherlands)

    Ramakers, J.J.C.; Culina, A.; Visser, M.E.; Gienapp, P.

    2017-01-01

    Additive genetic variance and selection are the key ingredients for evolution. In wild populations, however, predicting evolutionary trajectories is difficult, potentially by an unrecognised underlying environment dependency of both (additive) genetic variance and selection (i.e. G×E and S×E).

  3. Genome-wide association analysis reveals distinct genetic architectures for single and combined stress responses in Arabidopsis thaliana

    NARCIS (Netherlands)

    Davila Olivas, Nelson H.; Kruijer, Willem; Gort, Gerrit; Wijnen, Cris L.; Loon, van Joop J.A.; Dicke, Marcel

    2017-01-01

    Plants are commonly exposed to abiotic and biotic stresses. We used 350 Arabidopsis thaliana accessions grown under controlled conditions. We employed genome-wide association analysis to investigate the genetic architecture and underlying loci involved in genetic variation in resistance to: two

  4. Low-density lipoprotein receptor genetic polymorphism in chronic hepatitis C virus Egyptian patients affects treatment response.

    Science.gov (United States)

    Naga, Mazen; Amin, Mona; Algendy, Dina; Elbadry, Ahmed; Fawzi, May; Foda, Ayman; Esmat, Serag; Sabry, Dina; Rashed, Laila; Gabal, Samia; Kamal, Manal

    2015-10-21

    To correlate a genetic polymorphism of the low-density lipoprotein (LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus (HCV) patients. Our study included 657 HCV-infected patients with genotype 4 who received interferon-based combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index (BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction (PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor (LDLR) genotype study of LDLR exon8c.1171G>A and exon10c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all cases. There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8c.1171G>A genotype between cases (AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls (AA: 3.8%, GA: 53.1% and GG: 43.1%) (P A polymorphism between responders (AA: 3.6%, GA: 15.2%, GG: 81.2%) and non-responders (AA: 52.2%, GA: 30.6%, GG: 17.2%) (P A predominated in cases and controls over the A allele, and a statistically significant association with

  5. Expression quantitative trait loci and genetic regulatory network analysis reveals that Gabra2 is involved in stress responses in the mouse.

    Science.gov (United States)

    Dai, Jiajuan; Wang, Xusheng; Chen, Ying; Wang, Xiaodong; Zhu, Jun; Lu, Lu

    2009-11-01

    Previous studies have revealed that the subunit alpha 2 (Gabra2) of the gamma-aminobutyric acid receptor plays a critical role in the stress response. However, little is known about the gentetic regulatory network for Gabra2 and the stress response. We combined gene expression microarray analysis and quantitative trait loci (QTL) mapping to characterize the genetic regulatory network for Gabra2 expression in the hippocampus of BXD recombinant inbred (RI) mice. Our analysis found that the expression level of Gabra2 exhibited much variation in the hippocampus across the BXD RI strains and between the parental strains, C57BL/6J, and DBA/2J. Expression QTL (eQTL) mapping showed three microarray probe sets of Gabra2 to have highly significant linkage likelihood ratio statistic (LRS) scores. Gene co-regulatory network analysis showed that 10 genes, including Gria3, Chka, Drd3, Homer1, Grik2, Odz4, Prkag2, Grm5, Gabrb1, and Nlgn1 are directly or indirectly associated with stress responses. Eleven genes were implicated as Gabra2 downstream genes through mapping joint modulation. The genetical genomics approach demonstrates the importance and the potential power of the eQTL studies in identifying genetic regulatory networks that contribute to complex traits, such as stress responses.

  6. Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI Genetics of Lipid Lowering Drugs and Diet Network (GOLDN).

    Science.gov (United States)

    Wojczynski, Mary K; Parnell, Laurence D; Pollin, Toni I; Lai, Chao Q; Feitosa, Mary F; O'Connell, Jeff R; Frazier-Wood, Alexis C; Gibson, Quince; Aslibekyan, Stella; Ryan, Kathy A; Province, Michael A; Tiwari, Hemant K; Ordovas, Jose M; Shuldiner, Alan R; Arnett, Donna K; Borecki, Ingrid B

    2015-10-01

    The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variants through a genome-wide association (GWA) study in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). The GOLDN GWAS discovery sample consisted of 872 participants within families of European ancestry. Genotypes for 2,543,887 variants were measured or imputed from HapMap. Replication of our top results was performed in the Heredity and Phenotype Intervention (HAPI) Heart Study (n = 843). PPL TG response phenotypes were constructed from plasma TG measured at baseline (fasting, 0 hour), 3.5 and 6 hours after a high-fat meal, using a random coefficient regression model. Association analyses were adjusted for covariates and principal components, as necessary, in a linear mixed model using the kinship matrix; additional models further adjusted for fasting TG were also performed. Meta-analysis of the discovery and replication studies (n = 1715) was performed on the top SNPs from GOLDN. GOLDN revealed 111 suggestive (p 5E-08). Of the two significant SNPs, rs964184 demonstrated evidence of replication (p = 1.20E-03) in the HAPI Heart Study and in a joint analysis, was GWA significant (p = 1.26E-09). Rs964184 has been associated with fasting lipids (TG and HDL) and is near ZPR1 (formerly ZNF259), close to the APOA1/C3/A4/A5 cluster. This association was attenuated upon additional adjustment for fasting TG. This is the first report of a genome-wide significant association with replication for a novel phenotype, namely PPL TG response. Future investigation into response phenotypes is warranted using pathway analyses, or newer genetic technologies such as metabolomics. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Lack of genetic variation in tree ring delta13C suggests a uniform, stomatally-driven response to drought stress across Pinus radiata genotypes.

    Science.gov (United States)

    Rowell, Douglas M; Ades, Peter K; Tausz, Michael; Arndt, Stefan K; Adams, Mark A

    2009-02-01

    We assessed the variation in delta(13)C signatures of Pinus radiata D. Don stemwood taken from three genetic trials in southern Australia. We sought to determine the potential of using delta(13)C signatures as selection criteria for drought tolerance. Increment cores were taken from P. radiata and were used to determine the basal area increment and the delta(13)C signature of extracted cellulose. Both growth increment and cellulose delta(13)C were affected by water availability. Growth increment and delta(13)C were negatively correlated suggesting that growth was water-limited. While there was significant genetic variation in growth, there was no significant genetic variation in cellulose delta(13)C of tree rings. This suggests that different genotypes of P. radiata display significant differences in growth and yet respond similarly to drought stress. The delta(13)C response to drought stress was more due to changes in stomatal conductance than to the variation in photosynthetic capacity, and this may explain the lack of genetic variation in delta(13)C. The lack of genetic variation in cellulose delta(13)C of tree rings precludes its use as a selection criterion for drought tolerance among P. radiata genotypes.

  8. A rapid, strong, and convergent genetic response to urban habitat fragmentation in four divergent and widespread vertebrates.

    Directory of Open Access Journals (Sweden)

    Kathleen Semple Delaney

    2010-09-01

    Full Text Available Urbanization is a major cause of habitat fragmentation worldwide. Ecological and conservation theory predicts many potential impacts of habitat fragmentation on natural populations, including genetic impacts. Habitat fragmentation by urbanization causes populations of animals and plants to be isolated in patches of suitable habitat that are surrounded by non-native vegetation or severely altered vegetation, asphalt, concrete, and human structures. This can lead to genetic divergence between patches and in turn to decreased genetic diversity within patches through genetic drift and inbreeding.We examined population genetic patterns using microsatellites in four common vertebrate species, three lizards and one bird, in highly fragmented urban southern California. Despite significant phylogenetic, ecological, and mobility differences between these species, all four showed similar and significant reductions in gene flow over relatively short geographic and temporal scales. For all four species, the greatest genetic divergence was found where development was oldest and most intensive. All four animals also showed significant reduction in gene flow associated with intervening roads and freeways, the degree of patch isolation, and the time since isolation.Despite wide acceptance of the idea in principle, evidence of significant population genetic changes associated with fragmentation at small spatial and temporal scales has been rare, even in smaller terrestrial vertebrates, and especially for birds. Given the striking pattern of similar and rapid effects across four common and widespread species, including a volant bird, intense urbanization may represent the most severe form of fragmentation, with minimal effective movement through the urban matrix.

  9. Genetic testing for colorectal carcinoma susceptibility: focus group responses of individuals with colorectal carcinoma and first-degree relatives.

    Science.gov (United States)

    Kinney, A Y; DeVellis, B M; Skrzynia, C; Millikan, R

    2001-01-01

    Colorectal carcinoma (CRC) may be the most frequent form of hereditary cancer. Genetic counseling and testing for heritable CRC is a promising approach for reducing the high incidence and mortality rates associated with the disease. Patients with CRC or those with at least one family member with the disease are the most likely persons to request or be offered genetic testing in the clinical or research setting. Currently, however, little is known about the behavioral, psychosocial, ethical, legal, and economic outcomes of CRC genetic counseling and testing. Eight focus group interviews, four for CRC patients (n = 28) and four for first-degree relatives (n = 33), were conducted to obtain insights into attitudes, beliefs, and informational needs about genetic testing for hereditary CRC. Focus group interviews revealed a general lack of knowledge about cancer genetics and genetic testing; worry about confidentiality issues; strong concern for family members, particularly children; and a need for primary care providers to be informed about these issues. Major perceived advantages of genetic testing included improving health-related decisions, guiding physicians in making recommendations for surveillance, and informing relatives about risk potential. Disadvantages included potential discrimination, adverse psychologic effects, and financial costs associated with testing. As knowledge and media coverage of genetics continue to expand, it becomes increasingly important to continue efforts on behalf of, and in partnership with, those individuals most affected by genetic testing for hereditary cancer syndromes. These findings provide data needed to develop and implement informational, educational, counseling, and research-oriented programs that are sensitive to individuals' concerns and preferences. Copyright 2001 American Cancer Society.

  10. Modeling lodgepole pine radial growth relative to climate and genetics using universal growth-trend response functions.

    Science.gov (United States)

    McLane, Sierra C; LeMay, Valerie M; Aitken, Sally N

    2011-04-01

    Forests strongly affect Earth's carbon cycles, making our ability to forecast forest-productivity changes associated with rising temperatures and changes in precipitation increasingly critical. In this study, we model the influence of climate on annual radial growth using lodgepole pine (Pinus contorta) trees grown for 34 years in a large provenance experiment in western Canada. We use a random-coefficient modeling approach to build universal growth-trend response functions that simultaneously incorporate the impacts of different provenance and site climates on radial growth trends under present and future annual (growth-year), summer, and winter climate regimes. This approach provides new depth to traditional quantitative genetics population response functions by illustrating potential changes in population dominance over time, as well as indicating the age and size at which annual growth begins declining for any population growing in any location under any present or future climate scenario within reason, given the ages and climatic conditions sampled. Our models indicate that lodgepole pine radial-growth levels maximize between 3.9 degrees and 5.1 degrees C mean growth-year temperature. This translates to productivity declining by the mid-21st century in southern and central British Columbia (BC), while increasing beyond the 2080s in northern BC and Yukon, as temperatures rise. Relative to summer climate indices, productivity is predicted to decline continuously through the 2080s in all locations, while relative to winter climate variables, the opposite trend occurs, with the growth increases caused by warmer winters potentially offsetting the summer losses. Trees from warmer provenances, i.e., from the center of the species range, perform best in nearly all of our present and future climate-scenario models. We recommend that similar models be used to analyze population growth trends relative to annual and intra-annual climate in other large-scale provenance

  11. An attempt to distinguish a modified genetic response of the mouse testis to X-ray exposure by the action of a spermatogonial chalone

    International Nuclear Information System (INIS)

    Cattanach, B.M.; Jones, J.T.; Andrews, S.J.; Crocker, M.

    1979-01-01

    The results of an experiment designed to distinguish whether the action of a spermatogonial chalone in the mouse testis could modify the genetic response of a depleted stem spermatogonial population to X-radiation are reported. The results are consistent with the view that the stem cell population of the depleted adult testis a few days after damage closely approximates that of the early post-natal or immature animal, do not provide any indication that the testis extract in any way influence the response of the depleted testis to the 500-rad challenging dose. The yield of genetic damage was almost identical to that in the two control groups and the sterile period and testis weight data provided little reason to suspect that the amount of spermatogonial killing was altered. (Auth.)

  12. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans

    OpenAIRE

    Schalling Martin; Lonsdorf Tina B; Jensen Karin B; Kosek Eva; Ingvar Martin

    2009-01-01

    Abstract Background There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expressio...

  13. Estimation of genetic variability and selection response for clutch length in dwarf brown-egg layers carrying or not the naked neck gene

    Directory of Open Access Journals (Sweden)

    Tixier-Boichard Michèle

    2003-03-01

    Full Text Available Abstract In order to investigate the possibility of using the dwarf gene for egg production, two dwarf brown-egg laying lines were selected for 16 generations on average clutch length; one line (L1 was normally feathered and the other (L2 was homozygous for the naked neck gene NA. A control line from the same base population, dwarf and segregating for the NA gene, was maintained during the selection experiment under random mating. The average clutch length was normalized using a Box-Cox transformation. Genetic variability and selection response were estimated either with the mixed model methodology, or with the classical methods for calculating genetic gain, as the deviation from the control line, and the realized heritability, as the ratio of the selection response on cumulative selection differentials. Heritability of average clutch length was estimated to be 0.42 ± 0.02, with a multiple trait animal model, whereas the estimates of the realized heritability were lower, being 0.28 and 0.22 in lines L1 and L2, respectively. REML estimates of heritability were found to decline with generations of selection, suggesting a departure from the infinitesimal model, either because a limited number of genes was involved, or their frequencies were changed. The yearly genetic gains in average clutch length, after normalization, were estimated to be 0.37 ± 0.02 and 0.33 ± 0.04 with the classical methods, 0.46 ± 0.02 and 0.43 ± 0.01 with animal model methodology, for lines L1 and L2 respectively, which represented about 30% of the genetic standard deviation on the transformed scale. Selection response appeared to be faster in line L2, homozygous for the NA gene, but the final cumulated selection response for clutch length was not different between the L1 and L2 lines at generation 16.

  14. Classical genetic analyses of responses to sedative-hypnotic drugs in crosses derived from long-sleep and short-sleep mice.

    Science.gov (United States)

    de Fiebre, C M; Marley, R J; Miner, L L; de Fiebre, N E; Wehner, J M; Collins, A C

    1992-06-01

    A classical (Mendelian) genetic analysis of responses to eight sedative-hypnotic compounds (ethanol, urethane, trifluoroethanol, chloral hydrate, barbital, paraldehyde, methyprylon, pentobarbital) was conducted in crosses derived from mouse lines that were selectively bred for differential duration of anesthesia following ethanol. The sleep-time responses of these mice, the long-sleep (LS) and short-sleep (SS) mouse lines, as well as the F1, F2 and backcross (F1 x LS, F1 x SS) generations were measured. Generally, differences in responses among the generations were greater for water soluble compounds than were differences for more lipid soluble compounds. Also, the inheritance of responses to water soluble compounds could be explained primarily by additive effects of alleles while the inheritance patterns for more lipid soluble compounds were more complex. Genetic correlation with ethanol response decreased with increasing lipophilicity. These results suggest that the selection of the LS-SS mouse lines was specific for water soluble anesthetic agents. Because several of these agents are known to act at GABA receptors, examination of the interactions of compounds which differ in lipid solubility at GABA receptors from LS and SS mice may prove useful in elucidating the mechanism of the anesthetic actions of ethanol and other drugs.

  15. Multi-objective parametric optimization of Inertance type pulse tube refrigerator using response surface methodology and non-dominated sorting genetic algorithm

    Science.gov (United States)

    Rout, Sachindra K.; Choudhury, Balaji K.; Sahoo, Ranjit K.; Sarangi, Sunil K.

    2014-07-01

    The modeling and optimization of a Pulse Tube Refrigerator is a complicated task, due to its complexity of geometry and nature. The aim of the present work is to optimize the dimensions of pulse tube and regenerator for an Inertance-Type Pulse Tube Refrigerator (ITPTR) by using Response Surface Methodology (RSM) and Non-Sorted Genetic Algorithm II (NSGA II). The Box-Behnken design of the response surface methodology is used in an experimental matrix, with four factors and two levels. The diameter and length of the pulse tube and regenerator are chosen as the design variables where the rest of the dimensions and operating conditions of the ITPTR are constant. The required output responses are the cold head temperature (Tcold) and compressor input power (Wcomp). Computational fluid dynamics (CFD) have been used to model and solve the ITPTR. The CFD results agreed well with those of the previously published paper. Also using the results from the 1-D simulation, RSM is conducted to analyse the effect of the independent variables on the responses. To check the accuracy of the model, the analysis of variance (ANOVA) method has been used. Based on the proposed mathematical RSM models a multi-objective optimization study, using the Non-sorted genetic algorithm II (NSGA-II) has been performed to optimize the responses.

  16. A comparative transcriptomic analysis reveals the core genetic components of salt and osmotic stress responses in Braya humilis.

    Directory of Open Access Journals (Sweden)

    Pengshan Zhao

    Full Text Available Braya humilis is a member of the Euclidieae tribe within the family Brassicaceae. This species exhibits a broad range of adaptations to different climatic zones and latitudes as it has a distribution that ranges from northern Asia to the arctic-alpine regions of northern North America. In China, B. humilis is mainly found on the Qinghai-Tibetan Plateau (QTP and in adjacent arid regions. In this study, we sequenced a sample from an arid region adjacent to the QTP using the Illumina platform generating a total of 46,485 highly accurate unigenes, of which 78.41% were annotated by BLASTing versus public protein databases. The B. humilis transcriptome is characterized by a high level of sequence conservation compared with its close relative, Arabidopsis thaliana. We also used reciprocal blast to identify shared orthologous genes between B. humilis and four other sequenced Brassicaceae species (i.e. A. thaliana, A. lyrata, Capsella rubella, and Thellungiella parvula. To enable precise characterization of orthologous genes, the early-diverging basal angiosperm Amborella trichopoda was also included. A total of 6,689 orthologous genes were identified before stricter criteria for the determination of e-values, amino acid hit lengths, and identity values was applied to further reduce this list. This led to a final list of 381 core orthologous genes for B. humilis; 39 out of these genes are involved in salt and osmotic stress responses and estimations of nonsynonymous/synonymous substitution ratios for this species and A. thaliana orthologs show that these genes are under purifying selection in B. humilis. Expression of six genes was detected in B. humilis seedlings under salt and osmotic stress treatments. Comparable expression patterns to their counterparts in Arabidopsis suggest that these orthologous genes are both sequence and functional conservation. The results of this study demonstrate that the environmental adaptations of B. humilis are mainly the

  17. Behavioural changes, sharing behaviour and psychological responses after receiving direct-to-consumer genetic test results: a systematic review and meta-analysis.

