WorldWideScience

Sample records for genetically separable functions

  1. Genetic separation of Escherichia coli recA functions for SOS mutagenesis and repressor cleavage

    International Nuclear Information System (INIS)

    Ennis, D.G.; Ossanna, N.; Mount, D.W.

    1989-01-01

    Evidence is presented that recA functions which promote the SOS functions of mutagenesis, LexA protein proteolysis, and lambda cI repressor proteolysis are each genetically separable from the others. This separation was observed in recombination-proficient recA mutants and rec+ (F' recA56) heterodiploids. recA430, recA433, and recA435 mutants and recA+ (F' recA56) heterodiploids were inducible for only one or two of the three functions and defective for mutagenesis. recA80 and recA432 mutants were constitutively activated for two of the three functions in that these mutants did not have to be induced to express the functions. We propose that binding of RecA protein to damaged DNA and subsequent interaction with small inducer molecules gives rise to conformational changes in RecA protein. These changes promote surface-surface interactions with other target proteins, such as cI and LexA proteins. By this model, the recA mutants are likely to have incorrect amino acids substituted as sites in the RecA protein structure which affect surface regions required for protein-protein interactions. The constitutively activated mutants could likewise insert altered amino acids at sites in RecA which are involved in the activation of RecA protein by binding small molecules or polynucleotides which metabolically regulate RecA protein

  2. Using an adoption design to separate genetic, prenatal, and temperament influences on toddler executive function.

    Science.gov (United States)

    Leve, Leslie D; DeGarmo, David S; Bridgett, David J; Neiderhiser, Jenae M; Shaw, Daniel S; Harold, Gordon T; Natsuaki, Misaki N; Reiss, David

    2013-06-01

    Poor executive functioning has been implicated in children's concurrent and future behavioral difficulties, making work aimed at understanding processes related to the development of early executive function (EF) critical for models of developmental psychopathology. Deficits in EF have been associated with adverse prenatal experiences, genetic influences, and temperament characteristics. However, our ability to disentangle the predictive and independent effects of these influences has been limited by a dearth of genetically informed research designs that also consider prenatal influences. The present study examined EF and language development in a sample of 361 toddlers who were adopted at birth and reared in nonrelative adoptive families. Predictors included genetic influences (as inherited from birth mothers), prenatal risk, and growth in child negative emotionality. Structural equation modeling indicated that the effect of prenatal risk on toddler effortful attention at age 27 months became nonsignificant once genetic influences were considered in the model. In addition, genetic influences had unique effects on toddler effortful attention. Latent growth modeling indicated that increases in toddler negative emotionality from 9 to 27 months were associated with poorer delay of gratification and poorer language development. Similar results were obtained in models incorporating birth father data. Mechanisms of intergenerational transmission of EF deficits are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved

  3. New separation technique. Catalytically functionated separation membrane

    Energy Technology Data Exchange (ETDEWEB)

    Urgami, Tadashi [Kansai Univ., Osaka (Japan)

    1989-02-01

    This report introduces research examples, showing the fundamental principle of the membrane by separating the catalytically functionated separation membrane into enzyme fixing separation membrane, polymerized metal complex separation membrane and polymer catalyst separation membrane. This membrane can achieve both functions of separation and catalytic reaction simultaneously and has sufficient possibility to combine powerful functions. Enzyme fixing separation membrane is prepared by carrier combination method, bridging method or covering method and the enzyme fixing method with polymerized complex in which enzyme is controlled to prevent the activity lowering as much as possible and enzyme is fixed from an aqueous solution into polymer membrane. This membrane is applied to the continuous manufacturing of invert sugar from cane sugar and adsorption and removing of harmful substances from blood by utilizing both micro-capsuled urease and active carbon. Alginic acid-copper (II) complex membrane is used for the polymerized metal complex membrane and polystyrene sulfonate membrane is used for the polymer catalyst separation membrane. 28 refs., 4 figs., 1 tabs.

  4. Genetic algorithm based separation cascade optimization

    International Nuclear Information System (INIS)

    Mahendra, A.K.; Sanyal, A.; Gouthaman, G.; Bera, T.K.

    2008-01-01

    The conventional separation cascade design procedure does not give an optimum design because of squaring-off, variation of flow rates and separation factor of the element with respect to stage location. Multi-component isotope separation further complicates the design procedure. Cascade design can be stated as a constrained multi-objective optimization. Cascade's expectation from the separating element is multi-objective i.e. overall separation factor, cut, optimum feed and separative power. Decision maker may aspire for more comprehensive multi-objective goals where optimization of cascade is coupled with the exploration of separating element optimization vector space. In real life there are many issues which make it important to understand the decision maker's perception of cost-quality-speed trade-off and consistency of preferences. Genetic algorithm (GA) is one such evolutionary technique that can be used for cascade design optimization. This paper addresses various issues involved in the GA based multi-objective optimization of the separation cascade. Reference point based optimization methodology with GA based Pareto optimality concept for separation cascade was found pragmatic and promising. This method should be explored, tested, examined and further developed for binary as well as multi-component separations. (author)

  5. A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression

    Science.gov (United States)

    Syed, Salahuddin; Desler, Claus; Rasmussen, Lene J.; Schmidt, Kristina H.

    2016-01-01

    In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186–212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each Rrm3 function are distinct. Although both lesion types activate the DNA-damage checkpoint, we find that the resultant increase in nucleotide levels is not sufficient for continued DNA synthesis under replication stress. Together, our findings suggest a role of Rrm3, via its Orc5-binding domain, in restricting DNA synthesis that is genetically and physically separable from its established catalytic role in facilitating fork progression through replication blocks. PMID:27923055

  6. A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression.

    Science.gov (United States)

    Syed, Salahuddin; Desler, Claus; Rasmussen, Lene J; Schmidt, Kristina H

    2016-12-01

    In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186-212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each Rrm3 function are distinct. Although both lesion types activate the DNA-damage checkpoint, we find that the resultant increase in nucleotide levels is not sufficient for continued DNA synthesis under replication stress. Together, our findings suggest a role of Rrm3, via its Orc5-binding domain, in restricting DNA synthesis that is genetically and physically separable from its established catalytic role in facilitating fork progression through replication blocks.

  7. A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression

    DEFF Research Database (Denmark)

    Syed, Salahuddin; Madsen, Claus Desler; Rasmussen, Lene J.

    2016-01-01

    hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5...

  8. Separating genetic and hemodynamic defects in neuropilin 1 knockout embryos.

    Science.gov (United States)

    Jones, Elizabeth A V; Yuan, Li; Breant, Christine; Watts, Ryan J; Eichmann, Anne

    2008-08-01

    Targeted inactivation of genes involved in murine cardiovascular development frequently leads to abnormalities in blood flow. As blood fluid dynamics play a crucial role in shaping vessel morphology, the presence of flow defects generally prohibits the precise assignment of the role of the mutated gene product in the vasculature. In this study, we show how to distinguish between genetic defects caused by targeted inactivation of the neuropilin 1 (Nrp1) receptor and hemodynamic defects occurring in homozygous knockout embryos. Our analysis of a Nrp1 null allele bred onto a C57BL/6 background shows that vessel remodeling defects occur concomitantly with the onset of blood flow and cause death of homozygous mutants at E10.5. Using mouse embryo culture, we establish that hemodynamic defects are already present at E8.5 and continuous circulation is never established in homozygous mutants. The geometry of yolk sac blood vessels is altered and remodeling into yolk sac arteries and veins does not occur. To separate flow-induced deficiencies from those caused by the Nrp1 mutation, we arrested blood flow in cultured wild-type and mutant embryos and followed their vascular development. We find that loss of Nrp1 function rather than flow induces the altered geometry of the capillary plexus. Endothelial cell migration, but not replication, is altered in Nrp1 mutants. Gene expression analysis of endothelial cells isolated from freshly dissected wild-type and mutants and after culture in no-flow conditions showed down-regulation of the arterial marker genes connexin 40 and ephrin B2 related to the loss of Nrp1 function. This method allows genetic defects caused by loss-of-function of a gene important for cardiovascular development to be isolated even in the presence of hemodynamic defects.

  9. Electrostatic separation for functional food ingredient production

    NARCIS (Netherlands)

    Wang, J.

    2016-01-01

    Summary

    Dry fractionation is a promising alternative to wet extraction processes for production of food ingredients, since it uses hardly any water, consumes less energy and retains the native functionality of the ingredients. It combines milling and dry separation to

  10. Consciousness cannot be separated from function.

    Science.gov (United States)

    Cohen, Michael A; Dennett, Daniel C

    2011-08-01

    Numerous theories of consciousness hold that there are separate neural correlates of conscious experience and cognitive function, aligning with the assumption that there are 'hard' and 'easy' problems of consciousness. Here, we argue that any neurobiological theory based on an experience/function division cannot be empirically confirmed or falsified and is thus outside the scope of science. A 'perfect experiment' illustrates this point, highlighting the unbreachable boundaries of the scientific study of consciousness. We describe a more nuanced notion of cognitive access that captures personal experience without positing the existence of inaccessible conscious states. Finally, we discuss the criteria necessary for forming and testing a falsifiable theory of consciousness. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Functionalized inorganic membranes for gas separation

    Science.gov (United States)

    Ku, Anthony Yu-Chung [Rexford, NY; Ruud, James Anthony [Delmar, NY; Molaison, Jennifer Lynn [Marietta, GA; Schick, Louis Andrew ,; Ramaswamy, Vidya [Niskayuna, NY

    2008-07-08

    A porous membrane for separation of carbon dioxide from a fluid stream at a temperature higher than about 200.degree. C. with selectivity higher than Knudsen diffusion selectivity. The porous membrane comprises a porous support layer comprising alumina, silica, zirconia or stabilized zirconia; a porous separation layer comprising alumina, silica, zirconia or stabilized zirconia, and a functional layer comprising a ceramic oxide contactable with the fluid stream to preferentially transport carbon dioxide. In particular, the functional layer may be MgO, CaO, SrO, BaO, La.sub.2O.sub.3, CeO.sub.2, ATiO.sub.3, AZrO.sub.3, AAl.sub.2O.sub.4, A.sup.1FeO.sub.3, A.sup.1MnO.sub.3, A.sup.1CoO.sub.3, A.sup.1NiO.sub.3, A.sup.2HfO.sub.3, A.sup.3CeO.sub.3, Li.sub.2ZrO.sub.3, Li.sub.2SiO.sub.3, Li.sub.2TiO.sub.3 or a mixture thereof; wherein A is Mg, Ca, Sr or Ba; A.sup.1 is La, Ca, Sr or Ba; A.sup.2 is Ca, Sr or Ba; and A.sup.3 is Sr or Ba.

  12. THE PRINCIPLE OF SEPARATION OF JUDICIAL FUNCTIONS

    Directory of Open Access Journals (Sweden)

    Denisa BARBU

    2016-05-01

    Full Text Available The fundamental principles of the criminal procedure are general rules applicable throughout the criminal procedure in order to achieve its purpose. The fundamental principles are covered by art. 2-12 C.C.P. and are: the legality of criminal procedure, separating the functions of the judiciary, the presumption of innocence, finding out the truth, ne bis in idem, a requirement for moving and exercising penal action, is fair and reasonable term of the criminal trial, the right to liberty and security, the right to defence, respect for human dignity and privacy, the official language and the right to an interpreter. The European Court of Human Rights is conscious that by protecting the fundamental principles it does not only aim at the protection of super eminence of the inextricably right tied to the state of law. These principles represent a set of obligations imposed on the State that has as the sole purpose the protection of fundamental rights and freedoms.

  13. 6 CFR 13.14 - Separation of functions.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Separation of functions. 13.14 Section 13.14 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.14 Separation of functions. (a) The Investigating Official, the Reviewing Official, and any...

  14. A Review of Function Allocation and En Route Separation Assurance

    Science.gov (United States)

    Lewis, Timothy A.; Aweiss, Arwa S.; Guerreiro, Nelson M.; Daiker, Ronald J.

    2016-01-01

    Today's air traffic control system has reached a limit to the number of aircraft that can be safely managed at the same time. This air traffic capacity bottleneck is a critical problem along the path to modernization for air transportation. The design of the next separation assurance system to address this problem is a cornerstone of air traffic management research today. This report reviews recent work by NASA and others in the areas of function allocation and en route separation assurance. This includes: separation assurance algorithms and technology prototypes; concepts of operations and designs for advanced separation assurance systems; and specific investigations into air-ground and human-automation function allocation.

  15. Using genetic programming to find Lyapunov functions

    NARCIS (Netherlands)

    Soute, I.A.C.; Molengraft, van de M.J.G.; Angelis, G.Z.; Ryan, C; Spector, L.

    2001-01-01

    In this paper Genetic Programming is used to find Lyapunov functions for (non)linear dif ferential equations of autonomous systems. As Lyapunov functions can be difficult to find, we use OP to make the decisions concerning the form of the Lyapunov function. As an e5cample two systems are taken to

  16. The genetic covariance between life cycle stages separated by metamorphosis.

    Science.gov (United States)

    Aguirre, J David; Blows, Mark W; Marshall, Dustin J

    2014-08-07

    Metamorphosis is common in animals, yet the genetic associations between life cycle stages are poorly understood. Given the radical changes that occur at metamorphosis, selection may differ before and after metamorphosis, and the extent that genetic associations between pre- and post-metamorphic traits constrain evolutionary change is a subject of considerable interest. In some instances, metamorphosis may allow the genetic decoupling of life cycle stages, whereas in others, metamorphosis could allow complementary responses to selection across the life cycle. Using a diallel breeding design, we measured viability at four ontogenetic stages (embryo, larval, juvenile and adult viability), in the ascidian Ciona intestinalis and examined the orientation of additive genetic variation with respect to the metamorphic boundary. We found support for one eigenvector of G: (gobsmax ), which contrasted larval viability against embryo viability and juvenile viability. Target matrix rotation confirmed that while gobsmax shows genetic associations can extend beyond metamorphosis, there is still considerable scope for decoupled phenotypic evolution. Therefore, although genetic associations across metamorphosis could limit that range of phenotypes that are attainable, traits on either side of the metamorphic boundary are capable of some independent evolutionary change in response to the divergent conditions encountered during each life cycle stage. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  17. 24 CFR 180.220 - Separation of functions.

    Science.gov (United States)

    2010-04-01

    ... AND BUSINESS OPPORTUNITY CONSOLIDATED HUD HEARING PROCEDURES FOR CIVIL RIGHTS MATTERS Administrative Law Judge § 180.220 Separation of functions. No officer, employee, or agent of the Federal Government...

  18. Methods for selective functionalization and separation of carbon nanotubes

    Science.gov (United States)

    Strano, Michael S. (Inventor); Usrey, Monica (Inventor); Barone, Paul (Inventor); Dyke, Christopher A. (Inventor); Tour, James M. (Inventor); Kittrell, W. Carter (Inventor); Hauge, Robert H (Inventor); Smalley, Richard E. (Inventor); Marek, legal representative, Irene Marie (Inventor)

    2011-01-01

    The present invention is directed toward methods of selectively functionalizing carbon nanotubes of a specific type or range of types, based on their electronic properties, using diazonium chemistry. The present invention is also directed toward methods of separating carbon nanotubes into populations of specific types or range(s) of types via selective functionalization and electrophoresis, and also to the novel compositions generated by such separations.

  19. When do evolutionary algorithms optimize separable functions in parallel?

    DEFF Research Database (Denmark)

    Doerr, Benjamin; Sudholt, Dirk; Witt, Carsten

    2013-01-01

    is that evolutionary algorithms make progress on all subfunctions in parallel, so that optimizing a separable function does not take not much longer than optimizing the hardest subfunction-subfunctions are optimized "in parallel." We show that this is only partially true, already for the simple (1+1) evolutionary...... algorithm ((1+1) EA). For separable functions composed of k Boolean functions indeed the optimization time is the maximum optimization time of these functions times a small O(log k) overhead. More generally, for sums of weighted subfunctions that each attain non-negative integer values less than r = o(log1...

  20. Theoretical investigation of gas separation in functionalized nanoporous graphene membranes

    Science.gov (United States)

    Wang, Yong; Yang, Qingyuan; Zhong, Chongli; Li, Jinping

    2017-06-01

    Graphene has enormous potential as a membrane-separation material with ultrahigh permeability and selectivity. The understanding of mass-transport mechanism in graphene membranes is crucial for applications in gas separation field. We computationally investigated the capability and mechanisms of functionalized nanoporous graphene membranes for gas separation. The functionalized graphene membranes with appropriate pore size and geometry possess excellent high selectivity for separating CO2/N2, CO2/CH4 and N2/CH4 gas mixtures with a gas permeance of ∼103-105 GPU, compared with ∼100 GPU for typical polymeric membranes. More important, we found that, for ultrathin graphene membranes, the gas separation performance has a great dependence not only with the energy barrier for gas getting into the pore of the graphene membranes, but also with the energy barrier for gas escaping from the pore to the other side of the membranes. The gas separation performance can be tuned by changing the two energy barriers, which can be realized by varying the chemical functional groups on the pore rim of the graphene. The novel mass-transport mechanism obtained in current study may provide a theoretical foundation for guiding the future design of graphene membranes with outstanding separation performance.

  1. On the Relativistic Separable Functions for the Breakup Reactions

    Science.gov (United States)

    Bondarenko, Serge G.; Burov, Valery V.; Rogochaya, Elena P.

    2018-02-01

    In the paper the so-called modified Yamaguchi function for the Bethe-Salpeter equation with a separable kernel is discussed. The type of the functions is defined by the analytic stucture of the hadron current with breakup - the reactions with interacting nucleon-nucleon pair in the final state (electro-, photo-, and nucleon-disintegration of the deuteron).

  2. Alternative separation of exchange and correlation energies in range-separated density-functional perturbation theory

    DEFF Research Database (Denmark)

    Cornaton, Y.; Stoyanova, A.; Jensen, Hans Jørgen Aagaard

    2013-01-01

    of the noninteracting Kohn-Sham one. When second-order corrections to the density are neglected, the energy expression reduces to a range-separated double-hybrid (RSDH) type of functional, RSDHf, where "f" stands for "full-range integrals" as the regular full-range interaction appears explicitly in the energy...

  3. Genetic variants associated with lung function

    DEFF Research Database (Denmark)

    Thyagarajan, Bharat; Wojczynski, Mary; Minster, Ryan L

    2014-01-01

    with exceptional longevity have not been identified. METHOD: We conducted a genome wide association study (GWAS) to identify novel genetic variants associated with lung function in the Long Life Family Study (LLFS) (n = 3,899). Replication was performed using data from the CHARGE/SpiroMeta consortia...

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

    Science.gov (United States)

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

    2018-01-09

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

  5. Functionalized Mesoporous Silica Membranes for CO2 Separation Applications

    Directory of Open Access Journals (Sweden)

    Hyung-Ju Kim

    2015-01-01

    Full Text Available Mesoporous silica molecular sieves are emerging candidates for a number of potential applications involving adsorption and molecular transport due to their large surface areas, high pore volumes, and tunable pore sizes. Recently, several research groups have investigated the potential of functionalized mesoporous silica molecular sieves as advanced materials in separation devices, such as membranes. In particular, mesoporous silica with a two- or three-dimensional pore structure is one of the most promising types of molecular sieve materials for gas separation membranes. However, several important challenges must first be addressed regarding the successful fabrication of mesoporous silica membranes. First, a novel, high throughput process for the fabrication of continuous and defect-free mesoporous silica membranes is required. Second, functionalization of mesopores on membranes is desirable in order to impart selective properties. Finally, the separation characteristics and performance of functionalized mesoporous silica membranes must be further investigated. Herein, the synthesis, characterization, and applications of mesoporous silica membranes and functionalized mesoporous silica membranes are reviewed with a focus on CO2 separation.

  6. A genetic basis for functional hypothalamic amenorrhea.

    OpenAIRE

    Caronia, L.M.; Martin, C.; Welt, C.K.; Sykiotis, G.P.; Quinton, R.; Thambundit, A.; Avbelj, M.; Dhruvakumar, S.; Plummer, L.; Hughes, V.A.; Seminara, S.B.; Boepple, P.A.; Sidis, Y.; Crowley, W.F.; Martin, K.A.

    2011-01-01

    Background: Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition of the reproductive axis by such stressors, but it is unknown whether this variability reflects a genetic predisposition to hypothalamic amenorrhea. We hypothesized that mutations in genes involved in idiopathic hypogon...

  7. Functional roles for noise in genetic circuits.

    Science.gov (United States)

    Eldar, Avigdor; Elowitz, Michael B

    2010-09-09

    The genetic circuits that regulate cellular functions are subject to stochastic fluctuations, or 'noise', in the levels of their components. Noise, far from just a nuisance, has begun to be appreciated for its essential role in key cellular activities. Noise functions in both microbial and eukaryotic cells, in multicellular development, and in evolution. It enables coordination of gene expression across large regulons, as well as probabilistic differentiation strategies that function across cell populations. At the longest timescales, noise may facilitate evolutionary transitions. Here we review examples and emerging principles that connect noise, the architecture of the gene circuits in which it is present, and the biological functions it enables. We further indicate some of the important challenges and opportunities going forward.

  8. Genetic architecture of the Delis-Kaplan Executive Function System Trail Making Test: evidence for distinct genetic influences on executive function.

    Science.gov (United States)

    Vasilopoulos, Terrie; Franz, Carol E; Panizzon, Matthew S; Xian, Hong; Grant, Michael D; Lyons, Michael J; Toomey, Rosemary; Jacobson, Kristen C; Kremen, William S

    2012-03-01

    To examine how genes and environments contribute to relationships among Trail Making Test (TMT) conditions and the extent to which these conditions have unique genetic and environmental influences. Participants included 1,237 middle-aged male twins from the Vietnam Era Twin Study of Aging. The Delis-Kaplan Executive Function System TMT included visual searching, number and letter sequencing, and set-shifting components. Phenotypic correlations among TMT conditions ranged from 0.29 to 0.60, and genes accounted for the majority (58-84%) of each correlation. Overall heritability ranged from 0.34 to 0.62 across conditions. Phenotypic factor analysis suggested a single factor. In contrast, genetic models revealed a single common genetic factor but also unique genetic influences separate from the common factor. Genetic variance (i.e., heritability) of number and letter sequencing was completely explained by the common genetic factor while unique genetic influences separate from the common factor accounted for 57% and 21% of the heritabilities of visual search and set shifting, respectively. After accounting for general cognitive ability, unique genetic influences accounted for 64% and 31% of those heritabilities. A common genetic factor, most likely representing a combination of speed and sequencing, accounted for most of the correlation among TMT 1-4. Distinct genetic factors, however, accounted for a portion of variance in visual scanning and set shifting. Thus, although traditional phenotypic shared variance analysis techniques suggest only one general factor underlying different neuropsychological functions in nonpatient populations, examining the genetic underpinnings of cognitive processes with twin analysis can uncover more complex etiological processes.

  9. Childhood separation anxiety disorder and adult onset panic attacks share a common genetic diathesis.

    Science.gov (United States)

    Roberson-Nay, Roxann; Eaves, Lindon J; Hettema, John M; Kendler, Kenneth S; Silberg, Judy L

    2012-04-01

    Childhood separation anxiety disorder (SAD) is hypothesized to share etiologic roots with panic disorder. The aim of this study was to estimate the genetic and environmental sources of covariance between childhood SAD and adult onset panic attacks (AOPA), with the primary goal to determine whether these two phenotypes share a common genetic diathesis. Participants included parents and their monozygotic or dizygotic twins (n = 1,437 twin pairs) participating in the Virginia Twin Study of Adolescent Behavioral Development and those twins who later completed the Young Adult Follow-Up (YAFU). The Child and Adolescent Psychiatric Assessment was completed at three waves during childhood/adolescence followed by the Structured Clinical Interview for DSM-III-R at the YAFU. Two separate, bivariate Cholesky models were fit to childhood diagnoses of SAD and overanxious disorder (OAD), respectively, and their relation with AOPA; a trivariate Cholesky model also examined the collective influence of childhood SAD and OAD on AOPA. In the best-fitting bivariate model, the covariation between SAD and AOPA was accounted for by genetic and unique environmental factors only, with the genetic factor associated with childhood SAD explaining significant variance in AOPA. Environmental risk factors were not significantly shared between SAD and AOPA. By contrast, the genetic factor associated with childhood OAD did not contribute significantly to AOPA. Results of the trivariate Cholesky reaffirmed outcomes of bivariate models. These data indicate that childhood SAD and AOPA share a common genetic diathesis that is not observed for childhood OAD, strongly supporting the hypothesis of a specific genetic etiologic link between the two phenotypes. © 2012 Wiley Periodicals, Inc.

  10. Magnetic separation of algae genetically modified for increased intracellular iron uptake

    Energy Technology Data Exchange (ETDEWEB)

    Buck, Amy [Case Western Reserve University, Cleveland, OH (United States); Cleveland Clinic, Cleveland, OH (United States); Moore, Lee R. [Cleveland Clinic, Cleveland, OH (United States); Lane, Christopher D.; Kumar, Anil; Stroff, Clayton; White, Nicolas [Phycal Inc., Cleveland, OH (United States); Xue, Wei; Chalmers, Jeffrey J. [The Ohio State University, Columbus, OH (United States); Zborowski, Maciej, E-mail: zborowm@ccf.org [Cleveland Clinic, Cleveland, OH (United States)

    2015-04-15

    Algae were investigated in the past as a potential source of biofuel and other useful chemical derivatives. Magnetic separation of algae by iron oxide nanoparticle binding to cells has been proposed by others for dewatering of cellular mass prior to lipid extraction. We have investigated feasibility of magnetic separation based on the presence of natural iron stores in the cell, such as the ferritin in Auxenochlorella protothecoides (A. protothecoides) strains. The A. protothecoides cell constructs were tested for inserted genes and for increased intracellular iron concentration by inductively coupled plasma atomic absorption (ICP–AA). They were grown in Sueoka’s modified high salt media with added vitamin B1 and increasing concentration of soluble iron compound (FeCl{sub 3} EDTA, from 1× to 8× compared to baseline). The cell magnetic separation conditions were tested using a thin rectangular flow channel pressed against interpolar gaps of a permanent magnet forming a separation system of a well-defined fluid flow and magnetic fringing field geometry (up to 2.2 T and 1000 T/m) dubbed “magnetic deposition microscopy”, or MDM. The presence of magnetic cells in suspension was detected by formation of characteristic deposition bands at the edges of the magnet interpolar gaps, amenable to optical scanning and microscopic examination. The results demonstrated increasing cellular Fe uptake with increasing Fe concentration in the culture media in wild type strain and in selected genetically-modified constructs, leading to magnetic separation without magnetic particle binding. The throughput in this study is not sufficient for an economical scale harvest. - Highlights: • Auxenochlorella protothecoides algae were genetically modified for biofuel production. • Algal iron metabolism was sufficient for their label-less magnetic separation. • High magnetic field and low flow required make the separation scale-up uneconomical.

  11. Magnetic separation of algae genetically modified for increased intracellular iron uptake

    International Nuclear Information System (INIS)

    Buck, Amy; Moore, Lee R.; Lane, Christopher D.; Kumar, Anil; Stroff, Clayton; White, Nicolas; Xue, Wei; Chalmers, Jeffrey J.; Zborowski, Maciej

    2015-01-01

    Algae were investigated in the past as a potential source of biofuel and other useful chemical derivatives. Magnetic separation of algae by iron oxide nanoparticle binding to cells has been proposed by others for dewatering of cellular mass prior to lipid extraction. We have investigated feasibility of magnetic separation based on the presence of natural iron stores in the cell, such as the ferritin in Auxenochlorella protothecoides (A. protothecoides) strains. The A. protothecoides cell constructs were tested for inserted genes and for increased intracellular iron concentration by inductively coupled plasma atomic absorption (ICP–AA). They were grown in Sueoka’s modified high salt media with added vitamin B1 and increasing concentration of soluble iron compound (FeCl 3 EDTA, from 1× to 8× compared to baseline). The cell magnetic separation conditions were tested using a thin rectangular flow channel pressed against interpolar gaps of a permanent magnet forming a separation system of a well-defined fluid flow and magnetic fringing field geometry (up to 2.2 T and 1000 T/m) dubbed “magnetic deposition microscopy”, or MDM. The presence of magnetic cells in suspension was detected by formation of characteristic deposition bands at the edges of the magnet interpolar gaps, amenable to optical scanning and microscopic examination. The results demonstrated increasing cellular Fe uptake with increasing Fe concentration in the culture media in wild type strain and in selected genetically-modified constructs, leading to magnetic separation without magnetic particle binding. The throughput in this study is not sufficient for an economical scale harvest. - Highlights: • Auxenochlorella protothecoides algae were genetically modified for biofuel production. • Algal iron metabolism was sufficient for their label-less magnetic separation. • High magnetic field and low flow required make the separation scale-up uneconomical

  12. Amine-functionalized magnetic mesoporous silica nanoparticles for DNA separation

    Energy Technology Data Exchange (ETDEWEB)

    Sheng, Wei; Wei, Wei; Li, Junjian; Qi, Xiaoliang; Zuo, Gancheng; Chen, Qi; Pan, Xihao; Dong, Wei, E-mail: weidong@njust.edu.cn

    2016-11-30

    Highlights: • Fe{sub 3}O{sub 4}@SiO{sub 2}@EDPS with uniform size and good dispersity is prepared. • We fabricated MMSN@EDPS with distinct core-shell–shell triple-layer composition. • DNA adsorption capacity of MMSN@EDPS is considerable. - Abstract: We report a modified approach for the functionalized magnetic mesoporous silica nanoparticles (MMSN) using polymer microspheres incorporated with magnetic nanoparticles in the presence of cetyltrimethylammonium bromide (CTAB) and the core-shell magnetic silica nanoparticles (MSN). These particles were functionalized with amino groups via the addition of aminosilane directly to the particle sol. We then evaluate their DNA separation abilities and find the capacity of DNA binding significantly increased (210.22 μg/mg) compared with normal magnetic silica spheres (138.44 μg/mg) by using an ultraviolet and visible spectrophotometer (UV). The morphologies, magnetic properties, particle size, pore size, core-shell structure and Zeta potential are characterized by Fourier transform infrared spectroscopy (FT-IR), vibrating sample magnetometer (VSM), Transmission electron microscopy (TEM), Powder X-ray diffraction (XRD), and dynamic light scattering (DLS). This work demonstrates that our MMSN own an excellent potential application in bioseparation and drug delivery.

  13. Functionalized Nanocellulose-Integrated Heterolayered Nanomats toward Smart Battery Separators.

    Science.gov (United States)

    Kim, Jung-Hwan; Gu, Minsu; Lee, Do Hyun; Kim, Jeong-Hoon; Oh, Yeon-Su; Min, Sa Hoon; Kim, Byeong-Su; Lee, Sang-Young

    2016-09-14

    Alternative materials obtained from natural resources have recently garnered considerable attention as an innovative solution to bring unprecedented advances in various energy storage systems. Here, we present a new class of heterolayered nanomat-based hierarchical/asymmetric porous membrane with synergistically coupled chemical activity as a nanocellulose-mediated green material strategy to develop smart battery separator membranes far beyond their current state-of-the-art counterparts. This membrane consists of a terpyridine (TPY)-functionalized cellulose nanofibril (CNF) nanoporous thin mat as the top layer and an electrospun polyvinylpyrrolidone (PVP)/polyacrylonitrile (PAN) macroporous thick mat as the support layer. The hierarchical/asymmetric porous structure of the heterolayered nanomat is rationally designed with consideration of the trade-off between leakage current and ion transport rate. The TPY (to chelate Mn(2+) ions) and PVP (to capture hydrofluoric acid)-mediated chemical functionalities bring a synergistic coupling in suppressing Mn(2+)-induced adverse effects, eventually enabling a substantial improvement in the high-temperature cycling performance of cells.

  14. A Genetic Basis for Functional Hypothalamic Amenorrhea

    Science.gov (United States)

    Caronia, Lisa M.; Martin, Cecilia; Welt, Corrine K.; Sykiotis, Gerasimos P.; Quinton, Richard; Thambundit, Apisadaporn; Avbelj, Magdalena; Dhruvakumar, Sadhana; Plummer, Lacey; Hughes, Virginia A.; Seminara, Stephanie B.; Boepple, Paul A.; Sidis, Yisrael; Crowley, William F.; Martin, Kathryn A.; Hall, Janet E.; Pitteloud, Nelly

    2011-01-01

    BACKGROUND Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition of the reproductive axis by such stressors, but it is unknown whether this variability reflects a genetic predisposition to hypothalamic amenorrhea. We hypothesized that mutations in genes involved in idiopathic hypogonadotropic hypogonadism, a congenital form of GnRH deficiency, are associated with hypothalamic amenorrhea. METHODS We analyzed the coding sequence of genes associated with idiopathic hypogonadotropic hypogonadism in 55 women with hypothalamic amenorrhea and performed in vitro studies of the identified mutations. RESULTS Six heterozygous mutations were identified in 7 of the 55 patients with hypothalamic amenorrhea: two variants in the fibroblast growth factor receptor 1 gene FGFR1 (G260E and R756H), two in the prokineticin receptor 2 gene PROKR2 (R85H and L173R), one in the GnRH receptor gene GNRHR (R262Q), and one in the Kall-mann syndrome 1 sequence gene KAL1 (V371I). No mutations were found in a cohort of 422 controls with normal menstrual cycles. In vitro studies showed that FGFR1 G260E, FGFR1 R756H, and PROKR2 R85H are loss-of-function mutations, as has been previously shown for PROKR2 L173R and GNRHR R262Q. CONCLUSIONS Rare variants in genes associated with idiopathic hypogonadotropic hypogonadism are found in women with hypothalamic amenorrhea, suggesting that these mutations may contribute to the variable susceptibility of women to the functional changes in GnRH secretion that characterize hypothalamic amenorrhea. Our observations provide evidence for the role of rare variants in common multifactorial disease. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00494169.) PMID:21247312

  15. A genetic basis for functional hypothalamic amenorrhea.

    Science.gov (United States)

    Caronia, Lisa M; Martin, Cecilia; Welt, Corrine K; Sykiotis, Gerasimos P; Quinton, Richard; Thambundit, Apisadaporn; Avbelj, Magdalena; Dhruvakumar, Sadhana; Plummer, Lacey; Hughes, Virginia A; Seminara, Stephanie B; Boepple, Paul A; Sidis, Yisrael; Crowley, William F; Martin, Kathryn A; Hall, Janet E; Pitteloud, Nelly

    2011-01-20

    Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition of the reproductive axis by such stressors, but it is unknown whether this variability reflects a genetic predisposition to hypothalamic amenorrhea. We hypothesized that mutations in genes involved in idiopathic hypogonadotropic hypogonadism, a congenital form of GnRH deficiency, are associated with hypothalamic amenorrhea. We analyzed the coding sequence of genes associated with idiopathic hypogonadotropic hypogonadism in 55 women with hypothalamic amenorrhea and performed in vitro studies of the identified mutations. Six heterozygous mutations were identified in 7 of the 55 patients with hypothalamic amenorrhea: two variants in the fibroblast growth factor receptor 1 gene FGFR1 (G260E and R756H), two in the prokineticin receptor 2 gene PROKR2 (R85H and L173R), one in the GnRH receptor gene GNRHR (R262Q), and one in the Kallmann syndrome 1 sequence gene KAL1 (V371I). No mutations were found in a cohort of 422 controls with normal menstrual cycles. In vitro studies showed that FGFR1 G260E, FGFR1 R756H, and PROKR2 R85H are loss-of-function mutations, as has been previously shown for PROKR2 L173R and GNRHR R262Q. Rare variants in genes associated with idiopathic hypogonadotropic hypogonadism are found in women with hypothalamic amenorrhea, suggesting that these mutations may contribute to the variable susceptibility of women to the functional changes in GnRH secretion that characterize hypothalamic amenorrhea. Our observations provide evidence for the role of rare variants in common multifactorial disease. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00494169.).

  16. Functionalized membranes for environmental remediation and selective separation

    Science.gov (United States)

    Xiao, Li

    Membrane process including microfiltration (MF), ultrafiltration (UF), nanofiltration (NF) and reverse osmosis (RO) have provided numerous successful applications ranging from drinking water purification, wastewater treatment, to material recovery. The addition of functional moiety in the membranes pores allows such membranes to be used in challenging areas including tunable separations, toxic metal capture, and catalysis. In this work, polyvinylidene fluoride (PVDF) MF membrane was functionalized with temperature responsive (poly(N-isopropylacrylamide), PNIPAAm) and pH responsive (polyacrylic acid, PAA) polymers. It's revealed that the permeation of various molecules (water, salt and dextran) through the membrane can be thermally or pH controlled. The introduction of PAA as a polyelectrolyte offers an excellent platform for the immobilization of metal nanoparticles (NPs) applied for degradation of toxic chlorinated organics with significantly increased longevity and stability. The advantage of using temperature and pH responsive polymers/hydrogels also includes the high reactivity and effectiveness in dechlorination. Further advancement on the PVDF functionalization involved the alkaline treatment to create partially defluorinated membrane (Def-PVDF) with conjugated double bounds allowing for the covalent attachment of different polymers. The PAA-Def-PVDF membrane shows pH responsive behavior on both the hydraulic permeability and solute retention. The sponge-like PVDF (SPVDF) membranes by phase inversion were developed through casting PVDF solution on polyester backing. The SPVDF membrane was demonstrated to have 4 times more surface area than commercial PVDF MF membrane, allowing for enhanced nanoparticles loading for chloro-organics degradation. The advanced functionalization method and process were also validated to be able to be scaled-up through the evaluation of full-scale functionalized membrane provided by Ultura Inc. California, USA. Nanofiltration (NF

  17. Human red cell 2,3-diphosphoglycerate mutase and monophosphoglycerate mutase: genetic evidence for two separate loci.

    Science.gov (United States)

    Chen, S H; Anderson, J E; Giblett, E R

    1977-01-01

    Rare genetic variants of human red cell 2,3-diphosphoglycerate mutase (DPGM) and monophosphoglycerate mutase (MPGM) were compared by starch gel electrophoresis. The isozyme patterns showed that genetic variation of the enzymes were independent from each other, thus DPGM and MPGM must be controlled by two separate loci. Images Fig. 1 PMID:195467

  18. Prenatal and postnatal genetic influence on lung function development

    DEFF Research Database (Denmark)

    Kreiner-Møller, Eskil; Bisgaard, Hans; Bønnelykke, Klaus

    2014-01-01

    BACKGROUND: It is unknown to what extent adult lung function genes affect lung function development from birth to childhood. OBJECTIVE: Our aim was to study the association of candidate genetic variants with neonatal lung function and lung function development until age 7 years. METHODS: Lung fun...

  19. Functional DNA: Teaching Infinite Series through Genetic Analogy

    Science.gov (United States)

    Kowalski, R. Travis

    2011-01-01

    This article presents an extended analogy that connects infinite sequences and series to the science of genetics, by identifying power series as "DNA for a function." This analogy allows standard topics such as convergence tests or Taylor approximations to be recast in a "forensic" light as mathematical analogs of genetic concepts such as DNA…

  20. Biological pathways and genetic mechanisms involved in social functioning.

    Science.gov (United States)

    Ordoñana, Juan R; Bartels, Meike; Boomsma, Dorret I; Cella, David; Mosing, Miriam; Oliveira, Joao R; Patrick, Donald L; Veenhoven, Ruut; Wagner, Gert G; Sprangers, Mirjam A G

    2013-08-01

    To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research. A search of Web of Science and PubMed databases was conducted using combinations of the following keywords: genetics, twins, heritability, social functioning, social adjustment, social interaction, and social dysfunction. Variability in the definitions and measures of social functioning was extensive. Moderate to high heritability was reported for social functioning and related concepts, including prosocial behavior, loneliness, and extraversion. Disorders characterized by impairments in social functioning also show substantial heritability. Genetic variants hypothesized to be involved in social functioning are related to the network of brain structures and processes that are known to affect social cognition and behavior. Better knowledge and understanding about the impact of genetic factors on social functioning is needed to help us to attain a more comprehensive view of health-related quality-of-life (HRQOL) and will ultimately enhance our ability to identify those patients who are vulnerable to poor social functioning.

  1. Joint modeling of genetically correlated diseases and functional annotations increases accuracy of polygenic risk prediction.

    Directory of Open Access Journals (Sweden)

    Yiming Hu

    2017-06-01

    Full Text Available Accurate prediction of disease risk based on genetic factors is an important goal in human genetics research and precision medicine. Advanced prediction models will lead to more effective disease prevention and treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome-wide association studies (GWAS in the past decade, accuracy of genetic risk prediction remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes. In this work, we introduce PleioPred, a principled framework that leverages pleiotropy and functional annotations in genetic risk prediction for complex diseases. PleioPred uses GWAS summary statistics as its input, and jointly models multiple genetically correlated diseases and a variety of external information including linkage disequilibrium and diverse functional annotations to increase the accuracy of risk prediction. Through comprehensive simulations and real data analyses on Crohn's disease, celiac disease and type-II diabetes, we demonstrate that our approach can substantially increase the accuracy of polygenic risk prediction and risk population stratification, i.e. PleioPred can significantly better separate type-II diabetes patients with early and late onset ages, illustrating its potential clinical application. Furthermore, we show that the increment in prediction accuracy is significantly correlated with the genetic correlation between the predicted and jointly modeled diseases.

  2. 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.

  3. Separable quotients for less-than-barrelled function spaces

    Czech Academy of Sciences Publication Activity Database

    Kąkol, Jerzy; Saxon, S. A.

    2018-01-01

    Roč. 459, č. 2 (2018), s. 1102-1105 ISSN 0022-247X R&D Projects: GA ČR GF16-34860L Institutional support: RVO:67985840 Keywords : separable quotients * weak barrelledness * dual locally complete Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 1.064, year: 2016 http://www.sciencedirect.com/science/article/pii/S0022247X17310351?via%3Dihub

  4. Separable quotients for less-than-barrelled function spaces

    Czech Academy of Sciences Publication Activity Database

    Kąkol, Jerzy; Saxon, S. A.

    2018-01-01

    Roč. 459, č. 2 (2018), s. 1102-1105 ISSN 0022-247X R&D Projects: GA ČR GF16-34860L Institutional support: RVO:67985840 Keywords : separable quotients * weak barrelledness * dual locally complete Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 1.064, year: 2016 http://www. science direct.com/ science /article/pii/S0022247X17310351?via%3Dihub

  5. Functional Determinants for Radially Separable Partial Differential Operators

    Directory of Open Access Journals (Sweden)

    G. V. Dunne

    2007-01-01

    Full Text Available Functional determinants of differential operators play a prominent role in many fields of theoretical and mathematical physics, ranging from condensed matter physics, to atomic, molecular and particle physics. They are, however, difficult to compute reliably in non-trivial cases. In one dimensional problems (i.e. functional determinants of ordinary differential operators, a classic result of Gel’fand and Yaglom greatly simplifies the computation of functional determinants. Here I report some recent progress in extending this approach to higher dimensions (i.e., functional determinants of partial differential operators, with applications in quantum field theory. 

  6. Genetic dissection reveals two separate retinal substrates for polarization vision in Drosophila.

    Science.gov (United States)

    Wernet, Mathias F; Velez, Mariel M; Clark, Damon A; Baumann-Klausener, Franziska; Brown, Julian R; Klovstad, Martha; Labhart, Thomas; Clandinin, Thomas R

    2012-01-10

    Linearly polarized light originates from atmospheric scattering or surface reflections and is perceived by insects, spiders, cephalopods, crustaceans, and some vertebrates. Thus, the neural basis underlying how this fundamental quality of light is detected is of broad interest. Morphologically unique, polarization-sensitive ommatidia exist in the dorsal periphery of many insect retinas, forming the dorsal rim area (DRA). However, much less is known about the retinal substrates of behavioral responses to polarized reflections. Drosophila exhibits polarotactic behavior, spontaneously aligning with the e-vector of linearly polarized light, when stimuli are presented either dorsally or ventrally. By combining behavioral experiments with genetic dissection and ultrastructural analyses, we show that distinct photoreceptors mediate the two behaviors: inner photoreceptors R7+R8 of DRA ommatidia are necessary and sufficient for dorsal polarotaxis, whereas ventral responses are mediated by combinations of outer and inner photoreceptors, both of which manifest previously unknown features that render them polarization sensitive. Drosophila uses separate retinal pathways for the detection of linearly polarized light emanating from the sky or from shiny surfaces. This work establishes a behavioral paradigm that will enable genetic dissection of the circuits underlying polarization vision. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Strong genetic overlap between executive functions and intelligence.

    Science.gov (United States)

    Engelhardt, Laura E; Mann, Frank D; Briley, Daniel A; Church, Jessica A; Harden, K Paige; Tucker-Drob, Elliot M

    2016-09-01

    Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic influences on EFs are very high, even in middle childhood, but the extent to which these genetic influences overlap with those on intelligence is unclear. We examined genetic and environmental overlap between EFs and intelligence in a racially and socioeconomically diverse sample of 811 twins ages 7 to 15 years (M = 10.91, SD = 1.74) from the Texas Twin Project. A general EF factor representing variance common to inhibition, switching, working memory, and updating domains accounted for substantial proportions of variance in intelligence, primarily via a genetic pathway. General EF continued to have a strong, genetically mediated association with intelligence even after controlling for processing speed. Residual variation in general intelligence was influenced only by shared and nonshared environmental factors, and there remained no genetic variance in general intelligence that was unique of EF. Genetic variance independent of EF did remain, however, in a more specific perceptual reasoning ability. These results provide evidence that genetic influences on general intelligence are highly overlapping with those on EF. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  8. Kosambi and the Genetic Mapping Function

    Indian Academy of Sciences (India)

    Research Centre, Indian. Agricultural ... Gregor Johann Mendel discovered that segregation of simple traits in pea ... Cytology furnishes mechanism that the experimental evidence demands” .... practice, however, the existence of interference may cause over .... Morgan's mapping function of true additivity; incomplete inter-.

