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Sample records for multiple genetic interactions

  1. Class II HLA interactions modulate genetic risk for multiple sclerosis

    Science.gov (United States)

    Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil

    2016-01-01

    Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388

  2. Class II HLA interactions modulate genetic risk for multiple sclerosis

    DEFF Research Database (Denmark)

    Moutsianas, Loukas; Jostins, Luke; Beecham, Ashley H

    2015-01-01

    Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17...

  3. Multiple genetic interaction experiments provide complementary information useful for gene function prediction.

    Directory of Open Access Journals (Sweden)

    Magali Michaut

    Full Text Available Genetic interactions help map biological processes and their functional relationships. A genetic interaction is defined as a deviation from the expected phenotype when combining multiple genetic mutations. In Saccharomyces cerevisiae, most genetic interactions are measured under a single phenotype - growth rate in standard laboratory conditions. Recently genetic interactions have been collected under different phenotypic readouts and experimental conditions. How different are these networks and what can we learn from their differences? We conducted a systematic analysis of quantitative genetic interaction networks in yeast performed under different experimental conditions. We find that networks obtained using different phenotypic readouts, in different conditions and from different laboratories overlap less than expected and provide significant unique information. To exploit this information, we develop a novel method to combine individual genetic interaction data sets and show that the resulting network improves gene function prediction performance, demonstrating that individual networks provide complementary information. Our results support the notion that using diverse phenotypic readouts and experimental conditions will substantially increase the amount of gene function information produced by genetic interaction screens.

  4. Genetic Risk by Experience Interaction for Childhood Internalizing Problems: Converging Evidence across Multiple Methods

    Science.gov (United States)

    Vendlinski, Matthew K.; Lemery-Chalfant, Kathryn; Essex, Marilyn J.; Goldsmith, H. Hill

    2011-01-01

    Background: Identifying how genetic risk interacts with experience to predict psychopathology is an important step toward understanding the etiology of mental health problems. Few studies have examined genetic risk by experience interaction (GxE) in the development of childhood psychopathology. Methods: We used both co-twin and parent mental…

  5. Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout.

    Science.gov (United States)

    McKinney, Cushla; Stamp, Lisa K; Dalbeth, Nicola; Topless, Ruth K; Day, Richard O; Kannangara, Diluk Rw; Williams, Kenneth M; Janssen, Matthijs; Jansen, Timothy L; Joosten, Leo A; Radstake, Timothy R; Riches, Philip L; Tausche, Anne-Kathrin; Lioté, Frederic; So, Alexander; Merriman, Tony R

    2015-10-13

    The acute gout flare results from a localised self-limiting innate immune response to monosodium urate (MSU) crystals deposited in joints in hyperuricaemic individuals. Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome by MSU crystals and production of mature interleukin-1β (IL-1β) is central to acute gouty arthritis. However very little is known about genetic control of the innate immune response involved in acute gouty arthritis. Therefore our aim was to test functional single nucleotide polymorphism (SNP) variants in the toll-like receptor (TLR)-inflammasome-IL-1β axis for association with gout. 1,494 gout cases of European and 863 gout cases of New Zealand (NZ) Polynesian (Māori and Pacific Island) ancestry were included. Gout was diagnosed by the 1977 ARA gout classification criteria. There were 1,030 Polynesian controls and 10,942 European controls including from the publicly-available Atherosclerosis Risk in Communities (ARIC) and Framingham Heart (FHS) studies. The ten SNPs were either genotyped by Sequenom MassArray or by Affymetrix SNP array or imputed in the ARIC and FHS datasets. Allelic association was done by logistic regression adjusting by age and sex with European and Polynesian data combined by meta-analysis. Sample sets were pooled for multiplicative interaction analysis, which was also adjusted by sample set. Eleven SNPs were tested in the TLR2, CD14, IL1B, CARD8, NLRP3, MYD88, P2RX7, DAPK1 and TNXIP genes. Nominally significant (P gout were detected at CARD8 rs2043211 (OR = 1.12, P = 0.007), IL1B rs1143623 (OR = 1.10, P = 0.020) and CD14 rs2569190 (OR = 1.08; P = 0.036). There was significant multiplicative interaction between CARD8 and IL1B (P = 0.005), with the IL1B risk genotype amplifying the risk effect of CARD8. There is evidence for association of gout with functional variants in CARD8, IL1B and CD14. The gout-associated allele of IL1B increases

  6. GENIE: a software package for gene-gene interaction analysis in genetic association studies using multiple GPU or CPU cores

    Directory of Open Access Journals (Sweden)

    Wang Kai

    2011-05-01

    Full Text Available Abstract Background Gene-gene interaction in genetic association studies is computationally intensive when a large number of SNPs are involved. Most of the latest Central Processing Units (CPUs have multiple cores, whereas Graphics Processing Units (GPUs also have hundreds of cores and have been recently used to implement faster scientific software. However, currently there are no genetic analysis software packages that allow users to fully utilize the computing power of these multi-core devices for genetic interaction analysis for binary traits. Findings Here we present a novel software package GENIE, which utilizes the power of multiple GPU or CPU processor cores to parallelize the interaction analysis. GENIE reads an entire genetic association study dataset into memory and partitions the dataset into fragments with non-overlapping sets of SNPs. For each fragment, GENIE analyzes: 1 the interaction of SNPs within it in parallel, and 2 the interaction between the SNPs of the current fragment and other fragments in parallel. We tested GENIE on a large-scale candidate gene study on high-density lipoprotein cholesterol. Using an NVIDIA Tesla C1060 graphics card, the GPU mode of GENIE achieves a speedup of 27 times over its single-core CPU mode run. Conclusions GENIE is open-source, economical, user-friendly, and scalable. Since the computing power and memory capacity of graphics cards are increasing rapidly while their cost is going down, we anticipate that GENIE will achieve greater speedups with faster GPU cards. Documentation, source code, and precompiled binaries can be downloaded from http://www.cceb.upenn.edu/~mli/software/GENIE/.

  7. Genetic and environmental interactions

    International Nuclear Information System (INIS)

    Strong, L.C.

    1977-01-01

    Cancer may result from a multistage process occurring over a long period of time. Presumably, initial and progressive stages of carcinogenesis may be modified by both genetic and environmental factors. Theoretically, genetic factors may alter susceptibility to the carcinogenic effects of an environmental agent at the initial exposure due to variation in metabolism of the carcinogen or variation in specific target cell response to the active carcinogen, or during the latent phase due to numerous factors that might increase the probability of tumor expression, including growth-promoting factors or immunodeficiency states. Observed genetic and environmental interactions in carcinogenesis include an association between genetically determined inducibility of aryl hydrocarbon hydroxylase and smoking-related cancers, familial susceptibility to certain environmental carcinogens, an association between hereditary disorders of mutagenesis and carcinogenesis, and enhancement of tissue-specific, dominantly inherited tumor predisposition by radiation. Multiple primary tumors occur frequently in genetically predisposed individuals. Specific markers for susceptibility must be sought in order that high-risk individuals be identified and appropriate measures taken for early cancer detection or prevention. Study of the nature of the genetically determined susceptibility and interactions with environmental agents may be revealing in the understanding of carcinogenesis in general

  8. Multiple sclerosis and herpesvirus interaction

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    Guilherme Sciascia do Olival

    2013-09-01

    Full Text Available Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.

  9. Interacting effects of genetic variation for seed dormancy and flowering time on phenology, life history, and fitness of experimental Arabidopsis thaliana populations over multiple generations in the field.

    Science.gov (United States)

    Taylor, Mark A; Cooper, Martha D; Sellamuthu, Reena; Braun, Peter; Migneault, Andrew; Browning, Alyssa; Perry, Emily; Schmitt, Johanna

    2017-10-01

    Major alleles for seed dormancy and flowering time are well studied, and can interact to influence seasonal timing and fitness within generations. However, little is known about how this interaction controls phenology, life history, and population fitness across multiple generations in natural seasonal environments. To examine how seed dormancy and flowering time shape annual plant life cycles over multiple generations, we established naturally dispersing populations of recombinant inbred lines of Arabidopsis thaliana segregating early and late alleles for seed dormancy and flowering time in a field experiment. We recorded seasonal phenology and fitness of each genotype over 2 yr and several generations. Strong seed dormancy suppressed mid-summer germination in both early- and late-flowering genetic backgrounds. Strong dormancy and late-flowering genotypes were both necessary to confer a winter annual life history; other genotypes were rapid-cycling. Strong dormancy increased within-season fecundity in an early-flowering background, but decreased it in a late-flowering background. However, there were no detectable differences among genotypes in population growth rates. Seasonal phenology, life history, and cohort fitness over multiple generations depend strongly upon interacting genetic variation for dormancy and flowering. However, similar population growth rates across generations suggest that different life cycle genotypes can coexist in natural populations. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  10. The interaction between smoking and HLA genes in multiple sclerosis

    DEFF Research Database (Denmark)

    Hedström, Anna Karin; Katsoulis, Michail; Hössjer, Ola

    2017-01-01

    Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We us...

  11. Genetic variations in multiple myeloma I

    DEFF Research Database (Denmark)

    Vangsted, A.; Klausen, T.W.; Vogel, Ulla Birgitte

    2012-01-01

    Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis of variab......Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B-cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis...

  12. Genetic variants and multiple myeloma risk

    DEFF Research Database (Denmark)

    Martino, Alessandro; Campa, Daniele; Jurczyszyn, Artur

    2014-01-01

    BACKGROUND: Genetic background plays a role in multiple myeloma susceptibility. Several single-nucleotide polymorphisms (SNP) associated with genetic susceptibility to multiple myeloma were identified in the last years, but only a few of them were validated in independent studies. METHODS...... with multiple myeloma risk (P value range, 0.055-0.981), possibly with the exception of the SNP rs2227667 (SERPINE1) in women. CONCLUSIONS: We can exclude that the selected polymorphisms are major multiple myeloma risk factors. IMPACT: Independent validation studies are crucial to identify true genetic risk...

  13. Predictability of Genetic Interactions from Functional Gene Modules

    Directory of Open Access Journals (Sweden)

    Jonathan H. Young

    2017-02-01

    Full Text Available Characterizing genetic interactions is crucial to understanding cellular and organismal response to gene-level perturbations. Such knowledge can inform the selection of candidate disease therapy targets, yet experimentally determining whether genes interact is technically nontrivial and time-consuming. High-fidelity prediction of different classes of genetic interactions in multiple organisms would substantially alleviate this experimental burden. Under the hypothesis that functionally related genes tend to share common genetic interaction partners, we evaluate a computational approach to predict genetic interactions in Homo sapiens, Drosophila melanogaster, and Saccharomyces cerevisiae. By leveraging knowledge of functional relationships between genes, we cross-validate predictions on known genetic interactions and observe high predictive power of multiple classes of genetic interactions in all three organisms. Additionally, our method suggests high-confidence candidate interaction pairs that can be directly experimentally tested. A web application is provided for users to query genes for predicted novel genetic interaction partners. Finally, by subsampling the known yeast genetic interaction network, we found that novel genetic interactions are predictable even when knowledge of currently known interactions is minimal.

  14. Multiple Parton Interactions in ALICE

    CERN Multimedia

    CERN. Geneva

    2013-01-01

    We will present in detail the measurement of the charged particle multiplicity dependence of per-trigger pair yields in azimuthal direction induced by low-energetic di-jets produced in proton-proton collisions. Using two-particle angular correlations with low transverse momentum thresholds, jet properties are measured on a statistical basis down to the lowest possible jet energies. The analysis can give information about the contribution from multiple parton interactions to particle production. Moreover, the results allow to optimize the parametrization of the jet fragmentation in phenomenological mode...

  15. Coffee, Genetic Variants, and Parkinson's Disease: Gene–Environment Interactions

    OpenAIRE

    Yamada-Fowler, Naomi; Söderkvist, Peter

    2015-01-01

    Studies of gene–environment interactions may help us to understand the disease mechanisms of common and complex diseases such as Parkinson's disease (PD). Sporadic PD, the common form of PD, is thought to be a multifactorial disorder caused by combinations of multiple genetic factors and environmental or life-style exposures. Since one of the most extensively studied life-style factors in PD is coffee/caffeine intake, here, the studies of genetic polymorphisms with life-style interactions of ...

  16. A map of directional genetic interactions in a metazoan cell.

    Science.gov (United States)

    Fischer, Bernd; Sandmann, Thomas; Horn, Thomas; Billmann, Maximilian; Chaudhary, Varun; Huber, Wolfgang; Boutros, Michael

    2015-03-06

    Gene-gene interactions shape complex phenotypes and modify the effects of mutations during development and disease. The effects of statistical gene-gene interactions on phenotypes have been used to assign genes to functional modules. However, directional, epistatic interactions, which reflect regulatory relationships between genes, have been challenging to map at large-scale. Here, we used combinatorial RNA interference and automated single-cell phenotyping to generate a large genetic interaction map for 21 phenotypic features of Drosophila cells. We devised a method that combines genetic interactions on multiple phenotypes to reveal directional relationships. This network reconstructed the sequence of protein activities in mitosis. Moreover, it revealed that the Ras pathway interacts with the SWI/SNF chromatin-remodelling complex, an interaction that we show is conserved in human cancer cells. Our study presents a powerful approach for reconstructing directional regulatory networks and provides a resource for the interpretation of functional consequences of genetic alterations.

  17. Genetic Algorithms for Multiple-Choice Problems

    Science.gov (United States)

    Aickelin, Uwe

    2010-04-01

    This thesis investigates the use of problem-specific knowledge to enhance a genetic algorithm approach to multiple-choice optimisation problems.It shows that such information can significantly enhance performance, but that the choice of information and the way it is included are important factors for success.Two multiple-choice problems are considered.The first is constructing a feasible nurse roster that considers as many requests as possible.In the second problem, shops are allocated to locations in a mall subject to constraints and maximising the overall income.Genetic algorithms are chosen for their well-known robustness and ability to solve large and complex discrete optimisation problems.However, a survey of the literature reveals room for further research into generic ways to include constraints into a genetic algorithm framework.Hence, the main theme of this work is to balance feasibility and cost of solutions.In particular, co-operative co-evolution with hierarchical sub-populations, problem structure exploiting repair schemes and indirect genetic algorithms with self-adjusting decoder functions are identified as promising approaches.The research starts by applying standard genetic algorithms to the problems and explaining the failure of such approaches due to epistasis.To overcome this, problem-specific information is added in a variety of ways, some of which are designed to increase the number of feasible solutions found whilst others are intended to improve the quality of such solutions.As well as a theoretical discussion as to the underlying reasons for using each operator,extensive computational experiments are carried out on a variety of data.These show that the indirect approach relies less on problem structure and hence is easier to implement and superior in solution quality.

  18. Multiplicities in high energy interactions

    International Nuclear Information System (INIS)

    Derrick, M.

    1984-01-01

    Charged particle multiplicities in hadronic collision have been measured for all energies up to √s = 540 GeV in the center of mass. Similar measurements in e + e - annihilation cover the much smaller range - up to √s = 40 GeV. Data are also available from deep inelastic neutrino scattering up to √s approx. 10 GeV. The experiments measure the mean charged multiplicity , the rapidity density at y = O, and the distributions in prong number. The mean number of photons associated with the events can be used to measure the π 0 and eta 0 multiplicities. Some information is also available on the charged pion, kaon, and nucleon fractions as well as the K 0 and Λ 0 rates and for the higher energy data, the identically equal fraction. We review this data and consider the implications of extrapolations to SSC energies. 13 references

  19. A genetic ensemble approach for gene-gene interaction identification

    Directory of Open Access Journals (Sweden)

    Ho Joshua WK

    2010-10-01

    Full Text Available Abstract Background It has now become clear that gene-gene interactions and gene-environment interactions are ubiquitous and fundamental mechanisms for the development of complex diseases. Though a considerable effort has been put into developing statistical models and algorithmic strategies for identifying such interactions, the accurate identification of those genetic interactions has been proven to be very challenging. Methods In this paper, we propose a new approach for identifying such gene-gene and gene-environment interactions underlying complex diseases. This is a hybrid algorithm and it combines genetic algorithm (GA and an ensemble of classifiers (called genetic ensemble. Using this approach, the original problem of SNP interaction identification is converted into a data mining problem of combinatorial feature selection. By collecting various single nucleotide polymorphisms (SNP subsets as well as environmental factors generated in multiple GA runs, patterns of gene-gene and gene-environment interactions can be extracted using a simple combinatorial ranking method. Also considered in this study is the idea of combining identification results obtained from multiple algorithms. A novel formula based on pairwise double fault is designed to quantify the degree of complementarity. Conclusions Our simulation study demonstrates that the proposed genetic ensemble algorithm has comparable identification power to Multifactor Dimensionality Reduction (MDR and is slightly better than Polymorphism Interaction Analysis (PIA, which are the two most popular methods for gene-gene interaction identification. More importantly, the identification results generated by using our genetic ensemble algorithm are highly complementary to those obtained by PIA and MDR. Experimental results from our simulation studies and real world data application also confirm the effectiveness of the proposed genetic ensemble algorithm, as well as the potential benefits of

  20. Inferring genetic interactions from comparative fitness data.

    Science.gov (United States)

    Crona, Kristina; Gavryushkin, Alex; Greene, Devin; Beerenwinkel, Niko

    2017-12-20

    Darwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations. We demonstrate that genetic interactions can often be inferred from fitness rank orders, where all genotypes are ordered according to fitness, and even from partial fitness orders. We provide a complete characterization of rank orders that imply higher order epistasis. Our theory applies to all common types of gene interactions and facilitates comprehensive investigations of diverse genetic interactions. We analyzed various genetic systems comprising HIV-1, the malaria-causing parasite Plasmodium vivax , the fungus Aspergillus niger , and the TEM-family of β-lactamase associated with antibiotic resistance. For all systems, our approach revealed higher order interactions among mutations.

  1. A Study of Multiplicities in Hadronic Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Estrada Tristan, Nora Patricia; /San Luis Potosi U.

    2006-02-01

    Using data from the SELEX (Fermilab E781) experiment obtained with a minimum-bias trigger, we study multiplicity and angular distributions of secondary particles produced in interactions in the experimental targets. We observe interactions of {Sigma}{sup -}, proton, {pi}{sup -}, and {pi}{sup +}, at beam momenta between 250 GeV/c and 650 GeV/c, in copper, polyethylene, graphite, and beryllium targets. We show that the multiplicity and angular distributions for meson and baryon beams at the same momentum are identical. We also show that the mean multiplicity increases with beam momentum, and presents only small variations with the target material.

  2. Uncovering the genetic landscape for multiple sleep-wake traits.

    Directory of Open Access Journals (Sweden)

    Christopher J Winrow

    Full Text Available Despite decades of research in defining sleep-wake properties in mammals, little is known about the nature or identity of genes that regulate sleep, a fundamental behaviour that in humans occupies about one-third of the entire lifespan. While genome-wide association studies in humans and quantitative trait loci (QTL analyses in mice have identified candidate genes for an increasing number of complex traits and genetic diseases, the resources and time-consuming process necessary for obtaining detailed quantitative data have made sleep seemingly intractable to similar large-scale genomic approaches. Here we describe analysis of 20 sleep-wake traits from 269 mice from a genetically segregating population that reveals 52 significant QTL representing a minimum of 20 genomic loci. While many (28 QTL affected a particular sleep-wake trait (e.g., amount of wake across the full 24-hr day, other loci only affected a trait in the light or dark period while some loci had opposite effects on the trait during the light vs. dark. Analysis of a dataset for multiple sleep-wake traits led to previously undetected interactions (including the differential genetic control of number and duration of REM bouts, as well as possible shared genetic regulatory mechanisms for seemingly different unrelated sleep-wake traits (e.g., number of arousals and REM latency. Construction of a Bayesian network for sleep-wake traits and loci led to the identification of sub-networks of linkage not detectable in smaller data sets or limited single-trait analyses. For example, the network analyses revealed a novel chain of causal relationships between the chromosome 17@29cM QTL, total amount of wake, and duration of wake bouts in both light and dark periods that implies a mechanism whereby overall sleep need, mediated by this locus, in turn determines the length of each wake bout. Taken together, the present results reveal a complex genetic landscape underlying multiple sleep-wake traits

  3. Sequential interactions of silver-silica nanocomposite (Ag-SiO2 NC) with cell wall, metabolism and genetic stability of Pseudomonas aeruginosa, a multiple antibiotic-resistant bacterium

    Digital Repository Service at National Institute of Oceanography (India)

    Anas, A.; Jiya, J.; Rameez, M.J.; Anand, P.B.; Anantharaman, M.R.; Nair, S.

    The study was carried out to understand the effect of silver–silica nanocomposite (Ag-SiO sub(2)NC) on the cell wall integrity, metabolism and genetic stability of Pseudomonas aeruginosa, a multiple drug-resistant bacterium. Bacterial sensitivity...

  4. Sequential interactions of silver-silica nanocomposite (Ag-SiO2NC) with cell wall, metabolism and genetic stability of Pseudomonas aeruginosa, a multiple antibiotic-resistant bacterium

    Digital Repository Service at National Institute of Oceanography (India)

    Anas, A.; Jiya, J.; Rameez, M.J.; Anand, P.B.; Anantharaman, M.R.; Nair, S.

    The study was carried out to understand the effect of silver-silica nanocomposite (Ag-SiO sub(2)NC) on the cell wall integrity, metabolism and genetic stability of Pseudomonas aeruginosa, a multiple drug-resistant bacterium Bacterial sensitivity...

  5. Environmental and genetic interactions in human cancer

    International Nuclear Information System (INIS)

    Paterson, M.C.

    Humans, depending upon their genetic make-up, differ in their susceptibility to the cancer-causing effects of extrinsic agents. Clinical and laboratory studies on the hereditary disorder, ataxia telangiectasia (AT) show that persons afflicted with this are cancer-prone and unusually sensitive to conventional radiotherapy. Their skin cells, when cultured, are hypersensitive to killing by ionizing radiation, being defective in the enzymatic repair of radiation-induced damange to the genetic material, deoxyribonucleic acid (DNA). This molecular finding implicates DNA damage and its imperfect repair as an early step in the induction of human cancer by radiation and other carcinogens. The parents of AT patients are clincally normal but their cultured cells are often moderately radiosensitive. The increased radiosensitivity of cultured cells offers a means of identifying a presumed cancer-prone subpopulation that should avoid undue exposure to certain carcinogens. The radioresponse of cells from patients with other cancer-associated genetic disorders and persons suspected of being genetically predisposed to radiation-induced cancer has also been measured. Increased cell killing by γ-rays appears in the complex genetic disease, tuberous sclerosis. Cells from cancer-stricken members of a leukemia-prone family are also radiosensitive, as are cells from one patient with radiation-associated breast cancer. These radiobiological data, taken together, strongly suggest that genetic factors can interact with extrinsic agents and thereby play a greater causative role in the development of common cancers in man than previously thought. (L.L.)

  6. Genetic variations in multiple myeloma II

    DEFF Research Database (Denmark)

    Vangsted, A.; Klausen, T.W.; Vogel, U.

    2012-01-01

    Association studies on genetic variation to treatment effect may serve as a predictive marker for effect of treatment and can also uncover biological pathways behind drug effect. Single-nucleotide polymorphisms (SNPs) have been studied in relation to high-dose treatment (HDT), thalidomide- and bo...

  7. Fashion sketch design by interactive genetic algorithms

    Science.gov (United States)

    Mok, P. Y.; Wang, X. X.; Xu, J.; Kwok, Y. L.

    2012-11-01

    Computer aided design is vitally important for the modern industry, particularly for the creative industry. Fashion industry faced intensive challenges to shorten the product development process. In this paper, a methodology is proposed for sketch design based on interactive genetic algorithms. The sketch design system consists of a sketch design model, a database and a multi-stage sketch design engine. First, a sketch design model is developed based on the knowledge of fashion design to describe fashion product characteristics by using parameters. Second, a database is built based on the proposed sketch design model to define general style elements. Third, a multi-stage sketch design engine is used to construct the design. Moreover, an interactive genetic algorithm (IGA) is used to accelerate the sketch design process. The experimental results have demonstrated that the proposed method is effective in helping laypersons achieve satisfied fashion design sketches.

  8. Genetics Home Reference: multiple epiphyseal dysplasia

    Science.gov (United States)

    ... Hamel BC, Spranger J, Zabel B, Cohn DH, Cole WG, Hecht JT, Superti-Furga A. Recessive multiple ... medicine? What is newborn screening? New Pages Lyme disease Fibromyalgia White-Sutton syndrome All New & Updated Pages ...

  9. The multiple genetic causes of central hypothyroidism.

    Science.gov (United States)

    Persani, Luca; Bonomi, Marco

    2017-03-01

    An insufficient stimulation by thyrotropin (TSH) of an otherwise normal thyroid gland represents the cause of Central Hypothyrodism (CeH). CeH is about 1000-folds rarer than Primary Hypothyroidism and often represents a real challenge for the clinicians, mainly because they cannot rely on adequately sensitive parameters for diagnosis or management, as it occurs with circulating TSH in PH. Therefore, CeH diagnosis can be frequently missed or delayed in patients with a previously unknown pituitary involvement. A series of genetic defects have been described to account for isolated CeH or combined pituitary hormone defects (CPHDs) with variable clinical characteristics and degrees of severity. The recently identified candidate gene IGSF1 appears frequently involved. This review provides an updated illustration of the different genetic defects accounting for CeH. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Stress Effects on Multiple Memory System Interactions

    Science.gov (United States)

    Ness, Deborah; Calabrese, Pasquale

    2016-01-01

    Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour. PMID:27034845

  11. Multiple parton interactions at the LHC

    CERN Document Server

    Gaunt, Jonathan Richard

    2018-01-01

    Many high-energy collider experiments (including the current Large Hadron Collider at CERN) involve the collision of hadrons. Hadrons are composite particles consisting of partons (quarks and gluons), and this means that in any hadron–hadron collision there will typically be multiple collisions of the constituents — i.e. multiple parton interactions (MPI). Understanding the nature of the MPI is important in terms of searching for new physics in the products of the scatters, and also in its own right to gain a greater understanding of hadron structure. This book aims at providing a pedagogical introduction and a comprehensive review of different research lines linked by an involvement of MPI phenomena. It is written by pioneers as well as young leading scientists, and reviews both experimental findings and theoretical developments, discussing also the remaining open issues.

  12. Stress Effects on Multiple Memory System Interactions

    Directory of Open Access Journals (Sweden)

    Deborah Ness

    2016-01-01

    Full Text Available Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour.

  13. Stress Effects on Multiple Memory System Interactions.

    Science.gov (United States)

    Ness, Deborah; Calabrese, Pasquale

    2016-01-01

    Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour.

  14. Genome complexity, robustness and genetic interactions in digital organisms

    Science.gov (United States)

    Lenski, Richard E.; Ofria, Charles; Collier, Travis C.; Adami, Christoph

    1999-08-01

    Digital organisms are computer programs that self-replicate, mutate and adapt by natural selection. They offer an opportunity to test generalizations about living systems that may extend beyond the organic life that biologists usually study. Here we have generated two classes of digital organism: simple programs selected solely for rapid replication, and complex programs selected to perform mathematical operations that accelerate replication through a set of defined `metabolic' rewards. To examine the differences in their genetic architecture, we introduced millions of single and multiple mutations into each organism and measured the effects on the organism's fitness. The complex organisms are more robust than the simple ones with respect to the average effects of single mutations. Interactions among mutations are common and usually yield higher fitness than predicted from the component mutations assuming multiplicative effects; such interactions are especially important in the complex organisms. Frequent interactions among mutations have also been seen in bacteria, fungi and fruitflies. Our findings support the view that interactions are a general feature of genetic systems.

  15. Genetic and genomic interactions of animals with different ploidy levels.

    Science.gov (United States)

    Bogart, J P; Bi, K

    2013-01-01

    Polyploid animals have independently evolved from diploids in diverse taxa across the tree of life. We review a few polyploid animal species or biotypes where recently developed molecular and cytogenetic methods have significantly improved our understanding of their genetics, reproduction and evolution. Mitochondrial sequences that target the maternal ancestor of a polyploid show that polyploids may have single (e.g. unisexual salamanders in the genus Ambystoma) or multiple (e.g. parthenogenetic polyploid lizards in the genus Aspidoscelis) origins. Microsatellites are nuclear markers that can be used to analyze genetic recombinations, reproductive modes (e.g. Ambystoma) and recombination events (e.g. polyploid frogs such as Pelophylax esculentus). Hom(e)ologous chromosomes and rare intergenomic exchanges in allopolyploids have been distinguished by applying genome-specific fluorescent probes to chromosome spreads. Polyploids arise, and are maintained, through perturbations of the 'normal' meiotic program that would include pre-meiotic chromosome replication and genomic integrity of homologs. When possible, asexual, unisexual and bisexual polyploid species or biotypes interact with diploid relatives, and genes are passed from diploid to polyploid gene pools, which increase genetic diversity and ultimately evolutionary flexibility in the polyploid. When diploid relatives do not exist, polyploids can interact with another polyploid (e.g. species of African Clawed Frogs in the genus Xenopus). Some polyploid fish (e.g. salmonids) and frogs (Xenopus) represent independent lineages whose ancestors experienced whole genome duplication events. Some tetraploid frogs (P. esculentus) and fish (Squaliusalburnoides) may be in the process of becoming independent species, but diploid and triploid forms of these 'species' continue to genetically interact with the comparatively few tetraploid populations. Genetic and genomic interaction between polyploids and diploids is a complex

  16. Synchronization in networks with multiple interaction layers

    Science.gov (United States)

    del Genio, Charo I.; Gómez-Gardeñes, Jesús; Bonamassa, Ivan; Boccaletti, Stefano

    2016-01-01

    The structure of many real-world systems is best captured by networks consisting of several interaction layers. Understanding how a multilayered structure of connections affects the synchronization properties of dynamical systems evolving on top of it is a highly relevant endeavor in mathematics and physics and has potential applications in several socially relevant topics, such as power grid engineering and neural dynamics. We propose a general framework to assess the stability of the synchronized state in networks with multiple interaction layers, deriving a necessary condition that generalizes the master stability function approach. We validate our method by applying it to a network of Rössler oscillators with a double layer of interactions and show that highly rich phenomenology emerges from this. This includes cases where the stability of synchronization can be induced even if both layers would have individually induced unstable synchrony, an effect genuinely arising from the true multilayer structure of the interactions among the units in the network. PMID:28138540

  17. Tests for genetic interactions in type 1 diabetes

    DEFF Research Database (Denmark)

    Morahan, Grant; Mehta, Munish; James, Ian

    2011-01-01

    Interactions between genetic and environmental factors lead to immune dysregulation causing type 1 diabetes and other autoimmune disorders. Recently, many common genetic variants have been associated with type 1 diabetes risk, but each has modest individual effects. Familial clustering of type 1...... diabetes has not been explained fully and could arise from many factors, including undetected genetic variation and gene interactions....

  18. Coulomb interaction in multiple scattering theory

    International Nuclear Information System (INIS)

    Ray, L.; Hoffmann, G.W.; Thaler, R.M.

    1980-01-01

    The treatment of the Coulomb interaction in the multiple scattering theories of Kerman-McManus-Thaler and Watson is examined in detail. By neglecting virtual Coulomb excitations, the lowest order Coulomb term in the Watson optical potential is shown to be a convolution of the point Coulomb interaction with the distributed nuclear charge, while the equivalent Kerman-McManus-Thaler Coulomb potential is obtained from an averaged, single-particle Coulombic T matrix. The Kerman-McManus-Thaler Coulomb potential is expressed as the Watson Coulomb term plus additional Coulomb-nuclear and Coulomb-Coulomb cross terms, and the omission of the extra terms in usual Kerman-McManus-Thaler applications leads to negative infinite total reaction cross section predictions and incorrect pure Coulomb scattering limits. Approximations are presented which eliminate these anomalies. Using the two-potential formula, the full projectile-nucleus T matrix is separated into two terms, one resulting from the distributed nuclear charge and the other being a Coulomb distorted nuclear T matrix. It is shown that the error resulting from the omission of the Kerman-McManus-Thaler Coulomb terms is effectively removed when the pure Coulomb T matrix in Kerman-McManus-Thaler is replaced by the analogous quantity in the Watson approach. Using the various approximations, theoretical angular distributions are obtained for 800 MeV p+ 208 Pb elastic scattering and compared with experimental data

  19. A yeast screening system for simultaneously monitoring multiple genetic endpoints

    International Nuclear Information System (INIS)

    Dixon, M.L.; Mortimer, R.K.

    1986-01-01

    Mutation, recombination, and mitochondrial deficiencies have been proposed to have roles in the carcinogenic process. The authors describe a diploid strain of the yeast Saccharomyces cerevisiae capable of detecting this wide spectrum of genetic changes. The markers used for monitoring these events have been especially well characterized genetically. Ultraviolet light was chosen as a model carcinogenic agent to test this system. In addition to highly significant increases in the frequencies of each genetic change, increases in the absolute numbers of each change indicated induction and not selective survival. The relative amounts of each type of genetic change varied with dose. The wide spectrum of endpoints monitored in the XD83 yeast system may allow the detection of certain carcinogens and other genetically toxic agents which have escaped detection in more limited systems. Since only one strain is required to simultaneously monitor these genetic changes, this assay system should facilitate comparisons of the induced changes and be more efficient than using multiple strains to monitor the same endpoints. (Auth.)

  20. Feature extraction from multiple data sources using genetic programming.

    Energy Technology Data Exchange (ETDEWEB)

    Szymanski, J. J. (John J.); Brumby, Steven P.; Pope, P. A. (Paul A.); Eads, D. R. (Damian R.); Galassi, M. C. (Mark C.); Harvey, N. R. (Neal R.); Perkins, S. J. (Simon J.); Porter, R. B. (Reid B.); Theiler, J. P. (James P.); Young, A. C. (Aaron Cody); Bloch, J. J. (Jeffrey J.); David, N. A. (Nancy A.); Esch-Mosher, D. M. (Diana M.)

    2002-01-01

    Feature extration from imagery is an important and long-standing problem in remote sensing. In this paper, we report on work using genetic programming to perform feature extraction simultaneously from multispectral and digital elevation model (DEM) data. The tool used is the GENetic Imagery Exploitation (GENIE) software, which produces image-processing software that inherently combines spatial and spectral processing. GENIE is particularly useful in exploratory studies of imagery, such as one often does in combining data from multiple sources. The user trains the software by painting the feature of interest with a simple graphical user interface. GENIE then uses genetic programming techniques to produce an image-processing pipeline. Here, we demonstrate evolution of image processing algorithms that extract a range of land-cover features including towns, grasslands, wild fire burn scars, and several types of forest. We use imagery from the DOE/NNSA Multispectral Thermal Imager (MTI) spacecraft, fused with USGS 1:24000 scale DEM data.

  1. Functional genetics of intraspecific ecological interactions in Arabidopsis thaliana

    OpenAIRE

    Wolf, Jason B.; Mutic, Joshua J.; Kover, Paula X.

    2011-01-01

    Studying the genetic basis of traits involved in ecological interactions is a fundamental part of elucidating the connections between evolutionary and ecological processes. Such knowledge allows one to link genetic models of trait evolution with ecological models describing interactions within and between species. Previous work has shown that connections between genetic and ecological processes in Arabidopsis thaliana may be mediated by the fact that quantitative trait loci (QTL) with ‘direct...

  2. Capturing the spectrum of interaction effects in genetic association studies by simulated evaporative cooling network analysis.

    Directory of Open Access Journals (Sweden)

    Brett A McKinney

    2009-03-01

    Full Text Available Evidence from human genetic studies of several disorders suggests that interactions between alleles at multiple genes play an important role in influencing phenotypic expression. Analytical methods for identifying Mendelian disease genes are not appropriate when applied to common multigenic diseases, because such methods investigate association with the phenotype only one genetic locus at a time. New strategies are needed that can capture the spectrum of genetic effects, from Mendelian to multifactorial epistasis. Random Forests (RF and Relief-F are two powerful machine-learning methods that have been studied as filters for genetic case-control data due to their ability to account for the context of alleles at multiple genes when scoring the relevance of individual genetic variants to the phenotype. However, when variants interact strongly, the independence assumption of RF in the tree node-splitting criterion leads to diminished importance scores for relevant variants. Relief-F, on the other hand, was designed to detect strong interactions but is sensitive to large backgrounds of variants that are irrelevant to classification of the phenotype, which is an acute problem in genome-wide association studies. To overcome the weaknesses of these data mining approaches, we develop Evaporative Cooling (EC feature selection, a flexible machine learning method that can integrate multiple importance scores while removing irrelevant genetic variants. To characterize detailed interactions, we construct a genetic-association interaction network (GAIN, whose edges quantify the synergy between variants with respect to the phenotype. We use simulation analysis to show that EC is able to identify a wide range of interaction effects in genetic association data. We apply the EC filter to a smallpox vaccine cohort study of single nucleotide polymorphisms (SNPs and infer a GAIN for a collection of SNPs associated with adverse events. Our results suggest an important

  3. Spin-orbit interaction in multiple quantum wells

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Ya-Fei, E-mail: haoyafei@zjnu.cn [Physics Department, Zhejiang Normal University, Zhejiang 321004 (China)

    2015-01-07

    In this paper, we investigate how the structure of multiple quantum wells affects spin-orbit interactions. To increase the interface-related Rashba spin splitting and the strength of the interface-related Rashba spin-orbit interaction, we designed three kinds of multiple quantum wells. We demonstrate that the structure of the multiple quantum wells strongly affected the interface-related Rashba spin-orbit interaction, increasing the interface-related Rashba spin splitting to up to 26% larger in multiple quantum wells than in a stepped quantum well. We also show that the cubic Dresselhaus spin-orbit interaction similarly influenced the spin relaxation time of multiple quantum wells and that of a stepped quantum well. The increase in the interface-related Rashba spin splitting originates from the relationship between interface-related Rashba spin splitting and electron probability density. Our results suggest that multiple quantum wells can be good candidates for spintronic devices.

  4. Spin-orbit interaction in multiple quantum wells

    International Nuclear Information System (INIS)

    Hao, Ya-Fei

    2015-01-01

    In this paper, we investigate how the structure of multiple quantum wells affects spin-orbit interactions. To increase the interface-related Rashba spin splitting and the strength of the interface-related Rashba spin-orbit interaction, we designed three kinds of multiple quantum wells. We demonstrate that the structure of the multiple quantum wells strongly affected the interface-related Rashba spin-orbit interaction, increasing the interface-related Rashba spin splitting to up to 26% larger in multiple quantum wells than in a stepped quantum well. We also show that the cubic Dresselhaus spin-orbit interaction similarly influenced the spin relaxation time of multiple quantum wells and that of a stepped quantum well. The increase in the interface-related Rashba spin splitting originates from the relationship between interface-related Rashba spin splitting and electron probability density. Our results suggest that multiple quantum wells can be good candidates for spintronic devices

  5. A Hybrid Genetic Algorithm for the Multiple Crossdocks Problem

    Directory of Open Access Journals (Sweden)

    Zhaowei Miao

    2012-01-01

    Full Text Available We study a multiple crossdocks problem with supplier and customer time windows, where any violation of time windows will incur a penalty cost and the flows through the crossdock are constrained by fixed transportation schedules and crossdock capacities. We prove this problem to be NP-hard in the strong sense and therefore focus on developing efficient heuristics. Based on the problem structure, we propose a hybrid genetic algorithm (HGA integrating greedy technique and variable neighborhood search method to solve the problem. Extensive experiments under different scenarios were conducted, and results show that HGA outperforms CPLEX solver, providing solutions in realistic timescales.

  6. Stress Effects on Multiple Memory System Interactions

    OpenAIRE

    Ness, Deborah; Calabrese, Pasquale

    2016-01-01

    Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory syst...

  7. Novel applications of multitask learning and multiple output regression to multiple genetic trait prediction.

    Science.gov (United States)

    He, Dan; Kuhn, David; Parida, Laxmi

    2016-06-15

    Given a set of biallelic molecular markers, such as SNPs, with genotype values encoded numerically on a collection of plant, animal or human samples, the goal of genetic trait prediction is to predict the quantitative trait values by simultaneously modeling all marker effects. Genetic trait prediction is usually represented as linear regression models. In many cases, for the same set of samples and markers, multiple traits are observed. Some of these traits might be correlated with each other. Therefore, modeling all the multiple traits together may improve the prediction accuracy. In this work, we view the multitrait prediction problem from a machine learning angle: as either a multitask learning problem or a multiple output regression problem, depending on whether different traits share the same genotype matrix or not. We then adapted multitask learning algorithms and multiple output regression algorithms to solve the multitrait prediction problem. We proposed a few strategies to improve the least square error of the prediction from these algorithms. Our experiments show that modeling multiple traits together could improve the prediction accuracy for correlated traits. The programs we used are either public or directly from the referred authors, such as MALSAR (http://www.public.asu.edu/~jye02/Software/MALSAR/) package. The Avocado data set has not been published yet and is available upon request. dhe@us.ibm.com. © The Author 2016. Published by Oxford University Press.

  8. Mapping DNA damage-dependent genetic interactions in yeast via party mating and barcode fusion genetics.

    Science.gov (United States)

    Díaz-Mejía, J Javier; Celaj, Albi; Mellor, Joseph C; Coté, Atina; Balint, Attila; Ho, Brandon; Bansal, Pritpal; Shaeri, Fatemeh; Gebbia, Marinella; Weile, Jochen; Verby, Marta; Karkhanina, Anna; Zhang, YiFan; Wong, Cassandra; Rich, Justin; Prendergast, D'Arcy; Gupta, Gaurav; Öztürk, Sedide; Durocher, Daniel; Brown, Grant W; Roth, Frederick P

    2018-05-28

    Condition-dependent genetic interactions can reveal functional relationships between genes that are not evident under standard culture conditions. State-of-the-art yeast genetic interaction mapping, which relies on robotic manipulation of arrays of double-mutant strains, does not scale readily to multi-condition studies. Here, we describe barcode fusion genetics to map genetic interactions (BFG-GI), by which double-mutant strains generated via en masse "party" mating can also be monitored en masse for growth to detect genetic interactions. By using site-specific recombination to fuse two DNA barcodes, each representing a specific gene deletion, BFG-GI enables multiplexed quantitative tracking of double mutants via next-generation sequencing. We applied BFG-GI to a matrix of DNA repair genes under nine different conditions, including methyl methanesulfonate (MMS), 4-nitroquinoline 1-oxide (4NQO), bleomycin, zeocin, and three other DNA-damaging environments. BFG-GI recapitulated known genetic interactions and yielded new condition-dependent genetic interactions. We validated and further explored a subnetwork of condition-dependent genetic interactions involving MAG1 , SLX4, and genes encoding the Shu complex, and inferred that loss of the Shu complex leads to an increase in the activation of the checkpoint protein kinase Rad53. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

  9. [The multiple interactions between infertility and sexuality].

    Science.gov (United States)

    Mimoun, S

    1993-03-01

    After investigating into literature and clinical experience, we shall line out in this study 4 types of interactions between sexuality and infertility: sexual causes to feminine (vaginism, with and without heavy dyspareunia) or masculine (impotency, ante-portas ejaculation, anejaculation, dysejaculation), infertility; influence of tests and of treatments for infertility on sexual life; influence of infertility on sexuality focusing on the various ambiguous feelings (of culpability, inferiority, aggressivity, passivity); and last, the psychological and sexual interactions with medical assisted procreation, reinforcing the sexual separation of man and woman if the body is considered a machine. Psychosomatic guidance of the couple during these steps (with reassurance as the being helped conception) will allow maintaining on removing sexual attraction.

  10. Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy.

    Science.gov (United States)

    Simpson, Siobhan; Dunning, Mark D; Brownlie, Serena; Patel, Janika; Godden, Megan; Cobb, Malcolm; Mongan, Nigel P; Rutland, Catrin S

    2016-01-01

    Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH) is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM), yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH.

  11. Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Siobhan Simpson

    2016-01-01

    Full Text Available Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM, yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH.

  12. Genomic multiple sequence alignments: refinement using a genetic algorithm

    Directory of Open Access Journals (Sweden)

    Lefkowitz Elliot J

    2005-08-01

    Full Text Available Abstract Background Genomic sequence data cannot be fully appreciated in isolation. Comparative genomics – the practice of comparing genomic sequences from different species – plays an increasingly important role in understanding the genotypic differences between species that result in phenotypic differences as well as in revealing patterns of evolutionary relationships. One of the major challenges in comparative genomics is producing a high-quality alignment between two or more related genomic sequences. In recent years, a number of tools have been developed for aligning large genomic sequences. Most utilize heuristic strategies to identify a series of strong sequence similarities, which are then used as anchors to align the regions between the anchor points. The resulting alignment is globally correct, but in many cases is suboptimal locally. We describe a new program, GenAlignRefine, which improves the overall quality of global multiple alignments by using a genetic algorithm to improve local regions of alignment. Regions of low quality are identified, realigned using the program T-Coffee, and then refined using a genetic algorithm. Because a better COFFEE (Consistency based Objective Function For alignmEnt Evaluation score generally reflects greater alignment quality, the algorithm searches for an alignment that yields a better COFFEE score. To improve the intrinsic slowness of the genetic algorithm, GenAlignRefine was implemented as a parallel, cluster-based program. Results We tested the GenAlignRefine algorithm by running it on a Linux cluster to refine sequences from a simulation, as well as refine a multiple alignment of 15 Orthopoxvirus genomic sequences approximately 260,000 nucleotides in length that initially had been aligned by Multi-LAGAN. It took approximately 150 minutes for a 40-processor Linux cluster to optimize some 200 fuzzy (poorly aligned regions of the orthopoxvirus alignment. Overall sequence identity increased only

  13. Architecture for Multiple Interacting Robot Intelligences

    Science.gov (United States)

    Peters, Richard Alan, II (Inventor)

    2008-01-01

    An architecture for robot intelligence enables a robot to learn new behaviors and create new behavior sequences autonomously and interact with a dynamically changing environment. Sensory information is mapped onto a Sensory Ego-Sphere (SES) that rapidly identifies important changes in the environment and functions much like short term memory. Behaviors are stored in a database associative memory (DBAM) that creates an active map from the robot's current state to a goal state and functions much like long term memory. A dream state converts recent activities stored in the SES and creates or modifies behaviors in the DBAM.

  14. An Efficient Stepwise Statistical Test to Identify Multiple Linked Human Genetic Variants Associated with Specific Phenotypic Traits.

    Directory of Open Access Journals (Sweden)

    Iksoo Huh

    Full Text Available Recent advances in genotyping methodologies have allowed genome-wide association studies (GWAS to accurately identify genetic variants that associate with common or pathological complex traits. Although most GWAS have focused on associations with single genetic variants, joint identification of multiple genetic variants, and how they interact, is essential for understanding the genetic architecture of complex phenotypic traits. Here, we propose an efficient stepwise method based on the Cochran-Mantel-Haenszel test (for stratified categorical data to identify causal joint multiple genetic variants in GWAS. This method combines the CMH statistic with a stepwise procedure to detect multiple genetic variants associated with specific categorical traits, using a series of associated I × J contingency tables and a null hypothesis of no phenotype association. Through a new stratification scheme based on the sum of minor allele count criteria, we make the method more feasible for GWAS data having sample sizes of several thousands. We also examine the properties of the proposed stepwise method via simulation studies, and show that the stepwise CMH test performs better than other existing methods (e.g., logistic regression and detection of associations by Markov blanket for identifying multiple genetic variants. Finally, we apply the proposed approach to two genomic sequencing datasets to detect linked genetic variants associated with bipolar disorder and obesity, respectively.

  15. On coding genotypes for genetic markers with multiple alleles in genetic association study of quantitative traits

    Directory of Open Access Journals (Sweden)

    Wang Tao

    2011-09-01

    Full Text Available Abstract Background In genetic association study of quantitative traits using F∞ models, how to code the marker genotypes and interpret the model parameters appropriately is important for constructing hypothesis tests and making statistical inferences. Currently, the coding of marker genotypes in building F∞ models has mainly focused on the biallelic case. A thorough work on the coding of marker genotypes and interpretation of model parameters for F∞ models is needed especially for genetic markers with multiple alleles. Results In this study, we will formulate F∞ genetic models under various regression model frameworks and introduce three genotype coding schemes for genetic markers with multiple alleles. Starting from an allele-based modeling strategy, we first describe a regression framework to model the expected genotypic values at given markers. Then, as extension from the biallelic case, we introduce three coding schemes for constructing fully parameterized one-locus F∞ models and discuss the relationships between the model parameters and the expected genotypic values. Next, under a simplified modeling framework for the expected genotypic values, we consider several reduced one-locus F∞ models from the three coding schemes on the estimability and interpretation of their model parameters. Finally, we explore some extensions of the one-locus F∞ models to two loci. Several fully parameterized as well as reduced two-locus F∞ models are addressed. Conclusions The genotype coding schemes provide different ways to construct F∞ models for association testing of multi-allele genetic markers with quantitative traits. Which coding scheme should be applied depends on how convenient it can provide the statistical inferences on the parameters of our research interests. Based on these F∞ models, the standard regression model fitting tools can be used to estimate and test for various genetic effects through statistical contrasts with the

  16. The genetic interacting landscape of 63 candidate genes in Major Depressive Disorder: an explorative study.

    Science.gov (United States)

    Lekman, Magnus; Hössjer, Ola; Andrews, Peter; Källberg, Henrik; Uvehag, Daniel; Charney, Dennis; Manji, Husseini; Rush, John A; McMahon, Francis J; Moore, Jason H; Kockum, Ingrid

    2014-01-01

    Genetic contributions to major depressive disorder (MDD) are thought to result from multiple genes interacting with each other. Different procedures have been proposed to detect such interactions. Which approach is best for explaining the risk of developing disease is unclear. This study sought to elucidate the genetic interaction landscape in candidate genes for MDD by conducting a SNP-SNP interaction analysis using an exhaustive search through 3,704 SNP-markers in 1,732 cases and 1,783 controls provided from the GAIN MDD study. We used three different methods to detect interactions, two logistic regressions models (multiplicative and additive) and one data mining and machine learning (MDR) approach. Although none of the interaction survived correction for multiple comparisons, the results provide important information for future genetic interaction studies in complex disorders. Among the 0.5% most significant observations, none had been reported previously for risk to MDD. Within this group of interactions, less than 0.03% would have been detectable based on main effect approach or an a priori algorithm. We evaluated correlations among the three different models and conclude that all three algorithms detected the same interactions to a low degree. Although the top interactions had a surprisingly large effect size for MDD (e.g. additive dominant model Puncorrected = 9.10E-9 with attributable proportion (AP) value = 0.58 and multiplicative recessive model with Puncorrected = 6.95E-5 with odds ratio (OR estimated from β3) value = 4.99) the area under the curve (AUC) estimates were low (< 0.54). Moreover, the population attributable fraction (PAF) estimates were also low (< 0.15). We conclude that the top interactions on their own did not explain much of the genetic variance of MDD. The different statistical interaction methods we used in the present study did not identify the same pairs of interacting markers. Genetic interaction studies may uncover previously

  17. Genetic susceptibility factors for multiple chemical sensitivity revisited

    DEFF Research Database (Denmark)

    Berg, Nikolaj Drimer; Rasmussen, Henrik Berg; Linneberg, Allan

    2010-01-01

    of this study was to investigate genetic susceptibility factors for MCS and self-reported chemical sensitivity in a population sample. Ninety six MCS patients and 1,207 controls from a general population divided into four severity groups of chemical sensitivity were genotyped for variants in the genes encoding......Multiple chemical sensitivity (MCS) is characterised by adverse effects due to exposure to low levels of chemical substances. Various genes, especially genes of importance to the metabolism of xenobiotic compounds, have been associated with MCS, but findings are inconsistent. The purpose...... significant (OR=1.2, p=0.28). Fast arylamine N-acetyltransferase 2 metaboliser status was associated with severity of chemical sensitivity only in the most severely affected group in the population sample (OR=3.1, p=0.04). The cholecystokinin 2 receptor allele with 21 CT repeats was associated with MCS when...

  18. Genetic evidence of multiple loci in dystocia - difficult labour

    Directory of Open Access Journals (Sweden)

    Westgren Magnus

    2010-06-01

    Full Text Available Abstract Background Dystocia, difficult labour, is a common but also complex problem during childbirth. It can be attributed to either weak contractions of the uterus, a large infant, reduced capacity of the pelvis or combinations of these. Previous studies have indicated that there is a genetic component in the susceptibility of experiencing dystocia. The purpose of this study was to identify susceptibility genes in dystocia. Methods A total of 104 women in 47 families were included where at least two sisters had undergone caesarean section at a gestational length of 286 days or more at their first delivery. Study of medical records and a telephone interview was performed to identify subjects with dystocia. Whole-genome scanning using Affymetrix genotyping-arrays and non-parametric linkage (NPL analysis was made in 39 women exhibiting the phenotype of dystocia from 19 families. In 68 women re-sequencing was performed of candidate genes showing suggestive linkage: oxytocin (OXT on chromosome 20 and oxytocin-receptor (OXTR on chromosome 3. Results We found a trend towards linkage with suggestive NPL-score (3.15 on chromosome 12p12. Suggestive linkage peaks were observed on chromosomes 3, 4, 6, 10, 20. Re-sequencing of OXT and OXTR did not reveal any causal variants. Conclusions Dystocia is likely to have a genetic component with variations in multiple genes affecting the patient outcome. We found 6 loci that could be re-evaluated in larger patient cohorts.

  19. Genetic evidence of multiple loci in dystocia - difficult labour

    Science.gov (United States)

    2010-01-01

    Background Dystocia, difficult labour, is a common but also complex problem during childbirth. It can be attributed to either weak contractions of the uterus, a large infant, reduced capacity of the pelvis or combinations of these. Previous studies have indicated that there is a genetic component in the susceptibility of experiencing dystocia. The purpose of this study was to identify susceptibility genes in dystocia. Methods A total of 104 women in 47 families were included where at least two sisters had undergone caesarean section at a gestational length of 286 days or more at their first delivery. Study of medical records and a telephone interview was performed to identify subjects with dystocia. Whole-genome scanning using Affymetrix genotyping-arrays and non-parametric linkage (NPL) analysis was made in 39 women exhibiting the phenotype of dystocia from 19 families. In 68 women re-sequencing was performed of candidate genes showing suggestive linkage: oxytocin (OXT) on chromosome 20 and oxytocin-receptor (OXTR) on chromosome 3. Results We found a trend towards linkage with suggestive NPL-score (3.15) on chromosome 12p12. Suggestive linkage peaks were observed on chromosomes 3, 4, 6, 10, 20. Re-sequencing of OXT and OXTR did not reveal any causal variants. Conclusions Dystocia is likely to have a genetic component with variations in multiple genes affecting the patient outcome. We found 6 loci that could be re-evaluated in larger patient cohorts. PMID:20587075

  20. Genetic Allee effects and their interaction with ecological Allee effects.

    Science.gov (United States)

    Wittmann, Meike J; Stuis, Hanna; Metzler, Dirk

    2018-01-01

    It is now widely accepted that genetic processes such as inbreeding depression and loss of genetic variation can increase the extinction risk of small populations. However, it is generally unclear whether extinction risk from genetic causes gradually increases with decreasing population size or whether there is a sharp transition around a specific threshold population size. In the ecological literature, such threshold phenomena are called 'strong Allee effects' and they can arise for example from mate limitation in small populations. In this study, we aim to (i) develop a meaningful notion of a 'strong genetic Allee effect', (ii) explore whether and under what conditions such an effect can arise from inbreeding depression due to recessive deleterious mutations, and (iii) quantify the interaction of potential genetic Allee effects with the well-known mate-finding Allee effect. We define a strong genetic Allee effect as a genetic process that causes a population's survival probability to be a sigmoid function of its initial size. The inflection point of this function defines the critical population size. To characterize survival-probability curves, we develop and analyse simple stochastic models for the ecology and genetics of small populations. Our results indicate that inbreeding depression can indeed cause a strong genetic Allee effect, but only if individuals carry sufficiently many deleterious mutations (lethal equivalents). Populations suffering from a genetic Allee effect often first grow, then decline as inbreeding depression sets in and then potentially recover as deleterious mutations are purged. Critical population sizes of ecological and genetic Allee effects appear to be often additive, but even superadditive interactions are possible. Many published estimates for the number of lethal equivalents in birds and mammals fall in the parameter range where strong genetic Allee effects are expected. Unfortunately, extinction risk due to genetic Allee effects

  1. Impact of genetic risk loci for multiple sclerosis on expression of proximal genes in patients

    KAUST Repository

    James, Tojo; Lindé n, Magdalena; Morikawa, Hiromasa; Fernandes, Sunjay Jude; Ruhrmann, Sabrina; Huss, Mikael; Brandi, Maya; Piehl, Fredrik; Jagodic, Maja; Tegner, Jesper; Khademi, Mohsen; Olsson, Tomas; Gomez-Cabrero, David; Kockum, Ingrid

    2018-01-01

    Despite advancements in genetic studies, it is difficult to understand and characterize the functional relevance of disease-associated genetic variants, especially in the context of a complex multifactorial disease such as Multiple Sclerosis (MS

  2. Social interactions predict genetic diversification: an experimental manipulation in shorebirds.

    Science.gov (United States)

    Cunningham, Charles; Parra, Jorge E; Coals, Lucy; Beltrán, Marcela; Zefania, Sama; Székely, Tamás

    2018-01-01

    Mating strategy and social behavior influence gene flow and hence affect levels of genetic differentiation and potentially speciation. Previous genetic analyses of closely related plovers Charadrius spp. found strikingly different population genetic structure in Madagascar: Kittlitz's plovers are spatially homogenous whereas white-fronted plovers have well segregated and geographically distinct populations. Here, we test the hypotheses that Kittlitz's plovers are spatially interconnected and have extensive social interactions that facilitate gene flow, whereas white-fronted plovers are spatially discrete and have limited social interactions. By experimentally removing mates from breeding pairs and observing the movements of mate-searching plovers in both species, we compare the spatial behavior of Kittlitz's and white-fronted plovers within a breeding season. The behavior of experimental birds was largely consistent with expectations: Kittlitz's plovers travelled further, sought new mates in larger areas, and interacted with more individuals than white-fronted plovers, however there was no difference in breeding dispersal. These results suggest that mating strategies, through spatial behavior and social interactions, are predictors of gene flow and thus genetic differentiation and speciation. Our study highlights the importance of using social behavior to understand gene flow. However, further work is needed to investigate the relative importance of social structure, as well as intra- and inter-season dispersal, in influencing the genetic structures of populations.

  3. Evolutionary Dynamics of Tumor-Stroma Interactions in Multiple Myeloma.

    Directory of Open Access Journals (Sweden)

    Javad Salimi Sartakhti

    Full Text Available Cancer cells and stromal cells cooperate by exchanging diffusible factors that sustain tumor growth, a form of frequency-dependent selection that can be studied in the framework of evolutionary game theory. In the case of multiple myeloma, three types of cells (malignant plasma cells, osteoblasts and osteoclasts exchange growth factors with different effects, and tumor-stroma interactions have been analysed using a model of cooperation with pairwise interactions. Here we show that a model in which growth factors have autocrine and paracrine effects on multiple cells, a more realistic assumption for tumor-stroma interactions, leads to different results, with implications for disease progression and treatment. In particular, the model reveals that reducing the number of malignant plasma cells below a critical threshold can lead to their extinction and thus to restore a healthy balance between osteoclast and osteoblast, a result in line with current therapies against multiple myeloma.

  4. A knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility.

    Science.gov (United States)

    Bush, W S; McCauley, J L; DeJager, P L; Dudek, S M; Hafler, D A; Gibson, R A; Matthews, P M; Kappos, L; Naegelin, Y; Polman, C H; Hauser, S L; Oksenberg, J; Haines, J L; Ritchie, M D

    2011-07-01

    Gene-gene interactions are proposed as an important component of the genetic architecture of complex diseases, and are just beginning to be evaluated in the context of genome-wide association studies (GWAS). In addition to detecting epistasis, a benefit to interaction analysis is that it also increases power to detect weak main effects. We conducted a knowledge-driven interaction analysis of a GWAS of 931 multiple sclerosis (MS) trios to discover gene-gene interactions within established biological contexts. We identify heterogeneous signals, including a gene-gene interaction between CHRM3 (muscarinic cholinergic receptor 3) and MYLK (myosin light-chain kinase) (joint P=0.0002), an interaction between two phospholipase C-β isoforms, PLCβ1 and PLCβ4 (joint P=0.0098), and a modest interaction between ACTN1 (actinin alpha 1) and MYH9 (myosin heavy chain 9) (joint P=0.0326), all localized to calcium-signaled cytoskeletal regulation. Furthermore, we discover a main effect (joint P=5.2E-5) previously unidentified by single-locus analysis within another related gene, SCIN (scinderin), a calcium-binding cytoskeleton regulatory protein. This work illustrates that knowledge-driven interaction analysis of GWAS data is a feasible approach to identify new genetic effects. The results of this study are among the first gene-gene interactions and non-immune susceptibility loci for MS. Further, the implicated genes cluster within inter-related biological mechanisms that suggest a neurodegenerative component to MS.

  5. Genetic and infectious profiles of Japanese multiple sclerosis patients.

    Directory of Open Access Journals (Sweden)

    Satoshi Yoshimura

    Full Text Available BACKGROUND: Nationwide surveys conducted in Japan over the past thirty years have revealed a four-fold increase in the estimated number of multiple sclerosis (MS patients, a decrease in the age at onset, and successive increases in patients with conventional MS, which shows an involvement of multiple sites in the central nervous system, including the cerebrum and cerebellum. We aimed to clarify whether genetic and infectious backgrounds correlate to distinct disease phenotypes of MS in Japanese patients. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed HLA-DRB1 and -DPB1 alleles, and IgG antibodies specific for Helicobacter pylori, Chlamydia pneumoniae, varicella zoster virus, and Epstein-Barr virus nuclear antigen (EBNA in 145 MS patients and 367 healthy controls (HCs. Frequencies of DRB1*0405 and DPB1*0301 were significantly higher, and DRB1*0901 and DPB1*0401 significantly lower, in MS patients as compared with HCs. MS patients with DRB1*0405 had a significantly earlier age of onset and lower Progression Index than patients without this allele. The proportion and absolute number of patients with DRB1*0405 successively increased with advancing year of birth. In MS patients without DRB1*0405, the frequency of the DRB1*1501 allele was significantly higher, while the DRB1*0901 allele was significantly lower, compared with HCs. Furthermore, DRB1*0405-negative MS patients were significantly more likely to be positive for EBNA antibodies compared with HCs. CONCLUSIONS: Our study suggests that MS patients harboring DRB1*0405, a genetic risk factor for MS in the Japanese population, have a younger age at onset and a relatively benign disease course, while DRB1*0405-negative MS patients have features similar to Western-type MS in terms of association with Epstein-Barr virus infection and DRB1*1501. The recent increase of MS in young Japanese people may be caused, in part, by an increase in DRB1*0405-positive MS patients.

  6. Engineering genetic circuit interactions within and between synthetic minimal cells

    Science.gov (United States)

    Adamala, Katarzyna P.; Martin-Alarcon, Daniel A.; Guthrie-Honea, Katriona R.; Boyden, Edward S.

    2017-05-01

    Genetic circuits and reaction cascades are of great importance for synthetic biology, biochemistry and bioengineering. An open question is how to maximize the modularity of their design to enable the integration of different reaction networks and to optimize their scalability and flexibility. One option is encapsulation within liposomes, which enables chemical reactions to proceed in well-isolated environments. Here we adapt liposome encapsulation to enable the modular, controlled compartmentalization of genetic circuits and cascades. We demonstrate that it is possible to engineer genetic circuit-containing synthetic minimal cells (synells) to contain multiple-part genetic cascades, and that these cascades can be controlled by external signals as well as inter-liposomal communication without crosstalk. We also show that liposomes that contain different cascades can be fused in a controlled way so that the products of incompatible reactions can be brought together. Synells thus enable a more modular creation of synthetic biology cascades, an essential step towards their ultimate programmability.

  7. Bayesian network model for identification of pathways by integrating protein interaction with genetic interaction data.

    Science.gov (United States)

    Fu, Changhe; Deng, Su; Jin, Guangxu; Wang, Xinxin; Yu, Zu-Guo

    2017-09-21

    Molecular interaction data at proteomic and genetic levels provide physical and functional insights into a molecular biosystem and are helpful for the construction of pathway structures complementarily. Despite advances in inferring biological pathways using genetic interaction data, there still exists weakness in developed models, such as, activity pathway networks (APN), when integrating the data from proteomic and genetic levels. It is necessary to develop new methods to infer pathway structure by both of interaction data. We utilized probabilistic graphical model to develop a new method that integrates genetic interaction and protein interaction data and infers exquisitely detailed pathway structure. We modeled the pathway network as Bayesian network and applied this model to infer pathways for the coherent subsets of the global genetic interaction profiles, and the available data set of endoplasmic reticulum genes. The protein interaction data were derived from the BioGRID database. Our method can accurately reconstruct known cellular pathway structures, including SWR complex, ER-Associated Degradation (ERAD) pathway, N-Glycan biosynthesis pathway, Elongator complex, Retromer complex, and Urmylation pathway. By comparing N-Glycan biosynthesis pathway and Urmylation pathway identified from our approach with that from APN, we found that our method is able to overcome its weakness (certain edges are inexplicable). According to underlying protein interaction network, we defined a simple scoring function that only adopts genetic interaction information to avoid the balance difficulty in the APN. Using the effective stochastic simulation algorithm, the performance of our proposed method is significantly high. We developed a new method based on Bayesian network to infer detailed pathway structures from interaction data at proteomic and genetic levels. The results indicate that the developed method performs better in predicting signaling pathways than previously

  8. The genetic legacy of multiple beaver reintroductions in Central Europe.

    Science.gov (United States)

    Frosch, Christiane; Kraus, Robert H S; Angst, Christof; Allgöwer, Rainer; Michaux, Johan; Teubner, Jana; Nowak, Carsten

    2014-01-01

    The comeback of the Eurasian beaver (Castor fiber) throughout western and central Europe is considered a major conservation success. Traditionally, several subspecies are recognised by morphology and mitochondrial haplotype, each linked to a relict population. During various reintroduction programs in the 20th century, beavers from multiple source localities were released and now form viable populations. These programs differed in their reintroduction strategies, i.e., using pure subspecies vs. mixed source populations. This inhomogeneity in management actions generated ongoing debates regarding the origin of present beaver populations and appropriate management plans for the future. By sequencing of the mitochondrial control region and microsatellite genotyping of 235 beaver individuals from five selected regions in Germany, Switzerland, Luxembourg, and Belgium we show that beavers from at least four source origins currently form admixed, genetically diverse populations that spread across the study region. While regional occurrences of invasive North American beavers (n = 20) were found, all but one C. fiber bore the mitochondrial haplotype of the autochthonous western Evolutionary Significant Unit (ESU). Considering this, as well as the viability of admixed populations and the fact that the fusion of different lineages is already progressing in all studied regions, we argue that admixture between different beaver source populations should be generally accepted.