    Science.gov (United States)

    Stewart, Kelly F J; Wesselius, Anke; Schreurs, Maartje A C; Schols, Annemie M W J; Zeegers, Maurice P

    2018-01-01

    It has been hypothesised that direct-to-consumer genetic tests (DTC-GTs) could stimulate health behaviour change. However, genetic testing may also lead to anxiety and distress or unnecessarily burden the health care system. The aim is to review and meta-analyse the effects of DTC-GT on (1) behaviour change, (2) psychological response and (3) medical consumption. A systematic literature search was performed in three databases, using "direct-to-consumer genetic testing" as a key search term. Random effects meta-analyses were performed when at least two comparable outcomes were available. After selection, 19 articles were included involving 11 unique studies. Seven studies involved actual consumers who paid the retail price, whereas four included participants who received free genetic testing as part of a research trial (non-actual consumers). In meta-analysis, 23% had a positive lifestyle change. More specifically, improved dietary and exercise practices were both reported by 12%, whereas 19% quit smoking. Seven percent of participants had subsequent preventive checks. Thirty-three percent shared their results with any health care professional and 50% with family and/or friends. Sub-analyses show that behaviour change was more prevalent among non-actual consumers, whereas sharing was more prevalent among actual consumers. Results on psychological responses showed that anxiety, distress and worry were low or absent and that the effect faded with time. DTC-GT has potential to be effective as a health intervention, but the right audience needs to be addressed with tailored follow-up. Research is needed to identify consumers who do and do not change behaviour or experience adverse psychological responses.

  18. Gene expression profiling of the local cecal response of genetic chicken lines that differ in their susceptibility to Campylobacter jejuni colonization.

    Directory of Open Access Journals (Sweden)

    Xianyao Li

    Full Text Available Campylobacter jejuni (C. jejuni is one of the most common causes of human bacterial enteritis worldwide primarily due to contaminated poultry products. Previously, we found a significant difference in C. jejuni colonization in the ceca between two genetically distinct broiler lines (Line A (resistant has less colony than line B (susceptible on day 7 post inoculation. We hypothesize that different mechanisms between these two genetic lines may affect their ability to resist C. jejuni colonization in chickens. The molecular mechanisms of the local host response to C. jejuni colonization in chickens have not been well understood. In the present study, to profile the cecal gene expression in the response to C. jejuni colonization and to compare differences between two lines at the molecular level, RNA of ceca from two genetic lines of chickens (A and B were applied to a chicken whole genome microarray for a pair-comparison between inoculated (I and non-inoculated (N chickens within each line and between lines. Our results demonstrated that metabolism process and insulin receptor signaling pathways are key contributors to the different response to C. jejuni colonization between lines A and B. With C. jejuni inoculation, lymphocyte activation and lymphoid organ development functions are important for line A host defenses, while cell differentiation, communication and signaling pathways are important for line B. Interestingly, circadian rhythm appears play a critical role in host response of the more resistant A line to C. jejuni colonization. A dramatic differential host response was observed between these two lines of chickens. The more susceptible line B chickens responded to C. jejuni inoculation with a dramatic up-regulation in lipid, glucose, and amino acid metabolism, which is undoubtedly for use in the response to the colonization with little or no change in immune host defenses. However, in more resistant line A birds the host defense

  19. Evolution of resistance to a multiple-herbivore community: genetic correlations, diffuse coevolution, and constraints on the plant's response to selection.

    Science.gov (United States)

    Wise, Michael J; Rausher, Mark D

    2013-06-01

    Although plants are generally attacked by a community of several species of herbivores, relatively little is known about the strength of natural selection for resistance in multiple-herbivore communities-particularly how the strength of selection differs among herbivores that feed on different plant organs or how strongly genetic correlations in resistance affect the evolutionary responses of the plant. Here, we report on a field study measuring natural selection for resistance in a diverse community of herbivores of Solanum carolinense. Using linear phenotypic-selection analyses, we found that directional selection acted to increase resistance to seven species. Selection was strongest to increase resistance to fruit feeders, followed by flower feeders, then leaf feeders. Selection favored a decrease in resistance to a stem borer. Bootstrapping analyses showed that the plant population contained significant genetic variation for each of 14 measured resistance traits and significant covariances in one-third of the pairwise combinations of resistance traits. These genetic covariances reduced the plant's overall predicted evolutionary response for resistance against the herbivore community by about 60%. Diffuse (co)evolution was widespread in this community, and the diffuse interactions had an overwhelmingly constraining (rather than facilitative) effect on the plant's evolution of resistance. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  20. Association of serotonin receptor 2a haplotypes with obsessive-compulsive disorder and its treatment response in Iranian patients: a genetic and pharmacogenetic study.

    Science.gov (United States)

    Sina, Marzie; Ahmadiani, Abolhassan; Asadi, Sareh; Shams, Jamal

    2018-01-01

    Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder causing intrusive thoughts or repetitive behaviors. Serotonin reuptake inhibitors are used for OCD treatment, but 40%-60% of patients do not respond to them adequately. In this study, the associations of serotonin receptor 2a polymorphisms rs6311 and rs6313 with OCD, its familial form and fluvoxamine treatment response in Iranian population were investigated. Association analyses were conducted in 293 OCD cases fulfilling the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR and 245 controls. Pharmacotherapy was defined as 12 weeks of treatment with fluvoxamine (150-300 mg). Treatment response was considered as >25% reduction in Yale-Brown Obsessive Compulsive Scale score. Genotyping was performed by means of PCR-RFLP. The results showed no association of rs6311 or rs6313 with OCD, but their haplotypes had different distribution patterns in cases and controls. Moreover, rs6313 was associated with the familial form of OCD in females significantly ( P =0.005) under the recessive genetic model. Moreover, rs6311-rs6313 haplotypes were associated with fluvoxamine treatment response in OCD patients with more AC and less AT in responders. HTR2A haplotypes are associated with OCD and its treatment response with a fluvoxamine in Iranian patients. Furthermore, the observed association of rs6313 with the familial form of OCD in females suggests different genetic background of OCD familial and non-familial forms, which needs further investigation.

  1. Associations Between Genetic Variants of NADPH Oxidase-Related Genes and Blood Pressure Responses to Dietary Sodium Intervention: The GenSalt Study.

    Science.gov (United States)

    Han, Xikun; Hu, Zunsong; Chen, Jing; Huang, Jianfeng; Huang, Chen; Liu, Fangchao; Gu, Charles; Yang, Xueli; Hixson, James E; Lu, Xiangfeng; Wang, Laiyuan; Liu, De-Pei; He, Jiang; Chen, Shufeng; Gu, Dongfeng

    2017-04-01

    The aim of this study was to comprehensively test the associations of genetic variants of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related genes with blood pressure (BP) responses to dietary sodium intervention in a Chinese population. We conducted a 7-day low-sodium intervention followed by a 7-day high-sodium intervention among 1,906 participants in rural China. BP measurements were obtained at baseline and each dietary intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the additive associations of 63 tag single-nucleotide polymorphisms in 11 NADPH oxidase-related genes with BP responses to dietary sodium intervention. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses. Systolic BP (SBP) response to high-sodium intervention significantly decreased with the number of minor T allele of marker rs6967221 in RAC1 (P = 4.51 × 10-4). SBP responses (95% confidence interval) for genotypes CC, CT, and TT were 5.03 (4.71, 5.36), 4.20 (3.54, 4.85), and 0.56 (-1.08, 2.20) mm Hg, respectively, during the high-sodium intervention. Gene-based analyses revealed that RAC1 was significantly associated with SBP response to high-sodium intervention (P = 1.00 × 10-6) and diastolic BP response to low-sodium intervention (P = 9.80 × 10-4). These findings suggested that genetic variants of NADPH oxidase-related genes may contribute to the variation of BP responses to sodium intervention in Chinese population. Further replication of these findings is warranted. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  2. Author's Response to Commentaries on: "An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics"

    Science.gov (United States)

    Molenaar, Peter C. M.

    2015-01-01

    In this article, Peter Molenaar responds to three commentaries (this issue) on his article, "An Interpretation of Part of Gilbert Gottlieb's Legacy: Developmental Systems Theory Contra Developmental Behavior Genetics." He addresses aspects of relational developmental systems (RDS) mentioned and questions raised in each of the…

  3. Skewed Helper T-Cell Responses to IL-12 Family Cytokines Produced by Antigen-Presenting Cells and the Genetic Background in Behcet’s Disease

    Directory of Open Access Journals (Sweden)

    Jun Shimizu

    2013-01-01

    Full Text Available Behcet’s disease (BD is a multisystemic inflammatory disease and is characterized by recurrent attacks on eyes, brain, skin, and gut. There is evidence that skewed T-cell responses contributed to its pathophysiology in patients with BD. Recently, we found that Th17 cells, a new helper T (Th cell subset, were increased in patients with BD, and both Th type 1 (Th1 and Th17 cell differentiation signaling pathways were overactivated. Several researches revealed that genetic polymorphisms in Th1/Th17 cell differentiation signaling pathways were associated with the onset of BD. Here, we summarize current findings on the Th cell subsets, their contribution to the pathogenesis of BD and the genetic backgrounds, especially in view of IL-12 family cytokine production and pattern recognition receptors of macrophages/monocytes.

  4. Individual and Group Responses of Fourteen and Fifteen Year Olds to Short Stories, Novels, Poems, and Thematic Apperception Tests: Case Studies Based on Piagetian Genetic Epistemology and Freudian Psychoanalytic Ego Psychology.

    Science.gov (United States)

    Petrosky, Anthony R.

    A descriptive profile of adolescent response to literature is presented in this study, which also examines findings in terms of psychoanalytic concepts that relate response to life styles in terms of Piaget's genetic epistemology. There are two primary questions in this investigation: What is the psychological dynamic of response to literature? By…

  5. Biological responsiveness to the phorbol esters and specific binding of [3H]phorbol 12,13-dibutyrate in the nematode Caenorhabditis elegans, a manipulable genetic system

    International Nuclear Information System (INIS)

    Lew, K.K.; Chritton, S.; Blumberg, P.M.

    1982-01-01

    Because of its suitability for genetic studies, the nematode Caenorhabditis elegans was examined for its responsiveness to the phorbol esters. Phorbol 12-myristate 13-acetate had three effects. It inhibited the increase in animal size during growth; it decreased the yield of progeny; and it caused uncoordinated movement of the adult. The effects on nematode size, progeny yield, and movement were quantitated. Concentrations of phorbol 12-myristate 13-acetate yielding half-maximal responses were 440, 460, and 170 nM, respectively. As was expected from the biological responsiveness of the nematodes, specific, saturable binding of phorbol ester to nematode extracts was found. [ 3 H]phorbol 12,13-dibutyrate bound with a dissociation constant of 26.8 +/- 3.9 nM. At saturation, 5.7 +/- 1.4 pmole/mg protein was bound

  6. ECOGENETICS AND PHARMACOGENETICS: THE IMPORTANCE OF GENETIC POLYMORPHISMS IN THE VARIABILITY OF ORGANISMS RESPONSE TO ENVIRONMENTAL FACTORS

    Directory of Open Access Journals (Sweden)

    Cristian Tudose

    2005-08-01

    protect confidentiality and privacy of individual genetic information may make such research infeasible. In the present paper we expose some general considerations about the importance of the borderline disciplines which are studying the cited aspects (ecogenetics, pharmacogenetics and pharmacogenomics, emphasising the importance of human populations genome polymorphisms affecting drug efficiency and producing adverse reactions; eventually we expose the most recent trends in pharmacogenomics related to the subject

  7. Extremely low genetic diversity across mangrove taxa reflects past sea level changes and hints at poor future responses.

    Science.gov (United States)

    Guo, Zixiao; Li, Xinnian; He, Ziwen; Yang, Yuchen; Wang, Wenqing; Zhong, Cairong; Greenberg, Anthony J; Wu, Chung-I; Duke, Norman C; Shi, Suhua

    2018-04-01

    The projected increases in sea levels are expected to affect coastal ecosystems. Tropical communities, anchored by mangrove trees and having experienced frequent past sea level changes, appear to be vibrant at present. However, any optimism about the resilience of these ecosystems is premature because the impact of past climate events may not be reflected in the current abundance. To assess the impact of historical sea level changes, we conducted an extensive genetic diversity survey on the Indo-Malayan coast, a hotspot with a large global mangrove distribution. A survey of 26 populations in six species reveals extremely low genome-wide nucleotide diversity and hence very small effective population sizes (N e ) in all populations. Whole-genome sequencing of three mangrove species further shows the decline in N e to be strongly associated with the speed of past changes in sea level. We also used a recent series of flooding events in Yalong Bay, southern China, to test the robustness of mangroves to sea level changes in relation to their genetic diversity. The events resulted in the death of half of the mangrove trees in this area. Significantly, less genetically diverse mangrove species suffered much greater destruction. The dieback was accompanied by a drastic reduction in local invertebrate biodiversity. We thus predict that tropical coastal communities will be seriously endangered as the global sea level rises. Well-planned coastal development near mangrove forests will be essential to avert this crisis. © 2017 John Wiley & Sons Ltd.

  8. The evolution of menstruation: a new model for genetic assimilation: explaining molecular origins of maternal responses to fetal invasiveness.

    Science.gov (United States)

    Emera, Deena; Romero, Roberto; Wagner, Günter

    2012-01-01

    Why do humans menstruate while most mammals do not? Here, we present our answer to this long-debated question, arguing that (i) menstruation occurs as a mechanistic consequence of hormone-induced differentiation of the endometrium (referred to as spontaneous decidualization, or SD); (ii) SD evolved because of maternal-fetal conflict; and (iii) SD evolved by genetic assimilation of the decidualization reaction, which is induced by the fetus in non-menstruating species. The idea that menstruation occurs as a consequence of SD has been proposed in the past, but here we present a novel hypothesis on how SD evolved. We argue that decidualization became genetically stabilized in menstruating lineages, allowing females to prepare for pregnancy without any signal from the fetus. We present three models for the evolution of SD by genetic assimilation, based on recent advances in our understanding of the mechanisms of endometrial differentiation and implantation. Testing these models will ultimately shed light on the evolutionary significance of menstruation, as well as on the etiology of human reproductive disorders like endometriosis and recurrent pregnancy loss. Copyright © 2012 WILEY Periodicals, Inc.

  9. Extended spectrum β-lactamases, carbapenemases and mobile genetic elements responsible for antibiotics resistance in Gram-negative bacteria.

    Science.gov (United States)

    El Salabi, Allaaeddin; Walsh, Timothey R; Chouchani, Chedly

    2013-05-01

    Infectious diseases due to Gram-negative bacteria are a leading cause of morbidity and mortality worldwide. Antimicrobial agents represent one major therapeutic tools implicated to treat these infections. The misuse of antimicrobial agents has resulted in the emergence of resistant strains of Gram-negatives in particular Enterobacteriaceae and non-fermenters; they have an effect not only on a human but on the public health when bacteria use the resistance mechanisms to spread in the hospital environment and to the community outside the hospitals by means of mobile genetic elements. Gram-negative bacteria have become increasingly resistant to antimicrobial agents. They have developed several mechanisms by which they can withstand to antimicrobials, these mechanisms include the production of Extended-spectrum β-lactamases (ESBLs) and carbapenemases, furthermore, Gram-negative bacteria are now capable of spreading such resistance between members of the family Enterobacteriaceae and non-fermenters using mobile genetic elements as vehicles for such resistance mechanisms rendering antibiotics useless. Therefore, addressing the issue of mechanisms of antimicrobial resistance is considered one of most urgent priorities. This review will help to illustrate different resistance mechanisms; ESBLs, carbapenemases encoded by genes carried by mobile genetic elements, which are used by Gram-negative bacteria to escape antimicrobial effect.

  10. Genetic and epigenetic inactivation of SESTRIN1 controls mTORC1 and response to EZH2 inhibition in follicular lymphoma.

    Science.gov (United States)

    Oricchio, Elisa; Katanayeva, Natalya; Donaldson, Maria Christine; Sungalee, Stephanie; Pasion, Joyce P; Béguelin, Wendy; Battistello, Elena; Sanghvi, Viraj R; Jiang, Man; Jiang, Yanwen; Teater, Matt; Parmigiani, Anita; Budanov, Andrei V; Chan, Fong Chun; Shah, Sohrab P; Kridel, Robert; Melnick, Ari M; Ciriello, Giovanni; Wendel, Hans-Guido

    2017-06-28

    Follicular lymphoma (FL) is an incurable form of B cell lymphoma. Genomic studies have cataloged common genetic lesions in FL such as translocation t(14;18), frequent losses of chromosome 6q, and mutations in epigenetic regulators such as EZH2 Using a focused genetic screen, we identified SESTRIN1 as a relevant target of the 6q deletion and demonstrate tumor suppression by SESTRIN1 in vivo. Moreover, SESTRIN1 is a direct target of the lymphoma-specific EZH2 gain-of-function mutation ( EZH2 Y641X ). SESTRIN1 inactivation disrupts p53-mediated control of mammalian target of rapamycin complex 1 (mTORC1) and enables mRNA translation under genotoxic stress. SESTRIN1 loss represents an alternative to RRAGC mutations that maintain mTORC1 activity under nutrient starvation. The antitumor efficacy of pharmacological EZH2 inhibition depends on SESTRIN1, indicating that mTORC1 control is a critical function of EZH2 in lymphoma. Conversely, EZH2 Y641X mutant lymphomas show increased sensitivity to RapaLink-1, a bifunctional mTOR inhibitor. Hence, SESTRIN1 contributes to the genetic and epigenetic control of mTORC1 in lymphoma and influences responses to targeted therapies. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  11. Genetic variation of habitual coffee consumption and glycemic changes in response to weight-loss diet intervention: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.

    Science.gov (United States)

    Han, Liyuan; Ma, Wenjie; Sun, Dianjianyi; Heianza, Yoriko; Wang, Tiange; Zheng, Yan; Huang, Tao; Duan, Donghui; Bray, J George A; Champagne, Catherine M; Sacks, Frank M; Qi, Lu

    2017-11-01

    Background: Coffee consumption has been associated with glucose metabolism and risk of type 2 diabetes. Objective: We examined whether the genetic variation determining habitual coffee consumption affected glycemic changes in response to weight-loss dietary intervention. Design: A genetic risk score (GRS) was calculated based on 8 habitual coffee consumption-associated single nucleotide polymorphisms. We used general linear models to test changes in glycemic traits in groups randomly assigned to high- and low-fat diets according to tertiles of the GRS. Results: We observed significant interactions between the GRS and low compared with high dietary fat intake on 6-mo changes in fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) ( P -interaction = 0.023 and 0.022, respectively), adjusting for age, sex, race, physical activity, smoking, alcohol, seasonal variation, and baseline values of the respective outcomes. Participants with a higher GRS of habitual coffee consumption showed a greater reduction in fasting insulin and a marginally greater decrease in HOMA-IR in the low-fat diet intervention group. Conclusions: Our data suggest that participants with genetically determined high coffee consumption may benefit more by eating a low-fat diet in improving fasting insulin and HOMA-IR in a short term. This trial was registered at clinicaltrials.gov as NCT00072995 and NCT03258203. © 2017 American Society for Nutrition.