  9. Assessing the genetic overlap between BMI and cognitive function

    Science.gov (United States)

    Marioni, R E; Yang, J; Dykiert, D; Mõttus, R; Campbell, A; Ibrahim-Verbaas, Carla A; Bressler, Jan; Debette, Stephanie; Schuur, Maaike; Smith, Albert V; Davies, Gail; Bennett, David A; Deary, Ian J; Ikram, M Arfan; Launer, Lenore J; Fitzpatrick, Annette L; Seshadri, Sudha; van Duijn, Cornelia M; Mosely Jr, Thomas H; Davies, G; Hayward, C; Porteous, D J; Visscher, P M; Deary, I J

    2016-01-01

    Obesity and low cognitive function are associated with multiple adverse health outcomes across the life course. They have a small phenotypic correlation (r=−0.11; high body mass index (BMI)−low cognitive function), but whether they have a shared genetic aetiology is unknown. We investigated the phenotypic and genetic correlations between the traits using data from 6815 unrelated, genotyped members of Generation Scotland, an ethnically homogeneous cohort from five sites across Scotland. Genetic correlations were estimated using the following: same-sample bivariate genome-wide complex trait analysis (GCTA)–GREML; independent samples bivariate GCTA–GREML using Generation Scotland for cognitive data and four other samples (n=20 806) for BMI; and bivariate LDSC analysis using the largest genome-wide association study (GWAS) summary data on cognitive function (n=48 462) and BMI (n=339 224) to date. The GWAS summary data were also used to create polygenic scores for the two traits, with within- and cross-trait prediction taking place in the independent Generation Scotland cohort. A large genetic correlation of −0.51 (s.e. 0.15) was observed using the same-sample GCTA–GREML approach compared with −0.10 (s.e. 0.08) from the independent-samples GCTA–GREML approach and −0.22 (s.e. 0.03) from the bivariate LDSC analysis. A genetic profile score using cognition-specific genetic variants accounts for 0.08% (P=0.020) of the variance in BMI and a genetic profile score using BMI-specific variants accounts for 0.42% (P=1.9 × 10−7) of the variance in cognitive function. Seven common genetic variants are significantly associated with both traits at Pcognitive function. PMID:26857597

  10. Genetic and anatomical basis of the barrier separating wakefulness and anesthetic-induced unresponsiveness.

    Directory of Open Access Journals (Sweden)

    William J Joiner

    Full Text Available A robust, bistable switch regulates the fluctuations between wakefulness and natural sleep as well as those between wakefulness and anesthetic-induced unresponsiveness. We previously provided experimental evidence for the existence of a behavioral barrier to transitions between these states of arousal, which we call neural inertia. Here we show that neural inertia is controlled by processes that contribute to sleep homeostasis and requires four genes involved in electrical excitability: Sh, sss, na and unc79. Although loss of function mutations in these genes can increase or decrease sensitivity to anesthesia induction, surprisingly, they all collapse neural inertia. These effects are genetically selective: neural inertia is not perturbed by loss-of-function mutations in all genes required for the sleep/wake cycle. These effects are also anatomically selective: sss acts in different neurons to influence arousal-promoting and arousal-suppressing processes underlying neural inertia. Supporting the idea that anesthesia and sleep share some, but not all, genetic and anatomical arousal-regulating pathways, we demonstrate that increasing homeostatic sleep drive widens the neural inertial barrier. We propose that processes selectively contributing to sleep homeostasis and neural inertia may be impaired in pathophysiological conditions such as coma and persistent vegetative states.

  11. Preparation of functional lupine protein fractions by dry separation

    NARCIS (Netherlands)

    Pelgrom, P.J.M.; Berghout, J.A.M.; Goot, van der A.J.; Boom, R.M.; Schutyser, M.A.I.

    2014-01-01

    Lupine protein concentrate is a promising ingredient that can be obtained by a combination of milling and air classification, generally called dry fractionation. This is a more sustainable route than conventional wet extraction and delivers a protein concentrate with native functional properties.

  12. High-functionalization of fiber-forming materials. Polymer membrane as separation media

    Energy Technology Data Exchange (ETDEWEB)

    Kamide, Kenji; Iijima, Hideki (Asahi Chemical Industry Co. Ltd., Osaka, (Japan))

    1989-07-05

    For obtaining higher functions by donating specific functions to the fiber, it is effective to change its structure. Various separating films which is known as an example of the high-functionalization of the fiber materials is an example of the fiber structure conversion from the view-point of substance-permeating function. This report firstly describes the features and types of the film separation method and the production of films, and then on the correlation between the structure and functions of the fibers, the correlation of the structure and the separating characteristics of the films, and the mechanism of the emergence of the film structure. Finally, applied examples of the film separating method in the medical field are described. In the medical liquid film separation, blood or plasma are the object of the separation. Blood has various components whose concentration and particle size are multiplicated, and yet requires a tremendous separating accuracy when compared with the industrial separation. Examples are a blood dialyzer film and an ultrafiltration film (film for plasma separation and virus separation), etc.. 28 refs., 6 figs., 2 tabs.

  13. Exchange functional by a range-separated exchange hole

    International Nuclear Information System (INIS)

    Toyoda, Masayuki; Ozaki, Taisuke

    2011-01-01

    An approximation to the exchange-hole density is proposed for the evaluation of the exact exchange energy in electronic structure calculations within the density-functional theory and the Kohn-Sham scheme. Based on the localized nature of density matrix, the exchange hole is divided into the short-range (SR) and long-range (LR) parts by using an adequate filter function, where the LR part is deduced by matching of moments with the exactly calculated SR counterpart, ensuring the correct asymptotic -1/r behavior of the exchange potential. With this division, the time-consuming integration is truncated at a certain interaction range, largely reducing the computation cost. The total energies, exchange energies, exchange potentials, and eigenvalues of the highest-occupied orbitals are calculated for the noble-gas atoms. The close agreement of the results with the exact values suggests the validity of the approximation.

  14. Alkylamine functionalized metal-organic frameworks for composite gas separations

    Science.gov (United States)

    Long, Jeffrey R.; McDonald, Thomas M.; D'Alessandro, Deanna M.

    2018-01-09

    Functionalized metal-organic framework adsorbents with ligands containing basic nitrogen groups such as alkylamines and alkyldiamines appended to the metal centers and method of isolating carbon dioxide from a stream of combined gases and carbon dioxide partial pressures below approximately 1 and 1000 mbar. The adsorption material has an isosteric heat of carbon dioxide adsorption of greater than -60 kJ/mol at zero coverage using a dual-site Langmuir model.

  15. Strong Genetic Overlap Between Executive Functions and Intelligence

    OpenAIRE

    Engelhardt, Laura E.; Mann, Frank D.; Briley, Daniel A.; Church, Jessica A.; Harden, K. Paige; Tucker-Drob, Elliot M.

    2016-01-01

    Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision-making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic infl...

  16. Genetic sex separation of the malaria vector, Anopheles arabiensis, by exposing eggs to dieldrin.

    Science.gov (United States)

    Yamada, Hanano; Benedict, Mark Q; Malcolm, Colin A; Oliva, Clelia F; Soliban, Sharon M; Gilles, Jeremie R L

    2012-06-19

    The sterile insect technique (SIT) has been used with success for suppressing or eliminating important insect pests of agricultural or veterinary importance. In order to develop SIT for mosquitoes, female elimination prior to release is essential as they are the disease-transmitting sex. A genetic sexing strain (GSS) of Anopheles arabiensis was created based on resistance to dieldrin, and methods of sex separation at the egg stage were developed. The use of this strain for SIT will require sexually sterile males: useful radiation doses for this purpose were determined for pupae and adults. For the creation of the sexing strain, dieldrin-resistant males were irradiated with 40 Gy using a 60Co source and were subsequently crossed to homozygous susceptible virgin females. Individual families were screened for semi-sterility and for male resistance to dieldrin. For sex separation, eggs of a resulting GSS, ANO IPCL1, were exposed to varying concentrations of dieldrin for different durations. Percent hatch, larval survival, and male and female emergence were recorded. Radiation induced sterility was determined following adult and pupa exposure to gamma rays at 0-105 Gy. Mortality induced by dieldrin treatment, and levels of sterility post radiation were investigated. ANO IPCL1 contains a complex chromosome aberration that pseudo-links the male-determining Y chromosome and dieldrin resistance, conferring high natural semi-sterility. Exposure of eggs to 2, 3, and 4 ppm dieldrin solutions resulted in complete female elimination without a significant decrease of male emergence compared to the controls. A dose of 75 Gy reduced the fertility to 3.8 and 6.9% when males were irradiated as pupae or adults respectively, but the proportions of progeny of these males reaching adulthood were 0.6 and 1.5% respectively The GSS ANO IPCL1 was shown to be a suitable strain for further testing for SIT though high semi-sterility is a disadvantage for mass rearing.

  17. The Information Content of Discrete Functions and Their Application in Genetic Data Analysis.

    Science.gov (United States)

    Sakhanenko, Nikita A; Kunert-Graf, James; Galas, David J

    2017-12-01

    The complex of central problems in data analysis consists of three components: (1) detecting the dependence of variables using quantitative measures, (2) defining the significance of these dependence measures, and (3) inferring the functional relationships among dependent variables. We have argued previously that an information theory approach allows separation of the detection problem from the inference of functional form problem. We approach here the third component of inferring functional forms based on information encoded in the functions. We present here a direct method for classifying the functional forms of discrete functions of three variables represented in data sets. Discrete variables are frequently encountered in data analysis, both as the result of inherently categorical variables and from the binning of continuous numerical variables into discrete alphabets of values. The fundamental question of how much information is contained in a given function is answered for these discrete functions, and their surprisingly complex relationships are illustrated. The all-important effect of noise on the inference of function classes is found to be highly heterogeneous and reveals some unexpected patterns. We apply this classification approach to an important area of biological data analysis-that of inference of genetic interactions. Genetic analysis provides a rich source of real and complex biological data analysis problems, and our general methods provide an analytical basis and tools for characterizing genetic problems and for analyzing genetic data. We illustrate the functional description and the classes of a number of common genetic interaction modes and also show how different modes vary widely in their sensitivity to noise.

  18. Neurocognitive functioning in parents of schizophrenia patients: Attentional and executive performance vary with genetic loading.

    Science.gov (United States)

    Schulze-Rauschenbach, Svenja; Lennertz, Leonhard; Ruhrmann, Stephan; Petrovsky, Nadine; Ettinger, Ulrich; Pukrop, Ralf; Dreher, Jan; Klosterkötter, Joachim; Maier, Wolfgang; Wagner, Michael

    2015-12-30

    Neuropsychological deficits are candidate endophenotypes of schizophrenia which can assist to explain the neurocognitive impact of genetic risk variants. The identification of endophenotypes is often based on the familiality of these phenotypes. Several studies demonstrate neuropsychological deficits in unaffected biological relatives of schizophrenia patients without differentiating between genetic and non-genetic factors underlying these deficits. We assessed N=129 unaffected biological parents of schizophrenia patients, N=28 schizophrenia patients (paranoid subtype), and N=143 controls without a family history of schizophrenia with an extensive neuropsychological test battery. Direct comparison of N=22 parents with an ancestral history of schizophrenia (more likely carriers, MLC) and N=17 of their spouses without such a history (less likely carriers, LLC) allowed the separation of genetic and non-genetic aspects in cognition. Overall, parents showed significant deficits in neuropsychological tasks from all cognitive domains with medium effect sizes. Direct comparisons of MLC- and LLC-parents showed that attentional and executive tasks were most strongly affected by genetic loading. To conclude, unaffected parents of schizophrenia patients showed modest yet significant impairments in attention, memory, and executive functioning. In particular, attentional and executive impairments varied most strongly with genetic loading for schizophrenia, prioritising these dysfunctions for genotype-endophenotype analyses. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Star-formation functions and the genetics of pulsar origin

    International Nuclear Information System (INIS)

    Guseinov, O.K.; Kasumov, F.K.; Yusifov, I.M.

    1982-01-01

    The star-formation function and the genetics of pulsar origin are discussed. It is shown that the progenitors of pulsars are main-sequence stars with masses of >5M/sub sun/ for almost all the kinds of initial mass functions discussed in the literature. Pulsars are genetically connected with supernova outbursts (mainly of type II). The probability of pulsar formation as a result of ''quiet collapse'' is extremely low. Thus, the hypothesis that pulsars are formed from objects of the extreme planar component of the Galaxy is confirmed on more complete and statistically uniform material

  20. Application of independent component analysis for speech-music separation using an efficient score function estimation

    Science.gov (United States)

    Pishravian, Arash; Aghabozorgi Sahaf, Masoud Reza

    2012-12-01

    In this paper speech-music separation using Blind Source Separation is discussed. The separating algorithm is based on the mutual information minimization where the natural gradient algorithm is used for minimization. In order to do that, score function estimation from observation signals (combination of speech and music) samples is needed. The accuracy and the speed of the mentioned estimation will affect on the quality of the separated signals and the processing time of the algorithm. The score function estimation in the presented algorithm is based on Gaussian mixture based kernel density estimation method. The experimental results of the presented algorithm on the speech-music separation and comparing to the separating algorithm which is based on the Minimum Mean Square Error estimator, indicate that it can cause better performance and less processing time

  1. The value function as a criterion of analysis in separation technologies

    International Nuclear Information System (INIS)

    Peculea, Marius

    2005-01-01

    Production costs of heavy water are described by two functions: φ(ε), the energy function which represents the variable costs and φ(τ), the technologic function which represents the stable costs. The Dirac value function related to the circulation in the separation cascade allows calculating φ(ε) and consequently the technologic function may be represented in relation to the specific separation process. This representation allows the qualitative analysis of different separation processes or, for a given process, provides the analysis of different technological solutions which were worked out. An example is given referring to the analysis of heavy water technologies of separation through the dual temperature process of H 2 O-H 2 S isotopic exchange

  2. Relations of mitochondrial genetic variants to measures of vascular function.

    Science.gov (United States)

    Fetterman, Jessica L; Liu, Chunyu; Mitchell, Gary F; Vasan, Ramachandran S; Benjamin, Emelia J; Vita, Joseph A; Hamburg, Naomi M; Levy, Daniel

    2018-05-01

    Mitochondrial genetic variation with resultant alterations in oxidative phosphorylation may influence vascular function and contribute to cardiovascular disease susceptibility. We assessed relations of peptide-encoding variants in the mitochondrial genome with measures of vascular function in Framingham Heart Study participants. Of 258 variants assessed, 40 were predicted to have functional consequences by bioinformatics programs. A maternal pattern of heritability was estimated to contribute to the variability of aortic stiffness. A putative association with a microvascular function measure was identified that requires replication. The methods we have developed can be applied to assess the relations of mitochondrial genetic variation to other phenotypes. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  3. Unexpected absence of genetic separation of a highly diverse population of hookworms from geographically isolated hosts.

    Science.gov (United States)

    Haynes, Benjamin T; Marcus, Alan D; Higgins, Damien P; Gongora, Jaime; Gray, Rachael; Šlapeta, Jan

    2014-12-01

    The high natal site fidelity of endangered Australian sea lions (Neophoca cinerea) along the southern Australian coast suggests that their maternally transmitted parasitic species, such as hookworms, will have restricted potential for dispersal. If this is the case, we would expect to find a hookworm haplotype structure corresponding to that of the host mtDNA haplotype structure; that is, restricted among geographically separated colonies. In this study, we used a fragment of the cytochrome c oxidase I mitochondrial DNA (mtDNA) gene to investigate the diversity of hookworms (Uncinaria sanguinis) in N. cinerea to assess the importance of host distribution and ecology on the evolutionary history of the parasite. High haplotype (h=0.986) and nucleotide diversity (π=0.013) were seen, with 45 unique hookworm mtDNA haplotypes across N. cinerea colonies; with most of the variation (78%) arising from variability within hookworms from individual colonies. This is supported by the low genetic differentiation co-efficient (GST=0.007) and a high gene flow (Nm=35.25) indicating a high migration rate between the populations of hookworms. The haplotype network demonstrated no clear distribution and delineation of haplotypes according to geographical location. Our data rejects the vicariance hypothesis; that female host natal site fidelity and the transmammary route of infection restrict hookworm gene flow between N. cinerea populations and highlights the value of studies of parasite diversity and dispersal to challenge our understanding of parasite and host ecology. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Associations between genetic risk, functional brain network organization and neuroticism

    NARCIS (Netherlands)

    Servaas, Michelle N.; Geerligs, Linda; Bastiaansen, Jojanneke A.; Renken, Remco J.; Marsman, Jan-Bernard C.; Nolte, Ilja M.; Ormel, Johan; Aleman, Andre; Riese, Harriette

    2017-01-01

    Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on

  5. 45 CFR 302.20 - Separation of cash handling and accounting functions.

    Science.gov (United States)

    2010-10-01

    ... accounting functions. The State plan shall provide that the following requirements and criteria to separate the cash handling and accounting functions are in effect. (a) IV-D responsibility. The IV-D agency... receipts of support do not participate in accounting or operating functions which would permit them to...

  6. Developmental imaging genetics: linking dopamine function to adolescent behavior.

    Science.gov (United States)

    Padmanabhan, Aarthi; Luna, Beatriz

    2014-08-01

    Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to non-invasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. A Multivariate Genetic Analysis of Specific Phobia, Separation Anxiety and Social Phobia in Early Childhood

    Science.gov (United States)

    Eley, Thalia C.; Rijsdijk, Fruhling V.; Perrin, Sean; O'Connor, Thomas G.; Bolton, Derek

    2008-01-01

    Background: Comorbidity amongst anxiety disorders is very common in children as in adults and leads to considerable distress and impairment, yet is poorly understood. Multivariate genetic analyses can shed light on the origins of this comorbidity by revealing whether genetic or environmental risks for one disorder also influence another. We…

  8. Functional and Genetic Analysis of Choroid Plexus Development in Zebrafish

    Directory of Open Access Journals (Sweden)

    Hannah Elizabeth Henson

    2014-11-01

    Full Text Available The choroid plexus, an epithelial-based structure localized in the brain ventricle, is the major component of the blood-cerebrospinal fluid barrier. The choroid plexus produces the cerebrospinal fluid and regulates the components of the cerebrospinal fluid. Abnormal choroid plexus function is associated with neurodegenerative diseases, tumor formation in the choroid plexus epithelium, and hydrocephaly. In this study, we used zebrafish (Danio rerio as a model system to understand the genetic components of choroid plexus development. We generated an enhancer trap line, Et(cp:EGFPsj2, that expresses enhanced green fluorescent protein (EGFP in the choroid plexus epithelium. Using immunohistochemistry and fluorescent tracers, we demonstrated that the zebrafish choroid plexus possesses brain barrier properties such as tight junctions and transporter activity. Thus, we have established zebrafish as a functionally relevant model to study choroid plexus development. Using an unbiased approach, we performed a forward genetic dissection of the choroid plexus to identify genes essential for its formation and function. Using Et(cp:EGFPsj2, we isolated 10 recessive mutant lines with choroid plexus abnormalities, which were grouped into five classes based on GFP intensity, epithelial localization, and overall choroid plexus morphology. We also mapped the mutation for two mutant lines to chromosomes 4 and 21, respectively. The mutants generated in this study can be used to elucidate specific genes and signaling pathways essential for choroid plexus development, function, and/or maintenance and will provide important insights into how these genetic mutations contribute to disease.

  9. A candidate multimodal functional genetic network for thermal adaptation

    Directory of Open Access Journals (Sweden)

    Katharina C. Wollenberg Valero

    2014-09-01

    Full Text Available Vertebrate ectotherms such as reptiles provide ideal organisms for the study of adaptation to environmental thermal change. Comparative genomic and exomic studies can recover markers that diverge between warm and cold adapted lineages, but the genes that are functionally related to thermal adaptation may be difficult to identify. We here used a bioinformatics genome-mining approach to predict and identify functions for suitable candidate markers for thermal adaptation in the chicken. We first established a framework of candidate functions for such markers, and then compiled the literature on genes known to adapt to the thermal environment in different lineages of vertebrates. We then identified them in the genomes of human, chicken, and the lizard Anolis carolinensis, and established a functional genetic interaction network in the chicken. Surprisingly, markers initially identified from diverse lineages of vertebrates such as human and fish were all in close functional relationship with each other and more associated than expected by chance. This indicates that the general genetic functional network for thermoregulation and/or thermal adaptation to the environment might be regulated via similar evolutionarily conserved pathways in different vertebrate lineages. We were able to identify seven functions that were statistically overrepresented in this network, corresponding to four of our originally predicted functions plus three unpredicted functions. We describe this network as multimodal: central regulator genes with the function of relaying thermal signal (1, affect genes with different cellular functions, namely (2 lipoprotein metabolism, (3 membrane channels, (4 stress response, (5 response to oxidative stress, (6 muscle contraction and relaxation, and (7 vasodilation, vasoconstriction and regulation of blood pressure. This network constitutes a novel resource for the study of thermal adaptation in the closely related nonavian reptiles and

  10. Functional characterization of genetic enzyme variations in human lipoxygenases

    Directory of Open Access Journals (Sweden)

    Thomas Horn

    2013-01-01

    Full Text Available Mammalian lipoxygenases play a role in normal cell development and differentiation but they have also been implicated in the pathogenesis of cardiovascular, hyperproliferative and neurodegenerative diseases. As lipid peroxidizing enzymes they are involved in the regulation of cellular redox homeostasis since they produce lipid hydroperoxides, which serve as an efficient source for free radicals. There are various epidemiological correlation studies relating naturally occurring variations in the six human lipoxygenase genes (SNPs or rare mutations to the frequency for various diseases in these individuals, but for most of the described variations no functional data are available. Employing a combined bioinformatical and enzymological strategy, which included structural modeling and experimental site-directed mutagenesis, we systematically explored the structural and functional consequences of non-synonymous genetic variations in four different human lipoxygenase genes (ALOX5, ALOX12, ALOX15, and ALOX15B that have been identified in the human 1000 genome project. Due to a lack of a functional expression system we resigned to analyze the functionality of genetic variations in the hALOX12B and hALOXE3 gene. We found that most of the frequent non-synonymous coding SNPs are located at the enzyme surface and hardly alter the enzyme functionality. In contrast, genetic variations which affect functional important amino acid residues or lead to truncated enzyme variations (nonsense mutations are usually rare with a global allele frequency<0.1%. This data suggest that there appears to be an evolutionary pressure on the coding regions of the lipoxygenase genes preventing the accumulation of loss-of-function variations in the human population.

  11. Validation of a simple isotopic technique for the measurement of global and separated renal function

    International Nuclear Information System (INIS)

    Chachati, A.; Meyers, A.; Rigo, P.; Godon, J.P.

    1986-01-01

    Schlegel and Gates described an isotopic method for the measurement of global and separated glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) based on the determination by scintillation camera of the fraction of the injected dose (99mTc-DTPA-[ 131 I]hippuran) present in the kidneys 1-3 min after its administration. This method requires counting of the injected dose and attenuation correction, but no blood or urine sampling. We validated this technique by the simultaneous infusion of inulin and para-amino hippuric acid (PAH) in patients with various levels of renal function (anuric to normal). To better define individual renal function we studied 9 kidneys in patients either nephrectomized or with a nephrostomy enabling separated function measurement. A good correlation between inulin, PAH clearance, and isotopic GFR-ERPF measurement for both global and separate renal function was observed

  12. 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.

  13. Alternative separation of exchange and correlation energies in multi-configuration range-separated density-functional theory.

    Science.gov (United States)

    Stoyanova, Alexandrina; Teale, Andrew M; Toulouse, Julien; Helgaker, Trygve; Fromager, Emmanuel

    2013-10-07

    The alternative separation of exchange and correlation energies proposed by Toulouse et al. [Theor. Chem. Acc. 114, 305 (2005)] is explored in the context of multi-configuration range-separated density-functional theory. The new decomposition of the short-range exchange-correlation energy relies on the auxiliary long-range interacting wavefunction rather than the Kohn-Sham (KS) determinant. The advantage, relative to the traditional KS decomposition, is that the wavefunction part of the energy is now computed with the regular (fully interacting) Hamiltonian. One potential drawback is that, because of double counting, the wavefunction used to compute the energy cannot be obtained by minimizing the energy expression with respect to the wavefunction parameters. The problem is overcome by using short-range optimized effective potentials (OEPs). The resulting combination of OEP techniques with wavefunction theory has been investigated in this work, at the Hartree-Fock (HF) and multi-configuration self-consistent-field (MCSCF) levels. In the HF case, an analytical expression for the energy gradient has been derived and implemented. Calculations have been performed within the short-range local density approximation on H2, N2, Li2, and H2O. Significant improvements in binding energies are obtained with the new decomposition of the short-range energy. The importance of optimizing the short-range OEP at the MCSCF level when static correlation becomes significant has also been demonstrated for H2, using a finite-difference gradient. The implementation of the analytical gradient for MCSCF wavefunctions is currently in progress.

  14. Pilot and Controller Evaluations of Separation Function Allocation in Air Traffic Management

    Science.gov (United States)

    Wing, David; Prevot, Thomas; Morey, Susan; Lewis, Timothy; Martin, Lynne; Johnson, Sally; Cabrall, Christopher; Como, Sean; Homola, Jeffrey; Sheth-Chandra, Manasi; style="text-decoration: none; " href="javascript:void(0); " onClick="displayelement('author_20130014930'); toggleEditAbsImage('author_20130014930_show'); toggleEditAbsImage('author_20130014930_hide'); "> style="display:inline; width:12px; height:12px; " src="images/arrow-up.gif" width="12" height="12" border="0" alt="hide" id="author_20130014930_show"> style="width:12px; height:12px; display:none; " src="images/arrow-down.gif" width="12" height="12" border="0" alt="hide" id="author_20130014930_hide">

    2013-01-01

    Two human-in-the-loop simulation experiments were conducted in coordinated fashion to investigate the allocation of separation assurance functions between ground and air and between humans and automation. The experiments modeled a mixed-operations concept in which aircraft receiving ground-based separation services shared the airspace with aircraft providing their own separation service (i.e., self-separation). Ground-based separation was provided by air traffic controllers without automation tools, with tools, or by ground-based automation with controllers in a managing role. Airborne self-separation was provided by airline pilots using self-separation automation enabled by airborne surveillance technology. The two experiments, one pilot-focused and the other controller-focused, addressed selected key issues of mixed operations, assuming the starting point of current-day operations and modeling an emergence of NextGen technologies and procedures. In the controller-focused experiment, the impact of mixed operations on controller performance was assessed at four stages of NextGen implementation. In the pilot-focused experiment, the limits to which pilots with automation tools could take full responsibility for separation from ground-controlled aircraft were tested. Results indicate that the presence of self-separating aircraft had little impact on the controllers' ability to provide separation services for ground-controlled aircraft. Overall performance was best in the most automated environment in which all aircraft were data communications equipped, ground-based separation was highly automated, and self-separating aircraft had access to trajectory intent information for all aircraft. In this environment, safe, efficient, and highly acceptable operations could be achieved for twice today's peak airspace throughput. In less automated environments, reduced trajectory intent exchange and manual air traffic control limited the safely achievable airspace throughput and

  15. Engineering and Functional Analysis of Mitotic Kinases Through Chemical Genetics.

    Science.gov (United States)

    Jones, Mathew J K; Jallepalli, Prasad V

    2016-01-01

    During mitosis, multiple protein kinases transform the cytoskeleton and chromosomes into new and highly dynamic structures that mediate the faithful transmission of genetic information and cell division. However, the large number and strong conservation of mammalian kinases in general pose significant obstacles to interrogating them with small molecules, due to the difficulty in identifying and validating those which are truly selective. To overcome this problem, a steric complementation strategy has been developed, in which a bulky "gatekeeper" residue within the active site of the kinase of interest is replaced with a smaller amino acid, such as glycine or alanine. The enlarged catalytic pocket can then be targeted in an allele-specific manner with bulky purine analogs. This strategy provides a general framework for dissecting kinase function with high selectivity, rapid kinetics, and reversibility. In this chapter we discuss the principles and techniques needed to implement this chemical genetic approach in mammalian cells.

  16. Range-separated density-functional theory for molecular excitation energies

    International Nuclear Information System (INIS)

    Rebolini, E.

    2014-01-01

    Linear-response time-dependent density-functional theory (TDDFT) is nowadays a method of choice to compute molecular excitation energies. However, within the usual adiabatic semi-local approximations, it is not able to describe properly Rydberg, charge-transfer or multiple excitations. Range separation of the electronic interaction allows one to mix rigorously density-functional methods at short range and wave function or Green's function methods at long range. When applied to the exchange functional, it already corrects most of these deficiencies but multiple excitations remain absent as they need a frequency-dependent kernel. In this thesis, the effects of range separation are first assessed on the excitation energies of a partially-interacting system in an analytic and numerical study in order to provide guidelines for future developments of range-separated methods for excitation energy calculations. It is then applied on the exchange and correlation TDDFT kernels in a single-determinant approximation in which the long-range part of the correlation kernel vanishes. A long-range frequency-dependent second-order correlation kernel is then derived from the Bethe-Salpeter equation and added perturbatively to the range-separated TDDFT kernel in order to take into account the effects of double excitations. (author)

  17. Functionalized copolyimide membranes for the separation of gaseous and liquid mixtures

    Directory of Open Access Journals (Sweden)

    Nadine Schmeling

    2010-08-01

    Full Text Available Functionalized copolyimides continue to attract much attention as membrane materials because they can fulfill the demands for industrial applications. Thus not only good separation characteristics but also high temperature stability and chemical resistance are required. Furthermore, it is very important that membrane materials are resistant to plasticization since it has been shown that this phenomenon leads to a significant increase in permeability with a dramatic loss in selectivity. Plasticization effects occur with most polymer membranes at high CO2 concentrations and pressures, respectively. Plasticization effects are also observed with higher hydrocarbons such as propylene, propane, aromatics or sulfur containing aromatics. Unfortunately, these components are present in mixtures of high commercial relevance and can be separated economically by single membrane units or hybrid processes where conventional separation units are combined with membrane-based processes. In this paper the advantages of carboxy group containing 6FDA (4,4′-hexafluoroisopropylidene diphthalic anhydride -copolyimides are discussed based on the experimental results for non cross-linked, ionically and covalently cross-linked membrane materials with respect to the separation of olefins/paraffins, e.g. propylene/propane, aromatic/aliphatic separation e.g. benzene/cyclohexane as well as high pressure gas separations, e.g. CO2/CH4 mixtures. In addition, opportunities for implementing the membrane units in conventional separation processes are discussed.

  18. High-Throughput Genetic Analysis and Combinatorial Chiral Separations Based on Capillary Electrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Wenwan [Iowa State Univ., Ames, IA (United States)

    2003-01-01

    Capillary electrophoresis (CE) offers many advantages over conventional analytical methods, such as speed, simplicity, high resolution, low cost, and small sample consumption, especially for the separation of enantiomers. However, chiral method developments still can be time consuming and tedious. They designed a comprehensive enantioseparation protocol employing neutral and sulfated cyclodextrins as chiral selectors for common basic, neutral, and acidic compounds with a 96-capillary array system. By using only four judiciously chosen separation buffers, successful enantioseparations were achieved for 49 out of 54 test compounds spanning a large variety of pKs and structures. Therefore, unknown compounds can be screened in this manner to identify optimal enantioselective conditions in just one rn. In addition to superior separation efficiency for small molecules, CE is also the most powerful technique for DNA separations. Using the same multiplexed capillary system with UV absorption detection, the sequence of a short DNA template can be acquired without any dye-labels. Two internal standards were utilized to adjust the migration time variations among capillaries, so that the four electropherograms for the A, T, C, G Sanger reactions can be aligned and base calling can be completed with a high level of confidence. the CE separation of DNA can be applied to study differential gene expression as well. Combined with pattern recognition techniques, small variations among electropherograms obtained by the separation of cDNA fragments produced from the total RNA samples of different human tissues can be revealed. These variations reflect the differences in total RNA expression among tissues. Thus, this Ce-based approach can serve as an alternative to the DNA array techniques in gene expression analysis.

  19. Straight-run vs. sex separate rearing for two broiler genetic lines Part 2: Economic analysis and processing advantages.

    Science.gov (United States)

    Da Costa, M J; Colson, G; Frost, T J; Halley, J; Pesti, G M

    2017-07-01

    The objective of this analysis was to evaluate the effects of raising broilers under sex separate and straight-run conditions for 2 broiler genetic lines. One-day-old Ross 308 and Ross 708 chicks (n = 1,344) were sex separated and placed in 48 pens according to rearing type: sex separate (28 males or 28 females) or straight-run (14 males + 14 females). There were 3 dietary phases: starter (zero to 17 d), grower (17 to 32 d), and finisher (32 to 48 d). Bird individual BW and group feed intakes were measured at 12, 17, 25, 32, 42, and 48 d to evaluate performance. At 33, 43, and 49 d 4 birds per pen (straight-run pens 2 males + 2 females) were sampled for carcass yield evaluation. Data were analyzed using linear and non-linear regression in order to estimate feed intake and cut-up weights at 3 separate market weights (1,700, 2,700, and 3,700 g). Returns over feed cost were estimated for a 1.8 million broiler complex for each rearing system and under 9 feed/meat price scenarios. Overall, rearing birds that were sex separated resulted in extra income that ranged from ${\\$}$48,824 to ${\\$}$330,300 per week, depending on the market targeted and feed and meat price scenarios. Sex separation was shown to be especially important in disadvantageous scenarios in which feed prices were high. Gains from sex separation were markedly higher for the Ross 708 than for the Ross 308 broilers. Bird variability also was evaluated at the 3 separate market ages under narrow ranges of BW that were targeted. Straight-run birds decreased the number of birds present in the desired range. Depending on market weight, straight-run rearing resulted in 9.1 to 16.6% fewer birds than sex separate rearing to meet marketing goals. It was concluded that sex separation can result in increased company profitability and have possible beneficial effects at the processing plant due to increased bird uniformity. © 2017 Poultry Science Association Inc.

  20. Function Allocation between Automation and Human Pilot for Airborne Separation Assurance

    Science.gov (United States)

    Idris, Husni; Enea, Gabriele; Lewis, TImothy A.

    2016-01-01

    Maintaining safe separation between aircraft is a key determinant of the airspace capacity to handle air transportation. With the advent of satellite-based surveillance, aircraft equipped with the needed technologies are now capable of maintaining awareness of their location in the airspace and sharing it with their surrounding traffic. As a result, concepts and cockpit automation are emerging to enable delegating the responsibility of maintaining safe separation from traffic to the pilot; thus increasing the airspace capacity by alleviating the limitation of the current non-scalable centralized ground-based system. In this paper, an analysis of allocating separation assurance functions to the human pilot and cockpit automation is presented to support the design of these concepts and technologies. A task analysis was conducted with the help of Petri nets to identify the main separation assurance functions and their interactions. Each function was characterized by three behavior levels that may be needed to perform the task: skill, rule and knowledge based levels. Then recommendations are made for allocating each function to an automation scale based on their behavior level characterization and with the help of Subject matter experts.

  1. Pelvic incidence variation among individuals: functional influence versus genetic determinism.

    Science.gov (United States)

    Chen, Hong-Fang; Zhao, Chang-Qing

    2018-03-20

    Pelvic incidence has become one of the most important sagittal parameters in spinal surgery. Despite its great importance, pelvic incidence can vary from 33° to 85° in the normal population. The reasons for this great variability in pelvic incidence remain unexplored. The objective of this article is to present some possible interpretations for the great variability in pelvic incidence under both normal and pathological conditions and to further understand the determinants of pelvic incidence from the perspective of the functional requirements for bipedalism and genetic backgrounds via a literature review. We postulate that both pelvic incidence and pelvic morphology may be genetically predetermined, and a great variability in pelvic incidence may already exist even before birth. This great variability may also serve as a further reminder that the sagittal profile, bipedal locomotion mode, and genetic background of every individual are unique and specific, and clinicians should avoid making universally applying broad generalizations of pelvic incidence. Although PI is an important parameter and there are many theories behind its variability, we still do not have clear mechanistic answers.

  2. A snapshot of functional genetic studies in Medicago truncatula

    Directory of Open Access Journals (Sweden)

    Yun Kang

    2016-08-01

    Full Text Available In the current context of food security, increase of plant protein production in a sustainable manner represents one of the major challenges of agronomic research, which could be partially resolved by increased cultivation of legume crops. Medicago truncatula is now a well-established model for legume genomic and genetic studies. With the establishment of genomics tools and mutant populations in M. truncatula, it has become an important resource to answer some of the basic biological questions related to plant development and stress tolerance. This review has an objective to overview a decade of genetic studies in this model plant from generation of mutant populations to nowadays. To date, the three biological fields, which have been extensively studied in M. truncatula, are the symbiotic nitrogen fixation, the seed development, and the abiotic stress tolerance, due to their significant agronomic impacts. In this review, we summarize functional genetic studies related to these three major biological fields. We integrated analyses of a nearly exhaustive list of genes into their biological contexts in order to provide an overview of the forefront research advances in this important legume model plant.

  3. Maternal separation affects dopamine transporter function in the Spontaneously Hypertensive Rat: An in vivo electrochemical study

    Directory of Open Access Journals (Sweden)

    Womersley Jacqueline S

    2011-12-01

    Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT in ways that distinguish SHR from control rat strains. Methods SHR and control Wistar-Kyoto (WKY rats were subjected to maternal separation for 3 hours per day from postnatal day 2 to 14. Rats were tested for separation-induced anxiety-like behaviour followed by in vivo chronoamperometry to determine whether changes had occurred in striatal clearance of dopamine by DAT. The rate of disappearance of ejected dopamine was used as a measure of DAT function. Results Consistent with a model for ADHD, SHR were more active than WKY in the open field. SHR entered the inner zone more frequently and covered a significantly greater distance than WKY. Maternal separation increased the time that WKY spent in the closed arms and latency to enter the open arms of the elevated plus maze, consistent with other rat strains. Of note is that, maternal separation failed to produce anxiety-like behaviour in SHR. Analysis of the chronoamperometric data revealed that there was no difference in DAT function in the striatum of non-separated SHR and WKY. Maternal separation decreased the rate of dopamine clearance (k-1 in SHR striatum. Consistent with this observation, the dopamine clearance time (T100 was increased in SHR. These results suggest that the chronic mild stress of

  4. [Scientific potential of phenomics - functional direction of genetics].

    Science.gov (United States)

    Marasanov, A V; Valtseva, E A

    In this paper on the based on the integration of known theories, doctrines and concepts - principles of consistency and self-regulation of physiological functions (Pavlov I.P., 1950), the theory offunctional systems (Anokhin P.K., 1973), the theory of adaptive reactions (Selye H., 1960 ; Garkavi LKh et al, 1979), the doctrine of the dominant (Ukhtomsky A.A., 1966), doctrine on health (Baevsky R.M.), doctrine on the body type of the human by Merlin VS. conception on the “the interrelationship between the function and genetic apparatus” by Meyerson F.Z., Pshennikova M.G., Platonov V.N., and others, there is proposed to select phenomics - functional division of genetics considering the poolability of specific mechanisms of the body in an integral system of the adaptive act in favor of the development of a personalized approach to the diagnosis and prevention of non-communicable diseases, increasing life expectancy of working age into the particular scientific direction. The task of phenomics is the establishment of the phenotypic characteristics of the person, norms of the response of systems of his body, determination of the deviation of the level of the functioning of the each system from the norm of its response and the elaboration of the tactics for the correction of the functional state of the organism (the optimization of its life activity), with taking into account the directedness of the interaction of body systems. The description of the shaping of the mechanism of stereotyped response of the organism generated an important contribution to the development of phenomics. Stereotyped response being initiated by the non-specific response of the body is aimed at the shaping of the activity of its systems after a fashion of norms of the activity, promotes the recovery of the specificity of the body, plays an important role in the establishment of cause-effect relations of the disease.

  5. Multicollinearity in spatial genetics: separating the wheat from the chaff using commonality analyses.

    Science.gov (United States)

    Prunier, J G; Colyn, M; Legendre, X; Nimon, K F; Flamand, M C

    2015-01-01

    Direct gradient analyses in spatial genetics provide unique opportunities to describe the inherent complexity of genetic variation in wildlife species and are the object of many methodological developments. However, multicollinearity among explanatory variables is a systemic issue in multivariate regression analyses and is likely to cause serious difficulties in properly interpreting results of direct gradient analyses, with the risk of erroneous conclusions, misdirected research and inefficient or counterproductive conservation measures. Using simulated data sets along with linear and logistic regressions on distance matrices, we illustrate how commonality analysis (CA), a detailed variance-partitioning procedure that was recently introduced in the field of ecology, can be used to deal with nonindependence among spatial predictors. By decomposing model fit indices into unique and common (or shared) variance components, CA allows identifying the location and magnitude of multicollinearity, revealing spurious correlations and thus thoroughly improving the interpretation of multivariate regressions. Despite a few inherent limitations, especially in the case of resistance model optimization, this review highlights the great potential of CA to account for complex multicollinearity patterns in spatial genetics and identifies future applications and lines of research. We strongly urge spatial geneticists to systematically investigate commonalities when performing direct gradient analyses. © 2014 John Wiley & Sons Ltd.

  6. Severe congenital malformations, family functioning and parents' separation/divorce: a longitudinal study.

    Science.gov (United States)

    Brenner, M; Côté, S M; Boivin, M; Tremblay, R E

    2016-01-01

    We aim to explore the association of a severe congenital malformation (SCM) with postnatal family functioning and parents' separation/divorce and to examine if this association might be moderated by birth order of the child and parental level of education. SCM refers to malformations that, without medical intervention, cause handicap or death. Using the Quebec Longitudinal Study of Child Development, an ongoing population-based birth cohort study initiated in 1998, we compared 1675 families of children with and without a SCM to identify if having a child with a SCM was associated with maternal perception of family functioning. We examined if an SCM was associated with parents' separation and examined parents' education level and birth order of the children to evaluate whether these factors had any moderating effect on the results. There were no significant differences in family functioning between families with and without a SCM child at 5 and 17 months. At 5 months, family functioning was significantly better (P = 0.03) for families with a SCM firstborn child than for families with a SCM child that is not firstborn. For parental separation, no significant differences were observed at 5 and 29 months and 4 years. No significant moderating effects were observed for birth order and parental education on parental separation. Families of children with a SCM do not appear to be at higher risk of family dysfunction within the first 17 months after birth nor of parental separation within the first 4 years after birth. Family functioning tends to be worst in families where the child with SCM is the second or subsequent child born. © 2015 John Wiley & Sons Ltd.

  7. The genetics of hair-cell function in zebrafish.

    Science.gov (United States)

    Nicolson, Teresa

    2017-09-01

    Our ears are remarkable sensory organs, providing the important senses of balance and hearing. The complex structure of the inner ear, or 'labyrinth', along with the assorted neuroepithelia, have evolved to detect head movements and sounds with impressive sensitivity. The rub is that the inner ear is highly vulnerable to genetic lesions and environmental insults. According to National Institute of Health estimates, hearing loss is one of the most commonly inherited or acquired sensorineural diseases. To understand the causes of deafness and balance disorders, it is imperative to understand the underlying biology of the inner ear, especially the inner workings of the sensory receptors. These receptors, which are termed hair cells, are particularly susceptible to genetic mutations - more than two dozen genes are associated with defects in this cell type in humans. Over the past decade, a substantial amount of progress has been made in working out the molecular basis of hair-cell function using vertebrate animal models. Given the transparency of the inner ear and the genetic tools that are available, zebrafish have become an increasingly popular animal model for the study of deafness and vestibular dysfunction. Mutagenesis screens for larval defects in hearing and balance have been fruitful in finding key components, many of which have been implicated in human deafness. This review will focus on the genes that are required for hair-cell function in zebrafish, with a particular emphasis on mechanotransduction. In addition, the generation of new tools available for the characterization of zebrafish hair-cell mutants will be discussed.