  9. Volatile terpenoids: multiple functions, biosynthesis, modulation and manipulation by genetic engineering.

    Science.gov (United States)

    Abbas, Farhat; Ke, Yanguo; Yu, Rangcai; Yue, Yuechong; Amanullah, Sikandar; Jahangir, Muhammad Muzammil; Fan, Yanping

    2017-11-01

    Terpenoids play several physiological and ecological functions in plant life through direct and indirect plant defenses and also in human society because of their enormous applications in the pharmaceutical, food and cosmetics industries. Through the aid of genetic engineering its role can by magnified to broad spectrum by improving genetic ability of crop plants, enhancing the aroma quality of fruits and flowers and the production of pharmaceutical terpenoids contents in medicinal plants. Terpenoids are structurally diverse and the most abundant plant secondary metabolites, playing an important role in plant life through direct and indirect plant defenses, by attracting pollinators and through different interactions between the plants and their environment. Terpenoids are also significant because of their enormous applications in the pharmaceutical, food and cosmetics industries. Due to their broad distribution and functional versatility, efforts are being made to decode the biosynthetic pathways and comprehend the regulatory mechanisms of terpenoids. This review summarizes the recent advances in biosynthetic pathways, including the spatiotemporal, transcriptional and post-transcriptional regulatory mechanisms. Moreover, we discuss the multiple functions of the terpene synthase genes (TPS), their interaction with the surrounding environment and the use of genetic engineering for terpenoid production in model plants. Here, we also provide an overview of the significance of terpenoid metabolic engineering in crop protection, plant reproduction and plant metabolic engineering approaches for pharmaceutical terpenoids production and future scenarios in agriculture, which call for sustainable production platforms by improving different plant traits.

  10. A Simple Interactive Introduction to Teaching Genetic Engineering

    Science.gov (United States)

    Child, Paula

    2013-01-01

    In the UK, at key stage 4, students aged 14-15 studying GCSE Core Science or Unit 1 of the GCSE Biology course are required to be able to describe the process of genetic engineering to produce bacteria that can produce insulin. The simple interactive introduction described in this article allows students to consider the problem, devise a model and…

  11. Evidence for multiple stressor interactions and effects on coral reefs.

    Science.gov (United States)

    Ban, Stephen S; Graham, Nicholas A J; Connolly, Sean R

    2014-03-01

    Concern is growing about the potential effects of interacting multiple stressors, especially as the global climate changes. We provide a comprehensive review of multiple stressor interactions in coral reef ecosystems, which are widely considered to be one of the most sensitive ecosystems to global change. First, we synthesized coral reef studies that examined interactions of two or more stressors, highlighting stressor interactions (where one stressor directly influences another) and potentially synergistic effects on response variables (where two stressors interact to produce an effect that is greater than purely additive). For stressor-stressor interactions, we found 176 studies that examined at least 2 of the 13 stressors of interest. Applying network analysis to analyze relationships between stressors, we found that pathogens were exacerbated by more costressors than any other stressor, with ca. 78% of studies reporting an enhancing effect by another stressor. Sedimentation, storms, and water temperature directly affected the largest number of other stressors. Pathogens, nutrients, and crown-of-thorns starfish were the most-influenced stressors. We found 187 studies that examined the effects of two or more stressors on a third dependent variable. The interaction of irradiance and temperature on corals has been the subject of more research (62 studies, 33% of the total) than any other combination of stressors, with many studies reporting a synergistic effect on coral symbiont photosynthetic performance (n = 19). Second, we performed a quantitative meta-analysis of existing literature on this most-studied interaction (irradiance and temperature). We found that the mean effect size of combined treatments was statistically indistinguishable from a purely additive interaction, although it should be noted that the sample size was relatively small (n = 26). Overall, although in aggregate a large body of literature examines stressor effects on coral reefs and coral

  12. Multiple parton interactions in photoproduction at HERA/H1

    Energy Technology Data Exchange (ETDEWEB)

    Magro, Lluis Marti

    2009-02-15

    Photoproduction data of HERA-I are analysed by requiring dijets with transverse momenta of at least 5 GeV. The two jets define in azimuth a towards region (leading jet), an away region (usually the 2nd jet) and transverse regions between them. The charged particle and jet with low transverse momentum multiplicity, so called minijets, are measured in these regions as a function of the variables x{sup obs}{sub {gamma}} and P{sup Jet{sub 1T}} (leading jet). The measurement is compared to predictions including parton showers and matrix elements at leading order in {alpha}{sub s}. Some predictions include contributions from multiple parton interactions and use different parton evolution equations. It was found that existing MC programs do not fully describe the measurements but the description can be improved by including multiple parton interactions. (orig.)

  13. THE MULTIPLE CHOICE PROBLEM WITH INTERACTIONS BETWEEN CRITERIA

    Directory of Open Access Journals (Sweden)

    Luiz Flavio Autran Monteiro Gomes

    2015-12-01

    Full Text Available ABSTRACT An important problem in Multi-Criteria Decision Analysis arises when one must select at least two alternatives at the same time. This can be denoted as a multiple choice problem. In other words, instead of evaluating each of the alternatives separately, they must be combined into groups of n alternatives, where n = 2. When the multiple choice problem must be solved under multiple criteria, the result is a multi-criteria, multiple choice problem. In this paper, it is shown through examples how this problemcan be tackled on a bipolar scale. The Choquet integral is used in this paper to take care of interactions between criteria. A numerical application example is conducted using data from SEBRAE-RJ, a non-profit private organization that has the mission of promoting competitiveness, sustainable developmentand entrepreneurship in the state of Rio de Janeiro, Brazil. The paper closes with suggestions for future research.

  14. Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    A. Dessa Sadovnick

    2016-07-01

    Full Text Available Multiple sclerosis (MS is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D in plasminogen (PLG as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351 in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117, despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87. To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.

  15. Hereditary multiple exostoses: from genetics to clinical syndrome and complications

    Energy Technology Data Exchange (ETDEWEB)

    Vanhoenacker, Filip M.; Hul, Wim van; Wuyts, Wim; Willems, P.J.; Schepper, Arthur M. de

    2001-12-01

    Objective: To give an overview of genetic, clinical and radiological aspects in two families over four generations with known hereditary multiple exostoses (HME). Methods and material: After linkage analysis in both families to localize the defective gene, mutation analysis was performed in these genes to identify the underlying mutation. In the 31 affected individuals, location, number and morphology and evolution of exostosis, evolution of remodeling defects at the metaphysis, and the extent of possible complications were evaluated on clinical and imaging (plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI)) data over a lifetime period. Results and conclusions: Both families demonstrate the gene defect in the same EXT-2 gene locus on chromosome 11p. Exostoses are preferentially located in the lower extremity (hip, knee and lower leg), humerus, and forearm. Any other bone may be involved, except for the calvaria of the skull and the mandible. Exostoses are rather sessile than pedunculated. Exostosis is rarely present at birth but develops gradually and may persist to grow slowly after closure of the growth plates. Preferential expression of the remodeling defect was seen in the hip, distal femur (trumpet-shaped metaphysis) and forearm (shortening of the ulna with secondary bowing of the radius and development of a pseudo-Madelung deformity). These radiological manifestations start at the age of 4-5 years and become more obvious as the enchondral bone formation progresses with age. Reported complications in these families consist of local entrapment phenomenons (vessel, tendon, nerve), frictional bursitis, and sarcomatous transformation. MRI was able to suggest these complications and is the imaging technique of choice in the evaluation of symptomatic exostoses.

  16. Hereditary multiple exostoses: from genetics to clinical syndrome and complications

    International Nuclear Information System (INIS)

    Vanhoenacker, Filip M.; Hul, Wim van; Wuyts, Wim; Willems, P.J.; Schepper, Arthur M. de

    2001-01-01

    Objective: To give an overview of genetic, clinical and radiological aspects in two families over four generations with known hereditary multiple exostoses (HME). Methods and material: After linkage analysis in both families to localize the defective gene, mutation analysis was performed in these genes to identify the underlying mutation. In the 31 affected individuals, location, number and morphology and evolution of exostosis, evolution of remodeling defects at the metaphysis, and the extent of possible complications were evaluated on clinical and imaging (plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI)) data over a lifetime period. Results and conclusions: Both families demonstrate the gene defect in the same EXT-2 gene locus on chromosome 11p. Exostoses are preferentially located in the lower extremity (hip, knee and lower leg), humerus, and forearm. Any other bone may be involved, except for the calvaria of the skull and the mandible. Exostoses are rather sessile than pedunculated. Exostosis is rarely present at birth but develops gradually and may persist to grow slowly after closure of the growth plates. Preferential expression of the remodeling defect was seen in the hip, distal femur (trumpet-shaped metaphysis) and forearm (shortening of the ulna with secondary bowing of the radius and development of a pseudo-Madelung deformity). These radiological manifestations start at the age of 4-5 years and become more obvious as the enchondral bone formation progresses with age. Reported complications in these families consist of local entrapment phenomenons (vessel, tendon, nerve), frictional bursitis, and sarcomatous transformation. MRI was able to suggest these complications and is the imaging technique of choice in the evaluation of symptomatic exostoses

  17. Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients

    Science.gov (United States)

    Sadovnick, A. Dessa; Traboulsee, Anthony L.; Bernales, Cecily Q.; Ross, Jay P.; Forwell, Amanda L.; Yee, Irene M.; Guillot-Noel, Lena; Fontaine, Bertrand; Cournu-Rebeix, Isabelle; Alcina, Antonio; Fedetz, Maria; Izquierdo, Guillermo; Matesanz, Fuencisla; Hilven, Kelly; Dubois, Bénédicte; Goris, An; Astobiza, Ianire; Alloza, Iraide; Antigüedad, Alfredo; Vandenbroeck, Koen; Akkad, Denis A.; Aktas, Orhan; Blaschke, Paul; Buttmann, Mathias; Chan, Andrew; Epplen, Joerg T.; Gerdes, Lisa-Ann; Kroner, Antje; Kubisch, Christian; Kümpfel, Tania; Lohse, Peter; Rieckmann, Peter; Zettl, Uwe K.; Zipp, Frauke; Bertram, Lars; Lill, Christina M; Fernandez, Oscar; Urbaneja, Patricia; Leyva, Laura; Alvarez-Cermeño, Jose Carlos; Arroyo, Rafael; Garagorri, Aroa M.; García-Martínez, Angel; Villar, Luisa M.; Urcelay, Elena; Malhotra, Sunny; Montalban, Xavier; Comabella, Manuel; Berger, Thomas; Fazekas, Franz; Reindl, Markus; Schmied, Mascha C.; Zimprich, Alexander; Vilariño-Güell, Carles

    2016-01-01

    Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility. PMID:27194806

  18. CRISPR genetic screens to discover host-virus interactions.

    Science.gov (United States)

    McDougall, William M; Perreira, Jill M; Reynolds, Erin C; Brass, Abraham L

    2018-04-01

    Viruses impose an immense burden on human health. With the goal of treating and preventing viral infections, researchers have carried out genetic screens to improve our understanding of viral dependencies and identify potential anti-viral strategies. The emergence of CRISPR genetic screening tools has facilitated this effort by enabling host-virus screens to be undertaken in a more versatile and fidelitous manner than previously possible. Here we review the growing number of CRISPR screens which continue to increase our understanding of host-virus interactions. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Functional genetics of intraspecific ecological interactions in Arabidopsis thaliana.

    Science.gov (United States)

    Wolf, Jason B; Mutic, Joshua J; Kover, Paula X

    2011-05-12

    Studying the genetic basis of traits involved in ecological interactions is a fundamental part of elucidating the connections between evolutionary and ecological processes. Such knowledge allows one to link genetic models of trait evolution with ecological models describing interactions within and between species. Previous work has shown that connections between genetic and ecological processes in Arabidopsis thaliana may be mediated by the fact that quantitative trait loci (QTL) with 'direct' effects on traits of individuals also have pleiotropic 'indirect' effects on traits expressed in neighbouring plants. Here, we further explore these connections by examining functional relationships between traits affected directly and indirectly by the same QTL. We develop a novel approach using structural equation models (SEMs) to determine whether observed pleiotropic effects result from traits directly affected by the QTL in focal individuals causing the changes in the neighbours' phenotypes. This hypothesis was assessed using SEMs to test whether focal plant phenotypes appear to mediate the connection between the focal plants' genotypes and the phenotypes of their neighbours, or alternatively, whether the connection between the focal plants' genotypes and the neighbours' phenotypes is mediated by unmeasured traits. We implement this analysis using a QTL of major effect that maps to the well-characterized flowering locus, FRIGIDA. The SEMs support the hypothesis that the pleiotropic indirect effects of this locus arise from size and developmental timing-related traits in focal plants affecting the expression of developmental traits in their neighbours. Our findings provide empirical insights into the genetics and nature of intraspecific ecological interactions. Our technique holds promise in directing future work into the genetic basis and functional relationship of traits mediating and responding to ecological interactions.

  20. Huntingtin interacting proteins are genetic modifiers of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Linda S Kaltenbach

    2007-05-01

    Full Text Available Huntington's disease (HD is a fatal neurodegenerative condition caused by expansion of the polyglutamine tract in the huntingtin (Htt protein. Neuronal toxicity in HD is thought to be, at least in part, a consequence of protein interactions involving mutant Htt. We therefore hypothesized that genetic modifiers of HD neurodegeneration should be enriched among Htt protein interactors. To test this idea, we identified a comprehensive set of Htt interactors using two complementary approaches: high-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs. We then tested an arbitrary set of 60 genes encoding interacting proteins for their ability to behave as genetic modifiers of neurodegeneration in a Drosophila model of HD. This high-content validation assay showed that 27 of 60 orthologs tested were high-confidence genetic modifiers, as modification was observed with more than one allele. The 45% hit rate for genetic modifiers seen among the interactors is an order of magnitude higher than the 1%-4% typically observed in unbiased genetic screens. Genetic modifiers were similarly represented among proteins discovered using yeast two-hybrid and pull-down/mass spectrometry methods, supporting the notion that these complementary technologies are equally useful in identifying biologically relevant proteins. Interacting proteins confirmed as modifiers of the neurodegeneration phenotype represent a diverse array of biological functions, including synaptic transmission, cytoskeletal organization, signal transduction, and transcription. Among the modifiers were 17 loss-of-function suppressors of neurodegeneration, which can be considered potential targets for therapeutic intervention. Finally, we show that seven interacting proteins from among 11 tested were able to

  1. Mean multiplicity of secondary particles in hadron-nuclear interactions

    International Nuclear Information System (INIS)

    Alaverdyan, G.B.; Pak, A.S.

    1980-01-01

    The mean multiplicity of secondary particles in hA interactions is examined in the framework of the multiplex scattering theory. The dependence of the secondary particle multiplicity coefficient Rsub(6)=anti nsub(hA)/anti nsub(hN) (where anti nsub(hA) and anti nsub(hN) are mean multiplicities of secondary relativistic particles in hA and hN interactions, respectively) on the energy and type of incident particles and atomic number of a target nucleus is analysed. It is shown that predictions of the leading particle cascade model are in satisfactory agreement with the experimental data if the uncertainties of the inelasticity in hN interactions are taken into account. The value Rsub(A) weakly depends both on the incident particle energy and the form of parametrization anti nsub(hN)(E). Allowance of energy losses fluctuation of leading particle results in the Rsub(A) value decrease. From the model of leading particles it does not follow that Rsub(a) strictly depends on the type of incident particles at the fixed value of mean number of collisions. But quantitative values of Rsub(A) for different types of particles and at one value of anti ν, (i.e. at properly chosen value) coincide. The value of Rsub(A) is profoundly dependent on the values of inelasticity factor in hN interactions

  2. Multiplicity distributions in high-energy neutrino interactions

    International Nuclear Information System (INIS)

    Chapman, J.W.; Coffin, C.T.; Diamond, R.N.; French, H.; Louis, W.; Roe, B.P.; Seidl, A.A.; Vander Velde, J.C.; Berge, J.P.; Bogert, D.V.; DiBianca, F.A.; Cundy, D.C.; Dunaitsev, A.; Efremenko, V.; Ermolov, P.; Fowler, W.; Hanft, R.; Harigel, G.; Huson, F.R.; Kolganov, V.; Mukhin, A.; Nezrick, F.A.; Rjabov, Y.; Scott, W.G.; Smart, W.

    1976-01-01

    Results from the Fermilab 15-ft bubble chamber on the charged-particle multiplicity distributions produced in high-energy charged-current neutrino-proton interactions are presented. Comparisons are made to γp, ep, μp, and inclusive pp scattering. The mean hadronic multiplicity appears to depend only on the mass of the excited hadronic state, independent of the mode of excitation. A fit to the neutrino data gives = (1.09+-0.38) +(1.09+-0.03)lnW 2

  3. Interaction dynamics of multiple mobile robots with simple navigation strategies

    Science.gov (United States)

    Wang, P. K. C.

    1989-01-01

    The global dynamic behavior of multiple interacting autonomous mobile robots with simple navigation strategies is studied. Here, the effective spatial domain of each robot is taken to be a closed ball about its mass center. It is assumed that each robot has a specified cone of visibility such that interaction with other robots takes place only when they enter its visibility cone. Based on a particle model for the robots, various simple homing and collision-avoidance navigation strategies are derived. Then, an analysis of the dynamical behavior of the interacting robots in unbounded spatial domains is made. The article concludes with the results of computer simulations studies of two or more interacting robots.

  4. Predictive value of testing for multiple genetic variants in multifactorial

    NARCIS (Netherlands)

    A.C.J.W. Janssens (Cécile); M.J. Khoury (Muin Joseph)

    2009-01-01

    textabstractMultifactorial diseases such as type 2 diabetes, osteoporosis, and cardiovascular disease are caused by a complex interplay of many genetic and nongenetic factors, each of which conveys a minor increase in the risk of disease. Unraveling the genetic origins of these diseases is

  5. Interactive Visualization of DGA Data Based on Multiple Views

    Science.gov (United States)

    Geng, Yujie; Lin, Ying; Ma, Yan; Guo, Zhihong; Gu, Chao; Wang, Mingtao

    2017-01-01

    The commission and operation of dissolved gas analysis (DGA) online monitoring makes up for the weakness of traditional DGA method. However, volume and high-dimensional DGA data brings a huge challenge for monitoring and analysis. In this paper, we present a novel interactive visualization model of DGA data based on multiple views. This model imitates multi-angle analysis by combining parallel coordinates, scatter plot matrix and data table. By offering brush, collaborative filter and focus + context technology, this model provides a convenient and flexible interactive way to analyze and understand the DGA data.

  6. Pareto-Zipf law in growing systems with multiplicative interactions

    Science.gov (United States)

    Ohtsuki, Toshiya; Tanimoto, Satoshi; Sekiyama, Makoto; Fujihara, Akihiro; Yamamoto, Hiroshi

    2018-06-01

    Numerical simulations of multiplicatively interacting stochastic processes with weighted selections were conducted. A feedback mechanism to control the weight w of selections was proposed. It becomes evident that when w is moderately controlled around 0, such systems spontaneously exhibit the Pareto-Zipf distribution. The simulation results are universal in the sense that microscopic details, such as parameter values and the type of control and weight, are irrelevant. The central ingredient of the Pareto-Zipf law is argued to be the mild control of interactions.

  7. Estimation in a multiplicative mixed model involving a genetic relationship matrix

    Directory of Open Access Journals (Sweden)

    Eccleston John A

    2009-04-01

    Full Text Available Abstract Genetic models partitioning additive and non-additive genetic effects for populations tested in replicated multi-environment trials (METs in a plant breeding program have recently been presented in the literature. For these data, the variance model involves the direct product of a large numerator relationship matrix A, and a complex structure for the genotype by environment interaction effects, generally of a factor analytic (FA form. With MET data, we expect a high correlation in genotype rankings between environments, leading to non-positive definite covariance matrices. Estimation methods for reduced rank models have been derived for the FA formulation with independent genotypes, and we employ these estimation methods for the more complex case involving the numerator relationship matrix. We examine the performance of differing genetic models for MET data with an embedded pedigree structure, and consider the magnitude of the non-additive variance. The capacity of existing software packages to fit these complex models is largely due to the use of the sparse matrix methodology and the average information algorithm. Here, we present an extension to the standard formulation necessary for estimation with a factor analytic structure across multiple environments.

  8. Neurofibromatosis type 1 and multiple sclerosis: Genetically related ...

    African Journals Online (AJOL)

    Solaf M. Elsayed

    2016-10-25

    Oct 25, 2016 ... a Genetics Unit, Children's Hospital, Ain Shams University, Egypt b Neurology Department ... Through the past 6 months, she started to develop short term memory loss with intact long term memory. There was no other motor ...

  9. Multiple-trait genetic evaluation using genomic matrix

    African Journals Online (AJOL)

    Jane

    2011-07-06

    Jul 6, 2011 ... relationships was estimated through computer simulation and was compared with the accuracy of ... programs, detect animals with superior genetic and select ... genomic matrices in the mixed model equations of BLUP.

  10. Population genetic diversity and fitness in multiple environments

    Directory of Open Access Journals (Sweden)

    McGreevy Thomas J

    2010-07-01

    Full Text Available Abstract Background When a large number of alleles are lost from a population, increases in individual homozygosity may reduce individual fitness through inbreeding depression. Modest losses of allelic diversity may also negatively impact long-term population viability by reducing the capacity of populations to adapt to altered environments. However, it is not clear how much genetic diversity within populations may be lost before populations are put at significant risk. Development of tools to evaluate this relationship would be a valuable contribution to conservation biology. To address these issues, we have created an experimental system that uses laboratory populations of an estuarine crustacean, Americamysis bahia with experimentally manipulated levels of genetic diversity. We created replicate cultures with five distinct levels of genetic diversity and monitored them for 16 weeks in both permissive (ambient seawater and stressful conditions (diluted seawater. The relationship between molecular genetic diversity at presumptive neutral loci and population vulnerability was assessed by AFLP analysis. Results Populations with very low genetic diversity demonstrated reduced fitness relative to high diversity populations even under permissive conditions. Population performance decreased in the stressful environment for all levels of genetic diversity relative to performance in the permissive environment. Twenty percent of the lowest diversity populations went extinct before the end of the study in permissive conditions, whereas 73% of the low diversity lines went extinct in the stressful environment. All high genetic diversity populations persisted for the duration of the study, although population sizes and reproduction were reduced under stressful environmental conditions. Levels of fitness varied more among replicate low diversity populations than among replicate populations with high genetic diversity. There was a significant correlation

  11. Genetics of simple and complex host-parasite interactions

    International Nuclear Information System (INIS)

    Sidhu, G.S.; Webster, J.M.

    1977-01-01

    In nature a host plant can be viewed as a miniature replica of an ecological system where true and incidental parasites share the same habitat. Consequently, they influence each other's presence directly by interspecific interaction, and indirectly by inducing changes in the host's physiology and so form disease complexes. Since all physiological phenomena have their counterpart in the respective genetic systems of interacting organisms, valuable genetic information can be derived from the analysis of complex parasitic systems. Disease complexes may be classified according to the nature of interaction between various parasites on the same host. One parasite may nullify the host's resistance to another (e.g. Tomato - Meloidogyne incognita + Fusarium oxysporum lycopersici system). Conversely, a parasite may invoke resistance in the host against another parasite (e.g. Tomato - Fusarium oxysporum lycopersici + Verticillium albo atrum system). From the study of simple parasitic systems we know that resistance versus susceptibility against a single parasite is normally monogenically controlled. However, when more than one parasite interacts to invoke or nullify each other's responses on the same host plant, the genetic results suggest epistatic ratios. Nevertheless, epistatic ratios have been obtained also from simple parasitic systems owing to gene interaction. The epistatic ratios obtained from complex and simple parasitic systems are contrasted and compared. It is suggested that epistatic ratios obtained from simple parasitic systems may, in fact, be artifacts resulting from complex parasitic associations that often occur in nature. Polygenic inheritance and the longevity of a cultivar is also discussed briefly in relation to complex parasitic associations. Induced mutations can play a significant role in the study of complex parasitic associations, and thus can be very useful in controlling plant diseases

  12. Obesity interacts with infectious mononucleosis in risk of multiple sclerosis.

    Science.gov (United States)

    Hedström, A K; Lima Bomfim, I; Hillert, J; Olsson, T; Alfredsson, L

    2015-03-01

    The possible interaction between adolescent obesity and past infectious mononucleosis (IM) was investigated with regard to multiple sclerosis (MS) risk. This report is based on two population-based case-control studies, one with incident cases (1780 cases, 3885 controls) and one with prevalent cases (4502 cases, 4039 controls). Subjects were categorized based on adolescent body mass index (BMI) and past IM and compared with regard to occurrence of MS by calculating odds ratios with 95% confidence intervals (CIs) employing logistic regression. A potential interaction between adolescent BMI and past IM was evaluated by calculating the attributable proportion due to interaction. Regardless of human leukocyte antigen (HLA) status, a substantial interaction was observed between adolescent obesity and past IM with regard to MS risk. The interaction was most evident when IM after the age of 10 was considered (attributable proportion due to interaction 0.8, 95% CI 0.6-1.0 in the incident study, and attributable proportion due to interaction 0.7, 95% CI 0.5-1.0 in the prevalent study). In the incident study, the odds ratio of MS was 14.7 (95% CI 5.9-36.6) amongst subjects with adolescent obesity and past IM after the age of 10, compared with subjects with none of these exposures. The corresponding odds ratio in the prevalent study was 13.2 (95% CI 5.2-33.6). An obese state both impacts the cellular immune response to infections and induces a state of chronic immune-mediated inflammation which may contribute to explain our finding of an interaction between adolescent BMI and past IM. Measures taken against adolescent obesity may thus be a preventive strategy against MS. © 2014 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

  13. A review for detecting gene-gene interactions using machine learning methods in genetic epidemiology.

    Science.gov (United States)

    Koo, Ching Lee; Liew, Mei Jing; Mohamad, Mohd Saberi; Salleh, Abdul Hakim Mohamed

    2013-01-01

    Recently, the greatest statistical computational challenge in genetic epidemiology is to identify and characterize the genes that interact with other genes and environment factors that bring the effect on complex multifactorial disease. These gene-gene interactions are also denoted as epitasis in which this phenomenon cannot be solved by traditional statistical method due to the high dimensionality of the data and the occurrence of multiple polymorphism. Hence, there are several machine learning methods to solve such problems by identifying such susceptibility gene which are neural networks (NNs), support vector machine (SVM), and random forests (RFs) in such common and multifactorial disease. This paper gives an overview on machine learning methods, describing the methodology of each machine learning methods and its application in detecting gene-gene and gene-environment interactions. Lastly, this paper discussed each machine learning method and presents the strengths and weaknesses of each machine learning method in detecting gene-gene interactions in complex human disease.

  14. The interaction between multiple bubbles and the free surface

    International Nuclear Information System (INIS)

    Zhang Aman; Yao Xiongliang

    2008-01-01

    The flow is assumed to be potential, and a boundary integral method is used to solve the Laplace equation for the velocity potential to investigate the shape and the position of the bubble. A 3D code to study the bubble dynamics is developed, and the calculation results agree well with the experimental data. Numerical analyses are carried out for the interaction between multiple bubbles near the free surface including in-phase and out-of-phase bubbles. The calculation result shows that the bubble period increases with the decrease of the distance between bubble centres because of the depression effect between multiple bubbles. The depression has no relationship with the free surface and it is more apparent for out-of-phase bubbles. There are great differences in dynamic behaviour between the in-phase bubbles and the out-of-phase bubbles due to the depression effect. Furthermore, the interaction among eight bubbles is simulated with a three-dimensional model, and the evolving process and the relevant physical phenomena are presented. These phenomena can give a reference to the future work on the power of bubbles induced by multiple charges exploding simultaneously or continuously

  15. Identification of genetic components involved in Lotus-endophyte interactions

    DEFF Research Database (Denmark)

    Zgadzaj, Rafal Lukasz

    of growth hormones or nitrogen fixation. However, the genes involved in plant-endophyte interactions and bacterial accomodation within plant tissues are not known. In order to shed some light on such processes, an approach “one host-one endophyte” was chosen. The focus on a single plant species and a single......Endophytes are microorganisms capable of colonising plant tissues without inducing host defense responses. They have a large impact on plants, since they can modulate plant responses to pathogens, herbivores and environmental stress. They can also induce plant growth promotion through synthesis...... bacterial strain aimed at obtaining a reliable and easy to handle system for plant-microsymbiont interaction research. Two different methods were tested for their usefulness in identification of genetic components involved in plant-endophyte interactions. The first method was based on measuring growth...

  16. [Application of Multiple Genetic Markers in a Case of Determination of Half Sibling].

    Science.gov (United States)

    Yang, Xue; Shi, Mei-sen; Yuan, Li; Lu, Di

    2016-02-01

    A case of half sibling was determined with multiple genetic markers, which could be potentially applied for determination of half sibling relationship from same father. Half sibling relationship was detected by 39 autosomal STR genetic markers, 23 Y-chromosomal STR genetic markers and 12 X -chromosomal STR genetic markers among ZHAO -1, ZHAO -2, ZHAO -3, ZHAO -4, and ZHAO-5. According to autosomal STR, Y-STR and X-STR genotyping results, it was determined that ZHAO-4 (alleged half sibling) was unrelated with ZHAO-1 and ZHAO-2; however, ZHAO-3 (alleged half sibling), ZHAO-5 (alleged half sibling) shared same genetic profile with ZHAO-1, and ZHAO-2 from same father. It is reliable to use multiple genetic markers and family gene reconstruction to determine half sibling relationship from same father, but it is difficult to determination by calculating half sibling index with ITO and discriminant functions.

  17. Genetic diagnosis of a Chinese multiple endocrine neoplasia type ...

    Indian Academy of Sciences (India)

    However, different families with MEN 2A due to the same RET mutation often have significant variability inthe clinical exhibition of disease and aggressiveness of the MTC, which implies additional genetic loci exsit beyondRET coding region. Whole genome sequencing (WGS) greatly expands the breadth of screening from ...

  18. Use of multiple genetic markers in prediction of breeding values.

    NARCIS (Netherlands)

    Arendonk, van J.A.M.; Tier, B.; Kinghorn, B.P.

    1994-01-01

    Genotypes at a marker locus give information on transmission of genes from parents to offspring and that information can be used in predicting the individuals' additive genetic value at a linked quantitative trait locus (MQTL). In this paper a recursive method is presented to build the gametic

  19. Genetics Home Reference: Noonan syndrome with multiple lentigines

    Science.gov (United States)

    ... of Noonan syndrome with multiple lentigines include brown skin spots called lentigines that are similar to freckles, heart ... individuals may have thousands of small dark brown skin spots by the time they reach puberty. Unlike freckles, ...

  20. Parallel Beam-Beam Simulation Incorporating Multiple Bunches and Multiple Interaction Regions

    CERN Document Server

    Jones, F W; Pieloni, T

    2007-01-01

    The simulation code COMBI has been developed to enable the study of coherent beam-beam effects in the full collision scenario of the LHC, with multiple bunches interacting at multiple crossing points over many turns. The program structure and input are conceived in a general way which allows arbitrary numbers and placements of bunches and interaction points (IP's), together with procedural options for head-on and parasitic collisions (in the strong-strong sense), beam transport, statistics gathering, harmonic analysis, and periodic output of simulation data. The scale of this problem, once we go beyond the simplest case of a pair of bunches interacting once per turn, quickly escalates into the parallel computing arena, and herein we will describe the construction of an MPI-based version of COMBI able to utilize arbitrary numbers of processors to support efficient calculation of multi-bunch multi-IP interactions and transport. Implementing the parallel version did not require extensive disruption of the basic ...

  1. Interaction of multiple biomimetic antimicrobial polymers with model bacterial membranes

    Energy Technology Data Exchange (ETDEWEB)

    Baul, Upayan, E-mail: upayanb@imsc.res.in; Vemparala, Satyavani, E-mail: vani@imsc.res.in [The Institute of Mathematical Sciences, C.I.T. Campus, Taramani, Chennai 600113 (India); Kuroda, Kenichi, E-mail: kkuroda@umich.edu [Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109 (United States)

    2014-08-28

    Using atomistic molecular dynamics simulations, interaction of multiple synthetic random copolymers based on methacrylates on prototypical bacterial membranes is investigated. The simulations show that the cationic polymers form a micellar aggregate in water phase and the aggregate, when interacting with the bacterial membrane, induces clustering of oppositely charged anionic lipid molecules to form clusters and enhances ordering of lipid chains. The model bacterial membrane, consequently, develops lateral inhomogeneity in membrane thickness profile compared to polymer-free system. The individual polymers in the aggregate are released into the bacterial membrane in a phased manner and the simulations suggest that the most probable location of the partitioned polymers is near the 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) clusters. The partitioned polymers preferentially adopt facially amphiphilic conformations at lipid-water interface, despite lacking intrinsic secondary structures such as α-helix or β-sheet found in naturally occurring antimicrobial peptides.

  2. Electron-electron interaction in Multiple Quantum Wells

    Science.gov (United States)

    Zybert, M.; Marchewka, M.; Tomaka, G.; Sheregii, E. M.

    2012-07-01

    The complex investigation of the magneto-transport effects in structures containing multiple quantum well (MQWs) based on the GaAs/AlGaAs-heterostructures has been performed. The MQWs investigated have different electron densities in QWs. The parameters of 2DEG in MQWs were determined from the data of the Integer Quantum Hall Effect (IQHE) and Shubnikov-de Haas oscillations (SdH) observed at low temperatures (0.6-4.2 K). The method of calculation of the electron states energies in MQWs has been developed which is based on the splitting of these states due to the exchange interaction (SAS-splitting, see D. Płoch et al., Phys. Rev. B 79 (2009) 195434) including the screening of this interaction. The IQHE and SdH observed in these multilayer structures with the third degree of freedom for electrons are interpreted from this.

  3. Genetic Interactions of STAT3 and Anticancer Drug Development

    International Nuclear Information System (INIS)

    Fang, Bingliang

    2014-01-01

    Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors

  4. The genetics of childhood obesity and interaction with dietary macronutrients.

    Science.gov (United States)

    Garver, William S; Newman, Sara B; Gonzales-Pacheco, Diana M; Castillo, Joseph J; Jelinek, David; Heidenreich, Randall A; Orlando, Robert A

    2013-05-01

    The genes contributing to childhood obesity are categorized into three different types based on distinct genetic and phenotypic characteristics. These types of childhood obesity are represented by rare monogenic forms of syndromic or non-syndromic childhood obesity, and common polygenic childhood obesity. In some cases, genetic susceptibility to these forms of childhood obesity may result from different variations of the same gene. Although the prevalence for rare monogenic forms of childhood obesity has not increased in recent times, the prevalence of common childhood obesity has increased in the United States and developing countries throughout the world during the past few decades. A number of recent genome-wide association studies and mouse model studies have established the identification of susceptibility genes contributing to common childhood obesity. Accumulating evidence suggests that this type of childhood obesity represents a complex metabolic disease resulting from an interaction with environmental factors, including dietary macronutrients. The objective of this article is to provide a review on the origins, mechanisms, and health consequences of obesity susceptibility genes and interaction with dietary macronutrients that predispose to childhood obesity. It is proposed that increased knowledge of these obesity susceptibility genes and interaction with dietary macronutrients will provide valuable insight for individual, family, and community preventative lifestyle intervention, and eventually targeted nutritional and medicinal therapies.

  5. Beyond clinical utility: The multiple values of DTC genetics

    Directory of Open Access Journals (Sweden)

    Mauro Turrini

    2016-03-01

    Full Text Available One point of consensus in the otherwise very controversial discussion about the benefits and dangers of DTC genetics in the health domain is the lack of substantial clinical utility. At the same time, both the empirical and conceptual literature indicate that health-related DTC tests can have value and utility outside of the clinic. We argue that a broader and multi-faceted conceptualization of utility and value would enrich the ethical and social discussion of DTC testing in several ways: First, looking at ways in which DTC testing can have personal and social value for users – in the form of entertainment, learning, or a way to relate to others – can help to explain why people still take DTC tests, and will, further down the line, foster a more nuanced understanding of secondary and tertiary uses of DTC test results (which could very well unearth new ethical and regulatory challenges. Second, considering the economic value and broader utility of DTC testing foregrounds wider social and political aspects than have been dominant in the ethical and regulatory debates surrounding DTC genetics so far. These wider political aspects include the profound power asymmetries that characterize the collection and use of personal genetic data in many contexts.

  6. Characterizing Male–Female Interactions Using Natural Genetic Variation in Drosophila melanogaster

    Science.gov (United States)

    Reinhart, Michael; Carney, Tara; Clark, Andrew G.

    2015-01-01

    Drosophila melanogaster females commonly mate with multiple males establishing the opportunity for pre- and postcopulatory sexual selection. Traits impacting sexual selection can be affected by a complex interplay of the genotypes of the competing males, the genotype of the female, and compatibilities between the males and females. We scored males from 96 2nd and 94 3rd chromosome substitution lines for traits affecting reproductive success when mated with females from 3 different genetic backgrounds. The traits included male-induced female refractoriness, male remating ability, the proportion of offspring sired under competitive conditions and male-induced female fecundity. We observed significant effects of male line, female genetic background, and strong male by female interactions. Some males appeared to be “generalists” and performed consistently across the different females; other males appeared to be “specialists” and performed very well with a particular female and poorly with others. “Specialist” males did not, however, prefer to court those females with whom they had the highest reproductive fitness. Using 143 polymorphisms in male reproductive genes, we mapped several genes that had consistent effects across the different females including a derived, high fitness allele in Acp26Aa that may be the target of adaptive evolution. We also identified a polymorphism upstream of PebII that may interact with the female genetic background to affect male-induced refractoriness to remating. These results suggest that natural variation in PebII might contribute to the observed male–female interactions. PMID:25425680

  7. Neurofibromatosis type 1 and multiple sclerosis: Genetically related ...

    African Journals Online (AJOL)

    Neurofibromatosis type I (NF1) is an autosomal dominant disorder with involvement of both the cutaneous and nervous systems. Patients are susceptible to neurological complication in the form of tumors of the brain and spinal cord. Multiple sclerosis (MS) is a chronic autoimmune disease that affects the myelinated axons ...

  8. New Genetic Insights and Therapy in Multiple Myeloma

    NARCIS (Netherlands)

    K.L. Wu

    2007-01-01

    textabstractIn the last decade, several significant advances in myeloma therapy have occurred with the pace of change accelerated with the introduction of new anti-myeloma agents. The approach to the treatment of multiple myeloma has become more complex with an array of therapeutic options,

  9. Multiple Epiphyseal Dysplasia: A Clinical and Molecular Genetic Study

    NARCIS (Netherlands)

    J.B.A. van Mourik (Jan)

    1998-01-01

    textabstractMultiple epiphyseal dysplasia (MED) is one of the most common osteochondrodysplasias [Wynne-Davies and Gormley 1985]. During childhood and adolescence it affects the epiphyses of the tubular bones, resulting in axial deformities and shorter limbs.·Later in life MED can lead to

  10. Multiple Syntrophic Interactions in a Terephthalate-Degrading Methanogenic Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Lykidis, Athanasios; Chen, Chia-Lung; Tringe, Susannah G.; McHardy, Alice C.; Copeland, Alex 5; Kyrpides, Nikos C.; Hugenholtz, Philip; Liu, Wen-Tso

    2010-08-05

    Terephthalate (TA) is one of the top 50 chemicals produced worldwide. Its production results in a TA-containing wastewater that is treated by anaerobic processes through a poorly understood methanogenic syntrophy. Using metagenomics, we characterized the methanogenic consortium tinside a hyper-mesophilic (i.e., between mesophilic and thermophilic), TA-degrading bioreactor. We identified genes belonging to dominant Pelotomaculum species presumably involved in TA degradation through decarboxylation, dearomatization, and modified ?-oxidation to H{sub 2}/CO{sub 2} and acetate. These intermediates are converted to CH{sub 4}/CO{sub 2} by three novel hyper-mesophilic methanogens. Additional secondary syntrophic interactions were predicted in Thermotogae, Syntrophus and candidate phyla OP5 and WWE1 populations. The OP5 encodes genes capable of anaerobic autotrophic butyrate production and Thermotogae, Syntrophus and WWE1 have the genetic potential to oxidize butyrate to COsub 2}/H{sub 2} and acetate. These observations suggest that the TA-degrading consortium consists of additional syntrophic interactions beyond the standard H{sub 2}-producing syntroph ? methanogen partnership that may serve to improve community stability.

  11. Genetic interactions between neurofibromin and endothelin receptor B in mice.

    Directory of Open Access Journals (Sweden)

    Mugdha Deo

    Full Text Available When mutations in two different genes produce the same mutant phenotype, it suggests that the encoded proteins either interact with each other, or act in parallel to fulfill a similar purpose. Haploinsufficiency of Neurofibromin and over-expression of Endothelin 3 both cause increased numbers of melanocytes to populate the dermis during mouse development, and thus we are interested in how these two signaling pathways might intersect. Neurofibromin is mutated in the human genetic disease, neurofibromatosis type 1, which is characterized by the development of Schwann cell based tumors and skin hyper-pigmentation. Neurofibromin is a GTPase activating protein, while the Endothelin 3 ligand activates Endothelin receptor B, a G protein coupled receptor. In order to study the genetic interactions between endothelin and neurofibromin, we defined the deletion breakpoints of the classical Ednrb piebald lethal allele (Ednrb(s-l and crossed these mice to mice with a loss-of-function mutation in neurofibromin, Dark skin 9 (Dsk9. We found that Neurofibromin haploinsufficiency requires Endothelin receptor B to darken the tail dermis. In contrast, Neurofibromin haploinsufficiency increases the area of the coat that is pigmented in Endothelin receptor B null mice. We also found an oncogenic mutation in the G protein alpha subunit, GNAQ, which couples to Endothelin receptor B, in a uveal melanoma from a patient with neurofibromatosis type 1. Thus, this data suggests that there is a complex relationship between Neurofibromin and Endothelin receptor B.

  12. Analysis and application of opinion model with multiple topic interactions.

    Science.gov (United States)

    Xiong, Fei; Liu, Yun; Wang, Liang; Wang, Ximeng

    2017-08-01

    To reveal heterogeneous behaviors of opinion evolution in different scenarios, we propose an opinion model with topic interactions. Individual opinions and topic features are represented by a multidimensional vector. We measure an agent's action towards a specific topic by the product of opinion and topic feature. When pairs of agents interact for a topic, their actions are introduced to opinion updates with bounded confidence. Simulation results show that a transition from a disordered state to a consensus state occurs at a critical point of the tolerance threshold, which depends on the opinion dimension. The critical point increases as the dimension of opinions increases. Multiple topics promote opinion interactions and lead to the formation of macroscopic opinion clusters. In addition, more topics accelerate the evolutionary process and weaken the effect of network topology. We use two sets of large-scale real data to evaluate the model, and the results prove its effectiveness in characterizing a real evolutionary process. Our model achieves high performance in individual action prediction and even outperforms state-of-the-art methods. Meanwhile, our model has much smaller computational complexity. This paper provides a demonstration for possible practical applications of theoretical opinion dynamics.

  13. MSAViewer: interactive JavaScript visualization of multiple sequence alignments.

    Science.gov (United States)

    Yachdav, Guy; Wilzbach, Sebastian; Rauscher, Benedikt; Sheridan, Robert; Sillitoe, Ian; Procter, James; Lewis, Suzanna E; Rost, Burkhard; Goldberg, Tatyana

    2016-11-15

    The MSAViewer is a quick and easy visualization and analysis JavaScript component for Multiple Sequence Alignment data of any size. Core features include interactive navigation through the alignment, application of popular color schemes, sorting, selecting and filtering. The MSAViewer is 'web ready': written entirely in JavaScript, compatible with modern web browsers and does not require any specialized software. The MSAViewer is part of the BioJS collection of components. The MSAViewer is released as open source software under the Boost Software License 1.0. Documentation, source code and the viewer are available at http://msa.biojs.net/Supplementary information: Supplementary data are available at Bioinformatics online. msa@bio.sh. © The Author 2016. Published by Oxford University Press.

  14. Mapping the genetic basis of symbiotic variation in legume-rhizobium interactions in Medicago truncatula.

    Science.gov (United States)

    Gorton, Amanda J; Heath, Katy D; Pilet-Nayel, Marie-Laure; Baranger, Alain; Stinchcombe, John R

    2012-11-01

    Mutualisms are known to be genetically variable, where the genotypes differ in the fitness benefits they gain from the interaction. To date, little is known about the loci that underlie such genetic variation in fitness or whether the loci influencing fitness are partner specific, and depend on the genotype of the interaction partner. In the legume-rhizobium mutualism, one set of potential candidate genes that may influence the fitness benefits of the symbiosis are the plant genes involved in the initiation of the signaling pathway between the two partners. Here we performed quantitative trait loci (QTL) mapping in Medicago truncatula in two different rhizobium strain treatments to locate regions of the genome influencing plant traits, assess whether such regions are dependent on the genotype of the rhizobial mutualist (QTL × rhizobium strain), and evaluate the contribution of sequence variation at known symbiosis signaling genes. Two of the symbiotic signaling genes, NFP and DMI3, colocalized with two QTL affecting average fruit weight and leaf number, suggesting that natural variation in nodulation genes may potentially influence plant fitness. In both rhizobium strain treatments, there were QTL that influenced multiple traits, indicative of either tight linkage between loci or pleiotropy, including one QTL with opposing effects on growth and reproduction. There was no evidence for QTL × rhizobium strain or genotype × genotype interactions, suggesting either that such interactions are due to small-effect loci or that more genotype-genotype combinations need to be tested in future mapping studies.

  15. Pooled-matrix protein interaction screens using Barcode Fusion Genetics.

    Science.gov (United States)

    Yachie, Nozomu; Petsalaki, Evangelia; Mellor, Joseph C; Weile, Jochen; Jacob, Yves; Verby, Marta; Ozturk, Sedide B; Li, Siyang; Cote, Atina G; Mosca, Roberto; Knapp, Jennifer J; Ko, Minjeong; Yu, Analyn; Gebbia, Marinella; Sahni, Nidhi; Yi, Song; Tyagi, Tanya; Sheykhkarimli, Dayag; Roth, Jonathan F; Wong, Cassandra; Musa, Louai; Snider, Jamie; Liu, Yi-Chun; Yu, Haiyuan; Braun, Pascal; Stagljar, Igor; Hao, Tong; Calderwood, Michael A; Pelletier, Laurence; Aloy, Patrick; Hill, David E; Vidal, Marc; Roth, Frederick P

    2016-04-22

    High-throughput binary protein interaction mapping is continuing to extend our understanding of cellular function and disease mechanisms. However, we remain one or two orders of magnitude away from a complete interaction map for humans and other major model organisms. Completion will require screening at substantially larger scales with many complementary assays, requiring further efficiency gains in proteome-scale interaction mapping. Here, we report Barcode Fusion Genetics-Yeast Two-Hybrid (BFG-Y2H), by which a full matrix of protein pairs can be screened in a single multiplexed strain pool. BFG-Y2H uses Cre recombination to fuse DNA barcodes from distinct plasmids, generating chimeric protein-pair barcodes that can be quantified via next-generation sequencing. We applied BFG-Y2H to four different matrices ranging in scale from ~25 K to 2.5 M protein pairs. The results show that BFG-Y2H increases the efficiency of protein matrix screening, with quality that is on par with state-of-the-art Y2H methods. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  16. Considering Interactions among Multiple Criteria for the Server Selection

    Directory of Open Access Journals (Sweden)

    Vesna Čančer

    2010-06-01

    Full Text Available Decision-making about server selection is one of the multi-criteria decision-making (MCDM processes where interactions among criteria should be considered. The paper introduces and develops some solutions for considering interactions among criteria in the MCDM problems. In the frame procedure for MCDM by using the group of methods, based on assigning weights, special attention is given to the synthesis of the local alternatives’ values into the aggregate values where the mutual preferential independence between two criteria is not assumed. Firstly, we delineate how to complete the additive model into the multiplicative one with synergic and redundancy elements in the case that criteria are structured in one level and in two levels. Furthermore, we adapted the concept of the fuzzy Choquet integral to the multi-attribute value theory. Studying and comparing the results of the example case of the server selection obtained by both aggregation approaches, the paper highlights the advantages of the first one since it does not require from decision makers to determine the weights of all possible combinations of the criteria and it enables the further use of the most preferred MCDM methods.

  17. An Advanced N -body Model for Interacting Multiple Stellar Systems

    Energy Technology Data Exchange (ETDEWEB)

    Brož, Miroslav [Astronomical Institute of the Charles University, Faculty of Mathematics and Physics, V Holešovičkách 2, CZ-18000 Praha 8 (Czech Republic)

    2017-06-01

    We construct an advanced model for interacting multiple stellar systems in which we compute all trajectories with a numerical N -body integrator, namely the Bulirsch–Stoer from the SWIFT package. We can then derive various observables: astrometric positions, radial velocities, minima timings (TTVs), eclipse durations, interferometric visibilities, closure phases, synthetic spectra, spectral energy distribution, and even complete light curves. We use a modified version of the Wilson–Devinney code for the latter, in which the instantaneous true phase and inclination of the eclipsing binary are governed by the N -body integration. If all of these types of observations are at one’s disposal, a joint χ {sup 2} metric and an optimization algorithm (a simplex or simulated annealing) allow one to search for a global minimum and construct very robust models of stellar systems. At the same time, our N -body model is free from artifacts that may arise if mutual gravitational interactions among all components are not self-consistently accounted for. Finally, we present a number of examples showing dynamical effects that can be studied with our code and we discuss how systematic errors may affect the results (and how to prevent this from happening).

  18. Genetic interactions between planar cell polarity genes cause diverse neural tube defects in mice

    Directory of Open Access Journals (Sweden)

    Jennifer N. Murdoch

    2014-10-01

    Full Text Available Neural tube defects (NTDs are among the commonest and most severe forms of developmental defect, characterized by disruption of the early embryonic events of central nervous system formation. NTDs have long been known to exhibit a strong genetic dependence, yet the identity of the genetic determinants remains largely undiscovered. Initiation of neural tube closure is disrupted in mice homozygous for mutations in planar cell polarity (PCP pathway genes, providing a strong link between NTDs and PCP signaling. Recently, missense gene variants have been identified in PCP genes in humans with NTDs, although the range of phenotypes is greater than in the mouse mutants. In addition, the sequence variants detected in affected humans are heterozygous, and can often be detected in unaffected individuals. It has been suggested that interactions between multiple heterozygous gene mutations cause the NTDs in humans. To determine the phenotypes produced in double heterozygotes, we bred mice with all three pairwise combinations of Vangl2Lp, ScribCrc and Celsr1Crsh mutations, the most intensively studied PCP mutants. The majority of double-mutant embryos had open NTDs, with the range of phenotypes including anencephaly and spina bifida, therefore reflecting the defects observed in humans. Strikingly, even on a uniform genetic background, variability in the penetrance and severity of the mutant phenotypes was observed between the different double-heterozygote combinations. Phenotypically, Celsr1Crsh;Vangl2Lp;ScribCrc triply heterozygous mutants were no more severe than doubly heterozygous or singly homozygous mutants. We propose that some of the variation between double-mutant phenotypes could be attributed to the nature of the protein disruption in each allele: whereas ScribCrc is a null mutant and produces no Scrib protein, Celsr1Crsh and Vangl2Lp homozygotes both express mutant proteins, consistent with dominant effects. The variable outcomes of these genetic

  19. Genetic and environmental factors interact to influence anxiety.

    Science.gov (United States)

    Gross, Cornelius; Hen, René

    2004-01-01

    Both genetic and environmental factors influence normal anxiety traits as well as anxiety disorders. In addition it is becoming increasingly clear that these factors interact to produce specific anxiety-related behaviors. For example, in humans and in monkeys mutations in the gene encoding for the serotonin transporter result in increased anxiety in adult life when combined with a stressful environment during development. Another recent example comes from twin studies suggesting that a small hippocampus can be a predisposing condition that renders individuals susceptible to post traumatic stress disorder. Such examples illustrate how specific mutations leading to abnormal brain development may increase vulnerability to environmental insults which may in turn lead to specific anxiety disorders.

  20. Identifying Interacting Genetic Variations by Fish-Swarm Logic Regression

    Science.gov (United States)

    Yang, Aiyuan; Yan, Chunxia; Zhu, Feng; Zhao, Zhongmeng; Cao, Zhi

    2013-01-01

    Understanding associations between genotypes and complex traits is a fundamental problem in human genetics. A major open problem in mapping phenotypes is that of identifying a set of interacting genetic variants, which might contribute to complex traits. Logic regression (LR) is a powerful multivariant association tool. Several LR-based approaches have been successfully applied to different datasets. However, these approaches are not adequate with regard to accuracy and efficiency. In this paper, we propose a new LR-based approach, called fish-swarm logic regression (FSLR), which improves the logic regression process by incorporating swarm optimization. In our approach, a school of fish agents are conducted in parallel. Each fish agent holds a regression model, while the school searches for better models through various preset behaviors. A swarm algorithm improves the accuracy and the efficiency by speeding up the convergence and preventing it from dropping into local optimums. We apply our approach on a real screening dataset and a series of simulation scenarios. Compared to three existing LR-based approaches, our approach outperforms them by having lower type I and type II error rates, being able to identify more preset causal sites, and performing at faster speeds. PMID:23984382

  1. Identifying Interacting Genetic Variations by Fish-Swarm Logic Regression

    Directory of Open Access Journals (Sweden)

    Xuanping Zhang

    2013-01-01

    Full Text Available Understanding associations between genotypes and complex traits is a fundamental problem in human genetics. A major open problem in mapping phenotypes is that of identifying a set of interacting genetic variants, which might contribute to complex traits. Logic regression (LR is a powerful multivariant association tool. Several LR-based approaches have been successfully applied to different datasets. However, these approaches are not adequate with regard to accuracy and efficiency. In this paper, we propose a new LR-based approach, called fish-swarm logic regression (FSLR, which improves the logic regression process by incorporating swarm optimization. In our approach, a school of fish agents are conducted in parallel. Each fish agent holds a regression model, while the school searches for better models through various preset behaviors. A swarm algorithm improves the accuracy and the efficiency by speeding up the convergence and preventing it from dropping into local optimums. We apply our approach on a real screening dataset and a series of simulation scenarios. Compared to three existing LR-based approaches, our approach outperforms them by having lower type I and type II error rates, being able to identify more preset causal sites, and performing at faster speeds.

  2. SLiM 2: Flexible, Interactive Forward Genetic Simulations.

    Science.gov (United States)

    Haller, Benjamin C; Messer, Philipp W

    2017-01-01

    Modern population genomic datasets hold immense promise for revealing the evolutionary processes operating in natural populations, but a crucial prerequisite for this goal is the ability to model realistic evolutionary scenarios and predict their expected patterns in genomic data. To that end, we present SLiM 2: an evolutionary simulation framework that combines a powerful, fast engine for forward population genetic simulations with the capability of modeling a wide variety of complex evolutionary scenarios. SLiM achieves this flexibility through scriptability, which provides control over most aspects of the simulated evolutionary scenarios with a simple R-like scripting language called Eidos. An example SLiM simulation is presented to illustrate the power of this approach. SLiM 2 also includes a graphical user interface for simulation construction, interactive runtime control, and dynamic visualization of simulation output, facilitating easy and fast model development with quick prototyping and visual debugging. We conclude with a performance comparison between SLiM and two other popular forward genetic simulation packages. © The Author 2016. 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.

  3. Restless legs syndrome in Czech patients with multiple sclerosis: An epidemiological and genetic study

    Czech Academy of Sciences Publication Activity Database

    Vávrová, J.; Kemlink, D.; Šonka, K.; Havrdová, E.; Horáková, D.; Pardini, Barbara; Müller-Myhsok, B.; Winkelmann, J.

    2012-01-01

    Roč. 13, č. 7 (2012), s. 848-851 ISSN 1389-9457 R&D Projects: GA MZd NR8563 Grant - others:GA ČR(CZ) GD309/08/H079; GA MZd(CZ) NT12141 Institutional research plan: CEZ:AV0Z50390512 Keywords : Secondary restless legs syndrome * Multiple sclerosis * Genetic association study Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.487, year: 2012

  4. Interactive Genetic Algorithm - An Adaptive and Interactive Decision Support Framework for Design of Optimal Groundwater Monitoring Plans

    Science.gov (United States)

    Babbar-Sebens, M.; Minsker, B. S.

    2006-12-01

    In the water resources management field, decision making encompasses many kinds of engineering, social, and economic constraints and objectives. Representing all of these problem dependant criteria through models (analytical or numerical) and various formulations (e.g., objectives, constraints, etc.) within an optimization- simulation system can be a very non-trivial issue. Most models and formulations utilized for discerning desirable traits in a solution can only approximate the decision maker's (DM) true preference criteria, and they often fail to consider important qualitative and incomputable phenomena related to the management problem. In our research, we have proposed novel decision support frameworks that allow DMs to actively participate in the optimization process. The DMs explicitly indicate their true preferences based on their subjective criteria and the results of various simulation models and formulations. The feedback from the DMs is then used to guide the search process towards solutions that are "all-rounders" from the perspective of the DM. The two main research questions explored in this work are: a) Does interaction between the optimization algorithm and a DM assist the system in searching for groundwater monitoring designs that are robust from the DM's perspective?, and b) How can an interactive search process be made more effective when human factors, such as human fatigue and cognitive learning processes, affect the performance of the algorithm? The application of these frameworks on a real-world groundwater long-term monitoring (LTM) case study in Michigan highlighted the following salient advantages: a) in contrast to the non-interactive optimization methodology, the proposed interactive frameworks were able to identify low cost monitoring designs whose interpolation maps respected the expected spatial distribution of the contaminants, b) for many same-cost designs, the interactive methodologies were able to propose multiple alternatives

  5. Population genetics of the Eastern Hellbender (Cryptobranchus alleganiensis alleganiensis across multiple spatial scales.

    Directory of Open Access Journals (Sweden)

    Shem D Unger

    Full Text Available Conservation genetics is a powerful tool to assess the population structure of species and provides a framework for informing management of freshwater ecosystems. As lotic habitats become fragmented, the need to assess gene flow for species of conservation management becomes a priority. The eastern hellbender (Cryptobranchus alleganiensis alleganiensis is a large, fully aquatic paedamorphic salamander. Many populations are experiencing declines throughout their geographic range, yet the genetic ramifications of these declines are currently unknown. To this end, we examined levels of genetic variation and genetic structure at both range-wide and drainage (hierarchical scales. We collected 1,203 individuals from 77 rivers throughout nine states from June 2007 to August 2011. Levels of genetic diversity were relatively high among all sampling locations. We detected significant genetic structure across populations (Fst values ranged from 0.001 between rivers within a single watershed to 0.218 between states. We identified two genetically differentiated groups at the range-wide scale: 1 the Ohio River drainage and 2 the Tennessee River drainage. An analysis of molecular variance (AMOVA based on landscape-scale sampling of basins within the Tennessee River drainage revealed the majority of genetic variation (∼94-98% occurs within rivers. Eastern hellbenders show a strong pattern of isolation by stream distance (IBSD at the drainage level. Understanding levels of genetic variation and differentiation at multiple spatial and biological scales will enable natural resource managers to make more informed decisions and plan effective conservation strategies for cryptic, lotic species.

  6. Interactions between Meteorus pulchricornis and Spodoptera exigua multiple nucleopolyhedrovirus.

    Science.gov (United States)

    Guo, Hui-Fang; Fang, Ji-Chao; Zhong, Wan-Fang; Liu, Bao-Sheng

    2013-01-01

    Baculoviruses may interact with parasitoids in the same host. A previous study has shown that infection of larvae with Spodoptera litura nucleopolyhedrovirus (SpltNPV) was deleterious to the survival and development of Meteorus pulchricornis (Wesmael) (Hymenoptera: Braconidae). In this paper, the interactions between M. pulchricornis and Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) in Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae), a permissive host of the virus and parasitoid, were investigated. The results showed that the effect of M. pulchricornis on SeMNPV and the effect of the virus on the parasitoid both depended on the concentration of the virus and the interval between viral infection and parasitism. Whether S. exigua was treated with the parasitoid and virus simultaneously or 1 day apart, the biological activities of 10(5), 10(6), and 10(7) OBs/mL SeMNPV were all significantly improved by M. pulchricornis. In contrast, the biological activity of 10(3) OBs/mL SeMNPV was significantly decreased when the host was exposed to the virus and parasitoid simultaneously. Regarding the impact of SeMNPV on M. pulchricornis, exposing the host to the parasitoid and SeMNPV with concentrations lower than 10(6) occlusion bodies (OBs)/mL produced no negative effects on the parasitoid. The results also showed that ingestion of SeMNPV by adult stage M. pulchricornis significantly increased the number of parasitoid offspring that successfully emerged from the host. Furthermore, M. pulchricornis was found to transmit SeMNPV among populations of S. exigua. Taken together, these findings indicate that M. pulchricornis integrated with an appropriate concentration of SeMNPV has the potential to improve the efficacy of biological control against S. exigua.

  7. Multiple Wins, Multiple Organizations—How to Manage Institutional Interaction in Financing Forest Landscape Restoration (FLR

    Directory of Open Access Journals (Sweden)

    Astrid Carrapatoso

    2018-03-01

    Full Text Available By restoring forest ecosystems and fostering resilient and sustainable land use practices, Forest Landscape Restoration (FLR contributes to climate change mitigation, adaptation and sustainable development as well as the protection of biological diversity and combating desertification. This integrative approach provides the opportunity for multiple wins, but it necessitates the management of complex institutional interactions arising from the involvement of multiple international organizations. Focusing on the pivotal aspect of financing, this article surveys the landscape of public international institutions supporting FLR and analyzes the effectiveness of existing mechanisms of inter-institutional coordination and harmonization. Methodologically, our research is based on a document analysis, complemented by participant observation of the two Bonn Climate Change Conferences in May and November 2017 as well as the Global Landscapes Forum in December 2017. We find that financial institutions have established fairly effective rules for the management of positive and negative externalities through the introduction of co-benefits and safeguards. The fact that each institution has their own safeguards provisions, however, leads to significant transaction costs for recipient countries. In the discussion, we thus recommend that institutions should refrain from an unnecessary duplication of standards and focus on best practice.

  8. Optimizing Sparse Matrix-Multiple Vectors Multiplication for Nuclear Configuration Interaction Calculations

    Energy Technology Data Exchange (ETDEWEB)

    Aktulga, Hasan Metin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Buluc, Aydin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Williams, Samuel [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Yang, Chao [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-08-14

    Obtaining highly accurate predictions on the properties of light atomic nuclei using the configuration interaction (CI) approach requires computing a few extremal Eigen pairs of the many-body nuclear Hamiltonian matrix. In the Many-body Fermion Dynamics for nuclei (MFDn) code, a block Eigen solver is used for this purpose. Due to the large size of the sparse matrices involved, a significant fraction of the time spent on the Eigen value computations is associated with the multiplication of a sparse matrix (and the transpose of that matrix) with multiple vectors (SpMM and SpMM-T). Existing implementations of SpMM and SpMM-T significantly underperform expectations. Thus, in this paper, we present and analyze optimized implementations of SpMM and SpMM-T. We base our implementation on the compressed sparse blocks (CSB) matrix format and target systems with multi-core architectures. We develop a performance model that allows us to understand and estimate the performance characteristics of our SpMM kernel implementations, and demonstrate the efficiency of our implementation on a series of real-world matrices extracted from MFDn. In particular, we obtain 3-4 speedup on the requisite operations over good implementations based on the commonly used compressed sparse row (CSR) matrix format. The improvements in the SpMM kernel suggest we may attain roughly a 40% speed up in the overall execution time of the block Eigen solver used in MFDn.

  9. A global genetic interaction network maps a wiring diagram of cellular function.

    Science.gov (United States)

    Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D; Pelechano, Vicent; Styles, Erin B; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F; Li, Sheena C; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; San Luis, Bryan-Joseph; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M; Moore, Claire L; Rosebrock, Adam P; Caudy, Amy A; Myers, Chad L; Andrews, Brenda; Boone, Charles

    2016-09-23

    We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and about 350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. Copyright © 2016, American Association for the Advancement of Science.

  10. Thymocyte migration: an affair of multiple cellular interactions?

    Directory of Open Access Journals (Sweden)

    Savino W.