  12. Population genetic and evolution analysis of controversial genus Edwardsiella by multilocus sequence typing.

    Science.gov (United States)

    Buján, Noemí; Balboa, Sabela; L Romalde, Jesús; E Toranzo, Alicia; Magariños, Beatriz

    2018-05-08

    At present, the genus Edwardsiella compiles five species: E. tarda, E. hoshinae, E. ictaluri, E. piscicida and E. anguillarum. Some species of this genus such us E. ictaluri and E. piscicida are important pathogens of numerous fish species. With the description of the two latter species, the phylogeny of Edwardsiella became more complicated. With the aim to clarify the relationships among all species in the genus, a multilocus sequence typing (MLST) approach was developed and applied to characterize 56 isolates and 6 reference strains belonging to the five Edwardsiella species. Moreover, several analyses based on the MLST scheme were performed to investigate the evolution within the genus, as well as the influence of recombination and mutation in the speciation. Edwardsiella isolates presented a high genetic variability reflected in the fourteen sequence types (ST) represented by a single isolates out of eighteen total ST. Mutation events were considerably more frequent than recombination, although both approximately equal influenced the genetic diversification. However, the speciation among species occurred mostly by recombination. Edwardsiella genus displays a non-clonal population structure with some degree of geographical isolation followed by a population expansion of E. piscicida. A database from this study was created and hosted on pubmlst.org (http://pubmlst.org/edwardsiella/). Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Plasma Taurine, Diabetes Genetic Predisposition, and Changes of Insulin Sensitivity in Response to Weight-Loss Diets.

    Science.gov (United States)

    Zheng, Yan; Ceglarek, Uta; Huang, Tao; Wang, Tiange; Heianza, Yoriko; Ma, Wenjie; Bray, George A; Thiery, Joachim; Sacks, Frank M; Qi, Lu

    2016-10-01

    Taurine metabolism disturbance is closely linked to obesity, insulin resistance, and diabetes. Previous evidence suggested that the preventative effects of taurine on diabetes might be through regulating the expression levels of diabetes-related genes. We estimated whether blood taurine levels modified the overall genetic susceptibility to diabetes on improvement of insulin sensitivity in a randomized dietary trial. We genotyped 31 diabetes-associated variants to calculate a genetic risk score (GRS) and measured plasma taurine levels and glycemic traits among participants from the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial. Seven-hundred eleven overweight or obese participants (age 30-70 y; 60% females) had genetic variants genotyped and blood taurine levels measured. Participants went on 2-year weight-loss diets, which were different in macronutrient composition. Improvements in glycemic traits were measured. We found that baseline taurine levels significantly modified the effects of diabetes GRS on changes in fasting glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) during the 2-year diet intervention (P-interaction = .04, .01, .002, respectively), regardless of weight loss. High baseline taurine levels were associated with a less reduction in both glucose and HOMA-IR among the participants with the lowest tertile of diabetes GRS (both P = .02), and with a greater reduction in both insulin and HOMA-IR among those with the highest tertile of diabetes GRS (both P = .04). Our data suggest that blood taurine levels might differentially modulate the effects of diabetes-related genes on improvement of insulin sensitivity among overweight/obese patients on weight-loss diets.

  14. 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 (PPARγ NestinCre ), 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 PPARγ NestinCre 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 PPARγ NestinCre 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

  15. Confirmation of an IRAK3 polymorphism as a genetic marker predicting response to anti-TNF treatment in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Sode, Jacob; Vogel, U; Bank, Steffen

    2018-01-01

    the IRAK3 rs11541076 variant as associated (odds ratio (OR)=1.33, 95% confidence interval (CI): 1.00-1.77, P-value=0.047) with a positive treatment response (EULAR (European League Against Rheumatism) good/moderate vs none response at 4±2 months), and found the NLRP3 rs461266 variant associated (OR=0...

  16. Functional consequences of inducible genetic elements from the p53 SOS response in a mammalian organ system.

    Science.gov (United States)

    Guthrie, O'neil W

    2017-10-01

    In response to DNA damage from ultraviolet (UV) radiation, bacteria deploy the SOS response in order to limit cell death. This bacterial SOS response is characterized by an increase in the recA gene that transactivates expression of multiple DNA repair genes. The current series of experiments demonstrate that a mammalian organ system (the cochlea) that is not evolutionarily conditioned to UV radiation can elicit SOS responses that are reminiscent of that of bacteria. This mammalian SOS response is characterized by an increase in the p53 gene with activation of multiple DNA repair genes that harbor p53 response elements in their promoters. Furthermore, the experimental results provide support for the notion of a convergent trigger paradox, where independent SOS triggers facilitate disparate physiologic sequelae (loss vs. recovery of function). Therefore, it is proposed that the mammalian SOS response is multifunctional and manipulation of this endogenous response could be exploited in future biomedical interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Genetic polymorphism in ATG16L1 gene influences the response to adalimumab in Crohn's disease patients

    NARCIS (Netherlands)

    Koder, Silvo; Repnik, Katja; Ferkolj, Ivan; Pernat, Cvetka; Skok, Pavel; Weersma, Rinse K.; Potocnik, Uros

    2015-01-01

    Aim: To see if SNPs could help predict response to biological therapy using adalimumab (ADA) in Crohn's disease (CD). Materials & methods: IBDQ index and CRP levels were used to monitor therapy response. We genotyped 31 CD-associated genes in 102 Slovenian CD patients. Results: The strongest

  18. Effects of mixed housing of birds from two genetic lines of laying hens on open field and manual restraint responses

    NARCIS (Netherlands)

    Uitdehaag, K.A.; Rodenburg, T.B.; Hierden, van Y.M.; Bolhuis, J.E.; Toscano, M.J.; Nicol, C.J.; Komen, J.

    2008-01-01

    Birds from Rhode Island Red (RIR) origin show a lower fear response and less feather pecking than birds from White Leghorn (WL) origin. This study investigated whether responses in fear eliciting tests were affected if RIR and WL birds were housed together. Experimental groups contained either birds

  19. Association of serotonin receptor 2a haplotypes with obsessive–compulsive disorder and its treatment response in Iranian patients: a genetic and pharmacogenetic study

    Science.gov (United States)

    Sina, Marzie; Ahmadiani, Abolhassan; Asadi, Sareh; Shams, Jamal

    2018-01-01

    Introduction Obsessive–compulsive disorder (OCD) is a debilitating psychiatric disorder causing intrusive thoughts or repetitive behaviors. Serotonin reuptake inhibitors are used for OCD treatment, but 40%–60% of patients do not respond to them adequately. In this study, the associations of serotonin receptor 2a polymorphisms rs6311 and rs6313 with OCD, its familial form and fluvoxamine treatment response in Iranian population were investigated. Patients and methods Association analyses were conducted in 293 OCD cases fulfilling the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR and 245 controls. Pharmacotherapy was defined as 12 weeks of treatment with fluvoxamine (150–300 mg). Treatment response was considered as >25% reduction in Yale–Brown Obsessive Compulsive Scale score. Genotyping was performed by means of PCR-RFLP. Results The results showed no association of rs6311 or rs6313 with OCD, but their haplotypes had different distribution patterns in cases and controls. Moreover, rs6313 was associated with the familial form of OCD in females significantly (P=0.005) under the recessive genetic model. Moreover, rs6311–rs6313 haplotypes were associated with fluvoxamine treatment response in OCD patients with more AC and less AT in responders. Conclusion HTR2A haplotypes are associated with OCD and its treatment response with a fluvoxamine in Iranian patients. Furthermore, the observed association of rs6313 with the familial form of OCD in females suggests different genetic background of OCD familial and non-familial forms, which needs further investigation. PMID:29785111

  20. Genetic ancestry in relation to the metabolic response to a US versus traditional Mexican diet: a randomized crossover feeding trial among women of Mexican descent.

    Science.gov (United States)

    Santiago-Torres, M; De Dieu Tapsoba, J; Kratz, M; Lampe, J W; Breymeyer, K L; Levy, L; Song, X; Villaseñor, A; Wang, C-Y; Fejerman, L; Neuhouser, M L; Carlson, C S

    2017-03-01

    Certain populations with a large proportion of indigenous American (IA) genetic ancestry may be evolutionarily adapted to traditional diets high in legumes and complex carbohydrates, and may have a detrimental metabolic response to US diets high in refined carbohydrates and added sugars. We tested whether IA ancestry modified the metabolic response to a US versus traditional Mexican diet in a controlled dietary intervention. First and second generation Mexican immigrant women (n=53) completed a randomized crossover feeding trial testing the effects of a US versus traditional Mexican diet. The metabolic response to the diets was measured by fasting serum concentrations of glucose, insulin, insulin-like growth factor-1 (IGF-1), IGF-binding protein-3 (IGFBP-3), adiponectin, C-reactive protein, interleukin-6 and computed homeostasis model assessment for insulin resistance (HOMA IR ). Blood collected at baseline was used for genotyping, and estimation of African, European and IA ancestries with the use of 214 ancestry informative markers. The genetic ancestral background was 56% IA, 38% European and 6% African. Women in the highest IA ancestry tertile (>62%) were shorter in height, less educated and less acculturated to the US lifestyle, and tended to have higher waist-to-hip ratio compared with women in the middle and lowest IA ancestry tertiles, respectively. Compared with the US diet, the traditional Mexican diet tended to reduce glucose, insulin, IGF-1, IGFBP-3 and HOMA IR among women in the middle IA ancestry group (IA ancestry ⩽45-62%), whereas having no effect on biomarkers related to inflammation. We observed modest interactions between IA ancestry and the metabolic response to a US versus traditional Mexican diet among Mexican immigrant women.

  1. Genetic Variability as a Regulator of TLR4 and NOD Signaling in Response to Bacterial Driven DNA Damage Response (DDR and Inflammation: Focus on the Gastrointestinal (GI Tract

    Directory of Open Access Journals (Sweden)

    Evagelia Spanou

    2017-05-01

    Full Text Available The fundamental role of human Toll-like receptors (TLRs and NOD-like receptors (NLRs, the two most studied pathogen recognition receptors (PRRs, is the protection against pathogens and excessive tissue injury. Recent evidence supports the association between TLR/NLR gene mutations and susceptibility to inflammatory, autoimmune, and malignant diseases. PRRs also interfere with several cellular processes, such as cell growth, apoptosis, cell proliferation, differentiation, autophagy, angiogenesis, cell motility and migration, and DNA repair mechanisms. We briefly review the impact of TLR4 and NOD1/NOD2 and their genetic variability in the process of inflammation, tumorigenesis and DNA repair, focusing in the gastrointestinal tract. We also review the available data on new therapeutic strategies utilizing TLR/NLR agonists and antagonists for cancer, allergic diseases, viral infections and vaccine development against both infectious diseases and cancer.

  2. Analysis of the genetic basis of plant height-related traits in response to ethylene by QTL mapping in maize (Zea mays L.).

    Science.gov (United States)

    Zhang, Weiqiang; Li, Zhi; Fang, Hui; Zhang, Mingcai; Duan, Liusheng

    2018-01-01

    Ethylene (ET) is critical importance in the growth, development, and stress responses of plants. Plant hormonal stress responses have been extensively studied, however, the role of ET in plant growth, especially plant height (PH) remains unclear. Understanding the genetic control for PH in response to ET will provide insights into the regulation of maize development. To clarify the genetic basis of PH-related traits of maize in response to ET, we mapped QTLs for PH, ear height (EH), and internode length above the uppermost ear (ILAU) in two recombinant inbred line (RIL) populations of Zea mays after ET treatment and in an untreated control (CK) group. Sixty QTLs for the three traits were identified. Twenty-two QTLs were simultaneously detected under both ET treatment and untreated control, and five QTLs were detected at two geographic locations under ET treatment only. Individual QTL can be explained 3.87-17.71% of the phenotypic variance. One QTL (q2PH9-1, q1PH9, q1EH9/q1ILAU9-1, q2ILAU9, and q2EH9) for the measured traits (PH, EH, ILAU) was consistent across both populations. Two QTLs (q2PH2-5, q2ILAU2-2, q1PH2-2, and q1ILAU2-2; q1PH8-1, q1EH8-1, q2PH8-1) were identified for up to two traits in both locations and populations under both ET treatment and untreated control. These consistent and stable regions are important QTLs of potential hot spots for PH, ear height (EH), and internode length above the uppermost ear (ILAU) response to ET in maize; therefore, QTL fine-mapping and putative candidate genes validation should enable the cloning of PH, EH, and ILAU related genes to ET response. These results will be valuable for further fine-mapping and quantitative trait nucleotides (QTNs) determination, and elucidate the underlying molecular mechanisms of ET responses in maize.

  3. Analysis of the genetic basis of plant height-related traits in response to ethylene by QTL mapping in maize (Zea mays L..

    Directory of Open Access Journals (Sweden)

    Weiqiang Zhang

    Full Text Available Ethylene (ET is critical importance in the growth, development, and stress responses of plants. Plant hormonal stress responses have been extensively studied, however, the role of ET in plant growth, especially plant height (PH remains unclear. Understanding the genetic control for PH in response to ET will provide insights into the regulation of maize development. To clarify the genetic basis of PH-related traits of maize in response to ET, we mapped QTLs for PH, ear height (EH, and internode length above the uppermost ear (ILAU in two recombinant inbred line (RIL populations of Zea mays after ET treatment and in an untreated control (CK group. Sixty QTLs for the three traits were identified. Twenty-two QTLs were simultaneously detected under both ET treatment and untreated control, and five QTLs were detected at two geographic locations under ET treatment only. Individual QTL can be explained 3.87-17.71% of the phenotypic variance. One QTL (q2PH9-1, q1PH9, q1EH9/q1ILAU9-1, q2ILAU9, and q2EH9 for the measured traits (PH, EH, ILAU was consistent across both populations. Two QTLs (q2PH2-5, q2ILAU2-2, q1PH2-2, and q1ILAU2-2; q1PH8-1, q1EH8-1, q2PH8-1 were identified for up to two traits in both locations and populations under both ET treatment and untreated control. These consistent and stable regions are important QTLs of potential hot spots for PH, ear height (EH, and internode length above the uppermost ear (ILAU response to ET in maize; therefore, QTL fine-mapping and putative candidate genes validation should enable the cloning of PH, EH, and ILAU related genes to ET response. These results will be valuable for further fine-mapping and quantitative trait nucleotides (QTNs determination, and elucidate the underlying molecular mechanisms of ET responses in maize.

  4. Analysis of the genetic basis of plant height-related traits in response to ethylene by QTL mapping in maize (Zea mays L.)

    Science.gov (United States)

    Li, Zhi; Fang, Hui; Zhang, Mingcai; Duan, Liusheng

    2018-01-01

    Ethylene (ET) is critical importance in the growth, development, and stress responses of plants. Plant hormonal stress responses have been extensively studied, however, the role of ET in plant growth, especially plant height (PH) remains unclear. Understanding the genetic control for PH in response to ET will provide insights into the regulation of maize development. To clarify the genetic basis of PH-related traits of maize in response to ET, we mapped QTLs for PH, ear height (EH), and internode length above the uppermost ear (ILAU) in two recombinant inbred line (RIL) populations of Zea mays after ET treatment and in an untreated control (CK) group. Sixty QTLs for the three traits were identified. Twenty-two QTLs were simultaneously detected under both ET treatment and untreated control, and five QTLs were detected at two geographic locations under ET treatment only. Individual QTL can be explained 3.87–17.71% of the phenotypic variance. One QTL (q2PH9-1, q1PH9, q1EH9/q1ILAU9-1, q2ILAU9, and q2EH9) for the measured traits (PH, EH, ILAU) was consistent across both populations. Two QTLs (q2PH2-5, q2ILAU2-2, q1PH2-2, and q1ILAU2-2; q1PH8-1, q1EH8-1, q2PH8-1) were identified for up to two traits in both locations and populations under both ET treatment and untreated control. These consistent and stable regions are important QTLs of potential hot spots for PH, ear height (EH), and internode length above the uppermost ear (ILAU) response to ET in maize; therefore, QTL fine-mapping and putative candidate genes validation should enable the cloning of PH, EH, and ILAU related genes to ET response. These results will be valuable for further fine-mapping and quantitative trait nucleotides (QTNs) determination, and elucidate the underlying molecular mechanisms of ET responses in maize. PMID:29466465

  5. Transferrin Level Before Treatment and Genetic Polymorphism in HFE Gene as Predictive Markers for Response to Adalimumab in Crohn's Disease Patients.

    Science.gov (United States)

    Repnik, Katja; Koder, Silvo; Skok, Pavel; Ferkolj, Ivan; Potočnik, Uroš

    2016-08-01

    Tumor necrosis factor α inhibitors (anti-TNF) have improved treatment of several complex diseases, including Crohn's disease (CD). However, the effect varies and approximately one-third of the patients do not respond. Since blood parameters as well as genetic factors have shown a great potential to predict response during treatment, the aim of the study was to evaluate response to anti-TNF treatment with adalimumab (ADA) between genes HFE and TF and haematological parameters in Slovenian refractory CD patients. Single nucleotide polymorphisms (SNPs) rs1799852 in gene TF and rs2071303 in gene HFE were genotyped in 68 refractory CD patients for which response has been measured using inflammatory bowel disease questionnaire (IBDQ) index. Haematological parameters and IBDQ index were determined before therapy and after 4, 12, 20 and 30 weeks. We found novel strong association between SNP rs2071303 in gene HFE and response to ADA treatment, particularly patients with G allele comparing to A allele had better response after 20 weeks (p = 0.008). Further, we found strong association between transferrin level at baseline and treatment response after 12, 20 and 30 weeks, where average transferrin level before therapy was lower in responders (2.38 g/L) compared to non-responders (2.89 g/L, p = 0.005). Association was found between transferrin level in week 30 and SNP rs1799852 (p = 0.023), and between MCHC level before treatment and SNP rs2071303 (p = 0.007). Our results suggest that SNP in gene HFE as well as haematological markers serve as promising prognostic markers of response to anti-TNF treatment in CD patients.