  8. Distinctive Correspondence Between Separable Visual Attention Functions and Intrinsic Brain Networks

    Science.gov (United States)

    Ruiz-Rizzo, Adriana L.; Neitzel, Julia; Müller, Hermann J.; Sorg, Christian; Finke, Kathrin

    2018-01-01

    Separable visual attention functions are assumed to rely on distinct but interacting neural mechanisms. Bundesen's “theory of visual attention” (TVA) allows the mathematical estimation of independent parameters that characterize individuals' visual attentional capacity (i.e., visual processing speed and visual short-term memory storage capacity) and selectivity functions (i.e., top-down control and spatial laterality). However, it is unclear whether these parameters distinctively map onto different brain networks obtained from intrinsic functional connectivity, which organizes slowly fluctuating ongoing brain activity. In our study, 31 demographically homogeneous healthy young participants performed whole- and partial-report tasks and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Report accuracy was modeled using TVA to estimate, individually, the four TVA parameters. Networks encompassing cortical areas relevant for visual attention were derived from independent component analysis of rs-fMRI data: visual, executive control, right and left frontoparietal, and ventral and dorsal attention networks. Two TVA parameters were mapped on particular functional networks. First, participants with higher (vs. lower) visual processing speed showed lower functional connectivity within the ventral attention network. Second, participants with more (vs. less) efficient top-down control showed higher functional connectivity within the dorsal attention network and lower functional connectivity within the visual network. Additionally, higher performance was associated with higher functional connectivity between networks: specifically, between the ventral attention and right frontoparietal networks for visual processing speed, and between the visual and executive control networks for top-down control. The higher inter-network functional connectivity was related to lower intra-network connectivity. These results demonstrate that separable visual attention

  9. Distinctive Correspondence Between Separable Visual Attention Functions and Intrinsic Brain Networks.

    Science.gov (United States)

    Ruiz-Rizzo, Adriana L; Neitzel, Julia; Müller, Hermann J; Sorg, Christian; Finke, Kathrin

    2018-01-01

    Separable visual attention functions are assumed to rely on distinct but interacting neural mechanisms. Bundesen's "theory of visual attention" (TVA) allows the mathematical estimation of independent parameters that characterize individuals' visual attentional capacity (i.e., visual processing speed and visual short-term memory storage capacity) and selectivity functions (i.e., top-down control and spatial laterality). However, it is unclear whether these parameters distinctively map onto different brain networks obtained from intrinsic functional connectivity, which organizes slowly fluctuating ongoing brain activity. In our study, 31 demographically homogeneous healthy young participants performed whole- and partial-report tasks and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Report accuracy was modeled using TVA to estimate, individually, the four TVA parameters. Networks encompassing cortical areas relevant for visual attention were derived from independent component analysis of rs-fMRI data: visual, executive control, right and left frontoparietal, and ventral and dorsal attention networks. Two TVA parameters were mapped on particular functional networks. First, participants with higher (vs. lower) visual processing speed showed lower functional connectivity within the ventral attention network. Second, participants with more (vs. less) efficient top-down control showed higher functional connectivity within the dorsal attention network and lower functional connectivity within the visual network. Additionally, higher performance was associated with higher functional connectivity between networks: specifically, between the ventral attention and right frontoparietal networks for visual processing speed, and between the visual and executive control networks for top-down control. The higher inter-network functional connectivity was related to lower intra-network connectivity. These results demonstrate that separable visual attention

  10. Distinctive Correspondence Between Separable Visual Attention Functions and Intrinsic Brain Networks

    Directory of Open Access Journals (Sweden)

    Adriana L. Ruiz-Rizzo

    2018-03-01

    Full Text Available Separable visual attention functions are assumed to rely on distinct but interacting neural mechanisms. Bundesen's “theory of visual attention” (TVA allows the mathematical estimation of independent parameters that characterize individuals' visual attentional capacity (i.e., visual processing speed and visual short-term memory storage capacity and selectivity functions (i.e., top-down control and spatial laterality. However, it is unclear whether these parameters distinctively map onto different brain networks obtained from intrinsic functional connectivity, which organizes slowly fluctuating ongoing brain activity. In our study, 31 demographically homogeneous healthy young participants performed whole- and partial-report tasks and underwent resting-state functional magnetic resonance imaging (rs-fMRI. Report accuracy was modeled using TVA to estimate, individually, the four TVA parameters. Networks encompassing cortical areas relevant for visual attention were derived from independent component analysis of rs-fMRI data: visual, executive control, right and left frontoparietal, and ventral and dorsal attention networks. Two TVA parameters were mapped on particular functional networks. First, participants with higher (vs. lower visual processing speed showed lower functional connectivity within the ventral attention network. Second, participants with more (vs. less efficient top-down control showed higher functional connectivity within the dorsal attention network and lower functional connectivity within the visual network. Additionally, higher performance was associated with higher functional connectivity between networks: specifically, between the ventral attention and right frontoparietal networks for visual processing speed, and between the visual and executive control networks for top-down control. The higher inter-network functional connectivity was related to lower intra-network connectivity. These results demonstrate that separable

  11. Ionomers of intrinsic microporosity: in silico development of ionic-functionalized gas-separation membranes.

    Science.gov (United States)

    Hart, Kyle E; Colina, Coray M

    2014-10-14

    This work presents the predictive molecular simulations of a functionalized polymer of intrinsic microporosity (PIM) with an ionic backbone (carboxylate) and extra-framework counterions (Na(+)) for CO2 gas storage and separation applications. The CO2-philic carboxylate-functionalized polymers are predicted to contain similar degrees of free volume to PIM-1, with Brunauer-Emmett-Teller (BET) surface areas from 510 to 890 m(2)/g, depending on concentration of ionic groups from 100% to 17%. As a result of ionic groups enhancing the CO2 enthalpy of adsorption (to 42-50 kJ/mol), the uptake of the proposed polymers at 293 K exceeded 1.7 mmol/g at 10 kPa and 3.3 mmol/g at 100 kPa for the polymers containing 100% and 50% ionic functional groups, respectively. In addition, CO2/CH4 and CO2/N2 mixed-gas separation performance was evaluated under several industrially relevant conditions, where the IonomIMs are shown to increase both the working capacity and selection performance in certain pressure swing applications (e.g., natural gas separations). These simulations reveal that intrinsically microporous ionomers show great potential as the future of energy-efficient gas-separation polymeric materials.

  12. Pattern separation: a common function for new neurons in hippocampus and olfactory bulb.

    Science.gov (United States)

    Sahay, Amar; Wilson, Donald A; Hen, René

    2011-05-26

    While adult-born neurons in the olfactory bulb (OB) and the dentate gyrus (DG) subregion of the hippocampus have fundamentally different properties, they may have more in common than meets the eye. Here, we propose that new granule cells in the OB and DG may function as modulators of principal neurons to influence pattern separation and that adult neurogenesis constitutes an adaptive mechanism to optimally encode contextual or olfactory information. See the related Perspective from Aimone, Deng, and Gage, "Resolving New Memories: A Critical Look at the Dentate Gyrus, Adult Neurogenesis, and Pattern Separation," in this issue of Neuron. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Functional modules, mutational load and human genetic disease.

    Science.gov (United States)

    Zaghloul, Norann A; Katsanis, Nicholas

    2010-04-01

    The ability to generate a massive amount of sequencing and genotyping data is transforming the study of human genetic disorders. Driven by such innovation, it is likely that whole exome and whole-genome resequencing will replace regionally focused approaches for gene discovery and clinical testing in the next few years. However, this opportunity brings a significant interpretative challenge to assigning function and phenotypic variance to common and rare alleles. Understanding the effect of individual mutations in the context of the remaining genomic variation represents a major challenge to our interpretation of disease. Here, we discuss the challenges of assigning mutation functionality and, drawing from the examples of ciliopathies as well as cohesinopathies and channelopathies, discuss possibilities for the functional modularization of the human genome. Functional modularization in addition to the development of physiologically relevant assays to test allele functionality will accelerate our understanding of disease architecture and enable the use of genome-wide sequence data for disease diagnosis and phenotypic prediction in individuals. Copyright 2010 Elsevier Ltd. All rights reserved.

  14. Gain-of-function HCN2 variants in genetic epilepsy.

    Science.gov (United States)

    Li, Melody; Maljevic, Snezana; Phillips, A Marie; Petrovski, Slave; Hildebrand, Michael S; Burgess, Rosemary; Mount, Therese; Zara, Federico; Striano, Pasquale; Schubert, Julian; Thiele, Holger; Nürnberg, Peter; Wong, Michael; Weisenberg, Judith L; Thio, Liu Lin; Lerche, Holger; Scheffer, Ingrid E; Berkovic, Samuel F; Petrou, Steven; Reid, Christopher A

    2018-02-01

    Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses seizure disorders characterized by spike-and-wave discharges (SWDs). Pacemaker hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are considered integral to SWD genesis, making them an ideal gene candidate for GGE. We identified HCN2 missense variants from a large cohort of 585 GGE patients, recruited by the Epilepsy Phenome-Genome Project (EPGP), and performed functional analysis using two-electrode voltage clamp recordings from Xenopus oocytes. The p.S632W variant was identified in a patient with idiopathic photosensitive occipital epilepsy and segregated in the family. This variant was also independently identified in an unrelated patient with childhood absence seizures from a European cohort of 238 familial GGE cases. The p.V246M variant was identified in a patient with photo-sensitive GGE and his father diagnosed with juvenile myoclonic epilepsy. Functional studies revealed that both p.S632W and p.V246M had an identical functional impact including a depolarizing shift in the voltage dependence of activation that is consistent with a gain-of-function. In contrast, no biophysical changes resulted from the introduction of common population variants, p.E280K and p.A705T, and the p.R756C variant from EPGP that did not segregate with disease. Our data suggest that HCN2 variants can confer susceptibility to GGE via a gain-of-function mechanism. © 2017 Wiley Periodicals, Inc.

  15. Genetic and sexual separation between insect resistant and susceptible Barbarea vulgaris plants in Denmark

    DEFF Research Database (Denmark)

    Toneatto, Fiorello; Nielsen, Jens Kvist; Ørgaard, Marian

    2010-01-01

    of these interactions, we tested how genetically divergent resistant and susceptible plants are, using microsatellite markers. To test whether they are reproductively fully compatible, resistant and susceptible plants were grown intermixed in an outdoor experiment, and the paternity of open-pollinated offspring......Co-evolution between herbivores and plants is believed to be one of the processes creating Earth’s biodiversity. However, it is difficult to disentangle to what extent diversification is really driven by herbivores or by other historical-geographical processes like allopatric isolation....... In the cruciferous plant Barbarea vulgaris, some Danish individuals are resistant to herbivory by flea beetles (Phyllotreta nemorum), whereas others are not. The flea beetles are, in parallel, either resistant or susceptible to the plants defenses. To understand the historical-evolutionary framework...

  16. Importance of the correlation contribution for local hybrid functionals: range separation and self-interaction corrections.

    Science.gov (United States)

    Arbuznikov, Alexei V; Kaupp, Martin

    2012-01-07

    Local hybrid functionals with their position-dependent exact-exchange admixture are a conceptually simple and promising extension of the concept of a hybrid functional. Local hybrids based on a simple mixing of the local spin density approximation (LSDA) with exact exchange have been shown to be successful for thermochemistry, reaction barriers, and a range of other properties. So far, the combination of this generation of local hybrids with an LSDA correlation functional has been found to give the most favorable results for atomization energies, for a range of local mixing functions (LMFs) governing the exact-exchange admixture. Here, we show that the choice of correlation functional to be used with local hybrid exchange crucially influences the parameterization also of the exchange part as well as the overall performance. A novel ansatz for the correlation part of local hybrids is suggested based on (i) range-separation of LSDA correlation into short-range (SR) and long-range (LR) parts, and (ii) partial or full elimination of the one-electron self-correlation from the SR part. It is shown that such modified correlation functionals allow overall larger exact exchange admixture in thermochemically competitive local hybrids than before. This results in improvements for reaction barriers and for other properties crucially influenced by self-interaction errors, as demonstrated by a number of examples. Based on the range-separation approach, a fresh view on the breakdown of the correlation energy into dynamical and non-dynamical parts is suggested.

  17. Estimation of Input Function from Dynamic PET Brain Data Using Bayesian Blind Source Separation

    Czech Academy of Sciences Publication Activity Database

    Tichý, Ondřej; Šmídl, Václav

    2015-01-01

    Roč. 12, č. 4 (2015), s. 1273-1287 ISSN 1820-0214 R&D Projects: GA ČR GA13-29225S Institutional support: RVO:67985556 Keywords : blind source separation * Variational Bayes method * dynamic PET * input function * deconvolution Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.623, year: 2015 http://library.utia.cas.cz/separaty/2015/AS/tichy-0450509.pdf

  18. Functionalized carbon nanotubes mixed matrix membranes of polymers of intrinsic microporosity for gas separation.

    Science.gov (United States)

    Khan, Muntazim Munir; Filiz, Volkan; Bengtson, Gisela; Shishatskiy, Sergey; Rahman, Mushfequr; Abetz, Volker

    2012-09-06

    The present work reports on the gas transport behavior of mixed matrix membranes (MMM) which were prepared from multi-walled carbon nanotubes (MWCNTs) and dispersed within polymers of intrinsic microporosity (PIM-1) matrix. The MWCNTs were chemically functionalized with poly(ethylene glycol) (PEG) for a better dispersion in the polymer matrix. MMM-incorporating functionalized MWCNTs (f-MWCNTs) were fabricated by dip-coating method using microporous polyacrylonitrile membrane as a support and were characterized for gas separation performance. Gas permeation measurements show that MMM incorporated with pristine or functionalized MWCNTs exhibited improved gas separation performance compared to pure PIM-1. The f-MWCNTs MMM show better performance in terms of permeance and selectivity in comparison to pristine MWCNTs. The gas permeances of the derived MMM are increased to approximately 50% without sacrificing the selectivity at 2 wt.% of f-MWCNTs' loading. The PEG groups on the MWCNTs have strong interaction with CO2 which increases the solubility of polar gas and limit the solubility of nonpolar gas, which is advantageous for CO2/N2 selectivity. The addition of f-MWCNTs inside the polymer matrix also improved the long-term gas transport stability of MMM in comparison with PIM-1. The high permeance, selectivity, and long term stability of the fabricated MMM suggest that the reported approach can be utilized in practical gas separation technology.

  19. SEPARATION OF CELL POPULATIONS BY SUPER-PARAMAGNETIC PARTICLES WITH CONTROLLED SURFACE FUNCTIONALITY

    Directory of Open Access Journals (Sweden)

    Lootsik M. D.

    2014-02-01

    Full Text Available The recognition and isolation of specific mammalian cells by the biocompatible polymer coated super-paramagnetic particles with determined surface functionality were studied. The method of synthesis of nanoscaled particles on a core of iron III oxide (Fe2O3, magemit coated with a polymer shell containing reactive oligoperoxide groups for attachment of ligands is described. By using the developed superparamagnetic particles functionalized with peanut agglutinin (PNA we have separated the sub-populations of PNA+ and PNA– cells from ascites of murine Nemeth-Kellner lymphoma. In another type of experiment, the particles were opsonized with proteins of the fetal calf serum that improved biocompatibility of the particles and their ingestion by cultivated murine macrophages J774.2. Macrophages loaded with the particles were effeciently separated from the particles free cells by using the magnet. Thus, the developed surface functionalized superparamagnetic particles showed to be a versatile tool for cell separation independent on the mode of particles’ binding with cell surface or their engulfment by the targeted cells.

  20. Recombinant spider silk genetically functionalized with affinity domains.

    Science.gov (United States)

    Jansson, Ronnie; Thatikonda, Naresh; Lindberg, Diana; Rising, Anna; Johansson, Jan; Nygren, Per-Åke; Hedhammar, My

    2014-05-12

    Functionalization of biocompatible materials for presentation of active protein domains is an area of growing interest. Herein, we describe a strategy for functionalization of recombinant spider silk via gene fusion to affinity domains of broad biotechnological use. Four affinity domains of different origin and structure; the IgG-binding domains Z and C2, the albumin-binding domain ABD, and the biotin-binding domain M4, were all successfully produced as soluble silk fusion proteins under nondenaturing purification conditions. Silk films and fibers produced from the fusion proteins were demonstrated to be chemically and thermally stable. Still, the bioactive domains are concluded to be folded and accessible, since their respective targets could be selectively captured from complex samples, including rabbit serum and human plasma. Interestingly, materials produced from mixtures of two different silk fusion proteins displayed combined binding properties, suggesting that tailor-made materials with desired stoichiometry and surface distributions of several binding domains can be produced. Further, use of the IgG binding ability as a general mean for presentation of desired biomolecules could be demonstrated for a human vascular endothelial growth factor (hVEGF) model system, via a first capture of anti-VEGF IgG to silk containing the Z-domain, followed by incubation with hVEGF. Taken together, this study demonstrates the potential of recombinant silk, genetically functionalized with affinity domains, for construction of biomaterials capable of presentation of almost any desired biomolecule.

  1. Multi-configuration time-dependent density-functional theory based on range separation

    DEFF Research Database (Denmark)

    Fromager, E.; Knecht, S.; Jensen, Hans Jørgen Aagaard

    2013-01-01

    Multi-configuration range-separated density-functional theory is extended to the time-dependent regime. An exact variational formulation is derived. The approximation, which consists in combining a long-range Multi-Configuration- Self-Consistent Field (MCSCF) treatment with an adiabatic short...... (srGGA) approximations. As expected, when modeling long-range interactions with the MCSCF model instead of the adiabatic Buijse-Baerends density-matrix functional as recently proposed by Pernal [J. Chem. Phys. 136, 184105 (2012)10.1063/1.4712019], the description of both the 1D doubly-excited state...

  2. Amine functionalized magnetic nanoparticles for removal of oil droplets from produced water and accelerated magnetic separation

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Saebom, E-mail: saebomko@austin.utexas.edu [University of Texas, Department of Petroleum and Geosystems Engineering (United States); Kim, Eun Song [University of Texas, Department of Biomedical Engineering (United States); Park, Siman [University of Texas, Department of Civil, Architectural and Environmental Engineering (United States); Daigle, Hugh [University of Texas, Department of Petroleum and Geosystems Engineering (United States); Milner, Thomas E. [University of Texas, Department of Biomedical Engineering (United States); Huh, Chun [University of Texas, Department of Petroleum and Geosystems Engineering (United States); Bennetzen, Martin V. [Maersk Oil Corporate (Denmark); Geremia, Giuliano A. [Maersk Oil Research and Technology Centre (Qatar)

    2017-04-15

    Magnetic nanoparticles (MNPs) with surface coatings designed for water treatment, in particular for targeted removal of contaminants from produced water in oil fields, have drawn considerable attention due to their environmental merit. The goal of this study was to develop an efficient method of removing very stable, micron-scale oil droplets dispersed in oilfield produced water. We synthesized MNPs in the laboratory with a prescribed surface coating. The MNPs were superparamagnetic magnetite, and the hydrodynamic size of amine functionalized MNPs ranges from 21 to 255 nm with an average size of 66 nm. The initial oil content of 0.25 wt.% was reduced by as much as 99.9% in separated water. The electrostatic attraction between negatively charged oil-in-water emulsions and positively charged MNPs controls, the attachment of MNPs to the droplet surface, and the subsequent aggregation of the electrically neutral oil droplets with attached MNPs (MNPs-oils) play a critical role in accelerated and efficient magnetic separation. The total magnetic separation time was dramatically reduced to as short as 1 s after MNPs, and oil droplets were mixed, in contrast with the case of free, individual MNPs with which separation took about 36∼72 h, depending on the MNP concentrations. Model calculations of magnetic separation velocity, accounting for the MNP magnetization and viscous drag, show that the total magnetic separation time will be approximately 5 min or less, when the size of the MNPs-oils is greater than 360 nm, which can be used as an optimum operating condition.

  3. Functional localization of a "Time Keeper" function separate from attentional resources and task strategy.

    Science.gov (United States)

    Tracy, J I; Faro, S H; Mohamed, F B; Pinsk, M; Pinus, A

    2000-03-01

    The functional neuroanatomy of time estimation has not been well-documented. This research investigated the fMRI measured brain response to an explicit, prospective time interval production (TIP) task. The study tested for the presence of brain activity reflecting a primary time keeper function, distinct from the brain systems involved either in conscious strategies to monitor time or attentional resource and other cognitive processes to accomplish the task. In the TIP task participants were given a time interval and asked to indicate when it elapsed. Two control tasks (counting forwards, backwards) were administered, in addition to a dual task format of the TIP task. Whole brain images were collected at 1.5 Tesla. Analyses (n = 6) yielded a statistical parametric map (SPM ¿z¿) reflecting time keeping and not strategy (counting, number manipulation) or attention resource utilization. Additional SPM ¿z¿s involving activation associated with the accuracy and magnitude the of time estimation response are presented. Results revealed lateral cerebellar and inferior temporal lobe activation were associated with primary time keeping. Behavioral data provided evidence that the procedures for the explicit time judgements did not occur automatically and utilized controlled processes. Activation sites associated with accuracy, magnitude, and the dual task provided indications of the other structures involved in time estimation that implemented task components related to controlled processing. The data are consistent with prior proposals that the cerebellum is a repository of codes for time processing, but also implicate temporal lobe structures for this type of time estimation task. Copyright 2000 Academic Press.

  4. Sequential fitting-and-separating reflectance components for analytical bidirectional reflectance distribution function estimation.

    Science.gov (United States)

    Lee, Yu; Yu, Chanki; Lee, Sang Wook

    2018-01-10

    We present a sequential fitting-and-separating algorithm for surface reflectance components that separates individual dominant reflectance components and simultaneously estimates the corresponding bidirectional reflectance distribution function (BRDF) parameters from the separated reflectance values. We tackle the estimation of a Lafortune BRDF model, which combines a nonLambertian diffuse reflection and multiple specular reflectance components with a different specular lobe. Our proposed method infers the appropriate number of BRDF lobes and their parameters by separating and estimating each of the reflectance components using an interval analysis-based branch-and-bound method in conjunction with iterative K-ordered scale estimation. The focus of this paper is the estimation of the Lafortune BRDF model. Nevertheless, our proposed method can be applied to other analytical BRDF models such as the Cook-Torrance and Ward models. Experiments were carried out to validate the proposed method using isotropic materials from the Mitsubishi Electric Research Laboratories-Massachusetts Institute of Technology (MERL-MIT) BRDF database, and the results show that our method is superior to a conventional minimization algorithm.

  5. Genetic Separation of Listeria monocytogenes Causing Central Nervous System Infections in Animals

    Directory of Open Access Journals (Sweden)

    Lisandra Aguilar-Bultet

    2018-02-01

    Full Text Available Listeria monocytogenes is a foodborne pathogen that causes abortion, septicemia, gastroenteritis and central nervous system (CNS infections in ruminants and humans. L. monocytogenes strains mainly belong to two distinct phylogenetic groups, named lineages I and II. In general, clinical cases in humans and animals, in particular CNS infections, are caused by lineage I strains, while most of the environmental and food strains belong to lineage II. Little is known about why lineage I is more virulent than lineage II, even though various molecular factors and mechanisms associated with pathogenesis are known. In this study, we have used a variety of whole genome sequence analyses and comparative genomic tools in order to find characteristics that distinguish lineage I from lineage II strains and CNS infection strains from non-CNS strains. We analyzed 225 strains and identified single nucleotide variants between lineages I and II, as well as differences in the gene content. Using a novel approach based on Reads Per Kilobase per Million Mapped (RPKM, we identified 167 genes predominantly absent in lineage II but present in lineage I. These genes are mostly encoding for membrane-associated proteins. Additionally, we found 77 genes that are largely absent in the non-CNS associated strains, while 39 genes are especially lacking in our defined “non-clinical” group. Based on the RPKM analysis and the metadata linked to the L. monocytogenes strains, we identified 6 genes potentially associated with CNS cases, which include a transcriptional regulator, an ABC transporter and a non-coding RNA. Although there is not a clear separation between pathogenic and non-pathogenic strains based on phylogenetic lineages, the presence of the genes identified in our study reveals potential pathogenesis traits in ruminant L. monocytogenes strains. Ultimately, the differences that we have found in our study will help steer future studies in understanding the virulence

  6. Genetic Separation of Listeria monocytogenes Causing Central Nervous System Infections in Animals

    Science.gov (United States)

    Aguilar-Bultet, Lisandra; Nicholson, Pamela; Rychener, Lorenz; Dreyer, Margaux; Gözel, Bulent; Origgi, Francesco C.; Oevermann, Anna; Frey, Joachim; Falquet, Laurent

    2018-01-01

    Listeria monocytogenes is a foodborne pathogen that causes abortion, septicemia, gastroenteritis and central nervous system (CNS) infections in ruminants and humans. L. monocytogenes strains mainly belong to two distinct phylogenetic groups, named lineages I and II. In general, clinical cases in humans and animals, in particular CNS infections, are caused by lineage I strains, while most of the environmental and food strains belong to lineage II. Little is known about why lineage I is more virulent than lineage II, even though various molecular factors and mechanisms associated with pathogenesis are known. In this study, we have used a variety of whole genome sequence analyses and comparative genomic tools in order to find characteristics that distinguish lineage I from lineage II strains and CNS infection strains from non-CNS strains. We analyzed 225 strains and identified single nucleotide variants between lineages I and II, as well as differences in the gene content. Using a novel approach based on Reads Per Kilobase per Million Mapped (RPKM), we identified 167 genes predominantly absent in lineage II but present in lineage I. These genes are mostly encoding for membrane-associated proteins. Additionally, we found 77 genes that are largely absent in the non-CNS associated strains, while 39 genes are especially lacking in our defined “non-clinical” group. Based on the RPKM analysis and the metadata linked to the L. monocytogenes strains, we identified 6 genes potentially associated with CNS cases, which include a transcriptional regulator, an ABC transporter and a non-coding RNA. Although there is not a clear separation between pathogenic and non-pathogenic strains based on phylogenetic lineages, the presence of the genes identified in our study reveals potential pathogenesis traits in ruminant L. monocytogenes strains. Ultimately, the differences that we have found in our study will help steer future studies in understanding the virulence mechanisms of the

  7. Artificial receptor-functionalized nanoshell: facile preparation, fast separation and specific protein recognition

    Science.gov (United States)

    Ouyang, Ruizhuo; Lei, Jianping; Ju, Huangxian

    2010-05-01

    This work combined molecular imprinting technology with superparamagnetic nanospheres as the core to prepare artificial receptor-functionalized magnetic nanoparticles for separation of homologous proteins. Using dopamine as a functional monomer, novel surface protein-imprinted superparamagnetic polydopamine (PDA) core-shell nanoparticles were successfully prepared in physiological conditions, which could maintain the natural structure of a protein template and achieved the development of molecularly imprinted polymers (MIPs) from one dimension to zero dimension for efficient recognition towards large biomolecules. The resultant nanoparticles could be used for convenient magnetic separation of homologous proteins with high specificity. The nanoparticles possessed good monodispersibility, uniform surface morphology and high saturation magnetization value. The bound amounts of template proteins measured by both indirect and direct methods were in good agreement. The maximum number of imprinted cavities on the surface of the bovine hemoglobin (Hb)-imprinted nanoshell was 2.21 × 1018 g - 1, which well matched their maximum binding capacity toward bovine Hb. Both the simple method for preparation of MIPs and the magnetic nanospheres showed good application potential in fast separation, effective concentration and selective biosensing of large protein molecules.

  8. Artificial receptor-functionalized nanoshell: facile preparation, fast separation and specific protein recognition

    Energy Technology Data Exchange (ETDEWEB)

    Ouyang, Ruizhuo; Lei Jianping; Ju Huangxian, E-mail: jpl@nju.edu.cn, E-mail: hxju@nju.edu.cn [Key Laboratory of Analytical Chemistry for Life Science (Education Ministry of China), Department of Chemistry, Nanjing University, Nanjing 210093 (China)

    2010-05-07

    This work combined molecular imprinting technology with superparamagnetic nanospheres as the core to prepare artificial receptor-functionalized magnetic nanoparticles for separation of homologous proteins. Using dopamine as a functional monomer, novel surface protein-imprinted superparamagnetic polydopamine (PDA) core-shell nanoparticles were successfully prepared in physiological conditions, which could maintain the natural structure of a protein template and achieved the development of molecularly imprinted polymers (MIPs) from one dimension to zero dimension for efficient recognition towards large biomolecules. The resultant nanoparticles could be used for convenient magnetic separation of homologous proteins with high specificity. The nanoparticles possessed good monodispersibility, uniform surface morphology and high saturation magnetization value. The bound amounts of template proteins measured by both indirect and direct methods were in good agreement. The maximum number of imprinted cavities on the surface of the bovine hemoglobin (Hb)-imprinted nanoshell was 2.21 x 10{sup 18} g{sup -1}, which well matched their maximum binding capacity toward bovine Hb. Both the simple method for preparation of MIPs and the magnetic nanospheres showed good application potential in fast separation, effective concentration and selective biosensing of large protein molecules.

  9. A general range-separated double-hybrid density-functional theory.

    Science.gov (United States)

    Kalai, Cairedine; Toulouse, Julien

    2018-04-28

    A range-separated double-hybrid (RSDH) scheme which generalizes the usual range-separated hybrids and double hybrids is developed. This scheme consistently uses a two-parameter Coulomb-attenuating-method (CAM)-like decomposition of the electron-electron interaction for both exchange and correlation in order to combine Hartree-Fock exchange and second-order Møller-Plesset (MP2) correlation with a density functional. The RSDH scheme relies on an exact theory which is presented in some detail. Several semi-local approximations are developed for the short-range exchange-correlation density functional involved in this scheme. After finding optimal values for the two parameters of the CAM-like decomposition, the RSDH scheme is shown to have a relatively small basis dependence and to provide atomization energies, reaction barrier heights, and weak intermolecular interactions globally more accurate or comparable to range-separated MP2 or standard MP2. The RSDH scheme represents a new family of double hybrids with minimal empiricism which could be useful for general chemical applications.

  10. Genetic association between human chitinases and lung function in COPD.

    Science.gov (United States)

    Aminuddin, F; Akhabir, L; Stefanowicz, D; Paré, P D; Connett, J E; Anthonisen, N R; Fahy, J V; Seibold, M A; Burchard, E G; Eng, C; Gulsvik, A; Bakke, P; Cho, M H; Litonjua, A; Lomas, D A; Anderson, W H; Beaty, T H; Crapo, J D; Silverman, E K; Sandford, A J

    2012-07-01

    Two primary chitinases have been identified in humans--acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host's immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to chronic obstructive pulmonary disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case-control populations. Chitinase activity and protein levels were also related to genotypes. In the caucasian LHS population, the baseline forced expiratory volume in one second (FEV(1)) was significantly different between the AA and GG genotypic groups of the AMCase rs3818822 polymorphism. Subjects with the GG genotype had higher AMCase protein and chitinase activity compared with AA homozygotes. For CHIT1 rs2494303, a significant association was observed between rate of decline in FEV(1) and the different genotypes. In the African American LHS population, CHIT1 rs2494303 and AMCase G339T genotypes were associated with rate of decline in FEV(1). Although a significant effect of chitinase gene alleles was found on lung function level and decline in the LHS, we were unable to replicate the associations with COPD affection status in the other COPD study groups.

  11. Genetic, functional and molecular features of glucocorticoid receptor binding.

    Directory of Open Access Journals (Sweden)

    Francesca Luca

    Full Text Available Glucocorticoids (GCs are key mediators of stress response and are widely used as pharmacological agents to treat immune diseases, such as asthma and inflammatory bowel disease, and certain types of cancer. GCs act mainly by activating the GC receptor (GR, which interacts with other transcription factors to regulate gene expression. Here, we combined different functional genomics approaches to gain molecular insights into the mechanisms of action of GC. By profiling the transcriptional response to GC over time in 4 Yoruba (YRI and 4 Tuscans (TSI lymphoblastoid cell lines (LCLs, we suggest that the transcriptional response to GC is variable not only in time, but also in direction (positive or negative depending on the presence of specific interacting transcription factors. Accordingly, when we performed ChIP-seq for GR and NF-κB in two YRI LCLs treated with GC or with vehicle control, we observed that features of GR binding sites differ for up- and down-regulated genes. Finally, we show that eQTLs that affect expression patterns only in the presence of GC are 1.9-fold more likely to occur in GR binding sites, compared to eQTLs that affect expression only in its absence. Our results indicate that genetic variation at GR and interacting transcription factors binding sites influences variability in gene expression, and attest to the power of combining different functional genomic approaches.

  12. Enhancement of biomembrane functions under phase-separated conditions: A self-organized criticality phenomenon?

    International Nuclear Information System (INIS)

    Eze, M.O.; Chela Flores, J.

    1993-12-01

    Self-organized criticality (SOC) is hereby proposed as a possible physical basis for explaining observations in the temperature-dependence of the rates of biological membrane-associated events. The biomembrane undergoes a reversible, cooperative, thermotropic gel-to-liquid crystalline phase transition which is broad, and involves lateral phase separation. The lateral phase separated (rather than the totally gel-, or the totally liquid crystalline-) membrane state has been observed to be the state in which vital membrane functions are facilitated. The membrane in this unique state is viewed, for our purposes here, as a dynamical, extended dissipative system with spatial and temporal degrees of freedom, exhibiting power law behaviour, typical of the self-organized critical state. Experiments are suggested for verifying this hypothesis. (author). 30 refs

  13. Function of One Regular Separable Relation Set Decided for the Minimal Covering in Multiple Valued Logic

    Directory of Open Access Journals (Sweden)

    Liu Yu Zhen

    2016-01-01

    Full Text Available Multiple-valued logic is an important branch of the computer science and technology. Multiple-valued logic studies the theory, multiple-valued circuit & multiple-valued system, and the applications of multiple-valued logic included.In the theory of multiple-valued logic, one primary and important problem is the completeness of function sets, which can be solved depending on the decision for all the precomplete sets(also called maximal closed sets of K-valued function sets noted by PK*, and another is the decision for Sheffer function, which can be totally solved by picking out all of the minimal covering of the precomplete sets. In the function structure theory of multi-logic, decision on Sheffer function is an important role. It contains structure and decision of full multi-logic and partial multi-logic. Its decision is closely related to decision of completeness of function which can be done by deciding the minimal covering of full multi-logic and partial-logic. By theory of completeness of partial multi-logic, we prove that function of one regular separable relation is not minimal covering of PK* under the condition of m = 2, σ = e.

  14. Fabrication of Functionalized MOFs Incorporated Mixed Matrix Hollow Fiber Membrane for Gas Separation

    Directory of Open Access Journals (Sweden)

    Haitao Zhu

    2017-01-01

    Full Text Available The metal-organic framework (MOFs of MIL-53 was functionalized by aminosilane grafting and then incorporated into Ultem®1000 polymer matrix to fabricate mixed matrix hollow fiber membrane (MMHFM with high separation performance. SEM, XRD, and TGA were performed to characterize the functionalized MIL-53 and prepared MMHFM. The filler particles were embedded in membrane successfully and dispersed well in the polymer matrix. The incorporation of MOFs endowed MMHFM better thermal stability. Moreover, effects of solvent ratio in spinning dope, spinning condition, and testing temperature on gas separation performance of MMHFM were investigated. By optimizing dope composition, air gap distance, and bore fluid composition, MMHFM containing functionalized MIL-53 achieved excellent gas permeance and CO2/N2 selectivity. The CO2 permeance increased from 12.2 GPU for pure Ultem HFM to 30.9 GPU and the ideal CO2/N2 selectivity was enhanced from 25.4 to 34.7 simultaneously. Additionally, gas permeance increased but the selectivity decreased with the temperature increase, which followed the solution-diffusion based transport mechanism.

  15. 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...

  16. Morphospaces of functionally analogous traits show ecological separation between birds and pterosaurs.

    Science.gov (United States)

    Chan, Nicholas R

    2017-10-25

    Birds originated and radiated in the presence of another group of flying vertebrates, the pterosaurs. Opinion is divided as to whether birds competitively displaced pterosaurs from small-body size niches or whether the two groups coexisted with little competition. Previous studies of Mesozoic birds and pterosaurs compared measurements of homologous limb bones to test these hypotheses. However, these characters probably reflect differing ancestries rather than ecologies. Here, competition and ecological separation were tested for using multivariate analyses of functionally equivalent morphological characters. As well as using characters from the fore- and hindlimbs, these analyses also included measurements of the lower jaw. The results of this study indicate that pterosaurs had relatively longer jaws, shorter metatarsals and shorter brachial regions compared with birds of similar size. Contrary to the results of previous studies, the distal wing was not important for separating the two clades in morphospace owing to the inclusion of the primary feathers in this unit. The differences found here indicate ecological separation based on differences in size, locomotory features and feeding adaptations. Thus, instead of one group displacing the other, birds and pterosaurs appear to have adopted distinctive ecological strategies throughout their period of coexistence. © 2017 The Author(s).

  17. Describing long-range charge-separation processes with subsystem density-functional theory

    Energy Technology Data Exchange (ETDEWEB)

    Solovyeva, Alisa; Neugebauer, Johannes, E-mail: j.neugebauer@uni-muenster.de [Theoretische Organische Chemie, Organisch-Chemisches Institut and Center for Multiscale Theory and Simulation, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster (Germany); Pavanello, Michele, E-mail: m.pavanello@rutgers.edu [Department of Chemistry, Rutgers University, 73 Warren St., Newark, New Jersey 07102 (United States)

    2014-04-28

    Long-range charge-transfer processes in extended systems are difficult to describe with quantum chemical methods. In particular, cost-effective (non-hybrid) approximations within time-dependent density functional theory (DFT) are not applicable unless special precautions are taken. Here, we show that the efficient subsystem DFT can be employed as a constrained DFT variant to describe the energetics of long-range charge-separation processes. A formal analysis of the energy components in subsystem DFT for such excitation energies is presented, which demonstrates that both the distance dependence and the long-range limit are correctly described. In addition, electronic couplings for these processes as needed for rate constants in Marcus theory can be obtained from this method. It is shown that the electronic structure of charge-separated states constructed by a positively charged subsystem interacting with a negatively charged one is difficult to converge — charge leaking from the negative subsystem to the positive one can occur. This problem is related to the delocalization error in DFT and can be overcome with asymptotically correct exchange–correlation (XC) potentials or XC potentials including a sufficiently large amount of exact exchange. We also outline an approximate way to obtain charge-transfer couplings between locally excited and charge-separated states.

  18. Describing long-range charge-separation processes with subsystem density-functional theory

    International Nuclear Information System (INIS)

    Solovyeva, Alisa; Neugebauer, Johannes; Pavanello, Michele

    2014-01-01

    Long-range charge-transfer processes in extended systems are difficult to describe with quantum chemical methods. In particular, cost-effective (non-hybrid) approximations within time-dependent density functional theory (DFT) are not applicable unless special precautions are taken. Here, we show that the efficient subsystem DFT can be employed as a constrained DFT variant to describe the energetics of long-range charge-separation processes. A formal analysis of the energy components in subsystem DFT for such excitation energies is presented, which demonstrates that both the distance dependence and the long-range limit are correctly described. In addition, electronic couplings for these processes as needed for rate constants in Marcus theory can be obtained from this method. It is shown that the electronic structure of charge-separated states constructed by a positively charged subsystem interacting with a negatively charged one is difficult to converge — charge leaking from the negative subsystem to the positive one can occur. This problem is related to the delocalization error in DFT and can be overcome with asymptotically correct exchange–correlation (XC) potentials or XC potentials including a sufficiently large amount of exact exchange. We also outline an approximate way to obtain charge-transfer couplings between locally excited and charge-separated states

  19. Strain screening, fermentation, separation, and encapsulation for production of nattokinase functional food.

    Science.gov (United States)

    Wei, Xuetuan; Luo, Mingfang; Xie, Yuchun; Yang, Liangrong; Li, Haojian; Xu, Lin; Liu, Huizhou

    2012-12-01

    This study presents a novel and integrated preparation technology for nattokinase functional food, including strain screening, fermentation, separation, and encapsulation. To rapidly screen a nattokinase-productive strain, PCR-based screening method was combined with fibrinolytic activity-based method, and a high productive strain, Bacillus subtilis LSSE-22, was isolated from Chinese soybean paste. Reduction of poly-γ-glutamic acid (γ-PGA) concentration may contribute to separation of nattokinase and reduction of late-onset anaphylaxis risk. Chickpeas were confirmed as the favorable substrate for enhancement of nattokinase production and reduction of γ-PGA yield. Using cracked chickpeas, the nattokinase activity reached 356.25 ± 17.18 FU/g (dry weight), which is much higher than previous reports. To further reduce γ-PGA concentration, ethanol fractional extraction and precipitation were applied for separation of nattokinase. By extraction with 50 % and precipitation with 75 % ethanol solution, 4,000.58 ± 192.98 FU/g of nattokinase powders were obtained, and the activity recovery reached 89 ± 1 %, while γ-PGA recovery was reduced to 21 ± 2 %. To improve the nattokinase stability at acidic pH condition, the nattokinase powders were encapsulated, and then coated with methacrylic acid-ethyl acrylate copolymer. After encapsulation, the nattokinase was protected from being denatured under various acid conditions, and pH-responsible controlled release at simulated intestinal fluid was realized.

  20. A comprehensive platform for highly multiplexed mammalian functional genetic screens

    Directory of Open Access Journals (Sweden)

    Cheung-Ong Kahlin

    2011-05-01

    Full Text Available Abstract Background Genome-wide screening in human and mouse cells using RNA interference and open reading frame over-expression libraries is rapidly becoming a viable experimental approach for many research labs. There are a variety of gene expression modulation libraries commercially available, however, detailed and validated protocols as well as the reagents necessary for deconvolving genome-scale gene screens using these libraries are lacking. As a solution, we designed a comprehensive platform for highly multiplexed functional genetic screens in human, mouse and yeast cells using popular, commercially available gene modulation libraries. The Gene Modulation Array Platform (GMAP is a single microarray-based detection solution for deconvolution of loss and gain-of-function pooled screens. Results Experiments with specially constructed lentiviral-based plasmid pools containing ~78,000 shRNAs demonstrated that the GMAP is capable of deconvolving genome-wide shRNA "dropout" screens. Further experiments with a larger, ~90,000 shRNA pool demonstrate that equivalent results are obtained from plasmid pools and from genomic DNA derived from lentivirus infected cells. Parallel testing of large shRNA pools using GMAP and next-generation sequencing methods revealed that the two methods provide valid and complementary approaches to deconvolution of genome-wide shRNA screens. Additional experiments demonstrated that GMAP is equivalent to similar microarray-based products when used for deconvolution of open reading frame over-expression screens. Conclusion Herein, we demonstrate four major applications for the GMAP resource, including deconvolution of pooled RNAi screens in cells with at least 90,000 distinct shRNAs. We also provide detailed methodologies for pooled shRNA screen readout using GMAP and compare next-generation sequencing to GMAP (i.e. microarray based deconvolution methods.

  1. Moderation of genetic factors by parental divorce in adolescents' evaluations of family functioning and subjective wellbeing.

    Science.gov (United States)

    van der Aa, Niels; Boomsma, Dorret I; Rebollo-Mesa, Irene; Hudziak, James J; Bartels, Meike

    2010-04-01

    Adolescents' evaluations of family functioning may have a significant impact on their subjective well-being and adjustment. The aim of the study was to investigate the degree to which genetic and environmental influences affect variation in evaluations of general family functioning, family conflict, and quality of life and the overlap between them. We assessed whether genetic and environmental influences are moderated by parental divorce by analyzing self-report data from 6,773 adolescent twins and their non-twin siblings. Genetic, shared, and nonshared environmental influences accounted for variation in general family functioning and family conflict, with genetic influences being relatively more important in girls than boys in general family functioning. Genetic and nonshared environmental influences accounted for variation in quality of life, with genetic influences being relatively more important in girls. Evidence was found for interaction between genetic factors and parental divorce: genetic influence on general family functioning was larger in participants from divorced families. The overlap between general family functioning and quality of life, and family conflict and quality of life was accounted for the largest part by genetic effects, with nonshared environmental effects accounting for the remaining part. By examining the data from monozygotic twins, we found evidence for interaction between genotype and nonshared, non-measured, environmental influences on evaluations of general family functioning, family conflict, and quality of life.

  2. Genetic modulation of energy metabolism in birds through mitochondrial function

    NARCIS (Netherlands)

    Tieleman, B. Irene; Versteegh, Maaike A.; Fries, Anthony; Helm, Barbara; Dingemanse, Niels J.; Gibbs, H. Lisle; Williams, Joseph B.

    2009-01-01

    Despite their central importance for the evolution of physiological variation, the genetic mechanisms that determine energy expenditure in animals have largely remained unstudied. We used quantitative genetics to confirm that both mass-specific and whole-organism basal metabolic rate (BMR) were

  3. Nanostructured Membranes Functionalized with Gold Nanoparticles for Separation and Recovery of Monoclonal Antibodies

    KAUST Repository

    Soldan, Giada

    2017-11-01

    The need of purified biomolecules, such as proteins or antibodies, has required the biopharmaceutical industries to look for new recovering solutions to reduce time and costs of bioseparations. In the last decade, the emergent field of membrane chromatography has gained attention as possible substituent of the common used protein A affinity chromatography for bioseparations. In this scenario, gold nanoparticles can be used as means for offering affinity, mainly because of their biocompatible and reversible binding behavior, together with their high surface area-to-volume ratio, which offers a large number of binding sites. This work introduces a new procedure for purification of monoclonal antibodies based on polymeric membranes functionalized with gold nanoparticles. This novel approach shortens the process of purification by promoting selective binding of antibodies, while separating a mixture of biomolecules during a filtration process. The effects of gold nanoparticles and the surrounding ligand on the proteins adsorption and filtration are investigated. The results confirm that the functionalization helps in inducing a selective binding, preventing the non-selective one, and it also improves the selectivity of the separation process.

  4. Evaluation of separate renal function by means of 99mTc-aprotinin uptake test

    International Nuclear Information System (INIS)

    Aprile, C.; Saponaro, R.; Villa, G.; Carena, M.; Chiari, G.; Salvadeo, A.; Lunghi, F.; Piazza, V.

    1986-01-01

    The possibility that relative kidney uptake of technetium-99m aprotinin (TcA) might be indicative of separate renal function was investigated in 89 patients who underwent both effective renal plasma flow (ERPFs) and glomerular filtration rate (GFR) determination. A reference group consisted of 27 healthy volunteers, studied only with TcA. The correlation with ERPFs (r = .73) was similar to that previously reported and confirmed. The correlation with GFR (r = .68) was better if a subgroup of renal units with TcA uptake lower than 16% (lower normal limit) was considered. Most likely, glomerular filtration is a limiting factor of the tubular uptake of TcA, and when GFR is reduced, both parameters decrease in the same manner, while if GFR is normal the two parameters are relatively independent. The correlation between TcA and GFR in 32 children was very similar to that found in adults. TcA uptake test seems to be a useful indicator of separate renal function, providing morphological information at, the same time

  5. Strategies for the design of functional MOFs: addressing energy-intensive separations

    KAUST Repository

    Eddaoudi, Mohamed

    2017-12-19

    Metal Organic Frameworks (MOFs) are a promising class of crystalline solid-state materials amenable to tailoring their porosity and functionality towards various applications. MOF reticular chemistry using the Molecular Building Block (MBB) approach offers potential to construct robust made-to-order MOFs, where desired structural and geometrical information are incorporated into the building blocks prior to the assembly process. We will discuss two recently implemented conceptual approaches facilitating the design and deliberate construction of metal–organic frameworks (MOFs), namely supermolecular building block (SBB) and supermolecular building layer (SBL) approaches. Additionally, the concept of net-coded building units (net-cBUs), where precise embedded geometrical information codes uniquely and matchlessly a selected net, as a compelling route for the rational design of MOFs will be presented. Our progress in the development of functional metal-organic frameworks (MOFs) to address some energy-intensive separations will be discussed. Namely, the successful practice of reticular chemistry affording the fabrication of various stable MOFs with controlled pore-aperture size and allowing effective separation of various gas or vapors pairs.