    2003-01-01

    Full Text Available Cell migration is a crucial event in the general process of thymocyte differentiation. The cellular interactions involved in the control of this migration are beginning to be defined. At least chemokines and extracellular matrix proteins appear to be part of the game. Cells of the thymic microenvironment produce these two groups of molecules, whereas developing thymocytes express the corresponding receptors. Moreover, although chemokines and extracellular matrix can drive thymocyte migration per se, a combined role for these molecules appears to contribute to the resulting migration patterns of thymocytes in their various stages of differentiation. The dynamics of chemokine and extracellular matrix production and degradation is not yet well understood. However, matrix metalloproteinases are likely to play a role in the breakdown of intrathymic extracellular matrix contents. Thus, the physiological migration of thymocytes should be envisioned as a resulting vector of multiple, simultaneous and/or sequential stimuli involving chemokines, adhesive and de-adhesive extracellular matrix proteins, as well as matrix metalloproteinases. Accordingly, it is conceivable that any pathological change in any of these loops may result in the alteration of normal thymocyte migration. This seems to be the case in murine infection by the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas' disease. A better knowledge of the physiological mechanisms governing thymocyte migration will provide new clues for designing therapeutic strategies targeting developing T cells.

  11. The effect of multiple paternity on genetic diversity of small populations during and after colonisation.

    Directory of Open Access Journals (Sweden)

    Marina Rafajlović

    Full Text Available Genetic variation within and among populations is influenced by the genetic content of the founders and the migrants following establishment. This is particularly true if populations are small, migration rate low and habitats arranged in a stepping-stone fashion. Under these circumstances the level of multiple paternity is critical since multiply mated females bring more genetic variation into founder groups than single mated females. One such example is the marine snail Littorina saxatilis that during postglacial times has invaded mainland refuge areas and thereafter small islands emerging due to isostatic uplift by occasional rafting of multiply mated females. We modelled effects of varying degrees of multiple paternity on the genetic variation of island populations colonised by the founders spreading from the mainland, by quantifying the population heterozygosity during both the transient colonisation process, and after a steady state (with migration has been reached. During colonisation, multiple mating by [Formula: see text] males increased the heterozygosity by [Formula: see text] in comparison with single paternity, while in the steady state the increase was [Formula: see text] compared with single paternity. In the steady state the increase of heterozygosity due to multiple paternity is determined by a corresponding increase in effective population size. During colonisation, by contrast, the increase in heterozygosity is larger and it cannot be explained in terms of the effective population size alone. During the steady-state phase bursts of high genetic variation spread through the system, and far from the mainland this led to short periods of high diversity separated by long periods of low diversity. The size of these fluctuations was boosted by multiple paternity. We conclude that following glacial periods of extirpation, recolonization of isolated habitats by this species has been supported by its high level of multiple paternity.

  12. The Effect of Multiple Paternity on Genetic Diversity of Small Populations during and after Colonisation

    KAUST Repository

    Rafajlović, Marina

    2013-10-28

    Genetic variation within and among populations is influenced by the genetic content of the founders and the migrants following establishment. This is particularly true if populations are small, migration rate low and habitats arranged in a stepping-stone fashion. Under these circumstances the level of multiple paternity is critical since multiply mated females bring more genetic variation into founder groups than single mated females. One such example is the marine snail Littorina saxatilis that during postglacial times has invaded mainland refuge areas and thereafter small islands emerging due to isostatic uplift by occasional rafting of multiply mated females. We modelled effects of varying degrees of multiple paternity on the genetic variation of island populations colonised by the founders spreading from the mainland, by quantifying the population heterozygosity during both the transient colonisation process, and after a steady state (with migration) has been reached. During colonisation, multiple mating by 2-10 males increased the heterozygosity by 10-300% in comparison with single paternity, while in the steady state the increase was 10-50% compared with single paternity. In the steady state the increase of heterozygosity due to multiple paternity is determined by a corresponding increase in effective population size. During colonisation, by contrast, the increase in heterozygosity is larger and it cannot be explained in terms of the effective population size alone. During the steady-state phase bursts of high genetic variation spread through the system, and far from the mainland this led to short periods of high diversity separated by long periods of low diversity. The size of these fluctuations was boosted by multiple paternity. We conclude that following glacial periods of extirpation, recolonization of isolated habitats by this species has been supported by its high level of multiple paternity. 2013 Rafajlovi? et al.

  13. Genetic diversity and population structure of Lantana camara in India indicates multiple introductions and gene flow.

    Science.gov (United States)

    Ray, A; Quader, S

    2014-05-01

    Lantana camara is a highly invasive plant, which has spread over 60 countries and island groups of Asia, Africa and Australia. In India, it was introduced in the early nineteenth century, since when it has expanded and gradually established itself in almost every available ecosystem. We investigated the genetic diversity and population structure of this plant in India in order to understand its introduction, subsequent range expansion and gene flow. A total of 179 individuals were sequenced at three chloroplast loci and 218 individuals were genotyped for six nuclear microsatellites. Both chloroplasts (nine haplotypes) and microsatellites (83 alleles) showed high genetic diversity. Besides, each type of marker confirmed the presence of private polymorphism. We uncovered low to medium population structure in both markers, and found a faint signal of isolation by distance with microsatellites. Bayesian clustering analyses revealed multiple divergent genetic clusters. Taken together, these findings (i.e. high genetic diversity with private alleles and multiple genetic clusters) suggest that Lantana was introduced multiple times and gradually underwent spatial expansion with recurrent gene flow. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

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

    Science.gov (United States)

    Liang, Yulan; Kelemen, Arpad

    2016-08-01

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

  15. A general framework for the evaluation of genetic association studies using multiple marginal models

    DEFF Research Database (Denmark)

    Kitsche, Andreas; Ritz, Christian; Hothorn, Ludwig A.

    2016-01-01

    OBJECTIVE: In this study, we present a simultaneous inference procedure as a unified analysis framework for genetic association studies. METHODS: The method is based on the formulation of multiple marginal models that reflect different modes of inheritance. The basic advantage of this methodology...

  16. Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles

    DEFF Research Database (Denmark)

    Mero, Inger-Lise; Gustavsen, Marte W; Sæther, Hanne S

    2013-01-01

    The presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) is a typical finding in multiple sclerosis (MS). We applied data from Norwegian, Swedish and Danish (i.e. Scandinavian) MS patients from a genome-wide association study (GWAS) to search for genetic differences in MS relating...

  17. Flame Interactions and Thermoacoustics in Multiple-Nozzle Combustors

    Science.gov (United States)

    Dolan, Brian

    The first major chapter of original research (Chapter 3) examines thermoacoustic oscillations in a low-emission staged multiple-nozzle lean direct injection (MLDI) combustor. This experimental program investigated a relatively practical combustor sector that was designed and built as part of a commercial development program. The research questions are both practical, such as under what conditions the combustor can be safely operated, and fundamental, including what is most significant to driving the combustion oscillations in this system. A comprehensive survey of operating conditions finds that the low-emission (and low-stability) intermediate and outer stages are necessary to drive significant thermoacoustics. Phase-averaged and time-resolved OH* imaging show that dramatic periodic strengthening and weakening of the reaction zone downstream of the low-emission combustion stages. An acoustic modal analysis shows the pressure wave shapes and identifies the dominant thermoacoustic behavior as the first longitudinal mode for this combustor geometry. Finally, a discussion of the likely significant coupling mechanisms is given. Periodic reaction zone behavior in the low-emission fuel stages is the primary contributor to unsteady heat release. Differences between the fuel stages in the air swirler design, the fuel number of the injectors, the lean blowout point, and the nominal operating conditions all likely contribute to the limit cycle behavior of the low-emission stages. Chapter 4 investigates the effects of interaction between two adjacent swirl-stabilized nozzles using experimental and numerical tools. These studies are more fundamental; while the nozzle hardware is the same as the lean direct injection nozzles used in the MLDI combustion concept, the findings are generally applicable to other swirl-stabilized combustion systems as well. Much of the work utilizes a new experiment where the distance between nozzles was varied to change the level of interaction

  18. Analysis of genetic effects of nuclear-cytoplasmic interaction on quantitative traits: genetic model for diploid plants.

    Science.gov (United States)

    Han, Lide; Yang, Jian; Zhu, Jun

    2007-06-01

    A genetic model was proposed for simultaneously analyzing genetic effects of nuclear, cytoplasm, and nuclear-cytoplasmic interaction (NCI) as well as their genotype by environment (GE) interaction for quantitative traits of diploid plants. In the model, the NCI effects were further partitioned into additive and dominance nuclear-cytoplasmic interaction components. Mixed linear model approaches were used for statistical analysis. On the basis of diallel cross designs, Monte Carlo simulations showed that the genetic model was robust for estimating variance components under several situations without specific effects. Random genetic effects were predicted by an adjusted unbiased prediction (AUP) method. Data on four quantitative traits (boll number, lint percentage, fiber length, and micronaire) in Upland cotton (Gossypium hirsutum L.) were analyzed as a worked example to show the effectiveness of the model.

  19. Investigation of heavy quark and multiple interactions at HERA

    International Nuclear Information System (INIS)

    Magro, L.M.

    2005-09-01

    This thesis is oriented to the study of heavy quark photoproduction and multiple interactions, MI. For this reason we search for D* Mesons, in order to tag the charm quark, and we restrict ourselves in the region: Q 2 2 . For the theoretical calculations we use two Monte Carlo event generators: RAPGAP 3.1 and PYTHIA 6.2. Heavy quark production provides a large hard scale and therefore a small α s , which allows to test the perturbative QCD theory. On the other hand, MI has been proven to be important in hadron-hadron collisions. In this thesis, using MC event generators, we search for possible signals of MI in heavy quark production in electron-proton, ep, collisions. The thesis begins with a Theoretical Overview, with an introduction to ep collisions physics and the heavy quark photoproduction. We also give an introduction to the MI model included in PYTHIA. The next chapter introduces the concept of jet and presents some methods for the Heavy Quark Identification. After these two theoretical chapters there is a study of the direct and photon resolved processes, as well as the parton showering with RAPGAP. Since this thesis is oriented to the study of MI, PYTHIA plays a very important role because it includes a MI model also for ep collisions. Therefore, the fourth chapter is oriented to study the different steps in the event generation in PYTHIA. Chapter 7 is a D* Meson photoproduction study, where we include a comparison between the data, taken from the PhD Thesis of Gero Flucke. Finally, chapter 8 is a search for possible signals on MI. In hadron-hadron collisions it is clear that MI play a role. In ep collisions it is not so clear although MI could play a role in resolved photon events. The aim of this chapter is to find signals where HERA measurements could be sensitive to MI. (orig.)

  20. Wise regulates bone deposition through genetic interactions with Lrp5.

    Science.gov (United States)

    Ellies, Debra L; Economou, Androulla; Viviano, Beth; Rey, Jean-Philippe; Paine-Saunders, Stephenie; Krumlauf, Robb; Saunders, Scott

    2014-01-01

    In this study using genetic approaches in mouse we demonstrate that the secreted protein Wise plays essential roles in regulating early bone formation through its ability to modulate Wnt signaling via interactions with the Lrp5 co-receptor. In Wise-/- mutant mice we find an increase in the rate of osteoblast proliferation and a transient increase in bone mineral density. This change in proliferation is dependent upon Lrp5, as Wise;Lrp5 double mutants have normal bone mass. This suggests that Wise serves as a negative modulator of Wnt signaling in active osteoblasts. Wise and the closely related protein Sclerostin (Sost) are expressed in osteoblast cells during temporally distinct early and late phases in a manner consistent with the temporal onset of their respective increased bone density phenotypes. These data suggest that Wise and Sost may have common roles in regulating bone development through their ability to control the balance of Wnt signaling. We find that Wise is also required to potentiate proliferation in chondrocytes, serving as a potential positive modulator of Wnt activity. Our analyses demonstrate that Wise plays a key role in processes that control the number of osteoblasts and chondrocytes during bone homeostasis and provide important insight into mechanisms regulating the Wnt pathway during skeletal development.

  1. I just ran a thousand analyses: benefits of multiple testing in understanding equivocal evidence on gene-environment interactions.

    Directory of Open Access Journals (Sweden)

    Vera E Heininga

    Full Text Available In psychiatric genetics research, the volume of ambivalent findings on gene-environment interactions (G x E is growing at an accelerating pace. In response to the surging suspicions of systematic distortion, we challenge the notion of chance capitalization as a possible contributor. Beyond qualifying multiple testing as a mere methodological issue that, if uncorrected, leads to chance capitalization, we advance towards illustrating the potential benefits of multiple tests in understanding equivocal evidence in genetics literature.We focused on the interaction between the serotonin-transporter-linked promotor region (5-HTTLPR and childhood adversities with regard to depression. After testing 2160 interactions with all relevant measures available within the Dutch population study of adolescents TRAILS, we calculated percentages of significant (p < .05 effects for several subsets of regressions. Using chance capitalization (i.e. overall significance rate of 5% alpha and randomly distributed findings as a competing hypothesis, we expected more significant effects in the subsets of regressions involving: 1 interview-based instead of questionnaire-based measures; 2 abuse instead of milder childhood adversities; and 3 early instead of later adversities. Furthermore, we expected equal significance percentages across 4 male and female subsamples, and 5 various genotypic models of 5-HTTLPR.We found differences in the percentages of significant interactions among the subsets of analyses, including those regarding sex-specific subsamples and genetic modeling, but often in unexpected directions. Overall, the percentage of significant interactions was 7.9% which is only slightly above the 5% that might be expected based on chance.Taken together, multiple testing provides a novel approach to better understand equivocal evidence on G x E, showing that methodological differences across studies are a likely reason for heterogeneity in findings - but chance

  2. Multiple depots vehicle routing based on the ant colony with the genetic algorithm

    Directory of Open Access Journals (Sweden)

    ChunYing Liu

    2013-09-01

    Full Text Available Purpose: the distribution routing plans of multi-depots vehicle scheduling problem will increase exponentially along with the adding of customers. So, it becomes an important studying trend to solve the vehicle scheduling problem with heuristic algorithm. On the basis of building the model of multi-depots vehicle scheduling problem, in order to improve the efficiency of the multiple depots vehicle routing, the paper puts forward a fusion algorithm on multiple depots vehicle routing based on the ant colony algorithm with genetic algorithm. Design/methodology/approach: to achieve this objective, the genetic algorithm optimizes the parameters of the ant colony algorithm. The fusion algorithm on multiple depots vehicle based on the ant colony algorithm with genetic algorithm is proposed. Findings: simulation experiment indicates that the result of the fusion algorithm is more excellent than the other algorithm, and the improved algorithm has better convergence effective and global ability. Research limitations/implications: in this research, there are some assumption that might affect the accuracy of the model such as the pheromone volatile factor, heuristic factor in each period, and the selected multiple depots. These assumptions can be relaxed in future work. Originality/value: In this research, a new method for the multiple depots vehicle routing is proposed. The fusion algorithm eliminate the influence of the selected parameter by optimizing the heuristic factor, evaporation factor, initial pheromone distribute, and have the strong global searching ability. The Ant Colony algorithm imports cross operator and mutation operator for operating the first best solution and the second best solution in every iteration, and reserves the best solution. The cross and mutation operator extend the solution space and improve the convergence effective and the global ability. This research shows that considering both the ant colony and genetic algorithm

  3. A Review for Detecting Gene-Gene Interactions Using Machine Learning Methods in Genetic Epidemiology

    Directory of Open Access Journals (Sweden)

    Ching Lee Koo

    2013-01-01

    Full Text Available Recently, the greatest statistical computational challenge in genetic epidemiology is to identify and characterize the genes that interact with other genes and environment factors that bring the effect on complex multifactorial disease. These gene-gene interactions are also denoted as epitasis in which this phenomenon cannot be solved by traditional statistical method due to the high dimensionality of the data and the occurrence of multiple polymorphism. Hence, there are several machine learning methods to solve such problems by identifying such susceptibility gene which are neural networks (NNs, support vector machine (SVM, and random forests (RFs in such common and multifactorial disease. This paper gives an overview on machine learning methods, describing the methodology of each machine learning methods and its application in detecting gene-gene and gene-environment interactions. Lastly, this paper discussed each machine learning method and presents the strengths and weaknesses of each machine learning method in detecting gene-gene interactions in complex human disease.

  4. Exploring Genetic Suppression Interactions on a Global Scale

    OpenAIRE

    van Leeuwen, Jolanda; Pons, Carles; Mellor, Joseph C.; Yamaguchi, Takafumi N.; Friesen, Helena; Koschwanez, John; Ušaj, Mojca Mattiazzi; Pechlaner, Maria; Takar, Mehmet; Ušaj, Matej; VanderSluis, Benjamin; Andrusiak, Kerry; Bansal, Pritpal; Baryshnikova, Anastasia; Boone, Claire

    2016-01-01

    Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene. To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insig...

  5. Low genetic diversity despite multiple introductions of the invasive plant species Impatiens glandulifera in Europe.

    Science.gov (United States)

    Hagenblad, Jenny; Hülskötter, Jennifer; Acharya, Kamal Prasad; Brunet, Jörg; Chabrerie, Olivier; Cousins, Sara A O; Dar, Pervaiz A; Diekmann, Martin; De Frenne, Pieter; Hermy, Martin; Jamoneau, Aurélien; Kolb, Annette; Lemke, Isgard; Plue, Jan; Reshi, Zafar A; Graae, Bente Jessen

    2015-08-20

    Invasive species can be a major threat to native biodiversity and the number of invasive plant species is increasing across the globe. Population genetic studies of invasive species can provide key insights into their invasion history and ensuing evolution, but also for their control. Here we genetically characterise populations of Impatiens glandulifera, an invasive plant in Europe that can have a major impact on native plant communities. We compared populations from the species' native range in Kashmir, India, to those in its invaded range, along a latitudinal gradient in Europe. For comparison, the results from 39 other studies of genetic diversity in invasive species were collated. Our results suggest that I. glandulifera was established in the wild in Europe at least twice, from an area outside of our Kashmir study area. Our results further revealed that the genetic diversity in invasive populations of I. glandulifera is unusually low compared to native populations, in particular when compared to other invasive species. Genetic drift rather than mutation seems to have played a role in differentiating populations in Europe. We find evidence of limitations to local gene flow after introduction to Europe, but somewhat less restrictions in the native range. I. glandulifera populations with significant inbreeding were only found in the species' native range and invasive species in general showed no increase in inbreeding upon leaving their native ranges. In Europe we detect cases of migration between distantly located populations. Human activities therefore seem to, at least partially, have facilitated not only introductions, but also further spread of I. glandulifera across Europe. Although multiple introductions will facilitate the retention of genetic diversity in invasive ranges, widespread invasive species can remain genetically relatively invariant also after multiple introductions. Phenotypic plasticity may therefore be an important component of the

  6. Local tax interaction with multiple tax instruments: evidence from Flemish municipalities

    OpenAIRE

    S. VAN PARYS; B. MERLEVEDE; T. VERBEKE

    2010-01-01

    We investigate the long run result of strategic interaction among local jurisdictions using multiple tax instruments. Most studies about local policy interaction only consider a single policy instrument. With multiple tax instruments, however, tax interaction is more complex. We construct a simple theoretical framework based on a basic spillover model, with two tax rates and immobile resources. We show that the signs of within and cross tax interaction crucially depend on the extent to which ...

  7. Optimization of Multiple Traveling Salesman Problem Based on Simulated Annealing Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Xu Mingji

    2017-01-01

    Full Text Available It is very effective to solve the multi variable optimization problem by using hierarchical genetic algorithm. This thesis analyzes both advantages and disadvantages of hierarchical genetic algorithm and puts forward an improved simulated annealing genetic algorithm. The new algorithm is applied to solve the multiple traveling salesman problem, which can improve the performance of the solution. First, it improves the design of chromosomes hierarchical structure in terms of redundant hierarchical algorithm, and it suggests a suffix design of chromosomes; Second, concerning to some premature problems of genetic algorithm, it proposes a self-identify crossover operator and mutation; Third, when it comes to the problem of weak ability of local search of genetic algorithm, it stretches the fitness by mixing genetic algorithm with simulated annealing algorithm. Forth, it emulates the problems of N traveling salesmen and M cities so as to verify its feasibility. The simulation and calculation shows that this improved algorithm can be quickly converged to a best global solution, which means the algorithm is encouraging in practical uses.

  8. Mapping genetic factors controlling potato - cyst nematode interactions

    NARCIS (Netherlands)

    Rouppe van der Voort, J.N.A.M.

    1998-01-01

    The thesis describes strategies for genetic mapping of the genomes of the potato cyst nematode and potato. Mapping in cyst nematodes was achieved by AFLP genotyping of single cysts and subsequent segregation analysis in a family of sibling populations. The genetic map of Globodera

  9. Behavioral phenotypes in schizophrenic animal models with multiple combinations of genetic and environmental factors.

    Science.gov (United States)

    Hida, Hirotake; Mouri, Akihiro; Noda, Yukihiro

    2013-01-01

    Schizophrenia is a multifactorial psychiatric disorder in which both genetic and environmental factors play a role. Genetic [e.g., Disrupted-in-schizophrenia 1 (DISC1), Neuregulin-1 (NRG1)] and environmental factors (e.g., maternal viral infection, obstetric complications, social stress) may act during the developmental period to increase the incidence of schizophrenia. In animal models, interactions between susceptibility genes and the environment can be controlled in ways not possible in humans; therefore, such models are useful for investigating interactions between or within factors in the pathogenesis and pathophysiology of schizophrenia. We provide an overview of schizophrenic animal models investigating interactions between or within factors. First, we reviewed gene-environment interaction animal models, in which schizophrenic candidate gene mutant mice were subjected to perinatal immune activation or adolescent stress. Next, environment-environment interaction animal models, in which mice were subjected to a combination of perinatal immune activation and adolescent administration of drugs, were described. These animal models showed interaction between or within factors; behavioral changes, which were obscured by each factor, were marked by interaction of factors and vice versa. Appropriate behavioral approaches with such models will be invaluable for translational research on novel compounds, and also for providing insight into the pathogenesis and pathophysiology of schizophrenia.

  10. Social and genetic interactions drive fitness variation in a free-living dolphin population.

    Science.gov (United States)

    Frère, Celine H; Krützen, Michael; Mann, Janet; Connor, Richard C; Bejder, Lars; Sherwin, William B

    2010-11-16

    The evolutionary forces that drive fitness variation in species are of considerable interest. Despite this, the relative importance and interactions of genetic and social factors involved in the evolution of fitness traits in wild mammalian populations are largely unknown. To date, a few studies have demonstrated that fitness might be influenced by either social factors or genes in natural populations, but none have explored how the combined effect of social and genetic parameters might interact to influence fitness. Drawing from a long-term study of wild bottlenose dolphins in the eastern gulf of Shark Bay, Western Australia, we present a unique approach to understanding these interactions. Our study shows that female calving success depends on both genetic inheritance and social bonds. Moreover, we demonstrate that interactions between social and genetic factors also influence female fitness. Therefore, our study represents a major methodological advance, and provides critical insights into the interplay of genetic and social parameters of fitness.

  11. Scaling laws and universality for the strength of genetic interactions in yeast

    Science.gov (United States)

    Velenich, Andrea; Dai, Mingjie; Gore, Jeff

    2012-02-01

    Genetic interactions provide a window to the organization of the thousands of biochemical reactions in living cells. If two mutations affect unrelated cellular functions, the fitness effects of their combination can be easily predicted from the two separate fitness effects. However, because of interactions, for some pairs of mutations their combined fitness effect deviates from the naive prediction. We study genetic interactions in yeast cells by analyzing a publicly available database containing experimental growth rates of 5 million double mutants. We show that the characteristic strength of genetic interactions has a simple power law dependence on the fitness effects of the two interacting mutations and that the probability distribution of genetic interactions is a universal function. We further argue that the strength of genetic interactions depends only on the fitness effects of the interacting mutations and not on their biological origin in terms of single point mutations, entire gene knockouts or even more complicated physiological perturbations. Finally, we discuss the implications of the power law scaling of genetic interactions on the ruggedness of fitness landscapes and the consequent evolutionary dynamics.

  12. Measuring the genetic influence on human life span: gene-environment interaction and sex-specific genetic effects

    DEFF Research Database (Denmark)

    Tan, Qihua; De Benedictis, G; Yashin, Annatoli

    2001-01-01

    New approaches are needed to explore the different ways in which genes affect the human life span. One needs to assess the genetic effects themselves, as well as gene–environment interactions and sex dependency. In this paper, we present a new model that combines both genotypic and demographicinf......New approaches are needed to explore the different ways in which genes affect the human life span. One needs to assess the genetic effects themselves, as well as gene–environment interactions and sex dependency. In this paper, we present a new model that combines both genotypic...

  13. A crack growth evaluation method for interacting multiple cracks

    International Nuclear Information System (INIS)

    Kamaya, Masayuki

    2003-01-01

    When stress corrosion cracking or corrosion fatigue occurs, multiple cracks are frequently initiated in the same area. According to section XI of the ASME Boiler and Pressure Vessel Code, multiple cracks are considered as a single combined crack in crack growth analysis, if the specified conditions are satisfied. In crack growth processes, however, no prescription for the interference between multiple cracks is given in this code. The JSME Post-Construction Code, issued in May 2000, prescribes the conditions of crack coalescence in the crack growth process. This study aimed to extend this prescription to more general cases. A simulation model was applied, to simulate the crack growth process, taking into account the interference between two cracks. This model made it possible to analyze multiple crack growth behaviors for many cases (e.g. different relative position and length) that could not be studied by experiment only. Based on these analyses, a new crack growth analysis method was suggested for taking into account the interference between multiple cracks. (author)

  14. The genetics of multiple sclerosis: review of current and emerging candidates

    Directory of Open Access Journals (Sweden)

    Muñoz-Culla M

    2013-08-01

    Full Text Available Maider Muñoz-Culla,1,2 Haritz Irizar,1,2 David Otaegui1,2 1Multiple Sclerosis Unit, Instituto Biodonostia, San Sebastián, Spain; 2Red Española de Esclerosis Múltiple (REEM, Barcelona, Spain Abstract: Multiple sclerosis (MS is a complex disease in which environmental, genetic, and epigenetic factors determine the risk of developing the disease. The human leukocyte antigen region is the strongest susceptibility locus linked to MS, but it does not explain the whole heritability of the disease. To find other non-human leukocyte antigen loci associated with the disease, high-throughput genotyping, sequencing, and gene-expression studies have been performed, producing a valuable quantity of information. An overview of the genomic and expression studies is provided in this review, as well as microRNA-expression studies, highlighting the importance of combining all the layers of information in order to elucidate the causes or pathological mechanisms occurring in the disease. Genetics in MS is a promising field that is presumably going to be very productive in the next decade understanding the cross talk between all the factors contributing to the development of MS. Keywords: multiple sclerosis, genetics, gene expression, microRNA

  15. Multiple-Trait Genomic Selection Methods Increase Genetic Value Prediction Accuracy

    Science.gov (United States)

    Jia, Yi; Jannink, Jean-Luc

    2012-01-01

    Genetic correlations between quantitative traits measured in many breeding programs are pervasive. These correlations indicate that measurements of one trait carry information on other traits. Current single-trait (univariate) genomic selection does not take advantage of this information. Multivariate genomic selection on multiple traits could accomplish this but has been little explored and tested in practical breeding programs. In this study, three multivariate linear models (i.e., GBLUP, BayesA, and BayesCπ) were presented and compared to univariate models using simulated and real quantitative traits controlled by different genetic architectures. We also extended BayesA with fixed hyperparameters to a full hierarchical model that estimated hyperparameters and BayesCπ to impute missing phenotypes. We found that optimal marker-effect variance priors depended on the genetic architecture of the trait so that estimating them was beneficial. We showed that the prediction accuracy for a low-heritability trait could be significantly increased by multivariate genomic selection when a correlated high-heritability trait was available. Further, multiple-trait genomic selection had higher prediction accuracy than single-trait genomic selection when phenotypes are not available on all individuals and traits. Additional factors affecting the performance of multiple-trait genomic selection were explored. PMID:23086217

  16. Gene interactions and genetics of blast resistance and yield ...

    Indian Academy of Sciences (India)

    2014-08-11

    Aug 11, 2014 ... of chemical measures for the control and management of blast, which are not .... tion of genetic components of variation, epistasis model and gene effects in two .... and environmental variance is estimated from mean variance.

  17. Exploring genetic suppression interactions on a global scale.

    Science.gov (United States)

    van Leeuwen, Jolanda; Pons, Carles; Mellor, Joseph C; Yamaguchi, Takafumi N; Friesen, Helena; Koschwanez, John; Ušaj, Mojca Mattiazzi; Pechlaner, Maria; Takar, Mehmet; Ušaj, Matej; VanderSluis, Benjamin; Andrusiak, Kerry; Bansal, Pritpal; Baryshnikova, Anastasia; Boone, Claire E; Cao, Jessica; Cote, Atina; Gebbia, Marinella; Horecka, Gene; Horecka, Ira; Kuzmin, Elena; Legro, Nicole; Liang, Wendy; van Lieshout, Natascha; McNee, Margaret; San Luis, Bryan-Joseph; Shaeri, Fatemeh; Shuteriqi, Ermira; Sun, Song; Yang, Lu; Youn, Ji-Young; Yuen, Michael; Costanzo, Michael; Gingras, Anne-Claude; Aloy, Patrick; Oostenbrink, Chris; Murray, Andrew; Graham, Todd R; Myers, Chad L; Andrews, Brenda J; Roth, Frederick P; Boone, Charles

    2016-11-04

    Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene. To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insights into the functional wiring diagram of the cell. In addition to suppressor mutations, we identified frequent secondary mutations,in a subset of genes, that likely cause a delay in the onset of stationary phase, which appears to promote their enrichment within a propagating population. These findings allow us to formulate and quantify general mechanisms of genetic suppression. Copyright © 2016, American Association for the Advancement of Science.

  18. Genetic structuring of northern myotis (Myotis septentrionalis) at multiple spatial scales

    Science.gov (United States)

    Johnson, Joshua B.; Roberts, James H.; King, Timothy L.; Edwards, John W.; Ford, W. Mark; Ray, David A.

    2014-01-01

    Although groups of bats may be genetically distinguishable at large spatial scales, the effects of forest disturbances, particularly permanent land use conversions on fine-scale population structure and gene flow of summer aggregations of philopatric bat species are less clear. We genotyped and analyzed variation at 10 nuclear DNA microsatellite markers in 182 individuals of the forest-dwelling northern myotis (Myotis septentrionalis) at multiple spatial scales, from within first-order watersheds scaling up to larger regional areas in West Virginia and New York. Our results indicate that groups of northern myotis were genetically indistinguishable at any spatial scale we considered, and the collective population maintained high genetic diversity. It is likely that the ability to migrate, exploit small forest patches, and use networks of mating sites located throughout the Appalachian Mountains, Interior Highlands, and elsewhere in the hibernation range have allowed northern myotis to maintain high genetic diversity and gene flow regardless of forest disturbances at local and regional spatial scales. A consequence of maintaining high gene flow might be the potential to minimize genetic founder effects following population declines caused currently by the enzootic White-nose Syndrome.

  19. The empirical content of models with multiple equilibria in economies with social interactions

    OpenAIRE

    Alberto Bisin; Andrea Moro; Giorgio Topa

    2011-01-01

    We study a general class of models with social interactions that might display multiple equilibria. We propose an estimation procedure for these models and evaluate its efficiency and computational feasibility relative to different approaches taken to the curse of dimensionality implied by the multiplicity. Using data on smoking among teenagers, we implement the proposed estimation procedure to understand how group interactions affect health-related choices. We find that interaction effects a...

  20. Phylogeographic and population genetic analyses reveal multiple species of Boa and independent origins of insular dwarfism.

    Science.gov (United States)

    Card, Daren C; Schield, Drew R; Adams, Richard H; Corbin, Andrew B; Perry, Blair W; Andrew, Audra L; Pasquesi, Giulia I M; Smith, Eric N; Jezkova, Tereza; Boback, Scott M; Booth, Warren; Castoe, Todd A

    2016-09-01

    Boa is a Neotropical genus of snakes historically recognized as monotypic despite its expansive distribution. The distinct morphological traits and color patterns exhibited by these snakes, together with the wide diversity of ecosystems they inhabit, collectively suggest that the genus may represent multiple species. Morphological variation within Boa also includes instances of dwarfism observed in multiple offshore island populations. Despite this substantial diversity, the systematics of the genus Boa has received little attention until very recently. In this study we examined the genetic structure and phylogenetic relationships of Boa populations using mitochondrial sequences and genome-wide SNP data obtained from RADseq. We analyzed these data at multiple geographic scales using a combination of phylogenetic inference (including coalescent-based species delimitation) and population genetic analyses. We identified extensive population structure across the range of the genus Boa and multiple lines of evidence for three widely-distributed clades roughly corresponding with the three primary land masses of the Western Hemisphere. We also find both mitochondrial and nuclear support for independent origins and parallel evolution of dwarfism on offshore island clusters in Belize and Cayos Cochinos Menor, Honduras. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. The Interaction Network Ontology-supported modeling and mining of complex interactions represented with multiple keywords in biomedical literature.

    Science.gov (United States)

    Özgür, Arzucan; Hur, Junguk; He, Yongqun

    2016-01-01

    The Interaction Network Ontology (INO) logically represents biological interactions, pathways, and networks. INO has been demonstrated to be valuable in providing a set of structured ontological terms and associated keywords to support literature mining of gene-gene interactions from biomedical literature. However, previous work using INO focused on single keyword matching, while many interactions are represented with two or more interaction keywords used in combination. This paper reports our extension of INO to include combinatory patterns of two or more literature mining keywords co-existing in one sentence to represent specific INO interaction classes. Such keyword combinations and related INO interaction type information could be automatically obtained via SPARQL queries, formatted in Excel format, and used in an INO-supported SciMiner, an in-house literature mining program. We studied the gene interaction sentences from the commonly used benchmark Learning Logic in Language (LLL) dataset and one internally generated vaccine-related dataset to identify and analyze interaction types containing multiple keywords. Patterns obtained from the dependency parse trees of the sentences were used to identify the interaction keywords that are related to each other and collectively represent an interaction type. The INO ontology currently has 575 terms including 202 terms under the interaction branch. The relations between the INO interaction types and associated keywords are represented using the INO annotation relations: 'has literature mining keywords' and 'has keyword dependency pattern'. The keyword dependency patterns were generated via running the Stanford Parser to obtain dependency relation types. Out of the 107 interactions in the LLL dataset represented with two-keyword interaction types, 86 were identified by using the direct dependency relations. The LLL dataset contained 34 gene regulation interaction types, each of which associated with multiple keywords. A

  2. Genetic variants are major determinants of CSF antibody levels in multiple sclerosis

    DEFF Research Database (Denmark)

    Goris, An; Pauwels, Ine; Gustavsen, Marte W

    2015-01-01

    Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index-the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying...... differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed...... a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals...

  3. A knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility

    NARCIS (Netherlands)

    Bush, W.S.; McCauley, J.L.; DeJager, P.L.; Dudek, S.M.; Hafler, D.A.; Gibson, R.A.; Matthews, P.M.; Kappos, L.; Naegelin, Y.; Polman, C.H.; Hauser, S.L.; Oksenberg, J.; Haines, J.L.; Ritchie, M.D.

    2011-01-01

    Gene-gene interactions are proposed as an important component of the genetic architecture of complex diseases, and are just beginning to be evaluated in the context of genome-wide association studies (GWAS). In addition to detecting epistasis, a benefit to interaction analysis is that it also

  4. Genetic architecture of carbon isotope composition and growth in Eucalyptus across multiple environments.

    Science.gov (United States)

    Bartholomé, Jérôme; Mabiala, André; Savelli, Bruno; Bert, Didier; Brendel, Oliver; Plomion, Christophe; Gion, Jean-Marc

    2015-06-01

    In the context of climate change, the water-use efficiency (WUE) of highly productive tree varieties, such as eucalypts, has become a major issue for breeding programmes. This study set out to dissect the genetic architecture of carbon isotope composition (δ(13) C), a proxy of WUE, across several environments. A family of Eucalyptus urophylla × E. grandis was planted in three trials and phenotyped for δ(13) C and growth traits. High-resolution genetic maps enabled us to target genomic regions underlying δ(13) C quantitative trait loci (QTLs) on the E. grandis genome. Of the 15 QTLs identified for δ(13) C, nine were stable across the environments and three displayed significant QTL-by-environment interaction, suggesting medium to high genetic determinism for this trait. Only one colocalization was found between growth and δ(13) C. Gene ontology (GO) term enrichment analysis suggested candidate genes related to foliar δ(13) C, including two involved in the regulation of stomatal movements. This study provides the first report of the genetic architecture of δ(13) C and its relation to growth in Eucalyptus. The low correlations found between the two traits at phenotypic and genetic levels suggest the possibility of improving the WUE of Eucalyptus varieties without having an impact on breeding for growth. © 2015 CIRAD. New Phytologist © 2015 New Phytologist Trust.

  5. Social Peer Interactions in Persons with Profound Intellectual and Multiple Disabilities: A Literature Review

    Science.gov (United States)

    Nijs, Sara; Maes, Bea

    2014-01-01

    Social interactions may positively influence developmental and quality of life outcomes. Research in persons with profound intellectual and multiple disabilities (PIMD) mostly investigated interactions with caregivers. This literature review focuses on peer interactions of persons with PIMD. A computerized literature search of three databases was…

  6. Potential games and interactive decisions with multiple criteria

    NARCIS (Netherlands)

    Voorneveld, M.

    1999-01-01

    Game theory is a mathematical theory for analyzing strategic interaction between decision makers. This thesis covers two game-theoretic topics. The first part of this thesis deals with potential games: noncooperative games in which the information about the goals of the separate players that is

  7. Framework for Modelling Multiple Input Complex Aggregations for Interactive Installations

    DEFF Research Database (Denmark)

    Padfield, Nicolas; Andreasen, Troels

    2012-01-01

    on fuzzy logic and provides a method for variably balancing interaction and user input with the intention of the artist or director. An experimental design is presented, demonstrating an intuitive interface for parametric modelling of a complex aggregation function. The aggregation function unifies...

  8. Legumes affect alpine tundra community composition via multiple biotic interactions

    NARCIS (Netherlands)

    Soudzilovskaia, N.A.; Aksenova, A.A.; Makarov, M.I.; Onipchenko, V.G.; Logvinenko, O.A.; Braak, ter C.J.F.; Cornelissen, J.H.C.

    2012-01-01

    The soil engineering function of legumes in natural ecosystems is paramount but associated solely with soil nitrogen (N) subsidies, ignoring concomitant biotic interactions such as competitive or inhibitory effects and exchange between mycorrhizas and rhizobia. We aim to (1) disentangle legume

  9. Plant interactions with multiple insect herbivores: from community to genes

    NARCIS (Netherlands)

    Stam, J.M.; Kroes, A.; Li, Y.; Gols, R.; Loon, van J.J.A.; Poelman, E.H.; Dicke, M.

    2014-01-01

    Every plant is a member of a complex insect community that consists of tens to hundreds of species that belong to different trophic levels. The dynamics of this community are critically influenced by the plant, which mediates interactions between community members that can occur on the plant

  10. Additive Main Effects and Multiplicative Interaction Analysis of ...

    African Journals Online (AJOL)

    This work deals with modeling and examining the GxE interaction pattern of the multi-environment trials of 43 genotypes and eight environments from Southern Ethiopia coffee (Coffea Arabica L.) collections using a randomized complete block design (RCBD) with four replications. The work further attempts to predict yield ...

  11. Gene interactions and genetics for yield and its attributes in grass pea

    Indian Academy of Sciences (India)

    [Parihar A. K., Dixit G. P. and Singh D. 2016 Gene interactions and genetics for yield and its attributes .... Biological yield. Seed yield factors. Plant height. Primary branches plant pod ..... indicates that these traits are under the control of several.

  12. Genetic Vulnerability Interacts with Parenting and Early Care and Education to Predict Increasing Externalizing Behavior

    Science.gov (United States)

    Lipscomb, Shannon T.; Laurent, Heidemarie; Neiderhiser, Jenae M.; Shaw, Daniel S.; Natsuaki, Misaki N.; Reiss, David; Leve, Leslie D.

    2014-01-01

    The current study examined interactions among genetic influences and children's early environments on the development of externalizing behaviors from 18 months to 6 years of age. Participants included 233 families linked through adoption (birth parents and adoptive families). Genetic influences were assessed by birth parent temperamental…

  13. Family Conflict Interacts with Genetic Liability in Predicting Childhood and Adolescent Depression

    Science.gov (United States)

    Rice, Frances; Harold, Gordon T.; Shelton, Katherine H.; Thapar, Anita

    2006-01-01

    Objective: To test for gene-environment interaction with depressive symptoms and family conflict. Specifically, to first examine whether the influence of family conflict in predicting depressive symptoms is increased in individuals at genetic risk of depression. Second, to test whether the genetic component of variance in depressive symptoms…

  14. The genetics of music accomplishment: evidence for gene-environment correlation and interaction.

    Science.gov (United States)

    Hambrick, David Z; Tucker-Drob, Elliot M

    2015-02-01

    Theories of skilled performance that emphasize training history, such as K. Anders Ericsson and colleagues' deliberate-practice theory, have received a great deal of recent attention in both the scientific literature and the popular press. Twin studies, however, have demonstrated evidence for moderate-to-strong genetic influences on skilled performance. Focusing on musical accomplishment in a sample of over 800 pairs of twins, we found evidence for gene-environment correlation, in the form of a genetic effect on music practice. However, only about one quarter of the genetic effect on music accomplishment was explained by this genetic effect on music practice, suggesting that genetically influenced factors other than practice contribute to individual differences in music accomplishment. We also found evidence for gene-environment interaction, such that genetic effects on music accomplishment were most pronounced among those engaging in music practice, suggesting that genetic potentials for skilled performance are most fully expressed and fostered by practice.

  15. Preimplantation genetic diagnosis for a patient with multiple endocrine neoplasia type 1: case report.

    Science.gov (United States)

    Lima, Aline Dt; Alves, Vanessa R; Rocha, Andressa R; Martinhago, Ana C; Martinhago, Ciro; Donadio, Nilka; Dzik, Artur; Cavagna, Mario; Gebrim, Luiz H

    2018-03-01

    Preimplantation genetic diagnosis was carried out for embryonic analysis in a patient with multiple endocrine neoplasia type 1 (MEN1). This is a rare autosomal-dominant cancer syndrome and the patients with MEN1 are characterized by the occurrence of tumors in multiple endocrine tissues, associated with germline and somatic inactivating mutations in the MEN1 gene. This case report documents a successful preimplantation genetic diagnosis (PGD) involving a couple at-risk for MEN1 syndrome, with a birth of a healthy infant. The couple underwent a cycle of controlled ovarian stimulation and intracytoplasmic sperm injection (ICSI). Embryos were biopsied at the blastocyst stage and cryopreserved; we used PCR-based DNA analysis for PGD testing. Only one of the five embryos analyzed for MEN1 syndrome was unaffected. This embryo was thawed and transferred following endometrial preparation. After positive βHCG test; clinical pregnancy was confirmed by ultrasound, and a healthy infant was born. PGD for single gene disorders has been an emerging therapeutic tool for couples who are at risk of passing a genetic disease on to their offspring.

  16. Analysis of the genetic variation in Mycobacterium tuberculosis strains by multiple genome alignments

    Directory of Open Access Journals (Sweden)

    Morales Juan

    2008-11-01

    Full Text Available Abstract Background The recent determination of the complete nucleotide sequence of several Mycobacterium tuberculosis (MTB genomes allows the use of comparative genomics as a tool for dissecting the nature and consequence of genetic variability within this species. The multiple alignment of the genomes of clinical strains (CDC1551, F11, Haarlem and C, along with the genomes of laboratory strains (H37Rv and H37Ra, provides new insights on the mechanisms of adaptation of this bacterium to the human host. Findings The genetic variation found in six M. tuberculosis strains does not involve significant genomic rearrangements. Most of the variation results from deletion and transposition events preferentially associated with insertion sequences and genes of the PE/PPE family but not with genes implicated in virulence. Using a Perl-based software islandsanalyser, which creates a representation of the genetic variation in the genome, we identified differences in the patterns of distribution and frequency of the polymorphisms across the genome. The identification of genes displaying strain-specific polymorphisms and the extrapolation of the number of strain-specific polymorphisms to an unlimited number of genomes indicates that the different strains contain a limited number of unique polymorphisms. Conclusion The comparison of multiple genomes demonstrates that the M. tuberculosis genome is currently undergoing an active process of gene decay, analogous to the adaptation process of obligate bacterial symbionts. This observation opens new perspectives into the evolution and the understanding of the pathogenesis of this bacterium.

  17. Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes.

    Science.gov (United States)

    Shen, Ding-Wu; Pouliot, Lynn M; Hall, Matthew D; Gottesman, Michael M

    2012-07-01

    Cisplatin is one of the most effective broad-spectrum anticancer drugs. Its effectiveness seems to be due to the unique properties of cisplatin, which enters cells via multiple pathways and forms multiple different DNA-platinum adducts while initiating a cellular self-defense system by activating or silencing a variety of different genes, resulting in dramatic epigenetic and/or genetic alternations. As a result, the development of cisplatin resistance in human cancer cells in vivo and in vitro by necessity stems from bewilderingly complex genetic and epigenetic changes in gene expression and alterations in protein localization. Extensive published evidence has demonstrated that pleiotropic alterations are frequently detected during development of resistance to this toxic metal compound. Changes occur in almost every mechanism supporting cell survival, including cell growth-promoting pathways, apoptosis, developmental pathways, DNA damage repair, and endocytosis. In general, dozens of genes are affected in cisplatin-resistant cells, including pathways involved in copper metabolism as well as transcription pathways that alter the cytoskeleton, change cell surface presentation of proteins, and regulate epithelial-to-mesenchymal transition. Decreased accumulation is one of the most common features resulting in cisplatin resistance. This seems to be a consequence of numerous epigenetic and genetic changes leading to the loss of cell-surface binding sites and/or transporters for cisplatin, and decreased fluid phase endocytosis.

  18. Multiplicity distribution and multiplicity moment of black and grey particles in high energy nucleus–nucleus interactions

    International Nuclear Information System (INIS)

    Ghosh, Dipak; Deb, Argha; Datta, Utpal; Bhattacharyya, S.

    2011-01-01

    In this paper we have studied the multiplicity distribution of black and grey particles emitted from 16 O–AgBr interactions at 2.1 AGeV and 60 AGeV. We have also calculated the multiplicity moment up to the fifth order for both the interactions and for both kinds of emitted particles. The variation of multiplicity moment with the order number has been investigated. It is seen that in the case of black particles multiplicity moment up to fourth order remains almost constant as energy increases from 2.1 AGeV to 60 AGeV. Fifth order multiplicity moment increases insignificantly with energy. However in the case of grey particles no such constancy of multiplicity moment with energy of the projectile beam is obtained. Later we have extended our study on the basis of Regge–Mueller approach to find the existence of second order correlation during the emission of black as well as the grey particles. The second Mueller moment is found to be positive and it increases as energy increases in the case of black particles. On the contrary in the case of grey particles the second Mueller moment decreases with energy. It can be concluded that as energy increases correlation among the black particles increases. On the other hand with the increase of energy correlation among the grey particles is found to diminish. (author)

  19. Complete restoration of multiple dystrophin isoforms in genetically corrected Duchenne muscular dystrophy patient–derived cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Susi Zatti

    2014-01-01

    Full Text Available Duchenne muscular dystrophy (DMD–associated cardiac diseases are emerging as a major cause of morbidity and mortality in DMD patients, and many therapies for treatment of skeletal muscle failed to improve cardiac function. The reprogramming of patients' somatic cells into pluripotent stem cells, combined with technologies for correcting the genetic defect, possesses great potential for the development of new treatments for genetic diseases. In this study, we obtained human cardiomyocytes from DMD patient–derived, induced pluripotent stem cells genetically corrected with a human artificial chromosome carrying the whole dystrophin genomic sequence. Stimulation by cytokines was combined with cell culturing on hydrogel with physiological stiffness, allowing an adhesion-dependent maturation and a proper dystrophin expression. The obtained cardiomyocytes showed remarkable sarcomeric organization of cardiac troponin T and α-actinin, expressed cardiac-specific markers, and displayed electrically induced calcium transients lasting less than 1 second. We demonstrated that the human artificial chromosome carrying the whole dystrophin genomic sequence is stably maintained throughout the cardiac differentiation process and that multiple promoters of the dystrophin gene are properly activated, driving expression of different isoforms. These dystrophic cardiomyocytes can be a valuable source for in vitro modeling of DMD-associated cardiac disease. Furthermore, the derivation of genetically corrected, patient-specific cardiomyocytes represents a step toward the development of innovative cell and gene therapy approaches for DMD.

  20. Multiple genetic variants associated with primary biliary cirrhosis in a Han Chinese population.

    Science.gov (United States)

    Dong, Ming; Li, Jinxin; Tang, Ruqi; Zhu, Ping; Qiu, Fang; Wang, Chan; Qiu, Jie; Wang, Lan; Dai, Yaping; Xu, Ping; Gao, Yueqiu; Han, Chongxu; Wang, Yongzhong; Wu, Jian; Wu, Xudong; Zhang, Kui; Dai, Na; Sun, Weihao; Zhou, Jianpo; Hu, Zhigang; Liu, Lei; Jiang, Yuzhang; Nie, Jinshan; Zhao, Yi; Gong, Yuhua; Tian, Ye; Ji, Hualiang; Jiao, Zhijun; Jiang, Po; Shi, Xingjuan; Jawed, Rohil; Zhang, Yu; Huang, Qinghai; Li, Enling; Wei, Yiran; Xie, Wei; Zhao, Weifeng; Liu, Xiang; Zhu, Xiang; Qiu, Hong; He, Gengsheng; Chen, Weichang; Seldin, Michael F; Gershwin, M Eric; Liu, Xiangdong; Ma, Xiong

    2015-06-01

    Multiple genome-wide association studies of primary biliary cirrhosis (PBC) in both European and Japanese ancestries have shown significant associations of many genetic loci contributing to the susceptibility to PBC. Major differences in susceptibility loci between these two population groups were observed. In this study, we examined whether the most significant loci observed in either European and/or Japanese cohorts are associated with PBC in a Han Chinese population. In 1070 PBC patients and 1198 controls, we observed highly significant associations at CD80 (rs2293370, P = 2.67 × 10(-8)) and TNFSF15 (rs4979462, P = 3.86 × 10(-8)) and significant associations at 17q12-21 (rs9303277), PDGFB (rs715505), NF-κB1 (rs7665090), IL12RB2 (rs11209050), and STAT4 (rs7574865; all corrected P values rs7574865) was strongly associated after additional control samples were analyzed. Our study is the first large-scale genetic analysis in a Han Chinese PBC cohort. These results do not only reflect that Han Chinese PBC patients share common genetic susceptibility genes with both their Japanese and European counterparts but also suggest a distinctly different genetic susceptibility profile.

  1. Inelastic multiple scattering of interacting bosons in weak random potentials

    International Nuclear Information System (INIS)

    Geiger, Tobias

    2013-01-01

    Within the present thesis we develop a diagrammatic scattering theory for interacting bosons in a three-dimensional, weakly disordered potential. Based on a microscopic N-body scattering theory, we identify the relevant diagrams including elastic and inelastic collision processes that are sufficient to describe quantum transport in the regime of weak disorder. By taking advantage of the statistical properties of the weak disorder potential, we demonstrate how the N-body dynamics can be reduced to a nonlinear integral equation of Boltzmann type for the single-particle diffusive flux. A presently available alternative description - based on the Gross-Pitaevskii equation - only includes elastic collisions. In contrast, we show that far from equilibrium the presence of inelastic collisions - even for weak interaction strength - must be accounted for and can induce the full thermalization of the single-particle current. In addition, we also determine the coherent corrections to the incoherent transport, leading to the effect of coherent backscattering. For the first time, we are able to analyze the influence of inelastic collisions on the coherent backscattering signal, which lead to an enhancement of the backscattered cone in a narrow spectral window, even for increasing non-linearity. With a short recollection of the presently available experimental techniques we furthermore show how an immediate implementation of our suggested setup with confined Bose-Einstein condensates can be accomplished. Thereby, the emergence of collective and/or thermodynamic behavior from fundamental, microscopic constituents can also be assessed experimentally. In a second part of this thesis, we present first results for light scattering off strongly interacting Rydberg atoms trapped in a one-dimensional, chain-like configuration. In order to monitor the time-dependence of this interacting many-body system, we devise a weak measurement scenario for which we derive a master equation for the

  2. Exclusive description of multiple production on nuclei in the additive quark model. Multiplicity distributions in interactions with heavy nuclei

    International Nuclear Information System (INIS)

    Levchenko, B.B.; Nikolaev, N.N.

    1985-01-01

    In the framework of the additive quark model of multiple production on nuclei we calculate the multiplicity distributions of secondary particles and the correlations between secondary particles in πA and pA interactions with heavy nuclei. We show that intranuclear cascades are responsible for up to 50% of the nuclear increase of the multiplicity of fast particles. We analyze the sensitivity of the multiplicities and their correlations to the choice of the quark-hadronization function. We show that with good accuracy the yield of relativistic secondary particles from heavy and intermediate nuclei depends only on the number N/sub p/ of protons knocked out of the nucleus, and not on the mass number of the nucleus (N/sub p/ scaling)

  3. The genetics of multiple sclerosis: review of current and emerging candidates

    Science.gov (United States)

    Muñoz-Culla, Maider; Irizar, Haritz; Otaegui, David

    2013-01-01

    Multiple sclerosis (MS) is a complex disease in which environmental, genetic, and epigenetic factors determine the risk of developing the disease. The human leukocyte antigen region is the strongest susceptibility locus linked to MS, but it does not explain the whole heritability of the disease. To find other non-human leukocyte antigen loci associated with the disease, high-throughput genotyping, sequencing, and gene-expression studies have been performed, producing a valuable quantity of information. An overview of the genomic and expression studies is provided in this review, as well as microRNA-expression studies, highlighting the importance of combining all the layers of information in order to elucidate the causes or pathological mechanisms occurring in the disease. Genetics in MS is a promising field that is presumably going to be very productive in the next decade understanding the cross talk between all the factors contributing to the development of MS. PMID:24019748

  4. Understanding protein–protein interactions by genetic suppression

    Indian Academy of Sciences (India)

    Unknown

    Protein–protein interactions influence many cellular processes and it is increasingly being felt that even a weak and ... In a bacterial system where the complete genome sequence is available, it is an arduous ... teins (primary mutations) are useful in these studies. ... of interaction of this antibiotic with the central enzyme.

  5. Biological interactions and cooperative management of multiple species.

    Science.gov (United States)

    Jiang, Jinwei; Min, Yong; Chang, Jie; Ge, Ying

    2017-01-01

    Coordinated decision making and actions have become the primary solution for the overexploitation of interacting resources within ecosystems. However, the success of coordinated management is highly sensitive to biological, economic, and social conditions. Here, using a game theoretic framework and a 2-species model that considers various biological relationships (competition, predation, and mutualism), we compute cooperative (or joint) and non-cooperative (or separate) management equilibrium outcomes of the model and investigate the effects of the type and strength of the relationships. We find that cooperation does not always show superiority to non-cooperation in all biological interactions: (1) if and only if resources are involved in high-intensity predation relationships, cooperation can achieve a win-win scenario for ecosystem services and resource diversity; (2) for competitive resources, cooperation realizes higher ecosystem services by sacrificing resource diversity; and (3) for mutual resources, cooperation has no obvious advantage for either ecosystem services or resource evenness but can slightly improve resource abundance. Furthermore, by using a fishery model of the North California Current Marine Ecosystem with 63 species and seven fleets, we demonstrate that the theoretical results can be reproduced in real ecosystems. Therefore, effective ecosystem management should consider the interconnection between stakeholders' social relationship and resources' biological relationships.

  6. Speech comprehension aided by multiple modalities: behavioural and neural interactions

    Science.gov (United States)

    McGettigan, Carolyn; Faulkner, Andrew; Altarelli, Irene; Obleser, Jonas; Baverstock, Harriet; Scott, Sophie K.

    2014-01-01

    Speech comprehension is a complex human skill, the performance of which requires the perceiver to combine information from several sources – e.g. voice, face, gesture, linguistic context – to achieve an intelligible and interpretable percept. We describe a functional imaging investigation of how auditory, visual and linguistic information interact to facilitate comprehension. Our specific aims were to investigate the neural responses to these different information sources, alone and in interaction, and further to use behavioural speech comprehension scores to address sites of intelligibility-related activation in multifactorial speech comprehension. In fMRI, participants passively watched videos of spoken sentences, in which we varied Auditory Clarity (with noise-vocoding), Visual Clarity (with Gaussian blurring) and Linguistic Predictability. Main effects of enhanced signal with increased auditory and visual clarity were observed in overlapping regions of posterior STS. Two-way interactions of the factors (auditory × visual, auditory × predictability) in the neural data were observed outside temporal cortex, where positive signal change in response to clearer facial information and greater semantic predictability was greatest at intermediate levels of auditory clarity. Overall changes in stimulus intelligibility by condition (as determined using an independent behavioural experiment) were reflected in the neural data by increased activation predominantly in bilateral dorsolateral temporal cortex, as well as inferior frontal cortex and left fusiform gyrus. Specific investigation of intelligibility changes at intermediate auditory clarity revealed a set of regions, including posterior STS and fusiform gyrus, showing enhanced responses to both visual and linguistic information. Finally, an individual differences analysis showed that greater comprehension performance in the scanning participants (measured in a post-scan behavioural test) were associated with

  7. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

    Science.gov (United States)

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui; Kim, Su Yeon; Korneliussen, Thorfinn; Vinckenbosch, Nicolas; Tian, Geng; Huerta-Sanchez, Emilia; Feder, Alison F; Grarup, Niels; Jørgensen, Torben; Jiang, Tao; Witte, Daniel R; Sandbæk, Annelli; Hellmann, Ines; Lauritzen, Torsten; Hansen, Torben; Pedersen, Oluf; Wang, Jun; Nielsen, Rasmus

    2011-10-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

  8. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti

    2011-01-01

    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown...... the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture...... underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working...

  9. A genetic algorithm for multiple relay selection in two-way relaying cognitive radio networks

    KAUST Repository

    Alsharoa, Ahmad M.

    2013-09-01

    In this paper, we investigate a multiple relay selection scheme for two-way relaying cognitive radio networks where primary users and secondary users operate on the same frequency band. More specifically, cooperative relays using Amplifyand- Forward (AF) protocol are optimally selected to maximize the sum rate of the secondary users without degrading the Quality of Service (QoS) of the primary users by respecting a tolerated interference threshold. A strong optimization tool based on genetic algorithm is employed to solve our formulated optimization problem where discrete relay power levels are considered. Our simulation results show that the practical heuristic approach achieves almost the same performance of the optimal multiple relay selection scheme either with discrete or continuous power distributions. Copyright © 2013 by the Institute of Electrical and Electronic Engineers, Inc.

  10. Comparison of weighting approaches for genetic risk scores in gene-environment interaction studies.

    Science.gov (United States)

    Hüls, Anke; Krämer, Ursula; Carlsten, Christopher; Schikowski, Tamara; Ickstadt, Katja; Schwender, Holger

    2017-12-16

    Weighted genetic risk scores (GRS), defined as weighted sums of risk alleles of single nucleotide polymorphisms (SNPs), are statistically powerful for detection gene-environment (GxE) interactions. To assign weights, the gold standard is to use external weights from an independent study. However, appropriate external weights are not always available. In such situations and in the presence of predominant marginal genetic effects, we have shown in a previous study that GRS with internal weights from marginal genetic effects ("GRS-marginal-internal") are a powerful and reliable alternative to single SNP approaches or the use of unweighted GRS. However, this approach might not be appropriate for detecting predominant interactions, i.e. interactions showing an effect stronger than the marginal genetic effect. In this paper, we present a weighting approach for such predominant interactions ("GRS-interaction-training") in which parts of the data are used to estimate the weights from the interaction terms and the remaining data are used to determine the GRS. We conducted a simulation study for the detection of GxE interactions in which we evaluated power, type I error and sign-misspecification. We compared this new weighting approach to the GRS-marginal-internal approach and to GRS with external weights. Our simulation study showed that in the absence of external weights and with predominant interaction effects, the highest power was reached with the GRS-interaction-training approach. If marginal genetic effects were predominant, the GRS-marginal-internal approach was more appropriate. Furthermore, the power to detect interactions reached by the GRS-interaction-training approach was only slightly lower than the power achieved by GRS with external weights. The power of the GRS-interaction-training approach was confirmed in a real data application to the Traffic, Asthma and Genetics (TAG) Study (N = 4465 observations). When appropriate external weights are unavailable, we

  11. A Fast Multiple-Kernel Method With Applications to Detect Gene-Environment Interaction.

    Science.gov (United States)

    Marceau, Rachel; Lu, Wenbin; Holloway, Shannon; Sale, Michèle M; Worrall, Bradford B; Williams, Stephen R; Hsu, Fang-Chi; Tzeng, Jung-Ying

    2015-09-01

    Kernel machine (KM) models are a powerful tool for exploring associations between sets of genetic variants and complex traits. Although most KM methods use a single kernel function to assess the marginal effect of a variable set, KM analyses involving multiple kernels have become increasingly popular. Multikernel analysis allows researchers to study more complex problems, such as assessing gene-gene or gene-environment interactions, incorporating variance-component based methods for population substructure into rare-variant association testing, and assessing the conditional effects of a variable set adjusting for other variable sets. The KM framework is robust, powerful, and provides efficient dimension reduction for multifactor analyses, but requires the estimation of high dimensional nuisance parameters. Traditional estimation techniques, including regularization and the "expectation-maximization (EM)" algorithm, have a large computational cost and are not scalable to large sample sizes needed for rare variant analysis. Therefore, under the context of gene-environment interaction, we propose a computationally efficient and statistically rigorous "fastKM" algorithm for multikernel analysis that is based on a low-rank approximation to the nuisance effect kernel matrices. Our algorithm is applicable to various trait types (e.g., continuous, binary, and survival traits) and can be implemented using any existing single-kernel analysis software. Through extensive simulation studies, we show that our algorithm has similar performance to an EM-based KM approach for quantitative traits while running much faster. We also apply our method to the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, examining gene-by-vitamin effects on recurrent stroke risk and gene-by-age effects on change in homocysteine level. © 2015 WILEY PERIODICALS, INC.

  12. IVisTMSA: Interactive Visual Tools for Multiple Sequence Alignments.

    Science.gov (United States)

    Pervez, Muhammad Tariq; Babar, Masroor Ellahi; Nadeem, Asif; Aslam, Naeem; Naveed, Nasir; Ahmad, Sarfraz; Muhammad, Shah; Qadri, Salman; Shahid, Muhammad; Hussain, Tanveer; Javed, Maryam

    2015-01-01

    IVisTMSA is a software package of seven graphical tools for multiple sequence alignments. MSApad is an editing and analysis tool. It can load 409% more data than Jalview, STRAP, CINEMA, and Base-by-Base. MSA comparator allows the user to visualize consistent and inconsistent regions of reference and test alignments of more than 21-MB size in less than 12 seconds. MSA comparator is 5,200% efficient and more than 40% efficient as compared to BALiBASE c program and FastSP, respectively. MSA reconstruction tool provides graphical user interfaces for four popular aligners and allows the user to load several sequence files at a time. FASTA generator converts seven formats of alignments of unlimited size into FASTA format in a few seconds. MSA ID calculator calculates identity matrix of more than 11,000 sequences with a sequence length of 2,696 base pairs in less than 100 seconds. Tree and Distance Matrix calculation tools generate phylogenetic tree and distance matrix, respectively, using neighbor joining% identity and BLOSUM 62 matrix.

  13. Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer

    Directory of Open Access Journals (Sweden)

    Harlid Sophia

    2012-06-01

    Full Text Available Abstract Background Breast cancer today has many established risk factors, both genetic and environmental, but these risk factors by themselves explain only part of the total cancer incidence. We have investigated potential interactions between certain known genetic and phenotypic risk factors, specifically nine single nucleotide polymorphisms (SNPs and height, body mass index (BMI and hormone replacement therapy (HRT. Methods We analyzed samples from three different study populations: two prospectively followed Swedish cohorts and one Icelandic case–control study. Totally 2884 invasive breast cancer cases and 4508 controls were analysed in the study. Genotypes were determined using Mass spectrometry-Maldi-TOF and phenotypic variables were derived from measurements and/or questionnaires. Odds Ratios and 95% confidence intervals were calculated using unconditional logistic regression with the inclusion of an interaction term in the logistic regression model. Results One SNP (rs851987 in ESR1 tended to interact with height, with an increasingly protective effect of the major allele in taller women (p = 0.007 and rs13281615 (on 8q24 tended to confer risk only in non users of HRT (p-for interaction = 0.03. There were no significant interactions after correction for multiple testing. Conclusions We conclude that much larger sample sets would be necessary to demonstrate interactions between low-risk genetic polymorphisms and the phenotypic variables height, BMI and HRT on the risk for breast cancer. However the present hypothesis-generating study has identified tendencies that would be of interest to evaluate for gene-environment interactions in independent materials.

  14. Expression Profiling of Human Genetic and Protein Interaction Networks in Type 1 Diabetes

    DEFF Research Database (Denmark)

    Brunak, Søren; Bergholdt, R; Brorsson, C

    2009-01-01

    Proteins contributing to a complex disease are often members of the same functional pathways. Elucidation of such pathways may provide increased knowledge about functional mechanisms underlying disease. By combining genetic interactions in Type 1 Diabetes (T1D) with protein interaction data we have...