  6. Handling ethical, legal and social issues in birth cohort studies involving genetic research: responses from studies in six countries

    Directory of Open Access Journals (Sweden)

    LeGrandeur Jane

    2010-03-01

    Full Text Available Abstract Background Research involving minors has been the subject of much ethical debate. The growing number of longitudinal, pediatric studies that involve genetic research present even more complex challenges to ensure appropriate protection of children and families as research participants. Long-term studies with a genetic component involve collection, retention and use of biological samples and personal information over many years. Cohort studies may be established to study specific conditions (e.g. autism, asthma or may have a broad aim to research a range of factors that influence the health and development of children. Studies are increasingly intended to serve as research platforms by providing access to data and biological samples to researchers over many years. This study examines how six birth cohort studies in North America and Europe that involve genetic research handle key ethical, legal and social (ELS issues: recruitment, especially parental authority to include a child in research; initial parental consent and subsequent assent and/or consent from the maturing child; withdrawal; confidentiality and sample/data protection; handling sensitive information; and disclosure of results. Methods Semi-structured telephone interviews were carried out in 2008/09 with investigators involved in six birth cohort studies in Canada, Denmark, England, France, the Netherlands and the United States. Interviewees self-identified as being knowledgeable about ELS aspects of the study. Interviews were conducted in English. Results The studies vary in breadth of initial consent, but none adopt a blanket consent for future use of samples/data. Ethics review of new studies is a common requirement. Studies that follow children past early childhood recognise a need to seek assent/consent as the child matures. All studies limit access to identifiable data and advise participants of the right to withdraw. The clearest differences among studies concern

  7. Genetic determination of the biological radiation response in inbred mice lines; Genetische Determination der biologischen Strahlenantwort in Mausinzuchtstaemmen

    Energy Technology Data Exchange (ETDEWEB)

    Gomolka, M.; Hornhardt, S.; Jung, T. [Bundesamt fuer Strahlenschutz Oberschleissheim (Germany). Institut fuer Strahlenhygiene

    2000-07-01

    Variation in radiation sensitivity and radiation resistance is influenced by the genetic constitution of an individual. Loss of function of genes involved in DNA repair, cell cycle or controlled cell death can have serious consequences on individual radiation sensitivity. For example, individuals suffering on the clinical syndrome of Ataxia telangiectasia exhibit radiation sensitivity in the order of 2-3 magnitudes higher than other cancer patients. For radiation protection it is important to clarify the role of genetic predisposition for radiation sensitivity in clinical healthy people. Therefore, data were collected from the literature describing the genetic variation (heritability) of radiation sensitivity in the mouse model. A heritability of 30-50% was calculated for 27 inbred mice lines by Roderick (1963) based on days of survival after a daily dose of 1 Gy {gamma}-irradiation. The following inbred lines were described in the literature as radiation sensitive (phenotypical markers were e.g., time of survival, mortality, reduction in fertility post exposure): SWR, RIII, NC, K, HLG, DBA, CBA, BALB/c, A, AKR. Radiation resistance was demonstrated in SJL, SEC, RF, MA, C58, C57BR, BDP and 129. Parameter of longevity, some physiological, biochemical and immunological parameters as given in the data bank of the Jackson Laboratory, U.S.A., were compared between radiation sensitive and radiation resistant inbred strains. No correlation was seen for the most of the parameters except for the development of breast cancer. In 6 out of 10 radiosensitive inbred strains breast cancer is described while only 1 of 8 strains exhibits breast cancer. The higher heritability of 30-50% in spite of a very complex phenotype like survival and the correlation between radiosensitivity and tumour incidence show that individual genetic susceptibility is important on the biological radiation reaction. (orig.) [German] Die phaenotypische Variation der Strahlensensitivitaet und

  8. BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses1

    Science.gov (United States)

    Belkina, Anna C.; Nikolajczyk, Barbara S.; Denis, Gerald V.

    2013-01-01

    Histone acetylation regulates activation and repression of multiple inflammatory genes known to play critical roles in chronic inflammatory diseases. However, proteins responsible for translating the histone acetylation code into an orchestrated pro-inflammatory cytokine response remain poorly characterized. Bromodomain extra terminal (BET) proteins are “readers” of histone acetylation marks with demonstrated roles in gene transcription, but the ability of BET proteins to coordinate the response of inflammatory cytokine genes through translation of histone marks is unknown. We hypothesize that members of the BET family of dual bromodomain-containing transcriptional regulators directly control inflammatory genes. We examined the genetic model of brd2 lo mice, a BET protein hypomorph, to show that Brd2 is essential for pro-inflammatory cytokine production in macrophages. Studies that utilize siRNA knockdown and a small molecule inhibitor of BET protein binding, JQ1, independently demonstrate BET proteins are critical for macrophage inflammatory responses. Furthermore, we show that Brd2 and Brd4 physically associate with the promoters of inflammatory cytokine genes in macrophages. This association is absent in the presence of BET inhibition by JQ1. Finally, we demonstrate that JQ1 ablates cytokine production in vitro and blunts the “cytokine storm” in endotoxemic mice by reducing levels of IL-6 and TNF-α while rescuing mice from LPS-induced death. We propose that targeting BET proteins with small molecule inhibitors will benefit hyper-inflammatory conditions associated with high levels of cytokine production. PMID:23420887

  9. BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses.

    Science.gov (United States)

    Belkina, Anna C; Nikolajczyk, Barbara S; Denis, Gerald V

    2013-04-01

    Histone acetylation regulates activation and repression of multiple inflammatory genes known to play critical roles in chronic inflammatory diseases. However, proteins responsible for translating the histone acetylation code into an orchestrated proinflammatory cytokine response remain poorly characterized. Bromodomain and extraterminal (BET) proteins are "readers" of histone acetylation marks, with demonstrated roles in gene transcription, but the ability of BET proteins to coordinate the response of inflammatory cytokine genes through translation of histone marks is unknown. We hypothesize that members of the BET family of dual bromodomain-containing transcriptional regulators directly control inflammatory genes. We examined the genetic model of brd2 lo mice, a BET protein hypomorph, to show that Brd2 is essential for proinflammatory cytokine production in macrophages. Studies that use small interfering RNA knockdown and a small-molecule inhibitor of BET protein binding, JQ1, independently demonstrate BET proteins are critical for macrophage inflammatory responses. Furthermore, we show that Brd2 and Brd4 physically associate with the promoters of inflammatory cytokine genes in macrophages. This association is absent in the presence of BET inhibition by JQ1. Finally, we demonstrate that JQ1 ablates cytokine production in vitro and blunts the "cytokine storm" in endotoxemic mice by reducing levels of IL-6 and TNF-α while rescuing mice from LPS-induced death. We propose that targeting BET proteins with small-molecule inhibitors will benefit hyperinflammatory conditions associated with high levels of cytokine production.

  10. QTL and systems genetics analysis of mouse grooming and behavioral responses to novelty in an open field.

    Science.gov (United States)

    Delprato, A; Algéo, M-P; Bonheur, B; Bubier, J A; Lu, L; Williams, R W; Chesler, E J; Crusio, W E

    2017-11-01

    The open field is a classic test used to assess exploratory behavior, anxiety and locomotor activity in rodents. Here, we mapped quantitative trait loci (QTLs) underlying behaviors displayed in an open field, using a panel of 53 BXD recombinant inbred mouse strains with deep replication (10 per strain and sex). The use of these strains permits the integration and comparison of data obtained in different laboratories, and also offers the possibility to study trait covariance by exploiting powerful bioinformatics tools and resources. We quantified behavioral traits during 20-min test sessions including (1) percent time spent and distance traveled near the wall (thigmotaxis), (2) leaning against the wall, (3) rearing, (4) jumping, (5) grooming duration, (6) grooming frequency, (7) locomotion and (8) defecation. All traits exhibit moderate heritability making them amenable to genetic analysis. We identified a significant QTL on chromosome M.m. 4 at approximately 104 Mb that modulates grooming duration in both males and females (likelihood ratio statistic values of approximately 18, explaining 25% and 14% of the variance, respectively) and a suggestive QTL modulating locomotion that maps to the same locus. Bioinformatic analysis indicates Disabled 1 (Dab1, a key protein in the reelin signaling pathway) as a particularly strong candidate gene modulating these behaviors. We also found 2 highly suggestive QTLs for a sex by strain interaction for grooming duration on chromosomes 13 and 17. In addition, we identified a pairwise epistatic interaction between loci on chromosomes 12 at 36-37 Mb and 14 at 34-36 Mb that influences rearing frequency in males. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  11. Different responsiveness to a high-fat/cholesterol diet in two inbred mice and underlying genetic factors: a whole genome microarray analysis

    Directory of Open Access Journals (Sweden)

    Jin Gang

    2009-10-01

    Full Text Available Abstract Background To investigate different responses to a high-fat/cholesterol diet and uncover their underlying genetic factors between C57BL/6J (B6 and DBA/2J (D2 inbred mice. Methods B6 and D2 mice were fed a high-fat/cholesterol diet for a series of time-points. Serum and bile lipid profiles, bile acid yields, hepatic apoptosis, gallstones and atherosclerosis formation were measured. Furthermore, a whole genome microarray was performed to screen hepatic genes expression profile. Quantitative real-time PCR, western blot and TUNEL assay were conducted to validate microarray data. Results After fed the high-fat/cholesterol diet, serum and bile total cholesterol, serum cholesterol esters, HDL cholesterol and Non-HDL cholesterol levels were altered in B6 but not significantly changed in D2; meanwhile, biliary bile acid was decreased in B6 but increased in D2. At the same time, hepatic apoptosis, gallstones and atherosclerotic lesions occurred in B6 but not in D2. The hepatic microarray analysis revealed distinctly different genes expression patterns between B6 and D2 mice. Their functional pathway groups included lipid metabolism, oxidative stress, immune/inflammation response and apoptosis. Quantitative real time PCR, TUNEL assay and western-blot results were consistent with microarray analysis. Conclusion Different genes expression patterns between B6 and D2 mice might provide a genetic basis for their distinctive responses to a high-fat/cholesterol diet, and give us an opportunity to identify novel pharmaceutical targets in related diseases in the future.

  12. An Overview of the Genetics of Plant Response to Salt Stress: Present Status and the Way Forward.

    Science.gov (United States)

    Kaleem, Fawad; Shabir, Ghulam; Aslam, Kashif; Rasul, Sumaira; Manzoor, Hamid; Shah, Shahid Masood; Khan, Abdul Rehman

    2018-04-02

    Salinity is one of the major threats faced by the modern agriculture today. It causes multidimensional effects on plants. These effects depend upon the plant growth stage, intensity, and duration of the stress. All these lead to stunted growth and reduced yield, ultimately inducing economic loss to the farming community in particular and to the country in general. The soil conditions of agricultural land are deteriorating at an alarming rate. Plants assess the stress conditions, transmit the specific stress signals, and then initiate the response against that stress. A more complete understanding of plant response mechanisms and their practical incorporation in crop improvement is an essential step towards achieving the goal of sustainable agricultural development. Literature survey shows that investigations of plant stresses response mechanism are the focus area of research for plant scientists. Although these efforts lead to reveal different plant response mechanisms against salt stress, yet many questions still need to be answered to get a clear picture of plant strategy to cope with salt stress. Moreover, these studies have indicated the presence of a complicated network of different integrated pathways. In order to work in a progressive way, a review of current knowledge is critical. Therefore, this review aims to provide an overview of our understanding of plant response to salt stress and to indicate some important yet unexplored dynamics to improve our knowledge that could ultimately lead towards crop improvement.

  13. Response to selection and genetic parameters of body and carcass weights in Japanese quail selected for 4-week body weight

    DEFF Research Database (Denmark)

    Khaldari, M; Pakdel, A; Yegane, H Mehrabani

    2010-01-01

    , respectively. There was a significant effect of sex, generation, and line (P difference for BW and carcass weights but not for carcass percentage components between sexes (P ... to improve carcass traits. Also, intense selection resulting in high rates of inbreeding might result in decreased response to selection due to inbreeding depression....

  14. Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects

    NARCIS (Netherlands)

    Santer, R.; Muhle, H.; Suormala, T.; Baumgartner, E. R.; Duran, M.; Yang, X.; Aoki, Y.; Suzuki, Y.; Stephani, U.

    2003-01-01

    We report the clinical course and biochemical findings of a 10-year-old, mentally retarded girl with late-onset holocarboxylase synthetase (HCS, gene symbol HLCS) deficiency and only partial response to biotin. On treatment, even with an unusually high dose of 200mg/day, activities of the

  15. SNP discovery and development of genetic markers for mapping immune response genes in common carp (Cyprinus carpio)

    Science.gov (United States)

    Single nucleotide polymorphisms (SNPs) in immune response genes have been reported as markers for susceptibility to infectious diseases in human and livestock. A disease caused by cyprinid herpesvirus 3 (CyHV-3) is highly contagious and virulent in common carp (Cyprinus carpio). With the aim to de...

  16. From observational to dynamic genetics

    Directory of Open Access Journals (Sweden)

    Claire M. A. Haworth

    2014-01-01

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

  17. Influence of NKG2D Genetic Variants on Response to Anti-TNF Agents in Patients with Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Milena Iwaszko

    2018-01-01

    Full Text Available A natural killer group 2 member D (NKG2D acts as a powerful activating and co-stimulatory receptor on immune effector cells including NK and T cells. Disruptions within the NKG2D signalling pathway may trigger an exacerbated immune response and promote autoimmune reactions. The objective of the study was to evaluate a plausible role of polymorphisms within the NKG2D gene as a predictor of how effective anti-tumor necrosis factor (TNF therapy is in rheumatoid arthritis (RA patients. A total of 280 RA patients receiving anti-TNF therapy were genotyped for NKG2D rs2255336 (A > G, rs1049174 (C > G, and rs1154831 (C > A. Clinical response was evaluated according to the European League against Rheumatism (EULAR criteria at the 12th and 24th week. Both the NKG2D rs225336 and rs1049174 polymorphisms were significantly associated with efficacy of TNF inhibitors. Inefficient therapy was more frequently observed in patients with rs2255336 GG or rs1049174 CC genotype as compared to other genotypes (p-value = 0.003 and p-value = 0.004, respectively. The presence of the rs2255336 G or the rs1049174 C allele correlated with a worse EULAR response (p-value = 0.002, p-value = 0.031, respectively. Moreover, patients carrying the rs2255336 or rs1049174 heterozygous genotype achieved better EULAR responses than patients with homozygous genotypes (p-value = 0.010 and p-value = 0.002, respectively. Data from the present study provides evidence that NKG2D polymorphisms may affect response to anti-TNF inhibitors in RA patients.

  18. Optimization of process parameters for ethanol production from sugar cane molasses by Zymomonas mobilis using response surface methodology and genetic algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Maiti, Bodhisatta; Shekhawat, Mitali; Srivastava, Pradeep [Banaras Hindu Univ., Varanasi (India). School of Biochemical Engineering; Rathore, Ankita [Nizam College, Hyderabad (India). Dept. of Biotechnology; Srivastava, Saurav [National Institute of Technology, Durgapur (India). Dept. of Biotechnology

    2011-04-15

    Ethanol is a potential energy source and its production from renewable biomass has gained lot of popularity. There has been worldwide research to produce ethanol from regional inexpensive substrates. The present study deals with the optimization of process parameters (viz. temperature, pH, initial total reducing sugar (TRS) concentration in sugar cane molasses and fermentation time) for ethanol production from sugar cane molasses by Zymomonas mobilis using Box-Behnken experimental design and genetic algorithm (GA). An empirical model was developed through response surface methodology to analyze the effects of the process parameters on ethanol production. The data obtained after performing the experiments based on statistical design was utilized for regression analysis and analysis of variance studies. The regression equation obtained after regression analysis was used as a fitness function for the genetic algorithm. The GA optimization technique predicted a maximum ethanol yield of 59.59 g/L at temperature 31 C, pH 5.13, initial TRS concentration 216 g/L and fermentation time 44 h. The maximum experimental ethanol yield obtained after applying GA was 58.4 g/L, which was in close agreement with the predicted value. (orig.)

  19. PROBLEM SETTING AND SOLUTION OF THE RESPONSE CORRECTION OF ARRIVAL AND DEPARTURE AIR TRAFFIC FLOW IN THE VICINITY OF THE FIELD BY MEANS OF THE GENETIC ALGORITHM

    Directory of Open Access Journals (Sweden)

    Georgii N. Lebedev

    2017-01-01

    Full Text Available The improvement in the effectiveness of airfield operation largely depends on the problem solving quality on the interaction boundaries of different technological sections. One of such hotspots is the use of the same runway by inbound and outbound aircraft. At certain intensity of outbound and inbound air traffic flow the conflict of aircraft interests appears, where it may be quite difficult to sort out priorities even for experienced controllers, in consequence of which mistakes in decision-making unavoidably appear.In this work the task of response correction of landing and takeoff time of the aircraft using the same RW, in condition of the conflict of interests “arrival – departure” at the increased operating intensity is formulated. The choice of optimal solution is made taking into account mutual interests without the complete sorting and the evaluation of all solutions.Accordingly, the genetic algorithm, which offers a simple and effective approach to optimal control problem solution by providing flight safety at an acceptably high level, is proposed. The estimation of additional aviation fuel consumption is used as optimal choice evaluation criterion.The advantages of the genetic algorithm application at decision-making in comparison with today’s “team” solution of the conflict “departure – arrival” in the airfield area are shown.

  20. Studies on the genetic control of murine humoral response to immunization with a peptidoglycan-containing fraction extracted from Brucella melitensis.

    Science.gov (United States)

    Cannat, A; Feingold, N; Caffin, J C; Serre, A

    1979-01-01

    A peptidoglycan containing fraction (fraction "5") extracted from Brucella melitensis has been injected in low infra-vaccinating doses into inbred mice. The genetic control of the resulting anti-Brucella humoral response has been studied in the C57BL/6 "good responder" X DBA2 "low responder" model. The results observed in F1, F2 and reciprocal backcrosses show that the "good responder" character, although transmitted as a dominant trait, is under polygenic control and independent of H2 haplotype, Ig allotype, sexual chromosoms or the "d" coat color gene. On the other hand, the phenotypic expression of at least one of the genes involved is sex-limited and influenced by hormonal environmental factors. Moreover the expression in females of one of these sex-dependent genes is associated with the "b" coat color gene. These results are discussed in terms of their possible relevance in spontaneous or vaccinal resistance to experimental brucellosis, of the relative role of the peptidoglycan and lipoprotein moieties in fraction "5" and of the possible importance of sex-dependent and chromosome 4-linked genetic factors for B-cell functions.

  1. Genetic polymorphisms and tissue expression of interleukin-22 associated with risk and therapeutic response of gastric mucosa-associated lymphoid tissue lymphoma

    International Nuclear Information System (INIS)

    Liao, F; Hsu, Y-C; Kuo, S-H; Yang, Y-C; Chen, J-P; Hsu, P-N; Lin, C-W; Chen, L-T; Cheng, A-L; Fann, C S J; Lin, J-T; Wu, M-S

    2014-01-01

    Chronic Helicobacter pylori-stimulated immune reactions determine the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We aimed to explore the genetic predisposition to this lymphoma and its clinical implication. A total of 68 patients and 140 unrelated controls were genotyped for 84 single-nucleotide polymorphisms in genes encoding cytokines, chemokines and related receptors that play important roles in T cell-mediated gastrointestinal immunity. Five genotypes in IL-22, namely CC at rs1179246, CC at rs2227485, AA at rs4913428, AA at rs1026788 and TT at rs7314777, were associated with disease susceptibility. The former four genotypes resided in the same linkage disequilibrium block (r 2 =0.99) that conferred an approximately threefold higher risk. In vitro experiments demonstrated that co-culturing peripheral mononuclear cells or CD4 + T cells with H. pylori stimulated the secretion of interleukin-22 (IL-22), and that IL-22 induced the expression of antimicrobial proteins, RegIIIα and lipocalin-2, in gastric epithelial cells. Furthermore, patients with gastric tissue expressing IL-22 were more likely to respond to H. pylori eradication (14/22 vs 4/19, P<0.006). We conclude that susceptibility of gastric MALT lymphoma is influenced by genetic polymorphisms in IL-22, the product of which is involved in mucosal immunity against H. pylori and associated with tumor response to H. pylori eradication

  2. Genetic risk of progression to type 2 diabetes and response to intensive lifestyle or metformin in prediabetic women with and without a history of gestational diabetes mellitus.