  6. Spatial separation and bidirectional trafficking of proteins using a multi-functional reporter

    Directory of Open Access Journals (Sweden)

    Klaubert Dieter H

    2008-04-01

    Full Text Available Abstract Background The ability to specifically label proteins within living cells can provide information about their dynamics and function. To study a membrane protein, we fused a multi-functional reporter protein, HaloTag®, to the extracellular domain of a truncated integrin. Results Using the HaloTag technology, we could study the localization, trafficking and processing of an integrin-HaloTag fusion, which we showed had cellular dynamics consistent with native integrins. By labeling live cells with different fluorescent impermeable and permeable ligands, we showed spatial separation of plasma membrane and internal pools of the integrin-HaloTag fusion, and followed these protein pools over time to study bi-directional trafficking. In addition to combining the HaloTag reporter protein with different fluorophores, we also employed an affinity tag to achieve cell capture. Conclusion The HaloTag technology was used successfully to study expression, trafficking, spatial separation and real-time translocation of an integrin-HaloTag fusion, thereby demonstrating that this technology can be a powerful tool to investigate membrane protein biology in live cells.

  7. Valence electronic structure of cobalt phthalocyanine from an optimally tuned range-separated hybrid functional.

    Science.gov (United States)

    Brumboiu, Iulia Emilia; Prokopiou, Georgia; Kronik, Leeor; Brena, Barbara

    2017-07-28

    We analyse the valence electronic structure of cobalt phthalocyanine (CoPc) by means of optimally tuning a range-separated hybrid functional. The tuning is performed by modifying both the amount of short-range exact exchange (α) included in the hybrid functional and the range-separation parameter (γ), with two strategies employed for finding the optimal γ for each α. The influence of these two parameters on the structural, electronic, and magnetic properties of CoPc is thoroughly investigated. The electronic structure is found to be very sensitive to the amount and range in which the exact exchange is included. The electronic structure obtained using the optimal parameters is compared to gas-phase photo-electron data and GW calculations, with the unoccupied states additionally compared with inverse photo-electron spectroscopy measurements. The calculated spectrum with tuned γ, determined for the optimal value of α = 0.1, yields a very good agreement with both experimental results and with GW calculations that well-reproduce the experimental data.

  8. Trinucleon wave functions from separable expansions of the N-N interaction

    International Nuclear Information System (INIS)

    Birrell, N.D.

    1976-09-01

    This work is intended to determine whether a separable expansion for the N-N interaction can be used to obtain trinucleon wave functions of high quality. The expansions used in the study are the Unitary Pole expansion of Harms, Afnan and Read, and the expansion of Adhikari and Sloan. We first compare the calculation of the RSC potential Triton binding energy with the two methods, and find that the results agree quite closely. However, while it is found necessary to use t-matrix perturbation theory to obtain the UPE result, such is not the case with the ASE, thus offering a considerable improvement on the previously used method. We then proceed to calculate the L-S coupling probabilities for the wave function, and in so doing, discover a source of inaccuracy in the work of other authors. We also find that the UPE and ASE give probabilities in good agreement with one another. The calculation of the He 3 charge form factor turns out to be the most critical judge of the accuracy of the wave function. Although both expansions give quite satisfactory results for the charge form factor, those obtained with the ASE are exceptionally pleasing. We finally apply both methods to the OBEP of Holinde and Machleidt, and find that the UPE is quite unsuitable for such application. The ASE, however, once again gives very good results, indicating the high quality of the trinucleon wave function obtained with it. (author)

  9. Cerebral functional connectivity and Mayer waves in mice: Phenomena and separability.

    Science.gov (United States)

    Bumstead, Jonathan R; Bauer, Adam Q; Wright, Patrick W; Culver, Joseph P

    2017-02-01

    Resting-state functional connectivity is a growing neuroimaging approach that analyses the spatiotemporal structure of spontaneous brain activity, often using low-frequency (Mayer waves. Despite how close in frequency these phenomena exist, there is little research on how vasomotion and Mayer waves are related to or affect resting-state functional connectivity. In this study, we analyze spontaneous hemodynamic fluctuations over the mouse cortex using optical intrinsic signal imaging. We found spontaneous occurrence of oscillatory hemodynamics ∼0.2 Hz consistent with the properties of Mayer waves reported in the literature. Across a group of mice (n = 19), there was a large variability in the magnitude of Mayer waves. However, regardless of the magnitude of Mayer waves, functional connectivity patterns could be recovered from hemodynamic signals when filtered to the lower frequency band, 0.01-0.08 Hz. Our results demonstrate that both Mayer waves and resting-state functional connectivity patterns can co-exist simultaneously, and that they can be separated by applying bandpass filters.

  10. Separable roles of UFO during floral development revealed by conditional restoration of gene function.

    Science.gov (United States)

    Laufs, Patrick; Coen, Enrico; Kronenberger, Jocelyne; Traas, Jan; Doonan, John

    2003-02-01

    The UNUSUAL FLORAL ORGANS (UFO) gene is required for several aspects of floral development in Arabidopsis including specification of organ identity in the second and third whorls and the proper pattern of primordium initiation in the inner three whorls. UFO is expressed in a dynamic pattern during the early phases of flower development. Here we dissect the role of UFO by ubiquitously expressing it in ufo loss-of-function flowers at different developmental stages and for various durations using an ethanol-inducible expression system. The previously known functions of UFO could be separated and related to its expression at specific stages of development. We show that a 24- to 48-hour period of UFO expression from floral stage 2, before any floral organs are visible, is sufficient to restore normal petal and stamen development. The earliest requirement for UFO is during stage 2, when the endogenous UFO gene is transiently expressed in the centre of the wild-type flower and is required to specify the initiation patterns of petal, stamen and carpel primordia. Petal and stamen identity is determined during stages 2 or 3, when UFO is normally expressed in the presumptive second and third whorl. Although endogenous UFO expression is absent from the stamen whorl from stage 4 onwards, stamen identity can be restored by UFO activation up to stage 6. We also observed floral phenotypes not observed in loss-of-function or constitutive gain-of-function backgrounds, revealing additional roles of UFO in outgrowth of petal primordia.

  11. Variable separation solutions for the Nizhnik-Novikov-Veselov equation via the extended tanh-function method

    International Nuclear Information System (INIS)

    Zhang Jiefang; Dai Chaoqing; Zong Fengde

    2007-01-01

    In this paper, with the variable separation approach and based on the general reduction theory, we successfully generalize this extended tanh-function method to obtain new types of variable separation solutions for the following Nizhnik-Novikov-Veselov (NNV) equation. Among the solutions, two solutions are new types of variable separation solutions, while the last solution is similar to the solution given by Darboux transformation in Hu et al 2003 Chin. Phys. Lett. 20 1413

  12. Potential of hybrid functionalized meso-porous materials for the separation and immobilization of radionuclides

    International Nuclear Information System (INIS)

    Luca, V.

    2013-01-01

    Functionalized meso-porous materials are a class of hybrid organic-inorganic material in which a meso-porous metal oxide framework is functionalized with multifunctional organic molecules. These molecules may contain one or more anchor groups that form strong bonds to the pore surfaces of the metal oxide framework and free functional groups that can impart and or modify the functionality of the material such as for binding metal ions in solution. Such materials have been extensively studied over the past decade and are of particular interest in absorption applications because of the tremendous versatility in choosing the composition and architecture of the metal oxide framework and the nature of the functional organic molecule as well as the efficient mass transfer that can occur through a well-designed hierarchically porous network. A sorbent for nuclear applications would have to be highly selective for particular radio nuclides, it would need to be hydrolytically and radiolytically stable, and it would have to possess reasonable capacity and fast kinetics. The sorbent would also have to be available in a form suitable for use in a column. Finally, it would also be desirable if once saturated with radio nuclides, the sorbent could be recycled or converted directly into a ceramic or glass waste form suitable for direct repository disposal or even converted directly into a material that could be used as a transmutation target. Such a cradle-to- grave strategy could have many benefits in so far as process efficiency and the generation of secondary wastes are concerned.This paper will provide an overview of work done on all of the above mentioned aspects of the development of functionalized meso-porous adsorbent materials for the selective separation of lanthanides and actinides and discuss the prospects for future implementation of a cradle-to-grave strategy with such materials. (author)

  13. EXOPLANET ALBEDO SPECTRA AND COLORS AS A FUNCTION OF PLANET PHASE, SEPARATION, AND METALLICITY

    International Nuclear Information System (INIS)

    Cahoy, Kerri L.; Marley, Mark S.; Fortney, Jonathan J.

    2010-01-01

    First generation space-based optical coronagraphic telescopes will obtain images of cool gas- and ice-giant exoplanets around nearby stars. Exoplanets lying at planet-star separations larger than about 1 AU-where an exoplanet can be resolved from its parent star-have spectra that are dominated by reflected light to beyond 1 μm and punctuated by molecular absorption features. Here, we consider how exoplanet albedo spectra and colors vary as a function of planet-star separation, metallicity, mass, and observed phase for Jupiter and Neptune analogs from 0.35 to 1 μm. We model Jupiter analogs with 1x and 3x the solar abundance of heavy elements, and Neptune analogs with 10x and 30x the solar abundance of heavy elements. Our model planets orbit a solar analog parent star at separations of 0.8 AU, 2 AU, 5 AU, and 10 AU. We use a radiative-convective model to compute temperature-pressure profiles. The giant exoplanets are found to be cloud-free at 0.8 AU, possess H 2 O clouds at 2 AU, and have both NH 3 and H 2 O clouds at 5 AU and 10 AU. For each model planet we compute moderate resolution (R = λ/Δλ ∼ 800) albedo spectra as a function of phase. We also consider low-resolution spectra and colors that are more consistent with the capabilities of early direct imaging capabilities. As expected, the presence and vertical structure of clouds strongly influence the albedo spectra since cloud particles not only affect optical depth but also have highly directional scattering properties. Observations at different phases also probe different volumes of atmosphere as the source-observer geometry changes. Because the images of the planets themselves will be unresolved, their phase will not necessarily be immediately obvious, and multiple observations will be needed to discriminate between the effects of planet-star separation, metallicity, and phase on the observed albedo spectra. We consider the range of these combined effects on spectra and colors. For example, we find that

  14. A rapid method for detection of genetically modified organisms based on magnetic separation and surface-enhanced Raman scattering.

    Science.gov (United States)

    Guven, Burcu; Boyacı, İsmail Hakkı; Tamer, Ugur; Çalık, Pınar

    2012-01-07

    In this study, a new method combining magnetic separation (MS) and surface-enhanced Raman scattering (SERS) was developed to detect genetically modified organisms (GMOs). An oligonucleotide probe which is specific for 35 S DNA target was immobilized onto gold coated magnetic nanospheres to form oligonucleotide-coated nanoparticles. A self assembled monolayer was formed on gold nanorods using 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) and the second probe of the 35 S DNA target was immobilized on the activated nanorod surfaces. Probes on the nanoparticles were hybridized with the target oligonucleotide. Optimization parameters for hybridization were investigated by high performance liquid chromatography. Optimum hybridization parameters were determined as: 4 μM probe concentration, 20 min immobilization time, 30 min hybridization time, 55 °C hybridization temperature, 750 mM buffer salt concentration and pH: 7.4. Quantification of the target concentration was performed via SERS spectra of DTNB on the nanorods. The correlation between the target concentration and the SERS signal was found to be linear within the range of 25-100 nM. The analyses were performed with only one hybridization step in 40 min. Real sample analysis was conducted using Bt-176 maize sample. The results showed that the developed MS-SERS assay is capable of detecting GMOs in a rapid and selective manner. This journal is © The Royal Society of Chemistry 2012

  15. AMD and the alternative complement pathway: genetics and functional implications.

    Science.gov (United States)

    Tan, Perciliz L; Bowes Rickman, Catherine; Katsanis, Nicholas

    2016-06-21

    Age-related macular degeneration (AMD) is an ocular neurodegenerative disorder and is the leading cause of legal blindness in Western societies, with a prevalence of up to 8 % over the age of 60, which continues to increase with age. AMD is characterized by the progressive breakdown of the macula (the central region of the retina), resulting in the loss of central vision including visual acuity. While its molecular etiology remains unclear, advances in genetics and genomics have illuminated the genetic architecture of the disease and have generated attractive pathomechanistic hypotheses. Here, we review the genetic architecture of AMD, considering the contribution of both common and rare alleles to susceptibility, and we explore the possible mechanistic links between photoreceptor degeneration and the alternative complement pathway, a cascade that has emerged as the most potent genetic driver of this disorder.

  16. Genetic, molecular and functional analyses of complement factor I deficiency

    DEFF Research Database (Denmark)

    Nilsson, S.C.; Trouw, L.A.; Renault, N.

    2009-01-01

    Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three patie...

  17. Systems genetic analysis of brown adipose tissue function

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Saba, L. M.; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šilhavý, Jan; Šimáková, Miroslava; Strnad, Hynek; Trnovská, J.; Škop, V.; Hüttl, M.; Marková, I.; Oliyarnyk, O.; Malínská, H.; Kazdová, L.; Smith, H.; Tabakoff, B.

    2018-01-01

    Roč. 50, č. 1 (2018), s. 52-66 ISSN 1094-8341 R&D Projects: GA ČR(CZ) GA13-04420S Institutional support: RVO:67985823 Keywords : brown adipose tissue * coexpression modules * quantitative trait locus * recombinant inbred strains * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Human genetics Impact factor: 3.044, year: 2016

  18. Biomarkers of brain function in psychosis and their genetic basis

    OpenAIRE

    Ranlund, S. M.

    2016-01-01

    Psychotic disorders, including schizophrenia and bipolar disorder, are amongst the most severe and enduring mental illnesses. Recent research has identified several genetic variants associated with an increased risk of developing psychosis; however, it remains largely unknown how these lead to the illness. This is where endophenotypes – heritable traits associated with the illness and observed in unaffected family members of patients – could be valuable. Endophenotypes are linked to the genet...

  19. Using Genetically Engineered Animal Models in the Postgenomic Era to Understand Gene Function in Alcoholism

    Science.gov (United States)

    Reilly, Matthew T.; Harris, R. Adron; Noronha, Antonio

    2012-01-01

    Over the last 50 years, researchers have made substantial progress in identifying genetic variations that underlie the complex phenotype of alcoholism. Not much is known, however, about how this genetic variation translates into altered biological function. Genetic animal models recapitulating specific characteristics of the human condition have helped elucidate gene function and the genetic basis of disease. In particular, major advances have come from the ability to manipulate genes through a variety of genetic technologies that provide an unprecedented capacity to determine gene function in the living organism and in alcohol-related behaviors. Even newer genetic-engineering technologies have given researchers the ability to control when and where a specific gene or mutation is activated or deleted, allowing investigators to narrow the role of the gene’s function to circumscribed neural pathways and across development. These technologies are important for all areas of neuroscience, and several public and private initiatives are making a new generation of genetic-engineering tools available to the scientific community at large. Finally, high-throughput “next-generation sequencing” technologies are set to rapidly increase knowledge of the genome, epigenome, and transcriptome, which, combined with genetically engineered mouse mutants, will enhance insight into biological function. All of these resources will provide deeper insight into the genetic basis of alcoholism. PMID:23134044

  20. Genetic analyses of the stability of executive functioning during childhood.

    NARCIS (Netherlands)

    Polderman, T.J.C.; Posthuma, D.; de Sonneville, L.M.J.; Stins, J.F.; Verhulst, F.C.; Boomsma, D.I.

    2007-01-01

    Executive functioning is an umbrella term for several related cognitive functions like selective- and sustained attention, working memory, and inhibition. Little is known about the stability of executive functioning during childhood. In this study the longitudinal stability of executive functioning

  1. Tailored functionalization of iron oxide nanoparticles for MRI, drug delivery, magnetic separation and immobilization of biosubstances.

    Science.gov (United States)

    Hola, Katerina; Markova, Zdenka; Zoppellaro, Giorgio; Tucek, Jiri; Zboril, Radek

    2015-11-01

    In this critical review, we outline various covalent and non-covalent approaches for the functionalization of iron oxide nanoparticles (IONPs). Tuning the surface chemistry and design of magnetic nanoparticles are described in relation to their applicability in advanced medical technologies and biotechnologies including magnetic resonance imaging (MRI) contrast agents, targeted drug delivery, magnetic separations and immobilizations of proteins, enzymes, antibodies, targeting agents and other biosubstances. We review synthetic strategies for the controlled preparation of IONPs modified with frequently used functional groups including amine, carboxyl and hydroxyl groups as well as the preparation of IONPs functionalized with other species, e.g., epoxy, thiol, alkane, azide, and alkyne groups. Three main coupling strategies for linking IONPs with active agents are presented: (i) chemical modification of amine groups on the surface of IONPs, (ii) chemical modification of bioactive substances (e.g. with fluorescent dyes), and (iii) the activation of carboxyl groups mainly for enzyme immobilization. Applications for drug delivery using click chemistry linking or biodegradable bonds are compared to non-covalent methods based on polymer modified condensed magnetic nanoclusters. Among many challenges, we highlight the specific surface engineering allowing both therapeutic and diagnostic applications (theranostics) of IONPs and magnetic/metallic hybrid nanostructures possessing a huge potential in biocatalysis, green chemistry, magnetic bioseparations and bioimaging. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Preparation of Al/Si functionally graded materials using ultrasonic separation method

    Directory of Open Access Journals (Sweden)

    Zhang Zhongtao

    2008-08-01

    Full Text Available Functionally graded materials (FGM have been widely used in many industries such as aerospace, energy and electronics. In this experimental study of fabricating FGM, an approach was developed to prepare Al/Si FGM using power ultrasonic separation method. Material sample with continuously changing composition and performance/properties was successfully produced. Results showed that the microstructure of the FGM sample transited, from its top to bottom, from the hypereutectic structure with a large quantity of primary Si gradually to the eutectic, and fi nally to the hypoeutectic with numerous primary Al dendrites. The distribution of primary Si and microhardness of the FGM sample also presented graded characteristics, resulting that the wear resistance of the FGM sample decreased from top to bottom. Preliminary discussion was made on the mechanism of the formation of Al/Si FGM.

  3. Perturbed invariant subspaces and approximate generalized functional variable separation solution for nonlinear diffusion-convection equations with weak source

    Science.gov (United States)

    Xia, Ya-Rong; Zhang, Shun-Li; Xin, Xiang-Peng

    2018-03-01

    In this paper, we propose the concept of the perturbed invariant subspaces (PISs), and study the approximate generalized functional variable separation solution for the nonlinear diffusion-convection equation with weak source by the approximate generalized conditional symmetries (AGCSs) related to the PISs. Complete classification of the perturbed equations which admit the approximate generalized functional separable solutions (AGFSSs) is obtained. As a consequence, some AGFSSs to the resulting equations are explicitly constructed by way of examples.

  4. 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.

  5. The impact of translocations on neutral and functional genetic diversity within and among populations of the Seychelles warbler.

    Science.gov (United States)

    Wright, David J; Spurgin, Lewis G; Collar, Nigel J; Komdeur, Jan; Burke, Terry; Richardson, David S

    2014-05-01

    Translocations are an increasingly common tool in conservation. The maintenance of genetic diversity through translocation is critical for both the short- and long-term persistence of populations and species. However, the relative spatio-temporal impacts of translocations on neutral and functional genetic diversity, and how this affects genetic structure among the conserved populations overall, have received little investigation. We compared the impact of translocating different numbers of founders on both microsatellite and major histocompatibility complex (MHC) class I diversity over a 23-year period in the Seychelles warbler (Acrocephalus sechellensis). We found low and stable microsatellite and MHC diversity in the source population and evidence for only a limited loss of either type of diversity in the four new populations. However, we found evidence of significant, but low to moderate, genetic differentiation between populations, with those populations established with fewer founders clustering separately. Stochastic genetic capture (as opposed to subsequent drift) was the main determinant of translocated population diversity. Furthermore, a strong correlation between microsatellite and MHC differentiation suggested that neutral processes outweighed selection in shaping MHC diversity in the new populations. These data provide important insights into how to optimize the use of translocation as a conservation tool. © 2014 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

  6. A scintillation camera technique for quantitative estimation of separate kidney function and its use before nephrectomy

    International Nuclear Information System (INIS)

    Larsson, I.; Lindstedt, E.; Ohlin, P.; Strand, S.E.; White, T.

    1975-01-01

    A scintillation camera technique was used for measuring renal uptake of [ 131 I]Hippuran 80-110 s after injection. Externally measured Hippuran uptake was markedly influenced by kidney depth, which was measured by lateral-view image after injection of [ 99 Tc]iron ascorbic acid complex or [ 197 Hg]chlormerodrine. When one kidney was nearer to the dorsal surface of the body than the other, it was necessary to correct the externally measured Hippuran uptake for kidney depth to obtain reliable information on the true partition of Hippuran between the two kidneys. In some patients the glomerular filtration rate (GFR) was measured before and after nephrectomy. Measured postoperative GFR was compared with preoperative predicted GFR, which was calculated by multiplying the preoperative Hippuran uptake of the kidney to be left in situ, as a fraction of the preoperative Hippuran uptake of both kidneys, by the measured preoperative GFR. The measured postoperative GFR was usually moderately higher than the preoperatively predicted GFR. The difference could be explained by a postoperative compensatory increase in function of the remaining kidney. Thus, the present method offers a possibility of estimating separate kidney function without arterial or ureteric catheterization. (auth)

  7. A controlled genetic algorithm by fuzzy logic and belief functions for job-shop scheduling.

    Science.gov (United States)

    Hajri, S; Liouane, N; Hammadi, S; Borne, P

    2000-01-01

    Most scheduling problems are highly complex combinatorial problems. However, stochastic methods such as genetic algorithm yield good solutions. In this paper, we present a controlled genetic algorithm (CGA) based on fuzzy logic and belief functions to solve job-shop scheduling problems. For better performance, we propose an efficient representational scheme, heuristic rules for creating the initial population, and a new methodology for mixing and computing genetic operator probabilities.

  8. A Genetic Toolkit for Dissecting Dopamine Circuit Function in Drosophila

    Directory of Open Access Journals (Sweden)

    Tingting Xie

    2018-04-01

    Full Text Available Summary: The neuromodulator dopamine (DA plays a key role in motor control, motivated behaviors, and higher-order cognitive processes. Dissecting how these DA neural networks tune the activity of local neural circuits to regulate behavior requires tools for manipulating small groups of DA neurons. To address this need, we assembled a genetic toolkit that allows for an exquisite level of control over the DA neural network in Drosophila. To further refine targeting of specific DA neurons, we also created reagents that allow for the conversion of any existing GAL4 line into Split GAL4 or GAL80 lines. We demonstrated how this toolkit can be used with recently developed computational methods to rapidly generate additional reagents for manipulating small subsets or individual DA neurons. Finally, we used the toolkit to reveal a dynamic interaction between a small subset of DA neurons and rearing conditions in a social space behavioral assay. : The rapid analysis of how dopaminergic circuits regulate behavior is limited by the genetic tools available to target and manipulate small numbers of these neurons. Xie et al. present genetic tools in Drosophila that allow rational targeting of sparse dopaminergic neuronal subsets and selective knockdown of dopamine signaling. Keywords: dopamine, genetics, behavior, neural circuits, neuromodulation, Drosophila

  9. Modal parameter identification based on combining transmissibility functions and blind source separation techniques

    Science.gov (United States)

    Araújo, Iván Gómez; Sánchez, Jesús Antonio García; Andersen, Palle

    2018-05-01

    Transmissibility-based operational modal analysis is a recent and alternative approach used to identify the modal parameters of structures under operational conditions. This approach is advantageous compared with traditional operational modal analysis because it does not make any assumptions about the excitation spectrum (i.e., white noise with a flat spectrum). However, common methodologies do not include a procedure to extract closely spaced modes with low signal-to-noise ratios. This issue is relevant when considering that engineering structures generally have closely spaced modes and that their measured responses present high levels of noise. Therefore, to overcome these problems, a new combined method for modal parameter identification is proposed in this work. The proposed method combines blind source separation (BSS) techniques and transmissibility-based methods. Here, BSS techniques were used to recover source signals, and transmissibility-based methods were applied to estimate modal information from the recovered source signals. To achieve this combination, a new method to define a transmissibility function was proposed. The suggested transmissibility function is based on the relationship between the power spectral density (PSD) of mixed signals and the PSD of signals from a single source. The numerical responses of a truss structure with high levels of added noise and very closely spaced modes were processed using the proposed combined method to evaluate its ability to identify modal parameters in these conditions. Colored and white noise excitations were used for the numerical example. The proposed combined method was also used to evaluate the modal parameters of an experimental test on a structure containing closely spaced modes. The results showed that the proposed combined method is capable of identifying very closely spaced modes in the presence of noise and, thus, may be potentially applied to improve the identification of damping ratios.

  10. Induction of DNA synthesis and apoptosis are separable functions of E2F-1

    DEFF Research Database (Denmark)

    Phillips, A C; Bates, S; Ryan, K M

    1997-01-01

    The family of E2F transcription factors have an essential role in mediating cell cycle progression, and recently, one of the E2F protein family, E2F-1, has been shown to participate in the induction of apoptosis. Cooperation between E2F and the p53 tumor suppressor protein in this apoptotic...... response had led to the suggestion that cell cycle progression induced by E2F-1 expression provides an apoptotic signal when placed in conflict with an arrest to cell cycle progression, such as provided by p53. We show here that although apoptosis is clearly enhanced by p53, E2F-1 can induce significant...... apoptosis in the absence of p53. Furthermore, this apoptotic function of E2F-1 is separable from the ability to accelerate entry into DNA synthesis. Analysis of E2F-1 mutants indicates that although DNA-binding is required, transcriptional transactivation is not necessary for the induction of apoptosis by E...

  11. Detection of carcinoembryonic antigen using functional magnetic and fluorescent nanoparticles in magnetic separators

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, H. Y., E-mail: annetsai@csmu.edu.tw [Chung Shan Medical University, Department of Applied Chemistry (China); Chang, C. Y.; Li, Y. C.; Chu, W. C.; Viswanathan, K.; Bor Fuh, C., E-mail: cbfuh@ncnu.edu.tw [National Chi Nan University, Department of Applied Chemistry (China)

    2011-06-15

    We combined a sandwich immunoassay, anti-CEA/CEA/anti-CEA, with functional magnetic ({approx}80 nm) and fluorescent ({approx}180 nm) nanoparticles in magnetic separators to demonstrate a detection method for carcinoembryonic antigen (CEA). Determination of CEA in serum can be used in clinical diagnosis and monitoring of tumor-related diseases. The CEA concentrations in samples were deduced and determined based on the reference plot using the measured fluorescent intensity of sandwich nanoparticles from the sample. The linear range of CEA detection was from 18 ng/mL to 1.8 pg/mL. The detection limit of CEA was 1.8 pg/mL. In comparison with most other detection methods, this method had advantages of lower detection limit and wider linear range. The recovery was higher than 94%. The CEA concentrations of two serum samples were determined to be 9.0 and 55 ng/mL, which differed by 6.7% (9.6 ng/mL) and 9.1% (50 ng/mL) from the measurements of enzyme-linked immunosorbent assay (ELISA), respectively. The analysis time can be reduced to one third of ELISA. This method has good potential for other biomarker detections and biochemical applications.

  12. Structure and functional regulation of RipA, a mycobacterial enzyme essential for daughter cell separation.

    Science.gov (United States)

    Ruggiero, Alessia; Marasco, Daniela; Squeglia, Flavia; Soldini, Silvia; Pedone, Emilia; Pedone, Carlo; Berisio, Rita

    2010-09-08

    Cell separation depends on cell-wall hydrolases that cleave the peptidoglycan layer connecting daughter cells. In Mycobacterium tuberculosis, this process is governed by the predicted endopeptidase RipA. In the absence of this enzyme, the bacterium is unable to divide and exhibits an abnormal phenotype. We here report the crystal structure of a relevant portion of RipA, containing its catalytic-domain and an extra-domain of hitherto unknown function. The structure clearly demonstrates that RipA is produced as a zymogen, which needs to be activated to achieve cell-division. Bacterial cell-wall degradation assays and proteolysis experiments strongly suggest that activation occurs via proteolytic processing of a fully solvent exposed loop identified in the crystal structure. Indeed, proteolytic cleavage at this loop produces an activated form, consisting of the sole catalytic domain. Our work provides the first evidence of self-inhibition in cell-disconnecting enzymes and opens a field for the design of novel antitubercular therapeutics. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Cationic flocculants carrying hydrophobic functionalities: applications for solid/liquid separation.

    Science.gov (United States)

    Schwarz, S; Jaeger, W; Paulke, B-R; Bratskaya, S; Smolka, N; Bohrisch, J

    2007-07-26

    The flocculation behaviors of three series of polycations with narrow molecular weight distributions carrying hydrophobic substituents on their backbones [poly(N-vinylbenzyl-N,N,N-trimethylammonium chloride), poly(N-vinylbenzyl-N,N-dimethyl-N-butylammonium chloride), and poly(N-vinylbenzylpyridinium chloride)] were investigated in dispersions of monodisperse polystyrene latexes and kaolin. Apparently, the charge density of the polycations decreases with increasing substituent hydrophobicity and increasing molecular weight of the polyelectrolytes. The necessary amount of flocculant for phase separation in dispersions with high substrate surface charge densities increases with increasing hydrophobicity of the polyelectrolyte. Nevertheless, the introduction of hydrophobic functionalities is beneficial, resulting in a substantial broadening of the range between the minimum and maximum amounts of flocculant necessary for efficient flocculation (flocculation window). An increase in ionic strength supports this effect. When the substrate has a low charge density, the hydrophobic interactions play a much more significant role in the flocculation process. Here, the minimum efficient doses remained the same for all three polyelectrolytes investigated, but the width of the flocculation window increased as the polycation hydrophobicity and the molecular weight increased. The necessary amount of flocculant increased with an increase in particle size at constant solid content of the dispersion, as well as with a decreasing number of particles at a constant particle size.

  14. 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.

  15. Amino-Functionalized ZIF-7 Nanocrystals: Improved Intrinsic Separation Ability and Interfacial Compatibility in Mixed-Matrix Membranes for CO2 /CH4 Separation.

    Science.gov (United States)

    Xiang, Long; Sheng, Luqian; Wang, Chongqing; Zhang, Lixiong; Pan, Yichang; Li, Yanshuo

    2017-08-01

    Highly permeable and selective, as well as plasticization-resistant membranes are desired as promising alternatives for cost- and energy-effective CO 2 separation. Here, robust mixed-matrix membranes based on an amino-functionalized zeolitic imidazolate framework ZIF-7 (ZIF-7-NH 2 ) and crosslinked poly(ethylene oxide) rubbery polymer are successfully fabricated with filler loadings up to 36 wt%. The ZIF-7-NH 2 materials synthesized from in situ substitution of 2-aminobenzimidazole into the ZIF-7 structure exhibit enlarged aperture size compared with monoligand ZIF-7. The intrinsic separation ability for CO 2 /CH 4 on ZIF-7-NH 2 is remarkably enhanced as a result of improved CO 2 uptake capacity and diffusion selectivity. The incorporation of ZIF-7-NH 2 fillers simultaneously makes the neat polymer more permeable and more selective, surpassing the state-of-the-art 2008 Robeson upper bound. The chelating effect between metal (zinc) nodes of fillers and ester groups of a polymer provides good bonding, enhancing the mechanical strength and plasticization resistance of the neat polymer membrane. The developed novel ZIF-7 structure with amino-function and the resulting nanocomposite membranes are very attractive for applications like natural-gas sweetening or biogas purification. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Genetic Influences on Pulmonary Function: A Large Sample Twin Study

    DEFF Research Database (Denmark)

    Ingebrigtsen, Truls S; Thomsen, Simon F; van der Sluis, Sophie

    2011-01-01

    Heritability of forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), and peak expiratory flow (PEF) has not been previously addressed in large twin studies. We evaluated the genetic contribution to individual differences observed in FEV(1), FVC, and PEF using data from...... the largest population-based twin study on spirometry. Specially trained lay interviewers with previous experience in spirometric measurements tested 4,314 Danish twins (individuals), 46-68 years of age, in their homes using a hand-held spirometer, and their flow-volume curves were evaluated. Modern variance...

  17. Catalyst functionalized buffer sorbent pebbles for rapid separation of carbon dioxide from gas mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Aines, Roger D

    2015-03-31

    A method for separating CO.sub.2 from gas mixtures uses a slurried media impregnated with buffer compounds and coating the solid media with a catalyst or enzyme that promotes the transformation of CO.sub.2 to carbonic acid. Buffer sorbent pebbles with a catalyst or enzyme coating are provided for rapid separation of CO.sub.2 from gas mixtures.

  18. Catalyst functionalized buffer sorbent pebbles for rapid separation of carbon dioxide from gas mixtures

    Science.gov (United States)

    Aines, Roger D.

    2013-03-12

    A method for separating CO.sub.2 from gas mixtures uses a slurried media impregnated with buffer compounds and coating the solid media with a catalyst or enzyme that promotes the transformation of CO.sub.2 to carbonic acid. Buffer sorbent pebbles with a catalyst or enzyme coating are provided for rapid separation of CO.sub.2 from gas mixtures.

  19. SANITY OF CORN GRAINS AS A FUNCTION OF GENETIC MATERIAL

    Directory of Open Access Journals (Sweden)

    L. F. Oliveira

    2018-02-01

    Full Text Available Diseases that occur in corn crops can cause great losses to farmers and consumers of its product and derivatives. So, was evaluated the sanity of maize grains in different genetic materials. The grains used were obtained from the crop of 2014/2015 on a farm in the city of Sorriso, State of Mato Grosso. For this, grain samples were collected from hybrids P3630H, 30F53YH, P2830H, and P3844H. The standard test ("Blotter Test" allowed noticing the incidence of Aspergillus sp., Fusarium sp. and Penicillium sp. Data were submitted to analysis of variance and Scott-Knott test at 5% probability. In treatments with the resistant genetic material the genus with the highest incidence was Penicillium sp. (82%, followed by Fusarium sp. (68.75% and Aspergillus sp. (15.25%. The hybrid with the lower incidence of Fusarium sp. was P2830H (59%. The hybrid with greater resistance to Aspergillus sp. and Penicillium sp. was P3844H (5 and 55%, respectively. The most susceptible hybrid to pathogens Aspergillus sp., Fusarium sp. and Penicillium sp. was 30F53YH (37, 79 and 94%, respectively. For the better sanitary quality of grains, based on the observed data, it is recommended to use the hybrid P2830H

  20. Arbitrariness is not enough: towards a functional approach to the genetic code.

    Science.gov (United States)

    Lacková, Ľudmila; Matlach, Vladimír; Faltýnek, Dan

    2017-12-01

    Arbitrariness in the genetic code is one of the main reasons for a linguistic approach to molecular biology: the genetic code is usually understood as an arbitrary relation between amino acids and nucleobases. However, from a semiotic point of view, arbitrariness should not be the only condition for definition of a code, consequently it is not completely correct to talk about "code" in this case. Yet we suppose that there exist a code in the process of protein synthesis, but on a higher level than the nucleic bases chains. Semiotically, a code should be always associated with a function and we propose to define the genetic code not only relationally (in basis of relation between nucleobases and amino acids) but also in terms of function (function of a protein as meaning of the code). Even if the functional definition of meaning in the genetic code has been discussed in the field of biosemiotics, its further implications have not been considered. In fact, if the function of a protein represents the meaning of the genetic code (the sign's object), then it is crucial to reconsider the notion of its expression (the sign) as well. In our contribution, we will show that the actual model of the genetic code is not the only possible and we will propose a more appropriate model from a semiotic point of view.

  1. Genetic and Environmental Basis in Phenotype Correlation Between Physical Function and Cognition in Aging Chinese Twins

    DEFF Research Database (Denmark)

    Xu, Chunsheng; Zhang, Dongfeng; Tian, Xiaocao

    2017-01-01

    for cognition with handgrip strength, FTSST, near visual acuity, and number of teeth lost. Cognitive function was genetically related to pulmonary function. The FTSST and cognition shared almost the same common environmental factors but only part of the unique environmental factors, both with negative......Although the correlation between cognition and physical function has been well studied in the general population, the genetic and environmental nature of the correlation has been rarely investigated. We conducted a classical twin analysis on cognitive and physical function, including forced...... and cognitive function. Bivariate analysis showed mildly positively genetic correlations between cognition and FEV1, r G = 0.23 [95% CI: 0.03, 0.62], as well as FVC, r G = 0.35 [95% CI: 0.06, 1.00]. We found that FTSST and cognition presented very high common environmental correlation, r C = -1.00 [95% CI: -1...

  2. m6ASNP: a tool for annotating genetic variants by m6A function.

    Science.gov (United States)

    Jiang, Shuai; Xie, Yubin; He, Zhihao; Zhang, Ya; Zhao, Yuli; Chen, Li; Zheng, Yueyuan; Miao, Yanyan; Zuo, Zhixiang; Ren, Jian

    2018-04-02

    Large-scale genome sequencing projects have identified many genetic variants for diverse diseases. A major goal of these projects is to characterize these genetic variants to provide insight into their function and roles in diseases. N6-methyladenosine (m6A) is one of the most abundant RNA modifications in eukaryotes. Recent studies have revealed that aberrant m6A modifications are involved in many diseases. In this study, we present a user-friendly web server called "m6ASNP" that is dedicated to the identification of genetic variants targeting m6A modification sites. A random forest model was implemented in m6ASNP to predict whether the methylation status of a m6A site is altered by the variants surrounding the site. In m6ASNP, genetic variants in a standard VCF format are accepted as the input data, and the output includes an interactive table containing the genetic variants annotated by m6A function. In addition, statistical diagrams and a genome browser are provided to visualize the characteristics and annotate the genetic variants. We believe that m6ASNP is a highly convenient tool that can be used to boost further functional studies investigating genetic variants. The web server "m6ASNP" is implemented in JAVA and PHP and is freely available at http://m6asnp.renlab.org.

  3. Gene cloning: exploring cotton functional genomics and genetic improvement

    Institute of Scientific and Technical Information of China (English)

    Diqiu LIU; Xianlong ZHANG

    2008-01-01

    Cotton is the most important natural fiber plant in the world. The genetic improvement of the quality of the cotton fiber and agricultural productivity is imperative under the situation of increasing consumption and rapid development of textile technology. Recently, the study of cotton molecular biology has progressed greatly. A lot of specifically or preferentially expressed cotton fiber genes were cloned and analyzed. On the other hand, identification of stress response genes expressed in cotton was performed by other research groups. The major stress factors were studied including the wilt pathogens Verticillium dahliae, Fusarium oxy-sporum f. sp. vasinfectum, bacterial blight, root-knot nematode, drought, and salt stress. What is more, a few genes related to the biosynthesis of gossypol, other sesquiterpene phytoalexins and the major seed oil fatty acids were isolated from cotton. In the present review, we focused on the major advances in cotton gene cloning and expression profiling in the recent years.

  4. Polytene chromosome analysis in relation to genetic sex separation in the Mediterranean fruit fly, Ceratitis capitata (Wied.)

    International Nuclear Information System (INIS)

    Kerremans, P.; Busch-Petersen, E.

    1990-01-01

    The development of stable genetic sexing strains in the Mediterranean fruit fly (medfly), Ceratitis capitata (Wiedemann), is hampered by the presence of low levels of male recombination. Such recombination may be reduced by minimizing the distance between the translocation breakpoint and the translocated 'sexing' allele. Cytogenetic analysis of mitotic/meiotic and polytene chromosomes could provide information on the selection of such potentially stable genetic sexing strains. Translocation breakpoints in two genetic sexing strains in the medfly, based on a white female/brown male pupal colour dimorphism, have been determined. Preliminary results are described and the advantages and limitations of polytene chromosome analysis for the isolation of stable genetic sexing strains of the medfly are discussed. (author). 31 refs

  5. Understanding the cognitive and genetic underpinnings of procrastination: Evidence for shared genetic influences with goal management and executive function abilities.

    Science.gov (United States)

    Gustavson, Daniel E; Miyake, Akira; Hewitt, John K; Friedman, Naomi P

    2015-12-01

    Previous research has suggested that individual differences in procrastination are tied to everyday goal-management abilities, but little research has been conducted on specific cognitive abilities that may underlie tendencies for procrastination, such as executive functions (EFs). In this study, we used behavioral genetics methodology to investigate 2 hypotheses about the relationships between procrastination and EF ability: (a) that procrastination is negatively correlated with general EF ability, and (b) that this relationship is due to the genetic components of procrastination that are most related to other everyday goal-management abilities. The results confirmed both of these hypotheses. Procrastination was related to worse general EF ability at both the phenotypic and genetic levels, and this relationship was due to the component of procrastination shared with self-report measures of everyday goal-management failures. These results were observed even after controlling for potential self-report biases stemming from the urge to respond in a socially desirable manner. Together, these findings provide strong evidence for growing theories of procrastination emphasizing the importance of goal-related cognitive abilities and further highlight important genetic influences that underlie procrastination. (c) 2015 APA, all rights reserved).

  6. Towards mosquito sterile insect technique programmes: Exploring genetic, molecular, mechanical and behavioural methods of sex separation in mosquitoes

    Czech Academy of Sciences Publication Activity Database

    Gilles, J. R. L.; Schetelig, M. F.; Scolari, F.; Marec, František; Capurro, M.L.; Franz, G.; Bourtzis, K.

    132S, č. 1 (2014), S178-S187 ISSN 0001-706X R&D Projects: GA ČR GA523/09/2106 Grant - others:Deutsche Forschungsgemeinschalft(DE) SCHE 1833/1 Institutional support: RVO:60077344 Keywords : female elimination * vector control * genetic sexing strains (GSS) Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.270, year: 2014 http://www.sciencedirect.com/science/article/pii/S0001706X13002209?via=ihub

  7. Novel strategy for diameter-selective separation and functionalization of single-wall carbon nanotubes.

    Science.gov (United States)

    Tromp, R M; Afzali, A; Freitag, M; Mitzi, D B; Chen, Zh

    2008-02-01

    The problem of separating single-wall carbon nanotubes (CNTs) by diameter and/or chirality is one of the greatest impediments toward the widespread application of these promising materials in nanoelectronics. In this paper, we describe a novel physical-chemical method for diameter-selective CNT separation that is both simple and effective and that allows up-scaling to large volumes at modest cost. Separation is based on size-selective noncovalent matching of an appropriate anchor molecule to the wall of the CNT, enabling suspension of the CNTs in solvents in which they would otherwise not be soluble. We demonstrate size-selective separation in the 1-2 nm diameter range using easily synthesized oligo-acene adducts as a diameter-selective molecular anchor. CNT field effect transistors fabricated from diameter-selected CNTs show markedly improved electrical properties as compared to nonselected CNTs.

  8. Preparation of a novel dual-function strong cation exchange/hydrophobic interaction chromatography stationary phase for protein separation.

    Science.gov (United States)

    Zhao, Kailou; Yang, Li; Wang, Xuejiao; Bai, Quan; Yang, Fan; Wang, Fei

    2012-08-30

    We have explored a novel dual-function stationary phase which combines both strong cation exchange (SCX) and hydrophobic interaction chromatography (HIC) characteristics. The novel dual-function stationary phase is based on porous and spherical silica gel functionalized with ligand containing sulfonic and benzyl groups capable of electrostatic and hydrophobic interaction functionalities, which displays HIC character in a high salt concentration, and IEC character in a low salt concentration in mobile phase employed. As a result, it can be employed to separate proteins with SCX and HIC modes, respectively. The resolution and selectivity of the dual-function stationary phase were evaluated under both HIC and SCX modes with standard proteins and can be comparable to that of conventional IEC and HIC columns. More than 96% of mass and bioactivity recoveries of proteins can be achieved in both HIC and SCX modes, respectively. The results indicated that the novel dual-function column could replace two individual SCX and HIC columns for protein separation. Mixed retention mechanism of proteins on this dual-function column based on stoichiometric displacement theory (SDT) in LC was investigated to find the optimal balance of the magnitude of electrostatic and hydrophobic interactions between protein and the ligand on the silica surface in order to obtain high resolution and selectivity for protein separation. In addition, the effects of the hydrophobicity of the ligand of the dual-function packings and pH of the mobile phase used on protein separation were also investigated in detail. The results show that the ligand with suitable hydrophobicity to match the electrostatic interaction is very important to prepare the dual-function stationary phase, and a better resolution and selectivity can be obtained at pH 6.5 in SCX mode. Therefore, the dual-function column can replace two individual SCX and HIC columns for protein separation and be used to set up two-dimensional liquid

  9. 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

  10. 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.

  11. Effects of functionally asexual reproduction on quantitative genetic variation in the evening primroses (Oenothera, Onagraceae).

    Science.gov (United States)

    Godfrey, Ryan M; Johnson, Marc T J

    2014-11-01

    It has long been predicted that a loss of sexual reproduction leads to decreased heritable variation within populations and increased differentiation between populations. Despite an abundance of theory, there are few empirical tests of how sex affects genetic variation in phenotypic traits, especially for plants. Here we test whether repeated losses of two critical components of sex (recombination and segregation) in the evening primroses (Oenothera L., Onagraceae) affect quantitative genetic variation within and between populations. We sampled multiple genetic families from 3-5 populations from each of eight Oenothera species, which represented four independent transitions between sexual reproduction and a functionally asexual genetic system called "permanent translocation heterozygosity." We used quantitative genetics methods to partition genetic variation within and between populations for eight plant traits related to growth, leaf physiology, flowering, and resistance to herbivores. Heritability was, on average, 74% higher in sexual Oenothera populations than in functionally asexual populations, with plant growth rate, specific leaf area, and the percentage of leaf water content showing the strongest differences. By contrast, genetic differentiation among populations was 2.8× higher in functionally asexual vs. sexual Oenothera species. This difference was particularly strong for specific leaf area. Sexual populations tended to exhibit higher genetic correlations among traits, but this difference was weakly supported. These results support the prediction that sexual reproduction maintains higher genetic variation within populations, which may facilitate adaptive evolution. We also found partial support for the prediction that a loss of sex leads to greater population differentiation, which may elevate speciation rates. © 2014 Botanical Society of America, Inc.

  12. Pair-Wise and Many-Body Dispersive Interactions Coupled to an Optimally Tuned Range-Separated Hybrid Functional.

    Science.gov (United States)

    Agrawal, Piyush; Tkatchenko, Alexandre; Kronik, Leeor

    2013-08-13

    We propose a nonempirical, pair-wise or many-body dispersion-corrected, optimally tuned range-separated hybrid functional. This functional retains the advantages of the optimal-tuning approach in the prediction of the electronic structure. At the same time, it gains accuracy in the prediction of binding energies for dispersively bound systems, as demonstrated on the S22 and S66 benchmark sets of weakly bound dimers.