  15. Learning Effects of Interactive Whiteboard Pedagogy for Students in Taiwan from the Perspective of Multiple Intelligences

    Science.gov (United States)

    Chen, Hong-Ren; Chiang, Chih-Hao; Lin, Wen-Shan

    2013-01-01

    With the rapid progress in information technology, interactive whiteboards have become IT-integrated in teaching activities. The theory of multiple intelligences argues that every person possesses multiple intelligences, emphasizing learners' cognitive richness and the possible role of these differences in enhanced learning. This study is the…

  16. Flexibility and Project Value: Interactions and Multiple Real Options

    Science.gov (United States)

    Čulík, Miroslav

    2010-06-01

    This paper is focused on a project valuation with embedded portfolio of real options including their interactions. Valuation is based on the criterion of Net Present Value on the simulation basis. Portfolio includes selected types of European-type real options: option to expand, contract, abandon and temporarily shut down and restart a project. Due to the fact, that in reality most of the managerial flexibility takes the form of portfolio of real options, selected types of options are valued not only individually, but also in combination. The paper is structured as follows: first, diffusion models for forecasting of output prices and variable costs are derived. Second, project value is estimated on the assumption, that no real options are present. Next, project value is calculated with the presence of selected European-type options; these options and their impact on project value are valued first in isolation and consequently in different combinations. Moreover, intrinsic value evolution of given real options with respect to the time of exercising is analysed. In the end, results are presented graphically; selected statistics and risk measures (Value at Risk, Expected Shortfall) of the NPV's distributions are calculated and commented.

  17. Effects of interactions between common genetic variants and alcohol consumption on colorectal cancer risk

    Science.gov (United States)

    Song, Nan; Shin, Aesun; Oh, Jae Hwan; Kim, Jeongseon

    2018-01-01

    Background Genome-wide association studies (GWAS) have identified approximately 40 common genetic loci associated with colorectal cancer risk. To investigate possible gene-environment interactions (GEIs) between GWAS-identified single-nucleotide polymorphisms (SNPs) and alcohol consumption with respect to colorectal cancer, a hospital-based case-control study was conducted. Results Higher levels of alcohol consumption as calculated based on a standardized definition of a drink (1 drink=12.5g of ethanol) were associated with increased risk of colorectal cancer (OR=2.47, 95% CI=1.62-3.76 for heavy drinkers [>50g/day] compared to never drinkers; ptrendcolorectal cancer associated with the G allele of rs6687758 tended to increase among individuals in the heavier alcohol consumption strata. A statistically significant association between rs6687758 and colorectal cancer risk was observed among moderate alcohol drinkers who consumed between >12.5 and ≤50g of alcohol per day (OR=1.46, 95% CI=1.01-2.11). Methods A total of 2,109 subjects (703 colorectal cancer patients and 1,406 healthy controls) were recruited from the Korean National Cancer Center. For genotyping, 30 GWAS-identified SNPs were selected. A logistic regression model was used to evaluate associations of SNPs and alcohol consumption with colorectal cancer risk. We also tested GEIs between SNPs and alcohol consumption using a logistic model with multiplicative interaction terms. Conclusions Our results suggest that SNP rs6687758 at 1q41 may interact with alcohol consumption in the etiology of colorectal cancer. PMID:29464080

  18. Effects of interactions between common genetic variants and alcohol consumption on colorectal cancer risk.

    Science.gov (United States)

    Song, Nan; Shin, Aesun; Oh, Jae Hwan; Kim, Jeongseon

    2018-01-19

    Genome-wide association studies (GWAS) have identified approximately 40 common genetic loci associated with colorectal cancer risk. To investigate possible gene-environment interactions (GEIs) between GWAS-identified single-nucleotide polymorphisms (SNPs) and alcohol consumption with respect to colorectal cancer, a hospital-based case-control study was conducted. Higher levels of alcohol consumption as calculated based on a standardized definition of a drink (1 drink=12.5g of ethanol) were associated with increased risk of colorectal cancer (OR=2.47, 95% CI=1.62-3.76 for heavy drinkers [>50g/day] compared to never drinkers; p trend colorectal cancer associated with the G allele of rs6687758 tended to increase among individuals in the heavier alcohol consumption strata. A statistically significant association between rs6687758 and colorectal cancer risk was observed among moderate alcohol drinkers who consumed between >12.5 and ≤50g of alcohol per day (OR=1.46, 95% CI=1.01-2.11). A total of 2,109 subjects (703 colorectal cancer patients and 1,406 healthy controls) were recruited from the Korean National Cancer Center. For genotyping, 30 GWAS-identified SNPs were selected. A logistic regression model was used to evaluate associations of SNPs and alcohol consumption with colorectal cancer risk. We also tested GEIs between SNPs and alcohol consumption using a logistic model with multiplicative interaction terms. Our results suggest that SNP rs6687758 at 1q41 may interact with alcohol consumption in the etiology of colorectal cancer.

  19. One Novel Multiple-Target Plasmid Reference Molecule Targeting Eight Genetically Modified Canola Events for Genetically Modified Canola Detection.

    Science.gov (United States)

    Li, Zhuqing; Li, Xiang; Wang, Canhua; Song, Guiwen; Pi, Liqun; Zheng, Lan; Zhang, Dabing; Yang, Litao

    2017-09-27

    Multiple-target plasmid DNA reference materials have been generated and utilized as good substitutes of matrix-based reference materials in the analysis of genetically modified organisms (GMOs). Herein, we report the construction of one multiple-target plasmid reference molecule, pCAN, which harbors eight GM canola event-specific sequences (RF1, RF2, MS1, MS8, Topas 19/2, Oxy235, RT73, and T45) and a partial sequence of the canola endogenous reference gene PEP. The applicability of this plasmid reference material in qualitative and quantitative PCR assays of the eight GM canola events was evaluated, including the analysis of specificity, limit of detection (LOD), limit of quantification (LOQ), and performance of pCAN in the analysis of various canola samples, etc. The LODs are 15 copies for RF2, MS1, and RT73 assays using pCAN as the calibrator and 10 genome copies for the other events. The LOQ in each event-specific real-time PCR assay is 20 copies. In quantitative real-time PCR analysis, the PCR efficiencies of all event-specific and PEP assays are between 91% and 97%, and the squared regression coefficients (R 2 ) are all higher than 0.99. The quantification bias values varied from 0.47% to 20.68% with relative standard deviation (RSD) from 1.06% to 24.61% in the quantification of simulated samples. Furthermore, 10 practical canola samples sampled from imported shipments in the port of Shanghai, China, were analyzed employing pCAN as the calibrator, and the results were comparable with those assays using commercial certified materials as the calibrator. Concluding from these results, we believe that this newly developed pCAN plasmid is one good candidate for being a plasmid DNA reference material in the detection and quantification of the eight GM canola events in routine analysis.

  20. AprioriGWAS, a new pattern mining strategy for detecting genetic variants associated with disease through interaction effects.

    Science.gov (United States)

    Zhang, Qingrun; Long, Quan; Ott, Jurg

    2014-06-01

    Identifying gene-gene interaction is a hot topic in genome wide association studies. Two fundamental challenges are: (1) how to smartly identify combinations of variants that may be associated with the trait from astronomical number of all possible combinations; and (2) how to test epistatic interaction when all potential combinations are available. We developed AprioriGWAS, which brings two innovations. (1) Based on Apriori, a successful method in field of Frequent Itemset Mining (FIM) in which a pattern growth strategy is leveraged to effectively and accurately reduce search space, AprioriGWAS can efficiently identify genetically associated genotype patterns. (2) To test the hypotheses of epistasis, we adopt a new conditional permutation procedure to obtain reliable statistical inference of Pearson's chi-square test for the [Formula: see text] contingency table generated by associated variants. By applying AprioriGWAS to age-related macular degeneration (AMD) data, we found that: (1) angiopoietin 1 (ANGPT1) and four retinal genes interact with Complement Factor H (CFH). (2) GO term "glycosaminoglycan biosynthetic process" was enriched in AMD interacting genes. The epistatic interactions newly found by AprioriGWAS on AMD data are likely true interactions, since genes interacting with CFH are retinal genes, and GO term enrichment also verified that interaction between glycosaminoglycans (GAGs) and CFH plays an important role in disease pathology of AMD. By applying AprioriGWAS on Bipolar disorder in WTCCC data, we found variants without marginal effect show significant interactions. For example, multiple-SNP genotype patterns inside gene GABRB2 and GRIA1 (AMPA subunit 1 receptor gene). AMPARs are found in many parts of the brain and are the most commonly found receptor in the nervous system. The GABRB2 mediates the fastest inhibitory synaptic transmission in the central nervous system. GRIA1 and GABRB2 are relevant to mental disorders supported by multiple

  1. Core neuropathological abnormalities in progranulin-deficient mice are penetrant on multiple genetic backgrounds.

    Science.gov (United States)

    Petkau, T L; Hill, A; Leavitt, B R

    2016-02-19

    Loss-of-function mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal lobar degeneration (FTLD). A high degree of heterogeneity in the age-of-onset, duration of disease, and clinical presentation of FTLD, even among families carrying the same GRN mutation, suggests that additional modifying genes may be important to pathogenesis. Progranulin-knockout mice display subtle behavioral abnormalities and progressive neuropathological changes, as well as altered dendritic morphology and synaptic deficits in the hippocampus. In this study we evaluated multiple neuropathological endpoints in aged progranulin knockout mice and their wild-type littermates on two different genetic backgrounds: C57Bl/6 and 129/SvImJ. We find that in most brain regions, both strains are susceptible to progranulin-mediated neuropathological phenotypes, including astrogliosis, microgliosis, and highly accelerated deposition of the aging pigment lipofuscin. Neuroinflammation due to progranulin deficiency is exaggerated in the B6 strain and present, but less pronounced, in the 129 strain. Differences between the strains in hippocampal neuron counts and neuronal morphology suggest a complex role for progranulin in the hippocampus. We conclude that core progranulin-mediated neurodegenerative phenotypes are penetrant on multiple inbred mouse strains, but that genetic background modulates progranulin's role in neuroinflammation and hippocampal biology. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Progranulin genetic polymorphisms influence progression of disability and relapse recovery in multiple sclerosis.

    Science.gov (United States)

    Vercellino, Marco; Fenoglio, Chiara; Galimberti, Daniela; Mattioda, Alessandra; Chiavazza, Carlotta; Binello, Eleonora; Pinessi, Lorenzo; Giobbe, Dario; Scarpini, Elio; Cavalla, Paola

    2016-07-01

    Progranulin (GRN) is a multifunctional protein involved in inflammation and repair, and also a neurotrophic factor critical for neuronal survival. Progranulin is strongly expressed in multiple sclerosis (MS) brains by macrophages and microglia. In this study we evaluated GRN genetic variability in 400 MS patients, in correlation with clinical variables such as disease severity and relapse recovery. We also evaluated serum progranulin levels in the different groups of GRN variants carriers. We found that incomplete recovery after a relapse is correlated with an increased frequency of the rs9897526 A allele (odds ratio (OR) 4.367, p = 0.005). A more severe disease course (Multiple Sclerosis Severity Score > 5) is correlated with an increased frequency of the rs9897526 A allele (OR 1.886, p = 0.002) and of the rs5848 T allele (OR 1.580, p = 0.019). Carriers of the variants associated with a more severe disease course (rs9897526 A, rs5848 T) have significantly lower levels of circulating progranulin (80.5 ± 9.1 ng/mL vs. 165.7 ng/mL, p = 0.01). GRN genetic polymorphisms likely influence disease course and relapse recovery in MS. © The Author(s), 2015.

  3. Maternal Smoking During Pregnancy and Offspring Birth Weight: A Genetically-Informed Approach Comparing Multiple Raters

    Science.gov (United States)

    Knopik, Valerie S.; Marceau, Kristine; Palmer, Rohan H. C.; Smith, Taylor F.; Heath, Andrew C.

    2016-01-01

    Maternal smoking during pregnancy (SDP) is a significant public health concern with adverse consequences to the health and well-being of the fetus. There is considerable debate about the best method of assessing SDP, including birth/medical records, timeline follow-back approaches, multiple reporters, and biological verification (e.g., cotinine). This is particularly salient for genetically-informed approaches where it is not always possible or practical to do a prospective study starting during the prenatal period when concurrent biological specimen samples can be collected with ease. In a sample of families (N = 173) specifically selected for sibling pairs discordant for prenatal smoking exposure, we: (1) compare rates of agreement across different types of report—maternal report of SDP, paternal report of maternal SDP, and SDP contained on birth records from the Department of Vital Statistics; (2) examine whether SDP is predictive of birth weight outcomes using our best SDP report as identified via step (1); and (3) use a sibling-comparison approach that controls for genetic and familial influences that siblings share in order to assess the effects of SDP on birth weight. Results show high agreement between reporters and support the utility of retrospective report of SDP. Further, we replicate a causal association between SDP and birth weight, wherein SDP results in reduced birth weight even when accounting for genetic and familial confounding factors via a sibling comparison approach. PMID:26494459

  4. Interaction between microbiome and host genetics in psoriatic arthritis.

    Science.gov (United States)

    Chimenti, Maria Sole; Perricone, Carlo; Novelli, Lucia; Caso, Francesco; Costa, Luisa; Bogdanos, Dimitrios; Conigliaro, Paola; Triggianese, Paola; Ciccacci, Cinzia; Borgiani, Paola; Perricone, Roberto

    2018-03-01

    Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, seen in combination with psoriasis. Both genetic and environmental factors are responsible for the development of PsA, however little is known about the different weight of these two distinctive components in the pathogenesis of the disease. Genomic variability in PsA is associated with the disease and/or some peculiar clinical phenotypes. Candidate genes involved are crucial in inflammation, immune system, and epithelial permeability. Moreover, the genesis and regulation of inflammation are influenced by the composition of the human intestinal microbiome that is able to modulate both mucosal and systemic immune system. It is possible that pro-inflammatory responses initiated in gut mucosa could contribute to the induction and progression of autoimmune conditions. Given such premises, the aim of this review is to summarize immune-mediated response and specific bacterial changes in the composition of fecal microbiota in PsA patients and to analyze the relationships between bacterial changes, immune system, and host genetic background. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy.

    Directory of Open Access Journals (Sweden)

    Ammar Al-Chalabi

    Full Text Available BACKGROUND: Multiple system atrophy (MSA is a progressive neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia and autonomic dysfunction. Pathogenic mechanisms remain obscure but the neuropathological hallmark is the presence of alpha-synuclein-immunoreactive glial cytoplasmic inclusions. Genetic variants of the alpha-synuclein gene, SNCA, are thus strong candidates for genetic association with MSA. One follow-up to a genome-wide association of Parkinson's disease has identified association of a SNP in SNCA with MSA. METHODOLOGY/FINDINGS: We evaluated 32 SNPs in the SNCA gene in a European population of 239 cases and 617 controls recruited as part of the Neuroprotection and Natural History in Parkinson Plus Syndromes (NNIPPS study. We used 161 independently collected samples for replication. Two SNCA SNPs showed association with MSA: rs3822086 (P = 0.0044, and rs3775444 (P = 0.012, although only the first survived correction for multiple testing. In the MSA-C subgroup the association strengthened despite more than halving the number of cases: rs3822086 P = 0.0024, OR 2.153, (95% CI 1.3-3.6; rs3775444 P = 0.0017, OR 4.386 (95% CI 1.6-11.7. A 7-SNP haplotype incorporating three SNPs either side of rs3822086 strengthened the association with MSA-C further (best haplotype, P = 8.7 x 10(-4. The association with rs3822086 was replicated in the independent samples (P = 0.035. CONCLUSIONS/SIGNIFICANCE: We report a genetic association between MSA and alpha-synuclein which has replicated in independent samples. The strongest association is with the cerebellar subtype of MSA. TRIAL REGISTRATION: ClinicalTrials.gov NCT00211224.

  6. Genetic Factors Associated with Risk and Disability Progression of Multiple Sclerosis in Slovak Population

    Directory of Open Access Journals (Sweden)

    Hanysova Sandra

    2017-08-01

    Full Text Available Objective: The aim of our study was to determine the relation of particular genetic variants in selected genes (GSTM1, GSTT1 null genotypes; rs1695 GSTP1; rs10735781 EVI5 to the risk of multiple sclerosis (MS development and find out the possible association with disease disability progression rate. Material and methods: Our study included 202 MS patients and 174 healthy control volunteers. MS patients were divided according to disability progression rate to three groups - slowly progressing, mid-rate progressing and rapidly progressing. All DNA samples were isolated from venous blood. Genotyping was performed by PCR-RFLP and multiplex PCR. Results: Our analysis showed that GSTT1 null genotype (OR 0.56; 95%CI 0.33 -0.95; p=0.04 and GSTM1, GSTT1 double null genotype (OR 0.32; 95%CI 0.14 - 0.74; p=0.006 are potentially protective in relation to MS. We observed similar result in GSTT1 null genotype in association with mid-rate progression (OR 0.48; 95%CI 0.24 - 0.97; p=0.05. Frequency of GSTM1 and GSTT1 double null genotype is significantly lower in subgroup of MS patients with progression rate defined as slow (OR 0.22; 95%CI 0.05 - 0.98; p=0.05 and middle (OR 0.33; 95%CI 0.11 - 0.99; p=0.045. We did not show any significant association of genetic changes rs1695 in GSTP1 and rs10735781 in EVI5 with MS or rate of disease progression. Conclusions: Genetic basis of multiple sclerosis is still not fully elucidated. Further research may clarify our results and confirm the value of studied factors for clinical practice.

  7. Attentional Processes in Interactions between People with Profound Intellectual and Multiple Disabilities and Direct Support Staff

    Science.gov (United States)

    Ine, Hostyn; Heleen, Neerinckx; Bea, Maes

    2011-01-01

    Few studies have examined joint attention in interactions with persons with profound intellectual and multiple disabilities (PIMD), despite its important role in high-quality interaction. The purpose of this study is to describe the attention-directing behaviours of persons with PIMD and their direct support staff and the attention episodes…

  8. Interaction between Persons with Profound Intellectual and Multiple Disabilities and Their Partners: A Literature Review

    Science.gov (United States)

    Hostyn, Ine; Maes, Bea

    2009-01-01

    Background: High quality interactions are of crucial importance for quality of life of persons with profound intellectual and multiple disabilities (PIMD). This literature review describes and synthesises studies addressing the interaction between persons with PIMD and their partners. Method: A computerised literature search using defined…

  9. Genetic variants are major determinants of CSF antibody levels in multiple sclerosis.

    Science.gov (United States)

    Goris, An; Pauwels, Ine; Gustavsen, Marte W; van Son, Brechtje; Hilven, Kelly; Bos, Steffan D; Celius, Elisabeth Gulowsen; Berg-Hansen, Pål; Aarseth, Jan; Myhr, Kjell-Morten; D'Alfonso, Sandra; Barizzone, Nadia; Leone, Maurizio A; Martinelli Boneschi, Filippo; Sorosina, Melissa; Liberatore, Giuseppe; Kockum, Ingrid; Olsson, Tomas; Hillert, Jan; Alfredsson, Lars; Bedri, Sahl Khalid; Hemmer, Bernhard; Buck, Dorothea; Berthele, Achim; Knier, Benjamin; Biberacher, Viola; van Pesch, Vincent; Sindic, Christian; Bang Oturai, Annette; Søndergaard, Helle Bach; Sellebjerg, Finn; Jensen, Poul Erik H; Comabella, Manuel; Montalban, Xavier; Pérez-Boza, Jennifer; Malhotra, Sunny; Lechner-Scott, Jeannette; Broadley, Simon; Slee, Mark; Taylor, Bruce; Kermode, Allan G; Gourraud, Pierre-Antoine; Sawcer, Stephen J; Andreassen, Bettina Kullle; Dubois, Bénédicte; Harbo, Hanne F

    2015-03-01

    Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index-the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA-DQA1*0301 (P comparing two haplotypes = 8.88 × 10(-16)). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 × 10(-7)). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 × 10(-37)). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 × 10(-22)), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 × 10(-6)). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such

  10. Genetic variants are major determinants of CSF antibody levels in multiple sclerosis

    Science.gov (United States)

    Pauwels, Ine; Gustavsen, Marte W.; van Son, Brechtje; Hilven, Kelly; Bos, Steffan D.; Celius, Elisabeth Gulowsen; Berg-Hansen, Pål; Aarseth, Jan; Myhr, Kjell-Morten; D’Alfonso, Sandra; Barizzone, Nadia; Leone, Maurizio A.; Martinelli Boneschi, Filippo; Sorosina, Melissa; Liberatore, Giuseppe; Kockum, Ingrid; Olsson, Tomas; Hillert, Jan; Alfredsson, Lars; Bedri, Sahl Khalid; Hemmer, Bernhard; Buck, Dorothea; Berthele, Achim; Knier, Benjamin; Biberacher, Viola; van Pesch, Vincent; Sindic, Christian; Bang Oturai, Annette; Søndergaard, Helle Bach; Sellebjerg, Finn; Jensen, Poul Erik H.; Comabella, Manuel; Montalban, Xavier; Pérez-Boza, Jennifer; Malhotra, Sunny; Lechner-Scott, Jeannette; Broadley, Simon; Slee, Mark; Taylor, Bruce; Kermode, Allan G.; Gourraud, Pierre-Antoine; Sawcer, Stephen J.; Andreassen, Bettina Kullle; Dubois, Bénédicte; Harbo, Hanne F.

    2015-01-01

    Immunological hallmarks of multiple sclerosis include the production of antibodies in the central nervous system, expressed as presence of oligoclonal bands and/or an increased immunoglobulin G index—the level of immunoglobulin G in the cerebrospinal fluid compared to serum. However, the underlying differences between oligoclonal band-positive and -negative patients with multiple sclerosis and reasons for variability in immunoglobulin G index are not known. To identify genetic factors influencing the variation in the antibody levels in the cerebrospinal fluid in multiple sclerosis, we have performed a genome-wide association screen in patients collected from nine countries for two traits, presence or absence of oligoclonal bands (n = 3026) and immunoglobulin G index levels (n = 938), followed by a replication in 3891 additional patients. We replicate previously suggested association signals for oligoclonal band status in the major histocompatibility complex region for the rs9271640*A-rs6457617*G haplotype, correlated with HLA-DRB1*1501, and rs34083746*G, correlated with HLA-DQA1*0301 (P comparing two haplotypes = 8.88 × 10−16). Furthermore, we identify a novel association signal of rs9807334, near the ELAC1/SMAD4 genes, for oligoclonal band status (P = 8.45 × 10−7). The previously reported association of the immunoglobulin heavy chain locus with immunoglobulin G index reaches strong evidence for association in this data set (P = 3.79 × 10−37). We identify two novel associations in the major histocompatibility complex region with immunoglobulin G index: the rs9271640*A-rs6457617*G haplotype (P = 1.59 × 10−22), shared with oligoclonal band status, and an additional independent effect of rs6457617*G (P = 3.68 × 10−6). Variants identified in this study account for up to 2-fold differences in the odds of being oligoclonal band positive and 7.75% of the variation in immunoglobulin G index. Both traits are associated with clinical features of disease such

  11. Log-Normal Distribution in a Growing System with Weighted and Multiplicatively Interacting Particles

    Science.gov (United States)

    Fujihara, Akihiro; Tanimoto, Satoshi; Yamamoto, Hiroshi; Ohtsuki, Toshiya

    2018-03-01

    A growing system with weighted and multiplicatively interacting particles is investigated. Each particle has a quantity that changes multiplicatively after a binary interaction, with its growth rate controlled by a weight parameter in a homogeneous symmetric kernel. We consider the system using moment inequalities and analytically derive the log-normal-type tail in the probability distribution function of quantities when the parameter is negative, which is different from the result for single-body multiplicative processes. We also find that the system approaches a winner-take-all state when the parameter is positive.

  12. Genetics-based interactions among plants, pathogens, and herbivores define arthropod community structure.

    Science.gov (United States)

    Busby, Posy E; Lamit, Louis J; Keith, Arthur R; Newcombe, George; Gehring, Catherine A; Whitham, Thomas G; Dirzo, Rodolfo

    2015-07-01

    Plant resistance to pathogens or insect herbivores is common, but its potential for indirectly influencing plant-associated communities is poorly known. Here, we test whether pathogens' indirect effects on arthropod communities and herbivory depend on plant resistance to pathogens and/or herbivores, and address the overarching interacting foundation species hypothesis that genetics-based interactions among a few highly interactive species can structure a much larger community. In a manipulative field experiment using replicated genotypes of two Populus species and their interspecific hybrids, we found that genetic variation in plant resistance to both pathogens and insect herbivores modulated the strength of pathogens' indirect effects on arthropod communities and insect herbivory. First, due in part to the pathogens' differential impacts on leaf biomass among the two Populus species and the hybrids, the pathogen most strongly impacted arthropod community composition, richness, and abundance on the pathogen-susceptible tree species. Second, we found similar patterns comparing pathogen-susceptible and pathogen-resistant genotypes within species. Third, within a plant species, pathogens caused a fivefold greater reduction in herbivory on insect-herbivore-susceptible plant genotypes than on herbivore-resistant genotypes, demonstrating that the pathogen-herbivore interaction is genotype dependent. We conclude that interactions among plants, pathogens, and herbivores can structure multitrophic communities, supporting the interacting foundation species hypothesis. Because these interactions are genetically based, evolutionary changes in genetic resistance could result in ecological changes in associated communities, which may in turn feed back to affect plant fitness.

  13. Physiology and Genetics of Tree-Phytophage Interactions

    Science.gov (United States)

    Frances Lieutier; William J. Mattson; Michael R. Wagner

    1999-01-01

    Interactions between trees and phytophagous organisms represent an important fundamental process in the evolution of forest ecosystems. Through evolutionary time, the special traits of trees have lead the herbivore populations to differentiate and evolve in order to cope with the variability in natural resistance mechanisms of their hosts. Conversely, damage by...

  14. Interaction between 5 genetic variants and allergy in glioma risk

    DEFF Research Database (Denmark)

    Schoemaker, Minouk J; Robertson, Lindsay; Wigertz, Annette

    2010-01-01

    , CDKN2A-CDKN2B), 11q23.3 (rs498872, PHLDB1), and 20q13.33 (rs6010620, RTEL1) as determinants of glioma risk. The authors investigated whether there is interaction between the effects of allergy and these 5 variants on glioma risk. Data from 5 case-control studies carried out in Denmark, Finland, Sweden...

  15. A rapid and efficient protocol for in vitro multiplication of genetically uniform Stevia rebaudiana (Bertoni).

    Science.gov (United States)

    Khan, A; Jayanthi, M; Gantasala, Nagavara Prasad; Bhooshan, N; Rao, Uma

    2016-07-01

    Stevia rebaudiana (Bertoni), commonly called candy leaf or sweet leaf, endemic to South America, is an important medicinal plant. As a source of low calorie natural sweetener 'stevoside', it is used in obesity, diabetes, treatment of heartburn and tooth decay, and also serves as a food supplement. Large scale commercial propagation of S. rebaudiana demands a suitable protocol. Here, we propose an improved protocol for in vitro multiplication of S. rebaudiana from nodal explants. In this protocol, the effect of laboratory grade urea on multiple shoot induction from nodal explants was studied. The nodal explants were initially cultured on Murashige and Skoog (MS) basal media for 2 weeks which facilitated the axillary bud break. Further, culturing of these explants on MS medium fortified with 6 benzyl amninopurine (BAP) (2 mg/L) and Naphthalene acetic acid (NAA) (1 mg/L) with and .without urea (5 mg/L) for a period of 40 days revealed maximum shoot production of 44.56 from a single nodal explant in media supplemented with urea as compared to 22.44 without urea. The differences in the number of shoots produced were significant and these shoots readily rooted in MS media with NAA (4 mg/L). Primary and secondary hardening was successful in these plants. There were no visible morphological abnormalities observed in the micropropagated plantlets. Genetic analysis from random samples also revealed that these plants are genetically uniform. The advantage of the present protocol is that the complete process of multiple shoot induction, rooting and hardening could be completed within a period of 6 months as compared to the existing protocols.

  16. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

    Science.gov (United States)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C.A.; Patsopoulos, Nikolaos A.; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Booth, David R.; Potter, Simon C.; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D’alfonso, Sandra; Blackburn, Hannah; Boneschi, Filippo Martinelli; Liddle, Jennifer; Harbo, Hanne F.; Perez, Marc L.; Spurkland, Anne; Waller, Matthew J; Mycko, Marcin P.; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T.; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J.; Barcellos, Lisa F.; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E.; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P.; Brassat, David; Broadley, Simon A.; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M.; Cavalla, Paola; Celius, Elisabeth G.; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B.; Cozen, Wendy; Cree, Bruce A.C.; Cross, Anne H.; Cusi, Daniele; Daly, Mark J.; Davis, Emma; de Bakker, Paul I.W.; Debouverie, Marc; D’hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F.A.; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans-Peter; Heard, Rob N.; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G.; Kilpatrick, Trevor J.; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S.; Leone, Maurizio A.; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R.; Link, Jenny; Liu, Jianjun; Lorentzen, Åslaug R.; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L.; Mentch, Frank; Mero, Inger-Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell-Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L.; Ramsay, Patricia P.; Reunanen, Mauri; Reynolds, Richard; Rioux, John D.; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P.; Rückert, Ina-Maria; Salvetti, Marco; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A.; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J.; Sellebjerg, Finn; Selmaj, Krzysztof W.; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M.A.; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C.; Sulonen, Anna-Maija; Sundqvist, Emilie; Syvänen, Ann-Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M.; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A.; Tronczynska, Ewa; Casas, Juan P.; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S.; Wang, Kai; Mathew, Christopher G.; Wason, James; Palmer, Colin N.A.; Wichmann, H-Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C.; Yaouanq, Jacqueline; Viswanathan, Ananth C.; Zhang, Haitao; Wood, Nicholas W.; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J.; De Jager, Philip L.; Peltonen, Leena; Stewart, Graeme J.; Hafler, David A.; Hauser, Stephen L.; McVean, Gil; Donnelly, Peter; Compston, Alastair

    2011-01-01

    Multiple sclerosis (OMIM 126200) is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability.1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals;2,3 and systematic attempts to identify linkage in multiplex families have confirmed that variation within the Major Histocompatibility Complex (MHC) exerts the greatest individual effect on risk.4 Modestly powered Genome-Wide Association Studies (GWAS)5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects play a key role in disease susceptibility.11 Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the Class I region. Immunologically relevant genes are significantly over-represented amongst those mapping close to the identified loci and particularly implicate T helper cell differentiation in the pathogenesis of multiple sclerosis. PMID:21833088

  17. Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders

    Science.gov (United States)

    Leblond, Claire S.; Heinrich, Jutta; Delorme, Richard; Proepper, Christian; Betancur, Catalina; Huguet, Guillaume; Konyukh, Marina; Chaste, Pauline; Ey, Elodie; Rastam, Maria; Anckarsäter, Henrik; Nygren, Gudrun; Gillberg, I. Carina; Melke, Jonas; Toro, Roberto; Regnault, Beatrice; Fauchereau, Fabien; Mercati, Oriane; Lemière, Nathalie; Skuse, David; Poot, Martin; Holt, Richard; Monaco, Anthony P.; Järvelä, Irma; Kantojärvi, Katri; Vanhala, Raija; Curran, Sarah; Collier, David A.; Bolton, Patrick; Chiocchetti, Andreas; Klauck, Sabine M.; Poustka, Fritz; Freitag, Christine M.; Waltes, Regina; Kopp, Marnie; Duketis, Eftichia; Bacchelli, Elena; Minopoli, Fiorella; Ruta, Liliana; Battaglia, Agatino; Mazzone, Luigi; Maestrini, Elena; Sequeira, Ana F.; Oliveira, Barbara; Vicente, Astrid; Oliveira, Guiomar; Pinto, Dalila; Scherer, Stephen W.; Zelenika, Diana; Delepine, Marc; Lathrop, Mark; Bonneau, Dominique; Guinchat, Vincent; Devillard, Françoise; Assouline, Brigitte; Mouren, Marie-Christine; Leboyer, Marion; Gillberg, Christopher; Boeckers, Tobias M.; Bourgeron, Thomas

    2012-01-01

    Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD. PMID:22346768

  18. Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Claire S Leblond

    2012-02-01

    Full Text Available Autism spectrum disorders (ASD are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls. We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4% patients and in 16 of 1,090 (1.5% controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70. In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013. Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.

  19. Risk score modeling of multiple gene to gene interactions using aggregated-multifactor dimensionality reduction

    Directory of Open Access Journals (Sweden)

    Dai Hongying

    2013-01-01

    Full Text Available Abstract Background Multifactor Dimensionality Reduction (MDR has been widely applied to detect gene-gene (GxG interactions associated with complex diseases. Existing MDR methods summarize disease risk by a dichotomous predisposing model (high-risk/low-risk from one optimal GxG interaction, which does not take the accumulated effects from multiple GxG interactions into account. Results We propose an Aggregated-Multifactor Dimensionality Reduction (A-MDR method that exhaustively searches for and detects significant GxG interactions to generate an epistasis enriched gene network. An aggregated epistasis enriched risk score, which takes into account multiple GxG interactions simultaneously, replaces the dichotomous predisposing risk variable and provides higher resolution in the quantification of disease susceptibility. We evaluate this new A-MDR approach in a broad range of simulations. Also, we present the results of an application of the A-MDR method to a data set derived from Juvenile Idiopathic Arthritis patients treated with methotrexate (MTX that revealed several GxG interactions in the folate pathway that were associated with treatment response. The epistasis enriched risk score that pooled information from 82 significant GxG interactions distinguished MTX responders from non-responders with 82% accuracy. Conclusions The proposed A-MDR is innovative in the MDR framework to investigate aggregated effects among GxG interactions. New measures (pOR, pRR and pChi are proposed to detect multiple GxG interactions.

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

    Science.gov (United States)

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

    2013-10-01

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

  1. Scaling of chaotic multiplicity: A new observation in high-energy interactions

    International Nuclear Information System (INIS)

    Ghosh, D.; Ghosh, P.; Roy, J.

    1990-01-01

    We analyze high-energy-interaction data to study the dependence of chaotic multiplicity on the pseudorapidity window and propose a new scaling function bar Ψ(bar z)=left-angle n 1 right-angle/left-angle n right-angle max where left-angle n 1 right-angle is the chaotic multiplicity and bar z=left-angle n right-angle/left-angle n right-angle max is the reduced multiplicity, following the quantum-optical concept of particle production. It has been observed that the proposed ''chaotic multiplicity scaling'' is obeyed by pp, p bar p, and AA collisions at different available energies

  2. Daf-2, Daf-16 and Daf-23: Genetically Interacting Genes Controlling Dauer Formation in Caenorhabditis Elegans

    OpenAIRE

    Gottlieb, S.; Ruvkun, G.

    1994-01-01

    Under conditions of high population density and low food, Caenorhabditis elegans forms an alternative third larval stage, called the dauer stage, which is resistant to desiccation and harsh environments. Genetic analysis of some dauer constitutive (Daf-c) and dauer defective (Daf-d) mutants has revealed a complex pathway that is likely to function in particular neurons and/or responding tissues. Here we analyze the genetic interactions between three genes which comprise a branch of the dauer ...

  3. Gene × Environment Interactions in Schizophrenia: Evidence from Genetic Mouse Models

    Directory of Open Access Journals (Sweden)

    Paula Moran

    2016-01-01

    Full Text Available The study of gene × environment, as well as epistatic interactions in schizophrenia, has provided important insight into the complex etiopathologic basis of schizophrenia. It has also increased our understanding of the role of susceptibility genes in the disorder and is an important consideration as we seek to translate genetic advances into novel antipsychotic treatment targets. This review summarises data arising from research involving the modelling of gene × environment interactions in schizophrenia using preclinical genetic models. Evidence for synergistic effects on the expression of schizophrenia-relevant endophenotypes will be discussed. It is proposed that valid and multifactorial preclinical models are important tools for identifying critical areas, as well as underlying mechanisms, of convergence of genetic and environmental risk factors, and their interaction in schizophrenia.

  4. Gene × Environment Interactions in Schizophrenia: Evidence from Genetic Mouse Models.

    Science.gov (United States)

    Moran, Paula; Stokes, Jennifer; Marr, Julia; Bock, Gavin; Desbonnet, Lieve; Waddington, John; O'Tuathaigh, Colm

    2016-01-01

    The study of gene × environment, as well as epistatic interactions in schizophrenia, has provided important insight into the complex etiopathologic basis of schizophrenia. It has also increased our understanding of the role of susceptibility genes in the disorder and is an important consideration as we seek to translate genetic advances into novel antipsychotic treatment targets. This review summarises data arising from research involving the modelling of gene × environment interactions in schizophrenia using preclinical genetic models. Evidence for synergistic effects on the expression of schizophrenia-relevant endophenotypes will be discussed. It is proposed that valid and multifactorial preclinical models are important tools for identifying critical areas, as well as underlying mechanisms, of convergence of genetic and environmental risk factors, and their interaction in schizophrenia.

  5. Gene × Environment Interactions in Schizophrenia: Evidence from Genetic Mouse Models

    Science.gov (United States)

    Marr, Julia; Bock, Gavin; Desbonnet, Lieve; Waddington, John

    2016-01-01

    The study of gene × environment, as well as epistatic interactions in schizophrenia, has provided important insight into the complex etiopathologic basis of schizophrenia. It has also increased our understanding of the role of susceptibility genes in the disorder and is an important consideration as we seek to translate genetic advances into novel antipsychotic treatment targets. This review summarises data arising from research involving the modelling of gene × environment interactions in schizophrenia using preclinical genetic models. Evidence for synergistic effects on the expression of schizophrenia-relevant endophenotypes will be discussed. It is proposed that valid and multifactorial preclinical models are important tools for identifying critical areas, as well as underlying mechanisms, of convergence of genetic and environmental risk factors, and their interaction in schizophrenia. PMID:27725886

  6. Synergistic interactions between Drosophila orthologues of genes spanned by de novo human CNVs support multiple-hit models of autism.

    Science.gov (United States)

    Grice, Stuart J; Liu, Ji-Long; Webber, Caleb

    2015-03-01

    Autism spectrum disorders (ASDs) are highly heritable and characterised by deficits in social interaction and communication, as well as restricted and repetitive behaviours. Although a number of highly penetrant ASD gene variants have been identified, there is growing evidence to support a causal role for combinatorial effects arising from the contributions of multiple loci. By examining synaptic and circadian neurological phenotypes resulting from the dosage variants of unique human:fly orthologues in Drosophila, we observe numerous synergistic interactions between pairs of informatically-identified candidate genes whose orthologues are jointly affected by large de novo copy number variants (CNVs). These CNVs were found in the genomes of individuals with autism, including a patient carrying a 22q11.2 deletion. We first demonstrate that dosage alterations of the unique Drosophila orthologues of candidate genes from de novo CNVs that harbour only a single candidate gene display neurological defects similar to those previously reported in Drosophila models of ASD-associated variants. We then considered pairwise dosage changes within the set of orthologues of candidate genes that were affected by the same single human de novo CNV. For three of four CNVs with complete orthologous relationships, we observed significant synergistic effects following the simultaneous dosage change of gene pairs drawn from a single CNV. The phenotypic variation observed at the Drosophila synapse that results from these interacting genetic variants supports a concordant phenotypic outcome across all interacting gene pairs following the direction of human gene copy number change. We observe both specificity and transitivity between interactors, both within and between CNV candidate gene sets, supporting shared and distinct genetic aetiologies. We then show that different interactions affect divergent synaptic processes, demonstrating distinct molecular aetiologies. Our study illustrates

  7. Efficient multiple-trait association and estimation of genetic correlation using the matrix-variate linear mixed model.

    Science.gov (United States)

    Furlotte, Nicholas A; Eskin, Eleazar

    2015-05-01

    Multiple-trait association mapping, in which multiple traits are used simultaneously in the identification of genetic variants affecting those traits, has recently attracted interest. One class of approaches for this problem builds on classical variance component methodology, utilizing a multitrait version of a linear mixed model. These approaches both increase power and provide insights into the genetic architecture of multiple traits. In particular, it is possible to estimate the genetic correlation, which is a measure of the portion of the total correlation between traits that is due to additive genetic effects. Unfortunately, the practical utility of these methods is limited since they are computationally intractable for large sample sizes. In this article, we introduce a reformulation of the multiple-trait association mapping approach by defining the matrix-variate linear mixed model. Our approach reduces the computational time necessary to perform maximum-likelihood inference in a multiple-trait model by utilizing a data transformation. By utilizing a well-studied human cohort, we show that our approach provides more than a 10-fold speedup, making multiple-trait association feasible in a large population cohort on the genome-wide scale. We take advantage of the efficiency of our approach to analyze gene expression data. By decomposing gene coexpression into a genetic and environmental component, we show that our method provides fundamental insights into the nature of coexpressed genes. An implementation of this method is available at http://genetics.cs.ucla.edu/mvLMM. Copyright © 2015 by the Genetics Society of America.

  8. Genetic interaction network of the Saccharomyces cerevisiae type 1 phosphatase Glc7

    Directory of Open Access Journals (Sweden)

    Neszt Michael

    2008-07-01

    Full Text Available Abstract Background Protein kinases and phosphatases regulate protein phosphorylation, a critical means of modulating protein function, stability and localization. The identification of functional networks for protein phosphatases has been slow due to their redundant nature and the lack of large-scale analyses. We hypothesized that a genome-scale analysis of genetic interactions using the Synthetic Genetic Array could reveal protein phosphatase functional networks. We apply this approach to the conserved type 1 protein phosphatase Glc7, which regulates numerous cellular processes in budding yeast. Results We created a novel glc7 catalytic mutant (glc7-E101Q. Phenotypic analysis indicates that this novel allele exhibits slow growth and defects in glucose metabolism but normal cell cycle progression and chromosome segregation. This suggests that glc7-E101Q is a hypomorphic glc7 mutant. Synthetic Genetic Array analysis of glc7-E101Q revealed a broad network of 245 synthetic sick/lethal interactions reflecting that many processes are required when Glc7 function is compromised such as histone modification, chromosome segregation and cytokinesis, nutrient sensing and DNA damage. In addition, mitochondrial activity and inheritance and lipid metabolism were identified as new processes involved in buffering Glc7 function. An interaction network among 95 genes genetically interacting with GLC7 was constructed by integration of genetic and physical interaction data. The obtained network has a modular architecture, and the interconnection among the modules reflects the cooperation of the processes buffering Glc7 function. Conclusion We found 245 genes required for the normal growth of the glc7-E101Q mutant. Functional grouping of these genes and analysis of their physical and genetic interaction patterns bring new information on Glc7-regulated processes.

  9. Wide range of interacting partners of pea Gβ subunit of G-proteins suggests its multiple functions in cell signalling.

    Science.gov (United States)

    Bhardwaj, Deepak; Lakhanpaul, Suman; Tuteja, Narendra

    2012-09-01

    Climate change is a major concern especially in view of the increasing global population and food security. Plant scientists need to look for genetic tools whose appropriate usage can contribute to sustainable food availability. G-proteins have been identified as some of the potential genetic tools that could be useful for protecting plants from various stresses. Heterotrimeric G-proteins consisting of three subunits Gα, Gβ and Gγ are important components of a number of signalling pathways. Their structure and functions are already well studied in animals but their potential in plants is now gaining attention for their role in stress tolerance. Earlier we have reported that over expressing pea Gβ conferred heat tolerance in tobacco plants. Here we report the interacting partners (proteins) of Gβ subunit of Pisum sativum and their putative role in stress and development. Out of 90 transformants isolated from the yeast-two-hybrid (Y2H) screening, seven were chosen for further investigation due to their recurrence in multiple experiments. These interacting partners were confirmed using β-galactosidase colony filter lift and ONPG (O-nitrophenyl-β-D-galactopyranoside) assays. These partners include thioredoxin H, histidine-containing phosphotransfer protein 5-like, pathogenesis-related protein, glucan endo-beta-1, 3-glucosidase (acidic isoform), glycine rich RNA binding protein, cold and drought-regulated protein (corA gene) and soluble inorganic pyrophosphatase 1. This study suggests the role of pea Gβ subunit in stress signal transduction and development pathways owing to its capability to interact with a wide range of proteins of multiple functions. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  10. Oscillations in the interactions among multiple solitons in an optical fibre

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Wen-Qiang; Gao, Yi-Tian; Zhao, Chen; Feng, Yu-Jie; Su, Chuan-Qi [Beijing University of Aeronautics and Astronautics (China). Ministry of Education Key Laboratory of Fluid Mechanics; Beijing University of Aeronautics and Astronautics (China). National Laboratory for Computational Fluid Dynamics

    2016-07-01

    In this article, under the investigation on the interactions among multiple solitons for an eighth-order nonlinear Schroedinger equation in an optical fibre, oscillations in the interaction zones are observed theoretically. With different coefficients of the operators in this equation, we find that (1) the oscillations in the solitonic interaction zones have different forms with different spectral parameters of this equation; (2) the oscillations in the interactions among the multiple solitons are affected by the choice of spectral parameters, the dispersive effects and nonlinearity of the eighth-order operator; (3) the second-, fifth-, sixth-, and seventh-order operators restrain oscillations in the solitonic interaction zones and the higher-order operators have stronger attenuated effects than the lower ones, while the third- and fourth-order operators stimulate and extend the scope of oscillations.

  11. Genetic susceptibility loci, environmental exposures, and Parkinson's disease: a case-control study of gene-environment interactions.

    Science.gov (United States)

    Chung, Sun Ju; Armasu, Sebastian M; Anderson, Kari J; Biernacka, Joanna M; Lesnick, Timothy G; Rider, David N; Cunningham, Julie M; Ahlskog, J Eric; Frigerio, Roberta; Maraganore, Demetrius M

    2013-06-01

    Prior studies causally linked mutations in SNCA, MAPT, and LRRK2 genes with familial Parkinsonism. Genome-wide association studies have demonstrated association of single nucleotide polymorphisms (SNPs) in those three genes with sporadic Parkinson's disease (PD) susceptibility worldwide. Here we investigated the interactions between SNPs in those three susceptibility genes and environmental exposures (pesticides application, tobacco smoking, coffee drinking, and alcohol drinking) also associated with PD susceptibility. Pairwise interactions between environmental exposures and 18 variants (16 SNPs and two variable number tandem repeats, or "VNTRs") in SNCA, MAPT and LRRK2, were investigated using data from 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Environmental exposures were assessed using a validated telephone interview script. Five pairwise interactions had uncorrected P-values coffee drinking × MAPT H1/H2 haplotype or MAPT rs16940806, and alcohol drinking × MAPT rs2435211. None of these interactions remained significant after Bonferroni correction. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not identify significant interactions after Bonferroni correction. This study documented limited pairwise interactions between established genetic and environmental risk factors for PD; however, the associations were not significant after correction for multiple testing. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Ras1 interacts with multiple new signaling and cytoskeletal loci in Drosophila eggshell patterning and morphogenesis.

    Science.gov (United States)

    Schnorr, J D; Holdcraft, R; Chevalier, B; Berg, C A

    2001-10-01

    Little is known about the genes that interact with Ras signaling pathways to regulate morphogenesis. The synthesis of dorsal eggshell structures in Drosophila melanogaster requires multiple rounds of Ras signaling followed by dramatic epithelial sheet movements. We took advantage of this process to identify genes that link patterning and morphogenesis; we screened lethal mutations on the second chromosome for those that could enhance a weak Ras1 eggshell phenotype. Of 1618 lethal P-element mutations tested, 13 showed significant enhancement, resulting in forked and fused dorsal appendages. Our genetic and molecular analyses together with information from the Berkeley Drosophila Genome Project reveal that 11 of these lines carry mutations in previously characterized genes. Three mutations disrupt the known Ras1 cell signaling components Star, Egfr, and Blistered, while one mutation disrupts Sec61beta, implicated in ligand secretion. Seven lines represent cell signaling and cytoskeletal components that are new to the Ras1 pathway; these are Chickadee (Profilin), Tec29, Dreadlocks, POSH, Peanut, Smt3, and MESK2, a suppressor of dominant-negative Ksr. A twelfth insertion disrupts two genes, Nrk, a "neurospecific" receptor tyrosine kinase, and Tpp, which encodes a neuropeptidase. These results suggest that Ras1 signaling during oogenesis involves novel components that may be intimately associated with additional signaling processes and with the reorganization of the cytoskeleton. To determine whether these Ras1 Enhancers function upstream or downstream of the Egf receptor, four mutations were tested for their ability to suppress an activated Egfr construct (lambdatop) expressed in oogenesis exclusively in the follicle cells. Mutations in Star and l(2)43Bb had no significant effect upon the lambdatop eggshell defect whereas smt3 and dock alleles significantly suppressed the lambdatop phenotype.

  13. Multiplicities of secondary hadrons produced in vp and overlinevp charged current interactions

    Science.gov (United States)

    Grässler, H.; Lanske, D.; Schulte, R.; Jones, G. T.; Middleton, R. P.; O'Neale, S. W.; Böckmann, K.; Gebel, W.; Geich-Gimbel, C.; Nellen, B.; Grant, A.; Klein, H.; Morrison, D. R. O.; Schmid, P.; Wachsmuth, H.; Chima, J. S.; Mobayyen, M. M.; Talebzadeh, M.; Villalobos-Baillie, O.; Aderholz, M.; Deck, L.; Schmitz, N.; Settles, R.; Wernhard, K. L.; Wittek, W.; Corrigan, G.; Myatt, G.; Radojicić, D.; Saitta, B.; Wells, J.; Aachen-Birmingham-Bonn-CERN-Imperial College-München (MPI)-Oxford Collaboration

    1983-08-01

    In an experiment with the hydrogen bubble chamber BEBC at CERN multiplicities of hadrons produced in νp and overlinevp interactions have been investigated. Results are presented on the multiplicities of charged hadrons and neutral pions, forward and backward multiplicities of charged hadrons and correlations between forward and backward multiplicities. Comparisons are made with hadronic reactions and e +e - annihilation. In the framework of the quark-parton model the data imply similar charged multiplicities for the fragments of a u- and a d-quark, and a larger multiplicities for the fragments of a uu- than for a ud-diquark. The correlation data suggest independent fragmentation of the quark and diquark for hadronic masses above ˜ 7 GeV and local charge compensation within an event.

  14. Multiplicities of secondary hadrons produced in vp and anti vp charged current interactions

    International Nuclear Information System (INIS)

    Graessler, H.; Lanske, D.; Schulte, R.; Chima, J.S.; Mobayyen, M.M.; Talebzadeh, M.; Villalobos-Baillie, O.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.

    1983-01-01

    In an experiment with the hydrogen bubble chamber BEBC at CERN multiplicities of hadrons produced in vp and anti vp interactions have been investigated. Results are presented on the multiplicities of charged hadrons and neutral pions, forward and backward multiplicities of charged hadrons and correlations between forward and backward multiplicities. Comparisons are made with hadronic reactions and e + e - annihilation. In the framework of the quark-parton model the data imply similar charged multiplicities for the fragments of a u- and a d-quark, and larger multiplicities for the fragments of a uu- than for a ud-diquark. The correlation data suggest independent fragmentation of the quark and diquark for hadronic masses above approx.= 7 GeV and local charge compensation within an event. (orig.)

  15. Cancer genetics education in a low- to middle-income country: evaluation of an interactive workshop for clinicians in Kenya.

    Directory of Open Access Journals (Sweden)

    Jessica A Hill

    Full Text Available Clinical genetic testing is becoming an integral part of medical care for inherited disorders. While genetic testing and counseling are readily available in high-income countries, in low- and middle-income countries like Kenya genetic testing is limited and genetic counseling is virtually non-existent. Genetic testing is likely to become widespread in Kenya within the next decade, yet there has not been a concomitant increase in genetic counseling resources. To address this gap, we designed an interactive workshop for clinicians in Kenya focused on the genetics of the childhood eye cancer retinoblastoma. The objectives were to increase retinoblastoma genetics knowledge, build genetic counseling skills and increase confidence in those skills.The workshop was conducted at the 2013 Kenyan National Retinoblastoma Strategy meeting. It included a retinoblastoma genetics presentation, small group discussion of case studies and genetic counseling role-play. Knowledge was assessed by standardized test, and genetic counseling skills and confidence by questionnaire.Knowledge increased significantly post-workshop, driven by increased knowledge of retinoblastoma causative genetics. One-year post-workshop, participant knowledge had returned to baseline, indicating that knowledge retention requires more frequent reinforcement. Participants reported feeling more confident discussing genetics with patients, and had integrated more genetic counseling into patient interactions.A comprehensive retinoblastoma genetics workshop can increase the knowledge and skills necessary for effective retinoblastoma genetic counseling.

  16. Cancer genetics education in a low- to middle-income country: evaluation of an interactive workshop for clinicians in Kenya.

    Science.gov (United States)

    Hill, Jessica A; Lee, Su Yeon; Njambi, Lucy; Corson, Timothy W; Dimaras, Helen

    2015-01-01

    Clinical genetic testing is becoming an integral part of medical care for inherited disorders. While genetic testing and counseling are readily available in high-income countries, in low- and middle-income countries like Kenya genetic testing is limited and genetic counseling is virtually non-existent. Genetic testing is likely to become widespread in Kenya within the next decade, yet there has not been a concomitant increase in genetic counseling resources. To address this gap, we designed an interactive workshop for clinicians in Kenya focused on the genetics of the childhood eye cancer retinoblastoma. The objectives were to increase retinoblastoma genetics knowledge, build genetic counseling skills and increase confidence in those skills. The workshop was conducted at the 2013 Kenyan National Retinoblastoma Strategy meeting. It included a retinoblastoma genetics presentation, small group discussion of case studies and genetic counseling role-play. Knowledge was assessed by standardized test, and genetic counseling skills and confidence by questionnaire. Knowledge increased significantly post-workshop, driven by increased knowledge of retinoblastoma causative genetics. One-year post-workshop, participant knowledge had returned to baseline, indicating that knowledge retention requires more frequent reinforcement. Participants reported feeling more confident discussing genetics with patients, and had integrated more genetic counseling into patient interactions. A comprehensive retinoblastoma genetics workshop can increase the knowledge and skills necessary for effective retinoblastoma genetic counseling.

  17. Transgene x environment interactions in genetically modified wheat.

    Science.gov (United States)

    Zeller, Simon L; Kalinina, Olena; Brunner, Susanne; Keller, Beat; Schmid, Bernhard

    2010-07-12

    The introduction of transgenes into plants may cause unintended phenotypic effects which could have an impact on the plant itself and the environment. Little is published in the scientific literature about the interrelation of environmental factors and possible unintended effects in genetically modified (GM) plants. We studied transgenic bread wheat Triticum aestivum lines expressing the wheat Pm3b gene against the fungus powdery mildew Blumeria graminis f.sp. tritici. Four independent offspring pairs, each consisting of a GM line and its corresponding non-GM control line, were grown under different soil nutrient conditions and with and without fungicide treatment in the glasshouse. Furthermore, we performed a field experiment with a similar design to validate our glasshouse results. The transgene increased the resistance to powdery mildew in all environments. However, GM plants reacted sensitive to fungicide spraying in the glasshouse. Without fungicide treatment, in the glasshouse GM lines had increased vegetative biomass and seed number and a twofold yield compared with control lines. In the field these results were reversed. Fertilization generally increased GM/control differences in the glasshouse but not in the field. Two of four GM lines showed up to 56% yield reduction and a 40-fold increase of infection with ergot disease Claviceps purpurea compared with their control lines in the field experiment; one GM line was very similar to its control. Our results demonstrate that, depending on the insertion event, a particular transgene can have large effects on the entire phenotype of a plant and that these effects can sometimes be reversed when plants are moved from the glasshouse to the field. However, it remains unclear which mechanisms underlie these effects and how they may affect concepts in molecular plant breeding and plant evolutionary ecology.

  18. Transgene x environment interactions in genetically modified wheat.

    Directory of Open Access Journals (Sweden)

    Simon L Zeller

    Full Text Available BACKGROUND: The introduction of transgenes into plants may cause unintended phenotypic effects which could have an impact on the plant itself and the environment. Little is published in the scientific literature about the interrelation of environmental factors and possible unintended effects in genetically modified (GM plants. METHODS AND FINDINGS: We studied transgenic bread wheat Triticum aestivum lines expressing the wheat Pm3b gene against the fungus powdery mildew Blumeria graminis f.sp. tritici. Four independent offspring pairs, each consisting of a GM line and its corresponding non-GM control line, were grown under different soil nutrient conditions and with and without fungicide treatment in the glasshouse. Furthermore, we performed a field experiment with a similar design to validate our glasshouse results. The transgene increased the resistance to powdery mildew in all environments. However, GM plants reacted sensitive to fungicide spraying in the glasshouse. Without fungicide treatment, in the glasshouse GM lines had increased vegetative biomass and seed number and a twofold yield compared with control lines. In the field these results were reversed. Fertilization generally increased GM/control differences in the glasshouse but not in the field. Two of four GM lines showed up to 56% yield reduction and a 40-fold increase of infection with ergot disease Claviceps purpurea compared with their control lines in the field experiment; one GM line was very similar to its control. CONCLUSIONS: Our results demonstrate that, depending on the insertion event, a particular transgene can have large effects on the entire phenotype of a plant and that these effects can sometimes be reversed when plants are moved from the glasshouse to the field. However, it remains unclear which mechanisms underlie these effects and how they may affect concepts in molecular plant breeding and plant evolutionary ecology.

  19. TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Gregory, Adam P; Dendrou, Calliope A; Attfield, Kathrine E

    2012-01-01

    ), but not with other autoimmune conditions such as rheumatoid arthritis, psoriasis and Crohn’s disease. By analysing MS GWAS data in conjunction with the 1000 Genomes Project data we provide genetic evidence that strongly implicates this SNP, rs1800693, as the causal variant in the TNFRSF1A region. We further...... make to disease risk has raised questions regarding their medical relevance. Here we have investigated a single nucleotide polymorphism (SNP) in the TNFRSF1A gene, that encodes tumour necrosis factor receptor 1 (TNFR1), which was discovered through GWAS to be associated with multiple sclerosis (MS...... substantiate this through functional studies showing that the MS risk allele directs expression of a novel, soluble form of TNFR1 that can block TNF. Importantly, TNF-blocking drugs can promote onset or exacerbation of MS, but they have proven highly efficacious in the treatment of autoimmune diseases...

  20. Application of genetic algorithm - multiple linear regressions to predict the activity of RSK inhibitors

    Directory of Open Access Journals (Sweden)

    Avval Zhila Mohajeri

    2015-01-01

    Full Text Available This paper deals with developing a linear quantitative structure-activity relationship (QSAR model for predicting the RSK inhibition activity of some new compounds. A dataset consisting of 62 pyrazino [1,2-α] indole, diazepino [1,2-α] indole, and imidazole derivatives with known inhibitory activities was used. Multiple linear regressions (MLR technique combined with the stepwise (SW and the genetic algorithm (GA methods as variable selection tools was employed. For more checking stability, robustness and predictability of the proposed models, internal and external validation techniques were used. Comparison of the results obtained, indicate that the GA-MLR model is superior to the SW-MLR model and that it isapplicable for designing novel RSK inhibitors.

  1. Genetic educational needs and the role of genetics in primary care: a focus group study with multiple perspectives

    Directory of Open Access Journals (Sweden)

    van der Vleuten Cees

    2011-02-01

    Full Text Available Abstract Background Available evidence suggests that improvements in genetics education are needed to prepare primary care providers for the impact of ongoing rapid advances in genomics. Postgraduate (physician training and master (midwifery training programmes in primary care and public health are failing to meet these perceived educational needs. The aim of this study was to explore the role of genetics in primary care (i.e. family medicine and midwifery care and the need for education in this area as perceived by primary care providers, patient advocacy groups and clinical genetics professionals. Methods Forty-four participants took part in three types of focus groups: mono-disciplinary groups of general practitioners and midwives, respectively and multidisciplinary groups composed of a diverse set of experts. The focus group sessions were audio-taped, transcribed verbatim and analysed using content analysis. Recurrent themes were identified. Results Four themes emerged regarding the educational needs and the role of genetics in primary care: (1 genetics knowledge, (2 family history, (3 ethical dilemmas and psychosocial effects in relation to genetics and (4 insight into the organisation and role of clinical genetics services. These themes reflect a shift in the role of genetics in primary care with implications for education. Although all focus group participants acknowledged the importance of genetics education, general practitioners felt this need more urgently than midwives and more strongly emphasized their perceived knowledge deficiencies. Conclusion The responsibilities of primary care providers with regard to genetics require further study. The results of this study will help to develop effective genetics education strategies to improve primary care providers' competencies in this area. More research into the educational priorities in genetics is needed to design courses that are suitable for postgraduate and master programmes for

  2. Acoustically mediated long-range interaction among multiple spherical particles exposed to a plane standing wave

    International Nuclear Information System (INIS)

    Zhang, Shenwei; Qiu, Chunyin; Wang, Mudi; Ke, Manzhu; Liu, Zhengyou

    2016-01-01

    In this work, we study the acoustically mediated interaction forces among multiple well-separated spherical particles trapped in the same node or antinode plane of a standing wave. An analytical expression of the acoustic interaction force is derived, which is accurate even for the particles beyond the Rayleigh limit. Interestingly, the multi-particle system can be decomposed into a series of independent two-particle systems described by pairwise interactions. Each pairwise interaction is a long-range interaction, as characterized by a soft oscillatory attenuation (at the power exponent of n  = −1 or −2). The vector additivity of the acoustic interaction force, which is not well expected considering the nonlinear nature of the acoustic radiation force, is greatly useful for exploring a system consisting of a large number of particles. The capability of self-organizing a big particle cluster can be anticipated through such acoustically controllable long-range interaction. (paper)

  3. Common genetic variants in the 9p21 region and their associations with multiple tumours.

    Science.gov (United States)

    Gu, F; Pfeiffer, R M; Bhattacharjee, S; Han, S S; Taylor, P R; Berndt, S; Yang, H; Sigurdson, A J; Toro, J; Mirabello, L; Greene, M H; Freedman, N D; Abnet, C C; Dawsey, S M; Hu, N; Qiao, Y-L; Ding, T; Brenner, A V; Garcia-Closas, M; Hayes, R; Brinton, L A; Lissowska, J; Wentzensen, N; Kratz, C; Moore, L E; Ziegler, R G; Chow, W-H; Savage, S A; Burdette, L; Yeager, M; Chanock, S J; Chatterjee, N; Tucker, M A; Goldstein, A M; Yang, X R

    2013-04-02

    The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers. We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9-32.8 Mb) in eight case-control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction. Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P=7 × 10(-6)). The CDKN2A-ESCC association was further supported by gene-based analyses (Pgene=0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (PASSET (P=0.007). Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Optimal planning approaches with multiple impulses for rendezvous based on hybrid genetic algorithm and control method

    Directory of Open Access Journals (Sweden)

    JingRui Zhang

    2015-03-01

    Full Text Available In this article, we focus on safe and effective completion of a rendezvous and docking task by looking at planning approaches and control with fuel-optimal rendezvous for a target spacecraft running on a near-circular reference orbit. A variety of existent practical path constraints are considered, including the constraints of field of view, impulses, and passive safety. A rendezvous approach is calculated by using a hybrid genetic algorithm with those constraints. Furthermore, a control method of trajectory tracking is adopted to overcome the external disturbances. Based on Clohessy–Wiltshire equations, we first construct the mathematical model of optimal planning approaches of multiple impulses with path constraints. Second, we introduce the principle of hybrid genetic algorithm with both stronger global searching ability and local searching ability. We additionally explain the application of this algorithm in the problem of trajectory planning. Then, we give three-impulse simulation examples to acquire an optimal rendezvous trajectory with the path constraints presented in this article. The effectiveness and applicability of the tracking control method are verified with the optimal trajectory above as control objective through the numerical simulation.

  6. An association study of 13 SNPs from seven candidate genes with pediatric asthma and a preliminary study for genetic testing by multiple variants in Taiwanese population.

    Science.gov (United States)

    Wang, Jiu-Yao; Liou, Ya-Huei; Wu, Ying-Jye; Hsiao, Ya-Hsin; Wu, Lawrence Shih-Hsin

    2009-03-01

    Asthma is one of the most common chronic diseases in children. It is caused by complex interactions between various genetic factors and exposures to environmental allergens and irritants. Because of the heterogeneity of the disease and the genetic and cultural differences among different populations, a proper association study and genetic testing for asthma and susceptibility genes is difficult to perform. We assessed 13 single-nucleotide polymorphisms (SNPs) in seven well-known asthma susceptibility genes and looked for association with pediatric asthma using 449 asthmatic subjects and 512 non-asthma subjects in Taiwanese population. CD14-159 C/T and MS4A2 Glu237Gly were identified to have difference in genotype/allele frequencies between the control group and asthma patients. Moreover, the genotype synergistic analysis showed that the co-contribution of two functional SNPs was riskier or more protective from asthma attack. Our study provided a genotype synergistic method for studying gene-gene interaction on polymorphism basis and genetic testing using multiple polymorphisms.

  7. Interaction between common breast cancer susceptibility variants, genetic ancestry, and nongenetic risk factors in Hispanic women.

    Science.gov (United States)

    Fejerman, Laura; Stern, Mariana C; John, Esther M; Torres-Mejía, Gabriela; Hines, Lisa M; Wolff, Roger K; Baumgartner, Kathy B; Giuliano, Anna R; Ziv, Elad; Pérez-Stable, Eliseo J; Slattery, Martha L

    2015-11-01

    Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population. We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions. We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74-1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26-2.26) for never, 12 months breastfeeding, respectively, Pinteraction 0.014]. The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women. These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk. ©2015 American Association for Cancer Research.

  8. How Genetic and Other Biological Factors Interact with Smoking Decisions.

    Science.gov (United States)

    Bierut, Laura; Cesarini, David

    2015-09-01

    Despite clear links between genes and smoking, effective public policy requires far richer measurement of the feedback between biological, behavioral, and environmental factors. The Kavli HUMAN Project (KHP) plans to exploit the plummeting costs of data gathering and to make creative use of new technologies to construct a longitudinal panel data set that would compare favorably to existing longitudinal surveys, both in terms of the richness of the behavioral measures and the cost-effectiveness of the data collection. By developing a more comprehensive approach to characterizing behavior than traditional methods, KHP will allow researchers to paint a much richer picture of an individual's life-cycle trajectory of smoking, alcohol, and drug use, and interactions with other choices and environmental factors. The longitudinal nature of KHP will be particularly valuable in light of the increasing evidence for how smoking behavior affects physiology and health. The KHP could have a transformative impact on the understanding of the biology of addictive behaviors such as smoking, and of a rich range of prevention and amelioration policies.