    Science.gov (United States)

    Sullivan, Shannon D; Jablonski, Kathleen A; Florez, Jose C; Dabelea, Dana; Franks, Paul W; Dagogo-Jack, Sam; Kim, Catherine; Knowler, William C; Christophi, Costas A; Ratner, Robert

    2014-04-01

    OBJECTIVE The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births. RESEARCH DESIGN AND METHODS We asked if genetic variability could account for these differences by comparing β-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM. RESULTS β-Cell function was reduced in women with GDM. The GRS was positively associated with a history of GDM; however, the GRS did not predict progression to diabetes or modulate response to intervention. CONCLUSIONS These data suggest that a diabetes-associated GRS is associated with development of GDM and may characterize women at risk for development of diabetes due to β-cell dysfunction.

  3. Genetic Variations of Circulating Adiponectin Levels Modulate Changes in Appetite in Response to Weight-Loss Diets.

    Science.gov (United States)

    Ma, Wenjie; Huang, Tao; Heianza, Yoriko; Wang, Tiange; Sun, Dianjianyi; Tong, Jenny; Williamson, Donald A; Bray, George A; Sacks, Frank M; Qi, Lu

    2017-01-01

    Adiponectin plays key roles in regulating appetite and food intake. To investigate interactions between the genetic risk score (GRS) for adiponectin levels and weight-loss diets varying in macronutrient intake on long-term changes in appetite and adiponectin levels. A GRS was calculated based on 5 adiponectin-associated variants in 692 overweight adults from the 2-year Preventing Overweight Using Novel Dietary Strategies trial. Repeated measurements of plasma adiponectin levels and appetite-related traits, including cravings, fullness, prospective consumption, and hunger. Dietary fat showed nominally significant interactions with the adiponectin GRS on changes in appetite score and prospective consumption from baseline to 6 months (P for interaction = 0.014 and 0.017, respectively) after adjusting for age, sex, ethnicity, baseline body mass index, and baseline respective outcome values. The GRS for lower adiponectin levels was associated with a greater decrease in appetite (P appetite and adiponectin levels to weight-loss diets varying in fat intake. Copyright © 2017 by the Endocrine Society

  4. Genetic and antigenic analysis of foot-and-mouth disease virus serotype O responsible for outbreaks in India during 2013.

    Science.gov (United States)

    Subramaniam, Saravanan; Mohapatra, Jajati K; Das, Biswajit; Sanyal, Aniket; Pattnaik, Bramhadev

    2015-03-01

    In recent times, majority of the foot-and-mouth disease (FMD) outbreaks in India are caused by serotype O Ind2001 lineage. The lineage has diverged into four sub-lineages (Ind2001a, b, c and d). We report here the genetic and antigenic analyses of nine Ind2001d isolates that caused outbreaks during April 2013-March 2014 in India. The length of the genomes of outbreak viruses varied between 8153 and 8181 nucleotides without any insertion or deletion in the coding region. Of the nine isolates analyzed antigenically against the currently used Indian vaccine strain INDR2/1975, eight showed good cross serological match (>0.3) indicating optimal antigenic coverage by the vaccine strain. An unprecedented deletion of 22 nucleotides between position 57 and 78 was observed in the 3' untranslated region of one of the isolates without compromising the virus viability, which imply that partial distortion in SL2 of 3'UTR may not have influence on virus viability at least under in-vitro conditions. Recently the Ind2001 lineage has been reported from several countries including Libya and spread of this lineage across a wide geographical area needs to be monitored carefully to avoid any future pandemic. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Ancestral genetic diversity associated with the rapid spread of stress-tolerant coral symbionts in response to Holocene climate change

    KAUST Repository

    Hume, Benjamin C. C.

    2016-04-05

    Coral communities in the Persian/Arabian Gulf (PAG) withstand unusually high salinity levels and regular summer temperature maxima of up to ∼35 °C that kill conspecifics elsewhere. Due to the recent formation of the PAG and its subsequent shift to a hot climate, these corals have had only <6, 000 y to adapt to these extreme conditions and can therefore inform on how coral reefs may respond to global warming. One key to coral survival in the world\\'s warmest reefs are symbioses with a newly discovered alga, Symbiodinium thermophilum. Currently, it is unknown whether this symbiont originated elsewhere or emerged from unexpectedly fast evolution catalyzed by the extreme environment. Analyzing genetic diversity of symbiotic algae across >5, 000 km of the PAG, the Gulf of Oman, and the Red Sea coastline, we show that S. thermophilum is a member of a highly diverse, ancient group of symbionts cryptically distributed outside the PAG. We argue that the adjustment to temperature extremes by PAG corals was facilitated by the positive selection of preadapted symbionts. Our findings suggest that maintaining the largest possible pool of potentially stress-tolerant genotypes by protecting existing biodiversity is crucial to promote rapid adaptation to present-day climate change, not only for coral reefs, but for ecosystems in general.

  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. Genetics and Molecular Biology of Epstein-Barr Virus-Encoded BART MicroRNA: A Paradigm for Viral Modulation of Host Immune Response Genes and Genome Stability

    Directory of Open Access Journals (Sweden)

    David H. Dreyfus

    2017-01-01

    Full Text Available Epstein-Barr virus, a ubiquitous human herpesvirus, is associated through epidemiologic evidence with common autoimmune syndromes and cancers. However, specific genetic mechanisms of pathogenesis have been difficult to identify. In this review, the author summarizes evidence that recently discovered noncoding RNAs termed microRNA encoded by Epstein-Barr virus BARF (BamHI A right frame termed BART (BamHI A right transcripts are modulators of human immune response genes and genome stability in infected and bystander cells. BART expression is apparently regulated by complex feedback loops with the host immune response regulatory NF-κB transcription factors. EBV-encoded BZLF-1 (ZEBRA protein could also regulate BART since ZEBRA contains a terminal region similar to ankyrin proteins such as IκBα that regulate host NF-κB. BALF-2 (BamHI A left frame transcript, a viral homologue of the immunoglobulin and T cell receptor gene recombinase RAG-1 (recombination-activating gene-1, may also be coregulated with BART since BALF-2 regulatory sequences are located near the BART locus. Viral-encoded microRNA and viral mRNA transferred to bystander cells through vesicles, defective viral particles, or other mechanisms suggest a new paradigm in which bystander or hit-and-run mechanisms enable the virus to transiently or chronically alter human immune response genes as well as the stability of the human genome.

  8. Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes.

    Science.gov (United States)

    Rotroff, Daniel M; Pijut, Sonja S; Marvel, Skylar W; Jack, John R; Havener, Tammy M; Pujol, Aurora; Schluter, Agatha; Graf, Gregory A; Ginsberg, Henry N; Shah, Hetal S; Gao, He; Morieri, Mario-Luca; Doria, Alessandro; Mychaleckyi, Josyf C; McLeod, Howard L; Buse, John B; Wagner, Michael J; Motsinger-Reif, Alison A

    2018-04-01

    Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin-treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed-up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10 -6 ). Rare variant and gene expression changes were assessed using a false discovery rate approach. AKR7A3 and HSD17B13 were associated with lipid changes in white subjects (q < 0.2). Mice fed fenofibrate displayed reductions in Hsd17b13 gene expression (q < 0.1). Associations of variants in SMAD3, IPO11, and HSD17B13, with gene expression changes in mice indicate that transforming growth factor-beta (TGF-β) and NRF2 signaling pathways may influence fenofibrate effects on dyslipidemia in patients with T2D. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  9. Improved phytoaccumulation of cadmium by genetically modified tobacco plants (Nicotiana tabacum L.). Physiological and biochemical response of the transformants to cadmium toxicity

    International Nuclear Information System (INIS)

    Gorinova, N.; Nedkovska, M.; Todorovska, E.; Simova-Stoilova, L.; Stoyanova, Z.; Georgieva, K.; Demirevska-Kepova, K.; Atanassov, A.; Herzig, R.

    2007-01-01

    The response of tobacco plants (Nicotiana tabacum L.)-non-transformed and transformed with a metallothionein gene MThis from Silene vulgaris L. - to increase cadmium supply in the nutrient solution was compared. The transgenic plants accumulated significantly more Cd both in the roots and the leaves. Visual toxicity symptoms and disturbance in water balance were correlated with Cd tissue content. Treatment with 300 μM CdCl 2 resulted in inhibition of photosynthesis and mobilization of the ascorbate-glutathione cycle. Treatment with 500 μM CdCl 2 led to irreversible damage of photosynthesis and oxidative stress. An appearance of a new peroxidase isoform and changes in the leaf polypeptide pattern were observed at the highest Cd concentration. The level of non-protein thiols gradually increased following the Cd treatment both in transgenic and non-transformed plants. - Genetic transformation of Nicotiana tabacum L. by metallothionein gene improved phytoaccumulation of cadmium

  10. Genetic Variation of the Dopamine Transporter (DAT1) Influences the Acute Subjective Responses to Cocaine in Volunteers with Cocaine Use Disorders

    Science.gov (United States)

    Brewer, Alex J.; Nielsen, David A.; Spellicy, Catherine J.; Hamon, Sara C.; Gingrich, Justin; Thompson-Lake, Daisy G. Y.; Nielsen, Ellen M.; Mahoney, James J.; Kosten, Thomas R.; Newton, Thomas F.; De La Garza, Richard

    2015-01-01

    Objective : The aim of this study was to identify gene variants of DAT1 (SLC6A3) that modulate subjective responses to acute cocaine exposure. Methods Non-treatment seeking volunteers with cocaine use disorders (CUDs) received a single bolus infusion of saline and cocaine (40 mg, IV) in randomized order. Subjective effects were assessed with visual analog scales administered before (-15 min) and up to 20 min after infusion. Subjective effects ratings were normalized to baseline and saline infusion values were subtracted. Data was analyzed using repeated measures ANOVA. DNA from subjects was genotyped for the DAT1 intron 8 (rs3836790) and 3’ UTR (rs28363170) variable number of tandem repeats. Results Participants were mostly male (~80%) and African American (~70%). No differences were found among drug use variables between groups for either polymorphism. Carriers of the 9-allele of the DAT1 3’ UTR (9,9 and 9,10) (n = 24) exhibited greater responses to cocaine for “high”, “any drug effect”, “anxious”, and “stimulated” (all p-values < 0.001) compared to individuals homozygous for the 10-allele (n = 33). For the intron 8 polymorphism, individuals homozygous for the 6 allele exhibited greater responses for “anxious” than carriers of the 5 allele (p < 0.001). Individuals possessing the genotype pattern of 10,10 and at least one 5-allele reported lower responses to “good effects”, “bad effects”, “depressed”, and “anxious” (all p-values < 0.01). Conclusions The data presented here support the hypothesis that genetic differences of DAT1 contribute to variation of subjective responses to cocaine among participants with CUDs. PMID:25850966

  11. Possible genetic implications in the response to cardiac resynchronisation therapy in a patient affected by heart failure

    Directory of Open Access Journals (Sweden)

    Natalia Pezzali

    2011-06-01

    Full Text Available This report presents a case of a patient with idiopathic dilated cardiomyopathy and severe left ventricular systolic dysfunction who underwent cardiac resynchronisation therapy (CRT. During the follow-up a progressive increase in left ventricular ejection fraction was observed, as well as clinical improvement. No cardiovascular events occurred during the follow-up, except for appropriate Implantable Cardioverter Defibrillator (ICD bursts for fast ventricular tachycardia. Genotyping for adrenoceptor gene polymorphisms detected that the patient was Glu27Glu homozygous carrier. There’s a large interindividual variability in response to CRT. Despite attempts to identify factors having an impact on this therapy, only QRS duration is accepted according to guidelines. Beta-adrenoceptors polymorphisms, modulating sympathetic drive in heart failure and left ventricular remodelling, may have a role in identifying patients with a better response to CRT, in order to target and individualise the patients’ treatment.

  12. Identification of genetic loci in Lactobacillus plantarum that modulate the immune response of dendritic cells using comparative genome hybridization.

    Directory of Open Access Journals (Sweden)

    Marjolein Meijerink

    Full Text Available BACKGROUND: Probiotics can be used to stimulate or regulate epithelial and immune cells of the intestinal mucosa and generate beneficial mucosal immunomodulatory effects. Beneficial effects of specific strains of probiotics have been established in the treatment and prevention of various intestinal disorders, including allergic diseases and diarrhea. However, the precise molecular mechanisms and the strain-dependent factors involved are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we aimed to identify gene loci in the model probiotic organism Lactobacillus plantarum WCFS1 that modulate the immune response of host dendritic cells. The amounts of IL-10 and IL-12 secreted by dendritic cells (DCs after stimulation with 42 individual L. plantarum strains were measured and correlated with the strain-specific genomic composition using comparative genome hybridisation and the Random Forest algorithm. This in silico "gene-trait matching" approach led to the identification of eight candidate genes in the L. plantarum genome that might modulate the DC cytokine response to L. plantarum. Six of these genes were involved in bacteriocin production or secretion, one encoded a bile salt hydrolase and one encoded a transcription regulator of which the exact function is unknown. Subsequently, gene deletions mutants were constructed in L. plantarum WCFS1 and compared to the wild-type strain in DC stimulation assays. All three bacteriocin mutants as well as the transcription regulator (lp_2991 had the predicted effect on cytokine production confirming their immunomodulatory effect on the DC response to L. plantarum. Transcriptome analysis and qPCR data showed that transcript level of gtcA3, which is predicted to be involved in glycosylation of cell wall teichoic acids, was substantially increased in the lp_2991 deletion mutant (44 and 29 fold respectively. CONCLUSION: Comparative genome hybridization led to the identification of gene loci in L

  13. Cellular analysis of the phenotypic correction of the genetically controlled low immune response to the polyproline determinant by macrophages

    International Nuclear Information System (INIS)

    Falkenberg, F.W.; Sulica, A.; Shearer, G.M.; Mozes, E.; Sela, M.

    1974-01-01

    SJL mice are high responders to the polyproline region of poly(Tyr,Glu)-polyPro-polyLys, (T,G)-Pro-L and of poly(Phe,Glu)-polyPro-polyLys, (Phe,G)-Pro-L, whereas DBA/l mice are the low responders to this moiety. The low responsiveness of DBA/l mice to polyproline could be enhanced by immunization with (T,G)-Pro-L 4 days after stimulation of peritoneal cells by thioglycolate. The same effect was observed when DBA/l mice were immunized with 10 7 syngeneic peritoneal exudate cells (PEC) preincubated in vitro with the immunogen. Similar treatments of SJL mice did not enhance the high response to polyproline, nor did it enhance low responses to other synthetic polypeptides tested. The enhancing effect of PEC on immunocompetent cells was established by transferring graded numbers of spleen cells together with 10 7 PEC into irradiated syngeneic DBA/l recipients. The effective cell type in the PEC was found to be the macrophage as the same results were observed with the adherent-cell population. Furthermore, the effect was not abolished after in vitro irradiation of PEC with 5000 R or by anti-theta treatment. In vivo irradiation of the PEC donors 2 days before the cells were harvested also did not influence the phenotypic correction of the low responsiveness. Transfer experiments in which graded inocula of either marrow cells or thymocytes from DBA/l donors were transferred into syngeneic recipients in the presence of an excess of the complementary cell type together with PEC indicated that the enhancing effect was reflected in the bone-marrow-cell population only

  14. The genetic origins of biosynthesis and light-responsive control of the chemical UV screen of land plants

    International Nuclear Information System (INIS)

    Jorgensen, R.

    1994-01-01

    Most land plants possess the capacity to protect themselves from UV light, and do so by producing pigments that absorb efficiently in the UV-A and UV-B regions of the spectrum while allowing transmission of nearly all photosynthetically useful wavelengths. These UV-absorbing pigments are mainly phenylpropanoids and flavonoids. This chapter summarizes current understanding of the mechanism of UV protection in higher land plants, evaluates the information available from lower land plants and their green-algal relatives, and then considers the possible evolutionary origins of this use of chemical filters for selectively screening UV light from solar radiation. It is proposed that photo control over the biosynthesis of UV-absorbing phenylpropanoids and flavonoids may have evolved in concert with the evolution of the high biosynthetic activity necessary for UV protection. The toxicity of phenylpropanoids and flavonoids has been postulated to have been a barrier to the evolution of an effective chemical UV screen, and that some means for sequestering these compounds and/or for controlling their synthesis probably evolved prior to, or in concert with, the evolution of high rates of biosynthesis. The original photoreceptor and signal transduction system is speculated to have been based on photo isomerization of a phenylpropanoid ester and a pre-existing product feedback mechanism for controlling phenylpropanoid biosynthesis. Understanding the original mechanism for photo control of the chemical UV screen of land plants could be valuable for understanding the adaptability of extant land plants to rising levels of solar UV-B radiation and may suggest genetic strategies for engineering improved UV tolerance in crop plants. (author)

  15. Genetic Mapping

    Science.gov (United States)

    ... greatly advanced genetics research. The improved quality of genetic data has reduced the time required to identify a ... cases, a matter of months or even weeks. Genetic mapping data generated by the HGP's laboratories is freely accessible ...

  16. Response

    Science.gov (United States)

    Higgins, Chris

    2012-01-01

    This article presents the author's response to the reviews of his book, "The Good Life of Teaching: An Ethics of Professional Practice." He begins by highlighting some of the main concerns of his book. He then offers a brief response, doing his best to address the main criticisms of his argument and noting where the four reviewers (Charlene…

  17. Genetic variations in the α(2A)-adrenoreceptor are associated with blood pressure response to the agonist dexmedetomidine.

    Science.gov (United States)

    Kurnik, Daniel; Muszkat, Mordechai; Li, Chun; Sofowora, Gbenga G; Friedman, Eitan A; Scheinin, Mika; Wood, Alastair J J; Stein, C Michael

    2011-04-01

    α(2A)-Adrenoceptors (α(2A)-ARs) have important roles in sympathetic cardiovascular regulation. Variants of ADRA2A affect gene transcription and expression and are associated with insulin release and risk for type 2 diabetes. We examined whether ADRA2A variants are also associated with cardiovascular responses to the selective α(2)-AR-agonist dexmedetomidine. Seventy-three healthy subjects participated in a placebo-controlled, single-blind study. After 3 infusions of placebo, subjects received 3 incremental infusions of dexmedetomidine (cumulative dose, 0.4 μg/kg). Primary outcomes were changes in systolic blood pressure (SBP) and plasma norepinephrine concentrations, measured as difference of the area-under-the-curve during placebo and dexmedetomidine infusions (ΔAUC). We used multiple linear regression analysis to examine the associations between 9 ADRA2A tagging variants and 5 inferred haplotypes and ΔAUC after adjustment for covariates. Homozygous carriers of rs553668 and the corresponding haplotype 4, previously associated with increased α(2A)-AR expression, had a 2.2-fold greater decrease in AUC(SBP) after dexmedetomidine (adjusted P=0.006); similarly, the maximum decrease in SBP was 24.7±8.1 mm Hg compared with 13.6±5.9 mm Hg in carriers of the wild-type allele (P=0.007). Carriers of haplotype 3, previously associated with reduced α(2A)-AR expression, had a 44% smaller decrease in AUC(SBP) (P=0.013). Haplotype information significantly improved the model predicting the decrease in SBP (Pblood pressure and heart rate. Genotypes were not significantly associated with norepinephrine responses. Common ADRA2A variants are associated with the hypotensive response to dexmedetomidine. Effects of specific variants/haplotypes in vivo are compatible with their known effects on gene expression in vitro.