  13. An EPR experiment testing the non-separability of the $K^{0} \\overline{K^{0}}$ wave function

    CERN Document Server

    Apostolakis, Alcibiades J; Backenstoss, Gerhard; Bargassa, P; Behnke, O; Benelli, A; Bertin, V; Blanc, F; Bloch, P; Carlson, P J; Carroll, M; Cawley, E; Chardin, G; Chertok, M B; Cody, A; Dejardin, M; Derré, J; Ealet, A; Eleftheriadis, C; Ferreira-Marques, R; Fetscher, W; Fidecaro, Maria; Filipcic, A; Francis, D; Fry, J; Gabathuler, Erwin; Gamet, R; Gerber, H J; Go, A; Guyot, C; Haselden, A; Hayman, P J; Henry-Coüannier, F; Hollander, R W; Hubert, E; Jon-And, K; Kettle, P R; Kochowski, Claude; Kokkas, P; Kreuger, R; Le Gac, R; Leimgruber, F; Mandic, I; Manthos, N; Marel, Gérard; Mikuz, M; Miller, J; Montanet, François; Müller, A; Nakada, Tatsuya; Pagels, B; Papadopoulos, I M; Pavlopoulos, P; Policarpo, Armando; Polivka, G; Rickenbach, R; Roberts, B L; Ruf, T; Schäfer, M; Schaller, L A; Schietinger, T; Schopper, A; Schune, P; Tauscher, Ludwig; Thibault, C; Touchard, F; Touramanis, C; van Eijk, C W E; Vlachos, S; Weber, P; Wigger, I; Wolter, M; Yéche, C; Zavrtanik, D

    1998-01-01

    The EPR-type strangeness correlation in the \\PKz \\PaKz ~system produced in the reaction $\\Pap \\Pp \\rightarrow \\PKz \\PaKz$ at rest has been tested using the CPLEAR detector. The strangeness was tagged via strong interaction with absorbers away from the creation point. The results are consistent with the QM non-separability of the wave function and exclude a spontaneous wave-function factorisation at creation (CL $> 99.99\\%$).

  14. Functional analysis of the Gonococcal Genetic Island of Neisseria gonorrhoeae.

    Directory of Open Access Journals (Sweden)

    Emilia Pachulec

    Full Text Available Neisseria gonorrhoeae is an obligate human pathogen that is responsible for the sexually-transmitted disease gonorrhea. N. gonorrhoeae encodes a T4SS within the Gonococcal Genetic Island (GGI, which secretes ssDNA directly into the external milieu. Type IV secretion systems (T4SSs play a role in horizontal gene transfer and delivery of effector molecules into target cells. We demonstrate that GGI-like T4SSs are present in other β-proteobacteria, as well as in α- and γ-proteobacteria. Sequence comparison of GGI-like T4SSs reveals that the GGI-like T4SSs form a highly conserved unit that can be found located both on chromosomes and on plasmids. To better understand the mechanism of DNA secretion by N. gonorrhoeae, we performed mutagenesis of all genes encoded within the GGI, and studied the effects of these mutations on DNA secretion. We show that genes required for DNA secretion are encoded within the yaa-atlA and parA-parB regions, while genes encoded in the yfeB-exp1 region could be deleted without any effect on DNA secretion. Genes essential for DNA secretion are encoded within at least four different operons.

  15. 14 CFR 406.105 - Separation of functions for prosecuting civil penalties and advising the FAA decisionmaker.

    Science.gov (United States)

    2010-01-01

    ... civil penalties and advising the FAA decisionmaker. 406.105 Section 406.105 Aeronautics and Space... INVESTIGATIONS, ENFORCEMENT, AND ADMINISTRATIVE REVIEW Rules of Practice in FAA Space Transportation Adjudications § 406.105 Separation of functions for prosecuting civil penalties and advising the FAA...

  16. Viscoelastic effects in three-dimensional microphase separation of block copolymers : Dynamic mean-field density functional approach

    NARCIS (Netherlands)

    Maurits, NM; Zvelindovsky, AV; Fraaije, JGEM

    1998-01-01

    In the present paper, we extend the dynamic mean-field density functional method which describes microphase separation phenomena in polymer liquids, to account for viscoelastic effects. The effect of simple steady shear on polymer orientation and elongation is taken into account by adapting the

  17. Coupled particle–fluid transport and magnetic separation in microfluidic systems with passive magnetic functionality

    International Nuclear Information System (INIS)

    Khashan, Saud A; Furlani, Edward P

    2013-01-01

    A study is presented of coupled particle–fluid transport and field-directed particle capture in microfluidic systems with passive magnetic functionality. These systems consist of a microfluidic flow cell on a substrate that contains embedded magnetic elements. Two systems are considered that utilize soft- and hard-magnetic elements, respectively. In the former, an external field is applied to magnetize the elements, and in the latter, they are permanently magnetized. The field produced by the magnetized elements permeates into the flow cell giving rise to an attractive force on magnetic particles that flow through it. The systems are studied using a novel numerical/closed-form modelling approach that combines numerical transport analysis with closed-form field analysis. Particle–fluid transport is computed using computational fluid dynamics (CFD), while the magnetic force that governs particle capture is obtained in closed form. The CFD analysis takes into account dominant particle forces and two-way momentum transfer between the particles and the fluid. The two-way particle–fluid coupling capability is an important feature of the model that distinguishes it from more commonly used and simplified one-way coupling analysis. The model is used to quantify the impact of two-way particle–fluid coupling on both the capture efficiency and the flow pattern in the systems considered. Many effects such as particle-induced flow-enhanced capture efficiency and flow circulation are studied that cannot be predicted using one-way coupling analysis. In addition, dilute particle dispersions are shown to exhibit significant localized particle–fluid coupling near the capture regions, which contradicts the commonly held view that two-way coupling can be ignored when analysing high-gradient magnetic separation involving such particle systems. Overall, the model demonstrates that two-way coupling needs to be taken into account for rigorous predictions of capture efficiency

  18. Assessment of Functional Effects of Unclassified Genetic Variants

    NARCIS (Netherlands)

    Couch, Fergus J.; Rasmussen, Lene Juel; Hofstra, Robert; Monteiro, Alvaro N. A.; Greenblatt, Marc S.; de Wind, Niels

    2008-01-01

    Inherited predisposition to disease is often linked to reduced activity of a disease associated gene product. Thus, quantitation of the influence of inherited variants on gene function can potentially be used to predict the disease relevance of these variants. While many disease genes have been

  19. Assessment of Functional Effects of Unclassified Genetic Variants

    NARCIS (Netherlands)

    Couch, Fergus J.; Rasmussen, Lene Juel; Hofstra, Robert; Monteiro, Alvaro N. A.; Greenblatt, Marc S.; de Wind, Niels

    Inherited predisposition to disease is often linked to reduced activity of a disease associated gene product. Thus, quantitation of the influence of inherited variants on gene function can potentially be used to predict the disease relevance of these variants. While many disease genes have been

  20. Hill functions for stochastic gene regulatory networks from master equations with split nodes and time-scale separation

    Science.gov (United States)

    Lipan, Ovidiu; Ferwerda, Cameron

    2018-02-01

    The deterministic Hill function depends only on the average values of molecule numbers. To account for the fluctuations in the molecule numbers, the argument of the Hill function needs to contain the means, the standard deviations, and the correlations. Here we present a method that allows for stochastic Hill functions to be constructed from the dynamical evolution of stochastic biocircuits with specific topologies. These stochastic Hill functions are presented in a closed analytical form so that they can be easily incorporated in models for large genetic regulatory networks. Using a repressive biocircuit as an example, we show by Monte Carlo simulations that the traditional deterministic Hill function inaccurately predicts time of repression by an order of two magnitudes. However, the stochastic Hill function was able to capture the fluctuations and thus accurately predicted the time of repression.

  1. THE MITOCHONDRIAL PARADIGM FOR CARDIOVASCULAR DISEASE SUSCEPTIBILITY AND CELLULAR FUNCTION: A COMPLEMENTARY CONCEPT TO MENDELIAN GENETICS

    OpenAIRE

    Kryzwanski, David M.; Moellering, Douglas; Fetterman, Jessica L.; Dunham-Snary, Kimberly J.; Sammy, Melissa J.; Ballinger, Scott W.

    2011-01-01

    While there is general agreement that cardiovascular disease (CVD) development is influenced by a combination of genetic, environmental, and behavioral contributors, the actual mechanistic basis of how these factors initiate or promote CVD development in some individuals while others with identical risk profiles do not, is not clearly understood. This review considers the potential role for mitochondrial genetics and function in determining CVD susceptibility from the standpoint that the orig...

  2. Combining extrapolation with ghost interaction correction in range-separated ensemble density functional theory for excited states

    Science.gov (United States)

    Alam, Md. Mehboob; Deur, Killian; Knecht, Stefan; Fromager, Emmanuel

    2017-11-01

    The extrapolation technique of Savin [J. Chem. Phys. 140, 18A509 (2014)], which was initially applied to range-separated ground-state-density-functional Hamiltonians, is adapted in this work to ghost-interaction-corrected (GIC) range-separated ensemble density-functional theory (eDFT) for excited states. While standard extrapolations rely on energies that decay as μ-2 in the large range-separation-parameter μ limit, we show analytically that (approximate) range-separated GIC ensemble energies converge more rapidly (as μ-3) towards their pure wavefunction theory values (μ → +∞ limit), thus requiring a different extrapolation correction. The purpose of such a correction is to further improve on the convergence and, consequently, to obtain more accurate excitation energies for a finite (and, in practice, relatively small) μ value. As a proof of concept, we apply the extrapolation method to He and small molecular systems (viz., H2, HeH+, and LiH), thus considering different types of excitations such as Rydberg, charge transfer, and double excitations. Potential energy profiles of the first three and four singlet Σ+ excitation energies in HeH+ and H2, respectively, are studied with a particular focus on avoided crossings for the latter. Finally, the extraction of individual state energies from the ensemble energy is discussed in the context of range-separated eDFT, as a perspective.

  3. A genetic approach to understanding asthma and lung function development

    DEFF Research Database (Denmark)

    Kreiner-Møller, Eskil

    2014-01-01

    that are most robustly associated with persistent and severe childhood onset asthma. However, it is unknown how the 17q21 common variants are associated with the persistence of symptoms into adulthood. In paper II,we investigated the effect of the 17q21 locus on current adult asthma and related traits......Asthma is a common heritable disease of the airways with recurrent episodes of symptoms and reversible airflow obstruction that has increased dramatically in prevalence. The disease is highly heterogeneous with varying age at onset and clinical presentation and most likely represents several...... responsiveness, but were associated with lung function growth. This suggests that these loci do not exert their effects prenatally and indicate a potential window of opportunity in early childhood for preventing lung function decline and maintaining respiratory health. The 17q21 locus harbors common variants...

  4. Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

    Science.gov (United States)

    Kosan, Christian; Godmann, Maren

    2016-01-01

    All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC) have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function. PMID:26798358

  5. A functional data analysis approach for genetic association studies

    OpenAIRE

    Reimherr, Matthew; Nicolae, Dan

    2014-01-01

    We present a new method based on Functional Data Analysis (FDA) for detecting associations between one or more scalar covariates and a longitudinal response, while correcting for other variables. Our methods exploit the temporal structure of longitudinal data in ways that are otherwise difficult with a multivariate approach. Our procedure, from an FDA perspective, is a departure from more established methods in two key aspects. First, the raw longitudinal phenotypes are assembled into functio...

  6. MARRVEL: Integration of Human and Model Organism Genetic Resources to Facilitate Functional Annotation of the Human Genome.

    Science.gov (United States)

    Wang, Julia; Al-Ouran, Rami; Hu, Yanhui; Kim, Seon-Young; Wan, Ying-Wooi; Wangler, Michael F; Yamamoto, Shinya; Chao, Hsiao-Tuan; Comjean, Aram; Mohr, Stephanie E; Perrimon, Norbert; Liu, Zhandong; Bellen, Hugo J

    2017-06-01

    One major challenge encountered with interpreting human genetic variants is the limited understanding of the functional impact of genetic alterations on biological processes. Furthermore, there remains an unmet demand for an efficient survey of the wealth of information on human homologs in model organisms across numerous databases. To efficiently assess the large volume of publically available information, it is important to provide a concise summary of the most relevant information in a rapid user-friendly format. To this end, we created MARRVEL (model organism aggregated resources for rare variant exploration). MARRVEL is a publicly available website that integrates information from six human genetic databases and seven model organism databases. For any given variant or gene, MARRVEL displays information from OMIM, ExAC, ClinVar, Geno2MP, DGV, and DECIPHER. Importantly, it curates model organism-specific databases to concurrently display a concise summary regarding the human gene homologs in budding and fission yeast, worm, fly, fish, mouse, and rat on a single webpage. Experiment-based information on tissue expression, protein subcellular localization, biological process, and molecular function for the human gene and homologs in the seven model organisms are arranged into a concise output. Hence, rather than visiting multiple separate databases for variant and gene analysis, users can obtain important information by searching once through MARRVEL. Altogether, MARRVEL dramatically improves efficiency and accessibility to data collection and facilitates analysis of human genes and variants by cross-disciplinary integration of 18 million records available in public databases to facilitate clinical diagnosis and basic research. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  7. Role of functional nanoparticles to enhance the polymeric membrane performance for mixture gas separation

    NARCIS (Netherlands)

    Ingole, Pravin G.; Baig, Muhammad Irshad; Choi, Wook; An, Xinghai; Choi, Won Kil; Lee, Hyung Keun

    2017-01-01

    To improve the water vapor/gas separation the hydroxylated TiO2(OH-TiO2) nanopartilces have been synthesized and surface of polysulfone (PSf) hollow fiber membrane (HFM) has been coated as thin film nanocomposite (TFN) membranes. To remove the water vapor from mixture gas, hollow fiber membrane has

  8. Functionalized ionic liquids : absorption solvents for carbon dioxide and olefin separation

    NARCIS (Netherlands)

    Galan Sanchez, L.M.

    2008-01-01

    Nowadays one of the most imperative challenges for the industry is to find alternatives that improve the efficiency of processes to make more sustainable use of energy. The processes where gas separations are present normally require a vast use of energy and therefore an improvement in these

  9. Production of functionalized polyhydroxyalkanoates by genetically modified Methylobacterium extorquens strains

    Directory of Open Access Journals (Sweden)

    Miguez Carlos B

    2010-09-01

    Full Text Available Abstract Background Methylotrophic (methanol-utilizing bacteria offer great potential as cell factories in the production of numerous products from biomass-derived methanol. Bio-methanol is essentially a non-food substrate, an advantage over sugar-utilizing cell factories. Low-value products as well as fine chemicals and advanced materials are envisageable from methanol. For example, several methylotrophic bacteria, including Methylobacterium extorquens, can produce large quantities of the biodegradable polyester polyhydroxybutyric acid (PHB, the best known polyhydroxyalkanoate (PHA. With the purpose of producing second-generation PHAs with increased value, we have explored the feasibility of using M. extorquens for producing functionalized PHAs containing C-C double bonds, thus, making them amenable to future chemical/biochemical modifications for high value applications. Results Our proprietary M. extorquens ATCC 55366 was found unable to yield functionalized PHAs when fed methanol and selected unsaturated carboxylic acids as secondary substrates. However, cloning of either the phaC1 or the phaC2 gene from P. fluorescens GK13, using an inducible and regulated expression system based on cumate as inducer (the cumate switch, yielded recombinant M. extorquens strains capable of incorporating modest quantities of C-C double bonds into PHA, starting from either C6= and/or C8=. The two recombinant strains gave poor results with C11=. The strain containing the phaC2 gene was better at using C8= and at incorporating C-C double bonds into PHA. Solvent fractioning indicated that the produced polymers were PHA blends that consequently originated from independent actions of the native and the recombinant PHA synthases. Conclusions This work constitutes an example of metabolic engineering applied to the construction of a methanol-utilizing bacterium capable of producing functionalized PHAs containing C-C double bonds. In this regard, the PhaC2 synthase

  10. Age-related decline in brain resources modulates genetic effects on cognitive functioning

    Directory of Open Access Journals (Sweden)

    Ulman Lindenberger

    2008-12-01

    Full Text Available Individual differences in cognitive performance increase from early to late adulthood, likely reflecting influences of a multitude of factors. We hypothesize that losses in neurochemical and anatomical brain resources in normal aging modulate the effects of common genetic variations on cognitive functioning. Our hypothesis is based on the assumption that the function relating brain resources to cognition is nonlinear, so that genetic differences exert increasingly large effects on cognition as resources recede from high to medium levels in the course of aging.Direct empirical support for this hypothesis comes from a study by Nagel et al. (2008, who reported that the effects of the Catechol-O-Methyltransferase (COMT gene on cognitive performance are magnified in old age and interacted with the Brain-Derived Neurotrophic Factor (BDNF gene. We conclude that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. Extensions of the hypothesis to other polymorphisms are discussed.

  11. A Twin Study of Normative Personality and DSM-IV Personality Disorder Criterion Counts: Evidence for Separate Genetic Influences.

    Science.gov (United States)

    Czajkowski, Nikolai; Aggen, Steven H; Krueger, Robert F; Kendler, Kenneth S; Neale, Michael C; Knudsen, Gun Peggy; Gillespie, Nathan A; Røysamb, Espen; Tambs, Kristian; Reichborn-Kjennerud, Ted

    2018-03-21

    Both normative personality and DSM-IV personality disorders have been found to be heritable. However, there is limited knowledge about the extent to which the genetic and environmental influences underlying DSM personality disorders are shared with those of normative personality. The aims of this study were to assess the phenotypic similarity between normative and pathological personality and to investigate the extent to which genetic and environmental influences underlying individual differences in normative personality account for symptom variance across DSM-IV personality disorders. A large population-based sample of adult twins was assessed for DSM-IV personality disorder criteria with structured interviews at two waves spanning a 10-year interval. At the second assessment, participants also completed the Big Five Inventory, a self-report instrument assessing the five-factor normative personality model. The proportion of genetic and environmental liabilities unique to the individual personality disorder measures, and hence not shared with the five Big Five Inventory domains, were estimated by means of multivariate Cholesky twin decompositions. The median percentage of genetic liability to the 10 DSM-IV personality disorders assessed at wave 1 that was not shared with the Big Five domains was 64%, whereas for the six personality disorders that were assessed concurrently at wave 2, the median was 39%. Conversely, the median proportions of unique environmental liability in the personality disorders for wave 1 and wave 2 were 97% and 96%, respectively. The results indicate that a moderate-to-sizable proportion of the genetic influence underlying DSM-IV personality disorders is not shared with the domain constructs of the Big Five model of normative personality. Caution should be exercised in assuming that normative personality measures can serve as proxies for DSM personality disorders when investigating the etiology of these disorders.

  12. Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

    Directory of Open Access Journals (Sweden)

    Christian Kosan

    2016-01-01

    Full Text Available All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function.

  13. The application of neutral network integrated with genetic algorithm and simulated annealing for the simulation of rare earths separation processes by the solvent extraction technique using EHEHPA agent

    International Nuclear Information System (INIS)

    Tran Ngoc Ha; Pham Thi Hong Ha

    2003-01-01

    In the present work, neutral network has been used for mathematically modeling equilibrium data of the mixture of two rare earth elements, namely Nd and Pr with PC88A agent. Thermo-genetic algorithm based on the idea of the genetic algorithm and the simulated annealing algorithm have been used in the training procedure of the neutral networks, giving better result in comparison with the traditional modeling approach. The obtained neutral network modeling the experimental data is further used in the computer program to simulate the solvent extraction process of two elements Nd and Pr. Based on this computer program, various optional schemes for the separation of Nd and Pr have been investigated and proposed. (author)

  14. Detecting phase separation of freeze-dried binary amorphous systems using pair-wise distribution function and multivariate data analysis

    DEFF Research Database (Denmark)

    Chieng, Norman; Trnka, Hjalte; Boetker, Johan

    2013-01-01

    The purpose of this study is to investigate the use of multivariate data analysis for powder X-ray diffraction-pair-wise distribution function (PXRD-PDF) data to detect phase separation in freeze-dried binary amorphous systems. Polymer-polymer and polymer-sugar binary systems at various ratios were...... freeze-dried. All samples were analyzed by PXRD, transformed to PDF and analyzed by principal component analysis (PCA). These results were validated by differential scanning calorimetry (DSC) through characterization of glass transition of the maximally freeze-concentrate solute (Tg'). Analysis of PXRD......-PDF data using PCA provides a more clear 'miscible' or 'phase separated' interpretation through the distribution pattern of samples on a score plot presentation compared to residual plot method. In a phase separated system, samples were found to be evenly distributed around the theoretical PDF profile...

  15. Genetic variants affecting cross-sectional lung function in adults show little or no effect on longitudinal lung function decline

    DEFF Research Database (Denmark)

    John, Catherine; Soler Artigas, María; Hui, Jennie

    2017-01-01

    BACKGROUND: Genome-wide association studies have identified numerous genetic regions that influence cross-sectional lung function. Longitudinal decline in lung function also includes a heritable component but the genetic determinants have yet to be defined. OBJECTIVES: We aimed to determine whether...... regions associated with cross-sectional lung function were also associated with longitudinal decline and to seek novel variants which influence decline. METHODS: We analysed genome-wide data from 4167 individuals from the Busselton Health Study cohort, who had undergone spirometry (12 695 observations...... across eight time points). A mixed model was fitted and weighted risk scores were calculated for the joint effect of 26 known regions on baseline and longitudinal changes in FEV1 and FEV1/FVC. Potential additional regions of interest were identified and followed up in two independent cohorts. RESULTS...

  16. Imprint-coating synthesis of selective functionalized ordered mesoporous sorbents for separation and sensors

    Science.gov (United States)

    Dai, Sheng; Burleigh, Mark C.; Shin, Yongsoon

    2001-01-01

    The present invention relates generally to mesoporous sorbent materials having high capacity, high selectivity, fast kinetics, and molecular recognition capability. The invention also relates to a process for preparing these mesoporous substrates through molecular imprinting techniques which differ from convention techniques in that a template molecule is bound to one end of bifunctional ligands to form a complex prior to binding of the bifunctional ligands to the substrate. The present invention also relates to methods of using the mesoporous sorbent materials, for example, in the separation of toxic metals from process effluents, paints, and other samples; detection of target molecules, such as amino acids, drugs, herbicides, fertilizers, and TNT, in samples; separation and/or detection of substances using chromatography; imaging agents; sensors; coatings; and composites.

  17. Utilization of the safety functional analysis techniques to optimize the separation requirements in case of fire

    International Nuclear Information System (INIS)

    Alvarez, L.M.

    1983-01-01

    The present philosophy for the fire protection of the safe shutdown capability in nuclear power plants is based on the separation of the safety-related systems in different fire areas in such a way that the redundant systems are not subject to damage from a single fire risk. The purpose ofthis paper is to show the experience gained in the application of a symmetric method of analysis to minimize the number of fire barriers being compatible with the regulatory requirements and with capability of achieving and maintaining the safe plant shutdown in the event of a fire. As a conclusion of the analysis, the separation criteria for the divisions involved in the safe plant shutdown are obtained

  18. Urea-functionalized crystalline capsules for recognition and separation of tetrahedral oxoanions

    Energy Technology Data Exchange (ETDEWEB)

    Custelcean, Radu [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Chemical Sciences Division

    2012-12-21

    We reviewed the persistent ability of tripodal TREN-based tris-urea receptors (TREN = tris(2-aminoethyl)amine) to self-assemble with a variety of oxoanions into dimeric capsules upon crystallization. The capsule crystallization allows for charge-, shape-, and size-selective encapsulation of tetrahedral XO4n-anions (n = 2,3), and provides an effective way to separate these anions from competitive aqueous environments.

  19. Pancreatic cancer cell lines as patient-derived avatars: genetic characterisation and functional utility.

    Science.gov (United States)

    Knudsen, Erik S; Balaji, Uthra; Mannakee, Brian; Vail, Paris; Eslinger, Cody; Moxom, Christopher; Mansour, John; Witkiewicz, Agnieszka K

    2018-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is a therapy recalcitrant disease with the worst survival rate of common solid tumours. Preclinical models that accurately reflect the genetic and biological diversity of PDAC will be important for delineating features of tumour biology and therapeutic vulnerabilities. 27 primary PDAC tumours were employed for genetic analysis and development of tumour models. Tumour tissue was used for derivation of xenografts and cell lines. Exome sequencing was performed on the originating tumour and developed models. RNA sequencing, histological and functional analyses were employed to determine the relationship of the patient-derived models to clinical presentation of PDAC. The cohort employed captured the genetic diversity of PDAC. From most cases, both cell lines and xenograft models were developed. Exome sequencing confirmed preservation of the primary tumour mutations in developed cell lines, which remained stable with extended passaging. The level of genetic conservation in the cell lines was comparable to that observed with patient-derived xenograft (PDX) models. Unlike historically established PDAC cancer cell lines, patient-derived models recapitulated the histological architecture of the primary tumour and exhibited metastatic spread similar to that observed clinically. Detailed genetic analyses of tumours and derived models revealed features of ex vivo evolution and the clonal architecture of PDAC. Functional analysis was used to elucidate therapeutic vulnerabilities of relevance to treatment of PDAC. These data illustrate that with the appropriate methods it is possible to develop cell lines that maintain genetic features of PDAC. Such models serve as important substrates for analysing the significance of genetic variants and create a unique biorepository of annotated cell lines and xenografts that were established simultaneously from same primary tumour. These models can be used to infer genetic and empirically determined

  20. Age-related individual variability in memory performance is associated with amygdala-hippocampal circuit function and emotional pattern separation

    Science.gov (United States)

    Leal, Stephanie L.; Noche, Jessica A.; Murray, Elizabeth A.; Yassa, Michael A.

    2018-01-01

    While aging is generally associated with episodic memory decline, not all older adults exhibit memory loss. Furthermore, emotional memories are not subject to the same extent of forgetting and appear preserved in aging. We conducted high-resolution fMRI during a task involving pattern separation of emotional information in older adults with and without age-related memory impairment (characterized by performance on a word-list learning task: low performers: LP vs. high performers: HP). We found signals consistent with emotional pattern separation in hippocampal dentate (DG)/CA3 in HP but not in LP individuals, suggesting a deficit in emotional pattern separation. During false recognition, we found increased DG/CA3 activity in LP individuals, suggesting that hyperactivity may be associated with overgeneralization. We additionally observed a selective deficit in basolateral amygdala—lateral entorhinal cortex—DG/CA3 functional connectivity in LP individuals during pattern separation of negative information. During negative false recognition, LP individuals showed increased medial temporal lobe functional connectivity, consistent with overgeneralization. Overall, these results suggest a novel mechanistic account of individual differences in emotional memory alterations exhibited in aging. PMID:27723500

  1. Age-related individual variability in memory performance is associated with amygdala-hippocampal circuit function and emotional pattern separation.

    Science.gov (United States)

    Leal, Stephanie L; Noche, Jessica A; Murray, Elizabeth A; Yassa, Michael A

    2017-01-01

    While aging is generally associated with episodic memory decline, not all older adults exhibit memory loss. Furthermore, emotional memories are not subject to the same extent of forgetting and appear preserved in aging. We conducted high-resolution fMRI during a task involving pattern separation of emotional information in older adults with and without age-related memory impairment (characterized by performance on a word-list learning task: low performers: LP vs. high performers: HP). We found signals consistent with emotional pattern separation in hippocampal dentate (DG)/CA3 in HP but not in LP individuals, suggesting a deficit in emotional pattern separation. During false recognition, we found increased DG/CA3 activity in LP individuals, suggesting that hyperactivity may be associated with overgeneralization. We additionally observed a selective deficit in basolateral amygdala-lateral entorhinal cortex-DG/CA3 functional connectivity in LP individuals during pattern separation of negative information. During negative false recognition, LP individuals showed increased medial temporal lobe functional connectivity, consistent with overgeneralization. Overall, these results suggest a novel mechanistic account of individual differences in emotional memory alterations exhibited in aging. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Electrospun Nanofibers for Sandwiched Polyimide/Poly (vinylidene fluoride)/Polyimide Separators with the Thermal Shutdown Function

    International Nuclear Information System (INIS)

    Wu, Dezhi; Shi, Chuan; Huang, Shaohua; Qiu, Xiaochun; Wang, Huan; Zhan, Zhan; Zhang, Peng; Zhao, Jinbao; Sun, Daoheng; Lin, Liwei

    2015-01-01

    Nanofibers fabricated by the electrospinning process have been used to construct sandwich-type Polyimide/Poly (vinylidene fluoride)/Polyimide (PI/PVDF/PI) separators with the thermal shutdown function for lithium ion batteries. This architecture uses the good thermal stability of PI as the top and bottom structure layers. Under high temperature operations, the middle layer made of PVDF nanofibers can melt and form a pore-free film to shut down the battery operation. The electrolyte uptake and ionic conductivity of the PI/PVDF/PI separator are superior to those of commercial polyolefin separators at 476% and 3.46 mS cm −1 , respectively, resulting better battery performances in terms of impedance, discharge capacity and cycle life. Under high temperature treatments above 170 °C, the self-shutdown function of the PI/PVDF/PI has been observed within 10 minutes, which could serve as the safety mechanism to defend the thermal runaway issue of lithium ion batteries. The effects of heating temperature and different time on the morphologies of each layer and electrolyte uptake of the separator are characterized as well

  3. On the universality of the long-/short-range separation in multiconfigurational density-functional theory

    DEFF Research Database (Denmark)

    Fromager, Emmanuel; Toulouse, Julien; Jensen, Hans Jørgen Aagaard

    2007-01-01

    In many cases, the dynamic correlation can be calculated quite accurately and at a fairly low computational cost in Kohn-Sham density-functional theory (KS-DFT), using current standard approximate functionals. However, in general, KS-DFT does not treat static correlation effects (near degeneracy...

  4. Zebrafish Functional Genetics Approach to the Pathogenesis of Well-Differentiated Liposarcoma

    Science.gov (United States)

    2015-12-01

    Roderick JE, LaBelle JL, Bird G, Mathieu R, Bodaar K, Colon D, Pyati U, Stevenson KE, Qi J, Harris M, Silverman LB, Sallan SE, Bradner JL, Neuberg DS...pathogenesis of high-risk T-cell acute lymphoblastic leukemia. Our approach combines human cancer genomics with functional genetics, biochemistry and

  5. Linear interpolation method in ensemble Kohn-Sham and range-separated density-functional approximations for excited states

    DEFF Research Database (Denmark)

    Senjean, Bruno; Knecht, Stefan; Jensen, Hans Jørgen Aa

    2015-01-01

    Gross-Oliveira-Kohn density-functional theory (GOK-DFT) for ensembles is, in principle, very attractive but has been hard to use in practice. A practical model based on GOK-DFT for the calculation of electronic excitation energies is discussed. The model relies on two modifications of GOK-DFT: use...... promising results have been obtained for both single (including charge transfer) and double excitations with spin-independent short-range local and semilocal functionals. Even at the Kohn-Sham ensemble DFT level, which is recovered when the range-separation parameter is set to 0, LIM performs better than...

  6. Distinct brain metabolic patterns separately associated with cognition, motor function, and aging in Parkinson's disease dementia.

    Science.gov (United States)

    Ko, Ji Hyun; Katako, Audrey; Aljuaid, Maram; Goertzen, Andrew L; Borys, Andrew; Hobson, Douglas E; Kim, Seok Min; Lee, Chong Sik

    2017-12-01

    We explored whether patients with Parkinson's disease dementia (PDD) show a distinct spatial metabolic pattern that characterizes cognitive deficits in addition to motor dysfunction. Eighteen patients with PDD underwent 3 separate positron emission tomography sessions with [ 18 F]fluorodeoxyglucose (for glucose metabolism), fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (for dopamine transporter density) and Pittsburgh compound-B (for beta-amyloid load). We confirmed in PDD versus normal controls, overall hypometabolism in the posterior and prefrontal brain regions accompanied with hypermetabolism in subcortical structures and the cerebellar vermis. A multivariate network analysis then revealed 3 metabolic patterns that are separately associated with cognitive performance (p = 0.042), age (p = 0.042), and motor symptom severity (p = 0.039). The age-related pattern's association with aging was replicated in healthy controls (p = 0.047) and patients with Alzheimer's disease (p = 0.002). The cognition-related pattern's association with cognitive performance was observed, with a trend-level of correlation, in patients with dementia with Lewy bodies (p = 0.084) but not in patients with Alzheimer's disease (p = 0.974). We found no association with fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane and Pittsburgh compound-B positron emission tomography with patients' cognitive performance. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. An Influence Function Method for Predicting Store Aerodynamic Characteristics during Weapon Separation,

    Science.gov (United States)

    1981-05-14

    8217 AO-Ail 777 GRUMMAN AEROSPACE CORP BETHPAGE NY F/G 20/4 AN INFLUENCE FUNCTION METHOD FOR PREDICTING STORE AERODYNAMIC C--ETCCU) MAY 8 1 R MEYER, A...CENKO, S YARDS UNCLASSIFIED N ’.**~~N**n I EHEEKI j~j .25 Q~4 111110 111_L 5. AN INFLUENCE FUNCTION METHOD FOR PREDICTING STORE AERODYNAMIC...extended to their logical conclusion one is led quite naturally to consideration of an " Influence Function Method" for I predicting store aerodynamic

  8. Strategies for the design of functional MOFs: addressing energy-intensive separations

    KAUST Repository

    Eddaoudi, Mohamed

    2017-01-01

    Metal Organic Frameworks (MOFs) are a promising class of crystalline solid-state materials amenable to tailoring their porosity and functionality towards various applications. MOF reticular chemistry using the Molecular Building Block (MBB) approach

  9. Vantage Sensitivity: Environmental Sensitivity to Positive Experiences as a Function of Genetic Differences.

    Science.gov (United States)

    Pluess, Michael

    2017-02-01

    A large number of gene-environment interaction studies provide evidence that some people are more likely to be negatively affected by adverse experiences as a function of specific genetic variants. However, such "risk" variants are surprisingly frequent in the population. Evolutionary analysis suggests that genetic variants associated with increased risk for maladaptive development under adverse environmental conditions are maintained in the population because they are also associated with advantages in response to different contextual conditions. These advantages may include (a) coexisting genetic resilience pertaining to other adverse influences, (b) a general genetic susceptibility to both low and high environmental quality, and (c) a coexisting propensity to benefit disproportionately from positive and supportive exposures, as reflected in the recent framework of vantage sensitivity. After introducing the basic properties of vantage sensitivity and highlighting conceptual similarities and differences with diathesis-stress and differential susceptibility patterns of gene-environment interaction, selected and recent empirical evidence for the notion of vantage sensitivity as a function of genetic differences is reviewed. The unique contribution that the new perspective of vantage sensitivity may make to our understanding of social inequality will be discussed after suggesting neurocognitive and molecular mechanisms hypothesized to underlie the propensity to benefit disproportionately from benevolent experiences. © 2015 Wiley Periodicals, Inc.

  10. 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

  11. Separation of lanthanides (III) and actinides (III) by calixarenes containing acetamide-phosphine oxides functions

    International Nuclear Information System (INIS)

    Garcia Carrera, A.; Dozol, J.F.; Rouquette, H.

    2001-01-01

    The carbamoyl methyl phosphine oxide CMPO is the well known extractant of the TRUEX process for extraction of actinides from highly salted acidic wastes. In the framework of an European research contract coordinated by CEA/DDCC. V. Boehmer (Mainz, Germany) synthesized calix(4)arenes bearing CMPO moieties either on the wide rim, or on the narrow rim. Some of these calixarenes used at a concentration 10 -3 M are more efficient than CMPO used at a two hundred fifty fold higher concentration. Moreover, calixarene skeleton leads to a strong selectivity among lanthanides, this selectivity is much less obvious for CMPO. Selectivity order is reversed according to whether CMPO unit is borne by the wide rim or the narrow rim. The most efficient calixarenes allow actinides to be separated from most of the lanthanides except the lightest ones. (authors)

  12. On the universality of the long-/short-range separation in multiconfigurational density-functional theory

    Science.gov (United States)

    Fromager, Emmanuel; Toulouse, Julien; Jensen, Hans Jørgen Aa.

    2007-02-01

    In many cases, the dynamic correlation can be calculated quite accurately and at a fairly low computational cost in Kohn-Sham density-functional theory (KS-DFT), using current standard approximate functionals. However, in general, KS-DFT does not treat static correlation effects (near degeneracy) adequately which, on the other hand, can be described in wave-function theory (WFT), for example, with a multiconfigurational self-consistent field (MCSCF) model. It is therefore of high interest to develop a hybrid model which combines the best of both WFT and DFT approaches. The merge of WFT and DFT can be achieved by splitting the two-electron interaction into long-range and short-range parts. The long-range part is then treated by WFT and the short-range part by DFT. In this work the authors consider the so-called "erf" long-range interaction erf(μr12)/r12, which is based on the standard error function, and where μ is a free parameter which controls the range of the long-/short-range decomposition. In order to formulate a general method, they propose a recipe for the definition of an optimal μopt parameter, which is independent of the approximate short-range functional and the approximate wave function, and they discuss its universality. Calculations on a test set consisting of He, Be, Ne, Mg, H2, N2, and H2O yield μopt≈0.4a.u.. A similar analysis on other types of test systems such as actinide compounds is currently in progress. Using the value of 0.4a.u. for μ, encouraging results are obtained with the hybrid MCSCF-DFT method for the dissociation energies of H2, N2, and H2O, with both short-range local-density approximation and PBE-type functionals.

  13. Genetic and environmental sources of covariation between early drinking and adult functioning.

    Science.gov (United States)

    Waldron, Jordan Sparks; Malone, Stephen M; McGue, Matt; Iacono, William G

    2017-08-01

    The vast majority of individuals initiate alcohol consumption for the first time in adolescence. Given the widespread nature of its use and evidence that adolescents may be especially vulnerable to its effects, there is concern about the long-term detrimental impact of adolescent drinking on adult functioning. While some researchers have suggested that genetic processes may confound the relationship, the mechanisms linking drinking and later adjustment remain unclear. The current study utilized a genetically informed sample and biometric modeling to examine the nature of the familial influences on this association and identify the potential for genetic confounding. The sample was drawn from the Minnesota Twin Family Study (MTFS), a longitudinal study consisting of 2,764 twins assessed in 2 cohorts at regular follow-ups from age 17 to age 29 (older cohort) or age 11 to age 29 (younger cohort). A broad range of adult measures was included assessing substance use, antisocial behavior, personality, socioeconomic status, and social functioning. A bivariate Cholesky decomposition was used to examine the common genetic and environmental influences on adolescent drinking and each of the measures of adult adjustment. The results revealed that genetic factors and nonshared environmental influences were generally most important in explaining the relationship between adolescent drinking and later functioning. While the presence of nonshared environmental influences on the association are not inconsistent with a causal impact of adolescent drinking, the findings suggest that many of the adjustment issues associated with adolescent alcohol consumption are best understood as genetically influenced vulnerabilities. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Investigation of H2S separation from H2S/CH4 mixtures using functionalized and non-functionalized vertically aligned carbon nanotube membranes

    Science.gov (United States)

    Gilani, Neda; Towfighi, Jafar; Rashidi, Alimorad; Mohammadi, Toraj; Omidkhah, Mohammad Reza; Sadeghian, Ahmad

    2013-04-01

    Separation of H2S from binary mixtures of H2S/CH4 using vertically aligned carbon nanotube membranes fabricated in anodic aluminum oxide (AAO) template was studied experimentally. Carbon nanotubes (CNTs) were grown in five AAO templates with different pore diameters using chemical vapor deposition, and CNT/AAO membranes with tubular carbon nanotube structure and open caps were selected for separation of H2S. For this, two tubular CNT/AAO membranes were fabricated with the CNT inner diameters of 23 and 8 nm. It was found that permeability and selectivity of the membrane with inner diameter of 23 nm for CNT were independent of upstream feed pressure and H2S feed concentration unlike that of CNT having an inner diameter of 8 nm. Selectivity of these membranes for separation of H2S was obtained in the ranges of 1.36-1.58 and 2.11-2.86, for CNTs with internal diameters of 23 and 8 nm, respectively. In order to enhance the separation of H2S from H2S/CH4 mixtures, dodecylamine was used to functionalize the CNT/AAO membrane with higher selectivity. The results showed that for amido-functionalized membrane, both upstream feed pressure and H2S partial pressure in the feed significantly increased H2S permeability, and selectivity for H2S being in the range of 3.0-5.57 respectively.

  15. Separation of the gluconeogenic and mitochondrial functions of pgc-1α through s6 kinase

    DEFF Research Database (Denmark)

    Lustig, Y.; Ruas, J.L.; Estall, J.L.

    2011-01-01

    PGC-1α is a transcriptional coactivator that powerfully regulates many pathways linked to energy homeostasis. Specifically, PGC-1α controls mitochondrial biogenesis in most tissues but also initiates important tissue-specific functions, including fiber type switching in skeletal muscle and glucon......PGC-1α is a transcriptional coactivator that powerfully regulates many pathways linked to energy homeostasis. Specifically, PGC-1α controls mitochondrial biogenesis in most tissues but also initiates important tissue-specific functions, including fiber type switching in skeletal muscle...... of gluconeogenesis in cultured hepatocytes and in vivo, while leaving the functions of PGC-1α as an activator of mitochondrial and fatty acid oxidation genes completely intact. These phosphorylations interfere with the ability of PGC-1α to bind to HNF4α, a transcription factor required for gluconeogenesis, while...

  16. 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...

  17. Genetic and environmental influences on motor function: a magnetoencephalographic study of twins

    Directory of Open Access Journals (Sweden)

    Toshihiko eAraki

    2014-06-01

    Full Text Available To investigate the effect of genetic and environmental influences on cerebral motor function, we determined similarities of movement-related cortical fields (MRCFs in middle-aged and elderly monozygotic (MZ twins. MRCFs were measured using a 160-channel MEG system when MZ twins were instructed to repeat lifting of the right index finger. We compared latency, amplitude, dipole location, and dipole intensity of movement-evoked field 1 (MEF1 between 16 MZ twins and 16 pairs of genetically unrelated pairs. Differences in latency and dipole location between MZ twins were significantly less than those between unrelated age-matched pairs. However, amplitude and dipole intensity were not significantly different. These results suggest that the latency and dipole location of MEF1 are determined early in life by genetic and early common environmental factors, whereas amplitude and dipole intensity are influenced by long-term environmental factors. Improved understanding of genetic and environmental factors that influence cerebral motor function may contribute to evaluation and improvement for individual motor function.

  18. Angle-dependent strong-field molecular ionization rates with tuned range-separated time-dependent density functional theory

    Energy Technology Data Exchange (ETDEWEB)

    Sissay, Adonay [Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803 (United States); Abanador, Paul; Mauger, François; Gaarde, Mette; Schafer, Kenneth J. [Department of Physics and Astronomy, Louisiana State University, Baton Rouge, Louisiana 70803 (United States); Lopata, Kenneth, E-mail: klopata@lsu.edu [Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803 (United States); Center for Computation and Technology, Louisiana State University, Baton Rouge, Louisiana 70803 (United States)

    2016-09-07

    Strong-field ionization and the resulting electronic dynamics are important for a range of processes such as high harmonic generation, photodamage, charge resonance enhanced ionization, and ionization-triggered charge migration. Modeling ionization dynamics in molecular systems from first-principles can be challenging due to the large spatial extent of the wavefunction which stresses the accuracy of basis sets, and the intense fields which require non-perturbative time-dependent electronic structure methods. In this paper, we develop a time-dependent density functional theory approach which uses a Gaussian-type orbital (GTO) basis set to capture strong-field ionization rates and dynamics in atoms and small molecules. This involves propagating the electronic density matrix in time with a time-dependent laser potential and a spatial non-Hermitian complex absorbing potential which is projected onto an atom-centered basis set to remove ionized charge from the simulation. For the density functional theory (DFT) functional we use a tuned range-separated functional LC-PBE*, which has the correct asymptotic 1/r form of the potential and a reduced delocalization error compared to traditional DFT functionals. Ionization rates are computed for hydrogen, molecular nitrogen, and iodoacetylene under various field frequencies, intensities, and polarizations (angle-dependent ionization), and the results are shown to quantitatively agree with time-dependent Schrödinger equation and strong-field approximation calculations. This tuned DFT with GTO method opens the door to predictive all-electron time-dependent density functional theory simulations of ionization and ionization-triggered dynamics in molecular systems using tuned range-separated hybrid functionals.

  19. Angle-dependent strong-field molecular ionization rates with tuned range-separated time-dependent density functional theory

    International Nuclear Information System (INIS)

    Sissay, Adonay; Abanador, Paul; Mauger, François; Gaarde, Mette; Schafer, Kenneth J.; Lopata, Kenneth

    2016-01-01

    Strong-field ionization and the resulting electronic dynamics are important for a range of processes such as high harmonic generation, photodamage, charge resonance enhanced ionization, and ionization-triggered charge migration. Modeling ionization dynamics in molecular systems from first-principles can be challenging due to the large spatial extent of the wavefunction which stresses the accuracy of basis sets, and the intense fields which require non-perturbative time-dependent electronic structure methods. In this paper, we develop a time-dependent density functional theory approach which uses a Gaussian-type orbital (GTO) basis set to capture strong-field ionization rates and dynamics in atoms and small molecules. This involves propagating the electronic density matrix in time with a time-dependent laser potential and a spatial non-Hermitian complex absorbing potential which is projected onto an atom-centered basis set to remove ionized charge from the simulation. For the density functional theory (DFT) functional we use a tuned range-separated functional LC-PBE*, which has the correct asymptotic 1/r form of the potential and a reduced delocalization error compared to traditional DFT functionals. Ionization rates are computed for hydrogen, molecular nitrogen, and iodoacetylene under various field frequencies, intensities, and polarizations (angle-dependent ionization), and the results are shown to quantitatively agree with time-dependent Schrödinger equation and strong-field approximation calculations. This tuned DFT with GTO method opens the door to predictive all-electron time-dependent density functional theory simulations of ionization and ionization-triggered dynamics in molecular systems using tuned range-separated hybrid functionals.