  9. Decomposition of the Total Effect in the Presence of Multiple Mediators and Interactions.

    Science.gov (United States)

    Bellavia, Andrea; Valeri, Linda

    2018-06-01

    Mediation analysis allows decomposing a total effect into a direct effect of the exposure on the outcome and an indirect effect operating through a number of possible hypothesized pathways. Recent studies have provided formal definitions of direct and indirect effects when multiple mediators are of interest and have described parametric and semiparametric methods for their estimation. Investigating direct and indirect effects with multiple mediators, however, can be challenging in the presence of multiple exposure-mediator and mediator-mediator interactions. In this paper we derive a decomposition of the total effect that unifies mediation and interaction when multiple mediators are present. We illustrate the properties of the proposed framework in a secondary analysis of a pragmatic trial for the treatment of schizophrenia. The decomposition is employed to investigate the interplay of side effects and psychiatric symptoms in explaining the effect of antipsychotic medication on quality of life in schizophrenia patients. Our result offers a valuable tool to identify the proportions of total effect due to mediation and interaction when more than one mediator is present, providing the finest decomposition of the total effect that unifies multiple mediators and interactions.

  10. Signal Timing Optimization for Corridors with Multiple Highway-Rail Grade Crossings Using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Yifeng Chen

    2018-01-01

    Full Text Available Safety and efficiency are two critical issues at highway-rail grade crossings (HRGCs and their nearby intersections. Standard traffic signal optimization programs are not designed to work on roadway networks that contain multiple HRGCs, because their underlying assumption is that the roadway traffic is in a steady-state. During a train event, steady-state conditions do not occur. This is particularly true for corridors that experience high train traffic (e.g., over 2 trains per hour. In this situation, the non-steady-state conditions predominate. This paper develops a simulation-based methodology for optimizing traffic signal timing plan on corridors of this kind. The primary goal is to maximize safety, and the secondary goal is to minimize delay. A Genetic Algorithm (GA was used as the optimization approach in the proposed methodology. A new transition preemption strategy for dual tracks (TPS_DT and a train arrival prediction model were integrated in the proposed methodology. An urban road network with multiple HRGCs in Lincoln, NE, was used as the study network. The microsimulation model VISSIM was used for evaluation purposes and was calibrated to local traffic conditions. A sensitivity analysis with different train traffic scenarios was conducted. It was concluded that the methodology can significantly improve both the safety and efficiency of traffic corridors with HRGCs.

  11. Supporting a child with multiple disabilities to participate in social interaction

    DEFF Research Database (Denmark)

    Norén, Niklas; Pilesjö, Maja Sigurd

    2016-01-01

    Asking a question can be a highly challenging task for a person with multiple disabilities, but questions have not received much attention in research on augmentative and alternative communication (AAC). Conversation analysis is employed to examine an instance of multiparty interaction where...... a speech and language therapist supports a child with multiple disabilities to ask a question with a communication board. The question is accomplished through a practice where the action is built as a trajectory of interactional steps. Each step is built using ways of involvement that establish different...

  12. Calculation of contribution of multiple interactions and efficiency of neutron detectors

    International Nuclear Information System (INIS)

    Androsenko, A.A.; Androsenko, P.A.; Kazakov, L.E.; Kononov, V.N.; Poletaev, E.D.

    1986-01-01

    Results of calculation of multiple neutron interactions contribution to efficiency of detectors with 6 Li glass and 10 B plate in the energy range of 0.01-1 MeV are given. The calculation was performed by the Monte-Carlo method using BRAND program complex. It is shown that a correction value for multiple neutron interaction in 6 Li glass of 1 mm thickness constitutes 4.5 % at energy of up to 100 keV and at higher energies has a complex energy dependence reaching 25 % at 440 keV

  13. On the use of sibling recurrence risks to select environmental factors liable to interact with genetic risk factors. : GxE interaction and sibling recurrence risk

    OpenAIRE

    Kazma, Rémi; Bonaïti-Pellié, Catherine; Norris, Jill,; Génin, Emmanuelle

    2010-01-01

    International audience; Gene-environment interactions are likely to be involved in the susceptibility to multifactorial diseases but are difficult to detect. Available methods usually concentrate on some particular genetic and environmental factors. In this paper, we propose a new method to determine whether a given exposure is susceptible to interact with unknown genetic factors. Rather than focusing on a specific genetic factor, the degree of familial aggregation is used as a surrogate for ...

  14. Genetic insight into yield-associated traits of wheat grown in multiple rain-fed environments.

    Directory of Open Access Journals (Sweden)

    Xianshan Wu

    Full Text Available BACKGROUND: Grain yield is a key economic driver of successful wheat production. Due to its complex nature, little is known regarding its genetic control. The goal of this study was to identify important quantitative trait loci (QTL directly and indirectly affecting grain yield using doubled haploid lines derived from a cross between Hanxuan 10 and Lumai 14. METHODOLOGY/PRINCIPAL FINDINGS: Ten yield-associated traits, including yield per plant (YP, number of spikes per plant (NSP, number of grains per spike (NGS, one-thousand grain weight (TGW, total number of spikelets per spike (TNSS, number of sterile spikelets per spike (NSSS, proportion of fertile spikelets per spike (PFSS, spike length (SL, density of spikelets per spike (DSS and plant height (PH, were assessed across 14 (for YP to 23 (for TGW year × location × water regime environments in China. Then, the genetic effects were partitioned into additive main effects (a, epistatic main effects (aa and their environment interaction effects (ae and aae by using composite interval mapping in a mixed linear model. CONCLUSIONS/SIGNIFICANCE: Twelve (YP to 33 (PH QTLs were identified on all 21 chromosomes except 6D. QTLs were more frequently observed on chromosomes 1B, 2B, 2D, 5A and 6B, and were concentrated in a few regions on individual chromosomes, exemplified by three striking yield-related QTL clusters on chromosomes 2B, 1B and 4B that explained the correlations between YP and other traits. The additive main-effect QTLs contributed more phenotypic variation than the epistasis and environmental interaction. Consistent with agronomic analyses, a group of progeny derived by selecting TGW and NGS, with higher grain yield, had an increased frequency of QTL for high YP, NGS, TGW, TNSS, PFSS, SL, PH and fewer NSSS, when compared to low yielding progeny. This indicated that it is feasible by marker-assisted selection to facilitate wheat production.

  15. Characterization of recombination features and the genetic basis in multiple cattle breeds.

    Science.gov (United States)

    Shen, Botong; Jiang, Jicai; Seroussi, Eyal; Liu, George E; Ma, Li

    2018-04-27

    Crossover generated by meiotic recombination is a fundamental event that facilitates meiosis and sexual reproduction. Comparative studies have shown wide variation in recombination rate among species, but the characterization of recombination features between cattle breeds has not yet been performed. Cattle populations in North America count millions, and the dairy industry has genotyped millions of individuals with pedigree information that provide a unique opportunity to study breed-level variations in recombination. Based on large pedigrees of Jersey, Ayrshire and Brown Swiss cattle with genotype data, we identified over 3.4 million maternal and paternal crossover events from 161,309 three-generation families. We constructed six breed- and sex-specific genome-wide recombination maps using 58,982 autosomal SNPs for two sexes in the three dairy cattle breeds. A comparative analysis of the six recombination maps revealed similar global recombination patterns between cattle breeds but with significant differences between sexes. We confirmed that male recombination map is 10% longer than the female map in all three cattle breeds, consistent with previously reported results in Holstein cattle. When comparing recombination hotspot regions between cattle breeds, we found that 30% and 10% of the hotspots were shared between breeds in males and females, respectively, with each breed exhibiting some breed-specific hotspots. Finally, our multiple-breed GWAS found that SNPs in eight loci affected recombination rate and that the PRDM9 gene associated with hotspot usage in multiple cattle breeds, indicating a shared genetic basis for recombination across dairy cattle breeds. Collectively, our results generated breed- and sex-specific recombination maps for multiple cattle breeds, provided a comprehensive characterization and comparison of recombination patterns between breeds, and expanded our understanding of the breed-level variations in recombination features within an

  16. Genetic vulnerability interacts with parenting and early care education to predict increasing externalizing behavior.

    Science.gov (United States)

    Lipscomb, Shannon T; Laurent, Heidemarie; Neiderhiser, Jenae M; Shaw, Daniel S; Natsuaki, Misaki N; Reiss, David; Leve, Leslie D

    2014-01-01

    The current study examined interactions among genetic influences and children's early environments on the development of externalizing behaviors from 18 months to 6 years of age. Participants included 233 families linked through adoption (birth parents and adoptive families). Genetic influences were assessed by birth parent temperamental regulation. Early environments included both family (overreactive parenting) and out-of-home factors (center-based Early Care and Education; ECE). Overreactive parenting predicted more child externalizing behaviors. Attending center-based ECE was associated with increasing externalizing behaviors only for children with genetic liability for dysregulation. Additionally, children who were at risk for externalizing behaviors due to both genetic variability and exposure to center-based ECE were more sensitive to the effects of overreactive parenting on externalizing behavior than other children.

  17. Effects of multiple modes interaction on the resistive wall mode instability

    International Nuclear Information System (INIS)

    Chen, Longxi; Lei, Wenqing; Ma, Zhiwei; Wu, Bin

    2013-01-01

    The effects of multiple modes interaction on the resistive wall mode (RWM) are studied in a slab geometry with and without plasma flow. The modes interaction can have a large effect on both the linear growth rate and the nonlinear saturation level of the RWM. We found that modes interaction can suppress the linear growth rate for the most unstable mode. The plasma flow can also help to control the growth of the RWM. The RWM can be stabilized completely by a plasma flow when considering the modes interaction. The effect of modes interaction on the RWM is stronger for the mode rational surface in the vacuum than that in the plasma. The modes interaction results in a substantially lowered saturation level for the most unstable RWM. (paper)

  18. Glucose levels and genetic variants across transcriptional pathways: interaction effects with BMI

    NARCIS (Netherlands)

    Povel, C.M.; Feskens, E.J.M.; Imholz, S.; Blaak, E.E.; Boer, J.M.A.; Dollé, M.E.T.

    2010-01-01

    Objective: Much of the genetic variation in glucose levels remains to be discovered. Especially, research on gene–environment interactions is scarce. Overweight is one of the main risk factors for hyperglycemia. As transcriptional regulation is important for both weight maintenance and glucose

  19. The Interaction of Selective Attention and Cognitive Development on Achievement in Nigerian Secondary School Genetics

    Science.gov (United States)

    Okoye, Namdi N. S.

    2009-01-01

    The study tried to examine the interaction between two independent variables of selective attention and cognitive development on Achievement in Genetics at the Secondary School level. In looking at the problem of this study three null hypotheses were generated for testing at 0.05 level of significance. Factorial Analysis of Variance design with…

  20. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations

    Directory of Open Access Journals (Sweden)

    Rajani Rai

    2015-11-01

    Full Text Available Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR and Classification and Regression Tree Analysis (CRT to investigate the gene–gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634; FAS (rs2234767; FASL (rs763110; DCC (rs2229080, rs4078288, rs7504990, rs714; PSCA (rs2294008, rs2978974; ADRA2A (rs1801253; ADRB1 (rs1800544; ADRB3 (rs4994; CYP17 (rs2486758 involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634, DCC (rs714, rs2229080, rs4078288 and ADRB3 (rs4994 polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994 to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10 or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10. Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility.

  1. Interactive genetic counseling role-play: a novel educational strategy for family physicians.

    Science.gov (United States)

    Blaine, Sean M; Carroll, June C; Rideout, Andrea L; Glendon, Gord; Meschino, Wendy; Shuman, Cheryl; Telner, Deanna; Van Iderstine, Natasha; Permaul, Joanne

    2008-04-01

    Family physicians (FPs) are increasingly involved in delivering genetic services. Familiarization with aspects of genetic counseling may enable FPs to help patients make informed choices. Exploration of interactive role-play as a means to raise FPs' awareness of the process and content of genetic counseling. FPs attending two large Canadian family medicine conferences in 2005 were eligible -- 93 participated. FPs discussed a case during a one-on-one session with a genetic counselor. Evaluation involved pre and post intervention questionnaires FPs' baseline genetic knowledge was self-rated as uniformly poor. Baseline confidence was highest in eliciting family history and providing psychosocial support and lowest in discussing risks/benefits of genetic testing and counseling process. Post-intervention, 80% of FPs had better appreciation of family history and 97% indicated this was an effective learning experience. Role-play with FPs is effective in raising awareness of the process and content of genetic counseling and may be applied to other health disciplines.

  2. Genetic interaction analysis of point mutations enables interrogation of gene function at a residue-level resolution

    Science.gov (United States)

    Braberg, Hannes; Moehle, Erica A.; Shales, Michael; Guthrie, Christine; Krogan, Nevan J.

    2014-01-01

    We have achieved a residue-level resolution of genetic interaction mapping – a technique that measures how the function of one gene is affected by the alteration of a second gene – by analyzing point mutations. Here, we describe how to interpret point mutant genetic interactions, and outline key applications for the approach, including interrogation of protein interaction interfaces and active sites, and examination of post-translational modifications. Genetic interaction analysis has proven effective for characterizing cellular processes; however, to date, systematic high-throughput genetic interaction screens have relied on gene deletions or knockdowns, which limits the resolution of gene function analysis and poses problems for multifunctional genes. Our point mutant approach addresses these issues, and further provides a tool for in vivo structure-function analysis that complements traditional biophysical methods. We also discuss the potential for genetic interaction mapping of point mutations in human cells and its application to personalized medicine. PMID:24842270

  3. XCluSim: a visual analytics tool for interactively comparing multiple clustering results of bioinformatics data

    Science.gov (United States)

    2015-01-01

    Background Though cluster analysis has become a routine analytic task for bioinformatics research, it is still arduous for researchers to assess the quality of a clustering result. To select the best clustering method and its parameters for a dataset, researchers have to run multiple clustering algorithms and compare them. However, such a comparison task with multiple clustering results is cognitively demanding and laborious. Results In this paper, we present XCluSim, a visual analytics tool that enables users to interactively compare multiple clustering results based on the Visual Information Seeking Mantra. We build a taxonomy for categorizing existing techniques of clustering results visualization in terms of the Gestalt principles of grouping. Using the taxonomy, we choose the most appropriate interactive visualizations for presenting individual clustering results from different types of clustering algorithms. The efficacy of XCluSim is shown through case studies with a bioinformatician. Conclusions Compared to other relevant tools, XCluSim enables users to compare multiple clustering results in a more scalable manner. Moreover, XCluSim supports diverse clustering algorithms and dedicated visualizations and interactions for different types of clustering results, allowing more effective exploration of details on demand. Through case studies with a bioinformatics researcher, we received positive feedback on the functionalities of XCluSim, including its ability to help identify stably clustered items across multiple clustering results. PMID:26328893

  4. Dependence of Xmax and multiplicity of electron and muon on different high energy interaction models

    Directory of Open Access Journals (Sweden)

    G Rastegarzadeh

    2010-06-01

    Full Text Available Different high energy interaction models are the applied in CORSIKA code to simulate Extensive Air Showers (EAS generated by Cosmic Rays (CR. In this work the effects of QGSJET01, QGSJETII, DPMJET, SIBYLL models on Xmax and multiplicity of secondary electrons and muons at observation level are studied.

  5. Computational Tools for Probing Interactions in Multiple Linear Regression, Multilevel Modeling, and Latent Curve Analysis

    Science.gov (United States)

    Preacher, Kristopher J.; Curran, Patrick J.; Bauer, Daniel J.

    2006-01-01

    Simple slopes, regions of significance, and confidence bands are commonly used to evaluate interactions in multiple linear regression (MLR) models, and the use of these techniques has recently been extended to multilevel or hierarchical linear modeling (HLM) and latent curve analysis (LCA). However, conducting these tests and plotting the…

  6. N-cadherin-mediated interaction with multiple myeloma cells inhibits osteoblast differentiation

    NARCIS (Netherlands)

    Groen, Richard W. J.; de Rooij, Martin F. M.; Kocemba, Kinga A.; Reijmers, Rogier M.; de Haan-Kramer, Anneke; Overdijk, Marije B.; Aalders, Linda; Rozemuller, Henk; Martens, Anton C. M.; Bergsagel, P. Leif; Kersten, Marie José; Pals, Steven T.; Spaargaren, Marcel

    2011-01-01

    Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow microenvironment plays

  7. N-cadherin-mediated interaction with multiple myeloma cells inhibits osteoblast differentiation

    NARCIS (Netherlands)

    Groen, R.W.J.; de Rooij, M.F.M.; Kocemba, K.A.; Reijmers, R.M.; de Haan-Kramer, A.; Overdijk, M.B.; Aalders, L.; Rozemuller, H.; Martens, A.C.M.; Bergsagel, P.L.; Kersten, M.J.; Pals, S.T.; Spaargaren, M.

    2011-01-01

    Background Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow

  8. Genetic complexity and multiple infections with more Parvovirus species in naturally infected cats

    Directory of Open Access Journals (Sweden)

    Battilani Mara

    2011-03-01

    Full Text Available Abstract Parvoviruses of carnivores include three closely related autonomous parvoviruses: canine parvovirus (CPV, feline panleukopenia virus (FPV and mink enteritis virus (MEV. These viruses cause a variety of serious diseases, especially in young patients, since they have a remarkable predilection for replication in rapidly dividing cells. FPV is not the only parvovirus species which infects cats; in addition to MEV, the new variants of canine parvovirus, CPV-2a, 2b and 2c have also penetrated the feline host-range, and they are able to infect and replicate in cats, causing diseases indistinguishable from feline panleukopenia. Furthermore, as cats are susceptible to both CPV-2 and FPV viruses, superinfection and co-infection with multiple parvovirus strains may occur, potentially facilitating recombination and high genetic heterogeneity. In the light of the importance of cats as a potential source of genetic diversity for parvoviruses and, since feline panleukopenia virus has re-emerged as a major cause of mortality in felines, the present study has explored the molecular characteristics of parvovirus strains circulating in cat populations. The most significant findings reported in this study were (a the detection of mixed infection FPV/CPV with the presence of one parvovirus variant which is a true intermediate between FPV/CPV and (b the quasispecies cloud size of one CPV sample variant 2c. In conclusion, this study provides new important results about the evolutionary dynamics of CPV infections in cats, showing that CPV has presumably started a new process of readaptation in feline hosts.

  9. Impact of genetic risk loci for multiple sclerosis on expression of proximal genes in patients

    KAUST Repository

    James, Tojo

    2018-01-06

    Despite advancements in genetic studies, it is difficult to understand and characterize the functional relevance of disease-associated genetic variants, especially in the context of a complex multifactorial disease such as Multiple Sclerosis (MS). Since a large proportion of expression quantitative trait loci (eQTLs) are context-specific, we performed RNA-Seq in peripheral blood mononuclear cells (PBMCs) from MS patients (n=145) to identify eQTLs in regions centered on 109 MS risk SNPs and seven associated HLA variants. We identified 77 statistically significant eQTL associations, including pseudogenes and non-coding RNAs. Thirty-eight out of 40 testable eQTL effects were colocalised with the disease association signal. Since many eQTLs are tissue specific, we aimed to detail their significance in different cell types. Approximately 70% of the eQTLs were replicated and characterized in at least one major PBMC derived cell type. Furthermore, 40% of eQTLs were found to be more pronounced in MS patients compared to noninflammatory neurological diseases patients. In addition, we found two SNPs to be significantly associated with the proportions of three different cell types. Mapping to enhancer histone marks and predicted transcription factor binding sites added additional functional evidence for eight eQTL regions. As an example, we found that rs71624119, shared with three other autoimmune diseases and located in a primed enhancer (H3K4me1) with potential binding for STAT transcription factors, significantly associates with ANKRD55 expression. This study provides many novel and validated targets for future functional characterization of MS and other diseases.

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

    Science.gov (United States)

    Neher, Richard

    2010-03-01

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

  11. Interaction of Multiple Particles with a Solidification Front: From Compacted Particle Layer to Particle Trapping.

    Science.gov (United States)

    Saint-Michel, Brice; Georgelin, Marc; Deville, Sylvain; Pocheau, Alain

    2017-06-13

    The interaction of solidification fronts with objects such as particles, droplets, cells, or bubbles is a phenomenon with many natural and technological occurrences. For an object facing the front, it may yield various fates, from trapping to rejection, with large implications regarding the solidification pattern. However, whereas most situations involve multiple particles interacting with each other and the front, attention has focused almost exclusively on the interaction of a single, isolated object with the front. Here we address experimentally the interaction of multiple particles with a solidification front by performing solidification experiments of a monodisperse particle suspension in a Hele-Shaw cell with precise control of growth conditions and real-time visualization. We evidence the growth of a particle layer ahead of the front at a close-packing volume fraction, and we document its steady-state value at various solidification velocities. We then extend single-particle models to the situation of multiple particles by taking into account the additional force induced on an entering particle by viscous friction in the compacted particle layer. By a force balance model this provides an indirect measure of the repelling mean thermomolecular pressure over a particle entering the front. The presence of multiple particles is found to increase it following a reduction of the thickness of the thin liquid film that separates particles and front. We anticipate the findings reported here to provide a relevant basis to understand many complex solidification situations in geophysics, engineering, biology, or food engineering, where multiple objects interact with the front and control the resulting solidification patterns.

  12. CRISPR/Cas9 : A molecular Swiss army knife for simultaneous introduction of multiple genetic modifications in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Mans, R.; Van Rossum, H.M.; Wijsman, M.; Backx, A.; Kuijpers, N.G.A.; van den Broek, M.; Daran-Lapujade, P.A.S.; Pronk, J.T.; Van Maris, A.J.A.; Daran, J.G.

    2015-01-01

    A variety of techniques for strain engineering in Saccharomyces cerevisiae have recently been developed. However, especially when multiple genetic manipulations are required, strain construction is still a time-consuming process. This study describes new CRISPR/Cas9-based approaches for easy, fast

  13. A simple method for combining genetic mapping data from multiple crosses and experimental designs.

    Directory of Open Access Journals (Sweden)

    Jeremy L Peirce

    Full Text Available BACKGROUND: Over the past decade many linkage studies have defined chromosomal intervals containing polymorphisms that modulate a variety of traits. Many phenotypes are now associated with enough mapping data that meta-analysis could help refine locations of known QTLs and detect many novel QTLs. METHODOLOGY/PRINCIPAL FINDINGS: We describe a simple approach to combining QTL mapping results for multiple studies and demonstrate its utility using two hippocampus weight loci. Using data taken from two populations, a recombinant inbred strain set and an advanced intercross population we demonstrate considerable improvements in significance and resolution for both loci. 1-LOD support intervals were improved 51% for Hipp1a and 37% for Hipp9a. We first generate locus-wise permuted P-values for association with the phenotype from multiple maps, which can be done using a permutation method appropriate to each population. These results are then assigned to defined physical positions by interpolation between markers with known physical and genetic positions. We then use Fisher's combination test to combine position-by-position probabilities among experiments. Finally, we calculate genome-wide combined P-values by generating locus-specific P-values for each permuted map for each experiment. These permuted maps are then sampled with replacement and combined. The distribution of best locus-specific P-values for each combined map is the null distribution of genome-wide adjusted P-values. CONCLUSIONS/SIGNIFICANCE: Our approach is applicable to a wide variety of segregating and non-segregating mapping populations, facilitates rapid refinement of physical QTL position, is complementary to other QTL fine mapping methods, and provides an appropriate genome-wide criterion of significance for combined mapping results.

  14. A Next-Generation Sequencing Strategy for Evaluating the Most Common Genetic Abnormalities in Multiple Myeloma.

    Science.gov (United States)

    Jiménez, Cristina; Jara-Acevedo, María; Corchete, Luis A; Castillo, David; Ordóñez, Gonzalo R; Sarasquete, María E; Puig, Noemí; Martínez-López, Joaquín; Prieto-Conde, María I; García-Álvarez, María; Chillón, María C; Balanzategui, Ana; Alcoceba, Miguel; Oriol, Albert; Rosiñol, Laura; Palomera, Luis; Teruel, Ana I; Lahuerta, Juan J; Bladé, Joan; Mateos, María V; Orfão, Alberto; San Miguel, Jesús F; González, Marcos; Gutiérrez, Norma C; García-Sanz, Ramón

    2017-01-01

    Identification and characterization of genetic alterations are essential for diagnosis of multiple myeloma and may guide therapeutic decisions. Currently, genomic analysis of myeloma to cover the diverse range of alterations with prognostic impact requires fluorescence in situ hybridization (FISH), single nucleotide polymorphism arrays, and sequencing techniques, which are costly and labor intensive and require large numbers of plasma cells. To overcome these limitations, we designed a targeted-capture next-generation sequencing approach for one-step identification of IGH translocations, V(D)J clonal rearrangements, the IgH isotype, and somatic mutations to rapidly identify risk groups and specific targetable molecular lesions. Forty-eight newly diagnosed myeloma patients were tested with the panel, which included IGH and six genes that are recurrently mutated in myeloma: NRAS, KRAS, HRAS, TP53, MYC, and BRAF. We identified 14 of 17 IGH translocations previously detected by FISH and three confirmed translocations not detected by FISH, with the additional advantage of breakpoint identification, which can be used as a target for evaluating minimal residual disease. IgH subclass and V(D)J rearrangements were identified in 77% and 65% of patients, respectively. Mutation analysis revealed the presence of missense protein-coding alterations in at least one of the evaluating genes in 16 of 48 patients (33%). This method may represent a time- and cost-effective diagnostic method for the molecular characterization of multiple myeloma. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  15. Role of the XRCC1 - APE1 interaction in the maintenance of genetic stability

    International Nuclear Information System (INIS)

    Sossou-Becker, M.

    2005-09-01

    This thesis is divided in four chapters: the first one concerns the genetic instability, the second one is devoted to the DNA repair, the third one is related to the XRCC1 and the chapter four concerns APE1. Then, are defined the objectives and the results. This work fits into the studies of repair mechanisms. The physical and functional characterisation of the interaction between XRCC1 and APE1 allowed to understand its involvement in the prevention of the genetic instability at the origin of cancer. (N.C.)

  16. A double-mutant collection targeting MAP kinase related genes in Arabidopsis for studying genetic interactions.

    Science.gov (United States)

    Su, Shih-Heng; Krysan, Patrick J

    2016-12-01

    Mitogen-activated protein kinase cascades are conserved in all eukaryotes. In Arabidopsis thaliana there are approximately 80 genes encoding MAP kinase kinase kinases (MAP3K), 10 genes encoding MAP kinase kinases (MAP2K), and 20 genes encoding MAP kinases (MAPK). Reverse genetic analysis has failed to reveal abnormal phenotypes for a majority of these genes. One strategy for uncovering gene function when single-mutant lines do not produce an informative phenotype is to perform a systematic genetic interaction screen whereby double-mutants are created from a large library of single-mutant lines. Here we describe a new collection of 275 double-mutant lines derived from a library of single-mutants targeting genes related to MAP kinase signaling. To facilitate this study, we developed a high-throughput double-mutant generating pipeline using a system for growing Arabidopsis seedlings in 96-well plates. A quantitative root growth assay was used to screen for evidence of genetic interactions in this double-mutant collection. Our screen revealed four genetic interactions, all of which caused synthetic enhancement of the root growth defects observed in a MAP kinase 4 (MPK4) single-mutant line. Seeds for this double-mutant collection are publicly available through the Arabidopsis Biological Resource Center. Scientists interested in diverse biological processes can now screen this double-mutant collection under a wide range of growth conditions in order to search for additional genetic interactions that may provide new insights into MAP kinase signaling. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  17. Interaction of a genetic risk score with physical activity, physical inactivity, and body mass index in relation to venous thromboembolism risk.

    Science.gov (United States)

    Kim, Jihye; Kraft, Peter; Hagan, Kaitlin A; Harrington, Laura B; Lindstroem, Sara; Kabrhel, Christopher

    2018-06-01

    Venous thromboembolism (VTE) is highly heritable. Physical activity, physical inactivity and body mass index (BMI) are also risk factors, but evidence of interaction between genetic and environmental risk factors is limited. Data on 2,134 VTE cases and 3,890 matched controls were obtained from the Nurses' Health Study (NHS), Nurses' Health Study II (NHS II), and Health Professionals Follow-up Study (HPFS). We calculated a weighted genetic risk score (wGRS) using 16 single nucleotide polymorphisms associated with VTE risk in published genome-wide association studies (GWAS). Data on three risk factors, physical activity (metabolic equivalent [MET] hours per week), physical inactivity (sitting hours per week) and BMI, were obtained from biennial questionnaires. VTE cases were incident since cohort inception; controls were matched to cases on age, cohort, and genotype array. Using conditional logistic regression, we assessed joint effects and interaction effects on both additive and multiplicative scales. We also ran models using continuous wGRS stratified by risk-factor categories. We observed a supra-additive interaction between wGRS and BMI. Having both high wGRS and high BMI was associated with a 3.4-fold greater risk of VTE (relative excess risk due to interaction = 0.69, p = 0.046). However, we did not find evidence for a multiplicative interaction with BMI. No interactions were observed for physical activity or inactivity. We found a synergetic effect between a genetic risk score and high BMI on the risk of VTE. Intervention efforts lowering BMI to decrease VTE risk may have particularly large beneficial effects among individuals with high genetic risk. © 2018 WILEY PERIODICALS, INC.

  18. Multiplicity distributions of charged hadrons in vp and charged current interactions

    Science.gov (United States)

    Jones, G. T.; Jones, R. W. L.; Kennedy, B. W.; Morrison, D. R. O.; Mobayyen, M. M.; Wainstein, S.; Aderholz, M.; Hantke, D.; Katz, U. F.; Kern, J.; Schmitz, N.; Wittek, W.; Borner, H. P.; Myatt, G.; Radojicic, D.; Burke, S.

    1992-03-01

    Using data on vp andbar vp charged current interactions from a bubble chamber experiment with BEBC at CERN, the multiplicity distributions of charged hadrons are investigated. The analysis is based on ˜20000 events with incident v and ˜10000 events with incidentbar v. The invariant mass W of the total hadronic system ranges from 3 GeV to ˜14 GeV. The experimental multiplicity distributions are fitted by the binomial function (for different intervals of W and in different intervals of the rapidity y), by the Levy function and the lognormal function. All three parametrizations give acceptable values for X 2. For fixed W, forward and backward multiplicities are found to be uncorrelated. The normalized moments of the charged multiplicity distributions are measured as a function of W. They show a violation of KNO scaling.

  19. Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

    International Nuclear Information System (INIS)

    Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I.; Barranger, J.A.

    1988-01-01

    Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is ∼80% informative in all Gaucher patients studied

  20. Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

    Energy Technology Data Exchange (ETDEWEB)

    Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I. (National Institute of Mental Health, Bethesda, MD (USA)); Barranger, J.A. (Childrens Hospital of Los Angeles, CA (USA))

    1988-04-01

    Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is {approx}80% informative in all Gaucher patients studied.

  1. Schedule Optimization of Imaging Missions for Multiple Satellites and Ground Stations Using Genetic Algorithm

    Science.gov (United States)

    Lee, Junghyun; Kim, Heewon; Chung, Hyun; Kim, Haedong; Choi, Sujin; Jung, Okchul; Chung, Daewon; Ko, Kwanghee

    2018-04-01

    In this paper, we propose a method that uses a genetic algorithm for the dynamic schedule optimization of imaging missions for multiple satellites and ground systems. In particular, the visibility conflicts of communication and mission operation using satellite resources (electric power and onboard memory) are integrated in sequence. Resource consumption and restoration are considered in the optimization process. Image acquisition is an essential part of satellite missions and is performed via a series of subtasks such as command uplink, image capturing, image storing, and image downlink. An objective function for optimization is designed to maximize the usability by considering the following components: user-assigned priority, resource consumption, and image-acquisition time. For the simulation, a series of hypothetical imaging missions are allocated to a multi-satellite control system comprising five satellites and three ground stations having S- and X-band antennas. To demonstrate the performance of the proposed method, simulations are performed via three operation modes: general, commercial, and tactical.

  2. Preimplantation genetic diagnosis for Duchenne muscular dystrophy by multiple displacement amplification.

    Science.gov (United States)

    Ren, Zi; Zeng, Hai-tao; Xu, Yan-wen; Zhuang, Guang-lun; Deng, Jie; Zhang, Cheng; Zhou, Can-quan

    2009-02-01

    To evaluate the use of multiple displacement amplification (MDA) in preimplantation genetic diagnosis (PGD) for female carriers with Duchenne muscular dystrophy (DMD). MDA was used to amplify a whole genome of single cells. Following the setup on single cells, the test was applied in two clinical cases of PGD. One mutant exon, six short tandem repeats (STR) markers within the dystrophin gene, and amelogenin were incorporated into singleplex polymerase chain reaction (PCR) assays on MDA products of single blastomeres. Center for reproductive medicine in First Affiliated Hospital, Sun Yat-sen University, China. Two female carriers with a duplication of exons 3-11 and a deletion of exons 47-50, respectively. The MDA of single cells and fluorescent PCR assays for PGD. The ability to analyze single blastomeres for DMD using MDA. The protocol setup previously allowed for the accurate diagnosis of each embryo. Two clinical cases resulted in a healthy girl, which was the first successful clinical application of MDA in PGD for DMD. We suggest that this protocol is reliable to increase the accuracy of the PGD for DMD.

  3. Application of Multiple-Population Genetic Algorithm in Optimizing the Train-Set Circulation Plan Problem

    Directory of Open Access Journals (Sweden)

    Yu Zhou

    2017-01-01

    Full Text Available The train-set circulation plan problem (TCPP belongs to the rolling stock scheduling (RSS problem and is similar to the aircraft routing problem (ARP in airline operations and the vehicle routing problem (VRP in the logistics field. However, TCPP involves additional complexity due to the maintenance constraint of train-sets: train-sets must conduct maintenance tasks after running for a certain time and distance. The TCPP is nondeterministic polynomial hard (NP-hard. There is no available algorithm that can obtain the optimal global solution, and many factors such as the utilization mode and the maintenance mode impact the solution of the TCPP. This paper proposes a train-set circulation optimization model to minimize the total connection time and maintenance costs and describes the design of an efficient multiple-population genetic algorithm (MPGA to solve this model. A realistic high-speed railway (HSR case is selected to verify our model and algorithm, and, then, a comparison of different algorithms is carried out. Furthermore, a new maintenance mode is proposed, and related implementation requirements are discussed.

  4. Visual detection of multiple genetically modified organisms in a capillary array.

    Science.gov (United States)

    Shao, Ning; Chen, Jianwei; Hu, Jiaying; Li, Rong; Zhang, Dabing; Guo, Shujuan; Hui, Junhou; Liu, Peng; Yang, Litao; Tao, Sheng-Ce

    2017-01-31

    There is an urgent need for rapid, low-cost multiplex methodologies for the monitoring of genetically modified organisms (GMOs). Here, we report a C[combining low line]apillary A[combining low line]rray-based L[combining low line]oop-mediated isothermal amplification for M[combining low line]ultiplex visual detection of nucleic acids (CALM) platform for the simple and rapid monitoring of GMOs. In CALM, loop-mediated isothermal amplification (LAMP) primer sets are pre-fixed to the inner surface of capillaries. The surface of the capillary array is hydrophobic while the capillaries are hydrophilic, enabling the simultaneous loading and separation of the LAMP reaction mixtures into each capillary by capillary forces. LAMP reactions in the capillaries are then performed in parallel, and the results are visually detected by illumination with a hand-held UV device. Using CALM, we successfully detected seven frequently used transgenic genes/elements and five plant endogenous reference genes with high specificity and sensitivity. Moreover, we found that measurements of real-world blind samples by CALM are consistent with results obtained by independent real-time PCRs. Thus, with an ability to detect multiple nucleic acids in a single easy-to-operate test, we believe that CALM will become a widely applied technology in GMO monitoring.

  5. Multiple system atrophy: genetic risks and alpha-synuclein mutations [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Heather T Whittaker

    2017-11-01

    Full Text Available Multiple system atrophy (MSA is one of the few neurodegenerative disorders where we have a significant understanding of the clinical and pathological manifestations but where the aetiology remains almost completely unknown. Research to overcome this hurdle is gaining momentum through international research collaboration and a series of genetic and molecular discoveries in the last few years, which have advanced our knowledge of this rare synucleinopathy. In MSA, the discovery of α-synuclein pathology and glial cytoplasmic inclusions remain the most significant findings. Families with certain types of α-synuclein mutations develop diseases that mimic MSA, and the spectrum of clinical and pathological features in these families suggests a spectrum of severity, from late-onset Parkinson’s disease to MSA. Nonetheless, controversies persist, such as the role of common α-synuclein variants in MSA and whether this disorder shares a common mechanism of spreading pathology with other protein misfolding neurodegenerative diseases. Here, we review these issues, specifically focusing on α-synuclein mutations.

  6. Genetic analysis of the isolated Faroe Islands reveals SORCS3 as a potential multiple sclerosis risk gene

    DEFF Research Database (Denmark)

    Binzer, Stefanie; Stenager, Egon; Binzer, Michael

    2016-01-01

    BACKGROUND: In search of the missing heritability in multiple sclerosis (MS), additional approaches adding to the genetic discoveries of large genome-wide association studies are warranted. OBJECTIVE: The objective of this research paper is to search for rare genetic MS risk variants...... in the genetically homogenous population of the isolated Faroe Islands. METHODS: Twenty-nine Faroese MS cases and 28 controls were genotyped with the HumanOmniExpressExome-chip. The individuals make up 1596 pair-combinations in which we searched for identical-by-descent shared segments using the PLINK...... of neurotrophin factors and involvement in glutamate homeostasis. Although additional work is needed to scrutinise the genetic effect of the SORCS3-covering haplotype, this study suggests that SORCS3 may also be important in MS pathogenesis....

  7. The genetic basis of alcoholism: multiple phenotypes, many genes, complex networks

    Science.gov (United States)

    2012-01-01

    Alcoholism is a significant public health problem. A picture of the genetic architecture underlying alcohol-related phenotypes is emerging from genome-wide association studies and work on genetically tractable model organisms. PMID:22348705

  8. The Effect of Multiple Paternity on Genetic Diversity of Small Populations during and after Colonisation

    KAUST Repository

    Rafajlović, Marina; Eriksson, Anders; Rimark, Anna; Hintz-Saltin, Sara; Charrier, Gré gory; Panova, Marina; André , Carl; Johannesson, Kerstin; Mehlig, Bernhard

    2013-01-01

    Genetic variation within and among populations is influenced by the genetic content of the founders and the migrants following establishment. This is particularly true if populations are small, migration rate low and habitats arranged in a stepping

  9. 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

  10. Evolving ideas about genetics underlying insect virulence to plant resistance in rice-brown planthopper interactions.

    Science.gov (United States)

    Kobayashi, Tetsuya

    2016-01-01

    Many plant-parasite interactions that include major plant resistance genes have subsequently been shown to exhibit features of gene-for-gene interactions between plant Resistance genes and parasite Avirulence genes. The brown planthopper (BPH) Nilaparvata lugens is an important pest of rice (Oryza sativa). Historically, major Resistance genes have played an important role in agriculture. As is common in gene-for-gene interactions, evolution of BPH virulence compromises the effectiveness of singly-deployed resistance genes. It is therefore surprising that laboratory studies of BPH have supported the conclusion that virulence is conferred by changes in many genes rather than a change in a single gene, as is proposed by the gene-for-gene model. Here we review the behaviour, physiology and genetics of the BPH in the context of host plant resistance. A problem for genetic understanding has been the use of various insect populations that differ in frequencies of virulent genotypes. We show that the previously proposed polygenic inheritance of BPH virulence can be explained by the heterogeneity of parental populations. Genetic mapping of Avirulence genes indicates that virulence is a monogenic trait. These evolving concepts, which have brought the gene-for-gene model back into the picture, are accelerating our understanding of rice-BPH interactions at the molecular level. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Interactions between Gut Microbiota, Host Genetics and Diet Modulate the Predisposition to Obesity and Metabolic Syndrome.

    Science.gov (United States)

    Ussar, Siegfried; Griffin, Nicholas W; Bezy, Olivier; Fujisaka, Shiho; Vienberg, Sara; Softic, Samir; Deng, Luxue; Bry, Lynn; Gordon, Jeffrey I; Kahn, C Ronald

    2015-09-01

    Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly used inbred strains of mice-obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ from Jackson Laboratory, and obesity-prone but diabetes-resistant 129S6/SvEvTac from Taconic-plus three derivative lines generated by breeding these strains in a new, common environment. Analysis of metabolic parameters and gut microbiota in all strains and their environmentally normalized derivatives revealed strong interactions between microbiota, diet, breeding site, and metabolic phenotype. Strain-dependent and strain-independent correlations were found between specific microbiota and phenotypes, some of which could be transferred to germ-free recipient animals by fecal transplantation. Environmental reprogramming of microbiota resulted in 129S6/SvEvTac becoming obesity resistant. Thus, development of obesity/metabolic syndrome is the result of interactions between gut microbiota, host genetics, and diet. In permissive genetic backgrounds, environmental reprograming of microbiota can ameliorate development of metabolic syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. A spatial theory for emergent multiple predator-prey interactions in food webs.

    Science.gov (United States)

    Northfield, Tobin D; Barton, Brandon T; Schmitz, Oswald J

    2017-09-01

    Predator-prey interaction is inherently spatial because animals move through landscapes to search for and consume food resources and to avoid being consumed by other species. The spatial nature of species interactions necessitates integrating spatial processes into food web theory and evaluating how predators combine to impact their prey. Here, we present a spatial modeling approach that examines emergent multiple predator effects on prey within landscapes. The modeling is inspired by the habitat domain concept derived from empirical synthesis of spatial movement and interactions studies. Because these principles are motivated by synthesis of short-term experiments, it remains uncertain whether spatial contingency principles hold in dynamical systems. We address this uncertainty by formulating dynamical systems models, guided by core habitat domain principles, to examine long-term multiple predator-prey spatial dynamics. To describe habitat domains, we use classical niche concepts describing resource utilization distributions, and assume species interactions emerge from the degree of overlap between species. The analytical results generally align with those from empirical synthesis and present a theoretical framework capable of demonstrating multiple predator effects that does not depend on the small spatial or temporal scales typical of mesocosm experiments, and help bridge between empirical experiments and long-term dynamics in natural systems.

  13. Genetic Interaction Maps in Escherichia coli Reveal Functional Crosstalk among Cell Envelope Biogenesis Pathways

    Science.gov (United States)

    Vlasblom, James; Gagarinova, Alla; Phanse, Sadhna; Graham, Chris; Yousif, Fouad; Ding, Huiming; Xiong, Xuejian; Nazarians-Armavil, Anaies; Alamgir, Md; Ali, Mehrab; Pogoutse, Oxana; Pe'er, Asaf; Arnold, Roland; Michaut, Magali; Parkinson, John; Golshani, Ashkan; Whitfield, Chris; Wodak, Shoshana J.; Moreno-Hagelsieb, Gabriel; Greenblatt, Jack F.; Emili, Andrew

    2011-01-01

    As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among >235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target. PMID:22125496

  14. Genetic interaction maps in Escherichia coli reveal functional crosstalk among cell envelope biogenesis pathways.

    Directory of Open Access Journals (Sweden)

    Mohan Babu

    2011-11-01

    Full Text Available As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium and prototrophic (minimal medium culture conditions. The differential patterns of genetic interactions detected among > 235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens and an important target.

  15. Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors.

    Science.gov (United States)

    Hauser, Kurt F; Knapp, Pamela E

    2014-01-01

    Considerable insight has been gained into the comorbid, interactive effects of HIV and drug abuse in the brain using experimental models. This review, which considers opiates, methamphetamine, and cocaine, emphasizes the importance of host genetics and glial plasticity in driving the pathogenic neuron remodeling underlying neuro-acquired immunodeficiency syndrome and drug abuse comorbidity. Clinical findings are less concordant than experimental work, and the response of individuals to HIV and to drug abuse can vary tremendously. Host-genetic variability is important in determining viral tropism, neuropathogenesis, drug responses, and addictive behavior. However, genetic differences alone cannot account for individual variability in the brain "connectome." Environment and experience are critical determinants in the evolution of synaptic circuitry throughout life. Neurons and glia both exercise control over determinants of synaptic plasticity that are disrupted by HIV and drug abuse. Perivascular macrophages, microglia, and to a lesser extent astroglia can harbor the infection. Uninfected bystanders, especially astroglia, propagate and amplify inflammatory signals. Drug abuse by itself derails neuronal and glial function, and the outcome of chronic exposure is maladaptive plasticity. The negative consequences of coexposure to HIV and drug abuse are determined by numerous factors including genetics, sex, age, and multidrug exposure. Glia and some neurons are generated throughout life, and their progenitors appear to be targets of HIV and opiates/psychostimulants. The chronic nature of HIV and drug abuse appears to result in sustained alterations in the maturation and fate of neural progenitors, which may affect the balance of glial populations within multiple brain regions. © 2014 Elsevier Inc. All rights reserved.

  16. Charged multiplicity distributions in anti np interactions at 6 GeV/c

    International Nuclear Information System (INIS)

    Batyunya, B.V.; Boguslavskij, I.B.; Gramenitskij, I.M.

    1980-01-01

    Inelastic topological anti np cross sections at 6 GeV/c have been determined based on a study of the charged multiplicity distribution in antideuteron-proton collisions at 12 GeV/c. The data were obtained in an exposure of the ''Ludmila'' JINR 2 m hydrogen bubble chamber at the Serpukhov accelerator. In anti np interactions average charged multiplicity and its ratio to dispersion, /D, were found to be 3.32+-0.13 and 1.86+-0.16, respectively. Comparison with anti pn, anti pp and pp data was made

  17. Temporal Sequence of Visuo-Auditory Interaction in Multiple Areas of the Guinea Pig Visual Cortex

    Science.gov (United States)

    Nishimura, Masataka; Song, Wen-Jie

    2012-01-01

    Recent studies in humans and monkeys have reported that acoustic stimulation influences visual responses in the primary visual cortex (V1). Such influences can be generated in V1, either by direct auditory projections or by feedback projections from extrastriate cortices. To test these hypotheses, cortical activities were recorded using optical imaging at a high spatiotemporal resolution from multiple areas of the guinea pig visual cortex, to visual and/or acoustic stimulations. Visuo-auditory interactions were evaluated according to differences between responses evoked by combined auditory and visual stimulation, and the sum of responses evoked by separate visual and auditory stimulations. Simultaneous presentation of visual and acoustic stimulations resulted in significant interactions in V1, which occurred earlier than in other visual areas. When acoustic stimulation preceded visual stimulation, significant visuo-auditory interactions were detected only in V1. These results suggest that V1 is a cortical origin of visuo-auditory interaction. PMID:23029483

  18. Comparison of charged particle multiplicity distributions in p tilde p and pp interactions and verification of the dual unitarization scheme

    International Nuclear Information System (INIS)

    Batyunya, B.V.; Boguslavsky, I.V.; Gramenitsky, I.M.

    1979-01-01

    The difference between antiproton annihilation and pp interactions has been discussed. Charged particle multiplicity distributions in anti pp-interactions at 22.4 GeV/c were used to obtain antiproton annihilation characteristics. The comparison of the topological cross section of antipp interactions with those of non-diffractive pp interactions confirms the validity of dual unitarization

  19. An information-gain approach to detecting three-way epistatic interactions in genetic association studies

    DEFF Research Database (Denmark)

    Hu, Ting; Chen, Yuanzhu; Kiralis, Jeff W

    2013-01-01

    Background Epistasis has been historically used to describe the phenomenon that the effect of a given gene on a phenotype can be dependent on one or more other genes, and is an essential element for understanding the association between genetic and phenotypic variations. Quantifying epistasis......-way epistasis. Methods Such a measure is based on information gain, and is able to separate all lower order effects from pure three-way epistasis. Results Our method was verified on synthetic data and applied to real data from a candidate-gene study of tuberculosis in a West African population....... In the tuberculosis data, we found a statistically significant pure three-way epistatic interaction effect that was stronger than any lower-order associations. Conclusion Our study provides a methodological basis for detecting and characterizing high-order gene-gene interactions in genetic association studies....

  20. Aging and a genetic KIBRA polymorphism interactively affect feedback- and observation-based probabilistic classification learning.

    Science.gov (United States)

    Schuck, Nicolas W; Petok, Jessica R; Meeter, Martijn; Schjeide, Brit-Maren M; Schröder, Julia; Bertram, Lars; Gluck, Mark A; Li, Shu-Chen

    2018-01-01

    Probabilistic category learning involves complex interactions between the hippocampus and striatum that may depend on whether acquisition occurs via feedback or observation. Little is known about how healthy aging affects these processes. We tested whether age-related behavioral differences in probabilistic category learning from feedback or observation depend on a genetic factor known to influence individual differences in hippocampal function, the KIBRA gene (single nucleotide polymorphism rs17070145). Results showed comparable age-related performance impairments in observational as well as feedback-based learning. Moreover, genetic analyses indicated an age-related interactive effect of KIBRA on learning: among older adults, the beneficial T-allele was positively associated with learning from feedback, but negatively with learning from observation. In younger adults, no effects of KIBRA were found. Our results add behavioral genetic evidence to emerging data showing age-related differences in how neural resources relate to memory functions, namely that hippocampal and striatal contributions to probabilistic category learning may vary with age. Our findings highlight the effects genetic factors can have on differential age-related decline of different memory functions. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Genetic and infectious profiles influence cerebrospinal fluid IgG abnormality in Japanese multiple sclerosis patients.

    Directory of Open Access Journals (Sweden)

    Satoshi Yoshimura

    Full Text Available BACKGROUND: Abnormal intrathecal synthesis of IgG, reflected by cerebrospinal fluid (CSF oligoclonal IgG bands (OBs and increased IgG index, is much less frequently observed in Japanese multiple sclerosis (MS cohorts compared with Western cohorts. We aimed to clarify whether genetic and common infectious backgrounds influence CSF IgG abnormality in Japanese MS patients. METHODOLOGY: We analyzed HLA-DRB1 alleles, and IgG antibodies against Chlamydia pneumoniae, Helicobacter pylori, Epstein-Barr virus nuclear antigen (EBNA, and varicella zoster virus (VZV in 94 patients with MS and 367 unrelated healthy controls (HCs. We defined CSF IgG abnormality as the presence of CSF OBs and/or increased IgG index (>0.658. PRINCIPAL FINDINGS: CSF IgG abnormality was found in 59 of 94 (62.8% MS patients. CSF IgG abnormality-positive patients had a significantly higher frequency of brain MRI lesions meeting the Barkhof criteria compared with abnormality-negative patients. Compared with HCs, CSF IgG abnormality-positive MS patients showed a significantly higher frequency of DRB1 1501, whereas CSF IgG abnormality-negative patients had a significantly higher frequency of DRB1 0405. CSF IgG abnormality-positive MS patients had a significantly higher frequency of anti-C. pneumoniae IgG antibodies compared with CSF IgG abnormality-negative MS patients, although there was no difference in the frequency of anti-C. pneumoniae IgG antibodies between HCs and total MS patients. Compared with HCs, anti-H. pylori IgG antibodies were detected significantly less frequently in the total MS patients, especially in CSF IgG abnormality-negative MS patients. The frequencies of antibodies against EBNA and VZV did not differ significantly among the groups. CONCLUSIONS: CSF IgG abnormality is associated with Western MS-like brain MRI features. DRB1 1501 and C. pneumoniae infection confer CSF IgG abnormality, while DRB1 0405 and H. pylori infection are positively and negatively

  2. Temporal scale dependent interactions between multiple environmental disturbances in microcosm ecosystems.

    Science.gov (United States)

    Garnier, Aurélie; Pennekamp, Frank; Lemoine, Mélissa; Petchey, Owen L

    2017-12-01

    Global environmental change has negative impacts on ecological systems, impacting the stable provision of functions, goods, and services. Whereas effects of individual environmental changes (e.g. temperature change or change in resource availability) are reasonably well understood, we lack information about if and how multiple changes interact. We examined interactions among four types of environmental disturbance (temperature, nutrient ratio, carbon enrichment, and light) in a fully factorial design using a microbial aquatic ecosystem and observed responses of dissolved oxygen saturation at three temporal scales (resistance, resilience, and return time). We tested whether multiple disturbances combine in a dominant, additive, or interactive fashion, and compared the predictability of dissolved oxygen across scales. Carbon enrichment and shading reduced oxygen concentration in the short term (i.e. resistance); although no other effects or interactions were statistically significant, resistance decreased as the number of disturbances increased. In the medium term, only enrichment accelerated recovery, but none of the other effects (including interactions) were significant. In the long term, enrichment and shading lengthened return times, and we found significant two-way synergistic interactions between disturbances. The best performing model (dominant, additive, or interactive) depended on the temporal scale of response. In the short term (i.e. for resistance), the dominance model predicted resistance of dissolved oxygen best, due to a large effect of carbon enrichment, whereas none of the models could predict the medium term (i.e. resilience). The long-term response was best predicted by models including interactions among disturbances. Our results indicate the importance of accounting for the temporal scale of responses when researching the effects of environmental disturbances on ecosystems. © 2017 The Authors. Global Change Biology Published by John Wiley

  3. Prostate cancer risk locus at 8q24 as a regulatory hub by physical interactions with multiple genomic loci across the genome.

    Science.gov (United States)

    Du, Meijun; Yuan, Tiezheng; Schilter, Kala F; Dittmar, Rachel L; Mackinnon, Alexander; Huang, Xiaoyi; Tschannen, Michael; Worthey, Elizabeth; Jacob, Howard; Xia, Shu; Gao, Jianzhong; Tillmans, Lori; Lu, Yan; Liu, Pengyuan; Thibodeau, Stephen N; Wang, Liang

    2015-01-01

    Chromosome 8q24 locus contains regulatory variants that modulate genetic risk to various cancers including prostate cancer (PC). However, the biological mechanism underlying this regulation is not well understood. Here, we developed a chromosome conformation capture (3C)-based multi-target sequencing technology and systematically examined three PC risk regions at the 8q24 locus and their potential regulatory targets across human genome in six cell lines. We observed frequent physical contacts of this risk locus with multiple genomic regions, in particular, inter-chromosomal interaction with CD96 at 3q13 and intra-chromosomal interaction with MYC at 8q24. We identified at least five interaction hot spots within the predicted functional regulatory elements at the 8q24 risk locus. We also found intra-chromosomal interaction genes PVT1, FAM84B and GSDMC and inter-chromosomal interaction gene CXorf36 in most of the six cell lines. Other gene regions appeared to be cell line-specific, such as RRP12 in LNCaP, USP14 in DU-145 and SMIN3 in lymphoblastoid cell line. We further found that the 8q24 functional domains more likely interacted with genomic regions containing genes enriched in critical pathways such as Wnt signaling and promoter motifs such as E2F1 and TCF3. This result suggests that the risk locus may function as a regulatory hub by physical interactions with multiple genes important for prostate carcinogenesis. Further understanding genetic effect and biological mechanism of these chromatin interactions will shed light on the newly discovered regulatory role of the risk locus in PC etiology and progression. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. 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.

  5. Trichoderma-plant-pathogen interactions: advances in genetics of biological control.

    Science.gov (United States)

    Mukherjee, Mala; Mukherjee, Prasun K; Horwitz, Benjamin A; Zachow, Christin; Berg, Gabriele; Zeilinger, Susanne

    2012-12-01

    Trichoderma spp. are widely used in agriculture as biofungicides. Induction of plant defense and mycoparasitism (killing of one fungus by another) are considered to be the most important mechanisms of Trichoderma-mediated biological control. Understanding these mechanisms at the molecular level would help in developing strains with superior biocontrol properties. In this article, we review our current understanding of the genetics of interactions of Trichoderma with plants and plant pathogens.

  6. Interactions between organic anions on multiple transporters in Caco-2 cells

    DEFF Research Database (Denmark)

    Grandvuinet, Anne Sophie; Steffansen, Bente

    2011-01-01

    Caco-2 cell line may be used as an overall model to predict interactions on multiple membrane transporters in the intestine. Taurocholic acid (TCA) and estrone-3-sulfate (E1S) were used as model substrates. Possible inhibitors studied were TCA, E1S, taurolithocholic acid, fluvastatin, and glipizide......-dependent bile acid transporter and the organic solute transporter α/β, and to less extent by the organic anion transporting polypeptide 2B1. However, interactions on efflux transporters were not detected, although they were expected from the literature on the investigated compounds. Biosimulation methods may...

  7. Interactome of Obesity: Obesidome : Genetic Obesity, Stress Induced Obesity, Pathogenic Obesity Interaction.

    Science.gov (United States)

    Geronikolou, Styliani A; Pavlopoulou, Athanasia; Cokkinos, Dennis; Chrousos, George

    2017-01-01

    Obesity is a chronic disease of increasing prevalence reaching epidemic proportions. Genetic defects as well as epigenetic effects contribute to the obesity phenotype. Investigating gene (e.g. MC4R defects)-environment (behavior, infectious agents, stress) interactions is a relative new field of great research interest. In this study, we have made an effort to create an interactome (henceforth referred to as "obesidome"), where extrinsic stressors response, intrinsic predisposition, immunity response to inflammation and autonomous nervous system implications are integrated. These pathways are presented in one interactome network for the first time. In our study, obesity-related genes/gene products were found to form a complex interactions network.

  8. Interactions between Gut Microbiota, Host Genetics and Diet Modulate the Predisposition to Obesity and Metabolic Syndrome

    OpenAIRE

    Ussar, Siegfried; Griffin, Nicholas W.; Bezy, Olivier; Fujisaka, Shiho; Vienberg, Sara; Softic, Samir; Deng, Luxue; Bry, Lynn; Gordon, Jeffrey I.; Kahn, C. Ronald

    2015-01-01

    Obesity, diabetes and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly-used inbred strains of mice – obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ, from Jackson Laboratory and obesity-prone, but diabetes resistant 129S6/SvEvTac from Taconic - plus three derivative lines generated by breeding these strains in a new, common environm...

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

    Science.gov (United States)

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

    2018-01-01

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

  10. Detecting Genetic Interactions for Quantitative Traits Using m-Spacing Entropy Measure

    Directory of Open Access Journals (Sweden)

    Jaeyong Yee

    2015-01-01

    Full Text Available A number of statistical methods for detecting gene-gene interactions have been developed in genetic association studies with binary traits. However, many phenotype measures are intrinsically quantitative and categorizing continuous traits may not always be straightforward and meaningful. Association of gene-gene interactions with an observed distribution of such phenotypes needs to be investigated directly without categorization. Information gain based on entropy measure has previously been successful in identifying genetic associations with binary traits. We extend the usefulness of this information gain by proposing a nonparametric evaluation method of conditional entropy of a quantitative phenotype associated with a given genotype. Hence, the information gain can be obtained for any phenotype distribution. Because any functional form, such as Gaussian, is not assumed for the entire distribution of a trait or a given genotype, this method is expected to be robust enough to be applied to any phenotypic association data. Here, we show its use to successfully identify the main effect, as well as the genetic interactions, associated with a quantitative trait.

  11. Interaction of multiple plasma plumes in an atmospheric pressure plasma jet array

    International Nuclear Information System (INIS)

    Ghasemi, M; Olszewski, P; Bradley, J W; Walsh, J L

    2013-01-01

    Plasma jet arrays are considered a viable means to enhance the scale of a downstream surface treatment beyond that possible using a single plasma jet. Of paramount importance in many processing applications is the uniformity of the plasma exposure on the substrate, which can be compromised when multiple plasma jets are arranged in close proximity due to their interaction. This contribution explores a dielectric barrier plasma jet array consisting of multiple individually ballasted jets. It is shown that capacitive ballasting is a promising technique to allow simultaneous operation of the plasma plumes without the losses associated with resistive ballasting. The interaction between adjacent plasma plumes and the background gas is investigated with Schlieren imaging; it is shown that the strong repulsive force between each plasma plume causes a divergence in propagation trajectory and a reduction in the laminar flow length with significant ramifications for any downstream surface treatment.

  12. 7th International Workshop on Multiple Partonic Interactions at the LHC

    CERN Document Server

    Treleani, Daniele; Strikman, Mark; van Buuren, Nadia

    2016-01-01

    From the start of the experimental activity of the Large Hadron Collider, Multiple Partonic Interactions (MPI) are experiencing a growing popularity and are widely invoked to account for observations that cannot be explained otherwise. This includes associated hadron production (Underlying Event) in high energy hadronic collisions with jets, the rates for multiple heavy flavor production, the survival probability of large rapidity gaps in hard diffraction, etc. In particular Double Parton Interactions were observed directly and studied by a number of the FNAL and LHC experiments in different reaction channels. At the LHC a new QCD regime has now been reached, where MPIs occur with high rates, in particular in central collisions, where the production of new particles is more likely to take place. Understanding MPIs is therefore crucial, both for their significant contribution to the background of various processes of interest for the search of new physics and because MPIs are an interesting topic of research b...

  13. MicroRNA expression in multiple myeloma is associated with genetic subtype, isotype and survival

    Directory of Open Access Journals (Sweden)

    Pezzella Francesco

    2011-05-01

    Full Text Available Abstract Background MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including hematological malignancies. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM is only poorly understood. We therefore used microarray analysis to elucidate the complete miRNome (miRBase version 13.0 of purified tumor (CD138+ cells from 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS and 9 controls. Results Unsupervised cluster analysis revealed that MM and MGUS samples have a distinct microRNA expression profile from control CD138+ cells. The majority of microRNAs aberrantly expressed in MM (109/129 were up-regulated. A comparison of these microRNAs with those aberrantly expressed in other B-cell and T-cell malignancies revealed a surprising degree of similarity (~40% suggesting the existence of a common lymphoma microRNA signature. We identified 39 microRNAs associated with the pre-malignant condition MGUS. Twenty-three (59% of these were also aberrantly expressed in MM suggesting common microRNA expression events in MM progression. MM is characterized by multiple chromosomal abnormalities of varying prognostic significance. We identified specific microRNA signatures associated with the most common IgH translocations (t(4;14 and t(11;14 and del(13q. Expression levels of these microRNAs were distinct between the genetic subtypes (by cluster analysis and correctly predicted these abnormalities in > 85% of cases using the support vector machine algorithm. Additionally, we identified microRNAs associated with light chain only myeloma, as well as IgG and IgA-type MM. Finally, we identified 32 microRNAs associated with event-free survival (EFS in MM, ten of which were significant by univariate (logrank survival analysis. Conclusions In summary, this work has identified aberrantly expressed microRNAs associated with the

  14. Hierarchical folding of multiple sequence alignments for the prediction of structures and RNA-RNA interactions

    DEFF Research Database (Denmark)

    Seemann, Ernst Stefan; Richter, Andreas S.; Gorodkin, Jan

    2010-01-01

    of that used for individual multiple alignments. Results: We derived a rather extensive algorithm. One of the advantages of our approach (in contrast to other RNARNA interaction prediction methods) is the application of covariance detection and prediction of pseudoknots between intra- and inter-molecular base...... pairs. As a proof of concept, we show an example and discuss the strengths and weaknesses of the approach....

  15. Genetic factors and multiple sclerosis in the Moroccan population: a role for HLA class II.

    Science.gov (United States)

    Ouadghiri, S; El Alaoui Toussi, K; Brick, C; Ait Benhaddou, E H; Benseffaj, N; Benomar, A; El Yahyaoui, M; Essakalli, M

    2013-12-01

    Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system that mainly affects young adults. The association between susceptibility to MS and HLA class II genes, in particular the DRB1*15 allele, has been reported in diverse ethnic groups. The aim of our study was to investigate the distribution of HLA-DRB1* and -DQB1* alleles in Moroccan population and their implication in the susceptibility to the disease. Fifty-seven MS patients were compared to 172 healthy controls unrelated to one another and matched by age, sex and ethnic origin. HLA class II (DRB1* and DQB1*) typing was performed by PCR-SSP and/or Luminex (PCR-SSO). Allelic and haplotypic frequencies, P-values, odds ratio (OR) and 95% confidence interval (CI) were calculated using the software SPSS. A significant increase of DRB1*15 allele frequency (17.6% vs 8.4%, OR=2.67, 95% CI=1.36-5.23, P=0.004) and HLA-DRB1*15-DQB1*06 haplotype (8.8% vs 4.08%, OR=2.78, 95% CI=1.41-5.48, P=0.002) were observed in Moroccan MS patients. No association of the DR15 allele with sex or age at onset was appreciated. Concerning HLA-DQB1* alleles, no significant difference between patients and controls was found. Our results reveal a role for HLA-DRB1*15 allele molecules in the predisposition of Moroccan patients to MS. Although this study should be confirmed on a larger sample size, it analyzes for the first time the possible role of a genetic marker for susceptibility to MS in Moroccan population. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Evaluation of genetically inactivated alpha toxin for protection in multiple mouse models of Staphylococcus aureus infection.