  18. NA{sup +}, K{sup +}-ATPase, histopathological, and genetic responses of Corbicula fluminea to sediment-associated copper

    Energy Technology Data Exchange (ETDEWEB)

    Brown, S. [Univ. of Mississippi, Oxford, MS (United States)

    1995-12-31

    Time-dependent responses to sediment-associated copper were studies at hierarchical levels of biological organization along an extreme concentration gradient (40 to 40,000 mg/kg total Cu). Laboratory and in situ estimates of molecular to tissue-level responses (Na/K-ATPase activity, DNA content, histopathology) were monitored in Corbicula fluminea (Asiatic clam), and compared with laboratory and field based survival of Corbicula and Elimia teres (an indigenous Gastropoda). Mollusc survival was, in turn, compared with effects on macrobenthic community composition along the stream/[Cu] gradient. Relationships between selected sediment characteristics and the bioavailability and toxicity of sediment associated copper were also investigated. Sediment-associated copper depressed Na/K-ATPase activity and led to histopathological damage of renal and gill epithelia (vacuolization, degeneration), indicating that impaired ion regulation was an important mechanism of toxicity. Concurrent reductions in DNA content were believed to be secondary effects due to cell death, not an indication of genotoxicity. Sublethal responses were significantly correlated with survival in both species; however, while survival in situ was indicative of differences in community structure, laboratory-based survival was not. Copper levels in tissues were indicative of exposure, but were not significantly correlated with adverse effects. Copper levels in sediments, interstitial water, and overlying water varied independently of sediment characteristics except pH. Cu/AVS ratios were predictive of Corbicula and Elimia survival, but were not significantly related to differences in community structure. Instead, macrobenthic community structure was influenced by other sediment factors (grain size, Eh, pH).

  19. Genetic Variations in Pattern Recognition Receptor Loci Are Associated with Anti-TNF Response in Patients with Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Sode, Jacob; Vogel, Ulla; Bank, Steffen

    2015-01-01

    : In a retrospective case-case study, we assessed 23 functional single nucleotide polymorphisms (SNPs) in 15 genes. We included 538 anti-TNF naïve Danish RA patients from the nationwide DANBIO database. Multivariable logistic regression analyses were performed to detect associations (p-value... and European League Against Rheumatism (EULAR) treatment responses. False Discovery Rate corrections for multiple testing (q-value) and stratified analyses were performed to investigate association with individual therapies and IgM-rheumatoid factor (RF) status. RESULTS: Six of twenty successfully genotyped...

  20. Optimisation of warpage on plastic injection moulding part using response surface methodology (RSM) and genetic algorithm method (GA)

    Science.gov (United States)

    Miza, A. T. N. A.; Shayfull, Z.; Nasir, S. M.; Fathullah, M.; Hazwan, M. H. M.

    2017-09-01

    In this study, Computer Aided Engineering was used for injection moulding simulation. The method of Design of experiment (DOE) was utilize according to the Latin Square orthogonal array. The relationship between the injection moulding parameters and warpage were identify based on the experimental data that used. Response Surface Methodology (RSM) was used as to validate the model accuracy. Then, the RSM and GA method were combine as to examine the optimum injection moulding process parameter. Therefore the optimisation of injection moulding is largely improve and the result shown an increasing accuracy and also reliability. The propose method by combining RSM and GA method also contribute in minimising the warpage from occur.

  1. Genetic Variation in the TLR5 Locus Is Associated with Anti-TNF Response Among Rheumatoid Arthritis Patients

    DEFF Research Database (Denmark)

    Sode, Jacob

    2014-01-01

    and interferon-gamma pathways were assessed in 538 anti-TNF naive Danish RA patients. Prospectively collected clinical data including functional status (HAQ), patient global score, smoking status, tender and swollen joint counts, treatments, rheumatoid factor (RF) status and C-reative protein (CRP) were obtained...... for seropositive RA in CARD8 (rs2043211), IL18 (rs187238) and TLR1 (rs4833095) (data not shown) but due to low power these results are preliminary. Conclusion: Our results confirm association between a TLR5 locus and EULAR response to anti-TNF treatment. Previous studies suggest that this polymorphism...

  2. Extracellular vesicle-mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation.

    Directory of Open Access Journals (Sweden)

    Kirsten Ridder

    2014-06-01

    Full Text Available Mechanisms behind how the immune system signals to the brain in response to systemic inflammation are not fully understood. Transgenic mice expressing Cre recombinase specifically in the hematopoietic lineage in a Cre reporter background display recombination and marker gene expression in Purkinje neurons. Here we show that reportergene expression in neurons is caused by intercellular transfer of functional Cre recombinase messenger RNA from immune cells into neurons in the absence of cell fusion. In vitro purified secreted extracellular vesicles (EVs from blood cells contain Cre mRNA, which induces recombination in neurons when injected into the brain. Although Cre-mediated recombination events in the brain occur very rarely in healthy animals, their number increases considerably in different injury models, particularly under inflammatory conditions, and extend beyond Purkinje neurons to other neuronal populations in cortex, hippocampus, and substantia nigra. Recombined Purkinje neurons differ in their miRNA profile from their nonrecombined counterparts, indicating physiological significance. These observations reveal the existence of a previously unrecognized mechanism to communicate RNA-based signals between the hematopoietic system and various organs, including the brain, in response to inflammation.

  3. Small molecule inhibitors uncover synthetic genetic interactions of human flap endonuclease 1 (FEN1 with DNA damage response genes.

    Directory of Open Access Journals (Sweden)

    Thomas A Ward

    Full Text Available Flap endonuclease 1 (FEN1 is a structure selective endonuclease required for proficient DNA replication and the repair of DNA damage. Cellularly active inhibitors of this enzyme have previously been shown to induce a DNA damage response and, ultimately, cell death. High-throughput screens of human cancer cell-lines identify colorectal and gastric cell-lines with microsatellite instability (MSI as enriched for cellular sensitivity to N-hydroxyurea series inhibitors of FEN1, but not the PARP inhibitor olaparib or other inhibitors of the DNA damage response. This sensitivity is due to a synthetic lethal interaction between FEN1 and MRE11A, which is often mutated in MSI cancers through instabilities at a poly(T microsatellite repeat. Disruption of ATM is similarly synthetic lethal with FEN1 inhibition, suggesting that disruption of FEN1 function leads to the accumulation of DNA double-strand breaks. These are likely a result of the accumulation of aberrant replication forks, that accumulate as a consequence of a failure in Okazaki fragment maturation, as inhibition of FEN1 is toxic in cells disrupted for the Fanconi anemia pathway and post-replication repair. Furthermore, RAD51 foci accumulate as a consequence of FEN1 inhibition and the toxicity of FEN1 inhibitors increases in cells disrupted for the homologous recombination pathway, suggesting a role for homologous recombination in the resolution of damage induced by FEN1 inhibition. Finally, FEN1 appears to be required for the repair of damage induced by olaparib and cisplatin within the Fanconi anemia pathway, and may play a role in the repair of damage associated with its own disruption.

  4. Capacity of lung stroma to educate dendritic cells inhibiting mycobacteria-specific T-cell response depends upon genetic susceptibility to tuberculosis.

    Science.gov (United States)

    Kapina, Marina A; Rubakova, Elvira I; Majorov, Konstantin B; Logunova, Nadezhda N; Apt, Alexander S

    2013-01-01

    The balance between activation and inhibition of local immune responses in affected tissues during prolonged chronic infections is important for host protection. There is ample evidence that regulatory, tolerogenic dendritic cells (DC) are developed and present in tissues and inhibit overwhelming inflammatory reactions. Also, it was firmly established that stromal microenvironment of many organs is able to induce development of immature regulatory DC (DCreg), an essential element of a general immune regulatory network. However, direct experimental data demonstrating inhibition of immune responses by stroma-instructed immature DCreg in infectious models are scarce, and virtually nothing is known about functioning of this axis of immunity during tuberculosis (TB) infection. In this study, we demonstrate that lung stromal cells are capable of supporting the development in culture of immature CD11b(+)CD11c(low)CD103(-) DCreg from lineage-negative (lin(-)) bone marrow precursors. DCreg developed on lung stroma isolated from mice of genetically TB-hyper-susceptible I/St and relatively resistant B6 inbred strains inhibited proliferative response of mycobacteria-specific CD4(+) T-cell lines a dose-dependent manner. Importantly, the inhibitory activity of B6 DCreg was substantially higher than that of I/St Dcreg. Moreover, when the donors of stromal cells were chronically infected with virulent mycobacteria, the capacity to instruct inhibitory DCreg was retained in B6, but further diminished in I/St stromal cells. DCreg-provided suppression was mediated by a few soluble mediators, including PGE2, NO and IL-10. The content of CD4(+)Foxp3(+) Treg cells in the mediastinal, lung-draining lymph nodes at the advanced stages of chronic infection did not change in I/St, but increased 2-fold in B6 mice, and lung pathology was much more pronounced in the former mice. Taken together, these data provide genetic evidence that the capacity to maintain populations of regulatory cells

  5. Capacity of lung stroma to educate dendritic cells inhibiting mycobacteria-specific T-cell response depends upon genetic susceptibility to tuberculosis.

    Directory of Open Access Journals (Sweden)

    Marina A Kapina

    Full Text Available The balance between activation and inhibition of local immune responses in affected tissues during prolonged chronic infections is important for host protection. There is ample evidence that regulatory, tolerogenic dendritic cells (DC are developed and present in tissues and inhibit overwhelming inflammatory reactions. Also, it was firmly established that stromal microenvironment of many organs is able to induce development of immature regulatory DC (DCreg, an essential element of a general immune regulatory network. However, direct experimental data demonstrating inhibition of immune responses by stroma-instructed immature DCreg in infectious models are scarce, and virtually nothing is known about functioning of this axis of immunity during tuberculosis (TB infection. In this study, we demonstrate that lung stromal cells are capable of supporting the development in culture of immature CD11b(+CD11c(lowCD103(- DCreg from lineage-negative (lin(- bone marrow precursors. DCreg developed on lung stroma isolated from mice of genetically TB-hyper-susceptible I/St and relatively resistant B6 inbred strains inhibited proliferative response of mycobacteria-specific CD4(+ T-cell lines a dose-dependent manner. Importantly, the inhibitory activity of B6 DCreg was substantially higher than that of I/St Dcreg. Moreover, when the donors of stromal cells were chronically infected with virulent mycobacteria, the capacity to instruct inhibitory DCreg was retained in B6, but further diminished in I/St stromal cells. DCreg-provided suppression was mediated by a few soluble mediators, including PGE2, NO and IL-10. The content of CD4(+Foxp3(+ Treg cells in the mediastinal, lung-draining lymph nodes at the advanced stages of chronic infection did not change in I/St, but increased 2-fold in B6 mice, and lung pathology was much more pronounced in the former mice. Taken together, these data provide genetic evidence that the capacity to maintain populations of regulatory

  6. Genetic characterization of H1N2 swine influenza virus isolated in China and its pathogenesis and inflammatory responses in mice.

    Science.gov (United States)

    Zhang, Yan; Wang, Nan; Cao, Jiyue; Chen, Huanchun; Jin, Meilin; Zhou, Hongbo

    2013-09-01

    In 2009, two H1N2 influenza viruses were isolated from trachea swabs of pigs in Hubei in China. We compared these sequences with the other 18 complete genome sequences of swine H1N2 isolates from China during 2004 to 2010 and undertook extensive analysis of their evolutionary patterns. Six different genotypes - two reassortants between triple reassortant (TR) H3N2 and classical swine (CS) H1N1 virus, three reassortants between TR H1N2, Eurasian avian-like H1N1 swine virus and H9N2 swine virus, and one reassortant between H1N1, H3N2 human virus and CS H1N1 virus - were observed in these 20 swine H1N2 isolates. The TR H1N2 swine virus is the predominant genotype, and the two Hubei H1N2 isolates were located in this cluster. We also used a mouse model to examine the pathogenesis and inflammatory responses of the two isolates. The isolates replicated efficiently in the lung, and exhibited a strong inflammatory response, serious pathological changes and mortality in infected mice. Given the role that swine can play as putative "genetic mixing vessels" and the observed transmission of TR H1N2 in ferrets, H1N2 influenza surveillance in pigs should be increased to minimize the potential threat to public health.

  7. Genetic Markers of Insulin Sensitivity and Insulin Secretion Are Associated With Spontaneous Postnatal Growth and Response to Growth Hormone Treatment in Short SGA Children

    DEFF Research Database (Denmark)

    Jensen, Rikke Beck; Thankamony, Ajay; Day, Felix

    2015-01-01

    with spontaneous postnatal weight gain (regression coefficient [B]: 0.12 SD scores per allele; 95% confidence interval [CI], 0.01-0.23; P = .03) and also in response to GH therapy with first-year height velocity (B: 0.18 cm/y per allele; 95% CI, 0.02-0.35; P = .03) and change in IGF-1 (B: 0.17 SD scores per allele......PURPOSE: The wide heterogeneity in the early growth and metabolism of children born small for gestational age (SGA), both before and during GH therapy, may reflect common genetic variations related to insulin secretion or sensitivity. METHOD: Combined multiallele single nucleotide polymorphism......; 95% CI, 0.00-0.32; P = .03). The association with first-year height velocity was independent of reported predictors of response to GH therapy (adjusted P = .04). The insulin secretion allele score (GS-InSec) was positively associated with spontaneous postnatal height gain (B: 0.15; 95% CI, 0...

  8. Assessing Basal and Acute Autophagic Responses in the Adult Drosophila Nervous System: The Impact of Gender, Genetics and Diet on Endogenous Pathway Profiles.

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    Eric P Ratliff

    Full Text Available The autophagy pathway is critical for the long-term homeostasis of cells and adult organisms and is often activated during periods of stress. Reduced pathway efficacy plays a central role in several progressive neurological disorders that are associated with the accumulation of cytotoxic peptides and protein aggregates. Previous studies have shown that genetic and transgenic alterations to the autophagy pathway impacts longevity and neural aggregate profiles of adult Drosophila. In this study, we have identified methods to measure the acute in vivo induction of the autophagy pathway in the adult fly CNS. Our findings indicate that the genotype, age, and gender of adult flies can influence pathway responses. Further, we demonstrate that middle-aged male flies exposed to intermittent fasting (IF had improved neuronal autophagic profiles. IF-treated flies also had lower neural aggregate profiles, maintained more youthful behaviors and longer lifespans, when compared to ad libitum controls. In summary, we present methodology to detect dynamic in vivo changes that occur to the autophagic profiles in the adult Drosophila CNS and that a novel IF-treatment protocol improves pathway response in the aging nervous system.

  9. A cascade of iron-containing proteins governs the genetic iron starvation response to promote iron uptake and inhibit iron storage in fission yeast.

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    Javier Encinar del Dedo

    2015-03-01

    Full Text Available Iron is an essential cofactor, but it is also toxic at high levels. In Schizosaccharomyces pombe, the sensor glutaredoxin Grx4 guides the activity of the repressors Php4 and Fep1 to mediate a complex transcriptional response to iron deprivation: activation of Php4 and inactivation of Fep1 leads to inhibition of iron usage/storage, and to promotion of iron import, respectively. However, the molecular events ruling the activity of this double-branched pathway remained elusive. We show here that Grx4 incorporates a glutathione-containing iron-sulfur cluster, alone or forming a heterodimer with the BolA-like protein Fra2. Our genetic study demonstrates that Grx4-Fra2, but not Fep1 nor Php4, participates not only in iron starvation signaling but also in iron-related aerobic metabolism. Iron-containing Grx4 binds and inactivates the Php4 repressor; upon iron deprivation, the cluster in Grx4 is probably disassembled, the proteins dissociate, and Php4 accumulates at the nucleus and represses iron consumption genes. Fep1 is also an iron-containing protein, and the tightly bound iron is required for transcriptional repression. Our data suggest that the cluster-containing Grx4-Fra2 heterodimer constitutively binds to Fep1, and upon iron deprivation the disassembly of the iron cluster between Grx4 and Fra2 promotes reverse metal transfer from Fep1 to Grx4-Fra2, and de-repression of iron-import genes. Our genetic and biochemical study demonstrates that the glutaredoxin Grx4 independently governs the Php4 and Fep1 repressors through metal transfer. Whereas iron loss from Grx4 seems to be sufficient to release Php4 and allow its nuclear accumulation, total or partial disassembly of the Grx4-Fra2 cluster actively participates in iron-containing Fep1 activation by sequestering its iron and decreasing its interaction with promoters.

  10. Early systemic bacterial dissemination and a rapid innate immune response characterize genetic resistance to plague of SEG mice.

    Science.gov (United States)

    Demeure, Christian E; Blanchet, Charlène; Fitting, Catherine; Fayolle, Corinne; Khun, Huot; Szatanik, Marek; Milon, Geneviève; Panthier, Jean-Jacques; Jaubert, Jean; Montagutelli, Xavier; Huerre, Michel; Cavaillon, Jean-Marc; Carniel, Elisabeth

    2012-01-01

    Although laboratory mice are usually highly susceptible to Yersinia pestis, we recently identified a mouse strain (SEG) that exhibited an exceptional capacity to resist bubonic plague and used it to identify immune mechanisms associated with resistance. The kinetics of infection, circulating blood cells, granulopoiesis, lesions, and cellular populations in the spleen, and cytokine production in various tissues were compared in SEG and susceptible C57BL/6J mice after subcutaneous infection with the virulent Y. pestis CO92. Bacterial invasion occurred early (day 2) but was transient in SEG/Pas mice, whereas in C57BL/6J mice it was delayed but continuous until death. The bacterial load in all organs significantly correlated with the production of 5 cytokines (granulocyte colony-stimulating factor, keratinocyte-derived chemokine (KC), macrophage cationic peptide-1 (MCP-1), interleukin 1α, and interleukin 6) involved in monocyte and neutrophil recruitment. Indeed, higher proportions of these 2 cell types in blood and massive recruitment of F4/80(+)CD11b(-) macrophages in the spleen were observed in SEG/Pas mice at an early time point (day 2). Later times after infection (day 4) were characterized in C57BL/6J mice by destructive lesions of the spleen and impaired granulopoiesis. A fast and efficient Y. pestis dissemination in SEG mice may be critical for the triggering of an early and effective innate immune response necessary for surviving plague.

  11. Genome-wide association study of genetic variants in LPS-stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α cytokine response in a Danish Cohort

    DEFF Research Database (Denmark)

    Larsen, Margit Hørup; Albrechtsen, Anders; Thørner, Lise Wegner

    2013-01-01

    Cytokine response plays a vital role in various human lipopolysaccharide (LPS) infectious and inflammatory diseases. This study aimed to find genetic variants that might affect the levels of LPS-induced interleukin (IL)-6, IL-8, IL-10, IL-1ra and tumor necrosis factor (TNF)-α cytokine production....