  20. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity

    Science.gov (United States)

    Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I.; Taylor, Kent D.; Azziz, Ricardo; Goodarzi, Mark O.

    2015-01-01

    Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS. PMID:26305227

  1. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    Directory of Open Access Journals (Sweden)

    Michelle R Jones

    2015-08-01

    Full Text Available Genome wide association studies (GWAS have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS, a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

  2. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    Science.gov (United States)

    Jones, Michelle R; Brower, Meredith A; Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I; Taylor, Kent D; Azziz, Ricardo; Goodarzi, Mark O

    2015-08-01

    Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

  3. Functionalized ultra-porous titania nanofiber membranes as nuclear waste separation and sequestration scaffolds for nuclear fuels recycle.

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Haiqing; Bell, Nelson S; Cipiti, Benjamin B.; Lewis, Tom Goslee,; Sava, Dorina Florentina; Nenoff, Tina Maria

    2012-09-01

    Advanced nuclear fuel cycle concept is interested in reducing separations to a simplified, one-step process if possible. This will benefit from the development of a one-step universal getter and sequestration material so as a simplified, universal waste form was proposed in this project. We have developed a technique combining a modified sol-gel chemistry and electrospinning for producing ultra-porous ceramic nanofiber membranes with controllable diameters and porous structures as the separation/sequestration materials. These ceramic nanofiber materials have been determined to have high porosity, permeability, loading capacity, and stability in extreme conditions. These porous fiber membranes were functionalized with silver nanoparticles and nanocrystal metal organic frameworks (MOFs) to introduce specific sites to capture gas species that are released during spent nuclear fuel reprocessing. Encapsulation into a durable waste form of ceramic composition was also demonstrated.

  4. A Constrained Genetic Algorithm with Adaptively Defined Fitness Function in MRS Quantification

    Science.gov (United States)

    Papakostas, G. A.; Karras, D. A.; Mertzios, B. G.; Graveron-Demilly, D.; van Ormondt, D.

    MRS Signal quantification is a rather involved procedure and has attracted the interest of the medical engineering community, regarding the development of computationally efficient methodologies. Significant contributions based on Computational Intelligence tools, such as Neural Networks (NNs), demonstrated a good performance but not without drawbacks already discussed by the authors. On the other hand preliminary application of Genetic Algorithms (GA) has already been reported in the literature by the authors regarding the peak detection problem encountered in MRS quantification using the Voigt line shape model. This paper investigates a novel constrained genetic algorithm involving a generic and adaptively defined fitness function which extends the simple genetic algorithm methodology in case of noisy signals. The applicability of this new algorithm is scrutinized through experimentation in artificial MRS signals interleaved with noise, regarding its signal fitting capabilities. Although extensive experiments with real world MRS signals are necessary, the herein shown performance illustrates the method's potential to be established as a generic MRS metabolites quantification procedure.

  5. Enhancing gas adsorption and separation capacity through ligand functionalization of microporous metal-organic framework structures.

    Science.gov (United States)

    Zhao, Yonggang; Wu, Haohan; Emge, Thomas J; Gong, Qihan; Nijem, Nour; Chabal, Yves J; Kong, Lingzhu; Langreth, David C; Liu, Hui; Zeng, Heping; Li, Jing

    2011-04-26

    Hydroxyl- and amino- functionalized [Zn(BDC)(TED)(0.5)]·2DMF·0.2H(2)O leads to two new structures, [Zn(BDC-OH)(TED)(0.5)]·1.5DMF·0.3H(2)O and [Zn(BDC-NH(2))(TED)(0.5)]·xDMF·yH(2)O (BDC=terephthalic acid, TED=triethylenediamine, BDC-OH=2-hydroxylterephthalic acid, BDC-NH(2)=2-aminoterephthalic acid). Single-crystal X-ray diffraction and powder X-ray diffraction studies confirmed that the structures of both functionalized compounds are very similar to that of their parent structure. Compound [Zn(BDC)(TED)(0.5)]·2DMF·0.2H(2)O can be considered a 3D porous structure with three interlacing 1D channels, whereas both [Zn(BDC-OH)(TED)(0.5)]·1.5DMF·0.3H(2)O and [Zn(BDC-NH(2))(TED)(0.5)]·xDMF·yH(2)O contain only 1D open channels as a result of functionalization of the BDC ligand by the OH and NH(2) groups. A notable decrease in surface area and pore size is thus observed in both compounds. Consequently, [Zn(BDC)(TED)(0.5)]·2DMF·0.2H(2)O takes up the highest amount of H(2) at low temperatures. Interestingly, however, both [Zn(BDC-OH)(TED)(0.5)]·1.5DMF·0.3H(2)O and [Zn(BDC-NH(2))(TED)(0.5)]·xDMF·yH(2)O show significant enhancement in CO(2) uptake at room temperature, suggesting that the strong interactions between CO(2) and the functionalized ligands, indicating that surface chemistry, rather than porosity, plays a more important role in CO(2) adsorption. A comparison of single-component CO(2), CH(4), CO, N(2), and O(2) adsorption isotherms demonstrates that the adsorption selectivity of CO(2) over other small gases is considerably enhanced through functionalization of the frameworks. Infrared absorption spectroscopic measurements and theoretical calculations are also carried out to assess the effect of functional groups on CO(2) and H(2) adsorption potentials. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Using non-empirically tuned range-separated functionals with simulated emission bands to model fluorescence lifetimes.

    Science.gov (United States)

    Wong, Z C; Fan, W Y; Chwee, T S; Sullivan, Michael B

    2017-08-09

    Fluorescence lifetimes were evaluated using TD-DFT under different approximations for the emitting molecule and various exchange-correlation functionals, such as B3LYP, BMK, CAM-B3LYP, LC-BLYP, M06, M06-2X, M11, PBE0, ωB97, ωB97X, LC-BLYP*, and ωB97X* where the range-separation parameters in the last two functionals were tuned in a non-empirical fashion. Changes in the optimised molecular geometries between the ground and electronically excited states were found to affect the quality of the calculated lifetimes significantly, while the inclusion of vibronic features led to further improvements over the assumption of a vertical electronic transition. The LC-BLYP* functional was found to return the most accurate fluorescence lifetimes with unsigned errors that are mostly within 1.5 ns of experimental values.

  7. Genetic and environmental links between cognitive and physical functions in old age

    DEFF Research Database (Denmark)

    Johnson, Wendy; Deary, Ian J; McGue, Matt

    2009-01-01

    of twins from the Longitudinal Study of Aging Danish Twins. Cognitive function was measured using forward and backward digit span, immediate and delayed memory, and fluency tasks. Physical function was measured using self-report of ability to carry out physical activities including walking, running......In old age, cognitive and physical functions are correlated. Knowing the correlations between genetic and environmental influences underlying this correlation can help to clarify the reasons for the observable (phenotypic) correlation. We estimated these correlations in a sample of 1,053 pairs...

  8. Time-Separating Heating and Sensor Functions of Thermistors in Precision Thermal Control Applications

    Science.gov (United States)

    Cho, Hyung J.; Sukhatme, Kalyani G.; Mahoney, John C.; Penanen, Konstantin Penanen; Vargas, Rudolph, Jr.

    2010-01-01

    A method allows combining the functions of a heater and a thermometer in a single device, a thermistor, with minimal temperature read errors. Because thermistors typically have a much smaller thermal mass than the objects they monitor, the thermal time to equilibrate the thermometer to the temperature of the object is typically much shorter than the thermal time of the object to change its temperature in response to an external perturbation.

  9. Shape functions for separable solutions to cross-field diffusion problems

    International Nuclear Information System (INIS)

    Luning, C.D.; Perry, W.L.

    1984-01-01

    The shape function S(x), which arises in the study of nonlinear diffusion for cross-field diffusion in plasmas, satisfies the equation S''(x)+lambdaa(x)S/sup α/(x) = 0, 0 0. In the cases of physical interest a(x) possesses an integrable singularity at some point in (0,1) but is otherwise continuous. Existence of a positive solution to this problem is established

  10. High-performance intrinsically microporous dihydroxyl-functionalized triptycene-based polyimide for natural gas separation

    KAUST Repository

    Alaslai, Nasser Y.; Ghanem, Bader; Alghunaimi, Fahd; Pinnau, Ingo

    2016-01-01

    A novel polyimide of intrinsic microporosity (PIM-PI) was synthesized from a 9,10-diisopropyl-triptycene-based dianhydride (TPDA) and dihydroxyl-functionalized 4,6-diaminoresorcinol (DAR). The unfunctionalized TPDA-m-phenylenediamine (mPDA) polyimide derivative was made as a reference material to evaluate the effect of the OH group in TPDA-DAR on its gas transport properties. Pure-gas permeability coefficients of He, H2, N2, O2, CH4, and CO2 were measured at 35 °C and 2 atm. The BET surface area based on nitrogen adsorption of dihydroxyl-functionalized TPDA-DAR (308 m2g-1) was 45% lower than that of TPDA-mPDA (565 m2g-1). TPDA-mPDA had a pure-gas CO2 permeability of 349 Barrer and CO2/CH4 selectivity of 32. The dihydroxyl-functionalized TPDA-DAR polyimide exhibited enhanced pure-gas CO2/CH4 selectivity of 46 with a moderate decrease in CO2 permeability to 215 Barrer. The CO2 permeability of TPDA-DAR was ∼30-fold higher than that of a commercial cellulose triacetate membrane coupled with 39% higher pure-gas CO2/CH4 selectivity. The TPDA-based dihydroxyl-containing polyimide showed good plasticization resistance and maintained high mixed-gas selectivity of 38 when tested at a typical CO2 natural gas wellhead CO2 partial pressure of 10 atm.

  11. High-performance intrinsically microporous dihydroxyl-functionalized triptycene-based polyimide for natural gas separation

    KAUST Repository

    Alaslai, Nasser Y.

    2016-03-22

    A novel polyimide of intrinsic microporosity (PIM-PI) was synthesized from a 9,10-diisopropyl-triptycene-based dianhydride (TPDA) and dihydroxyl-functionalized 4,6-diaminoresorcinol (DAR). The unfunctionalized TPDA-m-phenylenediamine (mPDA) polyimide derivative was made as a reference material to evaluate the effect of the OH group in TPDA-DAR on its gas transport properties. Pure-gas permeability coefficients of He, H2, N2, O2, CH4, and CO2 were measured at 35 °C and 2 atm. The BET surface area based on nitrogen adsorption of dihydroxyl-functionalized TPDA-DAR (308 m2g-1) was 45% lower than that of TPDA-mPDA (565 m2g-1). TPDA-mPDA had a pure-gas CO2 permeability of 349 Barrer and CO2/CH4 selectivity of 32. The dihydroxyl-functionalized TPDA-DAR polyimide exhibited enhanced pure-gas CO2/CH4 selectivity of 46 with a moderate decrease in CO2 permeability to 215 Barrer. The CO2 permeability of TPDA-DAR was ∼30-fold higher than that of a commercial cellulose triacetate membrane coupled with 39% higher pure-gas CO2/CH4 selectivity. The TPDA-based dihydroxyl-containing polyimide showed good plasticization resistance and maintained high mixed-gas selectivity of 38 when tested at a typical CO2 natural gas wellhead CO2 partial pressure of 10 atm.

  12. Galápagos and Californian sea lions are separate species: Genetic analysis of the genus Zalophus and its implications for conservation management

    Directory of Open Access Journals (Sweden)

    Wolf Jochen BW

    2007-09-01

    Full Text Available Abstract Background Accurate formal taxonomic designations are thought to be of critical importance for the conservation of endangered taxa. The Galápagos sea lion (GSL, being appreciated as a key element of the Galápagos marine ecosystem, has lately been listed as 'vulnerable' by the IUCN. To date there is, however, hardly any scientific evidence, whether it constitutes a separate entity from its abundant Californian neighbour (CSL. In this paper, we delineate the taxonomic relationships within the genus Zalophus being comprised of the Galápagos sea lion, the Californian sea lion and the already extinct Japanese sea lion (JSL. Results Using a set of different phylogenetic reconstruction approaches, we find support for monophyly of all three taxa without evidence of reticulation events. Molecular clock estimates place time to common ancestry of the Galápagos sea lion and the Californian sea lion at about 2.3 ± 0.5 mya. Genetic separation is further suggested by diagnostic SNPs in the mitochondrial and nuclear genome. Microsatellite markers confirm this trend, showing numerous private alleles at most of the 25 investigated loci. Microsatellite-based estimates of genetic differentiation between the Galápagos sea lion and the Californian sea lion indicate significant genetic differentiation. Gene diversity is 14% lower in the Galápagos sea lion than in the Californian sea lion, but there is no evidence for recent bottleneck events in the Galápagos sea lion. Conclusion Based on molecular evidence we build a case for classifying the Galápagos sea lion (Zalophus wollebaeki, the Californian sea lion (Zalophus californianus and the Japanese sea lion (Zalophus japonicus as true species. As morphological characters do not necessarily fully reflect the rapid divergence on the molecular level, the study can be considered as a test case for deriving species status from molecular evidence. We further use the results to discuss the role of genetics in

  13. Separation of Trace Amount Zn (II Using Additional Carbonyl and Carboxyl Groups Functionalized-Nano Graphene

    Directory of Open Access Journals (Sweden)

    A. Moghimi

    2013-01-01

    Full Text Available A novel and selective method for the fast determination of trace amounts of Zn(IIions in water samples has been developed.  The first additional carbonyl and carboxyl functionalized-nano graphene (SPFNano graphene. The presence of additional carbonyl and carboxyl groups located at the edge of the sheets makes GO sheets strongly hydrophilic, allowing them to readily swell and disperse in water. Based on these oxygen functionalities, different model structures of GO were used as absorbent for extraction of Zn (II   ions by solid phase extraction method. The complexes were eluted with HNO3 (2M10% V.V-1 methanol in acetone and determined the analyte by flame atomic absorption spectrometry.  The procedure is based on the selective formation of Zn (II at optimum pH by elution with organic eluents and determination by flame atomic absorption spectrometry. The method is based on complex formation on the surface of the ENVI-18 DISKTM disks modified carbonyl and carboxyl functionalized-nano graphene oxide molecules covalently bonded together followed by stripping of the retained species by minimum amounts of appropriate organic solvents. The elution is efficient and quantitative. The effect of potential interfering ions, pH, SPFNano graphene, amount, stripping solvent, and sample flow rate were also investigated. Under the optimal experimental conditions, the break-through volume was found to about 1000mL providing a preconcentration factor of 500. The maximum capacity of the disks was found to be 456± 3 µg for Zn2+.The limit of detection of the proposed method is 5ng per 1000mL.The method was applied to the extraction and recovery of Zn in different water samples.

  14. The Separation of Powers and the Judicial Functions in John Locke, Montesquieu e Hamilton, Madison e Jay.

    Directory of Open Access Journals (Sweden)

    Maurício Pires Guedes

    2015-12-01

    Full Text Available Currently there are emerging on the world political scene several movements that search for the foundation of a new philosophical paradigm related to new techniques of constitutional hermeneutics. This movement is the result of a long historical and political development whose immediate bases are directly attached to the consolidation of the modern state. This paper pretend to study the separation of powers, of diverse cultural matrices, from the judiciary function view, pretending to show these influences. From the perspective on history and law experience, these are the parameters we pretend to study, trying, at the end, an adequate understanding of institutional reality in which we live today.

  15. An efficient method for minimizing a convex separable logarithmic function subject to a convex inequality constraint or linear equality constraint

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available We consider the problem of minimizing a convex separable logarithmic function over a region defined by a convex inequality constraint or linear equality constraint, and two-sided bounds on the variables (box constraints. Such problems are interesting from both theoretical and practical point of view because they arise in some mathematical programming problems as well as in various practical problems such as problems of production planning and scheduling, allocation of resources, decision making, facility location problems, and so forth. Polynomial algorithms are proposed for solving problems of this form and their convergence is proved. Some examples and results of numerical experiments are also presented.

  16. Separation of photo-induced radical pair in cryptochrome to a functionally critical distance

    DEFF Research Database (Denmark)

    Solov'yov, Ilia; Domratcheva, Tatiana; Schulten, Klaus

    2014-01-01

    Cryptochrome is a blue light receptor that acts as a sensor for the geomagnetic field and assists many animals in long-range navigation. The magnetoreceptor function arises from light-induced formation of a radical pair through electron transfer between a flavin cofactor (FAD) and a triad...... of tryptophan residues. Here, this electron transfer is investigated by quantum chemical and classical molecular dynamics calculations. The results reveal how sequential electron transfer, assisted by rearrangement of polar side groups in the cryptochrome interior, can yield a FAD-Trp radical pair state...... step can overcome in speed both recombination (electron back-transfer) and proton transfer involving the radical pair reached after primary electron transfer....

  17. Genetic and environmental influences on cardiovascular risk factors and cognitive function

    DEFF Research Database (Denmark)

    Xu, Chunsheng; Tian, Xiaocao; Sun, Jianping

    2018-01-01

    AIM: To explore the genetic and environmental influences on cardiovascular risk factors (CVRF) and cognitive function in the world's largest and rapidly aging Chinese population. METHODS: Cognitive function and CVRF, including body mass index, systolic blood pressure, diastolic blood pressure......, pulse pressure, glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol were measured in 379 complete twin pairs. Univariate and bivariate twin models were fitted to estimate the genetic and environmental components in the variance...... and covariance of CVRF and cognition. RESULTS: Mild-to-high heritability was estimated for CVRF and cognition (0.27-0.74). Unique environmental factors showed low-to-moderate contributions (0.23-0.56). Only HDLC presented significant common environmental contribution (0.50). Bivariate analysis showed...

  18. Density fractions versus size separates: does physical fractionation isolate functional soil compartments?

    Directory of Open Access Journals (Sweden)

    C. Moni

    2012-12-01

    Full Text Available Physical fractionation is a widely used methodology to study soil organic matter (SOM dynamics, but concerns have been raised that the available fractionation methods do not well describe functional SOM pools. In this study we explore whether physical fractionation techniques isolate soil compartments in a meaningful and functionally relevant way for the investigation of litter-derived nitrogen dynamics at the decadal timescale. We do so by performing aggregate density fractionation (ADF and particle size-density fractionation (PSDF on mineral soil samples from two European beech forests a decade after application of 15N labelled litter.

    Both density and size-based fractionation methods suggested that litter-derived nitrogen became increasingly associated with the mineral phase as decomposition progressed, within aggregates and onto mineral surfaces. However, scientists investigating specific aspects of litter-derived nitrogen dynamics are pointed towards ADF when adsorption and aggregation processes are of interest, whereas PSDF is the superior tool to research the fate of particulate organic matter (POM.

    Some methodological caveats were observed mainly for the PSDF procedure, the most important one being that fine fractions isolated after sonication can not be linked to any defined decomposition pathway or protective mechanism. This also implies that historical assumptions about the "adsorbed" state of carbon associated with fine fractions need to be re-evaluated. Finally, this work demonstrates that establishing a comprehensive picture of whole soil OM dynamics requires a combination of both methodologies and we offer a suggestion for an efficient combination of the density and size-based approaches.

  19. Functionalization of Polymer Surfaces by Radiation-Induced Grafting for Separation of Heavy Metal Ions

    Energy Technology Data Exchange (ETDEWEB)

    Przybytniak, G; Kornacka, E M; Fuks, L; Walo, M; Lyczko, K; Mirkowski, K [Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland)

    2012-09-15

    The reported investigations were focused on the elucidation of the most important factors influencing radiation-induced grafting; particularly (1) the effect of radical population generated in polymeric matrix on degree of grafting, (2) parameters determined grafting and its procedure, (3) correlation between layer structure formed via copolymerization and content of monomers in the initial solution. Sorption capacity of the adsorbants was evaluated using {sup 152}Eu{sup 3+} as a marker monitoring depletion of the radioisotope from the initial solution by gamma radiometer. Electron spin resonance spectroscopy (EPR) and gas chromatography (GC) studies confirmed that yield of radiation-induced radicals increases in the following order polystyrene (PS) < polypropylene (PP) < polyethylene (PE). The same relationship was found for efficiency of radiation grafting. It was concluded that under comparable conditions the content of radicals in polymeric matrices determines grafting degree. It was found that application of the simultaneous method of grafting introduces to the grafted layers crosslinking or/and branching as well as degradation of functional groups. All these phenomena reduce access of Eu{sup 3+} to the studied sorbent therefore sorption capacity of the polyamide functionalized via pre-irradiation (indirect) method is higher than that determined for the sorbent prepared by simultaneous method of grafting. When two monomers, acrylic acid (AAc) and acrylamide (AAm) , contributed in the formation of grafted layer, their input into copolymerization was not proportional to the concentrations in the feed solution. It was confirmed that grafting of the monomers shows synergetic effect as the yield of copolymerization exceeds degree of grafting achieved for individual components. (author)

  20. Genetic and Environmental Influences on Motor Function: A Magnetoencephalographic Study of Twins

    OpenAIRE

    Araki, Toshihiko; Hirata, Masayuki; Sugata, Hisato; Yanagisawa, Takufumi; Onishi, Mai; Watanabe, Yoshiyuki; Omura, Kayoko; Honda, Chika; Hayakawa, Kazuo; Yorifuji, Shiro

    2014-01-01

    To investigate the effect of genetic and environmental influences on cerebral motor function, we determined similarities and differences of movement-related cortical fields (MRCFs) in middle-aged and elderly monozygotic (MZ) twins. MRCFs were measured using a 160-channel magnetoencephalogram system when MZ twins were instructed to repeat lifting of the right index finger. We compared latency, amplitude, dipole location, and dipole intensity of movement-evoked field 1 (MEF1) between 16 MZ twin...

  1. Integrative Functional Genomics for Systems Genetics in GeneWeaver.org.

    Science.gov (United States)

    Bubier, Jason A; Langston, Michael A; Baker, Erich J; Chesler, Elissa J

    2017-01-01

    The abundance of existing functional genomics studies permits an integrative approach to interpreting and resolving the results of diverse systems genetics studies. However, a major challenge lies in assembling and harmonizing heterogeneous data sets across species for facile comparison to the positional candidate genes and coexpression networks that come from systems genetic studies. GeneWeaver is an online database and suite of tools at www.geneweaver.org that allows for fast aggregation and analysis of gene set-centric data. GeneWeaver contains curated experimental data together with resource-level data such as GO annotations, MP annotations, and KEGG pathways, along with persistent stores of user entered data sets. These can be entered directly into GeneWeaver or transferred from widely used resources such as GeneNetwork.org. Data are analyzed using statistical tools and advanced graph algorithms to discover new relations, prioritize candidate genes, and generate function hypotheses. Here we use GeneWeaver to find genes common to multiple gene sets, prioritize candidate genes from a quantitative trait locus, and characterize a set of differentially expressed genes. Coupling a large multispecies repository curated and empirical functional genomics data to fast computational tools allows for the rapid integrative analysis of heterogeneous data for interpreting and extrapolating systems genetics results.

  2. 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.

  3. Functional Connectivity and Genetic Profile of a “Double-Cortex”-Like Malformation

    Science.gov (United States)

    Sprugnoli, Giulia; Vatti, Giampaolo; Rossi, Simone; Cerase, Alfonso; Renieri, Alessandra; Mencarelli, Maria A.; Zara, Federico; Rossi, Alessandro; Santarnecchi, Emiliano

    2018-01-01

    Laminar heterotopia is a rare condition consisting in an extra layer of gray matter under properly migrated cortex; it configures an atypical presentation of periventricular nodular heterotopia (PNH) or a double cortex (DC) syndrome. We conducted an original functional MRI (fMRI) analysis in a drug-resistant epilepsy patient with “double-cortex”-like malformation to reveal her functional connectivity (FC) as well as a wide genetic analysis to identify possible genetic substrates. Heterotopias were segmented into region of interests (ROIs), whose voxel-wise FC was compared to that of (i) its normally migrated counterpart, (ii) its contralateral homologous, and (iii) those of 30 age-matched healthy controls. Extensive genetic analysis was conducted to screen cortical malformations-associated genes. Compared to healthy controls, both laminar heterotopias and the overlying cortex showed significant reduction of FC with the contralateral hemisphere. Two heterozygous variants of uncertain clinical significance were found, involving autosomal recessive disease-causing genes, FAT4 and COL18A1. This first FC analysis of a unique case of “double-cortex”-like malformation revealed a hemispheric connectivity segregation both in the laminar cortex as in the correctly migrated one, with a new pattern of genes’ mutations. Our study suggests the altered FC could have an electrophysiological and functional impact on large-scale brain networks, and the involvement of not yet identified genes in “double-cortex”-like malformation with a possible role of rare variants in recessive genes as pathogenic cofactors. PMID:29946244

  4. Separating depressive comorbidity from panic disorder: A combined functional magnetic resonance imaging and machine learning approach.

    Science.gov (United States)

    Lueken, Ulrike; Straube, Benjamin; Yang, Yunbo; Hahn, Tim; Beesdo-Baum, Katja; Wittchen, Hans-Ulrich; Konrad, Carsten; Ströhle, Andreas; Wittmann, André; Gerlach, Alexander L; Pfleiderer, Bettina; Arolt, Volker; Kircher, Tilo

    2015-09-15

    Depression is frequent in panic disorder (PD); yet, little is known about its influence on the neural substrates of PD. Difficulties in fear inhibition during safety signal processing have been reported as a pathophysiological feature of PD that is attenuated by depression. We investigated the impact of comorbid depression in PD with agoraphobia (AG) on the neural correlates of fear conditioning and the potential of machine learning to predict comorbidity status on the individual patient level based on neural characteristics. Fifty-nine PD/AG patients including 26 (44%) with a comorbid depressive disorder (PD/AG+DEP) underwent functional magnetic resonance imaging (fMRI). Comorbidity status was predicted using a random undersampling tree ensemble in a leave-one-out cross-validation framework. PD/AG-DEP patients showed altered neural activation during safety signal processing, while +DEP patients exhibited generally decreased dorsolateral prefrontal and insular activation. Comorbidity status was correctly predicted in 79% of patients (sensitivity: 73%; specificity: 85%) based on brain activation during fear conditioning (corrected for potential confounders: accuracy: 73%; sensitivity: 77%; specificity: 70%). No primary depressed patients were available; only medication-free patients were included. Major depression and dysthymia were collapsed (power considerations). Neurofunctional activation during safety signal processing differed between patients with or without comorbid depression, a finding which may explain heterogeneous results across previous studies. These findings demonstrate the relevance of comorbidity when investigating neurofunctional substrates of anxiety disorders. Predicting individual comorbidity status may translate neurofunctional data into clinically relevant information which might aid in planning individualized treatment. The study was registered with the ISRCTN80046034. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Genetic and Environmental Influences on Pulmonary Function and Muscle Strength: The Chinese Twin Study of Aging

    DEFF Research Database (Denmark)

    Tian, Xiaocao; Xu, Chunsheng; Wu, Yili

    2017-01-01

    Genetic and environmental influences on predictors of decline in daily functioning, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), handgrip, and five-times-sit-to-stand test (FTSST), have not been addressed in the aging Chinese population. We performed classical twin...... was moderate for FEV1, handgrip, and FTSST (55-60%) but insignificant for FVC. Only FVC showed moderate control, with shared environmental factors accounting for about 50% of the total variance. In contrast, all measures of pulmonary function and muscle strength showed modest influences from the unique...

  6. Functional relevance for associations between genetic variants and systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Fei-Yan Deng

    Full Text Available Systemic lupus erythematosus (SLE is a serious prototype autoimmune disease characterized by chronic inflammation, auto-antibody production and multi-organ damage. Recent association studies have identified a long list of loci that were associated with SLE with relatively high statistical power. However, most of them only established the statistical associations of genetic markers and SLE at the DNA level without supporting evidence of functional relevance. Here, using publically available datasets, we performed integrative analyses (gene relationship across implicated loci analysis, differential gene expression analysis and functional annotation clustering analysis and combined with expression quantitative trait loci (eQTLs results to dissect functional mechanisms underlying the associations for SLE. We found that 14 SNPs, which were significantly associated with SLE in previous studies, have cis-regulation effects on four eQTL genes (HLA-DQA1, HLA-DQB1, HLA-DQB2, and IRF5 that were also differentially expressed in SLE-related cell groups. The functional evidence, taken together, suggested the functional mechanisms underlying the associations of 14 SNPs and SLE. The study may serve as an example of mining publically available datasets and results in validation of significant disease-association results. Utilization of public data resources for integrative analyses may provide novel insights into the molecular genetic mechanisms underlying human diseases.

  7. THE MITOCHONDRIAL PARADIGM FOR CARDIOVASCULAR DISEASE SUSCEPTIBILITY AND CELLULAR FUNCTION: A COMPLEMENTARY CONCEPT TO MENDELIAN GENETICS

    Science.gov (United States)

    Kryzwanski, David M.; Moellering, Douglas; Fetterman, Jessica L.; Dunham-Snary, Kimberly J.; Sammy, Melissa J.; Ballinger, Scott W.

    2013-01-01

    While there is general agreement that cardiovascular disease (CVD) development is influenced by a combination of genetic, environmental, and behavioral contributors, the actual mechanistic basis of how these factors initiate or promote CVD development in some individuals while others with identical risk profiles do not, is not clearly understood. This review considers the potential role for mitochondrial genetics and function in determining CVD susceptibility from the standpoint that the original features that molded cellular function were based upon mitochondrial-nuclear relationships established millions of years ago and were likely refined during prehistoric environmental selection events that today, are largely absent. Consequently, contemporary risk factors that influence our susceptibility to a variety of age-related diseases, including CVD were probably not part of the dynamics that defined the processes of mitochondrial – nuclear interaction, and thus, cell function. In this regard, the selective conditions that contributed to cellular functionality and evolution should be given more consideration when interpreting and designing experimental data and strategies. Finally, future studies that probe beyond epidemiologic associations are required. These studies will serve as the initial steps for addressing the provocative concept that contemporary human disease susceptibility is the result of selection events for mitochondrial function that increased chances for prehistoric human survival and reproductive success. PMID:21647091

  8. Association study of functional genetic variants of innate immunity related genes in celiac disease

    Directory of Open Access Journals (Sweden)

    Martín J

    2005-08-01

    Full Text Available Abstract Background Recent evidence suggest that the innate immune system is implicated in the early events of celiac disease (CD pathogenesis. In this work for the first time we have assessed the relevance of different proinflammatory mediators typically related to innate immunity in CD predisposition. Methods We performed a familial study in which 105 celiac families characterized by the presence of an affected child with CD were genotyped for functional polymorphisms located at regulatory regions of IL-1α, IL-1β, IL-1RN, IL-18, RANTES and MCP-1 genes. Familial data was analysed with a transmission disequilibrium test (TDT that revealed no statistically significant differences in the transmission pattern of the different genetic markers considered. Results The TDT analysis for IL-1α, IL-1β, IL-1RN, IL-18, and MCP-1 genes genetic variants did not reveal biased transmission to the affected offspring. Only a borderline association of RANTES promoter genetic variants with CD predisposition was observed. Conclusion Our results suggest that the analysed polymorphisms of IL-1α, IL-1β, IL-1RN, IL-18, RANTES and MCP-1 genes do not seem to play a major role in CD genetic predisposition in our population.

  9. High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography.

    Directory of Open Access Journals (Sweden)

    Ruth Hershberg

    2008-12-01

    Full Text Available Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC. However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis.

  10. The CogBIAS longitudinal study protocol: cognitive and genetic factors influencing psychological functioning in adolescence.

    Science.gov (United States)

    Booth, Charlotte; Songco, Annabel; Parsons, Sam; Heathcote, Lauren; Vincent, John; Keers, Robert; Fox, Elaine

    2017-12-29

    Optimal psychological development is dependent upon a complex interplay between individual and situational factors. Investigating the development of these factors in adolescence will help to improve understanding of emotional vulnerability and resilience. The CogBIAS longitudinal study (CogBIAS-L-S) aims to combine cognitive and genetic approaches to investigate risk and protective factors associated with the development of mood and impulsivity-related outcomes in an adolescent sample. CogBIAS-L-S is a three-wave longitudinal study of typically developing adolescents conducted over 4 years, with data collection at age 12, 14 and 16. At each wave participants will undergo multiple assessments including a range of selective cognitive processing tasks (e.g. attention bias, interpretation bias, memory bias) and psychological self-report measures (e.g. anxiety, depression, resilience). Saliva samples will also be collected at the baseline assessment for genetic analyses. Multilevel statistical analyses will be performed to investigate the developmental trajectory of cognitive biases on psychological functioning, as well as the influence of genetic moderation on these relationships. CogBIAS-L-S represents the first longitudinal study to assess multiple cognitive biases across adolescent development and the largest study of its kind to collect genetic data. It therefore provides a unique opportunity to understand how genes and the environment influence the development and maintenance of cognitive biases and provide insight into risk and protective factors that may be key targets for intervention.

  11. Genetic Variation in GSTP1, Lung Function, Risk of Lung Cancer, and Mortality

    DEFF Research Database (Denmark)

    Nørskov, Marianne S.; Dahl, Morten; Tybjærg-Hansen, Anne

    2017-01-01

    66,069 individuals from the white general population for two common functional variants in the glutathione S-transferase pi 1 gene (GSTP1)—amino acid isoleucine 105 changed to a valine (Ile105Val) and amino acid alanine 114 changed to a valine (Ala114Val)—and recorded lung function, lung cancer......Introduction Glutathione S-transferase pi 1 metabolizes carcinogens from tobacco smoke in the lung. We tested whether genetically altered glutathione S-transferase pi 1 activity affects lung function and risk for tobacco-related cancer and mortality in the general population. Methods We genotyped......, tobacco-related cancer, and death as outcomes. Results Lung function was increased stepwise with the Ile105Val genotype overall (p

  12. Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function.

    Science.gov (United States)

    Di Iorio, Christina R; Carey, Caitlin E; Michalski, Lindsay J; Corral-Frias, Nadia S; Conley, Emily Drabant; Hariri, Ahmad R; Bogdan, Ryan

    2017-06-01

    Early life stress may precipitate psychopathology, at least in part, by influencing amygdala function. Converging evidence across species suggests that links between childhood stress and amygdala function may be dependent upon hypothalamic-pituitary-adrenal (HPA) axis function. Using data from college-attending non-Hispanic European-Americans (n=308) who completed the Duke Neurogenetics Study, we examined whether early life stress (ELS) and HPA axis genetic variation interact to predict threat-related amygdala function as well as psychopathology symptoms. A biologically-informed multilocus profile score (BIMPS) captured HPA axis genetic variation (FKBP5 rs1360780, CRHR1 rs110402; NR3C2 rs5522/rs4635799) previously associated with its function (higher BIMPS are reflective of higher HPA axis activity). BOLD fMRI data were acquired while participants completed an emotional face matching task. ELS and depression and anxiety symptoms were measured using the childhood trauma questionnaire and the mood and anxiety symptom questionnaire, respectively. The interaction between HPA axis BIMPS and ELS was associated with right amygdala reactivity to threat-related stimuli, after accounting for multiple testing (empirical-p=0.016). Among individuals with higher BIMPS (i.e., the upper 21.4%), ELS was positively coupled with threat-related amygdala reactivity, which was absent among those with average or low BIMPS. Further, higher BIMPS were associated with greater self-reported anxious arousal, though there was no evidence that amygdala function mediated this relationship. Polygenic variation linked to HPA axis function may moderate the effects of early life stress on threat-related amygdala function and confer risk for anxiety symptomatology. However, what, if any, neural mechanisms may mediate the relationship between HPA axis BIMPS and anxiety symptomatology remains unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Genetic and functional characterization of culturable plant-beneficial actinobacteria associated with yam rhizosphere.

    Science.gov (United States)

    Arunachalam Palaniyandi, Sasikumar; Yang, Seung Hwan; Damodharan, Karthiyaini; Suh, Joo-Won

    2013-12-01

    Actinobacteria were isolated from the rhizosphere of yam plants from agricultural fields from Yeoju, South Korea and analyzed for their genetic and plant-beneficial functional diversity. A total of 29 highly occurring actinobacterial isolates from the yam rhizosphere were screened for various plant-beneficial traits such as antimicrobial activity on fungi and bacteria; biocontrol traits such as production of siderophore, protease, chitinase, endo-cellulase, and β-glucanase. The isolates were also screened for plant growth-promoting (PGP) traits such as auxin production, phosphate solubilization, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity, and in vitro Arabidopsis growth promotion. 16S rDNA sequence-based phylogenetic analysis was carried out on the actinobacterial isolates to determine their genetic relatedness to known actinobacteria. BOX-PCR analysis revealed high genetic diversity among the isolates. Several isolates were identified to belong to the genus Streptomyces and a few to Kitasatospora. The actinobacterial strains exhibited high diversity in their functionality and were identified as novel and promising candidates for future development into biocontrol and PGP agents. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. 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

  15. Genetic Studies on CRISPR-Cas Functions in Invader Defense in Sulfolobus islandicus

    DEFF Research Database (Denmark)

    Peng, Wenfang

    Archaea and bacteria contain CRISPR-Cas (clustered regularly interspaced short palindromic repeat-CRISPR-associated) systems that protect themselves against invasion by viruses and plasmids. There are three major types of CRISPR-Cas systems, type I, II and III, that are further divided...... into at least 11 subtypes. I employed Sulfolobus islandicus Rey15A as the model to study CRISPR mechanisms. The model archaeon encodes one subtype I-A (Cascade) and two subtype III-B (Cmr-α and Cmr-β) interference systems with no apparent redundancy in cas genes or in CRISPR systems, which is ideal for genetic...... analysis of cas gene function. Furthermore, a range of genetic tools have been developed for S. islandicus Rey15A in our laboratory and a plasmid interference assay has been successfully developed for testing CRISPR-directed DNA targeting activity, which have provided a solid basis for studying...

  16. Genetically engineered tissue to screen for glycan function in tissue formation

    DEFF Research Database (Denmark)

    M., Adamopoulou; E.M., Pallesen; A., Levann

    2017-01-01

    engineered GlycoSkin tissue models can be used to study biological interactions involving glycan structure on lipids, or glycosaminoglycans. This engineering approach will allow us to investigate the functions of glycans in homeostasis and elucidate the role of glycans in normal epithelial formation....... We use genetic engineering with CRISPR/Cas9 combined with 3D organotypic skin models to examine how distinct glycans influence epithelial formation. We have performed knockout and knockin of more than 100 select genes in the genome of human immortalized human keratinocytes, enabling a systematic...... analysis of the impact of specific glycans in the formation and transformation of the human skin. The genetic engineered human skin models (GlycoSkin) was designed with and without all major biosynthetic pathways in mammalian glycan biosynthesis, including GalNAc-O-glycans, O-fucosylation, O...

  17. Searching for globally optimal functional forms for interatomic potentials using genetic programming with parallel tempering.

    Science.gov (United States)

    Slepoy, A; Peters, M D; Thompson, A P

    2007-11-30

    Molecular dynamics and other molecular simulation methods rely on a potential energy function, based only on the relative coordinates of the atomic nuclei. Such a function, called a force field, approximately represents the electronic structure interactions of a condensed matter system. Developing such approximate functions and fitting their parameters remains an arduous, time-consuming process, relying on expert physical intuition. To address this problem, a functional programming methodology was developed that may enable automated discovery of entirely new force-field functional forms, while simultaneously fitting parameter values. The method uses a combination of genetic programming, Metropolis Monte Carlo importance sampling and parallel tempering, to efficiently search a large space of candidate functional forms and parameters. The methodology was tested using a nontrivial problem with a well-defined globally optimal solution: a small set of atomic configurations was generated and the energy of each configuration was calculated using the Lennard-Jones pair potential. Starting with a population of random functions, our fully automated, massively parallel implementation of the method reproducibly discovered the original Lennard-Jones pair potential by searching for several hours on 100 processors, sampling only a minuscule portion of the total search space. This result indicates that, with further improvement, the method may be suitable for unsupervised development of more accurate force fields with completely new functional forms. Copyright (c) 2007 Wiley Periodicals, Inc.

  18. Leaching of spent fuel in simulated disposal condition and separation of plutonium species as a function of oxidation state

    International Nuclear Information System (INIS)

    Kim, Seung Soo; Chun, Kwan Sik; Kang, Chul Hyung

    2000-11-01

    The influences of compacted bentonite on the leaching of spent fuel in bentonite-saturated ground water at room temperature were investigated by analyzing the components of leachates as well as the alterated surface of them. And the plutonium species was separated by ion exchangers. The amounts of Cs, Sb, Sr, Am, Ru, Pu and U released from spent fuel by bentonite-saturated solution for the initial 165 days were 2.0, 0.2, 0.2, 0.02, 0.005, 5x10 - 4, 0.05 % of inventory, respectively. These values correspond to several ∼ several tens times as much as those through bentonite block which were compacted to 1.4 g/cm 3 . The comparison of the cesium released in groundwater and bentonite-saturated solution through bentonite block is simular values, whose lower concentration in leachant indicates that most of radionuclides are retained by compacted bentonite, even though alkali metal such as Cs. The separation of plutonium species as a function of oxidation state by ion exchanger was succeed by two columns' method with packing materials as SiO - , SiO-SO 3 -

  19. A new hybrid genetic algorithm for optimizing the single and multivariate objective functions

    Energy Technology Data Exchange (ETDEWEB)

    Tumuluru, Jaya Shankar [Idaho National Laboratory; McCulloch, Richard Chet James [Idaho National Laboratory

    2015-07-01

    In this work a new hybrid genetic algorithm was developed which combines a rudimentary adaptive steepest ascent hill climbing algorithm with a sophisticated evolutionary algorithm in order to optimize complex multivariate design problems. By combining a highly stochastic algorithm (evolutionary) with a simple deterministic optimization algorithm (adaptive steepest ascent) computational resources are conserved and the solution converges rapidly when compared to either algorithm alone. In genetic algorithms natural selection is mimicked by random events such as breeding and mutation. In the adaptive steepest ascent algorithm each variable is perturbed by a small amount and the variable that caused the most improvement is incremented by a small step. If the direction of most benefit is exactly opposite of the previous direction with the most benefit then the step size is reduced by a factor of 2, thus the step size adapts to the terrain. A graphical user interface was created in MATLAB to provide an interface between the hybrid genetic algorithm and the user. Additional features such as bounding the solution space and weighting the objective functions individually are also built into the interface. The algorithm developed was tested to optimize the functions developed for a wood pelleting process. Using process variables (such as feedstock moisture content, die speed, and preheating temperature) pellet properties were appropriately optimized. Specifically, variables were found which maximized unit density, bulk density, tapped density, and durability while minimizing pellet moisture content and specific energy consumption. The time and computational resources required for the optimization were dramatically decreased using the hybrid genetic algorithm when compared to MATLAB's native evolutionary optimization tool.

  20. A Global Overview of the Genetic and Functional Diversity in the Helicobacter pylori cag Pathogenicity Island

    Science.gov (United States)

    Moodley, Yoshan; Uhr, Markus; Stamer, Christiana; Vauterin, Marc; Suerbaum, Sebastian; Achtman, Mark

    2010-01-01

    The Helicobacter pylori cag pathogenicity island (cagPAI) encodes a type IV secretion system. Humans infected with cagPAI–carrying H. pylori are at increased risk for sequelae such as gastric cancer. Housekeeping genes in H. pylori show considerable genetic diversity; but the diversity of virulence factors such as the cagPAI, which transports the bacterial oncogene CagA into host cells, has not been systematically investigated. Here we compared the complete cagPAI sequences for 38 representative isolates from all known H. pylori biogeographic populations. Their gene content and gene order were highly conserved. The phylogeny of most cagPAI genes was similar to that of housekeeping genes, indicating that the cagPAI was probably acquired only once by H. pylori, and its genetic diversity reflects the isolation by distance that has shaped this bacterial species since modern humans migrated out of Africa. Most isolates induced IL-8 release in gastric epithelial cells, indicating that the function of the Cag secretion system has been conserved despite some genetic rearrangements. More than one third of cagPAI genes, in particular those encoding cell-surface exposed proteins, showed signatures of diversifying (Darwinian) selection at more than 5% of codons. Several unknown gene products predicted to be under Darwinian selection are also likely to be secreted proteins (e.g. HP0522, HP0535). One of these, HP0535, is predicted to code for either a new secreted candidate effector protein or a protein which interacts with CagA because it contains two genetic lineages, similar to cagA. Our study provides a resource that can guide future research on the biological roles and host interactions of cagPAI proteins, including several whose function is still unknown. PMID:20808891

  1. Functional separation in telecommunications

    DEFF Research Database (Denmark)

    Jess Olsen, Ole; Henten, Anders; Falch, Morten

    2008-01-01

    During the past 20 to 30 years, public utilities have been subject to market reforms in most parts of the world. Liberalisation has been introduced to improve efficiency in terms of lower costs and more and better services. The subject of this paper is the Danish reforms of its public utilities....... The focus is on the utilities where the reforms were first introduced, i.e. telecommunications and electricity. The paper examines the following questions: Which are the main reasons for the different regulatory approaches to the liberalisation of telecommunications and electricity supply? In which...

  2. Genetic variation in HTR4 and lung function: GWAS follow-up in mouse.

    Science.gov (United States)

    House, John S; Li, Huiling; DeGraff, Laura M; Flake, Gordon; Zeldin, Darryl C; London, Stephanie J

    2015-01-01

    Human genome-wide association studies (GWASs) have identified numerous associations between single nucleotide polymorphisms (SNPs) and pulmonary function. Proving that there is a causal relationship between GWAS SNPs, many of which are noncoding and without known functional impact, and these traits has been elusive. Furthermore, noncoding GWAS-identified SNPs may exert trans-regulatory effects rather than impact the proximal gene. Noncoding variants in 5-hydroxytryptamine (serotonin) receptor 4 (HTR4) are associated with pulmonary function in human GWASs. To gain insight into whether this association is causal, we tested whether Htr4-null mice have altered pulmonary function. We found that HTR4-deficient mice have 12% higher baseline lung resistance and also increased methacholine-induced airway hyperresponsiveness (AHR) as measured by lung resistance (27%), tissue resistance (48%), and tissue elastance (30%). Furthermore, Htr4-null mice were more sensitive to serotonin-induced AHR. In models of exposure to bacterial lipopolysaccharide, bleomycin, and allergic airway inflammation induced by house dust mites, pulmonary function and cytokine profiles in Htr4-null mice differed little from their wild-type controls. The findings of altered baseline lung function and increased AHR in Htr4-null mice support a causal relationship between genetic variation in HTR4 and pulmonary function identified in human GWAS. © FASEB.