    Directory of Open Access Journals (Sweden)

    Rebecca A Brady

    Full Text Available Staphylococcus aureus is a major human pathogen and a leading cause of nosocomial and community-acquired infections. Development of a vaccine against this pathogen is an important goal. While S. aureus protective antigens have been identified in the literature, the majority have only been tested in a single animal model of disease. We wished to evaluate the ability of one S. aureus vaccine antigen to protect in multiple mouse models, thus assessing whether protection in one model translates to protection in other models encompassing the full breadth of infections the pathogen can cause. We chose to focus on genetically inactivated alpha toxin mutant HlaH35L. We evaluated the protection afforded by this antigen in three models of infection using the same vaccine dose, regimen, route of immunization, adjuvant, and challenge strain. When mice were immunized with HlaH35L and challenged via a skin and soft tissue infection model, HlaH35L immunization led to a less severe infection and decreased S. aureus levels at the challenge site when compared to controls. Challenge of HlaH35L-immunized mice using a systemic infection model resulted in a limited, but statistically significant decrease in bacterial colonization as compared to that observed with control mice. In contrast, in a prosthetic implant model of chronic biofilm infection, there was no significant difference in bacterial levels when compared to controls. These results demonstrate that vaccines may confer protection against one form of S. aureus disease without conferring protection against other disease presentations and thus underscore a significant challenge in S. aureus vaccine development.

  17. Clinical and Genetic Analysis of Multiple Endocrine Neoplasia Type 1-Related Primary Hyperparathyroidism in Chinese.

    Directory of Open Access Journals (Sweden)

    Jing Kong

    Full Text Available Multiple endocrine neoplasia type 1-related primary hyperparathyroidism (MHPT differs in many aspects from sporadic PHPT (SHPT. The aims of this study were to summarize the clinical features and genetic background of Chinese MHPT patients and compare the severity of the disease with those of SHPT.A total of 40 MHPT (27 sporadic, 7 families and 169 SHPT cases of Chinese descent were retrospectively analyzed. X-rays and ultrasound were used to assess the bone and urinary system. Dual energy x-ray absorptiometry (DXA were performed to measure bone mineral density (BMD. Besides direct sequencing of the MEN1 and CDKN1B genes, multiplex ligation-dependent probe amplification (MLPA was used to screen gross deletion for the MEN1 gene.Compared with SHPT patients, MHPT patients showed lower prevalence of typical X-ray changes related to PHPT (26.3% vs. 55.7%, P = 0.001 but higher prevalence of urolithiasis/renal calcification (40.2% vs. 60.0%, P = 0.024. MHPT patients showed higher phosphate level (0.84 vs. 0.73mmol/L, P<0.05 but lower ALP (103.0 vs. 174.0U/L, P<0.001 and PTH (4.0 vs. 9.8×upper limit, P<0.001 levels than SHPT patients. There were no significant differences in BMD Z-scores at the lumbar spine and femoral neck between the two groups. Mutations in the MEN1 gene were detected in 27 MHPT cases. Among the nine novel mutations were novel, one of them involved the deletion of exon 5 and 6.MHPT patients experienced more common kidney complications but less skeletal issues, and a milder biochemical manifestation compared with SHPT patients. MEN1 mutation detection rate was 79.4% and 9 of the identified mutations were novel.

  18. Heat Recovery from Multiple-Fracture Enhanced Geothermal Systems: The Effect of Thermoelastic Fracture Interactions

    DEFF Research Database (Denmark)

    Vik, Hedda Slatlem; Salimzadeh, Saeed; Nick, Hamid

    2018-01-01

    This study investigates the effect of thermoelastic interactions between multiple parallel fractures on energy production from a multiple-fracture enhanced geothermal system. A coupled thermo-hydro-mechanical finite element model has been developed that accounts for non-isothermal fluid flow within...... increased to maximise the net energy production from the system. Otherwise, the multiple-fracture system fails to improve the energy recovery from the geothermal reservoir, as initially intended....... aperture in the adjacent fracture, and facilitates the creation of favourable flow pathways between the injection and production wells. These flow paths reduce the energy production from the system. The effects of fracture spacing, reservoir temperature gradient and mechanical properties of the rock matrix...

  19. Social evolution and genetic interactions in the short and long term.

    Science.gov (United States)

    Van Cleve, Jeremy

    2015-08-01

    The evolution of social traits remains one of the most fascinating and feisty topics in evolutionary biology even after half a century of theoretical research. W.D. Hamilton shaped much of the field initially with his 1964 papers that laid out the foundation for understanding the effect of genetic relatedness on the evolution of social behavior. Early theoretical investigations revealed two critical assumptions required for Hamilton's rule to hold in dynamical models: weak selection and additive genetic interactions. However, only recently have analytical approaches from population genetics and evolutionary game theory developed sufficiently so that social evolution can be studied under the joint action of selection, mutation, and genetic drift. We review how these approaches suggest two timescales for evolution under weak mutation: (i) a short-term timescale where evolution occurs between a finite set of alleles, and (ii) a long-term timescale where a continuum of alleles are possible and populations evolve continuously from one monomorphic trait to another. We show how Hamilton's rule emerges from the short-term analysis under additivity and how non-additive genetic interactions can be accounted for more generally. This short-term approach reproduces, synthesizes, and generalizes many previous results including the one-third law from evolutionary game theory and risk dominance from economic game theory. Using the long-term approach, we illustrate how trait evolution can be described with a diffusion equation that is a stochastic analogue of the canonical equation of adaptive dynamics. Peaks in the stationary distribution of the diffusion capture classic notions of convergence stability from evolutionary game theory and generally depend on the additive genetic interactions inherent in Hamilton's rule. Surprisingly, the peaks of the long-term stationary distribution can predict the effects of simple kinds of non-additive interactions. Additionally, the peaks

  20. N-way FRET microscopy of multiple protein-protein interactions in live cells.

    Directory of Open Access Journals (Sweden)

    Adam D Hoppe

    Full Text Available Fluorescence Resonance Energy Transfer (FRET microscopy has emerged as a powerful tool to visualize nanoscale protein-protein interactions while capturing their microscale organization and millisecond dynamics. Recently, FRET microscopy was extended to imaging of multiple donor-acceptor pairs, thereby enabling visualization of multiple biochemical events within a single living cell. These methods require numerous equations that must be defined on a case-by-case basis. Here, we present a universal multispectral microscopy method (N-Way FRET to enable quantitative imaging for any number of interacting and non-interacting FRET pairs. This approach redefines linear unmixing to incorporate the excitation and emission couplings created by FRET, which cannot be accounted for in conventional linear unmixing. Experiments on a three-fluorophore system using blue, yellow and red fluorescent proteins validate the method in living cells. In addition, we propose a simple linear algebra scheme for error propagation from input data to estimate the uncertainty in the computed FRET images. We demonstrate the strength of this approach by monitoring the oligomerization of three FP-tagged HIV Gag proteins whose tight association in the viral capsid is readily observed. Replacement of one FP-Gag molecule with a lipid raft-targeted FP allowed direct observation of Gag oligomerization with no association between FP-Gag and raft-targeted FP. The N-Way FRET method provides a new toolbox for capturing multiple molecular processes with high spatial and temporal resolution in living cells.

  1. Numerical Simulations for Nonlinear Waves Interaction with Multiple Perforated Quasi-Ellipse Caissons

    Directory of Open Access Journals (Sweden)

    Xiaozhong Ren

    2015-01-01

    Full Text Available A three-dimensional numerical flume is developed to study cnoidal wave interaction with multiple arranged perforated quasi-ellipse caissons. The continuity equation and the Navier-Stokes equations are used as the governing equation, and the VOF method is adopted to capture the free surface elevation. The equations are discretized on staggered cells and then solved using a finite difference method. The generation and propagation of cnoidal waves in the numerical flume are tested first. And the ability of the present model to simulate interactions between waves and structures is verified by known experimental results. Then cnoidal waves with varying incident wave height and period are generated and interact with multiple quasi-ellipse caissons with and without perforation. It is found that the perforation plays an effective role in reducing wave runup/rundown and wave forces on the caissons. The wave forces on caissons reduce with the decreasing incident wave period. The influence of the transverse distance of multiple caissons on wave forces is also investigated. A closer transverse distance between caissons can produce larger wave forces. But when relative adjacent distance L/D (L is the transverse distance and D is the width of the quasi-ellipse caisson is larger than 3, the effect of adjacent distance is limited.

  2. Genetic differentiation across multiple spatial scales of the Red Sea of the corals Stylophora pistillata and Pocillopora verrucosa

    KAUST Repository

    Monroe, Alison

    2015-12-01

    Observing populations at different spatial scales gives greater insight into the specific processes driving genetic differentiation and population structure. Here we determined population connectivity across multiple spatial scales in the Red Sea to determine the population structures of two reef building corals Stylophora pistillata and Pocillopora verrucosa. The Red sea is a 2,250 km long body of water with extremely variable latitudinal environmental gradients. Mitochondrial and microsatellite markers were used to determine distinct lineages and to look for genetic differentiation among sampling sites. No distinctive population structure across the latitudinal gradient was discovered within this study suggesting a phenotypic plasticity of both these species to various environments. Stylophora pistillata displayed a heterogeneous distribution of three distinct genetic populations on both a fine and large scale. Fst, Gst, and Dest were all significant (p-value<0.05) and showed moderate genetic differentiation between all sampling sites. However this seems to be byproduct of the heterogeneous distribution, as no distinct genetic population breaks were found. Stylophora pistillata showed greater population structure on a fine scale suggesting genetic selection based on fine scale environmental variations. However, further environmental and oceanographic data is needed to make more inferences on this structure at small spatial scales. This study highlights the deficits of knowledge of both the Red Sea and coral plasticity in regards to local environmental conditions.

  3. Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain.

    Science.gov (United States)

    Matthes, Michaela; Preusse, Martin; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Theis, Fabian; Prakash, Nilima; Wurst, Wolfgang; Trümbach, Dietrich

    2014-01-01

    The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior-posterior, dorsal-ventral and medial- lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson's disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/β-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. http://mouseidgenes.helmholtz-muenchen.de. © The Author(s) 2014. Published by Oxford University Press.

  4. TheCellMap.org: A Web-Accessible Database for Visualizing and Mining the Global Yeast Genetic Interaction Network.

    Science.gov (United States)

    Usaj, Matej; Tan, Yizhao; Wang, Wen; VanderSluis, Benjamin; Zou, Albert; Myers, Chad L; Costanzo, Michael; Andrews, Brenda; Boone, Charles

    2017-05-05

    Providing access to quantitative genomic data is key to ensure large-scale data validation and promote new discoveries. TheCellMap.org serves as a central repository for storing and analyzing quantitative genetic interaction data produced by genome-scale Synthetic Genetic Array (SGA) experiments with the budding yeast Saccharomyces cerevisiae In particular, TheCellMap.org allows users to easily access, visualize, explore, and functionally annotate genetic interactions, or to extract and reorganize subnetworks, using data-driven network layouts in an intuitive and interactive manner. Copyright © 2017 Usaj et al.

  5. Identification of New Genetic Susceptibility Loci for Breast Cancer Through Consideration of Gene-Environment Interactions

    Science.gov (United States)

    Schoeps, Anja; Rudolph, Anja; Seibold, Petra; Dunning, Alison M.; Milne, Roger L.; Bojesen, Stig E.; Swerdlow, Anthony; Andrulis, Irene; Brenner, Hermann; Behrens, Sabine; Orr, Nicholas; Jones, Michael; Ashworth, Alan; Li, Jingmei; Cramp, Helen; Connley, Dan; Czene, Kamila; Darabi, Hatef; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Knight, Julia; Glendon, Gord; Mulligan, Anna M.; Dumont, Martine; Severi, Gianluca; Baglietto, Laura; Olson, Janet; Vachon, Celine; Purrington, Kristen; Moisse, Matthieu; Neven, Patrick; Wildiers, Hans; Spurdle, Amanda; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Hamann, Ute; Ko, Yon-Dschun; Dieffenbach, Aida K.; Arndt, Volker; Stegmaier, Christa; Malats, Núria; Arias Perez, JoséI.; Benítez, Javier; Flyger, Henrik; Nordestgaard, Børge G.; Truong, Théresè; Cordina-Duverger, Emilie; Menegaux, Florence; Silva, Isabel dos Santos; Fletcher, Olivia; Johnson, Nichola; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Braaf, Linde; Atsma, Femke; van den Broek, Alexandra J.; Makalic, Enes; Schmidt, Daniel F.; Southey, Melissa C.; Cox, Angela; Simard, Jacques; Giles, Graham G.; Lambrechts, Diether; Mannermaa, Arto; Brauch, Hiltrud; Guénel, Pascal; Peto, Julian; Fasching, Peter A.; Hopper, John; Flesch-Janys, Dieter; Couch, Fergus; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Schmidt, Marjanka K.; Hall, Per; Easton, Douglas F.; Chang-Claude, Jenny

    2014-01-01

    Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10−07), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m2 (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m2 or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10−05). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci. PMID:24248812

  6. Large Display Interaction via Multiple Acceleration Curves and Multifinger Pointer Control

    Directory of Open Access Journals (Sweden)

    Andrey Esakia

    2014-01-01

    Full Text Available Large high-resolution displays combine high pixel density with ample physical dimensions. The combination of these factors creates a multiscale workspace where interactive targeting of on-screen objects requires both high speed for distant targets and high accuracy for small targets. Modern operating systems support implicit dynamic control-display gain adjustment (i.e., a pointer acceleration curve that helps to maintain both speed and accuracy. However, large high-resolution displays require a broader range of control-display gains than a single acceleration curve can usably enable. Some interaction techniques attempt to solve the problem by utilizing multiple explicit modes of interaction, where different modes provide different levels of pointer precision. Here, we investigate the alternative hypothesis of using a single mode of interaction for continuous pointing that enables both (1 standard implicit granularity control via an acceleration curve and (2 explicit switching between multiple acceleration curves in an efficient and dynamic way. We evaluate a sample solution that augments standard touchpad accelerated pointer manipulation with multitouch capability, where the choice of acceleration curve dynamically changes depending on the number of fingers in contact with the touchpad. Specifically, users can dynamically switch among three different acceleration curves by using one, two, or three fingers on the touchpad.

  7. Effects of Pilates exercises on sensory interaction, postural control and fatigue in patients with multiple sclerosis.

    Science.gov (United States)

    Soysal Tomruk, Melda; Uz, Muhammed Zahid; Kara, Bilge; İdiman, Egemen

    2016-05-01

    Decreased postural control, sensory integration deficits and fatigue are important problems that cause functional impairments in patients with multiple sclerosis (pwMS). To examine the effect of modified clinical Pilates exercises on sensory interaction and balance, postural control and fatigue in pwMS. Eleven patients with multiple sclerosis and 12 healthy matched controls were recruited in this study. Limits of stability and postural stability tests were used to evaluate postural control by Biodex Balance System and sensory interaction assessed. Fatigue was assessed by Modified Fatigue Impact Scale. Pilates exercises were applied two times a week for 10 weeks and measurements were repeated to pwMS after exercise training. Postural control and fatigue (except psychosocial parameter) of pwMS were significantly worser than healthy controls (pPilates training (ppilates exercises (p>0.05). Ten-week Pilates training is effective to improve sensory interaction and to decrease fatigue. Pilates exercises can be applied safely in ambulatory pwMS for enhance sensory interaction and balance and combat fatigue. More investigations are needed. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Game Theory of Tumor–Stroma Interactions in Multiple Myeloma: Effect of Nonlinear Benefits

    Directory of Open Access Journals (Sweden)

    Javad Salimi Sartakhti

    2018-05-01

    Full Text Available Cancer cells and stromal cells often exchange growth factors with paracrine effects that promote cell growth: a form of cooperation that can be studied by evolutionary game theory. Previous models have assumed that interactions between cells are pairwise or that the benefit of a growth factor is a linear function of its concentration. Diffusible factors, however, affect multiple cells and generally have nonlinear effects, and these differences are known to have important consequences for evolutionary dynamics. Here, we study tumor–stroma paracrine signaling using a model with multiplayer collective interactions in which growth factors have nonlinear effects. We use multiple myeloma as an example, modelling interactions between malignant plasma cells, osteoblasts, and osteoclasts. Nonlinear benefits can lead to results not observed in linear models, including internal mixed stable equilibria and cyclical dynamics. Models with linear effects, therefore, do not lead to a meaningful characterization of the dynamics of tumor–stroma interactions. To understand the dynamics and the effect of therapies it is necessary to estimate the shape of the benefit functions experimentally and parametrize models based on these functions.

  9. Measurement of Reconstructed Charged Particle Multiplicities of Neutrino Interactions in MicroBooNE

    Energy Technology Data Exchange (ETDEWEB)

    Rafique, Aleena [Kansas State Univ., Manhattan, KS (United States)

    2017-09-25

    Here, we compare the observed charged particle multiplicity distributions in the MicroBooNE liquid argon time projection chamber from neutrino interactions in a restricted final state phase space to predictions of this distribution from several GENIE models. The measurement uses a data sample consisting of neutrino interactions with a final state muon candidate fully contained within the MicroBooNE detector. These data were collected in 2015-2016 with the Fermilab Booster Neutrino Beam (BNB), which has an average neutrino energy of 800 MeV, using an exposure corresponding to 5e19 protons-on-target. The analysis employs fully automatic event selection and charged particle track reconstruction and uses a data-driven technique to determine the contribution to each multiplicity bin from neutrino interactions and cosmic-induced backgrounds. The restricted phase space employed makes the measurement most sensitive to the higher-energy charged particles expected from primary neutrino-argon collisions and less sensitive to lower energy protons expected to be produced in final state interactions of collision products with the target argon nucleus.

  10. Probability distributions in conservative energy exchange models of multiple interacting agents

    International Nuclear Information System (INIS)

    Scafetta, Nicola; West, Bruce J

    2007-01-01

    Herein we study energy exchange models of multiple interacting agents that conserve energy in each interaction. The models differ regarding the rules that regulate the energy exchange and boundary effects. We find a variety of stochastic behaviours that manifest energy equilibrium probability distributions of different types and interaction rules that yield not only the exponential distributions such as the familiar Maxwell-Boltzmann-Gibbs distribution of an elastically colliding ideal particle gas, but also uniform distributions, truncated exponential distributions, Gaussian distributions, Gamma distributions, inverse power law distributions, mixed exponential and inverse power law distributions, and evolving distributions. This wide variety of distributions should be of value in determining the underlying mechanisms generating the statistical properties of complex phenomena including those to be found in complex chemical reactions

  11. Directional genetic selection by pulp mill effluent on multiple natural populations of three-spined stickleback (Gasterosteus aculeatus).

    Science.gov (United States)

    Lind, Emma E; Grahn, Mats

    2011-05-01

    Contamination can cause a rapid environmental change which may require populations to respond with evolutionary changes. To evaluate the effects of pulp mill effluents on population genetics, we sampled three-spined sticklebacks (Gasterosteus aculeatus) near four pulp mills and four adjacent reference sites and analyzed Amplified Fragment Length Polymorphism (AFLP) to compare genetic variability. A fine scale genetic structure was detected and samples from polluted sites separated from reference sites in multidimensional scaling plots (Pselection. When removing 13 F(ST)-outlier loci, significant at the Pselective agent on natural populations of G. aculeatus, causing a convergence in genotype composition change at multiple sites in an open environment. © The Author(s) 2011. This article is published with open access at Springerlink.com

  12. Defining conservation units in a stocking-induced genetic melting pot: unraveling native and multiple exotic genetic imprints of recent and historical secondary contact in Adriatic grayling.

    Science.gov (United States)

    Meraner, Andreas; Cornetti, Luca; Gandolfi, Andrea

    2014-04-01

    The definition of conservation units is crucial for the sustainable management of endangered species, though particularly challenging when recent and past anthropogenic and natural gene flow might have played a role. The conservation of the European grayling, Thymallus thymallus, is particularly complex in its southern distribution area, where the Adriatic evolutionary lineage is endangered by a long history of anthropogenic disturbance, intensive stocking and potentially widespread genetic introgression. We provide mtDNA sequence and microsatellite data of 683 grayling from 30 sites of Adriatic as well as Danubian and Atlantic origin. We apply Bayesian clustering and Approximate Bayesian Computation (ABC) to detect microgeographic population structure and to infer the demographic history of the Adriatic populations, to define appropriate conservation units. Varying frequencies of indigenous genetic signatures of the Adriatic grayling were revealed, spanning from marginal genetic introgression to the collapse of native gene pools. Genetic introgression involved multiple exotic source populations of Danubian and Atlantic origin, thus evidencing the negative impact of few decades of stocking. Within the Adige River system, a contact zone of western Adriatic and eastern Danubian populations was detected, with ABC analyses suggesting a historical anthropogenic origin of eastern Adige populations, most likely founded by medieval translocations. Substantial river-specific population substructure within the Adriatic grayling Evolutionary Significant Unit points to the definition of different conservation units. We finally propose a catalog of management measures, including the legal prohibition of stocking exotic grayling and the use of molecular markers in supportive- and captive-breeding programs.

  13. Hypothesis: Genetic and epigenetic risk factors interact to modulate vulnerability and resilience to FASD

    Directory of Open Access Journals (Sweden)

    Elif eTunc-Ozcan

    2014-08-01

    Full Text Available Fetal alcohol spectrum disorder (FASD presents a collection of symptoms representing physiological and behavioral phenotypes caused by maternal alcohol consumption. Symptom severity is modified by genetic differences in fetal susceptibility and resistance as well as maternal genetic factors such as maternal alcohol sensitivity. Animal models demonstrate that both maternal and paternal genetics contribute to the variation in the fetus’ vulnerability to alcohol exposure. Maternal and paternal genetics define the variations in these phenotypes even without the effect of alcohol in utero, as most of these traits are polygenic, non-Mendelian, in their inheritance. In addition, the epigenetic alterations that instigate the alcohol induced neurodevelopmental deficits can interact with the polygenic inheritance of respective traits. Here, based on specific examples, we present the hypothesis that the principles of non-Mendelian inheritance, or ‘exceptions’ to Mendelian genetics, can be the driving force behind the severity of the prenatal alcohol-exposed individual’s symptomology. One such exception is when maternal alleles lead to an altered intrauterine hormonal environment and, therefore, produce variations in the long-term consequences on the development of the alcohol-exposed fetus. Another exception is when epigenetic regulation of allele-specific gene expression generates disequilibrium between the maternal versus paternal genetic contributions, and thereby, modifies the effect of prenatal alcohol exposure on the fetus. We propose that these situations in which one parent has an exaggerated influence over the offspring’s vulnerability to prenatal alcohol are major contributing mechanisms responsible for the variations in the symptomology of FASD in the exposed generation and beyond.

  14. Research on interactive genetic-geological models to evaluate favourability for undiscovered uranium resources

    International Nuclear Information System (INIS)

    Finch, W.I.; Granger, H.C.; Lupe, R.; McCammon, R.B.

    1980-01-01

    Current methods of evaluating favourability for undiscovered uranium resources are unduly subjective, quite possibly inconsistent and, as a consequence, of questionable reliability. This research is aimed at reducing the subjectivity and increasing the reliability by designing an improved method that depends largely on geological data and their statistical frequency of occurrence. This progress report outlines a genetic approach to modelling the geological factors that controlled uranium mineralization in order to evaluate the favourability for the occurrence of undiscovered uranium deposits of the type modelled. A genetic model is constructed from all the factors that describe the processes, in chronological sequence, that formed uranium deposits thought to have a common origin. The field and laboratory evidence for the processes constitute a geologic-occurrence base that parallels the chronological sequence of events. The genetic model and the geologic-occurrence base are portrayed as two columns of an interactive matrix called the ''genetic-geologic model''. For each column, eight chronological stages are used to describe the overall formation of the uranium deposits. These stages consist of (1) precursor processes; (2) host-rock formation; (3) preparation of host-rock; (4) uranium-source development; (5) transport of uranium; (6) primary uranium deposition; (7) post-deposition modification; and (8) preservation. To apply the genetic-geological model to evaluate favourability, a question is posed that determines the presence or absence of each attribute listed under the geologic-occurrence base. By building a logic circuit of the attributes according to either their essential or non-essential nature, the resultant match between a well-documented control area and the test area may be determined. The degree of match is a measure of favourability for uranium occurrence as hypothesized in the genetic model

  15. Neighborhood alcohol outlet density and genetic influences on alcohol use: evidence for gene-environment interaction.

    Science.gov (United States)

    Slutske, Wendy S; Deutsch, Arielle R; Piasecki, Thomas M

    2018-05-07

    Genetic influences on alcohol involvement are likely to vary as a function of the 'alcohol environment,' given that exposure to alcohol is a necessary precondition for genetic risk to be expressed. However, few gene-environment interaction studies of alcohol involvement have focused on characteristics of the community-level alcohol environment. The goal of this study was to examine whether living in a community with more alcohol outlets would facilitate the expression of the genetic propensity to drink in a genetically-informed national survey of United States young adults. The participants were 2434 18-26-year-old twin, full-, and half-sibling pairs from Wave III of the National Longitudinal Study of Adolescent to Adult Health. Participants completed in-home interviews in which alcohol use was assessed. Alcohol outlet densities were extracted from state-level liquor license databases aggregated at the census tract level to derive the density of outlets. There was evidence that the estimates of genetic and environmental influences on alcohol use varied as a function of the density of alcohol outlets in the community. For example, the heritability of the frequency of alcohol use for those residing in a neighborhood with ten or more outlets was 74% (95% confidence limits = 55-94%), compared with 16% (95% confidence limits = 0-34%) for those in a neighborhood with zero outlets. This moderating effect of alcohol outlet density was not explained by the state of residence, population density, or neighborhood sociodemographic characteristics. The results suggest that living in a neighborhood with many alcohol outlets may be especially high-risk for those individuals who are genetically predisposed to frequently drink.

  16. Multiple caregivers' touch interactions with young children among the Bofi foragers in Central Africa.

    Science.gov (United States)

    Jung, Min-Jung; Fouts, Hillary N

    2011-02-01

    The current study examined the use of three types of touch (caregiving, active social-affectionate, and passive social-affectionate) by caregivers with young children among the Bofi foragers, a seminomadic group of hunter-gatherers in Central Africa. With the purpose of providing a more holistic view of touch interactions in early childhood, compared to extant Western mother-centric views, this study documents stylistic touch patterns used by multiple caregivers (mother, father, adult relatives, and juvenile relatives) with Bofi forager children. Thirty-five Bofi forager children, between 18 and 59 months of age, and their various caregivers were naturalistically observed over 12 daylight hours using a focal child observational technique. Frequencies of each type of touch and the rank order of types of touch that children received were compared between caregivers and examined by child age and gender. Even though nonmaternal caregivers showed high physical involvement with children, mothers exemplified the highest level of involvement. Overall, passive social-affectionate touch was utilized the most by all types of caregivers. Mothers used more caregiving touch, and fathers and adult relatives had similar frequencies of caregiving touch and active social-affectionate touch. In contrast, juvenile relatives showed more active social-affectionate touch with focal children. This study highlights the importance of examining multiple caregivers and physical interactions when studying early childhood experiences. Furthermore, by focusing on multiple caregivers and multiple types of touch, this study provides a more thorough characterization of the touch experiences of young children than previous studies of touch. Finally, the current study exemplifies the value of considering non-Western populations when investigating touch interactions.

  17. Developmental and genetic modulation of arsenic biotransformation: A gene by environment interaction?

    International Nuclear Information System (INIS)

    Meza, Mercedes; Gandolfi, A. Jay; Klimecki, Walter T.

    2007-01-01

    The complexity of arsenic toxicology has confounded the identification of specific pathways of disease causation. One focal point of arsenic research is aimed at fully characterizing arsenic biotransformation in humans, a process that appears to be quite variable, producing a mixture of several arsenic species with greatly differing toxic potencies. In an effort to characterize genetic determinants of variability in arsenic biotransformation, a genetic association study of 135 subjects in western Sonora, Mexico was performed by testing 23 polymorphic sites in three arsenic biotransformation candidate genes. One gene, arsenic 3 methyltransferase (AS3MT), was strongly associated with the ratio of urinary dimethylarsinic acid to monomethylarsonic acid (D/M) in children (7-11 years) but not in adults (18-79 years). Subsequent analyses revealed that the high D/M values associated with variant AS3MT alleles were primarily due to lower levels of monomethylarsonic acid as percent of total urinary arsenic (%MMA5). In light of several reports of arsenic-induced disease being associated with relatively high %MMA5 levels, these findings raise the possibility that variant AS3MT individuals may suffer less risk from arsenic exposure than non-variant individuals. These analyses also provide evidence that, in this population, regardless of AS3MT variant status, children tend to have lower %MMA5 values than adults, suggesting that the global developmental regulation of arsenic biotransformation may interact with genetic variants in metabolic genes to result in novel genetic effects such as those in this report

  18. Detecting high-order interactions of single nucleotide polymorphisms using genetic programming.

    Science.gov (United States)

    Nunkesser, Robin; Bernholt, Thorsten; Schwender, Holger; Ickstadt, Katja; Wegener, Ingo

    2007-12-15

    Not individual single nucleotide polymorphisms (SNPs), but high-order interactions of SNPs are assumed to be responsible for complex diseases such as cancer. Therefore, one of the major goals of genetic association studies concerned with such genotype data is the identification of these high-order interactions. This search is additionally impeded by the fact that these interactions often are only explanatory for a relatively small subgroup of patients. Most of the feature selection methods proposed in the literature, unfortunately, fail at this task, since they can either only identify individual variables or interactions of a low order, or try to find rules that are explanatory for a high percentage of the observations. In this article, we present a procedure based on genetic programming and multi-valued logic that enables the identification of high-order interactions of categorical variables such as SNPs. This method called GPAS cannot only be used for feature selection, but can also be employed for discrimination. In an application to the genotype data from the GENICA study, an association study concerned with sporadic breast cancer, GPAS is able to identify high-order interactions of SNPs leading to a considerably increased breast cancer risk for different subsets of patients that are not found by other feature selection methods. As an application to a subset of the HapMap data shows, GPAS is not restricted to association studies comprising several 10 SNPs, but can also be employed to analyze whole-genome data. Software can be downloaded from http://ls2-www.cs.uni-dortmund.de/~nunkesser/#Software

  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. Multiplicities and forward-backward correlations in anti pp interactions at 22.4 GeV/c

    International Nuclear Information System (INIS)

    Boos, E.G.; Samojlov, V.V.; Tashimov, M.A.

    1977-01-01

    Forward-backward multiplicity correlations in anti pp -interactions at 22.4 GeV/c and multiplicities in a simple icle multiplicity distribution is divided into even and odd components, the probability of producting an odd state is found to be higher than that of producing an even state, which may be interpreted to be due to diffraction forward-backward and to everall multiplicities is discussed

  1. The actin-binding protein capulet genetically interacts with the microtubule motor kinesin to maintain neuronal dendrite homeostasis.

    Directory of Open Access Journals (Sweden)

    Paul M B Medina

    Full Text Available BACKGROUND: Neurons require precise cytoskeletal regulation within neurites, containing microtubule tracks for cargo transport in axons and dendrites or within synapses containing organized actin. Due to the unique architecture and specialized function of neurons, neurons are particularly susceptible to perturbation of the cytoskeleton. Numerous actin-binding proteins help maintain proper cytoskeletal regulation. METHODOLOGY/PRINCIPAL FINDINGS: From a Drosophila forward genetic screen, we identified a mutation in capulet--encoding a conserved actin-binding protein--that causes abnormal aggregates of actin within dendrites. Through interaction studies, we demonstrate that simultaneous genetic inactivation of capulet and kinesin heavy chain, a microtubule motor protein, produces elongate cofilin-actin rods within dendrites but not axons. These rods resemble actin-rich structures induced in both mammalian neurodegenerative and Drosophila Alzheimer's models, but have not previously been identified by loss of function mutations in vivo. We further demonstrate that mitochondria, which are transported by Kinesin, have impaired distribution along dendrites in a capulet mutant. While Capulet and Cofilin may biochemically cooperate in certain circumstances, in neuronal dendrites they genetically antagonize each other. CONCLUSIONS/SIGNIFICANCE: The present study is the first molecularly defined loss of function demonstration of actin-cofilin rods in vivo. This study suggests that simultaneous, seemingly minor perturbations in neuronal dendrites can synergize producing severe abnormalities affecting actin, microtubules and mitochondria/energy availability in dendrites. Additionally, as >90% of Alzheimer's and Parkinson's cases are sporadic this study suggests mechanisms by which multiple mutations together may contribute to neurodegeneration instead of reliance on single mutations to produce disease.

  2. Proceedings of the first international workshop on multiple partonic interactions at the LHC. MPI'08

    Energy Technology Data Exchange (ETDEWEB)

    Bartalini, Paolo [National Taiwan Univ., Taipei (China); Fano, Livio [Istituto Nazionale di Fisica Nucleare, Perugia (Italy)

    2009-06-15

    The objective of this first workshop on Multiple Partonic Interactions (MPI) at the LHC, that can be regarded as a continuation and extension of the dedicated meetings held at DESY in the years 2006 and 2007, is to raise the profile of MPI studies, summarizing the legacy from the older phenomenology at hadronic colliders and favouring further specific contacts between the theory and experimental communities. The MPI are experiencing a growing popularity and are currently widely invoked to account for observations that would not be explained otherwise: the activity of the Underlying Event, the cross sections for multiple heavy flavour production, the survival probability of large rapidity gaps in hard diffraction, etc. At the same time, the implementation of the MPI effects in the Monte Carlo models is quickly proceeding through an increasing level of sophistication and complexity that in perspective achieves deep general implications for the LHC physics. The ultimate ambition of this workshop is to promote the MPI as unification concept between seemingly heterogeneous research lines and to profit of the complete experimental picture in order to constrain their implementation in the models, evaluating the spin offs on the LHC physics program. The workshop is structured in five sections, with the first one dedicated to few selected hot highlights in the High Energy Physics and directly connected to the other ones: Multiple Parton Interactions (in both the soft and the hard regimes), Diffraction, Monte Carlo Generators and Heavy Ions. (orig.)

  3. Proceedings of the first international workshop on multiple partonic interactions at the LHC. MPI'08

    International Nuclear Information System (INIS)

    Bartalini, Paolo; Fano, Livio

    2009-06-01

    The objective of this first workshop on Multiple Partonic Interactions (MPI) at the LHC, that can be regarded as a continuation and extension of the dedicated meetings held at DESY in the years 2006 and 2007, is to raise the profile of MPI studies, summarizing the legacy from the older phenomenology at hadronic colliders and favouring further specific contacts between the theory and experimental communities. The MPI are experiencing a growing popularity and are currently widely invoked to account for observations that would not be explained otherwise: the activity of the Underlying Event, the cross sections for multiple heavy flavour production, the survival probability of large rapidity gaps in hard diffraction, etc. At the same time, the implementation of the MPI effects in the Monte Carlo models is quickly proceeding through an increasing level of sophistication and complexity that in perspective achieves deep general implications for the LHC physics. The ultimate ambition of this workshop is to promote the MPI as unification concept between seemingly heterogeneous research lines and to profit of the complete experimental picture in order to constrain their implementation in the models, evaluating the spin offs on the LHC physics program. The workshop is structured in five sections, with the first one dedicated to few selected hot highlights in the High Energy Physics and directly connected to the other ones: Multiple Parton Interactions (in both the soft and the hard regimes), Diffraction, Monte Carlo Generators and Heavy Ions. (orig.)

  4. The genetic basis of resistance and matching-allele interactions of a host-parasite system: The Daphnia magna-Pasteuria ramosa model.

    Directory of Open Access Journals (Sweden)

    Gilberto Bento

    2017-02-01

    Full Text Available Negative frequency-dependent selection (NFDS is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR- locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into

  5. The genetic basis of resistance and matching-allele interactions of a host-parasite system: The Daphnia magna-Pasteuria ramosa model.

    Science.gov (United States)

    Bento, Gilberto; Routtu, Jarkko; Fields, Peter D; Bourgeois, Yann; Du Pasquier, Louis; Ebert, Dieter

    2017-02-01

    Negative frequency-dependent selection (NFDS) is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR-) locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into its molecular basis.

  6. The Legionella pneumophila IcmSW complex interacts with multiple Dot/Icm effectors to facilitate type IV translocation.

    Directory of Open Access Journals (Sweden)

    Eric D Cambronne

    2007-12-01

    Full Text Available Many gram-negative pathogens use a type IV secretion system (T4SS to deliver effector proteins into eukaryotic host cells. The fidelity of protein translocation depends on the efficient recognition of effector proteins by the T4SS. Legionella pneumophila delivers a large number of effector proteins into eukaryotic cells using the Dot/Icm T4SS. How the Dot/Icm system is able to recognize and control the delivery of effectors is poorly understood. Recent studies suggest that the IcmS and IcmW proteins interact to form a stable complex that facilitates translocation of effector proteins by the Dot/Icm system by an unknown mechanism. Here we demonstrate that the IcmSW complex is necessary for the productive translocation of multiple Dot/Icm effector proteins. Effector proteins that were able to bind IcmSW in vitro required icmS and icmW for efficient translocation into eukaryotic cells during L. pneumophila infection. We identified regions in the effector protein SidG involved in icmSW-dependent translocation. Although the full-length SidG protein was translocated by an icmSW-dependent mechanism, deletion of amino terminal regions in the SidG protein resulted in icmSW-independent translocation, indicating that the IcmSW complex is not contributing directly to recognition of effector proteins by the Dot/Icm system. Biochemical and genetic studies showed that the IcmSW complex interacts with a central region of the SidG protein. The IcmSW interaction resulted in a conformational change in the SidG protein as determined by differences in protease sensitivity in vitro. These data suggest that IcmSW binding to effectors could enhance effector protein delivery by mediating a conformational change that facilitates T4SS recognition of a translocation domain located in the carboxyl region of the effector protein.

  7. Unravelling Darwin's entangled bank: architecture and robustness of mutualistic networks with multiple interaction types.

    Science.gov (United States)

    Dáttilo, Wesley; Lara-Rodríguez, Nubia; Jordano, Pedro; Guimarães, Paulo R; Thompson, John N; Marquis, Robert J; Medeiros, Lucas P; Ortiz-Pulido, Raul; Marcos-García, Maria A; Rico-Gray, Victor

    2016-11-30

    Trying to unravel Darwin's entangled bank further, we describe the architecture of a network involving multiple forms of mutualism (pollination by animals, seed dispersal by birds and plant protection by ants) and evaluate whether this multi-network shows evidence of a structure that promotes robustness. We found that species differed strongly in their contributions to the organization of the multi-interaction network, and that only a few species contributed to the structuring of these patterns. Moreover, we observed that the multi-interaction networks did not enhance community robustness compared with each of the three independent mutualistic networks when analysed across a range of simulated scenarios of species extinction. By simulating the removal of highly interacting species, we observed that, overall, these species enhance network nestedness and robustness, but decrease modularity. We discuss how the organization of interlinked mutualistic networks may be essential for the maintenance of ecological communities, and therefore the long-term ecological and evolutionary dynamics of interactive, species-rich communities. We suggest that conserving these keystone mutualists and their interactions is crucial to the persistence of species-rich mutualistic assemblages, mainly because they support other species and shape the network organization. © 2016 The Author(s).

  8. The Mechanisms of Water Exchange: The Regulatory Roles of Multiple Interactions in Social Wasps.

    Science.gov (United States)

    Agrawal, Devanshu; Karsai, Istvan

    2016-01-01

    Evolutionary benefits of task fidelity and improving information acquisition via multiple transfers of materials between individuals in a task partitioned system have been shown before, but in this paper we provide a mechanistic explanation of these phenomena. Using a simple mathematical model describing the individual interactions of the wasps, we explain the functioning of the common stomach, an information center, which governs construction behavior and task change. Our central hypothesis is a symmetry between foragers who deposit water and foragers who withdraw water into and out of the common stomach. We combine this with a trade-off between acceptance and resistance to water transfer. We ultimately derive a mathematical function that relates the number of interactions that foragers complete with common stomach wasps during a foraging cycle. We use field data and additional model assumptions to calculate values of our model parameters, and we use these to explain why the fullness of the common stomach stabilizes just below 50 percent, why the average number of successful interactions between foragers and the wasps forming the common stomach is between 5 and 7, and why there is a variation in this number of interactions over time. Our explanation is that our proposed water exchange mechanism places natural bounds on the number of successful interactions possible, water exchange is set to optimize mediation of water through the common stomach, and the chance that foragers abort their task prematurely is very low.

  9. Effects of biotic interactions and dispersal on the presence-absence of multiple species

    International Nuclear Information System (INIS)

    Mohd, Mohd Hafiz; Murray, Rua; Plank, Michael J.; Godsoe, William

    2017-01-01

    One of the important issues in ecology is to predict which species will be present (or absent) across a geographical region. Dispersal is thought to have an important influence on the range limits of species, and understanding this problem in a multi-species community with priority effects (i.e. initial abundances determine species presence-absence) is a challenging task because dispersal also interacts with biotic and abiotic factors. Here, we propose a simple multi-species model to investigate the joint effects of biotic interactions and dispersal on species presence-absence. Our results show that dispersal can substantially expand species ranges when biotic and abiotic forces are present; consequently, coexistence of multiple species is possible. The model also exhibits ecologically interesting priority effects, mediated by intense biotic interactions. In the absence of dispersal, competitive exclusion of all but one species occurs. We find that dispersal reduces competitive exclusion effects that occur in no-dispersal case and promotes coexistence of multiple species. These results also show that priority effects are still prevalent in multi-species communities in the presence of dispersal process. We also illustrate the existence of threshold values of competitive strength (i.e. transcritical bifurcations), which results in different species presence-absence in multi-species communities with and without dispersal.

  10. Genetic interactions of MAF1 identify a role for Med20 in transcriptional repression of ribosomal protein genes.

    Directory of Open Access Journals (Sweden)

    Ian M Willis

    2008-07-01

    Full Text Available Transcriptional repression of ribosomal components and tRNAs is coordinately regulated in response to a wide variety of environmental stresses. Part of this response involves the convergence of different nutritional and stress signaling pathways on Maf1, a protein that is essential for repressing transcription by RNA polymerase (pol III in Saccharomyces cerevisiae. Here we identify the functions buffering yeast cells that are unable to down-regulate transcription by RNA pol III. MAF1 genetic interactions identified in screens of non-essential gene-deletions and conditionally expressed essential genes reveal a highly interconnected network of 64 genes involved in ribosome biogenesis, RNA pol II transcription, tRNA modification, ubiquitin-dependent proteolysis and other processes. A survey of non-essential MAF1 synthetic sick/lethal (SSL genes identified six gene-deletions that are defective in transcriptional repression of ribosomal protein (RP genes following rapamycin treatment. This subset of MAF1 SSL genes included MED20 which encodes a head module subunit of the RNA pol II Mediator complex. Genetic interactions between MAF1 and subunits in each structural module of Mediator were investigated to examine the functional relationship between these transcriptional regulators. Gene expression profiling identified a prominent and highly selective role for Med20 in the repression of RP gene transcription under multiple conditions. In addition, attenuated repression of RP genes by rapamycin was observed in a strain deleted for the Mediator tail module subunit Med16. The data suggest that Mediator and Maf1 function in parallel pathways to negatively regulate RP mRNA and tRNA synthesis.

  11. Toward a community ecology of landscapes: predicting multiple predator-prey interactions across geographic space.

    Science.gov (United States)

    Schmitz, Oswald J; Miller, Jennifer R B; Trainor, Anne M; Abrahms, Briana

    2017-09-01

    Community ecology was traditionally an integrative science devoted to studying interactions between species and their abiotic environments in order to predict species' geographic distributions and abundances. Yet for philosophical and methodological reasons, it has become divided into two enterprises: one devoted to local experimentation on species interactions to predict community dynamics; the other devoted to statistical analyses of abiotic and biotic information to describe geographic distribution. Our goal here is to instigate thinking about ways to reconnect the two enterprises and thereby return to a tradition to do integrative science. We focus specifically on the community ecology of predators and prey, which is ripe for integration. This is because there is active, simultaneous interest in experimentally resolving the nature and strength of predator-prey interactions as well as explaining patterns across landscapes and seascapes. We begin by describing a conceptual theory rooted in classical analyses of non-spatial food web modules used to predict species interactions. We show how such modules can be extended to consideration of spatial context using the concept of habitat domain. Habitat domain describes the spatial extent of habitat space that predators and prey use while foraging, which differs from home range, the spatial extent used by an animal to meet all of its daily needs. This conceptual theory can be used to predict how different spatial relations of predators and prey could lead to different emergent multiple predator-prey interactions such as whether predator consumptive or non-consumptive effects should dominate, and whether intraguild predation, predator interference or predator complementarity are expected. We then review the literature on studies of large predator-prey interactions that make conclusions about the nature of multiple predator-prey interactions. This analysis reveals that while many studies provide sufficient information

  12. Possible Synergistic Interactions Among Multiple HPV Genotypes in Women Suffering from Genital Neoplasia

    Science.gov (United States)

    Hajia, Massoud; Sohrabi, Amir

    2018-03-27

    Objective: Persistence of HPV infection is the true cause of cervical disorders. It is reported that competition may exist among HPV genotypes for colonization. This survey was designed to establish the multiple HPV genotype status in our community and the probability of multiple HPV infections involvement. Methods: All multiple HPV infections were selected for investigation in women suffering from genital infections referred to private laboratories in Tehran, Iran. A total of 160 multi HPV positive specimens from cervical scraping were identified by the HPV genotyping methods, "INNO-LiPA and Geno Array". Result: In present study, HPV 6 (LR), 16 (HR), 53 (pHR), 31 (HR) and 11 (LR) were included in 48.8% of detected infections as the most five dominant genotypes. HPV 16 was detected at the highest rate with genotypes 53, 31 and 52, while HPV 53 appeared linked with HPV 16, 51 and 56 in concurrent infections. It appears that HPV 16 and 53 may have significant tendencies to associate with each other rather than with other genotypes. Analysis of the data revealed there may be some synergistic interactions with a few particular genotypes such as "HPV 53". Conclusion: Multiple HPV genotypes appear more likely to be linked with development of cervical abnormalities especially in patients with genital infections. Since, there are various patterns of dominant HPV genotypes in different regions of world, more investigations of this type should be performed for careHPV programs in individual countries. Creative Commons Attribution License

  13. Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population.

    Directory of Open Access Journals (Sweden)

    Dan E Arking

    Full Text Available Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD; thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072. The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005 and Black (P = 3.6 x 10(-5 participants, with the same direction of effect in Hispanics (P = 0.17, and further showed a significant SNP x sex-interaction (P = 0.03. A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01, with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC and Cardiovascular Health Study (CHS cohorts, we validated both the second locus at rs16856785 (P = 7.63 x 10(-8, as well as the sex-interaction with rs16847548 (P = 8.68 x 10(-6. These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval.

  14. Multiple-trait estimates of genetic parameters for metabolic disease traits, fertility disorders, and their predictors in Canadian Holsteins.

    Science.gov (United States)

    Jamrozik, J; Koeck, A; Kistemaker, G J; Miglior, F

    2016-03-01

    Producer-recorded health data for metabolic disease traits and fertility disorders on 35,575 Canadian Holstein cows were jointly analyzed with selected indicator traits. Metabolic diseases included clinical ketosis (KET) and displaced abomasum (DA); fertility disorders were metritis (MET) and retained placenta (RP); and disease indicators were fat-to-protein ratio, milk β-hydroxybutyrate, and body condition score (BCS) in the first lactation. Traits in first and later (up to fifth) lactations were treated as correlated in the multiple-trait (13 traits in total) animal linear model. Bayesian methods with Gibbs sampling were implemented for the analysis. Estimates of heritability for disease incidence were low, up to 0.06 for DA in first lactation. Among disease traits, the environmental herd-year variance constituted 4% of the total variance for KET and less for other traits. First- and later-lactation disease traits were genetically correlated (from 0.66 to 0.72) across all traits, indicating different genetic backgrounds for first and later lactations. Genetic correlations between KET and DA were relatively strong and positive (up to 0.79) in both first- and later-lactation cows. Genetic correlations between fertility disorders were slightly lower. Metritis was strongly genetically correlated with both metabolic disease traits in the first lactation only. All other genetic correlations between metabolic and fertility diseases were statistically nonsignificant. First-lactation KET and MET were strongly positively correlated with later-lactation performance for these traits due to the environmental herd-year effect. Indicator traits were moderately genetically correlated (from 0.30 to 0.63 in absolute values) with both metabolic disease traits in the first lactation. Smaller and mostly nonsignificant genetic correlations were among indicators and metabolic diseases in later lactations. The only significant genetic correlations between indicators and fertility

  15. Stable coexistence of genetically divergent Atlantic cod ecotypes at multiple spatial scales

    DEFF Research Database (Denmark)

    Knutsen, Halvor; Jorde, Per Erik; Hutchings, Jeffrey A.

    2018-01-01

    Coexistence in the same habitat of closely related yet genetically different populations is a phenomenon that challenges our understanding of local population structure and adaptation. Identifying the underlying mechanisms for such coexistence can yield new insight into adaptive evolution...

  16. Interactive effects of genetic polymorphisms and childhood adversity on brain morphologic changes in depression.

    Science.gov (United States)

    Kim, Yong-Ku; Ham, Byung-Joo; Han, Kyu-Man

    2018-03-10

    The etiology of depression is characterized by the interplay of genetic and environmental factors and brain structural alteration. Childhood adversity is a major contributing factor in the development of depression. Interactions between childhood adversity and candidate genes for depression could affect brain morphology via the modulation of neurotrophic factors, serotonergic neurotransmission, or the hypothalamus-pituitary-adrenal (HPA) axis, and this pathway may explain the subsequent onset of depression. Childhood adversity is associated with structural changes in the hippocampus, amygdala, anterior cingulate cortex (ACC), and prefrontal cortex (PFC), as well as white matter tracts such as the corpus callosum, cingulum, and uncinate fasciculus. Childhood adversity showed an interaction with the brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism, serotonin transporter-linked promoter region (5-HTTLPR), and FK506 binding protein 51 (FKBP5) gene rs1360780 in brain morphologic changes in patients with depression and in a non-clinical population. Individuals with the Met allele of BDNF Val66Met and a history of childhood adversity had reduced volume in the hippocampus and its subfields, amygdala, and PFC and thinner rostral ACC in a study of depressed patients and healthy controls. The S allele of 5-HTTLPR combined with exposure to childhood adversity or a poorer parenting environment was associated with a smaller hippocampal volume and subsequent onset of depression. The FKBP5 gene rs160780 had a significant interaction with childhood adversity in the white matter integrity of brain regions involved in emotion processing. This review identified that imaging genetic studies on childhood adversity may deepen our understanding on the neurobiological background of depression by scrutinizing complicated pathways of genetic factors, early psychosocial environments, and the accompanying morphologic changes in emotion-processing neural circuitry. Copyright

  17. Quantum correlation approach to criticality in the XX spin chain with multiple interaction

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, W.W., E-mail: weien.cheng@gmail.com [Institute of Signal Processing and Transmission, Nanjing University of Posts and Telecommunication, Nanjing 210003 (China); Department of Physics, Hubei Normal University, Huangshi 435002 (China); Key Lab of Broadband Wireless Communication and Sensor Network Technology, Ministry of Education (China); Shan, C.J. [Department of Physics, Hubei Normal University, Huangshi 435002 (China); Sheng, Y.B.; Gong, L.Y.; Zhao, S.M. [Institute of Signal Processing and Transmission, Nanjing University of Posts and Telecommunication, Nanjing 210003 (China); Key Lab of Broadband Wireless Communication and Sensor Network Technology, Ministry of Education (China)

    2012-09-01

    We investigate the quantum critical behavior in the XX spin chain with a XZY-YZX type multiple interaction by means of quantum correlation (Concurrence C, quantum discord D{sub Q} and geometric discord D{sub G}). Around the critical point, the values of these quantum correlations and corresponding derivatives are investigated numerically and analytically. The results show that the non-analyticity property of the concurrence cannot signal well the quantum phase transition, but both the quantum discord and geometric discord can characterize the critical behavior in such model exactly.

  18. Analysis of multiplicities in e+e- interactions using 2-jet rates from different jet algorithms

    International Nuclear Information System (INIS)

    Dahiya, S.; Kaur, M.; Dhamija, S.

    2002-01-01

    The shoulder structure of charged particle multiplicity distribution measured in full phase space in e + e - interactions at various c.m. energies from 91 to 189 GeV has been analysed in terms of weighted superposition of two negative binomial distributions associated with 2-jet and multi-jet production. The 2-jet rates have been obtained from various jet algorithms. This phenomenological parametrization reproduces the shoulder structure behaviour quantitatively and improves the agreement with the experimental distributions than the conventional negative binomial distribution. The analysis at the higher energies where the shoulder structure appears more prominently, is important for the understanding of underlying structure. (author)

  19. Genetic by environment interaction for post weaning growth traits in tropical cattle

    OpenAIRE

    Navès, Michel; Menendez Buxadera, Alberto; Farant, Alain; Mandonnet, Nathalie

    2006-01-01

    Genetic by environment interactions for post weaning traits were studied in a local breed of cattle, well adapted to tropical conditions. After weaning, 444 beef calves of both sexes were separated within two management systems, either in intensive fattening or at pasture. The traits analysed included weights at standard age, of 365 days (W12), 455 days (W15) and 545 days (W18), and post weaning growth rates from weaning until 15 months (PWG15) or 18 months (PWG18). (Co)varianc...

  20. No interactions between genetic polymorphisms and stressful life events on outcome of antidepressant treatment

    DEFF Research Database (Denmark)

    Bukh, Jens Drachmann; Bock, Camilla; Vinberg, Maj

    2009-01-01

    Genetic polymorphisms seem to influence the response on antidepressant treatment and moderate the impact of stress on depression. The present study aimed to assess, whether allelic variants and stressful life events interact on the clinical outcome of depression. In a sample of 290 systematically...... recruited patients diagnosed with a single depressive episode according to ICD-10, we assessed the outcome of antidepressant treatment and the presence of stressful life events in a 6-month period preceding onset of depression by means of structured interviews. Further, we genotyped nine polymorphisms...... dependent on stressful life events experienced by the individual prior to onset of depression....

  1. Age of Onset in Schizophrenia Spectrum Disorders: Complex Interactions between Genetic and Environmental Factors.

    Science.gov (United States)

    Mandelli, Laura; Toscano, Elena; Porcelli, Stefano; Fabbri, Chiara; Serretti, Alessandro

    2016-03-01

    In this study we evaluated the role of a candidate gene for major psychosis, Sialyltransferase (ST8SIA2), in the risk to develop a schizophrenia spectrum disorders, taking into account exposure to stressful life events (SLEs). Eight polymorphisms (SNPs) were tested in 94 Schizophreniainpatients and 176 healthy controls. Schizophrenia patients were also evaluated for SLEs in different life periods. None of the SNPs showed association with schizophrenia. Nevertheless, when crossing genetic variants with childhood SLEs, we could observe trends of interaction with age of onset. Though several limitations, our results support a protective role of ST8SIA2 in individuals exposed to moderate childhood stress.

  2. Laser-Bioplasma Interaction: The Blood Type Transmutation Induced by Multiple Ultrashort Wavelength Laser Beams

    Science.gov (United States)

    Stefan, V. Alexander

    2015-11-01

    The interaction of ultrashort wavelength multi laser beams with the flowing blood thin films leads to the transmutation of the blood types A, B, and AB into O type. This is a novel mechanism of importance for the transfusion medicine. Laser radiation is in resonance with the eigen-frequency modes of the antigen proteins and forces the proteins to parametrically oscillate until they get kicked out from the surface. The stripping away of antigens is done by the scanning-multiple-lasers of a high repetition rate in the blue-purple frequency domain. The guiding-lasers are in the red-green frequency domain. The laser force, (parametric interaction with the antigen eigen-oscillation), upon the antigen protein molecule must exceed its weight. The scanning laser beam is partially reflected as long as the antigen(s) is not eliminated. The process of the protein detachment can last a few minutes. Supported by Nikola Tesla Labs., Stefan University.

  3. Interactions between SNPs affecting inflammatory response genes are associated with multiple myeloma disease risk and survival

    DEFF Research Database (Denmark)

    Nielsen, Kaspar René; Rodrigo-Domingo, Maria; Steffensen, Rudi

    2017-01-01

    The origin of multiple myeloma depends on interactions with stromal cells in the course of normal B-cell differentiation and evolution of immunity. The concept of the present study is that genes involved in MM pathogenesis, such as immune response genes, can be identified by screening for single......3L1 gene promoters. The occurrence of single polymorphisms, haplotypes and SNP-SNP interactions were statistically analyzed for association with disease risk and outcome following high-dose therapy. Identified genes that carried SNPs or haplotypes that were identified as risk or prognostic factors......= .005). The 'risk genes' were analyzed for expression in normal B-cell subsets (N = 6) from seven healthy donors and we found TNFA and IL-6 expressed both in naïve and in memory B cells when compared to preBI, II, immature and plasma cells. The 'prognosis genes' CHI3L1, IL-6 and IL-10 were differential...

  4. A Vietnamese man with selective mutism: the relevance of multiple interacting 'cultures' in clinical psychiatry.

    Science.gov (United States)

    Hollifield, Michael; Geppert, Cynthia; Johnson, Yuam; Fryer, Carol

    2003-09-01

    Multiple cultural variables have effects on the psychobiology and behavioral manifestations of illness, as do patient and physician perceptions of illness. The interaction among these variables is at the heart of clinical psychiatry. This case of a Vietnamese man with selective mutism underscores the relevance of the 'cultures' of medicine, psychiatry, and war and trauma on the manifestations of illness and illness perceptions by patient and physician. The discussion focuses on how these cultures interact and play a crucial role in formulating diagnosis and treatment planning. Suggestions are given for shifts in medical education that will encourage relevant cultural paradigms to make their way into educational and clinical systems, which in turn should improve cultural competence in clinical psychiatry.

  5. Effects of multiple substitution upon the P...N noncovalent interaction

    International Nuclear Information System (INIS)

    Scheiner, Steve

    2011-01-01

    Graphical abstract: The presence of one halogen opposite the N results in strong attraction between P and N. This force is little affected by identity of Y atoms, whether H or halogen. Highlights: → Strong attractive force directly between trivalent P and N atoms. → P...N force is unlike H-bonds or halogen bonds, but stronger than both. → Multiple halogenation beyond a single atom on P slightly weakens the interaction. - Abstract: The attractive noncovalent interaction of a P atom with N is derived primarily from two sources. Charge transfer from the N lone pair into the σ * antibonding orbital of a P-X bond that is turned away from the N atom combines with attractive Coulombic forces. As in the case of H-bonding, which is parallel in some ways to P...N attraction, placement of an electron-withdrawing substituent on the P atom enhances both of these components, and strengthens the overall interaction. However, in stark contrast with H-bonding, halogenation beyond monosubstitution does not lead to any further strengthening of the P...N noncovalent bond. Indeed, di and tri-substitution lead to small reductions in the interaction energy. In all cases, the geometry which contains a P...N bond is more stable than other candidate structures, some of which contain hydrogen or halogen bonds.

  6. Brain Interaction during Cooperation: Evaluating Local Properties of Multiple-Brain Network.

    Science.gov (United States)

    Sciaraffa, Nicolina; Borghini, Gianluca; Aricò, Pietro; Di Flumeri, Gianluca; Colosimo, Alfredo; Bezerianos, Anastasios; Thakor, Nitish V; Babiloni, Fabio

    2017-07-21

    Subjects' interaction is the core of most human activities. This is the reason why a lack of coordination is often the cause of missing goals, more than individual failure. While there are different subjective and objective measures to assess the level of mental effort required by subjects while facing a situation that is getting harder, that is, mental workload, to define an objective measure based on how and if team members are interacting is not so straightforward. In this study, behavioral, subjective and synchronized electroencephalographic data were collected from couples involved in a cooperative task to describe the relationship between task difficulty and team coordination, in the sense of interaction aimed at cooperatively performing the assignment. Multiple-brain connectivity analysis provided information about the whole interacting system. The results showed that averaged local properties of a brain network were affected by task difficulty. In particular, strength changed significantly with task difficulty and clustering coefficients strongly correlated with the workload itself. In particular, a higher workload corresponded to lower clustering values over the central and parietal brain areas. Such results has been interpreted as less efficient organization of the network when the subjects' activities, due to high workload tendencies, were less coordinated.

  7. Assessing interactions among multiple physiological systems during walking outside a laboratory: An Android based gait monitor

    Science.gov (United States)

    Sejdić, E.; Millecamps, A.; Teoli, J.; Rothfuss, M. A.; Franconi, N. G.; Perera, S.; Jones, A. K.; Brach, J. S.; Mickle, M. H.

    2015-01-01

    Gait function is traditionally assessed using well-lit, unobstructed walkways with minimal distractions. In patients with subclinical physiological abnormalities, these conditions may not provide enough stress on their ability to adapt to walking. The introduction of challenging walking conditions in gait can induce responses in physiological systems in addition to the locomotor system. There is a need for a device that is capable of monitoring multiple physiological systems in various walking conditions. To address this need, an Android-based gait-monitoring device was developed that enabled the recording of a patient's physiological systems during walking. The gait-monitoring device was tested during self-regulated overground walking sessions of fifteen healthy subjects that included 6 females and 9 males aged 18 to 35 years. The gait-monitoring device measures the patient's stride interval, acceleration, electrocardiogram, skin conductance and respiratory rate. The data is stored on an Android phone and is analyzed offline through the extraction of features in the time, frequency and time-frequency domains. The analysis of the data depicted multisystem physiological interactions during overground walking in healthy subjects. These interactions included locomotion-electrodermal, locomotion-respiratory and cardiolocomotion couplings. The current results depicting strong interactions between the locomotion system and the other considered systems (i.e., electrodermal, respiratory and cardivascular systems) warrant further investigation into multisystem interactions during walking, particularly in challenging walking conditions with older adults. PMID:26390946

  8. [Genetics and epigenetics in autism].

    Science.gov (United States)

    Nakayama, Atsuo; Masaki, Shiego; Aoki, Eiko

    2006-11-01

    Autism is a behaviorally defined syndrome characterized by impaired social interaction and communication, and restricted, stereotyped interests and behaviors. Several lines of evidence support the contention that genetic factors are a large component to autism etiology. However, in spite of vigorous genetic studies, no single causative or susceptibility gene common in autism has been identified. Thus multiple susceptibility genes in interaction are considered to account for the disorder. Furthermore, environmental risk factors can accelerate the autism development of. Recent advances in understanding the epigenetic regulation may shed light on the interaction among multiple genetic factors and environmental factors.

  9. A major and stable QTL associated with seed weight in soybean across multiple environments and genetic backgrounds.

    Science.gov (United States)

    Kato, Shin; Sayama, Takashi; Fujii, Kenichiro; Yumoto, Setsuzo; Kono, Yuhi; Hwang, Tae-Young; Kikuchi, Akio; Takada, Yoshitake; Tanaka, Yu; Shiraiwa, Tatsuhiko; Ishimoto, Masao

    2014-06-01

    We detected a QTL for single seed weight in soybean that was stable across multiple environments and genetic backgrounds with the use of two recombinant inbred line populations. Single seed weight (SSW) in soybean is a key determinant of both seed yield and the quality of soy food products, and it exhibits wide variation. SSW is under genetic control, but the molecular mechanisms of such control remain unclear. We have now investigated quantitative trait loci (QTLs) for SSW in soybean and have identified such a QTL that is stable across multiple environments and genetic backgrounds. Two populations of 225 and 250 recombinant inbred lines were developed from crosses between Japanese and US cultivars of soybean that differ in SSW by a factor of ~2, and these populations were grown in at least three different environments. A whole-genome panel comprising 304 simple sequence repeat (SSR) loci was applied to mapping in each population. We identified 15 significant QTLs for SSW dispersed among 11 chromosomes in the two populations. One QTL located between Sat_284 and Sat_292 on chromosome 17 was detected (3.6 soybean.

  10. The Genetics Underlying Natural Variation in the Biotic Interactions of Arabidopsis thaliana: The Challenges of Linking Evolutionary Genetics and Community Ecology.

    Science.gov (United States)

    Roux, F; Bergelson, J

    2016-01-01

    In the context of global change, predicting the responses of plant communities in an ever-changing biotic environment calls for a multipronged approach at the interface of evolutionary genetics and community ecology. However, our understanding of the genetic basis of natural variation involved in mediating biotic interactions, and associated adaptive dynamics of focal plants in their natural communities, is still in its infancy. Here, we review the genetic and molecular bases of natural variation in the response to biotic interactions (viruses, bacteria, fungi, oomycetes, herbivores, and plants) in the model plant Arabidopsis thaliana as well as the adaptive value of these bases. Among the 60 identified genes are a number that encode nucleotide-binding site leucine-rich repeat (NBS-LRR)-type proteins, consistent with early examples of plant defense genes. However, recent studies have revealed an extensive diversity in the molecular mechanisms of defense. Many types of genetic variants associate with phenotypic variation in biotic interactions, even among the genes of large effect that tend to be identified. In general, we found that (i) balancing selection rather than directional selection explains the observed patterns of genetic diversity within A. thaliana and (ii) the cost/benefit tradeoffs of adaptive alleles can be strongly dependent on both genomic and environmental contexts. Finally, because A. thaliana rarely interacts with only one biotic partner in nature, we highlight the benefit of exploring diffuse biotic interactions rather than tightly associated host-enemy pairs. This challenge would help to improve our understanding of coevolutionary quantitative genetics within the context of realistic community complexity. © 2016 Elsevier Inc. All rights reserved.

  11. Exploitation of genetic interaction network topology for the prediction of epistatic behavior

    KAUST Repository

    Alanis Lobato, Gregorio

    2013-10-01

    Genetic interaction (GI) detection impacts the understanding of human disease and the ability to design personalized treatment. The mapping of every GI in most organisms is far from complete due to the combinatorial amount of gene deletions and knockdowns required. Computational techniques to predict new interactions based only on network topology have been developed in network science but never applied to GI networks.We show that topological prediction of GIs is possible with high precision and propose a graph dissimilarity index that is able to provide robust prediction in both dense and sparse networks.Computational prediction of GIs is a strong tool to aid high-throughput GI determination. The dissimilarity index we propose in this article is able to attain precise predictions that reduce the universe of candidate GIs to test in the lab. © 2013 Elsevier Inc.