  12. cAMP response element binding protein (CREB activates transcription via two distinct genetic elements of the human glucose-6-phosphatase gene

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    Stefano Luisa

    2005-01-01

    Full Text Available Abstract Background The enzyme glucose-6-phosphatase catalyzes the dephosphorylation of glucose-6-phosphatase to glucose, the final step in the gluconeogenic and glycogenolytic pathways. Expression of the glucose-6-phosphatase gene is induced by glucocorticoids and elevated levels of intracellular cAMP. The effect of cAMP in regulating glucose-6-phosphatase gene transcription was corroborated by the identification of two genetic motifs CRE1 and CRE2 in the human and murine glucose-6-phosphatase gene promoter that resemble cAMP response elements (CRE. Results The cAMP response element is a point of convergence for many extracellular and intracellular signals, including cAMP, calcium, and neurotrophins. The major CRE binding protein CREB, a member of the basic region leucine zipper (bZIP family of transcription factors, requires phosphorylation to become a biologically active transcriptional activator. Since unphosphorylated CREB is transcriptionally silent simple overexpression studies cannot be performed to test the biological role of CRE-like sequences of the glucose-6-phosphatase gene. The use of a constitutively active CREB2/CREB fusion protein allowed us to uncouple the investigation of target genes of CREB from the variety of signaling pathways that lead to an activation of CREB. Here, we show that this constitutively active CREB2/CREB fusion protein strikingly enhanced reporter gene transcription mediated by either CRE1 or CRE2 derived from the glucose-6-phosphatase gene. Likewise, reporter gene transcription was enhanced following expression of the catalytic subunit of cAMP-dependent protein kinase (PKA in the nucleus of transfected cells. In contrast, activating transcription factor 2 (ATF2, known to compete with CREB for binding to the canonical CRE sequence 5'-TGACGTCA-3', did not transactivate reporter genes containing CRE1, CRE2, or both CREs derived from the glucose-6-phosphatase gene. Conclusions Using a constitutively active CREB2

  13. Association between genetic variants of the ADD1 and GNB3 genes and blood pressure response to the cold pressor test in a Chinese Han population: the GenSalt Study.

    Science.gov (United States)

    Wang, Laiyuan; Chen, Shufeng; Zhao, Qi; Hixson, James E; Rao, Dabeeru C; Jaquish, Cashell E; Huang, Jianfeng; Lu, Xiangfeng; Chen, Jichun; Cao, Jie; Li, Jianxin; Li, Hongfan; He, Jiang; Liu, De-Pei; Gu, Dongfeng

    2012-08-01

    Genetic factors influence blood pressure (BP) response to the cold pressor test (CPT), which is a phenotype related to hypertension risk. We examined the association between variants of the α-adducin (ADD1) and guanine nucleotide binding protein (G protein) β-polypeptide 3 (GNB3) genes and BP response to the CPT. A total of 1998 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity completed the CPT. The area under the curve (AUC) above the baseline BP during the CPT was used to measure the BP response. Twelve single-nucleotide polymorphisms (SNPs) of the ADD1 and GNB3 genes were selected and genotyped. Both single-marker and haplotype association analyses were conducted using linear mixed models. The rs17833172 and rs3775067 SNPs of the ADD1 gene and the rs4963516 SNP of the GNB3 gene were significantly associated with the BP response to CPT, even after adjusting for multiple testing. For the ADD1 gene, the AA genotype of SNP rs17833172 was associated with lower systolic BP (SBP) reactivity (PAUC (P=0.003). Haplotype analysis indicated that the CCGC haplotype of ADD1 constructed by rs1263359, rs3775067, rs4961 and rs4963 was significantly associated with the BP response to CPT. These data suggest that genetic variants of the ADD1 and GNB3 genes may have important roles in BP response to the CPT. Future studies aimed at replicating these novel findings are warranted.

  14. Genetics of nonsyndromic obesity.

    Science.gov (United States)

    Lee, Yung Seng

    2013-12-01

    Common obesity is widely regarded as a complex, multifactorial trait influenced by the 'obesogenic' environment, sedentary behavior, and genetic susceptibility contributed by common and rare genetic variants. This review describes the recent advances in understanding the role of genetics in obesity. New susceptibility loci and genetic variants are being uncovered, but the collective effect is relatively small and could not explain most of the BMI heritability. Yet-to-be identified common and rare variants, epistasis, and heritable epigenetic changes may account for part of the 'missing heritability'. Evidence is emerging about the role of epigenetics in determining obesity susceptibility, mediating developmental plasticity, which confers obesity risk from early life experiences. Genetic prediction scores derived from selected genetic variants, and also differential DNA methylation levels and methylation scores, have been shown to correlate with measures of obesity and response to weight loss intervention. Genetic variants, which confer susceptibility to obesity-related morbidities like nonalcoholic fatty liver disease, were also discovered recently. We can expect discovery of more rare genetic variants with the advent of whole exome and genome sequencing, and also greater understanding of epigenetic mechanisms by which environment influences genetic expression and which mediate the gene-environment interaction.

  15. Genetic Variation for Thermotolerance in Lettuce Seed Germination Is Associated with Temperature-Sensitive Regulation of ETHYLENE RESPONSE FACTOR1 (ERF1)1[OPEN

    Science.gov (United States)

    O’Brien, Laurel K.; Truco, Maria Jose; Huo, Heqiang; Sideman, Rebecca; Hayes, Ryan; Michelmore, Richard W.

    2016-01-01

    Seeds of most lettuce (Lactuca sativa) cultivars are susceptible to thermoinhibition, or failure to germinate at temperatures above approximately 28°C, creating problems for crop establishment in the field. Identifying genes controlling thermoinhibition would enable the development of cultivars lacking this trait and, therefore, being less sensitive to high temperatures during planting. Seeds of a primitive accession (PI251246) of lettuce exhibited high-temperature germination capacity up to 33°C. Screening a recombinant inbred line population developed from PI215246 and cv Salinas identified a major quantitative trait locus (Htg9.1) from PI251246 associated with the high-temperature germination phenotype. Further genetic analyses discovered a tight linkage of the Htg9.1 phenotype with a specific DNA marker (NM4182) located on a single genomic sequence scaffold. Expression analyses of the 44 genes encoded in this genomic region revealed that only a homolog of Arabidopsis (Arabidopsis thaliana) ETHYLENE RESPONSE FACTOR1 (termed LsERF1) was differentially expressed between PI251246 and cv Salinas seeds imbibed at high temperature (30°C). LsERF1 belongs to a large family of transcription factors associated with the ethylene-signaling pathway. Physiological assays of ethylene synthesis, response, and action in parental and near-isogenic Htg9.1 genotypes strongly implicate LsERF1 as the gene responsible for the Htg9.1 phenotype, consistent with the established role for ethylene in germination thermotolerance of Compositae seeds. Expression analyses of genes associated with the abscisic acid and gibberellin biosynthetic pathways and results of biosynthetic inhibitor and hormone response experiments also support the hypothesis that differential regulation of LsERF1 expression in PI251246 seeds elevates their upper temperature limit for germination through interactions among pathways regulated by these hormones. Our results support a model in which LsERF1 acts through

  16. Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients

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    Cristiana C. Garcia

    2018-05-01

    Full Text Available Influenza A virus (IAV infection causes severe pulmonary disease characterized by intense leukocyte infiltration. Phosphoinositide-3 kinases (PI3Ks are central signaling enzymes, involved in cell growth, survival, and migration. Class IB PI3K or phosphatidyl inositol 3 kinase-gamma (PI3Kγ, mainly expressed by leukocytes, is involved in cell migration during inflammation. Here, we investigated the contribution of PI3Kγ for the inflammatory and antiviral responses to IAV. PI3Kγ knockout (KO mice were highly susceptible to lethality following infection with influenza A/WSN/33 H1N1. In the early time points of infection, infiltration of neutrophils was higher than WT mice whereas type-I and type-III IFN expression and p38 activation were reduced in PI3Kγ KO mice resulting in higher viral loads when compared with WT mice. Blockade of p38 in WT macrophages infected with IAV reduced levels of interferon-stimulated gene 15 protein to those induced in PI3Kγ KO macrophages, suggesting that p38 is downstream of antiviral responses mediated by PI3Kγ. PI3Kγ KO-derived fibroblasts or macrophages showed reduced type-I IFN transcription and altered pro-inflammatory cytokines suggesting a cell autonomous imbalance between inflammatory and antiviral responses. Seven days after IAV infection, there were reduced infiltration of natural killer cells and CD8+ T lymphocytes, increased concentration of inflammatory cytokines in bronchoalveolar fluid, reduced numbers of resolving macrophages, and IL-10 levels in PI3Kγ KO. This imbalanced environment in PI3Kγ KO-infected mice culminated in enhanced lung neutrophil infiltration, reactive oxygen species release, and lung damage that together with the increased viral loads, contributed to higher mortality in PI3Kγ KO mice compared with WT mice. In humans, we tested the genetic association of disease severity in influenza A/H1N1pdm09-infected patients with three potentially functional PIK3CG single

  17. Genetic variation in STAT4 predicts response to interferon-α therapy for hepatitis B e antigen-positive chronic hepatitis B.

    Science.gov (United States)

    Jiang, De-Ke; Wu, Xiaopan; Qian, Ji; Ma, Xiao-Pin; Yang, Jingmin; Li, Zhuo; Wang, Runhua; Sun, Li; Liu, Fang; Zhang, Pengyin; Zhu, Xilin; Wu, Jia; Chen, Kangmei; Conran, Carly; Zheng, S Lilly; Lu, Daru; Yu, Long; Liu, Ying; Xu, Jianfeng

    2016-04-01

    Interferon (IFN)-α is a first-line therapy for chronic hepatitis B (CHB) patients but only initiates a response in a minority of patients. A genetic variant, rs7574865 in STAT4, was recently reported to be associated with risk of developing CHB and hepatitis B virus-related hepatocellular carcinoma. We aimed to determine whether this variant is associated with the response to IFNα treatment for hepatitis B e antigen (HBeAg)-positive CHB patients. We studied 466 HBeAg-positive CHB patients who received either IFNα-2b (n = 224) or pegylated IFNα-2a (n = 242) therapy for 48 weeks and were followed for an additional 24 weeks. The rate of sustained virologic response (SVR), defined as HBeAg seroconversion along with hepatitis B virus DNA level rs7574865. After 48 weeks of treatment and 24 weeks off treatment, the SVR rates in the IFNα-2b and pegylated IFNα-2a therapy groups were 30.4% and 28.9%, respectively. Compared to the rs7574865 GT/TT genotype, the GG genotype (a risk factor of CHB and hepatitis B virus-related hepatocellular carcinoma) was significantly associated with a reduced SVR rate in both patients who received IFNα-2b therapy (21.1% versus 37.2%, P = 0.01) and those who received pegylated IFNα-2a therapy (18.0% versus 41.2%, P = 9.74 × 10(-5) ). In joint analysis of the 466 patients, the GG genotype was associated with an approximately half SVR rate compared to the GT/TT genotype (19.3% versus 39.1%, P = 4.15 × 10(-6) ). A multivariate logistic regression model including rs7574865 and clinical variables showed that rs7574865 was the most significant factor for the prediction of SVR. STAT4 rs7574865 is a reliable predictor of response to IFNα therapy for HBeAg-positive CHB patients and may be used for optimizing the treatment of CHB. © 2015 by the American Association for the Study of Liver Diseases.

  18. Concholepas concholepas Ferritin H-like subunit (CcFer): Molecular characterization and single nucleotide polymorphism associated to innate immune response.

    Science.gov (United States)

    Chávez-Mardones, Jacqueline; Valenzuela-Muñoz, Valentina; Núñez-Acuña, Gustavo; Maldonado-Aguayo, Waleska; Gallardo-Escárate, Cristian

    2013-09-01

    Ferritin has been identified as the principal protein of iron storage and iron detoxification, playing a pivotal role for the cellular homeostasis in living organisms. However, recent studies in marine invertebrates have suggested its association with innate immune system. In the present study, one Ferritin subunit was identified from the gastropod Concholepas concholepas (CcFer), which was fully characterized by Rapid Amplification of cDNA Ends technique. Simultaneously, a challenge test was performed to evaluate the immune response against Vibrio anguillarum. The full length of cDNA Ccfer was 1030 bp, containing 513 bp of open reading frame that encodes to 170 amino acid peptide, which was similar to the Ferritin H subunit described in vertebrates. Untranslated Regions (UTRs) were identified with a 5'UTR of 244 bp that contains iron responsive element (IRE), and a 3'UTR of 273 bp. The predicted molecular mass of deduced amino acid of CcFer was 19.66 kDa and isoelectric point of 4.92. Gene transcription analysis revealed that CcFer increases against infections with V. anguillarum, showing a peak expression at 6 h post-infection. Moreover, a single nucleotide polymorphism was detected at -64 downstream 5'UTR sequence (SNP-64). Quantitative real time analysis showed that homozygous mutant allele (TT) was significantly associated with higher expression levels of the challenged group compared to wild (CC) and heterozygous (CT) variants. Our findings suggest that CcFer is associated to innate immune response in C. concholepas and that the presence of SNPs may involve differential transcriptional expression of CcFer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Trace determination of safranin O dye using ultrasound assisted dispersive solid-phase micro extraction: Artificial neural network-genetic algorithm and response surface methodology.

    Science.gov (United States)

    Dil, Ebrahim Alipanahpour; Ghaedi, Mehrorang; Asfaram, Arash; Mehrabi, Fatemeh; Bazrafshan, Ali Akbar; Ghaedi, Abdol Mohammad

    2016-11-01

    In this study, ultrasound assisted dispersive solid-phase micro extraction combined with spectrophotometry (USA-DSPME-UV) method based on activated carbon modified with Fe2O3 nanoparticles (Fe2O3-NPs-AC) was developed for pre-concentration and determination of safranin O (SO). It is known that the efficiency of USA-DSPME-UV method may be affected by pH, amount of adsorbent, ultrasound time and eluent volume and the extent and magnitude of their contribution on response (in term of main and interaction part) was studied by using central composite design (CCD) and artificial neural network-genetic algorithms (ANN-GA). Accordingly by adjustment of experimental conditions suggested by ANN-GA at pH 6.5, 1.1mg of adsorbent, 10min ultrasound and 150μL of eluent volume led to achievement of best operation performance like low LOD (6.3ngmL(-1)) and LOQ (17.5ngmL(-1)) in the range of 25-3500ngmL(-1). In following stage, the SO content in real water and wastewater samples with recoveries between 93.27-99.41% with RSD lower than 3% was successfully determined. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. The binary response of the GAL/MEL genetic switch of Saccharomyces cerevisiae is critically dependent on Gal80p-Gal4p interaction.

    Science.gov (United States)

    Das Adhikari, Akshay Kumar; Bhat, Paike Jayadeva

    2016-09-01

    Studies on the Saccharomyces cerevisiae GAL/MEL genetic switch have revealed that its bistability is dependent on ultrasensitivity that can be altered or abolished by disabling different combinations of nested feedback loops. In contrast, we have previously demonstrated that weakening of the interaction between Gal80p and Gal4p alone is sufficient to abolish the ultrasensitivity (Das Adhikari et al. 2014). Here, we demonstrate that altering the epistatic interaction between Gal80p and Gal4p also abolishes the bistability, and the switch response to galactose becomes graded instead of binary. However, the GAL/MEL switch of wild-type and epistatically altered strains responded in a graded fashion to melibiose. The properties of the epistatically altered strain resemble Kluyveromyces lactis, which separated from the Saccharomyces lineage 100 mya before whole-genome duplication (WGD). Based on the results reported here, we propose that epistatic interactions played a crucial role in the evolution of the fine regulation of S. cerevisiae GAL/MEL switch following WGD. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Medium optimization for pyrroloquinoline quinone (PQQ) production by Methylobacillus sp. zju323 using response surface methodology and artificial neural network-genetic algorithm.

    Science.gov (United States)

    Wei, Peilian; Si, Zhenjun; Lu, Yao; Yu, Qingfei; Huang, Lei; Xu, Zhinan

    2017-08-09

    Methylobacillus sp. zju323 was adopted to improve the biosynthesis of pyrroloquinoline quinone (PQQ) by systematic optimization of the fermentation medium. The Plackett-Burman design was implemented to screen for the key medium components for the PQQ production. CoCl 2  · 6H 2 O, ρ-amino benzoic acid, and MgSO 4  · 7H 2 O were found capable of enhancing the PQQ production most significantly. A five-level three-factor central composite design was used to investigate the direct and interactive effects of these variables. Both response surface methodology (RSM) and artificial neural network-genetic algorithm (ANN-GA) were used to predict the PQQ production and to optimize the medium composition. The results showed that the medium optimized by ANN-GA was better than that by RSM in maximizing PQQ production and the experimental PQQ concentration in the ANN-GA-optimized medium was improved by 44.3% compared with that in the unoptimized medium. Further study showed that this ANN-GA-optimized medium was also effective in improving PQQ production by fed-batch mode, reaching the highest PQQ accumulation of 232.0 mg/L, which was about 47.6% increase relative to that in the original medium. The present work provided an optimized medium and developed a fed-batch strategy which might be potentially applicable in industrial PQQ production.

  2. Cancer Patient T Cells Genetically Targeted to Prostate-Specific Membrane Antigen Specifically Lyse Prostate Cancer Cells and Release Cytokines in Response to Prostate-Specific Membrane Antigen

    Directory of Open Access Journals (Sweden)

    Michael C. Gong

    1999-06-01

    Full Text Available The expression of immunoglobulin-based artificial receptors in normal T lymphocytes provides a means to target lymphocytes to cell surface antigens independently of major histocompatibility complex restriction. Such artificial receptors have been previously shown to confer antigen-specific tumoricidal properties in murine T cells. We constructed a novel ζ chain fusion receptor specific for prostate-specific membrane antigen (PSMA termed Pz-1. PSMA is a cell-surface glycoprotein expressed on prostate cancer cells and the neovascular endothelium of multiple carcinomas. We show that primary T cells harvested from five of five patients with different stages of prostate cancer and transduced with the Pz-1 receptor readily lyse prostate cancer cells. Having established a culture system using fibroblasts that express PSMA, we next show that T cells expressing the Pz-1 receptor release cytokines in response to cell-bound PSMA. Furthermore, we show that the cytokine release is greatly augmented by B7.1-mediated costimulation. Thus, our findings support the feasibility of adoptive cell therapy by using genetically engineered T cells in prostate cancer patients and suggest that both CD4+ and CD8+ T lymphocyte functions can be synergistically targeted against tumor cells.

  3. Genetic Polymorphisms in the Long Noncoding RNA MIR2052HG Offer a Pharmacogenomic Basis for the Response of Breast Cancer Patients to Aromatase Inhibitor Therapy.