  3. Three-dimensional habitat structure and landscape genetics: a step forward in estimating functional connectivity.

    Science.gov (United States)

    Milanesi, P; Holderegger, R; Bollmann, K; Gugerli, F; Zellweger, F

    2017-02-01

    Estimating connectivity among fragmented habitat patches is crucial for evaluating the functionality of ecological networks. However, current estimates of landscape resistance to animal movement and dispersal lack landscape-level data on local habitat structure. Here, we used a landscape genetics approach to show that high-fidelity habitat structure maps derived from Light Detection and Ranging (LiDAR) data critically improve functional connectivity estimates compared to conventional land cover data. We related pairwise genetic distances of 128 Capercaillie (Tetrao urogallus) genotypes to least-cost path distances at multiple scales derived from land cover data. Resulting β values of linear mixed effects models ranged from 0.372 to 0.495, while those derived from LiDAR ranged from 0.558 to 0.758. The identification and conservation of functional ecological networks suffering from habitat fragmentation and homogenization will thus benefit from the growing availability of detailed and contiguous data on three-dimensional habitat structure and associated habitat quality. © 2016 by the Ecological Society of America.

  4. SAP modulates B cell functions in a genetic background-dependent manner.

    Science.gov (United States)

    Detre, Cynthia; Yigit, Burcu; Keszei, Marton; Castro, Wilson; Magelky, Erica M; Terhorst, Cox

    2013-06-01

    Mutations affecting the SLAM-associated protein (SAP) are responsible for the X-linked lympho-proliferative syndrome (XLP), a severe primary immunodeficiency syndrome with disease manifestations that include fatal mononucleosis, B cell lymphoma and dysgammaglobulinemia. It is well accepted that insufficient help by SAP-/- CD4+ T cells, in particular during the germinal center reaction, is a component of dysgammaglobulinemia in XLP patients and SAP-/- animals. It is however not well understood whether in XLP patients and SAP-/- mice B cell functions are affected, even though B cells themselves do not express SAP. Here we report that B cell intrinsic responses to haptenated protein antigens are impaired in SAP-/- mice and in Rag-/- mice into which B cells derived from SAP-/- mice together with wt CD4+ T cells had been transferred. This impaired B cells functions are in part depending on the genetic background of the SAP-/- mouse, which affects B cell homeostasis. Surprisingly, stimulation with an agonistic anti-CD40 causes strong in vivo and in vitro B cell responses in SAP-/- mice. Taken together, the data demonstrate that genetic factors play an important role in the SAP-related B cell functions. The finding that anti-CD40 can in part restore impaired B cell responses in SAP-/- mice, suggests potentially novel therapeutic interventions in subsets of XLP patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Genetic influences on variation in female orgasmic function: a twin study

    Science.gov (United States)

    Dunn, Kate M; Cherkas, Lynn F; Spector, Tim D

    2005-01-01

    Orgasmic dysfunction in females is commonly reported in the general population with little consensus on its aetiology. We performed a classical twin study to explore whether there were observable genetic influences on female orgasmic dysfunction. Adult females from the TwinsUK register were sent a confidential survey including questions on sexual problems. Complete responses to the questions on orgasmic dysfunction were obtained from 4037 women consisting of 683 monozygotic and 714 dizygotic pairs of female twins aged between 19 and 83 years. One in three women (32%) reported never or infrequently achieving orgasm during intercourse, with a corresponding figure of 21% during masturbation. A significant genetic influence was seen with an estimated heritability for difficulty reaching orgasm during intercourse of 34% (95% confidence interval 27–40%) and 45% (95% confidence interval 38–52%) for orgasm during masturbation. These results show that the wide variation in orgasmic dysfunction in females has a genetic basis and cannot be attributed solely to cultural influences. These results should stimulate further research into the biological and perhaps evolutionary processes governing female sexual function. PMID:17148182

  6. Functional genetic divergence in high CO2 adapted Emiliania huxleyi populations.

    Science.gov (United States)

    Lohbeck, Kai T; Riebesell, Ulf; Collins, Sinéad; Reusch, Thorsten B H

    2013-07-01

    Predicting the impacts of environmental change on marine organisms, food webs, and biogeochemical cycles presently relies almost exclusively on short-term physiological studies, while the possibility of adaptive evolution is often ignored. Here, we assess adaptive evolution in the coccolithophore Emiliania huxleyi, a well-established model species in biological oceanography, in response to ocean acidification. We previously demonstrated that this globally important marine phytoplankton species adapts within 500 generations to elevated CO2 . After 750 and 1000 generations, no further fitness increase occurred, and we observed phenotypic convergence between replicate populations. We then exposed adapted populations to two novel environments to investigate whether or not the underlying basis for high CO2 -adaptation involves functional genetic divergence, assuming that different novel mutations become apparent via divergent pleiotropic effects. The novel environment "high light" did not reveal such genetic divergence whereas growth in a low-salinity environment revealed strong pleiotropic effects in high CO2 adapted populations, indicating divergent genetic bases for adaptation to high CO2 . This suggests that pleiotropy plays an important role in adaptation of natural E. huxleyi populations to ocean acidification. Our study highlights the potential mutual benefits for oceanography and evolutionary biology of using ecologically important marine phytoplankton for microbial evolution experiments. © 2012 The Author(s). Evolution © 2012 The Society for the Study of Evolution.

  7. HEPATIC FUNCTION AFTER GENETICALLY-ENGINEERED PIG LIVER TRANSPLANTATION IN BABOONS

    Science.gov (United States)

    Ekser, Burcin; Echeverri, Gabriel J.; Hassett, Andrea Cortese; Yazer, Mark H.; Long, Cassandra; Meyer, Michael; Ezzelarab, Mohamed; Lin, Chih Che; Hara, Hidetaka; van der Windt, Dirk J.; Dons, Eefje M.; Phelps, Carol; Ayares, David; Cooper, David K.C.; Gridelli, Bruno

    2010-01-01

    Background If ‘bridging’ to allotransplantation is to be achieved by a pig liver xenograft, adequate hepatic function needs to be assured. Methods We have studied hepatic function in baboons after transplantation of livers from α1,3-galactosyltransferase gene-knockout (GTKO,n=1) or GTKO pigs transgenic for CD46 (GTKO/CD46,n=5). Monitoring was by liver function tests and coagulation parameters. Pig-specific proteins in the baboon serum/plasma were identified by Western blot. In 4 baboons, coagulation factors were measured. The results were compared with values from healthy humans, baboons, and pigs. Results Recipient baboons died or were euthanized after 4-7 days following internal bleeding associated with profound thrombocytopenia. However, parameters of liver function, including coagulation, remained in the near-normal range, except for some cholestasis. Western blot demonstrated that pig proteins (albumin, fibrinogen, haptoglobin, plasminogen) were produced by the liver from day 1. Production of several pig coagulation factors was confirmed. Conclusions After the transplantation of genetically-engineered pig livers into baboons (1) many parameters of hepatic function, including coagulation, were normal or near-normal; (2) there was evidence for production of pig proteins, including coagulation factors, and (3) these appeared to function adequately in baboons, though inter-species compatibility of such proteins remains to be confirmed. PMID:20606605

  8. Genetic and environmental components of female depression as a function of the severity of the disorder.

    Science.gov (United States)

    Rusby, James S M; Tasker, Fiona; Cherkas, Lynn

    2016-10-01

    Both clinical care and genome-wide studies need to account for levels of severity in the etiology of depression. The purpose of the study is to estimate the genetic and environmental components of female depression as a function of the severity of the disorder. A genetic and environmental model analysis of depression incidence was made using the IOP Depression Severity Measure (IDSM). Details of lifetime depression incidence were obtained by questionnaire from twins on the DTR registry. Data from 1449 matched female twin pairs in the age range 19-85 years in four ordinal categories of increasing severity were employed in the analysis. Estimates of additive and dominance genetic components of 27% and 25% were found when all three levels of depression were included, and near zero and 33% when the recurrent/severe level was excluded. Shared environmental effects were not significant in either case, but the estimate for random environmental effects was greater when the severe level was excluded. These results suggest that the incidence of severe depression is associated with homozygotic alleles and the less severe with heterozygotic alleles. This is in accord with the finding that the hereditary component of severe depression is relatively high and that milder forms are more dependent on life-time environmental factors. Such conclusions have clinical implications for the diagnosis and treatment of the disorder by practicing psychiatrists. They also lead to the importance of focusing future genome-wide and linkage studies on those females with severe levels of depression if progress in identifying genetic risk loci is to be made.

  9. Forecasting nonlinear chaotic time series with function expression method based on an improved genetic-simulated annealing algorithm.

    Science.gov (United States)

    Wang, Jun; Zhou, Bi-hua; Zhou, Shu-dao; Sheng, Zheng

    2015-01-01

    The paper proposes a novel function expression method to forecast chaotic time series, using an improved genetic-simulated annealing (IGSA) algorithm to establish the optimum function expression that describes the behavior of time series. In order to deal with the weakness associated with the genetic algorithm, the proposed algorithm incorporates the simulated annealing operation which has the strong local search ability into the genetic algorithm to enhance the performance of optimization; besides, the fitness function and genetic operators are also improved. Finally, the method is applied to the chaotic time series of Quadratic and Rossler maps for validation. The effect of noise in the chaotic time series is also studied numerically. The numerical results verify that the method can forecast chaotic time series with high precision and effectiveness, and the forecasting precision with certain noise is also satisfactory. It can be concluded that the IGSA algorithm is energy-efficient and superior.

  10. Quantitative Assessment of Eye Phenotypes for Functional Genetic Studies Using Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Janani Iyer

    2016-05-01

    Full Text Available About two-thirds of the vital genes in the Drosophila genome are involved in eye development, making the fly eye an excellent genetic system to study cellular function and development, neurodevelopment/degeneration, and complex diseases such as cancer and diabetes. We developed a novel computational method, implemented as Flynotyper software (http://flynotyper.sourceforge.net, to quantitatively assess the morphological defects in the Drosophila eye resulting from genetic alterations affecting basic cellular and developmental processes. Flynotyper utilizes a series of image processing operations to automatically detect the fly eye and the individual ommatidium, and calculates a phenotypic score as a measure of the disorderliness of ommatidial arrangement in the fly eye. As a proof of principle, we tested our method by analyzing the defects due to eye-specific knockdown of Drosophila orthologs of 12 neurodevelopmental genes to accurately document differential sensitivities of these genes to dosage alteration. We also evaluated eye images from six independent studies assessing the effect of overexpression of repeats, candidates from peptide library screens, and modifiers of neurotoxicity and developmental processes on eye morphology, and show strong concordance with the original assessment. We further demonstrate the utility of this method by analyzing 16 modifiers of sine oculis obtained from two genome-wide deficiency screens of Drosophila and accurately quantifying the effect of its enhancers and suppressors during eye development. Our method will complement existing assays for eye phenotypes, and increase the accuracy of studies that use fly eyes for functional evaluation of genes and genetic interactions.

  11. Functional genetic variants in the vesicular monoamine transporter 1 (VMAT1) modulate emotion processing

    Science.gov (United States)

    Lohoff, Falk W.; Hodge, Rachel; Narasimhan, Sneha; Nall, Aleksandra; Ferraro, Thomas N.; Mickey, Brian J.; Heitzeg, Mary M.; Langenecker, Scott A.; Zubieta, Jon-Kar; Bogdan, Ryan; Nikolova, Yuliya S.; Drabant, Emily; Hariri, Ahmad R.; Bevilacqua, Laura; Goldman, David; Doyle, Glenn A.

    2012-01-01

    SUMMARY Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits, and risk for psychopathology. PMID:23337945

  12. Genetic Variation in Functional Traits Influences Arthropod Community Composition in Aspen (Populus tremula L.)

    Science.gov (United States)

    Robinson, Kathryn M.; Ingvarsson, Pär K.; Jansson, Stefan; Albrectsen, Benedicte R.

    2012-01-01

    We conducted a study of natural variation in functional leaf traits and herbivory in 116 clones of European aspen, Populus tremula L., the Swedish Aspen (SwAsp) collection, originating from ten degrees of latitude across Sweden and grown in a common garden. In surveys of phytophagous arthropods over two years, we found the aspen canopy supports nearly 100 morphospecies. We identified significant broad-sense heritability of plant functional traits, basic plant defence chemistry, and arthropod community traits. The majority of arthropods were specialists, those coevolved with P. tremula to tolerate and even utilize leaf defence compounds. Arthropod abundance and richness were more closely related to plant growth rates than general chemical defences and relationships were identified between the arthropod community and stem growth, leaf and petiole morphology, anthocyanins, and condensed tannins. Heritable genetic variation in plant traits in young aspen was found to structure arthropod community; however no single trait drives the preferences of arthropod folivores among young aspen genotypes. The influence of natural variation in plant traits on the arthropod community indicates the importance of maintaining genetic variation in wild trees as keystone species for biodiversity. It further suggests that aspen can be a resource for the study of mechanisms of natural resistance to herbivores. PMID:22662190

  13. Genetic variation in functional traits influences arthropod community composition in aspen (Populus tremula L..

    Directory of Open Access Journals (Sweden)

    Kathryn M Robinson

    Full Text Available We conducted a study of natural variation in functional leaf traits and herbivory in 116 clones of European aspen, Populus tremula L., the Swedish Aspen (SwAsp collection, originating from ten degrees of latitude across Sweden and grown in a common garden. In surveys of phytophagous arthropods over two years, we found the aspen canopy supports nearly 100 morphospecies. We identified significant broad-sense heritability of plant functional traits, basic plant defence chemistry, and arthropod community traits. The majority of arthropods were specialists, those coevolved with P. tremula to tolerate and even utilize leaf defence compounds. Arthropod abundance and richness were more closely related to plant growth rates than general chemical defences and relationships were identified between the arthropod community and stem growth, leaf and petiole morphology, anthocyanins, and condensed tannins. Heritable genetic variation in plant traits in young aspen was found to structure arthropod community; however no single trait drives the preferences of arthropod folivores among young aspen genotypes. The influence of natural variation in plant traits on the arthropod community indicates the importance of maintaining genetic variation in wild trees as keystone species for biodiversity. It further suggests that aspen can be a resource for the study of mechanisms of natural resistance to herbivores.

  14. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

  15. Functional significance of genetically different symbiotic algae Symbiodinium in a coral reef symbiosis.

    Science.gov (United States)

    Loram, J E; Trapido-Rosenthal, H G; Douglas, A E

    2007-11-01

    The giant sea anemone Condylactis gigantea associates with members of two clades of the dinoflagellate alga Symbiodinium, either singly or in mixed infection, as revealed by clade-specific quantitative polymerase chain reaction of large subunit ribosomal DNA. To explore the functional significance of this molecular variation, the fate of photosynthetically fixed carbon was investigated by (14)C radiotracer experiments. Symbioses with algae of clades A and B released ca. 30-40% of fixed carbon to the animal tissues. Incorporation into the lipid fraction and the low molecular weight fraction dominated by amino acids was significantly higher in symbioses with algae of clade A than of clade B, suggesting that the genetically different algae in C. gigantea are not functionally equivalent. Symbioses with mixed infections yielded intermediate values, such that this functional trait of the symbiosis can be predicted from the traits of the contributing algae. Coral and sea anemone symbioses with Symbiodinium break down at elevated temperature, a process known as 'coral bleaching'. The functional response of the C. gigantea symbiosis to heat stress varied between the algae of clades A and B, with particularly depressed incorporation of photosynthetic carbon into lipid of the clade B algae, which are more susceptible to high temperature than the algae of clade A. This study provides a first exploration of how the core symbiotic function of photosynthate transfer to the host varies with the genotype of Symbiodinium, an algal symbiont which underpins corals and, hence, coral reef ecosystems.

  16. Do motifs reflect evolved function?--No convergent evolution of genetic regulatory network subgraph topologies.

    Science.gov (United States)

    Knabe, Johannes F; Nehaniv, Chrystopher L; Schilstra, Maria J

    2008-01-01

    Methods that analyse the topological structure of networks have recently become quite popular. Whether motifs (subgraph patterns that occur more often than in randomized networks) have specific functions as elementary computational circuits has been cause for debate. As the question is difficult to resolve with currently available biological data, we approach the issue using networks that abstractly model natural genetic regulatory networks (GRNs) which are evolved to show dynamical behaviors. Specifically one group of networks was evolved to be capable of exhibiting two different behaviors ("differentiation") in contrast to a group with a single target behavior. In both groups we find motif distribution differences within the groups to be larger than differences between them, indicating that evolutionary niches (target functions) do not necessarily mold network structure uniquely. These results show that variability operators can have a stronger influence on network topologies than selection pressures, especially when many topologies can create similar dynamics. Moreover, analysis of motif functional relevance by lesioning did not suggest that motifs were of greater importance to the functioning of the network than arbitrary subgraph patterns. Only when drastically restricting network size, so that one motif corresponds to a whole functionally evolved network, was preference for particular connection patterns found. This suggests that in non-restricted, bigger networks, entanglement with the rest of the network hinders topological subgraph analysis.

  17. Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation.

    Science.gov (United States)

    Pagliaccio, David; Luby, Joan L; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S; Belden, Andrew C; Botteron, Kelly N; Harms, Michael P; Barch, Deanna M

    2015-11-01

    Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N = 120). Whole-brain regression analyses indicated that increasing genetic "risk" predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic "risk" and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. (c) 2015 APA, all rights reserved).

  18. Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation

    Science.gov (United States)

    Pagliaccio, David; Luby, Joan L.; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Belden, Andrew C.; Botteron, Kelly N.; Harms, Michael P.; Barch, Deanna M.

    2015-01-01

    Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9–14 year olds; N=120). Whole-brain regression analyses indicated that increasing genetic ‘risk’ predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic ‘risk’ and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. PMID:26595470

  19. Maternal separation diminishes α-adrenergic receptor density and function in renal vasculature from male Wistar-Kyoto rats.

    Science.gov (United States)

    Loria, Analia S; Osborn, Jeffrey L

    2017-07-01

    Adult rats exposed to maternal separation (MatSep) are normotensive but display lower glomerular filtration rate and increased renal neuroadrenergic drive. The aim of this study was to determine the renal α-adrenergic receptor density and the renal vascular responsiveness to adrenergic stimulation in male rats exposed to MatSep. In addition, baroreflex sensitivity was assessed to determine a component of neural control of the vasculature. Using tissue collected from 4-mo-old MatSep and control rats, α 1 -adrenergic receptors (α 1 -ARs) were measured in renal cortex and isolated renal vasculature using receptor binding assay, and the α-AR subtype gene expression was determined by RT-PCR. Renal cortical α 1 -AR density was similar between MatSep and control tissues (B max = 44 ± 1 vs. 42 ± 2 fmol/mg protein, respectively); however, MatSep reduced α 1 -AR density in renal vasculature (B max = 47 ± 4 vs. 62 ± 4 fmol/mg protein, P adrenergic receptor expression and function in the renal vasculature could develop secondary to MatSep-induced overactivation of the renal neuroadrenergic tone. Copyright © 2017 the American Physiological Society.

  20. Perceived Parental Functioning, Self-Esteem, and Psychological Distress in Adults Whose Parents are Separated/Divorced

    Science.gov (United States)

    Verrocchio, Maria C.; Marchetti, Daniela; Fulcheri, Mario

    2015-01-01

    Objective: The objective of this research was to identify retrospectively the alienating behaviors and the parental bonding that occurred in an Italian sample of adults whose had parents separated or divorced and their associations with self-esteem and psychological distress. Methods: Four hundred seventy adults in Chieti, Italy, completed an anonymous and confidential survey regarding their childhood exposure to parental alienating behaviors (using the Baker Strategy Questionnaire), quality of the parent–child relationship (using Parental Bonding Instruments), self-esteem (using Rosenberg Self-Esteem Scale), and global psychological distress (using Global Severity Index of Symptom Checklist-90-Revised). Results: About 80% of the sample reported some exposure to parental alienating behaviors; about 65–70% of the sample has perceived non-optimal parenting by mother and by father; individuals who experienced affectionless control (low care and high overprotection) reported significantly higher exposure to parental loyalty conflict behaviors. Overall rates of reported exposure to low care, and overprotection and parental loyalty conflict behaviors were statistically significantly associated with self-esteem as well as the measure of current psychological distress. Results revealed that exposure to parental loyalty conflict behaviors and self-esteem were associated with psychological distress over and above the effects of parental bonding and age. Conclusion: The pattern of findings supports the theory that children exposed to dysfunctional parenting, and with low self-esteem are at risk for their long-term psychological functioning. Implications for health policy changes and strengthening social services are discussed. PMID:26635670

  1. Perceived Parental Functioning, Self-Esteem, and Psychological Distress in Adults Whose Parents are Separated/Divorced.

    Science.gov (United States)

    Verrocchio, Maria C; Marchetti, Daniela; Fulcheri, Mario

    2015-01-01

    The objective of this research was to identify retrospectively the alienating behaviors and the parental bonding that occurred in an Italian sample of adults whose had parents separated or divorced and their associations with self-esteem and psychological distress. Four hundred seventy adults in Chieti, Italy, completed an anonymous and confidential survey regarding their childhood exposure to parental alienating behaviors (using the Baker Strategy Questionnaire), quality of the parent-child relationship (using Parental Bonding Instruments), self-esteem (using Rosenberg Self-Esteem Scale), and global psychological distress (using Global Severity Index of Symptom Checklist-90-Revised). About 80% of the sample reported some exposure to parental alienating behaviors; about 65-70% of the sample has perceived non-optimal parenting by mother and by father; individuals who experienced affectionless control (low care and high overprotection) reported significantly higher exposure to parental loyalty conflict behaviors. Overall rates of reported exposure to low care, and overprotection and parental loyalty conflict behaviors were statistically significantly associated with self-esteem as well as the measure of current psychological distress. RESULTS revealed that exposure to parental loyalty conflict behaviors and self-esteem were associated with psychological distress over and above the effects of parental bonding and age. The pattern of findings supports the theory that children exposed to dysfunctional parenting, and with low self-esteem are at risk for their long-term psychological functioning. Implications for health policy changes and strengthening social services are discussed.

  2. Perceived parental functioning, self-esteem, and psychological distress in adults whose parents are separated/divorced

    Directory of Open Access Journals (Sweden)

    Maria Cristina eVerrocchio

    2015-11-01

    Full Text Available Objective. The objective of this research was to identify retrospectively the alienating behaviors and the parental bonding that occurred in an Italian sample of adults whose had parents separated or divorced and their associations with self-esteem and psychological distress. Methods. Four hundred seventy adults in Chieti, Italy, completed an anonymous and confidential survey regarding their childhood exposure to parental alienating behaviors (using the Baker Strategy Questionnaire, quality of the parent-child relationship (using Parental Bonding Instruments, self-esteem (using Rosenberg Self-Esteem Scale, and global psychological distress (using Global Severity Index of Symptom Checklist-90-Revised. Results. About 80% of the sample reported some exposure to parental alienating behaviors; about 65-70% of the sample has perceived non optimal parenting by mother and by father; individuals who experienced affectionless control (low care and high overprotection reported significantly higher exposure to parental loyalty conflict behaviors. Overall rates of reported exposure to low care, and overprotection and parental loyalty conflict behaviors were statistically significantly associated with self-esteem as well as the measure of current psychological distress. Results revealed that exposure to parental loyalty conflict behaviors and self-esteem were associated with psychological distress over and above the effects of parental bonding and age. Conclusions. The pattern of findings supports the theory that children exposed to dysfunctional parenting, and with low self-esteem are at risk for their long-term psychological functioning. Implications for health policy changes and strengthening social services are discussed.

  3. Incorporating Functional Genomic Information in Genetic Association Studies Using an Empirical Bayes Approach.

    Science.gov (United States)

    Spencer, Amy V; Cox, Angela; Lin, Wei-Yu; Easton, Douglas F; Michailidou, Kyriaki; Walters, Kevin

    2016-04-01

    There is a large amount of functional genetic data available, which can be used to inform fine-mapping association studies (in diseases with well-characterised disease pathways). Single nucleotide polymorphism (SNP) prioritization via Bayes factors is attractive because prior information can inform the effect size or the prior probability of causal association. This approach requires the specification of the effect size. If the information needed to estimate a priori the probability density for the effect sizes for causal SNPs in a genomic region isn't consistent or isn't available, then specifying a prior variance for the effect sizes is challenging. We propose both an empirical method to estimate this prior variance, and a coherent approach to using SNP-level functional data, to inform the prior probability of causal association. Through simulation we show that when ranking SNPs by our empirical Bayes factor in a fine-mapping study, the causal SNP rank is generally as high or higher than the rank using Bayes factors with other plausible values of the prior variance. Importantly, we also show that assigning SNP-specific prior probabilities of association based on expert prior functional knowledge of the disease mechanism can lead to improved causal SNPs ranks compared to ranking with identical prior probabilities of association. We demonstrate the use of our methods by applying the methods to the fine mapping of the CASP8 region of chromosome 2 using genotype data from the Collaborative Oncological Gene-Environment Study (COGS) Consortium. The data we analysed included approximately 46,000 breast cancer case and 43,000 healthy control samples. © 2016 The Authors. *Genetic Epidemiology published by Wiley Periodicals, Inc.

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

    International Nuclear Information System (INIS)

    Ji Zhilong; Ma Yuanwei; Wang Dezhong

    2014-01-01

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

  5. From the genome to the phenome and back: linking genes with human brain function and structure using genetically informed neuroimaging

    DEFF Research Database (Denmark)

    Siebner, H R; Callicott, J H; Sommer, T

    2009-01-01

    In recent years, an array of brain mapping techniques has been successfully employed to link individual differences in circuit function or structure in the living human brain with individual variations in the human genome. Several proof-of-principle studies provided converging evidence that brain...... imaging can establish important links between genes and behaviour. The overarching goal is to use genetically informed brain imaging to pinpoint neurobiological mechanisms that contribute to behavioural intermediate phenotypes or disease states. This special issue on "Linking Genes to Brain Function...... in Health and Disease" provides an overview over how the "imaging genetics" approach is currently applied in the various fields of systems neuroscience to reveal the genetic underpinnings of complex behaviours and brain diseases. While the rapidly emerging field of imaging genetics holds great promise...

  6. Genetic ancestry-smoking interactions and lung function in African Americans: a cohort study.

    Directory of Open Access Journals (Sweden)

    Melinda C Aldrich

    Full Text Available BACKGROUND: Smoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated a prospective ongoing cohort of 1,281 African Americans participating in the Health, Aging, and Body Composition (Health ABC Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV₁ per pack-year of smoking (-5.7 ml FEV₁/ smoking pack-year compared with smokers with lower African ancestry (-4.6 ml in FEV₁/ smoking pack-year (interaction P value  = 0.17. Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV(1 decline in Health ABC and independently replicated in CARDIA. CONCLUSIONS/SIGNIFICANCE: African American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking.

  7. Estimation of genetic parameters for morphological and functional traits in a Menorca horse population

    Directory of Open Access Journals (Sweden)

    Marina Solé

    2014-01-01

    Full Text Available Functional conformation and performance in Classic and Menorca Dressage are the main selection criteria in the Menorca Horse breeding program. Menorca Dressage is an alternative Classical Dressage discipline which is exclusive of the Menorca Island, but including a series of movements that the animals perform in the traditional festivities called “Jaleo Menorquín”. One of these movements involves the horse raising its forelimbs and standing or walking on its hindlimbs, which is called “el bot”. To make the Menorca horse breed more competitive in the equestrian market, it is necessary to understand the genetic background that characterizes the aptitude for Menorca Dressage and its relationship with conformation traits. The analysed data consisted of 15 conformation traits from 347 Menorca horses (200 males and 147 females, with 1,550 performance records in Menorca Dressage competitions. Genetic parameters were estimated using linear and threshold animal models. The heritabilities for heights and lengths were high (0.45-0.76, those for angulations and binary conformation traits were low to moderate (0.10-0.36 as were the scores for dressage performance (0.13-0.21. The results suggest that the analyzed traits could be used as an efficient tool for selecting breeding horses.

  8. Genetic disruption of SOD1 gene causes glucose intolerance and impairs β-cell function.

    Science.gov (United States)

    Muscogiuri, Giovanna; Salmon, Adam B; Aguayo-Mazzucato, Cristina; Li, Mengyao; Balas, Bogdan; Guardado-Mendoza, Rodolfo; Giaccari, Andrea; Reddick, Robert L; Reyna, Sara M; Weir, Gordon; Defronzo, Ralph A; Van Remmen, Holly; Musi, Nicolas

    2013-12-01

    Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. β-Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo β-cell insulin secretion and decreased β-cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow-fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to β-cell dysfunction.

  9. Estimation of genetic parameters for morphological and functional traits in a Menorca horse population

    Energy Technology Data Exchange (ETDEWEB)

    Sole, M.; Cervantes, I.; Gutierrez, J. P.; Gomez, M. D.; Valera, M.

    2014-06-01

    Functional conformation and performance in Classic and Menorca Dressage are the main selection criteria in the Menorca Horse breeding program. Menorca Dressage is an alternative Classical Dressage discipline which is exclusive of the Menorca Island, but including a series of movements that the animals perform in the traditional festivities called Jaleo Menorquin. One of these movements involves the horse raising its forelimbs and standing or walking on its hindlimbs, which is called el bot. To make the Menorca horse breed more competitive in the equestrian market, it is necessary to understand the genetic background that characterizes the aptitude for Menorca Dressage and its relationship with conformation traits. The analysed data consisted of 15 conformation traits from 347 Menorca horses (200 males and 147 females), with 1,550 performance records in Menorca Dressage competitions. Genetic parameters were estimated using linear and threshold animal models. The heritabilities for heights and lengths were high (0.45-0.76), those for angulations and binary conformation traits were low to moderate (0.10-0.36) as were the scores for dressage performance (0.13-0.21). The results suggest that the analyzed traits could be used as an efficient tool for selecting breeding horses. (Author)

  10. Examining the Effects of Mexican Serial Migration and Family Separations on Acculturative Stress, Depression, and Family Functioning

    Science.gov (United States)

    Rusch, Dana; Reyes, Karina

    2013-01-01

    This study examined the role of parent-child separations during serial migration to the United States in predicting individual- and family-level outcomes in Mexican immigrant families. We assessed parents' subjective appraisals of their family's separation and reunion experiences to explore associations with self-reported acculturative stress,…

  11. Function of all-metal separators for waste fuels. Phase 1; Funktion av allmetallseparatorer foer avfallsbraenslen. Etapp 1

    Energy Technology Data Exchange (ETDEWEB)

    Jacoby, Juergen; Wrangensten, Lars

    2004-08-01

    Various waste incineration facilities, which use different types of waste fuels, have difficulties with a high content of non-magnetic metal, especially aluminum in their fuels. Aluminum may melt on the grate and can lead to corrosion or fouling in the furnace. Additionally, a high content of aluminum in the flyash may cause difficulties in terms of storage or further use of the ash as e.g. construction material. The industrial demand for efficient separators for non-magnetic metals from a fuel stream is rather large. There is however some uncertainty in the performance and efficiency of metal separators. Two types of separators can be found, the first type is called eddy current separator, the other type is based upon a metal detector with a sorting unit in the form of a chute or similar afterwards. An eddy current separator consists of a fast rotating drum containing several permanent magnets with alternating polarity. Due to the rotation, the change in the magnetic field induces eddy currents in conducting materials. The eddy currents cause a force in non-magnetic metal, the Lorentz force, which repels the material away from the rotating drum while all other material follows the systems flow direction. Systems equipped with a metal detector activate a mechanical sorting device, separate chute or air nozzles, when a metal particle is detected. In contrast to eddy current separators all types of metals can be detected and sorted out by systems based on metal detector. Several technical solutions for metal separation supplied by various manufacturers are described in the report. The companies have been asked to supply product information on the working principle, technical data, efficiency and limits for different types of metals. Two reference power plants have been visited and their experiences with all-metal separators are described. Haendeloeverket in Norrkoeping uses eddy current separators for separation of non-magnetic metals from household waste

  12. Comparison between Genetic Algorithms and Particle Swarm Optimization Methods on Standard Test Functions and Machine Design

    DEFF Research Database (Denmark)

    Nica, Florin Valentin Traian; Ritchie, Ewen; Leban, Krisztina Monika

    2013-01-01

    , genetic algorithm and particle swarm are shortly presented in this paper. These two algorithms are tested to determine their performance on five different benchmark test functions. The algorithms are tested based on three requirements: precision of the result, number of iterations and calculation time....... Both algorithms are also tested on an analytical design process of a Transverse Flux Permanent Magnet Generator to observe their performances in an electrical machine design application.......Nowadays the requirements imposed by the industry and economy ask for better quality and performance while the price must be maintained in the same range. To achieve this goal optimization must be introduced in the design process. Two of the best known optimization algorithms for machine design...

  13. Estimating genetic covariance functions assuming a parametric correlation structure for environmental effects

    Directory of Open Access Journals (Sweden)

    Meyer Karin

    2001-11-01

    Full Text Available Abstract A random regression model for the analysis of "repeated" records in animal breeding is described which combines a random regression approach for additive genetic and other random effects with the assumption of a parametric correlation structure for within animal covariances. Both stationary and non-stationary correlation models involving a small number of parameters are considered. Heterogeneity in within animal variances is modelled through polynomial variance functions. Estimation of parameters describing the dispersion structure of such model by restricted maximum likelihood via an "average information" algorithm is outlined. An application to mature weight records of beef cow is given, and results are contrasted to those from analyses fitting sets of random regression coefficients for permanent environmental effects.

  14. Genetic and functional analysis of the gene encoding GAP-43 in schizophrenia.

    Science.gov (United States)

    Shen, Yu-Chih; Tsai, Ho-Min; Cheng, Min-Chih; Hsu, Shih-Hsin; Chen, Shih-Fen; Chen, Chia-Hsiang

    2012-02-01

    In earlier reports, growth-associated protein 43 (GAP-43) has been shown to be critical for initial establishment or reorganization of synaptic connections, a process thought to be disrupted in schizophrenia. Additionally, abnormal GAP-43 expression in different brain regions has been linked to this disorder in postmortem brain studies. In this study, we investigated the involvement of the gene encoding GAP-43 in the susceptibility to schizophrenia. We searched for genetic variants in the promoter region and 3 exons (including both UTR ends) of the GAP-43 gene using direct sequencing in a sample of patients with schizophrenia (n=586) and non-psychotic controls (n=576), both being Han Chinese from Taiwan, and conducted an association and functional study. We identified 11 common polymorphisms in the GAP-43 gene. SNP and haplotype-based analyses displayed no associations with schizophrenia. Additionally, we identified 4 rare variants in 5 out of 586 patients, including 1 variant located at the promoter region (c.-258-4722G>T) and 1 synonymous (V110V) and 2 missense (G150R and P188L) variants located at exon 2. No rare variants were found in the control subjects. The results of the reporter gene assay demonstrated that the regulatory activity of construct containing c.-258-4722T was significantly lower as compared to the wild type construct (c.-258-4722G; panalysis also demonstrated the functional relevance of other rare variants. Our study lends support to the hypothesis of multiple rare mutations in schizophrenia, and it provides genetic clues that indicate the involvement of GAP-43 in this disorder. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Genetic architecture of HIV-1 genes circulating in north India & their functional implications.

    Science.gov (United States)

    Neogi, Ujjwal; Sood, Vikas; Ronsard, Larence; Singh, Jyotsna; Lata, Sneh; Ramachandran, V G; Das, S; Wanchu, Ajay; Banerjea, Akhil C

    2011-12-01

    This review presents data on genetic and functional analysis of some of the HIV-1 genes derived from HIV-1 infected individuals from north India (Delhi, Punjab and Chandigarh). We found evidence of novel B/C recombinants in HIV-1 LTR region showing relatedness to China/Myanmar with 3 copies of Nfκb sites; B/C/D mosaic genomes for HIV-1 Vpr and novel B/C Tat. We reported appearance of a complex recombinant form CRF_02AG of HIV-1 envelope sequences which is predominantly found in Central/Western Africa. Also one Indian HIV-1 envelope subtype C sequence suggested exclusive CXCR4 co-receptor usage. This extensive recombination, which is observed in about 10 per cent HIV-1 infected individuals in the Vpr genes, resulted in remarkably altered functions when compared with prototype subtype B Vpr. The Vpu C was found to be more potent in causing apoptosis when compared with Vpu B when analyzed for subG1 DNA content. The functional implications of these changes as well as in other genes of HIV-1 are discussed in detail with possible implications for subtype-specific pathogenesis highlighted.

  16. A Functional-genetic Scheme for Seizure Forecasting in Canine Epilepsy.

    Science.gov (United States)

    Bou Assi, E; Nguyen, D K; Rihana, S; Sawan, M

    2017-09-13

    The objective of this work is the development of an accurate seizure forecasting algorithm that considers brain's functional connectivity for electrode selection. We start by proposing Kmeans-directed transfer function, an adaptive functional connectivity method intended for seizure onset zone localization in bilateral intracranial EEG recordings. Electrodes identified as seizure activity sources and sinks are then used to implement a seizure-forecasting algorithm on long-term continuous recordings in dogs with naturallyoccurring epilepsy. A precision-recall genetic algorithm is proposed for feature selection in line with a probabilistic support vector machine classifier. Epileptic activity generators were focal in all dogs confirming the diagnosis of focal epilepsy in these animals while sinks spanned both hemispheres in 2 of 3 dogs. Seizure forecasting results show performance improvement compared to previous studies, achieving average sensitivity of 84.82% and time in warning of 0.1. Achieved performances highlight the feasibility of seizure forecasting in canine epilepsy. The ability to improve seizure forecasting provides promise for the development of EEGtriggered closed-loop seizure intervention systems for ambulatory implantation in patients with refractory epilepsy.

  17. Versatile Gene-Specific Sequence Tags for Arabidopsis Functional Genomics: Transcript Profiling and Reverse Genetics Applications

    Science.gov (United States)

    Hilson, Pierre; Allemeersch, Joke; Altmann, Thomas; Aubourg, Sébastien; Avon, Alexandra; Beynon, Jim; Bhalerao, Rishikesh P.; Bitton, Frédérique; Caboche, Michel; Cannoot, Bernard; Chardakov, Vasil; Cognet-Holliger, Cécile; Colot, Vincent; Crowe, Mark; Darimont, Caroline; Durinck, Steffen; Eickhoff, Holger; de Longevialle, Andéol Falcon; Farmer, Edward E.; Grant, Murray; Kuiper, Martin T.R.; Lehrach, Hans; Léon, Céline; Leyva, Antonio; Lundeberg, Joakim; Lurin, Claire; Moreau, Yves; Nietfeld, Wilfried; Paz-Ares, Javier; Reymond, Philippe; Rouzé, Pierre; Sandberg, Goran; Segura, Maria Dolores; Serizet, Carine; Tabrett, Alexandra; Taconnat, Ludivine; Thareau, Vincent; Van Hummelen, Paul; Vercruysse, Steven; Vuylsteke, Marnik; Weingartner, Magdalena; Weisbeek, Peter J.; Wirta, Valtteri; Wittink, Floyd R.A.; Zabeau, Marc; Small, Ian

    2004-01-01

    Microarray transcript profiling and RNA interference are two new technologies crucial for large-scale gene function studies in multicellular eukaryotes. Both rely on sequence-specific hybridization between complementary nucleic acid strands, inciting us to create a collection of gene-specific sequence tags (GSTs) representing at least 21,500 Arabidopsis genes and which are compatible with both approaches. The GSTs were carefully selected to ensure that each of them shared no significant similarity with any other region in the Arabidopsis genome. They were synthesized by PCR amplification from genomic DNA. Spotted microarrays fabricated from the GSTs show good dynamic range, specificity, and sensitivity in transcript profiling experiments. The GSTs have also been transferred to bacterial plasmid vectors via recombinational cloning protocols. These cloned GSTs constitute the ideal starting point for a variety of functional approaches, including reverse genetics. We have subcloned GSTs on a large scale into vectors designed for gene silencing in plant cells. We show that in planta expression of GST hairpin RNA results in the expected phenotypes in silenced Arabidopsis lines. These versatile GST resources provide novel and powerful tools for functional genomics. PMID:15489341

  18. Model of pediatric pituitary hormone deficiency separates the endocrine and neural functions of the LHX3 transcription factor in vivo

    Science.gov (United States)

    Colvin, Stephanie C.; Malik, Raleigh E.; Showalter, Aaron D.; Sloop, Kyle W.; Rhodes, Simon J.

    2011-01-01

    The etiology of most pediatric hormone deficiency diseases is poorly understood. Children with combined pituitary hormone deficiency (CPHD) have insufficient levels of multiple anterior pituitary hormones causing short stature, metabolic disease, pubertal failure, and often have associated nervous system symptoms. Mutations in developmental regulatory genes required for the specification of the hormone-secreting cell types of the pituitary gland underlie severe forms of CPHD. To better understand these diseases, we have created a unique mouse model of CPHD with a targeted knockin mutation (Lhx3 W227ter), which is a model for the human LHX3 W224ter disease. The LHX3 gene encodes a LIM-homeodomain transcription factor, which has essential roles in pituitary and nervous system development in mammals. The introduced premature termination codon results in deletion of the carboxyl terminal region of the LHX3 protein, which is critical for pituitary gene activation. Mice that lack all LHX3 function do not survive beyond birth. By contrast, the homozygous Lhx3 W227ter mice survive, but display marked dwarfism, thyroid disease, and female infertility. Importantly, the Lhx3 W227ter mice have no apparent nervous system deficits. The Lhx3 W227ter mouse model provides a unique array of hormone deficits and facilitates experimental approaches that are not feasible with human patients. These experiments demonstrate that the carboxyl terminus of the LHX3 transcription factor is not required for viability. More broadly, this study reveals that the in vivo actions of a transcription factor in different tissues are molecularly separable. PMID:21149718

  19. Genetic and Environmental Influences on Correlations Between Hearing and Cognitive Functions in Middle and Older Chinese Twins

    DEFF Research Database (Denmark)

    Xu, Chunsheng; Zhang, Dongfeng; Tian, Xiaocao

    2017-01-01

    , including 0.5 kHz, 1 kHz, 2 kHz, 4 kHz, 8 kHz, and 12.5 kHz, with the lower hearing thresholds indicating better hearing function. Cognitive and hearing functions were measured on 379 complete twin pairs (240 monozygotic and 139 dizygotic pairs) with a median age of 50 years (range: 40-80 years). Bivariate...... twin models were fitted to quantify the genetic and environmental components of the correlations between hearing and cognitive functions. The analysis showed significantly high genetic correlation between 2 kHz of hearing and cognition (r G = -1.00, 95% CI [-1.00, -0.46]) and moderate genetic...

  20. Brain structure–function associations in multi-generational families genetically enriched for bipolar disorder

    Science.gov (United States)

    Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K.; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C.; Aldana, Ileana; Teshiba, Terri M.; Abaryan, Zvart; Al-Sharif, Noor B.; Navarro, Linda; Tishler, Todd A.; Altshuler, Lori; Bartzokis, George; Escobar, Javier I.; Glahn, David C.; Thompson, Paul M.; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I.; Sabatti, Chiara; Cantor, Rita M.; Freimer, Nelson B.; Bearden, Carrie E.

    2015-01-01

    Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain–behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain–behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18–87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain–behaviour associations and test whether brain–behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain–behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non

  1. Replicated landscape genetic and network analyses reveal wide variation in functional connectivity for American pikas.

    Science.gov (United States)

    Castillo, Jessica A; Epps, Clinton W; Jeffress, Mackenzie R; Ray, Chris; Rodhouse, Thomas J; Schwalm, Donelle

    2016-09-01

    Landscape connectivity is essential for maintaining viable populations, particularly for species restricted to fragmented habitats or naturally arrayed in metapopulations and facing rapid climate change. The importance of assessing both structural connectivity (physical distribution of favorable habitat patches) and functional connectivity (how species move among habitat patches) for managing such species is well understood. However, the degree to which functional connectivity for a species varies among landscapes, and the resulting implications for conservation, have rarely been assessed. We used a landscape genetics approach to evaluate resistance to gene flow and, thus, to determine how landscape and climate-related variables influence gene flow for American pikas (Ochotona princeps) in eight federally managed sites in the western United States. We used empirically derived, individual-based landscape resistance models in conjunction with predictive occupancy models to generate patch-based network models describing functional landscape connectivity. Metareplication across landscapes enabled identification of limiting factors for dispersal that would not otherwise have been apparent. Despite the cool microclimates characteristic of pika habitat, south-facing aspects consistently represented higher resistance to movement, supporting the previous hypothesis that exposure to relatively high temperatures may limit dispersal in American pikas. We found that other barriers to dispersal included areas with a high degree of topographic relief, such as cliffs and ravines, as well as streams and distances greater than 1-4 km depending on the site. Using the empirically derived network models of habitat patch connectivity, we identified habitat patches that were likely disproportionately important for maintaining functional connectivity, areas in which habitat appeared fragmented, and locations that could be targeted for management actions to improve functional connectivity

  2. Functional genetic research for radiation and drug resistant adenocarcinoma and its application

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Gyu; Kim, Kug Chan; Jung, Il Lae; Chul, Shin Byung; Kook, Park Hyo; Lee, Hee Min

    2012-01-15

    The work scope of 'Functional genetic research for radiation and drug resistant adenocarcinoma and its application' had contained the research about effect of transgelin(SM22a), neurotensin, metallothionein-1G transgelin-2 genes on the cell death triggered ionizing radiation, cisplatin, MMS, luteolin and H{sub 2}O{sub 2}(toxic agents), which are highly expressed in radiation-induced mutant cells. In this study, to elucidate the role of these proteins in the ionizing radiation (toxic chemicals)-induced cell death, we utilized sensed (or antisense, small interference RNA) cells, which overexpress (or down-regulate) RNAs associated with these proteins biosynthesis, and investigated the effects of these genes on the cytotoxicity caused by ionizing radiation, H{sub 2}O{sub 2} and toxic chemicals. We also investigated the functions of downstream target genes of transgelin such as IGF-1Rβ/PI3K/AKT pathway and transgelin/metallothioneine in A-549 and HepG2 cells because such target genes are able to potentiate the cell-killing or cell protecting effects against radiation.