  12. Exploitation of genetic interaction network topology for the prediction of epistatic behavior

    KAUST Repository

    Alanis Lobato, Gregorio; Cannistraci, Carlo; Ravasi, Timothy

    2013-01-01

    Genetic interaction (GI) detection impacts the understanding of human disease and the ability to design personalized treatment. The mapping of every GI in most organisms is far from complete due to the combinatorial amount of gene deletions and knockdowns required. Computational techniques to predict new interactions based only on network topology have been developed in network science but never applied to GI networks.We show that topological prediction of GIs is possible with high precision and propose a graph dissimilarity index that is able to provide robust prediction in both dense and sparse networks.Computational prediction of GIs is a strong tool to aid high-throughput GI determination. The dissimilarity index we propose in this article is able to attain precise predictions that reduce the universe of candidate GIs to test in the lab. © 2013 Elsevier Inc.

  13. A VR Based Interactive Genetic Algorithm Framework For Design of Support Schemes to Deep Excavations

    International Nuclear Information System (INIS)

    Wei, Riyu; Wu, Heng

    2002-01-01

    An interactive genetic algorithm (IGA) framework for the design of support schemes to deep excavations is proposed in this paper, in which virtual reality (VR) is used as an aid to the evaluation of design schemes that is performed interactively. The fitness of a scheme individual is evaluated by two steps. Firstly a fitness value is automatically assigned to a scheme individual according to the the estimated construction cost of the individual. And the human evaluation is introduced to modify the fitness value by taking into account other factors, such as the feasibility factor. The design scheme is composed of four basic categories, i. e., cantilever walls, reinforced soil walls, tieback systems and bracing systems, each of which is encoded by a binary string. To assist human evaluation, 3D models of design schemes are created and visualized in a virtual reality environment, providing designers with a reality sense of various schemes

  14. Multiple organ histopathological changes in broiler chickens fed on genetically modified organism.

    Science.gov (United States)

    Cîrnatu, Daniela; Jompan, A; Sin, Anca Ileana; Zugravu, Cornelia Aurelia

    2011-01-01

    Diet can influence the structural characteristics of internal organs. An experiment involving 130 meat broilers was conducted during 42 days (life term for a meat broiler) to study the effect of feed with protein from genetically modified soy. The 1-day-old birds were randomly allocated to five study groups, fed with soy, sunflower, wheat, fish flour, PC starter. In the diet of each group, an amount of protein from soy was replaced with genetically modified soy (I - 0%, II - 25%, III - 50%, IV - 75%, V - 100% protein from genetically modified soy). The level of protein in soy, either modified, or non-modified, was the same. Organs and carcass weights were measured at about 42 days of age of the birds and histopathology exams were performed during May-June 2009. No statistically significant differences were observed in mortality, growth performance variables or carcass and organ yields between broilers consuming diets produced with genetically modified soybean fractions and those consuming diets produced with near-isoline control soybean fractions. Inflammatory and degenerative liver lesions, muscle hypertrophy, hemorrhagic necrosis of bursa, kidney focal tubular necrosis, necrosis and superficial ulceration of bowel and pancreatic dystrophies were found in tissues from broilers fed on protein from genetically modified soy. Different types of lesions found in our study might be due to other causes (parasites, viral) superimposed but their presence exclusively in groups fed with modified soy raises some serious questions about the consequences of use of this type of feed.

  15. Gene interaction at seed-awning loci in the genetic background of wild rice.

    Science.gov (United States)

    Ikemoto, Mai; Otsuka, Mitsuharu; Thanh, Pham Thien; Phan, Phuong Dang Thai; Ishikawa, Ryo; Ishii, Takashige

    2017-09-12

    Seed awning is one of the important traits for successful propagation in wild rice. During the domestication of rice by ancient humans, plants with awnless seeds may have been selected because long awns hindered collection and handling activities. To investigate domestication of awnless rice, QTL analysis for seed awning was first carried out using backcross recombinant inbred lines between Oryza sativa Nipponbare (recurrent parent) and O. rufipogon W630 (donor parent). Two strong QTLs were detected in the same regions as known major seed-awning loci, An-1 and RAE2. Subsequent causal mutation surveying and fine mapping confirmed that O. rufipogon W630 has functional alleles at both loci. The gene effects and interactions at these loci were examined using two backcross populations with reciprocal genetic backgrounds of O. sativa Nipponbare and O. rufipogon W630. As awn length in wild rice varied among seeds even in the same plant, awn length was measured based on spikelet position. In the genetic background of cultivated rice, the wild alleles at An-1 and RAE2 had awning effects, and plants having both wild homozygous alleles produced awns whose length was about 70% of those of the wild parent. On the other hand, in the genetic background of wild rice, the substitution of cultivated alleles at An-1 and RAE2 contributed little to awn length reduction. These results indicate that the domestication process of awnless seeds was complicated because many genes are involved in awn formation in wild rice.

  16. Persistent genetic instability induced by synergistic interaction between x-irradiation and 6-thioguanine

    International Nuclear Information System (INIS)

    Grosovsky, A.J.; Nelson, S.L.; Smith, L.E.

    1995-01-01

    Clonal karyotypic analysis was performed using G-banding on four groups of clones derived from TK6 human lymphoblasts: 25 HPRT - total gene deletion mutants induced by exposure to 2 Gy of x-rays; 8 spontaneous HPRT - total gene deletion mutants; 25 clones irradiated with 2 Gy, not selected with 6-thioguanine. Ten to twenty metaphases were examined for each clone. Extensive karyotypic heterogeneity was observed among x-ray induced HPRT - mutants involving translocations, deletions, duplications and aneuploidy; recovery of chromosomal aberrations and karyotypic heterogeneity was greater than the additive effects of clones treated with x-irradiation or 6-thioguanine alone. This synergistic interaction between x-irradiation and 6-thioguanine was observed despite a 7 day phenotypic expression interval between exposure to the two agents. Thus, x-irradiated TK6 cells appear to be persistently hypersensitive to the induction of genetic instability. Several mutants appeared to exhibit evidence of clonal evolution since aberrant chromosomes observed in one metaphase, were found to be further modified in other metaphases. In order to determine if genetic instability, identified by clonal karyotypic heterogeneity, affected specific locus mutation rates, we utilized the heterozygous thymidine kinase (tk) locus as a genetic marker. Four x-ray induced HPRT - mutants with extensive karyotypic heterogeneity, exhibited mutation rates at tk ranging from 5 to 8 fold higher than the parental TK6 cells. Further analysis, using fractionated low dose radiation exposure, is currently in progress

  17. Natural selection affects multiple aspects of genetic variation at putatively peutral sites across the human genome

    DEFF Research Database (Denmark)

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui

    2011-01-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries...... these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination...... and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations...

  18. Interactions Between SNP Alleles at Multiple Loci and Variation in Skin Pigmentation in 122 Caucasians

    Directory of Open Access Journals (Sweden)

    Sumiko Anno

    2007-01-01

    Full Text Available This study was undertaken to clarify the molecular basis for human skin color variation and the environmental adaptability to ultraviolet irradiation, with the ultimate goal of predicting the impact of changes in future environments on human health risk. One hundred twenty-two Caucasians living in Toledo, Ohio participated. Back and cheek skin were assayed for melanin as a quantitative trait marker. Buccal cell samples were collected and used for DNA extraction. DNA was used for SNP genotyping using the Masscode™ system, which entails two-step PCR amplification and a platform chemistry which allows cleavable mass spectrometry tags. The results show gene-gene interaction between SNP alleles at multiple loci (not necessarily on the same chromosome contributes to inter-individual skin color variation while suggesting a high probability of linkage disequilibrium. Confirmation of these findings requires further study with other ethic groups to analyze the associations between SNP alleles at multiple loci and human skin color variation. Our overarching goal is to use remote sensing data to clarify the interaction between atmospheric environments and SNP allelic frequency and investigate human adaptability to ultraviolet irradiation. Such information should greatly assist in the prediction of the health effects of future environmental changes such as ozone depletion and increased ultraviolet exposure. If such health effects are to some extent predictable, it might be possible to prepare for such changes in advance and thus reduce the extent of their impact.

  19. Use of multiple correspondence analysis (MCA) to identify interactive meteorological conditions affecting relative throughfall

    Science.gov (United States)

    Van Stan, John T.; Gay, Trent E.; Lewis, Elliott S.

    2016-02-01

    Forest canopies alter rainfall reaching the surface by redistributing it as throughfall. Throughfall supplies water and nutrients to a variety of ecohydrological components (soil microbial communities, stream water discharge/chemistry, and stormflow pathways) and is controlled by canopy structural interactions with meteorological conditions across temporal scales. This work introduces and applies multiple correspondence analyses (MCAs) to a range of meteorological thresholds (median intensity, median absolute deviation (MAD) of intensity, median wind-driven droplet inclination angle, and MAD of wind speed) for an example throughfall problem: identification of interacting storm conditions corresponding to temporal concentration in relative throughfall beyond the median observation (⩾73% of rain). MCA results from the example show that equalling or exceeding rain intensity thresholds (median and MAD) corresponded with temporal concentration of relative throughfall across all storms. Under these intensity conditions, two wind mechanisms produced significant correspondences: (1) high, steady wind-driven droplet inclination angles increased surface wetting; and (2) sporadic winds shook entrained droplets from surfaces. A discussion is provided showing that these example MCA findings agree well with previous work relying on more historically common methods (e.g., multiple regression and analytical models). Meteorological threshold correspondences to temporal concentration of relative throughfall at our site may be a function of heavy Tillandsia usneoides coverage. Applications of MCA within other forests may provide useful insights to how temporal throughfall dynamics are affected for drainage pathways dependent on different structures (leaves, twigs, branches, etc.).

  20. Prediction of protein interaction hot spots using rough set-based multiple criteria linear programming.

    Science.gov (United States)

    Chen, Ruoying; Zhang, Zhiwang; Wu, Di; Zhang, Peng; Zhang, Xinyang; Wang, Yong; Shi, Yong

    2011-01-21

    Protein-protein interactions are fundamentally important in many biological processes and it is in pressing need to understand the principles of protein-protein interactions. Mutagenesis studies have found that only a small fraction of surface residues, known as hot spots, are responsible for the physical binding in protein complexes. However, revealing hot spots by mutagenesis experiments are usually time consuming and expensive. In order to complement the experimental efforts, we propose a new computational approach in this paper to predict hot spots. Our method, Rough Set-based Multiple Criteria Linear Programming (RS-MCLP), integrates rough sets theory and multiple criteria linear programming to choose dominant features and computationally predict hot spots. Our approach is benchmarked by a dataset of 904 alanine-mutated residues and the results show that our RS-MCLP method performs better than other methods, e.g., MCLP, Decision Tree, Bayes Net, and the existing HotSprint database. In addition, we reveal several biological insights based on our analysis. We find that four features (the change of accessible surface area, percentage of the change of accessible surface area, size of a residue, and atomic contacts) are critical in predicting hot spots. Furthermore, we find that three residues (Tyr, Trp, and Phe) are abundant in hot spots through analyzing the distribution of amino acids. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Association of Multiple Genetic Variants with the Extension and Severity of Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Simone Cristina Pinto Matheus Fischer

    2018-02-01

    Full Text Available Abstract Background: Metabolic syndrome (MS is a condition that, when associated with ischemic heart disease and cardiovascular events, can be influenced by genetic variants and determine more severe coronary atherosclerosis. Objectives: To examine the contribution of genetic polymorphisms to the extension and severity of coronary disease in subjects with MS and recent acute coronary syndrome (ACS. Methods: Patients (n = 116, 68% males aged 56 (9 years, with criteria for MS, were prospectively enrolled to the study during the hospitalization period after an ACS. Clinical and laboratory parameters, high-sensitivity C-reactive protein, thiobarbituric acid reactive substances, adiponectin, endothelial function, and the Gensini score were assessed. Polymorphisms of paraoxonase-1 (PON-1, methylenotetrahydrofolate reductase (MTHFR, endothelial nitric oxide synthase (ENOS, angiotensin-converting enzyme (ACE, angiotensin II type 1 receptor (AT1R, apolipoprotein C3 (APOC3, lipoprotein lipase (LPL were analysed by polymerase chain reaction (PCR technique, followed by the identification of restriction fragment length polymorphisms (RFLP, and a genetic score was calculated. Parametric and non-parametric tests were used, as appropriate. Significance was set at p < 0.05. Results: Polymorphisms of PON-1, MTHFR and ENOS were not in the Hardy-Weinberg equilibrium. The DD genotype of LPL was associated with higher severity and greater extension of coronary lesions. Genetic score tended to be higher in patients with Gensini score < P50 (13.7 ± 1.5 vs. 13.0 ± 1.6, p = 0.066, with an inverse correlation between genetic and Gensini scores (R = -0.194, p = 0.078. Conclusions: The LPL polymorphism contributed to the severity of coronary disease in patients with MS and recent ACS. Combined polymorphisms were associated with the extension of coronary disease, and the lower the genetic score the more severe the disease.

  2. Thermo-kinetic mechanisms for grain boundary structure multiplicity, thermal instability and defect interactions

    International Nuclear Information System (INIS)

    Burbery, N.J.; Das, R.; Ferguson, W.G.

    2016-01-01

    Grain boundaries (GBs) provide a source and/or a sink for crystal defects and store elastic energy due to the non-uniform atomic bonding structure of the GB core. GB structures are thermodynamically driven to transition to the lowest energy configuration possible; however to date there has been little evidence to explain why specific GB structures have a low energy state. Furthermore, there is little quantitative demonstration of the significance of physical and GB structure characteristics on the GB energy, thermal stability, and the effect of temporary local GB structure transformations on defect interactions. This paper evaluates the defect interactions and structure stability of multiple Σ5(310) GB structures in bi-crystals of pure aluminium, and systematically investigates the features at 0 K to characterise multiple metastable structures. Structure stability is evaluated by utilising unstable vacancy defects to initiate GB transformations, and using nudged elastic band simulations to quantify this with the activation energy. The emission of stable vacancy defects from the ‘stable’ and metastable grain boundaries is also evaluated in the same manner. A detailed analysis of dislocation nucleation at the atomistic scale demonstrates that local transformations of GB structure between stable and metastable intermediates can provide a mechanism to accommodate the generation of crystal defects. Kinetic (time-dependent) effects that compete with energetic driving forces for structural transformations of GBs are shown to cause a significant effect on the activation properties that may exceed the influence of GB potential energy. The results demonstrate that GB structural multiplicity can be associated with the generation and absorption of dislocations and vacancies. This paper demonstrates the suitability of atomistic simulations coupled with nudged elastic band simulations to evaluate fundamental thermodynamic properties of pure FCC metals. Overall, this paper

  3. Thermo-kinetic mechanisms for grain boundary structure multiplicity, thermal instability and defect interactions

    Energy Technology Data Exchange (ETDEWEB)

    Burbery, N.J. [Department of Mechanical Engineering, University of Auckland, Auckland 1010 (New Zealand); Das, R., E-mail: r.das@auckland.ac.nz [Department of Mechanical Engineering, University of Auckland, Auckland 1010 (New Zealand); Ferguson, W.G. [Department of Chemical and Materials Engineering, University of Auckland, Auckland 1010 (New Zealand)

    2016-08-15

    Grain boundaries (GBs) provide a source and/or a sink for crystal defects and store elastic energy due to the non-uniform atomic bonding structure of the GB core. GB structures are thermodynamically driven to transition to the lowest energy configuration possible; however to date there has been little evidence to explain why specific GB structures have a low energy state. Furthermore, there is little quantitative demonstration of the significance of physical and GB structure characteristics on the GB energy, thermal stability, and the effect of temporary local GB structure transformations on defect interactions. This paper evaluates the defect interactions and structure stability of multiple Σ5(310) GB structures in bi-crystals of pure aluminium, and systematically investigates the features at 0 K to characterise multiple metastable structures. Structure stability is evaluated by utilising unstable vacancy defects to initiate GB transformations, and using nudged elastic band simulations to quantify this with the activation energy. The emission of stable vacancy defects from the ‘stable’ and metastable grain boundaries is also evaluated in the same manner. A detailed analysis of dislocation nucleation at the atomistic scale demonstrates that local transformations of GB structure between stable and metastable intermediates can provide a mechanism to accommodate the generation of crystal defects. Kinetic (time-dependent) effects that compete with energetic driving forces for structural transformations of GBs are shown to cause a significant effect on the activation properties that may exceed the influence of GB potential energy. The results demonstrate that GB structural multiplicity can be associated with the generation and absorption of dislocations and vacancies. This paper demonstrates the suitability of atomistic simulations coupled with nudged elastic band simulations to evaluate fundamental thermodynamic properties of pure FCC metals. Overall, this paper

  4. Frontiers of torenia research: innovative ornamental traits and study of ecological interaction networks through genetic engineering

    Science.gov (United States)

    2013-01-01

    Advances in research in the past few years on the ornamental plant torenia (Torenia spps.) have made it notable as a model plant on the frontier of genetic engineering aimed at studying ornamental characteristics and pest control in horticultural ecosystems. The remarkable advantage of torenia over other ornamental plant species is the availability of an easy and high-efficiency transformation system for it. Unfortunately, most of the current torenia research is still not very widespread, because this species has not become prominent as an alternative to other successful model plants such as Arabidopsis, snapdragon and petunia. However, nowadays, a more global view using not only a few selected models but also several additional species are required for creating innovative ornamental traits and studying horticultural ecosystems. We therefore introduce and discuss recent research on torenia, the family Scrophulariaceae, for secondary metabolite bioengineering, in which global insights into horticulture, agriculture and ecology have been advanced. Floral traits, in torenia particularly floral color, have been extensively studied by manipulating the flavonoid biosynthetic pathways in flower organs. Plant aroma, including volatile terpenoids, has also been genetically modulated in order to understand the complicated nature of multi-trophic interactions that affect the behavior of predators and pollinators in the ecosystem. Torenia would accordingly be of great use for investigating both the variation in ornamental plants and the infochemical-mediated interactions with arthropods. PMID:23803155

  5. Caenorhabditis elegans ABCRNAi transporters interact genetically with rde-2 and mut-7.

    Science.gov (United States)

    Sundaram, Prema; Han, Wang; Cohen, Nancy; Echalier, Benjamin; Albin, John; Timmons, Lisa

    2008-02-01

    RNA interference (RNAi) mechanisms are conserved and consist of an interrelated network of activities that not only respond to exogenous dsRNA, but also perform endogenous functions required in the fine tuning of gene expression and in maintaining genome integrity. Not surprisingly, RNAi functions have widespread influences on cellular function and organismal development. Previously, we observed a reduced capacity to mount an RNAi response in nine Caenorhabditis elegans mutants that are defective in ABC transporter genes (ABC(RNAi) mutants). Here, we report an exhaustive study of mutants, collectively defective in 49 different ABC transporter genes, that allowed for the categorization of one additional transporter into the ABC(RNAi) gene class. Genetic complementation tests reveal functions for ABC(RNAi) transporters in the mut-7/rde-2 branch of the RNAi pathway. These second-site noncomplementation interactions suggest that ABC(RNAi) proteins and MUT-7/RDE-2 function together in parallel pathways and/or as multiprotein complexes. Like mut-7 and rde-2, some ABC(RNAi) mutants display transposon silencing defects. Finally, our analyses reveal a genetic interaction network of ABC(RNAi) gene function with respect to this part of the RNAi pathway. From our results, we speculate that the coordinated activities of ABC(RNAi) transporters, through their effects on endogenous RNAi-related mechanisms, ultimately affect chromosome function and integrity.

  6. Could age modify the effect of genetic variants in IL6 and TNF-α genes in multiple myeloma?

    Science.gov (United States)

    Martino, Alessandro; Buda, Gabriele; Maggini, Valentina; Lapi, Francesco; Lupia, Antonella; Di Bello, Domenica; Orciuolo, Enrico; Galimberti, Sara; Barale, Roberto; Petrini, Mario; Rossi, Anna Maria

    2012-05-01

    Cytokines play a central role in multiple myeloma (MM) pathogenesis thus genetic variations within cytokines coding genes could influence MM susceptibility and therapy outcome. We investigated the impact of 8 SNPs in these genes in 202 MM cases and 235 controls also evaluating their impact on therapy outcome in a subset of 91 patients. Despite the overall negative findings, we found a significant age-modified effect of IL6 and TNF-α SNPs, on MM risk and therapy outcome, respectively. Therefore, this observation suggests that genetic variation in inflammation-related genes could be an important mediator of the complex interplay between ageing and cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Quantitative Seq-LGS: Genome-Wide Identification of Genetic Drivers of Multiple Phenotypes in Malaria Parasites

    KAUST Repository

    Abkallo, Hussein M.

    2016-10-01

    Identifying the genetic determinants of phenotypes that impact on disease severity is of fundamental importance for the design of new interventions against malaria. Traditionally, such discovery has relied on labor-intensive approaches that require significant investments of time and resources. By combining Linkage Group Selection (LGS), quantitative whole genome population sequencing and a novel mathematical modeling approach (qSeq-LGS), we simultaneously identified multiple genes underlying two distinct phenotypes, identifying novel alleles for growth rate and strain specific immunity (SSI), while removing the need for traditionally required steps such as cloning, individual progeny phenotyping and marker generation. The detection of novel variants, verified by experimental phenotyping methods, demonstrates the remarkable potential of this approach for the identification of genes controlling selectable phenotypes in malaria and other apicomplexan parasites for which experimental genetic crosses are amenable.

  8. Interaction of amidated single-walled carbon nanotubes with protein by multiple spectroscopic methods

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lili [China Pharmaceutical University, Nanjing 210009 (China); The Nursing College of Pingdingshan University, Pingdingshan 467000 (China); Lin, Rui [Yancheng Health Vocational and Technical College, Yancheng 224005 (China); He, Hua, E-mail: dochehua@163.com [China Pharmaceutical University, Nanjing 210009 (China); Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009 (China); Sun, Meiling, E-mail: sml-nir@sohu.com [China Pharmaceutical University, Nanjing 210009 (China); Jiang, Li; Gao, Mengmeng [China Pharmaceutical University, Nanjing 210009 (China)

    2014-01-15

    The aim of this work was to investigate the detailed interaction between BSA and amidated single walled carbon nanotubes (e-SWNTs) in vitro. Ethylenediamine (EDA) was successfully linked on the surface of single-walled carbon nanotubes (SWNTs) via acylation to improve their dispersion and to introduce active groups. Bovine serum albumin (BSA) was selected as the template protein to inspect the interaction of e-SWNTs with protein. Decreases in fluorescence intensity of BSA induced by e-SWNTs demonstrated the occurrence of interaction between BSA and e-SWNTs. Quenching parameters and different absorption spectra for e-SWNTs–BSA show that the quenching effect of e-SWNTs was static quenching. Hydrophobic force had a leading contribution to the binding roles of BSA on e-SWNTs, which was confirmed by positive enthalpy change and entropy change. The interference of Na{sup +} with the quenching effect of e-SWNTs authenticated that electrostatic force existed in the interactive process simultaneously. The hydrophobicity of amino acid residues markedly increased with the addition of e-SWNTs viewed from UV spectra of BSA. The content of α-helix structure in BSA decreased by 6.8% due to the addition of e-SWNTs, indicating that e-SWNTs have an effect on the secondary conformation of BSA. -- Highlights: • The interaction between e-SWNTs and BSA was investigated by multiple spectroscopic methods. • Quenching mechanism was static quenching. • Changes in structure of BSA were inspected by synchronous fluorescence, UV–vis and CD spectrum.

  9. Designing Kerr interactions using multiple superconducting qubit types in a single circuit

    Science.gov (United States)

    Elliott, Matthew; Joo, Jaewoo; Ginossar, Eran

    2018-02-01

    The engineering of Kerr interactions is of great interest for processing quantum information in multipartite quantum systems and for investigating many-body physics in a complex cavity-qubit network. We study how coupling multiple different types of superconducting qubits to the same cavity modes can be used to modify the self- and cross-Kerr effects acting on the cavities and demonstrate that this type of architecture could be of significant benefit for quantum technologies. Using both analytical perturbation theory results and numerical simulations, we first show that coupling two superconducting qubits with opposite anharmonicities to a single cavity enables the effective self-Kerr interaction to be diminished, while retaining the number splitting effect that enables control and measurement of the cavity field. We demonstrate that this reduction of the self-Kerr effect can maintain the fidelity of coherent states and generalised Schrödinger cat states for much longer than typical coherence times in realistic devices. Next, we find that the cross-Kerr interaction between two cavities can be modified by coupling them both to the same pair of qubit devices. When one of the qubits is tunable in frequency, the strength of entangling interactions between the cavities can be varied on demand, forming the basis for logic operations on the two modes. Finally, we discuss the feasibility of producing an array of cavities and qubits where intermediary and on-site qubits can tune the strength of self- and cross-Kerr interactions across the whole system. This architecture could provide a way to engineer interesting many-body Hamiltonians and be a useful platform for quantum simulation in circuit quantum electrodynamics.

  10. Genetic patterns across multiple introductions of the globally invasive crab genus Carcinus

    Science.gov (United States)

    The European green crab Carcinus maenas is one of the world's most successful aquatic invaders, having established populations on every continent with temperate shores. Here we describe patterns of genetic diversity across both the native and introduced ranges of C. maenas and it...

  11. A silicon multiplicity detector system for an experiment on the interaction of antiprotons with nuclei at BNL

    International Nuclear Information System (INIS)

    Ahmad, S.; Bonner, B.E.; Buchanan, J.A.; Clement, J.M.; Empl, A.; Mutchler, G.S.; Toshkov, S.; Chan, C.S.; Kramer, M.A.; Lindenbaum, S.J.; Hallman, T.J.; Madansky, L.; Peaslee, D.C.

    1991-01-01

    A Large Angle Multiplicity Detector (LAMD) system has been developed and used at the BNL experiment E854: Antiproton Nucleus Interactions. This system performed well with an energetic antiproton beam. Charged particle multiplicity distributions from pbar annihilations were measured. We discuss the design and performance of the LAMD system in this paper. 6 refs., 10 figs

  12. Risk factors for colorectal cancer in patients with multiple serrated polyps: a cross-sectional case series from genetics clinics.

    Directory of Open Access Journals (Sweden)

    Daniel D Buchanan

    2010-07-01

    Full Text Available Patients with multiple serrated polyps are at an increased risk for developing colorectal cancer (CRC. Recent reports have linked cigarette smoking with the subset of CRC that develops from serrated polyps. The aim of this work therefore was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps.We identified 151 Caucasian individuals with multiple serrated polyps including at least 5 outside the rectum, and classified patients into non-smokers, current or former smokers at the time of initial diagnosis of polyposis. Cases were individuals with multiple serrated polyps who presented with CRC. Controls were individuals with multiple serrated polyps and no CRC. Multivariate logistic regression was performed to estimate associations between smoking and CRC with adjustment for age at first presentation, sex and co-existing traditional adenomas, a feature that has been consistently linked with CRC risk in patients with multiple serrated polyps. CRC was present in 56 (37% individuals at presentation. Patients with at least one adenoma were 4 times more likely to present with CRC compared with patients without adenomas (OR = 4.09; 95%CI 1.27 to 13.14; P = 0.02. For females, the odds of CRC decreased by 90% in current smokers as compared to never smokers (OR = 0.10; 95%CI 0.02 to 0.47; P = 0.004 after adjusting for age and adenomas. For males, there was no relationship between current smoking and CRC. There was no statistical evidence of an association between former smoking and CRC for both sexes.A decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.

  13. A low-complexity interacting multiple model filter for maneuvering target tracking

    KAUST Repository

    Khalid, Syed Safwan

    2017-01-22

    In this work, we address the target tracking problem for a coordinate-decoupled Markovian jump-mean-acceleration based maneuvering mobility model. A novel low-complexity alternative to the conventional interacting multiple model (IMM) filter is proposed for this class of mobility models. The proposed tracking algorithm utilizes a bank of interacting filters where the interactions are limited to the mixing of the mean estimates, and it exploits a fixed off-line computed Kalman gain matrix for the entire filter bank. Consequently, the proposed filter does not require matrix inversions during on-line operation which significantly reduces its complexity. Simulation results show that the performance of the low-complexity proposed scheme remains comparable to that of the traditional (highly-complex) IMM filter. Furthermore, we derive analytical expressions that iteratively evaluate the transient and steady-state performance of the proposed scheme, and establish the conditions that ensure the stability of the proposed filter. The analytical findings are in close accordance with the simulated results.

  14. Embracing interactions in ocean acidification research: confronting multiple stressor scenarios and context dependence.

    Science.gov (United States)

    Kroeker, Kristy J; Kordas, Rebecca L; Harley, Christopher D G

    2017-03-01

    Changes in the Earth's environment are now sufficiently complex that our ability to forecast the emergent ecological consequences of ocean acidification (OA) is limited. Such projections are challenging because the effects of OA may be enhanced, reduced or even reversed by other environmental stressors or interactions among species. Despite an increasing emphasis on multifactor and multispecies studies in global change biology, our ability to forecast outcomes at higher levels of organization remains low. Much of our failure lies in a poor mechanistic understanding of nonlinear responses, a lack of specificity regarding the levels of organization at which interactions can arise, and an incomplete appreciation for linkages across these levels. To move forward, we need to fully embrace interactions. Mechanistic studies on physiological processes and individual performance in response to OA must be complemented by work on population and community dynamics. We must also increase our understanding of how linkages and feedback among multiple environmental stressors and levels of organization can generate nonlinear responses to OA. This will not be a simple undertaking, but advances are of the utmost importance as we attempt to mitigate the effects of ongoing global change. © 2017 The Authors.

  15. A low-complexity interacting multiple model filter for maneuvering target tracking

    KAUST Repository

    Khalid, Syed Safwan; Abrar, Shafayat

    2017-01-01

    In this work, we address the target tracking problem for a coordinate-decoupled Markovian jump-mean-acceleration based maneuvering mobility model. A novel low-complexity alternative to the conventional interacting multiple model (IMM) filter is proposed for this class of mobility models. The proposed tracking algorithm utilizes a bank of interacting filters where the interactions are limited to the mixing of the mean estimates, and it exploits a fixed off-line computed Kalman gain matrix for the entire filter bank. Consequently, the proposed filter does not require matrix inversions during on-line operation which significantly reduces its complexity. Simulation results show that the performance of the low-complexity proposed scheme remains comparable to that of the traditional (highly-complex) IMM filter. Furthermore, we derive analytical expressions that iteratively evaluate the transient and steady-state performance of the proposed scheme, and establish the conditions that ensure the stability of the proposed filter. The analytical findings are in close accordance with the simulated results.

  16. Confidence intervals for distinguishing ordinal and disordinal interactions in multiple regression.

    Science.gov (United States)

    Lee, Sunbok; Lei, Man-Kit; Brody, Gene H

    2015-06-01

    Distinguishing between ordinal and disordinal interaction in multiple regression is useful in testing many interesting theoretical hypotheses. Because the distinction is made based on the location of a crossover point of 2 simple regression lines, confidence intervals of the crossover point can be used to distinguish ordinal and disordinal interactions. This study examined 2 factors that need to be considered in constructing confidence intervals of the crossover point: (a) the assumption about the sampling distribution of the crossover point, and (b) the possibility of abnormally wide confidence intervals for the crossover point. A Monte Carlo simulation study was conducted to compare 6 different methods for constructing confidence intervals of the crossover point in terms of the coverage rate, the proportion of true values that fall to the left or right of the confidence intervals, and the average width of the confidence intervals. The methods include the reparameterization, delta, Fieller, basic bootstrap, percentile bootstrap, and bias-corrected accelerated bootstrap methods. The results of our Monte Carlo simulation study suggest that statistical inference using confidence intervals to distinguish ordinal and disordinal interaction requires sample sizes more than 500 to be able to provide sufficiently narrow confidence intervals to identify the location of the crossover point. (c) 2015 APA, all rights reserved).

  17. Emotional pictures and sounds: A review of multimodal interactions of emotion cues in multiple domains

    Directory of Open Access Journals (Sweden)

    Antje B M Gerdes

    2014-12-01

    Full Text Available In everyday life, multiple sensory channels jointly trigger emotional experiences and one channel may alter processing in another channel. For example, seeing an emotional facial expression and hearing the voice’s emotional tone will jointly create the emotional experience. This example, where auditory and visual input is related to social communication, has gained considerable attention by researchers. However, interactions of visual and auditory emotional information are not limited to social communication but can extend to much broader contexts including human, animal, and environmental cues. In this article, we review current research on audiovisual emotion processing beyond face-voice stimuli to develop a broader perspective on multimodal interactions in emotion processing. We argue that current concepts of multimodality should be extended in considering an ecologically valid variety of stimuli in audiovisual emotion processing. Therefore, we provide an overview of studies in which emotional sounds and interactions with complex pictures of scenes were investigated. In addition to behavioral studies, we focus on neuroimaging, electro- and peripher-physiological findings. Furthermore, we integrate these findings and identify similarities or differences. We conclude with suggestions for future research.

  18. Multiplicity fluctuations of identified hadrons in p+p interactions at SPS energies

    CERN Document Server

    Maćkowiak-Pawłowska, Maja

    2014-01-01

    Study of energy and system size fluctuations of identified hadrons is one of the key goals of NA61/SHINE at the CERN SPS. Results may allow to discover the critical point (CP) of strongly interacting matter as well as to uncover properties of the onset of deconfinement (OD). But fluctuations exhibit numerous other sources starting from most basic ones like volume effects and conservation laws. NA49 seems to observe fluctuations related to CP in collisions of medium size nuclei at top SPS energy. However, this result will remain inconclusive until systematic data on energy and system size dependence will be available. Moreover, fluctuations in p+p as well as in Pb+Pb interactions should be better understood. In this contribution results on multiplicity fluctuations of identified hadrons in p+p interactions at the CERN SPS energies will be presented. The NA61 data will be compared with the corresponding results from central Pb+Pb collisions of NA49 in the common acceptance region of both experiments. Moreover, ...

  19. Attentional processes in interactions between people with profound intellectual and multiple disabilities and direct support staff.

    Science.gov (United States)

    Hostyn, Ine; Ine, Hostyn; Neerinckx, Heleen; Heleen, Neerinckx; Maes, Bea; Bea, Maes

    2011-01-01

    Few studies have examined joint attention in interactions with persons with profound intellectual and multiple disabilities (PIMD), despite its important role in high-quality interaction. The purpose of this study is to describe the attention-directing behaviours of persons with PIMD and their direct support staff and the attention episodes resulting from their interactions, and to understand how these variables relate to each other. Video observations of 17 staff-client dyads were coded using partial interval recording. The results showed considerable variation across individuals and dyads. In general, persons with PIMD directed the attention of staff members infrequently. The staff members frequently directed their clients' attention towards a topic of interest but did not often use the tactile modality. Within the staff-client dyad, there was not much joint attention; however, shared attention episodes occurred frequently. Shared attention and joint attention are strongly correlated. A negative correlation was found between clients not using attention-directing behaviours and staff members using tactile methods to direct the attention, and joint attention episodes. This study presents both directions for future research and practical implications. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. A genetic algorithm for multiple relay selection in two-way relaying cognitive radio networks

    KAUST Repository

    Alsharoa, Ahmad M.; Ghazzai, Hakim; Alouini, Mohamed-Slim

    2013-01-01

    In this paper, we investigate a multiple relay selection scheme for two-way relaying cognitive radio networks where primary users and secondary users operate on the same frequency band. More specifically, cooperative relays using Amplifyand- Forward

  1. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti

    2011-01-01

    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that g...

  2. A multiobjective non-dominated sorting genetic algorithm (NSGA-II for the Multiple Traveling Salesman Problem

    Directory of Open Access Journals (Sweden)

    Rubén Iván Bolaños

    2015-06-01

    Full Text Available This paper considers a multi-objective version of the Multiple Traveling Salesman Problem (MOmTSP. In particular, two objectives are considered: the minimization of the total traveled distance and the balance of the working times of the traveling salesmen. The problem is formulated as an integer multi-objective optimization model. A non-dominated sorting genetic algorithm (NSGA-II is proposed to solve the MOmTSP. The solution scheme allows one to find a set of ordered solutions in Pareto fronts by considering the concept of dominance. Tests on real world instances and instances adapted from the literature show the effectiveness of the proposed algorithm.

  3. A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway.

    Science.gov (United States)

    Salašová, Alena; Yokota, Chika; Potěšil, David; Zdráhal, Zbyněk; Bryja, Vítězslav; Arenas, Ernest

    2017-07-11

    Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients. Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis' early development. Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo. Our study shows for the first time that LRRK2 activates the WNT

  4. Reducing bias in population and landscape genetic inferences: the effects of sampling related individuals and multiple life stages.

    Science.gov (United States)

    Peterman, William; Brocato, Emily R; Semlitsch, Raymond D; Eggert, Lori S

    2016-01-01

    In population or landscape genetics studies, an unbiased sampling scheme is essential for generating accurate results, but logistics may lead to deviations from the sample design. Such deviations may come in the form of sampling multiple life stages. Presently, it is largely unknown what effect sampling different life stages can have on population or landscape genetic inference, or how mixing life stages can affect the parameters being measured. Additionally, the removal of siblings from a data set is considered best-practice, but direct comparisons of inferences made with and without siblings are limited. In this study, we sampled embryos, larvae, and adult Ambystoma maculatum from five ponds in Missouri, and analyzed them at 15 microsatellite loci. We calculated allelic richness, heterozygosity and effective population sizes for each life stage at each pond and tested for genetic differentiation (F ST and D C ) and isolation-by-distance (IBD) among ponds. We tested for differences in each of these measures between life stages, and in a pooled population of all life stages. All calculations were done with and without sibling pairs to assess the effect of sibling removal. We also assessed the effect of reducing the number of microsatellites used to make inference. No statistically significant differences were found among ponds or life stages for any of the population genetic measures, but patterns of IBD differed among life stages. There was significant IBD when using adult samples, but tests using embryos, larvae, or a combination of the three life stages were not significant. We found that increasing the ratio of larval or embryo samples in the analysis of genetic distance weakened the IBD relationship, and when using D C , the IBD was no longer significant when larvae and embryos exceeded 60% of the population sample. Further, power to detect an IBD relationship was reduced when fewer microsatellites were used in the analysis.

  5. Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia.

    Science.gov (United States)

    Tang, Jinsong; Fan, Yu; Li, Hong; Xiang, Qun; Zhang, Deng-Feng; Li, Zongchang; He, Ying; Liao, Yanhui; Wang, Ya; He, Fan; Zhang, Fengyu; Shugart, Yin Yao; Liu, Chunyu; Tang, Yanqing; Chan, Raymond C K; Wang, Chuan-Yue; Yao, Yong-Gang; Chen, Xiaogang

    2017-06-20

    Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive. We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia. Eight non-synonymous DNMs (including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes (p.V24689I mutation in TTN, p.S2506T mutation in GCN1L1, IVS3+1G > T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function (LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations (CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. All rights reserved.

  6. Reducing bias in population and landscape genetic inferences: the effects of sampling related individuals and multiple life stages

    Directory of Open Access Journals (Sweden)

    William Peterman

    2016-03-01

    Full Text Available In population or landscape genetics studies, an unbiased sampling scheme is essential for generating accurate results, but logistics may lead to deviations from the sample design. Such deviations may come in the form of sampling multiple life stages. Presently, it is largely unknown what effect sampling different life stages can have on population or landscape genetic inference, or how mixing life stages can affect the parameters being measured. Additionally, the removal of siblings from a data set is considered best-practice, but direct comparisons of inferences made with and without siblings are limited. In this study, we sampled embryos, larvae, and adult Ambystoma maculatum from five ponds in Missouri, and analyzed them at 15 microsatellite loci. We calculated allelic richness, heterozygosity and effective population sizes for each life stage at each pond and tested for genetic differentiation (FST and DC and isolation-by-distance (IBD among ponds. We tested for differences in each of these measures between life stages, and in a pooled population of all life stages. All calculations were done with and without sibling pairs to assess the effect of sibling removal. We also assessed the effect of reducing the number of microsatellites used to make inference. No statistically significant differences were found among ponds or life stages for any of the population genetic measures, but patterns of IBD differed among life stages. There was significant IBD when using adult samples, but tests using embryos, larvae, or a combination of the three life stages were not significant. We found that increasing the ratio of larval or embryo samples in the analysis of genetic distance weakened the IBD relationship, and when using DC, the IBD was no longer significant when larvae and embryos exceeded 60% of the population sample. Further, power to detect an IBD relationship was reduced when fewer microsatellites were used in the analysis.

  7. African genetic ancestry interacts with body mass index to modify risk for uterine fibroids.

    Science.gov (United States)

    Giri, Ayush; Edwards, Todd L; Hartmann, Katherine E; Torstenson, Eric S; Wellons, Melissa; Schreiner, Pamela J; Velez Edwards, Digna R

    2017-07-01

    Race, specifically African ancestry, and obesity are important risk factors for uterine fibroids, and likely interact to provide the right conditions for fibroid growth. However, existing studies largely focus on the main-effects rather than their interaction. Here, we firstly provide evidence for interaction between categories of body mass index (BMI) and reported-race in relation to uterine fibroids. We then investigate whether the association between inferred local European ancestry and fibroid risk is modified by BMI in African American (AA) women in the Vanderbilt University Medical Center bio-repository (BioVU) (539 cases and 794 controls) and the Coronary Artery Risk Development in Young Adults study (CARDIA, 264 cases and 173 controls). We used multiple logistic regression to evaluate interactions between local European ancestry and BMI in relation to fibroid risk, then performed fixed effects meta-analysis. Statistical significance threshold for local-ancestry and BMI interactions was empirically estimated with 10,000 permutations (p-value = 1.18x10-4). Admixture mapping detected an association between European ancestry and fibroid risk which was modified by BMI (continuous-interaction p-value = 3.75x10-5) around ADTRP (chromosome 6p24); the strongest association was found in the obese category (ancestry odds ratio (AOR) = 0.51, p-value = 2.23x10-5). Evaluation of interaction between genotyped/imputed variants and BMI in this targeted region suggested race-specific interaction, present in AAs only; strongest evidence was found for insertion/deletion variant (6:11946435), again in the obese category (OR = 1.66, p-value = 1.72x10-6). We found nominal evidence for interaction between local ancestry and BMI at a previously reported region in chromosome 2q31-32, which includes COL5A2, and TFPI, an immediate downstream target of ADTRP. Interactions between BMI and SNPs (single nucleotide polymorphisms) found in this region in AA women were also detected in an

  8. Clustering and Genetic Algorithm Based Hybrid Flowshop Scheduling with Multiple Operations

    Directory of Open Access Journals (Sweden)

    Yingfeng Zhang

    2014-01-01

    Full Text Available This research is motivated by a flowshop scheduling problem of our collaborative manufacturing company for aeronautic products. The heat-treatment stage (HTS and precision forging stage (PFS of the case are selected as a two-stage hybrid flowshop system. In HTS, there are four parallel machines and each machine can process a batch of jobs simultaneously. In PFS, there are two machines. Each machine can install any module of the four modules for processing the workpeices with different sizes. The problem is characterized by many constraints, such as batching operation, blocking environment, and setup time and working time limitations of modules, and so forth. In order to deal with the above special characteristics, the clustering and genetic algorithm is used to calculate the good solution for the two-stage hybrid flowshop problem. The clustering is used to group the jobs according to the processing ranges of the different modules of PFS. The genetic algorithm is used to schedule the optimal sequence of the grouped jobs for the HTS and PFS. Finally, a case study is used to demonstrate the efficiency and effectiveness of the designed genetic algorithm.

  9. Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout

    NARCIS (Netherlands)

    McKinney, Cushla; Stamp, Lisa K.; Dalbeth, Nicola; Topless, Ruth K.; Day, Richard O.; Kannangara, Diluk R. W.; Williams, Kenneth M.; Janssen, Matthijs; Jansen, Timothy L.; Joosten, Leo A.; Radstake, Timothy R.; Riches, Philip L.; Tausche, Anne-Kathrin; Liote, Frederic; So, Alexander; Merriman, Tony R.

    2015-01-01

    Introduction: The acute gout flare results from a localised self-limiting innate immune response to monosodium urate (MSU) crystals deposited in joints in hyperuricaemic individuals. Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3

  10. Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout

    NARCIS (Netherlands)

    McKinney, C.; Stamp, L.K.; Dalbeth, N.; Topless, R.K.; Day, R.O.; Kannangara, D.R.; Williams, K.M.; Janssen, M; Jansen, T.L.Th.A.; Joosten, L.A.B.; Radstake, T.R.; Riches, P.L.; Tausche, A.K.; Liote, F.; So, A.; Merriman, T.R.

    2015-01-01

    INTRODUCTION: The acute gout flare results from a localised self-limiting innate immune response to monosodium urate (MSU) crystals deposited in joints in hyperuricaemic individuals. Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3

  11. Infectious Bursal Disease Virus-Host Interactions: Multifunctional Viral Proteins that Perform Multiple and Differing Jobs

    Directory of Open Access Journals (Sweden)

    Yao Qin

    2017-01-01

    Full Text Available Infectious bursal disease (IBD is an acute, highly contagious and immunosuppressive poultry disease caused by IBD virus (IBDV. The consequent immunosuppression increases susceptibility to other infectious diseases and the risk of subsequent vaccination failure as well. Since the genome of IBDV is relatively small, it has a limited number of proteins inhibiting the cellular antiviral responses and acting as destroyers to the host defense system. Thus, these virulence factors must be multifunctional in order to complete the viral replication cycle in a host cell. Insights into the roles of these viral proteins along with their multiple cellular targets in different pathways will give rise to a rational design for safer and effective vaccines. Here we summarize the recent findings that focus on the virus–cell interactions during IBDV infection at the protein level.

  12. Multi-sensor fusion with interacting multiple model filter for improved aircraft position accuracy.

    Science.gov (United States)

    Cho, Taehwan; Lee, Changho; Choi, Sangbang

    2013-03-27

    The International Civil Aviation Organization (ICAO) has decided to adopt Communications, Navigation, and Surveillance/Air Traffic Management (CNS/ATM) as the 21st century standard for navigation. Accordingly, ICAO members have provided an impetus to develop related technology and build sufficient infrastructure. For aviation surveillance with CNS/ATM, Ground-Based Augmentation System (GBAS), Automatic Dependent Surveillance-Broadcast (ADS-B), multilateration (MLAT) and wide-area multilateration (WAM) systems are being established. These sensors can track aircraft positions more accurately than existing radar and can compensate for the blind spots in aircraft surveillance. In this paper, we applied a novel sensor fusion method with Interacting Multiple Model (IMM) filter to GBAS, ADS-B, MLAT, and WAM data in order to improve the reliability of the aircraft position. Results of performance analysis show that the position accuracy is improved by the proposed sensor fusion method with the IMM filter.

  13. Multiple hard interactions in $\\gamma\\gamma$ and $\\gamma$p physics at LEP and HERA

    CERN Document Server

    Butterworth, J.M.; Seymour, M.H.; Storrow, J.K.; Walker, R.

    1995-01-01

    At e^+e^- and ep colliders, the large fluxes of almost on-shell photons accompanying the lepton beams lead to the photoproduction of jets. As the centre-of-mass energy is increased, regions of smaller x in the parton densities are explored and these are regions of high parton density. As a result, the probability for more than one hard partonic scattering occurring in a single \\gamma \\gamma or \\gamma p collision can become significant. This effect has been simulated using an eikonal prescription combined with the HERWIG Monte Carlo program. The possible effects of multiple hard interactions on event shapes and jet cross sections have been studied in this framework at a range of energies relevant to HERA and LEPII. The results indicate that the effects could be significant.

  14. The interaction between 4-aminoantipyrine and bovine serum albumin: Multiple spectroscopic and molecular docking investigations

    International Nuclear Information System (INIS)

    Teng Yue; Liu Rutao; Li Chao; Xia Qing; Zhang Pengjun

    2011-01-01

    4-Aminoantipyrine (AAP) is widely used in the pharmaceutical industry, in biochemical experiments and in environmental monitoring. AAP as an aromatic pollutant in the environment poses a great threat to human health. To evaluate the toxicity of AAP at the protein level, the effects of AAP on bovine serum albumin (BSA) were investigated by multiple spectroscopic techniques and molecular modeling. After the inner filter effect was eliminated, the experimental results showed that AAP effectively quenched the intrinsic fluorescence of BSA via static quenching. The number of binding sites, the binding constant, the thermodynamic parameters and binding subdomain were measured, and indicated that AAP could spontaneously bind with BSA on subdomain IIIA through electrostatic forces. Molecular docking results revealed that AAP interacted with the Glu 488 and Glu 502 residues of BSA. Furthermore, the conformation of BSA was demonstrably changed in the presence of AAP. The skeletal structure of BSA loosened, exposing internal hydrophobic aromatic ring amino acids and peptide strands to the solution.

  15. Giant graviton interactions and M2-branes ending on multiple M5-branes

    Science.gov (United States)

    Hirano, Shinji; Sato, Yuki

    2018-05-01

    We study splitting and joining interactions of giant gravitons with angular momenta N 1/2 ≪ J ≪ N in the type IIB string theory on AdS 5 × S 5 by describing them as instantons in the tiny graviton matrix model introduced by Sheikh-Jabbari. At large J the instanton equation can be mapped to the four-dimensional Laplace equation and the Coulomb potential for m point charges in an n-sheeted Riemann space corresponds to the m-to- n interaction process of giant gravitons. These instantons provide the holographic dual of correlators of all semi-heavy operators and the instanton amplitudes exactly agree with the pp-wave limit of Schur polynomial correlators in N = 4 SYM computed by Corley, Jevicki and Ramgoolam. By making a slight change of variables the same instanton equation is mathematically transformed into the Basu-Harvey equation which describes the system of M2-branes ending on M5-branes. As it turns out, the solutions to the sourceless Laplace equation on an n-sheeted Riemann space correspond to n M5-branes connected by M2-branes and we find general solutions representing M2-branes ending on multiple M5-branes. Among other solutions, the n = 3 case describes an M2-branes junction ending on three M5-branes. The effective theory on the moduli space of our solutions might shed light on the low energy effective theory of multiple M5-branes.

  16. Invasion genetics of a freshwater mussel (Dreissena rostriformis bugensis) in eastern Europe: high gene flow and multiple introductions.

    Science.gov (United States)

    Therriault, T W; Orlova, M I; Docker, M F; Macisaac, H J; Heath, D D

    2005-07-01

    In recent years, the quagga mussel, Dreissena rostriformis bugensis, native to the Dnieper and Bug Limans of the northern Black Sea, has been dispersed by human activities across the basin, throughout much of the Volga River system, and to the Laurentian Great Lakes. We used six published microsatellite markers to survey populations throughout its native and introduced range to identify relationships among potential source populations and introduced ones. Mussels from 12 sites in Eurasia, including the central Caspian Sea and one in North America (Lake Erie), were sampled. Field surveys in the Volga River basin suggested that the species first colonized the middle reach of the river near Kubyshev Reservoir, and thereafter spread both upstream and downstream. Evidence of considerable gene flow among populations was observed and genetic diversity was consistent with a larger, metapopulation that has not experienced bottlenecks or founder effects. We propose that high gene flow, possibly due to multiple invasions, has facilitated establishment of quagga mussel populations in the Volga River system. The Caspian Sea population (D. rostriformis rostriformis (=distincta)) was genetically more distinct than other populations, a finding that may be related to habitat differences. The geographical pattern of genetic divergence is not characteristic of isolation-by-distance but, rather, of long-distance dispersal, most likely mediated by commercial ships' ballast water transfer.

  17. Patterns of genetic diversity of the cryptogenic red alga Polysiphonia morrowii (Ceramiales, Rhodophyta) suggest multiple origins of the Atlantic populations.

    Science.gov (United States)

    Geoffroy, Alexandre; Destombe, Christophe; Kim, Byeongseok; Mauger, Stéphane; Raffo, María Paula; Kim, Myung Sook; Le Gall, Line

    2016-08-01

    The red alga Polysiphonia morrowii, native to the North Pacific (Northeast Asia), has recently been reported worldwide. To determine the origin of the French and Argentine populations of this introduced species, we compared samples from these two areas with samples collected in Korea and at Hakodate, Japan, the type locality of the species. Combined analyses of chloroplastic (rbcL) and mitochondrial (cox1) DNA revealed that the French and Argentine populations are closely related and differ substantially from the Korean and Japanese populations. The genetic structure of P. morrowii populations from South Atlantic and North Atlantic, which showed high haplotype diversity compared with populations from the North Pacific, suggested the occurrence of multiple introduction events from areas outside of the so-called native regions. Although similar, the French and Argentine populations are not genetically identical. Thus, the genetic structure of these two introduced areas may have been modified by cryptic and recurrent introduction events directly from Asia or from other introduced areas that act as introduction relays. In addition, the large number of private cytoplasmic types identified in the two introduced regions strongly suggests that local populations of P. morrowii existed before the recent detection of these invasions. Our results suggest that the most likely scenario is that the source population(s) of the French and Argentine populations was not located only in the North Pacific and/or that P. morrowii is a cryptogenic species.

  18. Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia

    Institute of Scientific and Technical Information of China (English)

    Jinsong Tang; Fan He; Fengyu Zhang; Yin Yao Shugart; Chunyu Liu; Yanqing Tang; Raymond C.K.Chan; Chuan-Yue Wang; Yong-Gang Yao; Xiaogang Chen; Yu Fan; Hong Li; Qun Xiang; Deng-Feng Zhang; Zongchang Li; Ying He; Yanhui Liao; Ya Wang

    2017-01-01

    Schizophrenia is a common disorder with a high heritability,but its genetic architecture is still elusive.We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia.Eight non-synonymous DNMs (including one splicing site) were identified and shared by twins,which were either located in previously reported schizophrenia risk genes (p.V24689I mutation in TTN,p.S2506T mutation in GCN1L1,IVS3+1G > T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis.By searching the inherited rare damaging or loss-of-function (LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes,we were able to distill genetic alterations in several schizophrenia risk genes,including GAD1,PLXNA2,RELN and FEZ1.Four inherited copy number variations (CNVs;including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families,respectively.Most of families carried both missense DNMs and inherited risk variants,which might suggest that DNMs,inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility.Our results support that schizophrenia is caused by a combination of multiple genetic factors,with each DNM/variant showing a relatively small effect size.

  19. The McGill Interactive Pediatric OncoGenetic Guidelines: An approach to identifying pediatric oncology patients most likely to benefit from a genetic evaluation.

    Science.gov (United States)

    Goudie, Catherine; Coltin, Hallie; Witkowski, Leora; Mourad, Stephanie; Malkin, David; Foulkes, William D

    2017-08-01

    Identifying cancer predisposition syndromes in children with tumors is crucial, yet few clinical guidelines exist to identify children at high risk of having germline mutations. The McGill Interactive Pediatric OncoGenetic Guidelines project aims to create a validated pediatric guideline in the form of a smartphone/tablet application using algorithms to process clinical data and help determine whether to refer a child for genetic assessment. This paper discusses the initial stages of the project, focusing on its overall structure, the methodology underpinning the algorithms, and the upcoming algorithm validation process. © 2017 Wiley Periodicals, Inc.

  20. Biflorin induces cytotoxicity by DNA interaction in genetically different human melanoma cell lines.

    Science.gov (United States)

    Ralph, Ana Carolina Lima; Calcagno, Danielle Queiroz; da Silva Souza, Luciana Gregório; de Lemos, Telma Leda Gomes; Montenegro, Raquel Carvalho; de Arruda Cardoso Smith, Marília; de Vasconcellos, Marne Carvalho

    2016-08-01

    Cancer is a public health problem and the second leading cause of death worldwide. The incidence of cutaneous melanoma has been notably increasing, resulting in high aggressiveness and poor survival rates. Taking into account the antitumor activity of biflorin, a substance isolated from Capraria biflora L. roots that is cytotoxic in vitro and in vivo, this study aimed to demonstrate the action of biflorin against three established human melanoma cell lines that recapitulate the molecular landscape of the disease in terms of genetic alterations and mutations, such as the TP53, NRAS and BRAF genes. The results presented here indicate that biflorin reduces the viability of melanoma cell lines by DNA interactions. Biflorin causes single and double DNA strand breaks, consequently inhibiting cell cycle progression, replication and DNA repair and promoting apoptosis. Our data suggest that biflorin could be considered as a future therapeutic option for managing melanoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Interactions between Genetic and Ecological Effects on the Evolution of Life Cycles.

    Science.gov (United States)

    Rescan, Marie; Lenormand, Thomas; Roze, Denis

    2016-01-01

    Sexual reproduction leads to an alternation between haploid and diploid phases, whose relative length varies widely across taxa. Previous genetical models showed that diploid or haploid life cycles may be favored, depending on dominance interactions and on effective recombination rates. By contrast, niche differentiation between haploids and diploids may favor biphasic life cycles, in which development occurs in both phases. In this article, we explore the interplay between genetical and ecological factors, assuming that deleterious mutations affect the competitivity of individuals within their ecological niche and allowing different effects of mutations in haploids and diploids (including antagonistic selection). We show that selection on a modifier gene affecting the relative length of both phases can be decomposed into a direct selection term favoring the phase with the highest mean fitness (due to either ecological differences or differential effects of mutations) and an indirect selection term favoring the phase in which selection is more efficient. When deleterious alleles occur at many loci and in the presence of ecological differentiation between haploids and diploids, evolutionary branching often occurs and leads to the stable coexistence of alleles coding for haploid and diploid cycles, while temporal variations in niche sizes may stabilize biphasic cycles.

  2. Genetic components to caste allocation in a multiple-queen ant species

    NARCIS (Netherlands)

    Libbrecht, Romain; Schwander, Tanja; Keller, Laurent

    2011-01-01

    Reproductive division of labor and the coexistence of distinct castes are hallmarks of insect societies. In social insect species with multiple queens per colony, the fitness of nestmate queens directly depends on the process of caste allocation (i.e., the relative investment in queen, sterile

  3. Multiple analytical approaches reveal distinct gene-environment interactions in smokers and non smokers in lung cancer.

    Directory of Open Access Journals (Sweden)

    Rakhshan Ihsan

    Full Text Available Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR, classification and regression tree (CART and multifactor dimensionality reduction (MDR, was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11-2.59,p = 0.01, whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25-0.65,p<0.001 and OR = 0.51;95%CI = 0.33-0.78,p = 0.002 respectively. In smokers, EPHX1 Tyr113His and SULT1A1 Arg213His polymorphisms reduced the risk of lung cancer, whereas CYP1A1*2A, CYP1A1*2C and GSTP1 Ile105Val imparted increased risk in non-smokers only. While exploring non-linear interactions through CART analysis, smokers carrying the combination of EPHX1 113TC (Tyr/His, SULT1A1 213GG (Arg/Arg or AA (His/His and GSTM1 null genotypes showed the highest risk for lung cancer (OR = 3.73;95%CI = 1.33-10.55,p = 0.006, whereas combined effect of CYP1A1*2A 6235CC or TC, SULT1A1 213GG (Arg/Arg and betel quid chewing showed maximum risk in non-smokers (OR = 2.93;95%CI = 1.15-7.51,p = 0.01. MDR analysis identified two distinct predictor models for the risk of lung cancer in smokers (tobacco chewing, EPHX1 Tyr113His, and SULT1A1 Arg213His and non-smokers (CYP1A1*2A, GSTP1 Ile105Val and SULT1A1 Arg213His with testing balance accuracy (TBA of 0.6436 and 0.6677 respectively. Interaction entropy interpretations of MDR results showed non-additive interactions of tobacco chewing with

  4. Chad Genetic Diversity Reveals an African History Marked by Multiple Holocene Eurasian Migrations.

    Science.gov (United States)

    Haber, Marc; Mezzavilla, Massimo; Bergström, Anders; Prado-Martinez, Javier; Hallast, Pille; Saif-Ali, Riyadh; Al-Habori, Molham; Dedoussis, George; Zeggini, Eleftheria; Blue-Smith, Jason; Wells, R Spencer; Xue, Yali; Zalloua, Pierre A; Tyler-Smith, Chris

    2016-12-01

    Understanding human genetic diversity in Africa is important for interpreting the evolution of all humans, yet vast regions in Africa, such as Chad, remain genetically poorly investigated. Here, we use genotype data from 480 samples from Chad, the Near East, and southern Europe, as well as whole-genome sequencing from 19 of them, to show that many populations today derive their genomes from ancient African-Eurasian admixtures. We found evidence of early Eurasian backflow to Africa in people speaking the unclassified isolate Laal language in southern Chad and estimate from linkage-disequilibrium decay that this occurred 4,750-7,200 years ago. It brought to Africa a Y chromosome lineage (R1b-V88) whose closest relatives are widespread in present-day Eurasia; we estimate from sequence data that the Chad R1b-V88 Y chromosomes coalesced 5,700-7,300 years ago. This migration could thus have originated among Near Eastern farmers during the African Humid Period. We also found that the previously documented Eurasian backflow into Africa, which occurred ∼3,000 years ago and was thought to be mostly limited to East Africa, had a more westward impact affecting populations in northern Chad, such as the Toubou, who have 20%-30% Eurasian ancestry today. We observed a decline in heterozygosity in admixed Africans and found that the Eurasian admixture can bias inferences on their coalescent history and confound genetic signals from adaptation and archaic introgression. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. The function of communities in protein interaction networks at multiple scales

    Directory of Open Access Journals (Sweden)

    Jones Nick S

    2010-07-01

    Full Text Available Abstract Background If biology is modular then clusters, or communities, of proteins derived using only protein interaction network structure should define protein modules with similar biological roles. We investigate the link between biological modules and network communities in yeast and its relationship to the scale at which we probe the network. Results Our results demonstrate that the functional homogeneity of communities depends on the scale selected, and that almost all proteins lie in a functionally homogeneous community at some scale. We judge functional homogeneity using a novel test and three independent characterizations of protein function, and find a high degree of overlap between these measures. We show that a high mean clustering coefficient of a community can be used to identify those that are functionally homogeneous. By tracing the community membership of a protein through multiple scales we demonstrate how our approach could be useful to biologists focusing on a particular protein. Conclusions We show that there is no one scale of interest in the community structure of the yeast protein interaction network, but we can identify the range of resolution parameters that yield the most functionally coherent communities, and predict which communities are most likely to be functionally homogeneous.

  6. Interaction effects among multiple job demands: an examination of healthcare workers across different contexts.

    Science.gov (United States)

    Jimmieson, Nerina L; Tucker, Michelle K; Walsh, Alexandra J

    2017-05-01

    Simultaneous exposure to time, cognitive, and emotional demands is a feature of the work environment for healthcare workers, yet effects of these common stressors in combination are not well established. Survey data were collected from 125 hospital employees (Sample 1, Study 1), 93 ambulance service employees (Sample 2, Study 1), and 380 aged care/disability workers (Study 2). Hierarchical multiple regressions were conducted. In Sample 1, high cognitive demand exacerbated high emotional demand on psychological strain and job burnout, whereas the negative effect of high emotional demand was not present at low cognitive demand. In Sample 2, a similar pattern between emotional demand and time demand on stress-remedial intentions was observed. In Study 2, emotional demand × time demand and time demand × cognitive demand interactions again revealed that high levels of two demands were stress-exacerbating and low levels of one demand neutralized the other. A three-way interaction on job satisfaction showed the negative impact of emotional demand was exacerbated when both time and cognitive demands were high, creating a "triple disadvantage" of job demands. The results demonstrate that reducing some job demands helps attenuate the stressful effects of other job demands on different employee outcomes.

  7. Using Nucleon Multiplicities to Analyze Anti-Neutrino Interactions with Nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Elkins, Miranda J. [Univ. of Minnesota, Duluth, MN (United States)

    2017-05-01

    The most commonly used, simple interaction models have not accurately described the nuclear effects on either neutrino-nucleus or anti-neutrino-nucleus interactions. Comparison of data collected by the MINERvA experiment and these models shows a discrepancy in the reconstructed hadronic energy distribution at momentum transfers below 0.8 GeV. Two nuclear model effects that were previously not modeled are possible culprits of this discrepancy. The first is known as random-phase-approximation and the second is the addition of a meson exchange current process, also known as two-particle two-hole due to its result in two particles leaving the nucleus with two holes left in their place. For the first time a neutron counting software algorithm has been created and used to compare the multiplicity and spatial distributions of neutrons between the simulation and data. There is localized sensitivity to the RPA and 2p2h effects and both help the simulation better describe the data. Ad ditional systematic or model effects are present which cause the simulation to overproduce neutrons, and potential causes are discussed.

  8. Urban land use decouples plant-herbivore-parasitoid interactions at multiple spatial scales.

    Directory of Open Access Journals (Sweden)

    Amanda E Nelson

    Full Text Available Intense urban and agricultural development alters habitats, increases fragmentation, and may decouple trophic interactions if plants or animals cannot disperse to needed resources. Specialist insects represent a substantial proportion of global biodiversity and their fidelity to discrete microhabitats provides a powerful framework for investigating organismal responses to human land use. We sampled site occupancy and densities for two plant-herbivore-parasitoid systems from 250 sites across a 360 km2 urban/agricultural landscape to ask whether and how human development decouples interactions between trophic levels. We compared patterns of site occupancy, host plant density, herbivory and parasitism rates of insects at two trophic levels with respect to landcover at multiple spatial scales. Geospatial analyses were used to identify landcover characters predictive of insect distributions. We found that herbivorous insect densities were decoupled from host tree densities in urban landcover types at several spatial scales. This effect was amplified for the third trophic level in one of the two insect systems: despite being abundant regionally, a parasitoid species was absent from all urban/suburban landcover even where its herbivore host was common. Our results indicate that human land use patterns limit distributions of specialist insects. Dispersal constraints associated with urban built development are specifically implicated as a limiting factor.