    Science.gov (United States)

    Ingle, James N; Xie, Fang; Ellis, Matthew J; Goss, Paul E; Shepherd, Lois E; Chapman, Judith-Anne W; Chen, Bingshu E; Kubo, Michiaki; Furukawa, Yoichi; Momozawa, Yukihide; Stearns, Vered; Pritchard, Kathleen I; Barman, Poulami; Carlson, Erin E; Goetz, Matthew P; Weinshilboum, Richard M; Kalari, Krishna R; Wang, Liewei

    2016-12-01

    Genetic risks in breast cancer remain only partly understood. Here, we report the results of a genome-wide association study of germline DNA from 4,658 women, including 252 women experiencing a breast cancer recurrence, who were entered on the MA.27 adjuvant trial comparing the aromatase inhibitors (AI) anastrozole and exemestane. Single-nucleotide polymorphisms (SNP) of top significance were identified in the gene encoding MIR2052HG, a long noncoding RNA of unknown function. Heterozygous or homozygous individuals for variant alleles exhibited a ∼40% or ∼63% decrease, respectively, in the hazard of breast cancer recurrence relative to homozygous wild-type individuals. Functional genomic studies in lymphoblastoid cell lines and ERα-positive breast cancer cell lines showed that expression from MIR2052HG and the ESR1 gene encoding estrogen receptor-α (ERα) was induced by estrogen and AI in a SNP-dependent manner. Variant SNP genotypes exhibited increased ERα binding to estrogen response elements, relative to wild-type genotypes, a pattern that was reversed by AI treatment. Further, variant SNPs were associated with lower expression of MIR2052HG and ERα. RNAi-mediated silencing of MIR2052HG in breast cancer cell lines decreased ERα expression, cell proliferation, and anchorage-independent colony formation. Mechanistic investigations revealed that MIR2052HG sustained ERα levels both by promoting AKT/FOXO3-mediated ESR1 transcription and by limiting ubiquitin-mediated, proteasome-dependent degradation of ERα. Taken together, our results define MIR2052HS as a functionally polymorphic gene that affects risks of breast cancer recurrence in women treated with AI. More broadly, our results offer a pharmacogenomic basis to understand differences in the response of breast cancer patients to AI therapy. Cancer Res; 76(23); 7012-23. ©2016 AACR. ©2016 American Association for Cancer Research.

  4. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans.

    Science.gov (United States)

    Kosek, Eva; Jensen, Karin B; Lonsdorf, Tina B; Schalling, Martin; Ingvar, Martin

    2009-07-01

    There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531). The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years) underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on micro-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG) as compared to those with high expression(LA/LA), p desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.

  5. 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

  6. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

    DEFF Research Database (Denmark)

    van den Berg, S. M.; de Moor, M. H. M.; McGue, Matt

    2014-01-01

    -analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size...

  7. [Genetic information and future medicine].

    Science.gov (United States)

    Sakurai, Akihiro

    2012-11-01

    Rapid technological advances in genetic analysis have revealed the genetic background of various diseases. Elucidation of the genes responsible for a disease enables better clinical management of the disease and helps to develop targeted drugs. Also, early diagnosis and management of at-risk family members can be made by identification of a genetic disease in the proband. On the other hand, genetic issues often cause psychological distress to the family. To perform genetic testing appropriately and to protect patients and family members from any harm, guidelines for genetic testing were released from the alliance of Japanese genetics-related academic societies in 2003. As genetic testing is becoming incorporated into clinical practice more broadly, the guideline was revised and released by the Japanese Society of Medical Sciences in 2011. All medical professionals in Japan are expected to follow this guideline.

  8. From Genetics to Genetic Algorithms

    Indian Academy of Sciences (India)

    Genetic algorithms (GAs) are computational optimisation schemes with an ... The algorithms solve optimisation problems ..... Genetic Algorithms in Search, Optimisation and Machine. Learning, Addison-Wesley Publishing Company, Inc. 1989.

  9. From Genetics to Genetic Algorithms

    Indian Academy of Sciences (India)

    artificial genetic system) string feature or ... called the genotype whereas it is called a structure in artificial genetic ... assigned a fitness value based on the cost function. Better ..... way it has produced complex, intelligent living organisms capable of ...

  10. CYP1A2 – a novel genetic marker for early aromatase inhibitor response in the treatment of breast cancer patients

    International Nuclear Information System (INIS)

    Simonsson, Maria; Veerla, Srinivas; Markkula, Andrea; Rose, Carsten; Ingvar, Christian; Jernström, Helena

    2016-01-01

    Endocrine resistance is a major obstacle to optimal treatment effect in breast cancer. Some genetic markers have been proposed to predict response to aromatase inhibitors (AIs) but the data is insufficient. The aim of the study was to find new genetic treatment predictive markers of AIs. The ongoing population-based BC-blood study in Lund, Sweden includes women with primary breast cancer. This paper is based on AI-treated patients with estrogen receptor positive tumors who underwent breast cancer surgery in 2002–2008. First, an exploratory analysis of 1931 SNPs in 227 genes involved in absorption, distribution, metabolism, and elimination of multiple medications, using DMET™ chips, was conducted in a subset of the cohort with last follow-up in December 31 st 2011 (13 cases, 11 controls). Second, selected SNPs from the first analysis were re-analyzed concerning risk for early breast cancer events in the extended cohort of 201 AI-treated with last follow-up in June 30 th 2014. Clinical data were obtained from medical records and population registries. Only CYP1A2 rs762551 C-allele was significantly associated with increased risk for early events in the 24 patients (P = 0.0007) and in the extended cohort, adjusted Hazard ratio (HR) 2.22 (95 % CI 1.03–4.80). However, the main prognostic impact was found within five years, adjusted HR 7.88 (95 % CI 2.13–29.19). The impact of the CYP1A2 rs762551 C-allele was modified by a functional polymorphism in the regulator gene AhR Arg554Lys (G > A). Compared to patients who were homozygous for the major allele in both genes (CYP1A2 A/A and AhR G/G), a 9-fold risk for early events was found in patients who had at least one minor allele in both genes, adjusted HR 8.95 (95 % CI 2.55–31.35), whereas patients with at least one minor allele in either but not both genes had a 3-fold risk for early events, adjusted HR 2.81 (95 % CI 1.07–7.33). The impact of CYP1A2 rs762551 C-allele was also modified by the CYP19A1 rs4646 C

  11. An ultrasound-assisted system for the optimization of biodiesel production from chicken fat oil using a genetic algorithm and response surface methodology.

    Science.gov (United States)

    Fayyazi, E; Ghobadian, B; Najafi, G; Hosseinzadeh, B; Mamat, R; Hosseinzadeh, J

    2015-09-01

    Biodiesel is a green (clean), renewable energy source and is an alternative for diesel fuel. Biodiesel can be produced from vegetable oil, animal fat and waste cooking oil or fat. Fats and oils react with alcohol to produce methyl ester, which is generally known as biodiesel. Because vegetable oil and animal fat wastes are cheaper, the tendency to produce biodiesel from these materials is increasing. In this research, the effect of some parameters such as the alcohol-to-oil molar ratio (4:1, 6:1, 8:1), the catalyst concentration (0.75%, 1% and 1.25% w/w) and the time for the transesterification reaction using ultrasonication on the rate of the fatty acids-to-methyl ester (biodiesel) conversion percentage have been studied (3, 6 and 9 min). In biodiesel production from chicken fat, when increasing the catalyst concentration up to 1%, the oil-to-biodiesel conversion percentage was first increased and then decreased. Upon increasing the molar ratio from 4:1 to 6:1 and then to 8:1, the oil-to-biodiesel conversion percentage increased by 21.9% and then 22.8%, respectively. The optimal point is determined by response surface methodology (RSM) and genetic algorithms (GAs). The biodiesel production from chicken fat by ultrasonic waves with a 1% w/w catalyst percentage, 7:1 alcohol-to-oil molar ratio and 9 min reaction time was equal to 94.8%. For biodiesel that was produced by ultrasonic waves under a similar conversion percentage condition compared to the conventional method, the reaction time was decreased by approximately 87.5%. The time reduction for the ultrasonic method compared to the conventional method makes the ultrasonic method superior. Copyright © 2015. Published by Elsevier B.V.

  12. Genetic variation for lettuce seed thermoinhibition is associated with temperature-sensitive expression of abscisic Acid, gibberellin, and ethylene biosynthesis, metabolism, and response genes.

    Science.gov (United States)

    Argyris, Jason; Dahal, Peetambar; Hayashi, Eiji; Still, David W; Bradford, Kent J

    2008-10-01

    Lettuce (Lactuca sativa 'Salinas') seeds fail to germinate when imbibed at temperatures above 25 degrees C to 30 degrees C (termed thermoinhibition). However, seeds of an accession of Lactuca serriola (UC96US23) do not exhibit thermoinhibition up to 37 degrees C in the light. Comparative genetics, physiology, and gene expression were analyzed in these genotypes to determine the mechanisms governing the regulation of seed germination by temperature. Germination of the two genotypes was differentially sensitive to abscisic acid (ABA) and gibberellin (GA) at elevated temperatures. Quantitative trait loci associated with these phenotypes colocated with a major quantitative trait locus (Htg6.1) from UC96US23 conferring germination thermotolerance. ABA contents were elevated in Salinas seeds that exhibited thermoinhibition, consistent with the ability of fluridone (an ABA biosynthesis inhibitor) to improve germination at high temperatures. Expression of many genes involved in ABA, GA, and ethylene biosynthesis, metabolism, and response was differentially affected by high temperature and light in the two genotypes. In general, ABA-related genes were more highly expressed when germination was inhibited, and GA- and ethylene-related genes were more highly expressed when germination was permitted. In particular, LsNCED4, a gene encoding an enzyme in the ABA biosynthetic pathway, was up-regulated by high temperature only in Salinas seeds and also colocated with Htg6.1. The temperature sensitivity of expression of LsNCED4 may determine the upper temperature limit for lettuce seed germination and may indirectly influence other regulatory pathways via interconnected effects of increased ABA biosynthesis.

  13. Changes in polyphenol and sugar concentrations in wild type and genetically modified Nicotiana langsdorffii Weinmann in response to water and heat stress.

    Science.gov (United States)

    Ancillotti, Claudia; Bogani, Patrizia; Biricolti, Stefano; Calistri, Elisa; Checchini, Leonardo; Ciofi, Lorenzo; Gonnelli, Cristina; Del Bubba, Massimo

    2015-12-01

    In this study wild type Nicotiana langsdorffii plants were genetically transformed by the insertion of the rat gene (gr) encoding the glucocorticoid receptor or the rolC gene and exposed to water and heat stress. Water stress was induced for 15 days by adding 20% PEG 6000 in the growth medium, whereas the heat treatment was performed at 50 °C for 2 h, after that a re-growing capability study was carried out. The plant response to stress was investigated by determining electrolyte leakage, dry weight biomass production and water content. These data were evaluated in relation to antiradical activity and concentrations of total polyphenols, selected phenolic compounds and some soluble sugars, as biochemical indicators of metabolic changes due to gene insertion and/or stress treatments. As regards the water stress, the measured physiological parameters evidenced an increasing stress level in the order rolC < gr < WT plants (e.g. about 100% and 50% electrolyte leakage increase in WT and gr samples, respectively) and complied with the biochemical pattern, which consisted in a general decrease of antiradical activity and phenolics, together with an increase in sugars. As regard heat stress, electrolyte leakage data were only in partial agreement with the re-growing capability study. In fact, according to this latter evaluation, gr was the genotype less affected by the heat shock. In this regard, sugars and especially phenolic compounds are informative of the long-term effects due to heat shock treatment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. About Genetic Counselors

    Science.gov (United States)

    ... clinical care in many areas of medicine. Assisted Reproductive Technology/Infertility Genetics Cancer Genetics Cardiovascular Genetics Cystic Fibrosis Genetics Fetal Intervention and Therapy Genetics Hematology Genetics Metabolic Genetics ...

  15. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531 influences the analgesic response to the short acting opioid Remifentanil in humans

    Directory of Open Access Journals (Sweden)

    Schalling Martin

    2009-07-01

    Full Text Available Abstract Background There is evidence from animal studies that serotonin (5-HT can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531. The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on μ-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS. All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. Results At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG as compared to those with high expression(LA/LA, p Conclusion This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of

  16. Genome-wide investigation and expression analysis suggest diverse roles and genetic redundancy of Pht1 family genes in response to Pi deficiency in tomato.

    Science.gov (United States)

    Chen, Aiqun; Chen, Xiao; Wang, Huimin; Liao, Dehua; Gu, Mian; Qu, Hongye; Sun, Shubin; Xu, Guohua

    2014-03-11

    . Additionally, the four paralogues, LePT1, LePT2, LePT6 and LePT7, were very significantly down-regulated in the mycorrhizal roots under low Pi supply condition. The results obtained from this study provide new insights into the evolutionary expansion, functional divergence and genetic redundancy of the Pht1 genes in response to Pi deficiency and mycorrhizal symbiosis in tomato.

  17. Improved humoral and cellular immune response against the gp120 V3 loop of HIV-1 following genetic immunization with a chimeric DNA vaccine encoding the V3 inserted into the hepatites B surface antigen

    DEFF Research Database (Denmark)

    Fomsgaard, A.; Nielsen, H.V.; Bryder, K.

    1998-01-01

    response and a uniform strong anti-HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V2/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks which peaked at 6-12 weeks and remained stable for at least 25 weeks. In addition, specific CTL...... responses were induced in all mice against both MN V3 and HBsAg already within the first 3 weeks, lasting at least 11 weeks. Thus, HBsAg acts as a `genetic vaccine adjuvant' augmenting and accelerating the cellular and humoral immune response against the inserted MN V3 loop. Such chimeric HIV-HbsAg plasmid...

  18. Improved humoral and cellular immune responses against the gp120 V3 loop of HIV-1 following genetic immunization with a chimeric DNA vaccine encoding the V3 inserted into the hepatitis B surface antigen

    DEFF Research Database (Denmark)

    Fomsgaard, A; Nielsen, H V; Bryder, K

    1998-01-01

    response and a uniform strong anti-HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V3/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks which peaked at 6-12 weeks and remained stable for at least 25 weeks. In addition, specific CTL...... responses were induced in all mice against both MN V3 and HBsAg already within the first 3 weeks, lasting at least 11 weeks. Thus, HBsAg acts as a 'genetic vaccine adjuvant' augmenting and accelerating the cellular and humoral immune response against the inserted MN V3 loop. Such chimeric HIV-HBsAg plasmid...

  19. AI-2 quorum-sensing inhibitors affect the starvation response and reduce virulence in several Vibrio species, most likely by interfering with LuxPQ.

    Science.gov (United States)

    Brackman, Gilles; Celen, Shari; Baruah, Kartik; Bossier, Peter; Van Calenbergh, Serge; Nelis, Hans J; Coenye, Tom

    2009-12-01

    The increase of disease outbreaks caused by Vibrio species in aquatic organisms as well as in humans, together with the emergence of antibiotic resistance in Vibrio species, has led to a growing interest in alternative disease control measures. Quorum sensing (QS) is a mechanism for regulating microbial gene expression in a cell density-dependent way. While there is good evidence for the involvement of auto-inducer 2 (AI-2)-based interspecies QS in the control of virulence in multiple Vibrio species, only few inhibitors of this system are known. From the screening of a small panel of nucleoside analogues for their ability to disturb AI-2-based QS, an adenosine derivative with a p-methoxyphenylpropionamide moiety at C-3' emerged as a promising hit. Its mechanism of inhibition was elucidated by measuring the effect on bioluminescence in a series of Vibrio harveyi AI-2 QS mutants. Our results indicate that this compound, as well as a truncated analogue lacking the adenine base, block AI-2-based QS without interfering with bacterial growth. The active compounds affected neither the bioluminescence system as such nor the production of AI-2, but most likely interfered with the signal transduction pathway at the level of LuxPQ in V. harveyi. The most active nucleoside analogue (designated LMC-21) was found to reduce the Vibrio species starvation response, to affect biofilm formation in Vibrio anguillarum, Vibrio vulnificus and Vibrio cholerae, to reduce pigment and protease production in V. anguillarum, and to protect gnotobiotic Artemia from V. harveyi-induced mortality.

  20. Optimization of biodiesel production from Thevetia peruviana seed oil by adaptive neuro-fuzzy inference system coupled with genetic algorithm and response surface methodology

    International Nuclear Information System (INIS)

    Ogaga Ighose, Benjamin; Adeleke, Ibrahim A.; Damos, Mueuji; Adeola Junaid, Hamidat; Ernest Okpalaeke, Kelechi; Betiku, Eriola

    2017-01-01

    Highlights: • Oil was extracted from Thevetia peruviana seeds and converted to FAME. • The FFA of the oil was first reduced to <1% by esterification process. • The conversion of the esterified oil to FAME was modeled using ANFIS and RSM. • The developed models by ANFIS and RSM for transesterification process had R"2 ≈ 1. • GA and RSM gave the maximum FAME yield of 99.8 wt.% and 98.8 wt.%, respectively. - Abstract: This work focused on the application of adaptive neuro-fuzzy inference system (ANFIS) and response surface methodology (RSM) as predictive tools for production of fatty acid methyl esters (FAME) from yellow oleander (Thevetia peruviana) seed oil. Two-step transesterification method was adopted, in the first step, the high free fatty acid (FFA) content of the oil was reduced to <1% by treating it with ferric sulfate in the presence of methanol. While in the second step, the pretreated oil was converted to FAME by reacting it with methanol using sodium methoxide as catalyst. To model the second step, central composite design was employed to study the effect of catalyst loading (1–2 wt.%), methanol/oil molar ratio (6:1–12:1) and time (20–60 min) on the T. peruviana methyl esters (TPME) yield. The reduction of FFA of the oil to 0.65 ± 0.05 wt.% was realized using ferric sulfate of 3 wt.%, methanol/FFA molar ratio of 9:1 and reaction time of 40 min. The model developed for the transesterification process by ANFIS (coefficient of determination, R"2 = 0.9999, standard error of prediction, SEP = 0.07 and mean absolute percentage deviation, MAPD = 0.05%) was significantly better than that of RSM (R"2 = 0.9670, SEP = 1.55 and MAPD = 0.84%) in terms of accuracy of the predicted TPME yield. For maximum TPME yield, the transesterification process input variables were optimized using genetic algorithm (GA) coupled with the ANFIS model and RSM optimization tool. TPME yield of 99.8 wt.% could be obtained with the combination of 0.79 w/v catalyst

  1. Genetic modification and genetic determinism

    Directory of Open Access Journals (Sweden)

    Vorhaus Daniel B

    2006-06-01

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

  2. 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)

  3. Genetic Romanticism

    DEFF Research Database (Denmark)

    Tupasela, Aaro

    2016-01-01

    inheritance as a way to unify populations within politically and geographically bounded areas. Thus, new genetics have contributed to the development of genetic romanticisms, whereby populations (human, plant, and animal) can be delineated and mobilized through scientific and medical practices to represent...

  4. Protocols in human molecular genetics

    National Research Council Canada - National Science Library

    Mathew, Christopher G

    1991-01-01

    ... sequences has led to the develop