  9. Design and cohort description of the InterAct Project: an examination of the interaction of genetic and lifestyle factors on the incidence of type 2 diabetes in the EPIC Study

    NARCIS (Netherlands)

    Langenberg, C.; Sharp, S.; Forouhi, N.G.; Feskens, E.J.M.

    2011-01-01

    Aims/Hypothesis: Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for

  10. Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Šimáková, Miroslava; Křen, Vladimír; Křenová, D.; Horký, K.; Jáchymová, M.; Míková, B.; Kazdová, L.; Aitman, T. J.; Churchill, P. C.; Webb, R. C.; Hingarh, N. H.; Yang, Y.; Wang, J. M.; St.Lezin, E. M.; Kurtz, W. T.

    1999-01-01

    Roč. 103, č. 12 (1999), s. 1651-1657 ISSN 0021-9738 R&D Projects: GA ČR GA306/97/0521; GA ČR GV204/98/K015 Grant - others:NIH(US) ROI HL-56028; NIH(US) PO1 HL-35018; NIH(US) HL-18575 Institutional research plan: CEZ:AV0Z5011922 Keywords : Cd36 * cardiovascular risk factors * spontaneous hypertension Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.921, year: 1999

  11. Effects of multiple genetic loci on the pathogenesis from serum urate to gout

    OpenAIRE

    Zheng Dong; Jingru Zhou; Shuai Jiang; Yuan Li; Dongbao Zhao; Chengde Yang; Yanyun Ma; Yi Wang; Hongjun He; Hengdong Ji; Yajun Yang; Xiaofeng Wang; Xia Xu; Yafei Pang; Hejian Zou

    2017-01-01

    Gout is a common arthritis resulting from increased serum urate, and many loci have been identified that are associated with serum urate and gout. However, their influence on the progression from elevated serum urate levels to gout is unclear. This study aims to explore systematically the effects of genetic variants on the pathogenesis in approximately 5,000 Chinese individuals. Six genes (PDZK1, GCKR, TRIM46, HNF4G, SLC17A1, LRRC16A) were determined to be associated with serum urate (P FDR?

  12. hamlet, a binary genetic switch between single- and multiple- dendrite neuron morphology.

    Science.gov (United States)

    Moore, Adrian W; Jan, Lily Yeh; Jan, Yuh Nung

    2002-08-23

    The dendritic morphology of neurons determines the number and type of inputs they receive. In the Drosophila peripheral nervous system (PNS), the external sensory (ES) neurons have a single nonbranched dendrite, whereas the lineally related multidendritic (MD) neurons have extensively branched dendritic arbors. We report that hamlet is a binary genetic switch between these contrasting morphological types. In hamlet mutants, ES neurons are converted to an MD fate, whereas ectopic hamlet expression in MD precursors results in transformation of MD neurons into ES neurons. Moreover, hamlet expression induced in MD neurons undergoing dendrite outgrowth drastically reduces arbor branching.

  13. Global map of physical interactions among differentially expressed genes in multiple sclerosis relapses and remissions.

    Science.gov (United States)

    Tuller, Tamir; Atar, Shimshi; Ruppin, Eytan; Gurevich, Michael; Achiron, Anat

    2011-09-15

    Multiple sclerosis (MS) is a central nervous system autoimmune inflammatory T-cell-mediated disease with a relapsing-remitting course in the majority of patients. In this study, we performed a high-resolution systems biology analysis of gene expression and physical interactions in MS relapse and remission. To this end, we integrated 164 large-scale measurements of gene expression in peripheral blood mononuclear cells of MS patients in relapse or remission and healthy subjects, with large-scale information about the physical interactions between these genes obtained from public databases. These data were analyzed with a variety of computational methods. We find that there is a clear and significant global network-level signal that is related to the changes in gene expression of MS patients in comparison to healthy subjects. However, despite the clear differences in the clinical symptoms of MS patients in relapse versus remission, the network level signal is weaker when comparing patients in these two stages of the disease. This result suggests that most of the genes have relatively similar expression levels in the two stages of the disease. In accordance with previous studies, we found that the pathways related to regulation of cell death, chemotaxis and inflammatory response are differentially expressed in the disease in comparison to healthy subjects, while pathways related to cell adhesion, cell migration and cell-cell signaling are activated in relapse in comparison to remission. However, the current study includes a detailed report of the exact set of genes involved in these pathways and the interactions between them. For example, we found that the genes TP53 and IL1 are 'network-hub' that interacts with many of the differentially expressed genes in MS patients versus healthy subjects, and the epidermal growth factor receptor is a 'network-hub' in the case of MS patients with relapse versus remission. The statistical approaches employed in this study enabled us

  14. Context, emotion, and the strategic pursuit of goals: Interactions among multiple brain systems controlling motivated behaviour

    Directory of Open Access Journals (Sweden)

    Aaron J Gruber

    2012-08-01

    Full Text Available Motivated behaviour exhibits properties that change with experience and partially dissociate among a number of brain structures. Here, we review evidence from rodent experiments demonstrating that multiple brain systems acquire information in parallel and either cooperate or compete for behavioural control. We propose a conceptual model of systems interaction wherein a ventral emotional memory network involving ventral striatum, amygdala, ventral hippocampus, and ventromedial prefrontal cortex triages behavioural responding to stimuli according to their associated affective outcomes. This system engages autonomic and postural responding (avoiding, ignoring, approaching in accordance with associated stimulus valence (negative, neutral, positive, but does not engage particular operant responses. Rather, this emotional system suppresses or invigorates actions that are selected through competition between goal-directed control involving dorsomedial striatum and habitual control involving dorsolateral striatum. The hippocampus provides contextual specificity to the emotional system, and provides an information rich input to the goal-directed system for navigation and discriminations involving ambiguous contexts, complex sensory configurations, or temporal ordering. The rapid acquisition and high capacity for episodic associations in the emotional system may unburden the more complex goal-directed system and reduce interference in the habit system from processing contingencies of neutral stimuli. Interactions among these systems likely involve inhibitory mechanisms and neuromodulation in the basal ganglia to form a dominant response strategy. Innate traits, training methods, and task demands contribute to the nature of these interactions, which can include incidental learning in non-dominant systems. Addition of these features to reinforcement learning models of decision making may better align theoretical predictions with behavioural and neural

  15. A field comparison of multiple techniques to quantify groundwater - surface-water interactions

    Science.gov (United States)

    González-Pinzón, Ricardo; Ward, Adam S; Hatch, Christine E; Wlostowski, Adam N; Singha, Kamini; Gooseff, Michael N.; Haggerty, Roy; Harvey, Judson; Cirpka, Olaf A; Brock, James T

    2015-01-01

    Groundwater–surface-water (GW-SW) interactions in streams are difficult to quantify because of heterogeneity in hydraulic and reactive processes across a range of spatial and temporal scales. The challenge of quantifying these interactions has led to the development of several techniques, from centimeter-scale probes to whole-system tracers, including chemical, thermal, and electrical methods. We co-applied conservative and smart reactive solute-tracer tests, measurement of hydraulic heads, distributed temperature sensing, vertical profiles of solute tracer and temperature in the stream bed, and electrical resistivity imaging in a 450-m reach of a 3rd-order stream. GW-SW interactions were not spatially expansive, but were high in flux through a shallow hyporheic zone surrounding the reach. NaCl and resazurin tracers suggested different surface–subsurface exchange patterns in the upper ⅔ and lower ⅓ of the reach. Subsurface sampling of tracers and vertical thermal profiles quantified relatively high fluxes through a 10- to 20-cm deep hyporheic zone with chemical reactivity of the resazurin tracer indicated at 3-, 6-, and 9-cm sampling depths. Monitoring of hydraulic gradients along transects with MINIPOINT streambed samplers starting ∼40 m from the stream indicated that groundwater discharge prevented development of a larger hyporheic zone, which progressively decreased from the stream thalweg toward the banks. Distributed temperature sensing did not detect extensive inflow of ground water to the stream, and electrical resistivity imaging showed limited large-scale hyporheic exchange. We recommend choosing technique(s) based on: 1) clear definition of the questions to be addressed (physical, biological, or chemical processes), 2) explicit identification of the spatial and temporal scales to be covered and those required to provide an appropriate context for interpretation, and 3) maximizing generation of mechanistic understanding and reducing costs of

  16. 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

  17. Multiple stressor effects in Chlamydomonas reinhardtii – Toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Korkaric, Muris [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland); Behra, Renata; Fischer, Beat B. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); Junghans, Marion [Swiss Center for Applied Ecotoxicology Eawag-EPFL, 8600, Duebendorf (Switzerland); Eggen, Rik I.L., E-mail: rik.eggen@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland)

    2015-05-15

    Highlights: • Systematic study of multiple stressor effects of UVR and chemicals in C. reinhardtii. • UVR and chemicals did not act independently on algal photosynthesis and reproduction. • Multiple stressor effects of UVR and chemicals depended on chemical MOA. • Synergistic effect interactions not limited to oxidative stress inducing chemicals. • Multiple MOAs of UVR may limit applicability of current prediction models. - Abstract: The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are

  18. Multiple stressor effects in Chlamydomonas reinhardtii – Toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants

    International Nuclear Information System (INIS)

    Korkaric, Muris; Behra, Renata; Fischer, Beat B.; Junghans, Marion; Eggen, Rik I.L.

    2015-01-01

    Highlights: • Systematic study of multiple stressor effects of UVR and chemicals in C. reinhardtii. • UVR and chemicals did not act independently on algal photosynthesis and reproduction. • Multiple stressor effects of UVR and chemicals depended on chemical MOA. • Synergistic effect interactions not limited to oxidative stress inducing chemicals. • Multiple MOAs of UVR may limit applicability of current prediction models. - Abstract: The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are

  19. Multiple structure-intrinsic disorder interactions regulate and coordinate Hox protein function

    Science.gov (United States)

    Bondos, Sarah

    During animal development, Hox transcription factors determine fate of developing tissues to generate diverse organs and appendages. Hox proteins are famous for their bizarre mutant phenotypes, such as replacing antennae with legs. Clearly, the functions of individual Hox proteins must be distinct and reliable in vivo, or the organism risks malformation or death. However, within the Hox protein family, the DNA-binding homeodomains are highly conserved and the amino acids that contact DNA are nearly invariant. These observations raise the question: How do different Hox proteins correctly identify their distinct target genes using a common DNA binding domain? One possible means to modulate DNA binding is through the influence of the non-homeodomain protein regions, which differ significantly among Hox proteins. However genetic approaches never detected intra-protein interactions, and early biochemical attempts were hindered because the special features of ``intrinsically disordered'' sequences were not appreciated. We propose the first-ever structural model of a Hox protein to explain how specific contacts between distant, intrinsically disordered regions of the protein and the homeodomain regulate DNA binding and coordinate this activity with other Hox molecular functions.

  20. Linear reaction norm models for genetic merit prediction of Angus cattle under genotype by environment interaction.

    Science.gov (United States)

    Cardoso, F F; Tempelman, R J

    2012-07-01

    The objectives of this work were to assess alternative linear reaction norm (RN) models for genetic evaluation of Angus cattle in Brazil. That is, we investigated the interaction between genotypes and continuous descriptors of the environmental variation to examine evidence of genotype by environment interaction (G×E) in post-weaning BW gain (PWG) and to compare the environmental sensitivity of national and imported Angus sires. Data were collected by the Brazilian Angus Improvement Program from 1974 to 2005 and consisted of 63,098 records and a pedigree file with 95,896 animals. Six models were implemented using Bayesian inference and compared using the Deviance Information Criterion (DIC). The simplest model was M(1), a traditional animal model, which showed the largest DIC and hence the poorest fit when compared with the 4 alternative RN specifications accounting for G×E. In M(2), a 2-step procedure was implemented using the contemporary group posterior means of M(1) as the environmental gradient, ranging from -92.6 to +265.5 kg. Moreover, the benefits of jointly estimating all parameters in a 1-step approach were demonstrated by M(3). Additionally, we extended M(3) to allow for residual heteroskedasticity using an exponential function (M(4)) and the best fitting (smallest DIC) environmental classification model (M(5)) specification. Finally, M(6) added just heteroskedastic residual variance to M(1). Heritabilities were less at harsh environments and increased with the improvement of production conditions for all RN models. Rank correlations among genetic merit predictions obtained by M(1) and by the best fitting RN models M(3) (homoskedastic) and M(5) (heteroskedastic) at different environmental levels ranged from 0.79 and 0.81, suggesting biological importance of G×E in Brazilian Angus PWG. These results suggest that selection progress could be optimized by adopting environment-specific genetic merit predictions. The PWG environmental sensitivity of

  1. Genetic moderation of multiple pathways linking early cumulative socioeconomic adversity and young adults' cardiometabolic disease risk.

    Science.gov (United States)

    Wickrama, Kandauda A S; Lee, Tae Kyoung; O'Neal, Catherine Walker

    2018-02-01

    Recent research suggests that psychosocial resources and life stressors are mediating pathways explaining socioeconomic variation in young adults' health risks. However, less research has examined both these pathways simultaneously and their genetic moderation. A nationally representative sample of 11,030 respondents with prospective data collected over 13 years from the National Study of Adolescent to Adult Health was examined. First, the association between early cumulative socioeconomic adversity and young adults' (ages 25-34) cardiometabolic disease risk, as measured by 10 biomarkers, through psychosocial resources (educational attainment) and life stressors (accelerated transition to adulthood) was examined. Second, moderation of these pathways by the serotonin transporter linked polymorphic region gene (5-HTTLPR) was examined. There was evidence for the association between early socioeconomic adversity and young adults' cardiometabolic disease risk directly and indirectly through educational attainment and accelerated transitions. These direct and mediating pathways were amplified by the 5-HTTLPR polymorphism. These findings elucidate how early adversity can have an enduring influence on young adults' cardiometabolic disease risk directly and indirectly through psychosocial resources and life stressors and their genetic moderation. This information suggests that effective intervention and prevention programs should focus on early adversity, youth educational attainment, and their transition to young adulthood.

  2. Multiple genetic variants associated with posttransplantation diabetes mellitus in Chinese Han populations.

    Science.gov (United States)

    Chen, Jie; Li, Lixin; An, Yunfei; Zhang, Junlong; Liao, Yun; Li, Yi; Wang, Lanlan

    2018-03-01

    Posttransplantation diabetes mellitus (PTDM) is a major complication after solid organ transplantation. This study is to investigate the association of nine genetic variant factors and PTDM in Chinese Han patients. HLA-DP (rs3077, rs9277535), HLA-DQ (rs7453920), signal transducer and activator of transcription 4 (STAT4) (rs7574865), IL-28B (rs12979860, rs8099917, and rs12980275), and IL-18 (rs1946518 and rs187238) were investigated in 260 liver transplant recipients (PTDM vs non-PTDM) by high-resolution melting curve analysis. Serum interleukin (IL)-1β, IL-6, IL-8, IL-17, interferon-γ, inducible protein-10, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1b were analyzed by a Bio-Plex suspension array system (Bio-Plex Multiplex Immunoassays, Bio-Rad, Hercules, CA, USA). Signal transducer and activator of transcription 4 (rs7574865) T allele and IL-18 (rs1946518) A allele increase the risk for insulin resistance and PTDM. Recipients with STAT4 (rs7574865) T allele are associated with an increased concentration of IL-1β, interferon-γ, monocyte chemoattractant protein, and macrophage inflammatory protein-1b. The genetic variants of STAT4 (rs7574865) and IL-18 (rs1946518) may be new important markers for PTDM. © 2017 Wiley Periodicals, Inc.

  3. Dietary Magnesium and Genetic Interactions in Diabetes and Related Risk Factors: A Brief Overview of Current Knowledge

    Science.gov (United States)

    Hruby, Adela; McKeown, Nicola M.; Song, Yiqing; Djoussé, Luc

    2013-01-01

    Nutritional genomics has exploded in the last decade, yielding insights—both nutrigenomic and nutrigenetic—into the physiology of dietary interactions and our genes. Among these are insights into the regulation of magnesium transport and homeostasis and mechanisms underlying magnesium’s role in insulin and glucose handling. Recent observational evidence has attempted to examine some promising research avenues on interaction between genetics and dietary magnesium in relation to diabetes and diabetes risk factors. This brief review summarizes the recent evidence on dietary magnesium’s role in diabetes and related traits in the presence of underlying genetic risk, and discusses future potential research directions. PMID:24322525

  4. Interacting Multiple Model (IMM) Fifth-Degree Spherical Simplex-Radial Cubature Kalman Filter for Maneuvering Target Tracking.

    Science.gov (United States)

    Liu, Hua; Wu, Wen

    2017-06-13

    For improving the tracking accuracy and model switching speed of maneuvering target tracking in nonlinear systems, a new algorithm named the interacting multiple model fifth-degree spherical simplex-radial cubature Kalman filter (IMM5thSSRCKF) is proposed in this paper. The new algorithm is a combination of the interacting multiple model (IMM) filter and the fifth-degree spherical simplex-radial cubature Kalman filter (5thSSRCKF). The proposed algorithm makes use of Markov process to describe the switching probability among the models, and uses 5thSSRCKF to deal with the state estimation of each model. The 5thSSRCKF is an improved filter algorithm, which utilizes the fifth-degree spherical simplex-radial rule to improve the filtering accuracy. Finally, the tracking performance of the IMM5thSSRCKF is evaluated by simulation in a typical maneuvering target tracking scenario. Simulation results show that the proposed algorithm has better tracking performance and quicker model switching speed when disposing maneuver models compared with the interacting multiple model unscented Kalman filter (IMMUKF), the interacting multiple model cubature Kalman filter (IMMCKF) and the interacting multiple model fifth-degree cubature Kalman filter (IMM5thCKF).

  5. Interacting Multiple Model (IMM Fifth-Degree Spherical Simplex-Radial Cubature Kalman Filter for Maneuvering Target Tracking

    Directory of Open Access Journals (Sweden)

    Hua Liu

    2017-06-01

    Full Text Available For improving the tracking accuracy and model switching speed of maneuvering target tracking in nonlinear systems, a new algorithm named the interacting multiple model fifth-degree spherical simplex-radial cubature Kalman filter (IMM5thSSRCKF is proposed in this paper. The new algorithm is a combination of the interacting multiple model (IMM filter and the fifth-degree spherical simplex-radial cubature Kalman filter (5thSSRCKF. The proposed algorithm makes use of Markov process to describe the switching probability among the models, and uses 5thSSRCKF to deal with the state estimation of each model. The 5thSSRCKF is an improved filter algorithm, which utilizes the fifth-degree spherical simplex-radial rule to improve the filtering accuracy. Finally, the tracking performance of the IMM5thSSRCKF is evaluated by simulation in a typical maneuvering target tracking scenario. Simulation results show that the proposed algorithm has better tracking performance and quicker model switching speed when disposing maneuver models compared with the interacting multiple model unscented Kalman filter (IMMUKF, the interacting multiple model cubature Kalman filter (IMMCKF and the interacting multiple model fifth-degree cubature Kalman filter (IMM5thCKF.

  6. Multiplicities of secondary hadrons produced in #betta#p and anti #betta#p charged current interactions

    International Nuclear Information System (INIS)

    Graessler, H.; Lanske, D.; Schulte, R.; Chima, J.S.; Mobayyen, M.M.; Talebzadeh, M.; Villalobos-Baillie, O.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.

    1983-02-01

    In an experiment with the hydrogen bubble chamber BEBC at CERN multiplicities of hadrons produced in #betta#p and anti #betta# interactions have been investigated. Results are presented on the multiplicities of charged hadrons and neutral pions, forward and backward multiplicities of charged hadrons and correlations between forward and backward multiplicities. Comparisons are made with hadronic reactions and e + e - annihilation. In the framework of the quark-parton model the data imply similar charged multiplicities for the fragments of a u- and a d-quark, and larger multiplicities for the fragments of a uu- than for a ud-diquark. The correlation data suggest independent fragmentation of the quark and diquark for hadronic masses above approx.=7 GeV and local charge compensation within an event. (orig.)

  7. 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...

  8. Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci

    DEFF Research Database (Denmark)

    Stender, Stefan; Kozlitina, Julia; Nordestgaard, Børge G.

    2017-01-01

    sequence variants (encoding PNPLA3 p.I148M, TM6SF2 p.E167K, and GCKR p.P446L) associated with nonalcoholic fatty liver disease (NAFLD). Synergy between adiposity and genotype promoted the full spectrum of NAFLD, from steatosis to hepatic inflammation to cirrhosis. We found no evidence of strong interaction...

  9. Multiple surveys employing a new sample-processing protocol reveal the genetic diversity of placozoans in Japan.

    Science.gov (United States)

    Miyazawa, Hideyuki; Nakano, Hiroaki

    2018-03-01

    Placozoans, flat free-living marine invertebrates, possess an extremely simple bauplan lacking neurons and muscle cells and represent one of the earliest-branching metazoan phyla. They are widely distributed from temperate to tropical oceans. Based on mitochondrial 16S rRNA sequences, 19 haplotypes forming seven distinct clades have been reported in placozoans to date. In Japan, placozoans have been found at nine locations, but 16S genotyping has been performed at only two of these locations. Here, we propose a new processing protocol, "ethanol-treated substrate sampling," for collecting placozoans from natural environments. We also report the collection of placozoans from three new locations, the islands of Shikine-jima, Chichi-jima, and Haha-jima, and we present the distribution of the 16S haplotypes of placozoans in Japan. Multiple surveys conducted at multiple locations yielded five haplotypes that were not reported previously, revealing high genetic diversity in Japan, especially at Shimoda and Shikine-jima Island. The observed geographic distribution patterns were different among haplotypes; some were widely distributed, while others were sampled only from a single location. However, samplings conducted on different dates at the same sites yielded different haplotypes, suggesting that placozoans of a given haplotype do not inhabit the same site constantly throughout the year. Continued sampling efforts conducted during all seasons at multiple locations worldwide and the development of molecular markers within the haplotypes are needed to reveal the geographic distribution pattern and dispersal history of placozoans in greater detail.

  10. The interaction of genetics and environmental toxicants in amyotrophic lateral sclerosis: results from animal models

    Institute of Scientific and Technical Information of China (English)

    Roger B. Sher

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in the progres-sive death of motor neurons, leading to paralysis and eventual death. There is presently no cure for ALS, and only two drugs are available, neither of which provide significant extension of life. The wide variation in onset and progression of the disease, both in sporadic and even in strongly penetrant monogenic famil-ial forms of ALS, indicate that in addition to background genetic variation impacting the disease process, environmental exposures are likely contributors. Epidemiological evidence worldwide implicates exposures to bacterial toxins, heavy metals, pesticides, and trauma as probable environmental factors. Here, we review current advances in gene-environment interactions in ALS animal models. We report our recent discov-eries in a zebrafish model of ALS in relation to exposure to the cyanobacterial toxin BMAA, and discuss several results from mouse models that show interactions with exposure to mercury and statin drugs, both leading to acceleration of the disease process. The increasing research into this combinatorial gene-environ-ment process is just starting, but shows early promise to uncover the underlying biochemical pathways that instigate the initial motor neuron defects and lead to their rapidly progressive dysfunction.

  11. Multi-location wheat stripe rust QTL analysis: genetic background and epistatic interactions.

    Science.gov (United States)

    Vazquez, M Dolores; Zemetra, Robert; Peterson, C James; Chen, Xianming M; Heesacker, Adam; Mundt, Christopher C

    2015-07-01

    Epistasis and genetic background were important influences on expression of stripe rust resistance in two wheat RIL populations, one with resistance conditioned by two major genes and the other conditioned by several minor QTL. Stripe rust is a foliar disease of wheat (Triticum aestivum L.) caused by the air-borne fungus Puccinia striiformis f. sp. tritici and is present in most regions around the world where commercial wheat is grown. Breeding for durable resistance to stripe rust continues to be a priority, but also is a challenge due to the complexity of interactions among resistance genes and to the wide diversity and continuous evolution of the pathogen races. The goal of this study was to detect chromosomal regions for resistance to stripe rust in two winter wheat populations, 'Tubbs'/'NSA-98-0995' (T/N) and 'Einstein'/'Tubbs' (E/T), evaluated across seven environments and mapped with diversity array technology and simple sequence repeat markers covering polymorphic regions of ≈1480 and 1117 cM, respectively. Analysis of variance for phenotypic data revealed significant (P located in chromosomes 2AS and 6AL, with epistatic interaction between them, were responsible for the main phenotypic response. For the T/N population, eight QTL were identified, with those in chromosomes 2AL and 2BL accounting for the largest percentage of the phenotypic variance.

  12. Construction and application of a protein and genetic interaction network (yeast interactome).

    Science.gov (United States)

    Stuart, Gregory R; Copeland, William C; Strand, Micheline K

    2009-04-01

    Cytoscape is a bioinformatic data analysis and visualization platform that is well-suited to the analysis of gene expression data. To facilitate the analysis of yeast microarray data using Cytoscape, we constructed an interaction network (interactome) using the curated interaction data available from the Saccharomyces Genome Database (www.yeastgenome.org) and the database of yeast transcription factors at YEASTRACT (www.yeastract.com). These data were formatted and imported into Cytoscape using semi-automated methods, including Linux-based scripts, that simplified the process while minimizing the introduction of processing errors. The methods described for the construction of this yeast interactome are generally applicable to the construction of any interactome. Using Cytoscape, we illustrate the use of this interactome through the analysis of expression data from a recent yeast diauxic shift experiment. We also report and briefly describe the complex associations among transcription factors that result in the regulation of thousands of genes through coordinated changes in expression of dozens of transcription factors. These cells are thus able to sensitively regulate cellular metabolism in response to changes in genetic or environmental conditions through relatively small changes in the expression of large numbers of genes, affecting the entire yeast metabolome.

  13. Genetic Variants in Epigenetic Pathways and Risks of Multiple Cancers in the GAME-ON Consortium.

    Science.gov (United States)

    Toth, Reka; Scherer, Dominique; Kelemen, Linda E; Risch, Angela; Hazra, Aditi; Balavarca, Yesilda; Issa, Jean-Pierre J; Moreno, Victor; Eeles, Rosalind A; Ogino, Shuji; Wu, Xifeng; Ye, Yuanqing; Hung, Rayjean J; Goode, Ellen L; Ulrich, Cornelia M

    2017-06-01

    Background: Epigenetic disturbances are crucial in cancer initiation, potentially with pleiotropic effects, and may be influenced by the genetic background. Methods: In a subsets (ASSET) meta-analytic approach, we investigated associations of genetic variants related to epigenetic mechanisms with risks of breast, lung, colorectal, ovarian and prostate carcinomas using 51,724 cases and 52,001 controls. False discovery rate-corrected P values (q values cancer type. For example, variants in BABAM1 were confirmed as a susceptibility locus for squamous cell lung, overall breast, estrogen receptor (ER)-negative breast, and overall prostate, and overall serous ovarian cancer; the most significant variant was rs4808076 [OR = 1.14; 95% confidence interval (CI) = 1.10-1.19; q = 6.87 × 10 -5 ]. DPF1 rs12611084 was inversely associated with ER-negative breast, endometrioid ovarian, and overall and aggressive prostate cancer risk (OR = 0.93; 95% CI = 0.91-0.96; q = 0.005). Variants in L3MBTL3 were associated with colorectal, overall breast, ER-negative breast, clear cell ovarian, and overall and aggressive prostate cancer risk (e.g., rs9388766: OR = 1.06; 95% CI = 1.03-1.08; q = 0.02). Variants in TET2 were significantly associated with overall breast, overall prostate, overall ovarian, and endometrioid ovarian cancer risk, with rs62331150 showing bidirectional effects. Analyses of subpathways did not reveal gene subsets that contributed disproportionately to susceptibility. Conclusions: Functional and correlative studies are now needed to elucidate the potential links between germline genotype, epigenetic function, and cancer etiology. Impact: This approach provides novel insight into possible pleiotropic effects of genes involved in epigenetic processes. Cancer Epidemiol Biomarkers Prev; 26(6); 816-25. ©2017 AACR . ©2017 American Association for Cancer Research.

  14. On the use of sibling recurrence risks to select environmental factors liable to interact with genetic risk factors.

    Science.gov (United States)

    Kazma, Rémi; Bonaïti-Pellié, Catherine; Norris, Jill M; Génin, Emmanuelle

    2010-01-01

    Gene-environment interactions are likely to be involved in the susceptibility to multifactorial diseases but are difficult to detect. Available methods usually concentrate on some particular genetic and environmental factors. In this paper, we propose a new method to determine whether a given exposure is susceptible to interact with unknown genetic factors. Rather than focusing on a specific genetic factor, the degree of familial aggregation is used as a surrogate for genetic factors. A test comparing the recurrence risks in sibs according to the exposure of indexes is proposed and its power is studied for varying values of model parameters. The Exposed versus Unexposed Recurrence Analysis (EURECA) is valuable for common diseases with moderate familial aggregation, only when the role of exposure has been clearly outlined. Interestingly, accounting for a sibling correlation for the exposure increases the power of EURECA. An application on a sample ascertained through one index affected with type 2 diabetes is presented where gene-environment interactions involving obesity and physical inactivity are investigated. Association of obesity with type 2 diabetes is clearly evidenced and a potential interaction involving this factor is suggested in Hispanics (P=0.045), whereas a clear gene-environment interaction is evidenced involving physical inactivity only in non-Hispanic whites (P=0.028). The proposed method might be of particular interest before genetic studies to help determine the environmental risk factors that will need to be accounted for to increase the power to detect genetic risk factors and to select the most appropriate samples to genotype.

  15. Genetics, mental illness, and complex disease: development and distribution of an interactive CD-ROM for genetic counselors. Final report for period 15 August 2000 - 31 December 2002

    Energy Technology Data Exchange (ETDEWEB)

    McInerney, Joseph D.

    2003-03-31

    "Genetics and Major Psychiatric Disorders: A Program for Genetic Counselors" provides an introduction to psychiatric genetics, with a focus on the genetics of common complex disease, for genetics professionals. The program is available as a CD-ROM and an online educational resource. The on-line version requires a direct internet connection. Each educational module begins with an interactive case study that raises significant issues addressed in each module. In addition, case studies provided throughout the educational materials support teaching of major concepts. Incorporated throughout the content are expert video clips, video clips from individuals affected by psychiatric illness, and optional "learn more" materials that offer greater depth about a particular topic. The structure of the CD-ROM permits self-navigation, but we have suggested a sequence that allows materials to build upon each other. At any point in the materials, users may pause and look up terms in the glossary or review the DSM-IV criteria for selected psychiatric disorders. A detailed site map is available for those who choose to self navigate through the content.

  16. Multiple interacting factors influence adherence, and outcomes associated with surgical safety checklists: a qualitative study.

    Directory of Open Access Journals (Sweden)

    Anna R Gagliardi

    Full Text Available The surgical safety checklist (SSC is meant to enhance patient safety but studies of its impact conflict. This study explored factors that influenced SSC adherence to suggest how its impact could be optimized.Participants were recruited purposively by profession, region, hospital type and time using the SSC. They were asked to describe how the SSC was adopted, associated challenges, perceived impact, and suggestions for improving its use. Grounded theory and thematic analysis were used to collect and analyse data. Findings were interpreted using an implementation fidelity conceptual framework.Fifty-one participants were interviewed (29 nurses, 13 surgeons, 9 anaesthetists; 18 small, 14 large and 19 teaching hospitals; 8 regions; 31 had used the SC for ≤12 months, 20 for 13+ months. The SSC was inconsistently reviewed, and often inaccurately documented as complete. Adherence was influenced by multiple issues. Extensive modification to accommodate existing practice patterns eliminated essential interaction at key time points to discuss patient management. Staff were often absent or not paying attention. They did not feel it was relevant to their work given limited evidence of its effectiveness, and because they were not engaged in its implementation. Organizations provided little support for implementation, training, monitoring and feedback, which are needed to overcome these, and other individual and team factors that challenged SSC adherence. Responses were similar across participants with different characteristics.Multiple processes and factors influenced SSC adherence. This may explain why, in studies evaluating SSC impact, outcomes were variable. Recommendations included continuing education, time for pilot-testing, and engaging all staff in SSC review. Others may use the implementation fidelity framework to plan SSC implementation or evaluate SSC adherence. Further research is needed to establish which SSC components can be modified

  17. Genetic variations of patients with familial or multiple melanoma in Southern Brazil.

    Science.gov (United States)

    Grazziotin, T C; Rey, M C W; Bica, C G; Pinto, L A; Bonamigo, R R; Puig-Butille, J A; Cuellar, F; Puig, S

    2013-02-01

    Patients with familial melanoma or multiple primary melanoma represent a high-risk population to hereditary melanoma. Mutations in susceptibility genes, such as CDKN2A, CDK4 and MC1R, have been associated with the development of melanoma. The purpose of this study was to determine the genotypic background of patients with familial and/or multiple melanoma in southern Brazil. This study analysed 33 cases (5 patients with multiple primary melanoma and 28 patients from families with at least two well documented cases) and 29 controls. Genomic analysis of CDKN2A and CDK4 genes by PCR-SSCP analysis and sequencing and direct sequencing of MC1R were performed in all individuals. No functional mutations in CDKN2A or CDK4 were detected in the 62 individuals. Infrequent variants in polymorphic loci of CDKN2A gene were identified in 15 participants (24.2%) and 24/33 (72.8%) cases and 19/27 (70.4%) controls reported at least one infrequent variant in MC1R (P = 0.372). Furthermore, a non-significant tendency towards an association between melanoma risk and MC1R variants G274A and C451T and a non-significant linear tendency to the number of infrequent high-risk variants in MC1R were observed. These results suggest that in southern Brazilian population, CDKN2A or CDK4 germinal alterations may have a weaker influence than previously thought and environmental risk factors may play a central role in melanoma susceptibility. However, considering the tendency observed for gene MC1R, low-penetrance genes may be a relevant aetiological factor in southern Brazil with fair skin population and high sunlight exposure. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  18. Possible modification of Alzheimer's disease by statins in midlife: interactions with genetic and non-genetic risk factors.

    Science.gov (United States)

    Shinohara, Mitsuru; Sato, Naoyuki; Shimamura, Munehisa; Kurinami, Hitomi; Hamasaki, Toshimitsu; Chatterjee, Amarnath; Rakugi, Hiromi; Morishita, Ryuichi

    2014-01-01

    The benefits of statins, commonly prescribed for hypercholesterolemia, in treating Alzheimer's disease (AD) have not yet been fully established. A recent randomized clinical trial did not show any therapeutic effects of two statins on cognitive function in AD. Interestingly, however, the results of the Rotterdam study, one of the largest prospective cohort studies, showed reduced risk of AD in statin users. Based on the current understanding of statin actions and AD pathogenesis, it is still worth exploring whether statins can prevent AD when administered decades before the onset of AD or from midlife. This review discusses the possible beneficial effects of statins, drawn from previous clinical observations, pathogenic mechanisms, which include β-amyloid (Aβ) and tau metabolism, genetic and non-genetic risk factors (apolipoprotein E, cholesterol, sex, hypertension, and diabetes), and other clinical features (vascular dysfunction and oxidative and inflammatory stress) of AD. These findings suggest that administration of statins in midlife might prevent AD in late life by modifying genetic and non-genetic risk factors for AD. It should be clarified whether statins inhibit Aβ accumulation, tau pathological features, and brain atrophy in humans. To answer this question, a randomized controlled study using amyloid positron emission tomography (PET), tau-PET, and magnetic resonance imaging would be useful. This clinical evaluation could help us to overcome this devastating disease.

  19. LES of n-Dodecane Spray Combustion Using a Multiple Representative Interactive Flamelets Model

    Directory of Open Access Journals (Sweden)

    Davidovic Marco

    2017-09-01

    Full Text Available A single-hole n-dodecane spray flame is studied in a Large-Eddy Simulation (LES framework under Diesel-relevant conditions using a Multiple Representative Interactive Flamelets (MRIF combustion model. Diesel spray combustion is strongly affected by the mixture formation process, which is dominated by several physical processes such as the flow within the injector, break-up of the liquid fuel jet, evaporation and turbulent mixing with the surrounding gas. While the effects of nozzle-internal flow and primary breakup are captured within tuned model parameters in traditional Lagrangian spray models, an alternative approach is applied in this study, where the initial droplet conditions and primary fuel jet breakup are modeled based on results from highly resolved multiphase simulations with resolved interface. A highly reduced chemical mechanism consisting of 57 species and 217 reactions has been developed for n-dodecane achiving a good computational performance at solving the chemical reactions. The MRIF model, which has demonstrated its capability of capturing combustion and pollutant formation under typical Diesel conditions in Reynolds-Averaged Navier-Stokes (RANS simulations is extended for the application in LES. In the standard RIF combustion model, representative chemistry conditioned on mixture fraction is solved interactively with the flow. Subfilter-scale mixing is modeled by the scalar dissipation rate. While the standard RIF model only includes temporal changes of the scalar dissipation rate, the spatial distribution can be accounted for by extending the model to multiple flamelets, which also enables the possibility of capturing different fuel residence times. Overall, the model shows good agreement with experimental data regarding both, low and high temperature combustion characteristics. It is shown that the ignition process and pollutant formation are affected by turbulent mixing. First, a cool flame is initiated at approximately

  20. Neutrino interactions with e+μ- and multiple K0's

    International Nuclear Information System (INIS)

    Stevenson, M.L.

    1976-07-01

    A scan for directly produced positrons in 5,000 neutrino interactions in the neon (21 percent) hydrogen filled bubble chamber at Fermilab has yielded 15 events, 9 of which have μ - 's identified in the external muon identifier. On correcting for detection efficiency one obtains sigma(e + μ - )/sigma(μ - ) approximately 1 x 10 -2 for E/sub e + / > .8 GeV and E/sub ν/ > 5 GeV. The kaon multiplicity is unexpectedly high. Eleven of the events have one or more Vees and three have two or more. Among the 11 events are two clear Λ's and two ambiguous K 0 /Λ. There are four events with identifiable charged kaons. A 16th e + event (9) is a definite ν/sub e/. From this information one concludes that the kaon multiplicity is 2 +- .6 K 0 's and 2 +- 1 K +- 's per interaction. From the observation - />/ + /> = 6.6, one concludes that the e + 's are probably not uniquely from heavy lepton decay. From a variety of analyses involving the e + and/or K 0 's one learns that the mass of the hadron (C) that produces the e + 's is greater than 1.6 GeV. By determining the fraction of normal charged current (CC) events that have K 0 /sub s/ → π + π - one is able to compare this fraction with the fraction of CC events that have e + μ - (K 0 /sub s/ → π + π - ) to establish a conservative lower limit to the semileptonic branching ratio, C → (e + and μ + ) ν/C → all > 0.33 (1 +- .42), provided that the same number of K 0 /sub s/ exists in thenonleptonic decays as in the semileptonic ones, and that the phase space for μ + and e + are nearly equal. There is no compelling evidence for an energy threshold and there is a hint of some neutral current events among the e + events

  1. The Interaction among Microbiota, Immunity, and Genetic and Dietary Factors Is the Condicio Sine Qua Non Celiac Disease Can Develop

    Directory of Open Access Journals (Sweden)

    D. Pagliari

    2015-01-01

    Full Text Available Celiac disease (CD is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. This is a complex disorder involving both environmental and immune-genetic factors. The major genetic risk factor for CD is determined by HLA-DQ genes. Dysfunction of the innate and adaptive immune systems can conceivably cause impairment of mucosal barrier function and development of localized or systemic inflammatory and autoimmune processes. Exposure to gluten is the main environmental trigger responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Thus, both genetic determination and environmental exposure to gluten are necessary for the full manifestation of CD; neither of them is sufficient alone. Epidemiological and clinical data suggest that other environmental factors, including infections, alterations in the intestinal microbiota composition, and early feeding practices, might also play a role in disease development. Thus, this interaction is the condicio sine qua non celiac disease can develop. The breakdown of the interaction among microbiota, innate immunity, and genetic and dietary factors leads to disruption of homeostasis and inflammation; and tissue damage occurs. Focusing attention on this interaction and its breakdown may allow a better understanding of the CD pathogenesis and lead to novel translational avenues for preventing and treating this widespread disease.

  2. Evolution in quantum leaps: multiple combinatorial transfers of HPI and other genetic modules in Enterobacteriaceae.

    Directory of Open Access Journals (Sweden)

    Armand Paauw

    Full Text Available Horizontal gene transfer is a key step in the evolution of Enterobacteriaceae. By acquiring virulence determinants of foreign origin, commensals can evolve into pathogens. In Enterobacteriaceae, horizontal transfer of these virulence determinants is largely dependent on transfer by plasmids, phages, genomic islands (GIs and genomic modules (GMs. The High Pathogenicity Island (HPI is a GI encoding virulence genes that can be transferred between different Enterobacteriaceae. We investigated the HPI because it was present in an Enterobacter hormaechei outbreak strain (EHOS. Genome sequence analysis showed that the EHOS contained an integration site for mobile elements and harbored two GIs and three putative GMs, including a new variant of the HPI (HPI-ICEEh1. We demonstrate, for the first time, that combinatorial transfers of GIs and GMs between Enterobacter cloacae complex isolates must have occurred. Furthermore, the excision and circularization of several combinations of the GIs and GMs was demonstrated. Because of its flexibility, the multiple integration site of mobile DNA can be considered an integration hotspot (IHS that increases the genomic plasticity of the bacterium. Multiple combinatorial transfers of diverse combinations of the HPI and other genomic elements among Enterobacteriaceae may accelerate the generation of new pathogenic strains.

  3. On the thermoluminescent interactive multiple-trap system (IMTS) model: is it a simple model?

    International Nuclear Information System (INIS)

    Gil T, M. I.; Perez C, L.; Cruz Z, E.; Furetta, C.; Roman L, J.

    2016-10-01

    In the thermally stimulated luminescence phenomenon, named thermoluminescence (Tl), the electrons and holes generated by the radiation-matter interaction can be trapped by the metastable levels in the band gap of the solid. Following, the electron can be thermally releases into the conduction band and a radiatively recombination with hole close to the recombination center occurred and the glow curve is emitted. However, the complex mechanism of trapping and thermally releases occurred in the band gap of solid. Some models, such as; first, second and general-order kinetics, have been well established to explain the behaviour of the glow curves and their defects recombination mechanism. In this work, expressions for and Interactive Multiple-Trap System model (IMTS) was obtained assuming: a set of discrete electron traps (active traps At), another set of thermally disconnected trap (TDT) and a recombination center (Rc) too. A numerical analysis based on the Levenberg-Marquardt method in conjunction with an implicit Rosenbrock method was taken into account to simulate the glow curve. The numerical method was tested through synthetic Tl glow curves for a wide range of trap parameters. The activation energy and kinetics order were determined using values from the General Order Kinetics (GOK) model as entry data to IMTS model. This model was tested using the experimental glow curves obtained from Ce or Eu-doped MgF 2 (LiF) polycrystals samples. Results shown that the IMTS model can predict more accurately the behavior of the Tl glow curves that those obtained by the GOK modified by Rasheedy and by the Mixed Order Kinetics model. (Author)

  4. On the thermoluminescent interactive multiple-trap system (IMTS) model: is it a simple model?

    Energy Technology Data Exchange (ETDEWEB)

    Gil T, M. I.; Perez C, L. [UNAM, Facultad de Quimica, Ciudad Universitaria, 04510 Ciudad de Mexico (Mexico); Cruz Z, E.; Furetta, C.; Roman L, J., E-mail: ecruz@nucleares.unam.mx [UNAM, Instituto de Ciencias Nucleares, Ciudad Universitaria, 04510 Ciudad de Mexico (Mexico)

    2016-10-15

    In the thermally stimulated luminescence phenomenon, named thermoluminescence (Tl), the electrons and holes generated by the radiation-matter interaction can be trapped by the metastable levels in the band gap of the solid. Following, the electron can be thermally releases into the conduction band and a radiatively recombination with hole close to the recombination center occurred and the glow curve is emitted. However, the complex mechanism of trapping and thermally releases occurred in the band gap of solid. Some models, such as; first, second and general-order kinetics, have been well established to explain the behaviour of the glow curves and their defects recombination mechanism. In this work, expressions for and Interactive Multiple-Trap System model (IMTS) was obtained assuming: a set of discrete electron traps (active traps At), another set of thermally disconnected trap (TDT) and a recombination center (Rc) too. A numerical analysis based on the Levenberg-Marquardt method in conjunction with an implicit Rosenbrock method was taken into account to simulate the glow curve. The numerical method was tested through synthetic Tl glow curves for a wide range of trap parameters. The activation energy and kinetics order were determined using values from the General Order Kinetics (GOK) model as entry data to IMTS model. This model was tested using the experimental glow curves obtained from Ce or Eu-doped MgF{sub 2}(LiF) polycrystals samples. Results shown that the IMTS model can predict more accurately the behavior of the Tl glow curves that those obtained by the GOK modified by Rasheedy and by the Mixed Order Kinetics model. (Author)

  5. Parametric optimization of multiple quality characteristics in laser cutting of Inconel-718 by using hybrid approach of multiple regression analysis and genetic algorithm

    Science.gov (United States)

    Shrivastava, Prashant Kumar; Pandey, Arun Kumar

    2018-06-01

    Inconel-718 has found high demand in different industries due to their superior mechanical properties. The traditional cutting methods are facing difficulties for cutting these alloys due to their low thermal potential, lower elasticity and high chemical compatibility at inflated temperature. The challenges of machining and/or finishing of unusual shapes and/or sizes in these materials have also faced by traditional machining. Laser beam cutting may be applied for the miniaturization and ultra-precision cutting and/or finishing by appropriate control of different process parameter. This paper present multi-objective optimization the kerf deviation, kerf width and kerf taper in the laser cutting of Incone-718 sheet. The second order regression models have been developed for different quality characteristics by using the experimental data obtained through experimentation. The regression models have been used as objective function for multi-objective optimization based on the hybrid approach of multiple regression analysis and genetic algorithm. The comparison of optimization results to experimental results shows an improvement of 88%, 10.63% and 42.15% in kerf deviation, kerf width and kerf taper, respectively. Finally, the effects of different process parameters on quality characteristics have also been discussed.

  6. Complex Genotype by Environment interactions and changing genetic architectures across thermal environments in the Australian field cricket, Teleogryllus oceanicus

    Directory of Open Access Journals (Sweden)

    Dowling Damian K

    2011-07-01

    Full Text Available Abstract Background Biologists studying adaptation under sexual selection have spent considerable effort assessing the relative importance of two groups of models, which hinge on the idea that females gain indirect benefits via mate discrimination. These are the good genes and genetic compatibility models. Quantitative genetic studies have advanced our understanding of these models by enabling assessment of whether the genetic architectures underlying focal phenotypes are congruent with either model. In this context, good genes models require underlying additive genetic variance, while compatibility models require non-additive variance. Currently, we know very little about how the expression of genotypes comprised of distinct parental haplotypes, or how levels and types of genetic variance underlying key phenotypes, change across environments. Such knowledge is important, however, because genotype-environment interactions can have major implications on the potential for evolutionary responses to selection. Results We used a full diallel breeding design to screen for complex genotype-environment interactions, and genetic architectures underlying key morphological traits, across two thermal environments (the lab standard 27°C, and the cooler 23°C in the Australian field cricket, Teleogryllus oceanicus. In males, complex three-way interactions between sire and dam parental haplotypes and the rearing environment accounted for up to 23 per cent of the scaled phenotypic variance in the traits we measured (body mass, pronotum width and testes mass, and each trait harboured significant additive genetic variance in the standard temperature (27°C only. In females, these three-way interactions were less important, with interactions between the paternal haplotype and rearing environment accounting for about ten per cent of the phenotypic variance (in body mass, pronotum width and ovary mass. Of the female traits measured, only ovary mass for crickets

  7. An interaction map of circulating metabolites, immune gene networks, and their genetic regulation.

    Science.gov (United States)

    Nath, Artika P; Ritchie, Scott C; Byars, Sean G; Fearnley, Liam G; Havulinna, Aki S; Joensuu, Anni; Kangas, Antti J; Soininen, Pasi; Wennerström, Annika; Milani, Lili; Metspalu, Andres; Männistö, Satu; Würtz, Peter; Kettunen, Johannes; Raitoharju, Emma; Kähönen, Mika; Juonala, Markus; Palotie, Aarno; Ala-Korpela, Mika; Ripatti, Samuli; Lehtimäki, Terho; Abraham, Gad; Raitakari, Olli; Salomaa, Veikko; Perola, Markus; Inouye, Michael

    2017-08-01

    Immunometabolism plays a central role in many cardiometabolic diseases. However, a robust map of immune-related gene networks in circulating human cells, their interactions with metabolites, and their genetic control is still lacking. Here, we integrate blood transcriptomic, metabolomic, and genomic profiles from two population-based cohorts (total N = 2168), including a subset of individuals with matched multi-omic data at 7-year follow-up. We identify topologically replicable gene networks enriched for diverse immune functions including cytotoxicity, viral response, B cell, platelet, neutrophil, and mast cell/basophil activity. These immune gene modules show complex patterns of association with 158 circulating metabolites, including lipoprotein subclasses, lipids, fatty acids, amino acids, small molecules, and CRP. Genome-wide scans for module expression quantitative trait loci (mQTLs) reveal five modules with mQTLs that have both cis and trans effects. The strongest mQTL is in ARHGEF3 (rs1354034) and affects a module enriched for platelet function, independent of platelet counts. Modules of mast cell/basophil and neutrophil function show temporally stable metabolite associations over 7-year follow-up, providing evidence that these modules and their constituent gene products may play central roles in metabolic inflammation. Furthermore, the strongest mQTL in ARHGEF3 also displays clear temporal stability, supporting widespread trans effects at this locus. This study provides a detailed map of natural variation at the blood immunometabolic interface and its genetic basis, and may facilitate subsequent studies to explain inter-individual variation in cardiometabolic disease.

  8. Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors.

    Science.gov (United States)

    Gianfrancesco, Milena A; Acuna, Brigid; Shen, Ling; Briggs, Farren B S; Quach, Hong; Bellesis, Kalliope H; Bernstein, Allan; Hedstrom, Anna K; Kockum, Ingrid; Alfredsson, Lars; Olsson, Tomas; Schaefer, Catherine; Barcellos, Lisa F

    2014-01-01

    To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied. In analyses stratified by gender, being overweight at ages 10 and 20 were associated with MS in females (pchildhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  9. Study of charged hadron multiplicities in charged-current neutrino-lead interactions in the OPERA detector

    Energy Technology Data Exchange (ETDEWEB)

    Agafonova, N.; Malgin, A.; Matveev, V.; Ryazhskaya, O.; Shakirianova, I. [INR - Institute for Nuclear Research, Russian Academy of Sciences, Moscow (Russian Federation); Aleksandrov, A.; Buontempo, S.; Consiglio, L.; Tioukov, V.; Voevodina, E. [INFN Sezione di Napoli, Naples (Italy); Anokhina, A.; Dzhatdoev, T.; Podgrudkov, D.; Roganova, T. [Lomonosov Moscow State University, SINP MSU - Skobeltsyn Institute of Nuclear Physics, Moscow (Russian Federation); Aoki, S.; Hara, T.; Mizutani, F.; Ozaki, K.; Shibayama, E.; Takahashi, S. [Kobe University, Kobe (Japan); Ariga, A.; Ereditato, A.; Kreslo, I.; Vuilleumier, J.L. [University of Bern, Laboratory for High Energy Physics (LHEP), Albert Einstein Center for Fundamental Physics, Bern (Switzerland); Ariga, T. [University of Bern, Laboratory for High Energy Physics (LHEP), Albert Einstein Center for Fundamental Physics, Bern (Switzerland); Kyushu University, Faculty of Arts and Science, Fukuoka (Japan); Bertolin, A.; Dusini, S.; Kose, U.; Longhin, A.; Pupilli, F.; Stanco, L. [INFN Sezione di Padova, Padua (Italy); Bodnarchuk, I.; Chukanov, A.; Dmitrievski, S.; Gornushkin, Y.; Sotnikov, A.; Vasina, S. [JINR - Joint Institute for Nuclear Research, Dubna (Russian Federation); Bozza, C.; Grella, G.; Stellacci, S.M. [Dipartimento di Fisica, Universita di Salerno (Italy); ' ' Gruppo Collegato' ' INFN, Fisciano, Salerno (Italy); Brugnera, R.; Garfagnini, A.; Laudisio, F.; Medinaceli, E.; Roda, M.; Sirignano, C. [INFN Sezione di Padova, Padua (Italy); Dipartimento di Fisica e Astronomia, Universita di Padova, Padua (Italy); Buonaura, A.; De Lellis, G.; Di Crescenzo, A.; Galati, G.; Hosseini, B.; Lauria, A.; Montesi, M.C.; Strolin, P. [INFN Sezione di Napoli, Naples (Italy); Dipartimento di Fisica, Universita Federico II di Napoli, Naples (Italy); Chernyavskiy, M.; Gorbunov, S.; Okateva, N.; Shchedrina, T.; Starkov, N. [LPI - Lebedev Physical Institute, Russian Academy of Sciences, Moscow (Russian Federation); D' Ambrosio, N.; Di Marco, N.; Schembri, A. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); De Serio, M.; Muciaccia, M.T.; Paparella, L.; Pastore, A.; Simone, S. [Dipartimento di Fisica, Universita di Bari, Bari (Italy); INFN Sezione di Bari, Bari (Italy); Amo Sanchez, P. del; Duchesneau, D.; Pessard, H. [LAPP, Universite Savoie Mont Blanc, CNRS/IN2P3, Annecy-le-Vieux (France); Di Ferdinando, D.; Mandrioli, G.; Patrizii, L.; Sirri, G.; Tenti, M. [INFN Sezione di Bologna, Bologna (Italy); Dracos, M.; Jollet, C.; Meregaglia, A. [IPHC, Universite de Strasbourg, CNRS/IN2P3, Strasbourg (France); Ebert, J.; Hagner, C.; Hollnagel, A.; Wonsak, B. [Hamburg University, Hamburg (Germany); Fini, R.A. [INFN Sezione di Bari, Bari (Italy); Fornari, F.; Mauri, N.; Pasqualini, L.; Pozzato, M. [INFN Sezione di Bologna, Bologna (Italy); Dipartimento di Fisica e Astronomia, Universita di Bologna, Bologna (Italy); Fukuda, T.; Hayakawa, T.; Ishiguro, K.; Kitagawa, N.; Komatsu, M.; Miyanishi, M.; Morishima, K.; Naganawa, N.; Naka, T.; Nakamura, M.; Nakano, T.; Niwa, K.; Rokujo, H.; Sato, O.; Shiraishi, T. [Nagoya University, Nagoya (Japan); Gentile, V. [Gran Sasso Science Institute, L' Aquila (Italy); Goldberg, J. [Technion, Department of Physics, Haifa (Israel); Guler, A.M.; Kamiscioglu, M. [METU - Middle East Technical University, Ankara (Turkey); Gustavino, C.; Loverre, P.; Monacelli, P.; Rosa, G. [INFN Sezione di Roma, Rome (Italy); Jakovcic, K.; Ljubicic, A.; Malenica, M. [Rudjer Boskovic Institute, Zagreb (Croatia); Kamiscioglu, C. [METU - Middle East Technical University, Ankara (Turkey); Ankara University, Ankara (Turkey); Kim, S.H.; Park, B.D.; Yoon, C.S. [Gyeongsang National University, Jinju (Korea, Republic of); Klicek, B.; Stipcevic, M. [Center of Excellence for Advanced Materials and Sensing Devices, Ruder Boskovic Institute, Zagreb (Croatia); Kodama, K. [Aichi University of Education, Kariya, Aichi (Japan); Matsuo, T.; Ogawa, S.; Shibuya, H. [Toho University, Funabashi (Japan); Mikado, S. [Nihon University, Narashino, Chiba (Japan); Paoloni, A.; Spinetti, M.; Votano, L. [INFN - Laboratori Nazionali di Frascati, Rome (Italy); Polukhina, N. [LPI - Lebedev Physical Institute, Russian Academy of Sciences, Moscow (Russian Federation); Moscow Engineering Physical Institute Moscow, Moscow (Russian Federation); Terranova, F. [Dipartimento di Fisica, Universita di Milano-Bicocca, Milan (Italy); Vilain, P.; Wilquet, G. [IIHE, Universite Libre de Bruxelles, Brussels (Belgium)

    2018-01-15

    The OPERA experiment was designed to search for ν{sub μ} → ν{sub τ} oscillations in appearance mode through the direct observation of tau neutrinos in the CNGS neutrino beam. In this paper, we report a study of the multiplicity of charged particles produced in charged-current neutrino interactions in lead. We present charged hadron average multiplicities, their dispersion and investigate the KNO scaling in different kinematical regions. The results are presented in detail in the form of tables that can be used in the validation of Monte Carlo generators of neutrino-lead interactions. (orig.)

  10. Multiplicity and transverse momentum fluctuations in inelastic proton-proton interactions at the CERN Super Proton Synchrotron

    International Nuclear Information System (INIS)

    Aduszkiewicz, A.; Dominik, W.; Kuich, M.; Matulewicz, T.; Posiadala, M.; Ali, Y.; Brzychczyk, J.; Larsen, D.; Planeta, R.; Richter-Was, E.; Staszel, P.; Wyszynski, O.; Andronov, E.; Feofilov, G.A.; Igolkin, S.; Kondratiev, V.P.; Seryakov, A.; Vechernin, V.V.; Vinogradov, L.; Anticic, T.; Kadija, K.; Susa, T.; Antoniou, N.; Christakoglou, P.; Davis, N.; Diakonos, F.; Kapoyannis, A.; Panagiotou, A.D.; Vassiliou, M.; Baatar, B.; Bunyatov, S.A.; Kolesnikov, V.I.; Krasnoperov, A.; Lyubushkin, V.V.; Malakhov, A.I.; Matveev, V.; Melkumov, G.L.; Tereshchenko, V.; Bay, F.; Di Luise, S.; Rubbia, A.; Sgalaberna, D.; Blondel, A.; Bravar, A.; Debieux, S.; Haesler, A.; Korzenev, A.; Ravonel, M.; Bluemer, J.; Dembinski, H.; Engel, R.; Herve, A.; Mathes, H.J.; Roth, M.; Szuba, M.; Ulrich, R.; Unger, M.; Veberic, D.; Bogomilov, M.; Kolev, D.; Tsenov, R.; Busygina, O.; Golubeva, M.; Guber, F.; Ivashkin, A.; Kurepin, A.; Morozov, S.; Petukhov, O.; Sadovsky, A.; Cirkovic, M.; Manic, D.; Puzovic, J.; Czopowicz, T.; Dynowski, K.; Grebieszkow, K.; Mackowiak-Pawlowska, M.; Maksiak, B.; Sarnecki, R.; Slodkowski, M.; Tefelska, A.; Tefelski, D.; Deveaux, M.; Koziel, M.; Renfordt, R.; Stroebele, H.; Dumarchez, J.; Robert, A.; Ereditato, A.; Hierholzer, M.; Nirkko, M.; Pistillo, C.; Redij, A.; Fodor, Z.; Garibov, A.; Gazdzicki, M.; Grzeszczuk, A.; Kaptur, E.; Kisiel, J.; Kowalski, S.; Pulawski, S.; Schmidt, K.; Wilczek, A.; Hasegawa, T.; Kobayashi, T.; Nakadaira, T.; Nishikawa, K.; Sakashita, K.; Sekiguchi, T.; Shibata, M.; Tada, M.; Kowalik, K.; Rondio, E.; Stepaniak, J.; Laszlo, A.; Marton, K.; Vesztergombi, G.; Lewicki, M.; Naskret, M.; Turko, L.; Marcinek, A.; Mrowczynski, S.; Rybczynski, M.; Seyboth, P.; Stefanek, G.; Wlodarczyk, Z.; Wojtaszek-Szwarc, A.; Pavin, M.; Popov, B.A.; Rauch, W.; Roehrich, D.; Rustamov, A.; Zambelli, L.

    2016-01-01

    Measurements of multiplicity and transverse momentum fluctuations of charged particles were performed in inelastic p+p interactions at 20, 31, 40, 80, and 158 GeV/c beam momentum. Results for the scaled variance of the multiplicity distribution and for three strongly intensive measures of multiplicity and transverse momentum fluctuations Δ[P_T,N], Σ[P_T,N] and Φ_p__T are presented. For the first time the results on fluctuations are fully corrected for experimental biases. The results on multiplicity and transverse momentum fluctuations significantly deviate from expectations for the independent particle production. They also depend on charges of selected hadrons. The string-resonance Monte Carlo models Epos and Urqmd do not describe the data. The scaled variance of multiplicity fluctuations is significantly higher in inelastic p+p interactions than in central Pb+Pb collisions measured by NA49 at the same energy per nucleon. This is in qualitative disagreement with the predictions of the Wounded Nucleon Model. Within the statistical framework the enhanced multiplicity fluctuations in inelastic p+p interactions can be interpreted as due to event-by-event fluctuations of the fireball energy and/or volume. (orig.)

  11. Multiplicity and transverse momentum fluctuations in inelastic proton-proton interactions at the CERN Super Proton Synchrotron

    Energy Technology Data Exchange (ETDEWEB)

    Aduszkiewicz, A.; Dominik, W.; Kuich, M.; Matulewicz, T.; Posiadala, M. [University of Warsaw, Faculty of Physics, Warsaw (Poland); Ali, Y.; Brzychczyk, J.; Larsen, D.; Planeta, R.; Richter-Was, E.; Staszel, P.; Wyszynski, O. [Jagiellonian University, Cracow (Poland); Andronov, E.; Feofilov, G.A.; Igolkin, S.; Kondratiev, V.P.; Seryakov, A.; Vechernin, V.V.; Vinogradov, L. [St. Petersburg State University, St. Petersburg (Russian Federation); Anticic, T.; Kadija, K.; Susa, T. [Ruder Boskovic Institute, Zagreb (Croatia); Antoniou, N.; Christakoglou, P.; Davis, N.; Diakonos, F.; Kapoyannis, A.; Panagiotou, A.D.; Vassiliou, M. [University of Athens, Athens (Greece); Baatar, B.; Bunyatov, S.A.; Kolesnikov, V.I.; Krasnoperov, A.; Lyubushkin, V.V.; Malakhov, A.I.; Matveev, V.; Melkumov, G.L.; Tereshchenko, V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Bay, F.; Di Luise, S.; Rubbia, A.; Sgalaberna, D. [ETH Zuerich, Zurich (Switzerland); Blondel, A.; Bravar, A.; Debieux, S.; Haesler, A.; Korzenev, A.; Ravonel, M. [University of Geneva, Geneva (Switzerland); Bluemer, J.; Dembinski, H.; Engel, R.; Herve, A.; Mathes, H.J.; Roth, M.; Szuba, M.; Ulrich, R.; Unger, M.; Veberic, D. [Karlsruhe Institute of Technology, Karlsruhe (Germany); Bogomilov, M.; Kolev, D.; Tsenov, R. [University of Sofia, Faculty of Physics, Sofia (Bulgaria); Busygina, O.; Golubeva, M.; Guber, F.; Ivashkin, A.; Kurepin, A.; Morozov, S.; Petukhov, O.; Sadovsky, A. [Institute for Nuclear Research, Moscow (Russian Federation); Cirkovic, M.; Manic, D.; Puzovic, J. [University of Belgrade, Belgrade (Serbia); Czopowicz, T.; Dynowski, K.; Grebieszkow, K.; Mackowiak-Pawlowska, M.; Maksiak, B.; Sarnecki, R.; Slodkowski, M.; Tefelska, A.; Tefelski, D. [Warsaw University of Technology, Warsaw (Poland); Deveaux, M.; Koziel, M.; Renfordt, R.; Stroebele, H. [University of Frankfurt, Frankfurt (Germany); Dumarchez, J.; Robert, A. [University of Paris VI and VII, LPNHE, Paris (France); Ereditato, A.; Hierholzer, M.; Nirkko, M.; Pistillo, C.; Redij, A. [University of Bern, Bern (Switzerland); Fodor, Z. [Wigner Research Centre for Physics of the Hungarian Academy of Sciences, Budapest (Hungary); University of Wroclaw, Wroclaw (Poland); Garibov, A. [National Nuclear Research Center, Baku (Azerbaijan); Gazdzicki, M. [University of Frankfurt, Frankfurt (Germany); Jan Kochanowski University in Kielce, Kielce (Poland); Grzeszczuk, A.; Kaptur, E.; Kisiel, J.; Kowalski, S.; Pulawski, S.; Schmidt, K.; Wilczek, A. [University of Silesia, Katowice (Poland); Hasegawa, T.; Kobayashi, T.; Nakadaira, T.; Nishikawa, K.; Sakashita, K.; Sekiguchi, T.; Shibata, M.; Tada, M. [Institute for Particle and Nuclear Studies, KEK, Tsukuba (Japan); Kowalik, K.; Rondio, E.; Stepaniak, J. [National Center for Nuclear Research, Warsaw (Poland); Laszlo, A.; Marton, K.; Vesztergombi, G. [Wigner Research Centre for Physics of the Hungarian Academy of Sciences, Budapest (Hungary); Lewicki, M.; Naskret, M.; Turko, L. [University of Wroclaw, Wroclaw (Poland); Marcinek, A. [Jagiellonian University, Cracow (Poland); University of Wroclaw, Wroclaw (Poland); Mrowczynski, S.; Rybczynski, M.; Seyboth, P.; Stefanek, G.; Wlodarczyk, Z.; Wojtaszek-Szwarc, A. [Jan Kochanowski University in Kielce, Kielce (Poland); Pavin, M. [Ruder Boskovic Institute, Zagreb (Croatia); University of Paris VI and VII, LPNHE, Paris (France); Popov, B.A. [University of Paris VI and VII, LPNHE, Paris (France); Joint Institute for Nuclear Research, Dubna (RU); Rauch, W. [Fachhochschule Frankfurt, Frankfurt (DE); Roehrich, D. [University of Bergen, Bergen (NO); Rustamov, A. [National Nuclear Research Center, Baku (AZ); University of Fra