  3. Functional genetic research for radiation and drug resistant adenocarcinoma and its application

    International Nuclear Information System (INIS)

    Kim, In Gyu; Kim, Kug Chan; Jung, Il Lae; Chul, Shin Byung; Kook, Park Hyo; Lee, Hee Min

    2012-01-01

    The work scope of 'Functional genetic research for radiation and drug resistant adenocarcinoma and its application' had contained the research about effect of transgelin(SM22a), neurotensin, metallothionein-1G transgelin-2 genes on the cell death triggered ionizing radiation, cisplatin, MMS, luteolin and H 2 O 2 (toxic agents), which are highly expressed in radiation-induced mutant cells. In this study, to elucidate the role of these proteins in the ionizing radiation (toxic chemicals)-induced cell death, we utilized sensed (or antisense, small interference RNA) cells, which overexpress (or down-regulate) RNAs associated with these proteins biosynthesis, and investigated the effects of these genes on the cytotoxicity caused by ionizing radiation, H 2 O 2 and toxic chemicals. We also investigated the functions of downstream target genes of transgelin such as IGF-1Rβ/PI3K/AKT pathway and transgelin/metallothioneine in A-549 and HepG2 cells because such target genes are able to potentiate the cell-killing or cell protecting effects against radiation

  4. Interactions between genetic background, insulin resistance and β-cell function.

    Science.gov (United States)

    Kahn, S E; Suvag, S; Wright, L A; Utzschneider, K M

    2012-10-01

    An interaction between genes and the environment is a critical component underlying the pathogenesis of the hyperglycaemia of type 2 diabetes. The development of more sophisticated techniques for studying gene variants and for analysing genetic data has led to the discovery of some 40 genes associated with type 2 diabetes. Most of these genes are related to changes in β-cell function, with a few associated with decreased insulin sensitivity and obesity. Interestingly, using quantitative traits based on continuous measures rather than dichotomous ones, it has become evident that not all genes associated with changes in fasting or post-prandial glucose are also associated with a diagnosis of type 2 diabetes. Identification of these gene variants has provided novel insights into the physiology and pathophysiology of the β-cell, including the identification of molecules involved in β-cell function that were not previously recognized as playing a role in this critical cell. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

  5. Designing mixed metal halide ammines for ammonia storage using density functional theory and genetic algorithms.

    Science.gov (United States)

    Jensen, Peter Bjerre; Lysgaard, Steen; Quaade, Ulrich J; Vegge, Tejs

    2014-09-28

    Metal halide ammines have great potential as a future, high-density energy carrier in vehicles. So far known materials, e.g. Mg(NH3)6Cl2 and Sr(NH3)8Cl2, are not suitable for automotive, fuel cell applications, because the release of ammonia is a multi-step reaction, requiring too much heat to be supplied, making the total efficiency lower. Here, we apply density functional theory (DFT) calculations to predict new mixed metal halide ammines with improved storage capacities and the ability to release the stored ammonia in one step, at temperatures suitable for system integration with polymer electrolyte membrane fuel cells (PEMFC). We use genetic algorithms (GAs) to search for materials containing up to three different metals (alkaline-earth, 3d and 4d) and two different halides (Cl, Br and I) - almost 27,000 combinations, and have identified novel mixtures, with significantly improved storage capacities. The size of the search space and the chosen fitness function make it possible to verify that the found candidates are the best possible candidates in the search space, proving that the GA implementation is ideal for this kind of computational materials design, requiring calculations on less than two percent of the candidates to identify the global optimum.

  6. Automatic Curve Fitting Based on Radial Basis Functions and a Hierarchical Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    G. Trejo-Caballero

    2015-01-01

    Full Text Available Curve fitting is a very challenging problem that arises in a wide variety of scientific and engineering applications. Given a set of data points, possibly noisy, the goal is to build a compact representation of the curve that corresponds to the best estimate of the unknown underlying relationship between two variables. Despite the large number of methods available to tackle this problem, it remains challenging and elusive. In this paper, a new method to tackle such problem using strictly a linear combination of radial basis functions (RBFs is proposed. To be more specific, we divide the parameter search space into linear and nonlinear parameter subspaces. We use a hierarchical genetic algorithm (HGA to minimize a model selection criterion, which allows us to automatically and simultaneously determine the nonlinear parameters and then, by the least-squares method through Singular Value Decomposition method, to compute the linear parameters. The method is fully automatic and does not require subjective parameters, for example, smooth factor or centre locations, to perform the solution. In order to validate the efficacy of our approach, we perform an experimental study with several tests on benchmarks smooth functions. A comparative analysis with two successful methods based on RBF networks has been included.

  7. Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association.

    Science.gov (United States)

    Brems, Hilde; Park, Caroline; Maertens, Ophélia; Pemov, Alexander; Messiaen, Ludwine; Messia, Ludwine; Upadhyaya, Meena; Claes, Kathleen; Beert, Eline; Peeters, Kristel; Mautner, Victor; Sloan, Jennifer L; Yao, Lawrence; Lee, Chyi-Chia Richard; Sciot, Raf; De Smet, Luc; Legius, Eric; Stewart, Douglas R

    2009-09-15

    Neurofibromatosis type 1 (NF1) is a common disorder that arises secondary to mutations in the tumor suppressor gene NF1. Glomus tumors are small, benign but painful tumors that originate from the glomus body, a thermoregulatory shunt concentrated in the fingers and toes. We report 11 individuals with NF1 who harbored 20 glomus tumors of the fingers and 1 in the toe; 5 individuals had multiple glomus tumors. We hypothesized that biallelic inactivation of NF1 underlies the pathogenesis of these tumors. In 12 NF1-associated glomus tumors, we used cell culture and laser capture microdissection to isolate DNA. We also analyzed two sporadic (not NF1-associated) glomus tumors. Genetic analysis showed germ line and somatic NF1 mutations in seven tumors. RAS mitogen-activated protein kinase hyperactivation was observed in cultured NF1(-/-) glomus cells, reflecting a lack of inhibition of the pathway by functional neurofibromin, the protein product of NF1. No abnormalities in NF1 or RAS mitogen-activated protein kinase activation were found in sporadic glomus tumors. By comparative genomic hybridization, we observed amplification of the 3'-end of CRTAC1 and a deletion of the 5'-end of WASF1 in two NF1-associated glomus tumors. For the first time, we show that loss of neurofibromin function is crucial in the pathogenesis of glomus tumors in NF1. Glomus tumors of the fingers or toes should be considered as part of the tumor spectrum of NF1.

  8. Measurement of R = σL/σT and the Separated Longitudinal and Transverse Structure Functions in the Nucleon Resonance Region

    International Nuclear Information System (INIS)

    Yongguang Liang; Michael Christy; Abdellah Ahmidouch; Christopher Armstrong; John Arrington; Arshak Asaturyan; Steven Avery; Baker, O.; Douglas Beck; Henk Blok; Bochna, C.W.; Werner Boeglin; Peter Bosted; Maurice Bouwhuis; Herbert Breuer; Daniel Brown; Antje Bruell; Roger Carlini; Jinseok Cha; Nicholas Chant; Anthony Cochran; Leon Cole; Samuel Danagoulian; Donal Day; James Dunne; Dipangkar Dutta; Rolf Ent; Howard Fenker; Fox, B.; Liping Gan; Haiyan Gao; Kenneth Garrow; David Gaskell; Ashot Gasparian; Don Geesaman; Ronald Gilman; Paul Gueye; Mark Harvey; Roy Holt; Xiaodong Jiang; Mark Jones; Cynthia Keppel; Edward Kinney; Wolfgang Lorenzon; Allison Lung; David Mack; Pete Markowitz; Martin, J.W.; Kevin McIlhany; Daniella Mckee; David Meekins; Miller, M.A.; Richard Milner; Joseph Mitchell; Hamlet Mkrtchyan; Robert Mueller; Alan Nathan; Gabriel Niculescu; Maria-Ioana Niculescu; Thomas O'neill; Vassilios Papavassiliou; Stephen Pate; Rodney Piercey; David Potterveld; Ronald Ransome; Joerg Reinhold; Rollinde, E.; Oscar Rondon-Aramayo; Philip Roos; Adam Sarty; Reyad Sawafta; Elaine Schulte; Edwin Segbefia; Smith, C.; Samuel Stepanyan; Steffen Strauch; Vardan Tadevosyan; Liguang Tang; Raphael Tieulent; Vladas Tvaskis; Alicia Uzzle; William Vulcan; Stephen Wood; Feng Xiong; Lulin Yuan; Markus Zeier; Benedikt Zihlmann; Vitaliy Ziskin

    2004-01-01

    We report on a detailed study of longitudinal strength in the nucleon resonance region, presenting new results from inclusive electron-proton cross sections measured at Jefferson Lab Hall C in the four-momentum transfer range 0.2 2 2 . The data have been used to accurately perform over 170 Rosenbluth-type longitudinal/transverse separations. The precision R σ L /σ T data are presented here, along with the first separate values of the inelastic structure functions F 1 and F L in this regime. The resonance longitudinal component is found to be significant. With the new data, quark-hadron duality is observed above Q 2 = 1 GeV 2 in the separated structure functions independently

  9. Understanding the Pathophysiology of Spinocerebellar Ataxias through genetics, neurophysiology, structural and functional neuroimaging

    Directory of Open Access Journals (Sweden)

    Pramod Kumar Pal

    2015-12-01

    largely absent with additional activity in contralateral cortices and in thalami in patients with SCA1; increased thalamic function could be one of the causes for disinhibition of the motor cortex contributing to uncoordinated movements.Studies on larger cohort of each subtype of SCAs to validate the above findings, follow-up studies to determine the rate and nature of progression of neurodegeneration and evaluation of pre-symptomatic genetically confirmed SCAs will help understand the pathophysiology of the SCAs.

  10. Effective ligand functionalization of zirconium-based metal-organic frameworks for the adsorption and separation of benzene and toluene: a multiscale computational study.

    Science.gov (United States)

    Wu, Ying; Chen, Huiyong; Liu, Defei; Xiao, Jing; Qian, Yu; Xi, Hongxia

    2015-03-18

    The adsorption and separation properties of benzene and toluene on the zirconium-based frameworks UiO-66, -67, -68, and their functional analogues UiO-Phe and UiO-Me2 were studied using grand canonical Monte Carlo simulations, density functional theory, and ideal adsorbed solution theory. Remarkable higher adsorption uptakes of benzene and toluene at low pressures on UiO-Phe and -Me2 were found compared to their parent framework UiO-67. It can be ascribed to the presence of functional groups (aromatic rings and methyl groups) that significantly intensified the adsorption, majorly by reducing the effective pore size and increasing the interaction strength with the adsorbates. At high pressures, the pore volumes and accessible surfaces of the frameworks turned out to be the dominant factors governing the adsorption. In the case of toluene/benzene separation, toluene selectivities of UiOs showed a two-stage separation behavior at the measured pressure range, resulting from the greater interaction affinities of toluene at low pressures and steric hindrance effects at high pressures. Additionally, the counterbalancing factors of enhanced π delocalization and suitable pore size of UiO-Phe gave rise to the highest toluene selectivity, suggesting the ligand functionalization strategy could reach both high adsorption capacity and separation selectivity from aromatic mixtures at low concentrations.

  11. Autonomic functioning in mothers with interpersonal violence-related posttraumatic stress disorder in response to separation-reunion.

    Science.gov (United States)

    Schechter, Daniel S; Moser, Dominik A; McCaw, Jaime E; Myers, Michael M

    2014-05-01

    This study characterizes autonomic nervous system activity reactive to separation-reunion among mothers with Interpersonal Violence-Related Posttraumatic Stress Disorder (IPV-PTSD). Heart-rate (HR) and high frequency heart-rate-variability (HF-HRV) were measured in 17 IPV-PTSD-mothers, 22 sub-threshold-mothers, and 15 non-PTSD mother-controls while interacting with their toddlers (12-48 months). Analyses showed IPV-PTSD-mothers having generally lower HR than other groups. All groups showed negative correlations between changes in HR and HF-HRV from sitting- to standing-baseline. During initial separation, controls no longer showed a negative relationship between HR and HF-HRV. But by the second reunion, the negative relationship reappeared. IPV-PTSD- and sub-threshold-mothers retained negative HR/HF-HRV correlations during the initial separation, but stopped showing them by the second reunion. Results support that mother-controls showed a pattern of autonomic regulation suggestive of hypervigilance during initial separation that resolved by the time of re-exposure. PTSD-mothers showed delayed onset of this pattern only upon re-exposure, and were perhaps exhibiting defensive avoidance or numbing during the initial separation/reunion. © 2013 Wiley Periodicals, Inc.

  12. Genetic algorithm based input selection for a neural network function approximator with applications to SSME health monitoring

    Science.gov (United States)

    Peck, Charles C.; Dhawan, Atam P.; Meyer, Claudia M.

    1991-01-01

    A genetic algorithm is used to select the inputs to a neural network function approximator. In the application considered, modeling critical parameters of the space shuttle main engine (SSME), the functional relationship between measured parameters is unknown and complex. Furthermore, the number of possible input parameters is quite large. Many approaches have been used for input selection, but they are either subjective or do not consider the complex multivariate relationships between parameters. Due to the optimization and space searching capabilities of genetic algorithms they were employed to systematize the input selection process. The results suggest that the genetic algorithm can generate parameter lists of high quality without the explicit use of problem domain knowledge. Suggestions for improving the performance of the input selection process are also provided.

  13. Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder.

    Science.gov (United States)

    Sun, Xiao; Wu, Zhaomin; Cao, Qingjiu; Qian, Ying; Liu, Yong; Yang, Binrang; Chang, Suhua; Yang, Li; Wang, Yufeng

    2018-05-16

    As a childhood-onset psychiatric disorder, attention deficit hyperactivity disorder (ADHD) is complicated by phenotypic and genetic heterogeneity. Lifelong executive function deficits in ADHD are described in many literatures and have been proposed as endophenotypes of ADHD. However, its genetic basis is still elusive. In this study, we performed a genome-wide association study of executive function, rated with Behavioral Rating Inventory of Executive Function (BRIEF), in ADHD children. We identified one significant variant (rs852004, P = 2.51e-08) for the overall score of BRIEF. The association analyses for each component of executive function found this locus was more associated with inhibit and monitor components. Further principle component analysis and confirmatory factor analysis provided an ADHD-specific executive function pattern including inhibit and monitor factors. SNP rs852004 was mainly associated with the Behavioral Regulation factor. Meanwhile, we found the significant locus was associated with ADHD symptom. The Behavioral Regulation factor mediated its effect on ADHD symptom. Functional magnetic resonance imaging (fMRI) analyses further showed evidence that this variant affected the activity of inhibition control related brain regions. It provided new insights for the genetic basis of executive function in ADHD.

  14. Genetic and functional analyses demonstrate a role for abnormal glycinergic signaling in autism.

    Science.gov (United States)

    Pilorge, M; Fassier, C; Le Corronc, H; Potey, A; Bai, J; De Gois, S; Delaby, E; Assouline, B; Guinchat, V; Devillard, F; Delorme, R; Nygren, G; Råstam, M; Meier, J C; Otani, S; Cheval, H; James, V M; Topf, M; Dear, T N; Gillberg, C; Leboyer, M; Giros, B; Gautron, S; Hazan, J; Harvey, R J; Legendre, P; Betancur, C

    2016-07-01

    Autism spectrum disorder (ASD) is a common neurodevelopmental condition characterized by marked genetic heterogeneity. Recent studies of rare structural and sequence variants have identified hundreds of loci involved in ASD, but our knowledge of the overall genetic architecture and the underlying pathophysiological mechanisms remains incomplete. Glycine receptors (GlyRs) are ligand-gated chloride channels that mediate inhibitory neurotransmission in the adult nervous system but exert an excitatory action in immature neurons. GlyRs containing the α2 subunit are highly expressed in the embryonic brain, where they promote cortical interneuron migration and the generation of excitatory projection neurons. We previously identified a rare microdeletion of the X-linked gene GLRA2, encoding the GlyR α2 subunit, in a boy with autism. The microdeletion removes the terminal exons of the gene (GLRA2(Δex8-9)). Here, we sequenced 400 males with ASD and identified one de novo missense mutation, p.R153Q, absent from controls. In vitro functional analysis demonstrated that the GLRA2(Δex8)(-)(9) protein failed to localize to the cell membrane, while the R153Q mutation impaired surface expression and markedly reduced sensitivity to glycine. Very recently, an additional de novo missense mutation (p.N136S) was reported in a boy with ASD, and we show that this mutation also reduced cell-surface expression and glycine sensitivity. Targeted glra2 knockdown in zebrafish induced severe axon-branching defects, rescued by injection of wild type but not GLRA2(Δex8-9) or R153Q transcripts, providing further evidence for their loss-of-function effect. Glra2 knockout mice exhibited deficits in object recognition memory and impaired long-term potentiation in the prefrontal cortex. Taken together, these results implicate GLRA2 in non-syndromic ASD, unveil a novel role for GLRA2 in synaptic plasticity and learning and memory, and link altered glycinergic signaling to social and cognitive

  15. Disturbed functional connectivity of cortical activation during semantic discrimination in patients with schizophrenia and subjects at genetic high-risk.

    Science.gov (United States)

    Li, Xiaobo; Branch, Craig A; Nierenberg, Jay; Delisi, Lynn E

    2010-03-01

    Schizophrenia has a strong genetic component that is relevant to the understanding of the pathophysiology of the syndrome. Thus, recent investigations have shifted from studies of diagnosed patients with schizophrenia to examining their unaffected relatives. Previous studies found that during language processing, relatives thought to be at genetic high-risk for the disorder exhibit aberrant functional activation in regions of language processing, specifically in the left inferior frontal gyrus (Broca's area). However, functional connectivity among the regions involved in language pathways is not well understood. In this study, we examined the functional connectivity between a seed located in Broca's area and the remainder of the brain during a visual lexical decision task, in 20 schizophrenia patients, 21 subjects at genetic high risk for the disorder and 21 healthy controls. Both the high-risk subjects and patients showed significantly reduced activation correlations between seed and regions related to visual language processing. Compared to the high-risk subjects, the schizophrenia patients showed even fewer regions that were correlated with the seed regions. These results suggest that there is aberrant functional connectivity within cortical language circuitry in high-risk subjects and patients with schizophrenia. Broca's area, which is one of the important regions for language processing in healthy controls, had a significantly reduced role in the high-risk subjects and patients with schizophrenia. Our findings are consistent with the existence of an underlying biological disturbance that begins in genetically at risk individuals and progresses to a greater extent in those who eventually develop schizophrenia.

  16. From Genetics to Genetic Algorithms

    Indian Academy of Sciences (India)

    artificial genetic system) string feature or ... called the genotype whereas it is called a structure in artificial genetic ... assigned a fitness value based on the cost function. Better ..... way it has produced complex, intelligent living organisms capable of ...

  17. Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

    Science.gov (United States)

    Fears, Scott C; Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C; Aldana, Ileana; Teshiba, Terri M; Abaryan, Zvart; Al-Sharif, Noor B; Navarro, Linda; Tishler, Todd A; Altshuler, Lori; Bartzokis, George; Escobar, Javier I; Glahn, David C; Thompson, Paul M; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I; Sabatti, Chiara; Cantor, Rita M; Freimer, Nelson B; Bearden, Carrie E

    2015-07-01

    Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family

  18. Distinct DNA-binding surfaces in the ATPase and linker domains of MutLγ determine its substrate specificities and exert separable functions in meiotic recombination and mismatch repair.

    Directory of Open Access Journals (Sweden)

    Corentin Claeys Bouuaert

    2017-05-01

    Full Text Available Mlh1-Mlh3 (MutLγ is a mismatch repair factor with a central role in formation of meiotic crossovers, presumably through resolution of double Holliday junctions. MutLγ has DNA-binding, nuclease, and ATPase activities, but how these relate to one another and to in vivo functions are unclear. Here, we combine biochemical and genetic analyses to characterize Saccharomyces cerevisiae MutLγ. Limited proteolysis and atomic force microscopy showed that purified recombinant MutLγ undergoes ATP-driven conformational changes. In vitro, MutLγ displayed separable DNA-binding activities toward Holliday junctions (HJ and, surprisingly, single-stranded DNA (ssDNA, which was not predicted from current models. MutLγ bound DNA cooperatively, could bind multiple substrates simultaneously, and formed higher-order complexes. FeBABE hydroxyl radical footprinting indicated that the DNA-binding interfaces of MutLγ for ssDNA and HJ substrates only partially overlap. Most contacts with HJ substrates were located in the linker regions of MutLγ, whereas ssDNA contacts mapped within linker regions as well as the N-terminal ATPase domains. Using yeast genetic assays for mismatch repair and meiotic recombination, we found that mutations within different DNA-binding surfaces exert separable effects in vivo. For example, mutations within the Mlh1 linker conferred little or no meiotic phenotype but led to mismatch repair deficiency. Interestingly, mutations in the N-terminal domain of Mlh1 caused a stronger meiotic defect than mlh1Δ, suggesting that the mutant proteins retain an activity that interferes with alternative recombination pathways. Furthermore, mlh3Δ caused more chromosome missegregation than mlh1Δ, whereas mlh1Δ but not mlh3Δ partially alleviated meiotic defects of msh5Δ mutants. These findings illustrate functional differences between Mlh1 and Mlh3 during meiosis and suggest that their absence impinges on chromosome segregation not only via reduced

  19. Genetic recombination is directed away from functional genomic elements in mice.

    Science.gov (United States)

    Brick, Kevin; Smagulova, Fatima; Khil, Pavel; Camerini-Otero, R Daniel; Petukhova, Galina V

    2012-05-13

    Genetic recombination occurs during meiosis, the key developmental programme of gametogenesis. Recombination in mammals has been recently linked to the activity of a histone H3 methyltransferase, PR domain containing 9 (PRDM9), the product of the only known speciation-associated gene in mammals. PRDM9 is thought to determine the preferred recombination sites--recombination hotspots--through sequence-specific binding of its highly polymorphic multi-Zn-finger domain. Nevertheless, Prdm9 knockout mice are proficient at initiating recombination. Here we map and analyse the genome-wide distribution of recombination initiation sites in Prdm9 knockout mice and in two mouse strains with different Prdm9 alleles and their F(1) hybrid. We show that PRDM9 determines the positions of practically all hotspots in the mouse genome, with the exception of the pseudo-autosomal region (PAR)--the only area of the genome that undergoes recombination in 100% of cells. Surprisingly, hotspots are still observed in Prdm9 knockout mice, and as in wild type, these hotspots are found at H3 lysine 4 (H3K4) trimethylation marks. However, in the absence of PRDM9, most recombination is initiated at promoters and at other sites of PRDM9-independent H3K4 trimethylation. Such sites are rarely targeted in wild-type mice, indicating an unexpected role of the PRDM9 protein in sequestering the recombination machinery away from gene-promoter regions and other functional genomic elements.

  20. Apoc2 loss-of-function zebrafish mutant as a genetic model of hyperlipidemia

    Directory of Open Access Journals (Sweden)

    Chao Liu

    2015-08-01

    Full Text Available Apolipoprotein C-II (APOC2 is an obligatory activator of lipoprotein lipase. Human patients with APOC2 deficiency display severe hypertriglyceridemia while consuming a normal diet, often manifesting xanthomas, lipemia retinalis and pancreatitis. Hypertriglyceridemia is also an important risk factor for development of cardiovascular disease. Animal models to study hypertriglyceridemia are limited, with no Apoc2-knockout mouse reported. To develop a genetic model of hypertriglyceridemia, we generated an apoc2 mutant zebrafish characterized by the loss of Apoc2 function. apoc2 mutants show decreased plasma lipase activity and display chylomicronemia and severe hypertriglyceridemia, which closely resemble the phenotype observed in human patients with APOC2 deficiency. The hypertriglyceridemia in apoc2 mutants is rescued by injection of plasma from wild-type zebrafish or by injection of a human APOC2 mimetic peptide. Consistent with a previous report of a transient apoc2 knockdown, apoc2 mutant larvae have a minor delay in yolk consumption and angiogenesis. Furthermore, apoc2 mutants fed a normal diet accumulate lipid and lipid-laden macrophages in the vasculature, which resemble early events in the development of human atherosclerotic lesions. In addition, apoc2 mutant embryos show ectopic overgrowth of pancreas. Taken together, our data suggest that the apoc2 mutant zebrafish is a robust and versatile animal model to study hypertriglyceridemia and the mechanisms involved in the pathogenesis of associated human diseases.

  1. From genetics to functional genomics: Improvement in drought signaling and tolerance in wheat

    Directory of Open Access Journals (Sweden)

    Hikmet eBudak

    2015-11-01

    Full Text Available Drought being a yield limiting factor has become a major threat to international food security. It is a complex trait and drought tolerance response is carried out by various genes, transcription factors (TFs, microRNAs (miRNAs, hormones, proteins, co-factors, ions and metabolites. This complexity has limited the development of wheat cultivars for drought tolerance by classical breeding. However, attempts have been made to fill the lost genetic diversity by crossing wheat with wild wheat relatives. In recent years, several molecular markers including single nucleotide polymorphisms (SNPs and quantitative trait loci (QTLs associated with genes for drought signaling pathways have been reported. Screening of large wheat collections by marker assisted selection (MAS and transformation of wheat with different genes/TFs has improved drought signaling pathways and tolerance. Several miRNAs also provide drought tolerance to wheat by regulating various TFs/genes. Emergence of OMICS techniques including transcriptomics, proteomics, metabolomics and ionomics has helped to identify and characterize the genes, proteins, metabolites and ions involved in drought signaling pathways. Together, all these efforts helped in understanding the complex drought tolerance mechanism. Here, we have reviewed the advances in wide hybridization, MAS, QTL mapping, miRNAs, transgenic technique, genome editing system and above mentioned functional genomics tools for identification and utility of signaling molecules for improvement in wheat drought tolerance

  2. The genetics of colony form and function in Caribbean Acropora corals.

    Science.gov (United States)

    Hemond, Elizabeth M; Kaluziak, Stefan T; Vollmer, Steven V

    2014-12-17

    Colonial reef-building corals have evolved a broad spectrum of colony morphologies based on coordinated asexual reproduction of polyps on a secreted calcium carbonate skeleton. Though cnidarians have been shown to possess and use similar developmental genes to bilaterians during larval development and polyp formation, little is known about genetic regulation of colony morphology in hard corals. We used RNA-seq to evaluate transcriptomic differences between functionally distinct regions of the coral (apical branch tips and branch bases) in two species of Caribbean Acropora, the staghorn coral, A. cervicornis, and the elkhorn coral, A. palmata. Transcriptome-wide gene profiles differed significantly between different parts of the coral colony as well as between species. Genes showing differential expression between branch tips and bases were involved in developmental signaling pathways, such as Wnt, Notch, and BMP, as well as pH regulation, ion transport, extracellular matrix production and other processes. Differences both within colonies and between species identify a relatively small number of genes that may contribute to the distinct "staghorn" versus "elkhorn" morphologies of these two sister species. The large number of differentially expressed genes supports a strong division of labor between coral branch tips and branch bases. Genes involved in growth of mature Acropora colonies include the classical signaling pathways associated with development of cnidarian larvae and polyps as well as morphological determination in higher metazoans.

  3. Invertebrate Trehalose-6-Phosphate Synthase Gene: Genetic Architecture, Biochemistry, Physiological Function, and Potential Applications

    Directory of Open Access Journals (Sweden)

    Bin Tang

    2018-01-01

    Full Text Available The non-reducing disaccharide trehalose is widely distributed among various organisms. It plays a crucial role as an instant source of energy, being the major blood sugar in insects. In addition, it helps countering abiotic stresses. Trehalose synthesis in insects and other invertebrates is thought to occur via the trehalose-6-phosphate synthase (TPS and trehalose-6-phosphate phosphatase (TPP pathways. In many insects, the TPP gene has not been identified, whereas multiple TPS genes that encode proteins harboring TPS/OtsA and TPP/OtsB conserved domains have been found and cloned in the same species. The function of the TPS gene in insects and other invertebrates has not been reviewed in depth, and the available information is quite fragmented. The present review discusses the current understanding of the trehalose synthesis pathway, TPS genetic architecture, biochemistry, physiological function, and potential sensitivity to insecticides. We note the variability in the number of TPS genes in different invertebrate species, consider whether trehalose synthesis may rely only on the TPS gene, and discuss the results of in vitro TPS overexpression experiment. Tissue expression profile and developmental characteristics of the TPS gene indicate that it is important in energy production, growth and development, metamorphosis, stress recovery, chitin synthesis, insect flight, and other biological processes. We highlight the molecular and biochemical properties of insect TPS that make it a suitable target of potential pest control inhibitors. The application of trehalose synthesis inhibitors is a promising direction in insect pest control because vertebrates do not synthesize trehalose; therefore, TPS inhibitors would be relatively safe for humans and higher animals, making them ideal insecticidal agents without off-target effects.

  4. Optimal formation of genetically modified and functional pancreatic islet spheroids by using hanging-drop strategy.

    Science.gov (United States)

    Kim, H J; Alam, Z; Hwang, J W; Hwang, Y H; Kim, M J; Yoon, S; Byun, Y; Lee, D Y

    2013-03-01

    Rejection and hypoxia are important factors causing islet loss at an early stage after pancreatic islet transplantation. Recently, islets have been dissociated into single cells for reaggregation into so-called islet spheroids. Herein, we used a hanging-drop strategy to form islet spheroids to achieve functional equivalence to intact islets. To obtain single islet cells, we dissociated islets with trypsin-EDTA digestion for 10 minutes. To obtain spheroids, we dropped various numbers of single cells (125, 250, or 500 cells/30 μL drop) onto a Petri dish, that was inverted for incubation in humidified air containing 5% CO(2) at 37 °C for 7 days. The aggregated spheroids in the droplets were harvested for further culture. The size of the aggregated islet spheroids depended on the number of single cells (125-500 cells/30 μL droplet). Their morphology was similar to that of intact islets without any cellular damage. When treated with various concentrations of glucose to evaluate responsiveness, their glucose-mediated stimulation index value was similar to that of intact islets, an observation that was attributed to strong cell-to-cell interactions in islet spheroids. However, islet spheroids aggregated in general culture dishes showed abnormal glucose responsiveness owing to weak cell-to-cell interactions. Cell-to-cell interactions in islet spheroids were confirmed with an anti-connexin-36 monoclonal antibody. Finally, nonviral poly(ethylene imine)-mediated interleukin-10 cytokine gene delivered beforehand into dissociated single cells before formation of islet spheroids increased the gene transfection efficacy and interleukin-10 secretion from islet spheroids >4-fold compared with intact islets. These results demonstrated the potential application of genetically modified, functional islet spheroids with of controlled size and morphology using an hanging-drop technique. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. How Am I Driving? Using Genetic Programming to Generate Scoring Functions for Urban Driving Behavior

    Directory of Open Access Journals (Sweden)

    Roberto López

    2018-04-01

    Full Text Available Road traffic injuries are a serious concern in emerging economies. Their death toll and economic impact are shocking, with 9 out of 10 deaths occurring in low or middle-income countries; and road traffic crashes representing 3% of their gross domestic product. One way to mitigate these issues is to develop technology to effectively assist the driver, perhaps making him more aware about how her (his decisions influence safety. Following this idea, in this paper we evaluate computational models that can score the behavior of a driver based on a risky-safety scale. Potential applications of these models include car rental agencies, insurance companies or transportation service providers. In a previous work, we showed that Genetic Programming (GP was a successful methodology to evolve mathematical functions with the ability to learn how people subjectively score a road trip. The input to this model was a vector of frequencies of risky maneuvers, which were supposed to be detected in a sensor layer. Moreover, GP was shown, even with statistical significance, to be better than six other Machine Learning strategies, including Neural Networks, Support Vector Regression and a Fuzzy Inference system, among others. A pending task, since then, was to evaluate if a more detailed comparison of different strategies based on GP could improve upon the best GP model. In this work, we evaluate, side by side, scoring functions evolved by three different variants of GP. In the end, the results suggest that two of these strategies are very competitive in terms of accuracy and simplicity, both generating models that could be implemented in current technology that seeks to assist the driver in real-world scenarios.

  6. Exploring genetic and non-genetic risk factors for delayed graft function, acute and subclinical rejection in renal transplant recipients

    NARCIS (Netherlands)

    Moes, Dirk Jan A. R.; Press, Rogier R.; Ackaert, Oliver; Ploeger, Bart A.; Bemelman, Frederike J.; Diack, Cheikh; Wessels, Judith A. M.; van der Straaten, Tahar; Danhof, Meindert; Sanders, Jan-Stephan F.; van der Heide, Jaap J. Homan; Guchelaar, Henk Jan; de Fijter, Johan W.

    AIMS This study aimed at identifying pharmacological factors such as pharmacogenetics and drug exposure as new predictive biomarkers for delayed graft function (DGF), acute rejection (AR) and/or subclinical rejection (SCR). METHODS Adult renal transplant recipients (n = 361) on cyclosporine-based

  7. Exploring genetic and non-genetic risk factors for delayed graft function, acute and subclinical rejection in renal transplant recipients

    NARCIS (Netherlands)

    Moes, Dirk Jan A. R.; Press, Rogier R.; Ackaert, Oliver; Ploeger, Bart A.; Bemelman, Frederike J.; Diack, Cheikh; Wessels, Judith A. M.; van der Straaten, Tahar; Danhof, Meindert; Sanders, Jan-Stephan F.; Homan van der Heide, Jaap J.; Guchelaar, Henk Jan; de Fijter, Johan W.

    2016-01-01

    This study aimed at identifying pharmacological factors such as pharmacogenetics and drug exposure as new predictive biomarkers for delayed graft function (DGF), acute rejection (AR) and/or subclinical rejection (SCR). Adult renal transplant recipients (n = 361) on cyclosporine-based

  8. Genetic variants in the choline acetyltransferase (ChAT) gene are modestly associated with normal cognitive function in the elderly

    DEFF Research Database (Denmark)

    Mengel-From, J; Christensen, K; Thinggaard, M

    2011-01-01

    Genetic variants in the choline acetyltransferase (ChAT) gene have been suggested as risk factors for neurodegenerative Alzheimer's disease (AD). Here we tested the importance of genetic variants in the ChAT gene in normal cognitive function of elderly in a study sample of Danish twins...... and singletons (N = 2070). The ChAT rs3810950 A allele, which has been associated with increased risk for AD, was found to be associated with a decrease cognitive status evaluated by a five-component cognitive composite score [P = 0.03, regression coefficient -0.30, 95% confidence interval (CI) -0.57 to -0...

  9. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma

    DEFF Research Database (Denmark)

    Reddy, Anupama; Zhang, Jenny; Davis, Nicholas S

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed...

  10. Separation of input function for rapid measurement of quantitative CMRO2 and CBF in a single PET scan with a dual tracer administration method

    International Nuclear Information System (INIS)

    Kudomi, Nobuyuki; Watabe, Hiroshi; Hayashi, Takuya; Iida, Hidehiro

    2007-01-01

    Cerebral metabolic rate of oxygen (CMRO 2 ), oxygen extraction fraction (OEF) and cerebral blood flow (CBF) images can be quantified using positron emission tomography (PET) by administrating 15 O-labelled water (H 15 2 O) and oxygen ( 15 O 2 ). Conventionally, those images are measured with separate scans for three tracers C 15 O for CBV, H 15 2 O for CBF and 15 O 2 for CMRO 2 , and there are additional waiting times between the scans in order to minimize the influence of the radioactivity from the previous tracers, which results in a relatively long study period. We have proposed a dual tracer autoradiographic (DARG) approach (Kudomi et al 2005), which enabled us to measure CBF, OEF and CMRO 2 rapidly by sequentially administrating H 15 2 O and 15 O 2 within a short time. Because quantitative CBF and CMRO 2 values are sensitive to arterial input function, it is necessary to obtain accurate input function and a drawback of this approach is to require separation of the measured arterial blood time-activity curve (TAC) into pure water and oxygen input functions under the existence of residual radioactivity from the first injected tracer. For this separation, frequent manual sampling was required. The present paper describes two calculation methods: namely a linear and a model-based method, to separate the measured arterial TAC into its water and oxygen components. In order to validate these methods, we first generated a blood TAC for the DARG approach by combining the water and oxygen input functions obtained in a series of PET studies on normal human subjects. The combined data were then separated into water and oxygen components by the present methods. CBF and CMRO 2 were calculated using those separated input functions and tissue TAC. The quantitative accuracy in the CBF and CMRO 2 values by the DARG approach did not exceed the acceptable range, i.e., errors in those values were within 5%, when the area under the curve in the input function of the second tracer

  11. Calibration and functional analysis of three genetically encoded Cl−/pH sensors

    Directory of Open Access Journals (Sweden)

    Marat eMukhtarov

    2013-04-01

    Full Text Available Monitoring of the intracellular concentrations of Cl− and H+ requires sensitive probes that allow reliable quantitative measurements without perturbation of cell functioning. For these purposes the most promising are genetically encoded fluorescent biosensors, which have become powerful tools for non-invasive intracellular monitoring of ions, molecules and enzymatic activity. A ratiometric CFP/YFP-based construct with a relatively good sensitivity to Cl− has been developed (Markova et al., 2008; Waseem et al., 2010. Recently, a combined Cl−/pH sensor (ClopHensor opened the way for simultaneous ratiometric measurement of these two ions (Arosio et al., 2010. ClopHensor was obtained by fusion of a red-fluorescent protein (DsRed-monomer to the E2GFP variant that contains a specific Cl−-binding site. This construct possesses pKa = 6.8 for H+ and Kd in the 40-50 mM range for Cl− at physiological pH (~7.3 As in the majority of cell types the intracellular Cl− concentration ([Cl−]i is about 10 mM, the development of sensors with higher sensitivity is highly desirable. Here we report the intracellular calibration and functional characterization of ClopHensor and its two derivatives: the membrane targeting PalmPalm-ClopHensor and the H148G/V224L mutant with improved Cl− affinity, reduced pH dependence and pKa shifted to more alkaline values. For functional analysis, constructs were expressed in CHO cells and [Cl−]i was changed by using pipettes with different Cl− concentrations during whole-cell recordings. Kd values for Cl− measured at 33°C and pH ~ 7.3 were, respectively, 39 mM, 47 mM and 21 mM for ClopHensor, PalmPalm-ClopHensor and the H148G/V224L mutant. PalmPalm-ClopHensor resolved responses to activation of Cl−-selective glycine receptor channels better than did ClopHensor. Our observations indicate that these different ClopHensor constructs are promising tools for non-invasive measurement of [Cl−]i in various living

  12. Genetic and functional diversity of soil microbial communities associated to grapevine plants and wine quality

    Science.gov (United States)

    Mocali, Stefano; Fabiani, Arturo; Kuramae, Eiko; de Hollander, Mattias; Kowalchuk, George A.; Vignozzi, Nadia; Valboa, Giuseppe; Costantini, Edoardo

    2013-04-01

    soils. The structure of soil microbial communities was assessed using 16S and 18S rRNA genes pyrosequencing and the determination of some soil microbial properties such as microbial respiration, microbial C-biomass were also determined. The role of both genetic and functional diversity of soil bacterial community on grape physiology and wine quality will be discussed.

  13. Analysis of self-consistency effects in range-separated density-functional theory with Møller-Plesset perturbation theory

    DEFF Research Database (Denmark)

    Fromager, Emmanuel; Jensen, Hans Jørgen Aagaard

    2011-01-01

    Range-separated density-functional theory combines wave function theory for the long-range part of the two-electron interaction with density-functional theory for the short-range part. When describing the long-range interaction with non-variational methods, such as perturbation or coupled......-cluster theories, self-consistency effects are introduced in the density functional part, which for an exact solution requires iterations. They are generally assumed to be small but no detailed study has been performed so far. Here, the authors analyze self-consistency when using Møller-Plesset-type (MP......) perturbation theory for the long range interaction. The lowest-order self-consistency corrections to the wave function and the energy, that enter the perturbation expansions at the second and fourth order, respectively, are both expressed in terms of the one-electron reduced density matrix. The computational...

  14. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes.

    Science.gov (United States)

    Rohde, Palle Duun; Demontis, Ditte; Cuyabano, Beatriz Castro Dias; Børglum, Anders D; Sørensen, Peter

    2016-08-01

    Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case-control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism and immunological responses, which previously have been implicated with schizophrenia based on experimental and observational studies. Copyright © 2016 by the Genetics Society of America.

  15. Separated structure functions for exclusive K+Λ and K+Σ0 electroproduction at 5.5 GeV measured with CLAS

    Science.gov (United States)

    Carman, D. S.; Park, K.; Raue, B. A.; Adhikari, K. P.; Adikaram, D.; Aghasyan, M.; Amaryan, M. J.; Anderson, M. D.; Anefalos Pereira, S.; Anghinolfi, M.; Avakian, H.; Baghdasaryan, H.; Ball, J.; Baltzell, N. A.; Battaglieri, M.; Batourine, V.; Bedlinskiy, I.; Biselli, A. S.; Bono, J.; Boiarinov, S.; Briscoe, W. J.; Brooks, W. K.; Burkert, V. D.; Celentano, A.; Chandavar, S.; Charles, G.; Cole, P. L.; Contalbrigo, M.; Cortes, O.; Crede, V.; D'Angelo, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Deur, A.; Djalali, C.; Doughty, D.; Dupre, R.; El Alaoui, A.; El Fassi, L.; Eugenio, P.; Fedotov, G.; Fegan, S.; Fersch, R.; Fleming, J. A.; Fradi, A.; Gabrielyan, M. Y.; Gevorgyan, N.; Giovanetti, K. L.; Girod, F. X.; Goetz, J. T.; Gohn, W.; Gothe, R. W.; Griffioen, K. A.; Guegan, B.; Guidal, M.; Guo, L.; Hafidi, K.; Hakobyan, H.; Hanretty, C.; Harrison, N.; Heddle, D.; Hicks, K.; Ho, D.; Holtrop, M.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Jo, H. S.; Joo, K.; Keller, D.; Khandaker, M.; Khetarpal, P.; Kim, A.; Kim, W.; Klein, A.; Klein, F. J.; Koirala, S.; Kubarovsky, A.; Kubarovsky, V.; Kuleshov, S. V.; Kvaltine, N. D.; Lewis, S.; Livingston, K.; Lu, H. Y.; MacGregor, I. J. D.; Mao, Y.; Martinez, D.; Mayer, M.; McKinnon, B.; Mestayer, M. D.; Meyer, C. A.; Mineeva, T.; Mirazita, M.; Mokeev, V.; Montgomery, R. A.; Moutarde, H.; Munevar, E.; Munoz Camacho, C.; Nadel-Turonski, P.; Nasseripour, R.; Nepali, C. S.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Osipenko, M.; Ostrovidov, A. I.; Pappalardo, L. L.; Paremuzyan, R.; Park, S.; Pasyuk, E.; Phelps, E.; Phillips, J. J.; Pisano, S.; Pogorelko, O.; Pozdniakov, S.; Price, J. W.; Procureur, S.; Prok, Y.; Protopopescu, D.; Puckett, A. J. R.; Ricco, G.; Rimal, D.; Ripani, M.; Rosner, G.; Rossi, P.; Sabatié, F.; Saini, M. S.; Salgado, C.; Saylor, N. A.; Schott, D.; Schumacher, R. A.; Seder, E.; Seraydaryan, H.; Sharabian, Y. G.; Smith, G. D.; Sober, D. I.; Sokhan, D.; Stepanyan, S. S.; Stepanyan, S.; Stoler, P.; Strakovsky, I. I.; Strauch, S.; Taiuti, M.; Tang, W.; Taylor, C. E.; Tian, Y.; Tkachenko, S.; Trivedi, A.; Ungaro, M.; Vernarsky, B.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Watts, D.; Weinstein, L. B.; Wood, M. H.; Zachariou, N.; Zana, L.; Zhang, J.; Zhao, Z. W.; Zonta, I.

    2013-02-01

    We report measurements of the exclusive electroproduction of K+Λ and K+Σ0 final states from an unpolarized proton target using the CLAS detector at the Thomas Jefferson National Accelerator Facility. The separated structure functions σU, σLT, σTT, and σLT' were extracted from the Φ-dependent differential cross sections acquired with a longitudinally polarized 5.499 GeV electron beam. The data span a broad range of momentum transfers Q2 from 1.4 to 3.9 GeV2, invariant energy W from threshold to 2.6 GeV, and nearly the full center-of-mass angular range of the kaon. The separated structure functions provide an unprecedented data sample, which, in conjunction with other meson photo- and electroproduction data, will help to constrain the higher-level analyses being performed to search for missing baryon resonances.

  16. Genetic differentiation for size at first reproduction through male versus female functions in the widespread Mediterranean tree Pinus pinaster.

    Science.gov (United States)

    Santos-del-Blanco, L; Climent, J; González-Martínez, S C; Pannell, J R

    2012-11-01

    The study of local adaptation in plant reproductive traits has received substantial attention in short-lived species, but studies conducted on forest trees are scarce. This lack of research on long-lived species represents an important gap in our knowledge, because inferences about selection on the reproduction and life history of short-lived species cannot necessarily be extrapolated to trees. This study considers whether the size for first reproduction is locally adapted across a broad geographical range of the Mediterranean conifer species Pinus pinaster. In particular, the study investigates whether this monoecious species varies genetically among populations in terms of whether individuals start to reproduce through their male function, their female function or both sexual functions simultaneously. Whether differences among populations could be attributed to local adaptation across a climatic gradient is then considered. Male and female reproduction and growth were measured during early stages of sexual maturity of a P. pinaster common garden comprising 23 populations sampled across the species range. Generalized linear mixed models were used to assess genetic variability of early reproductive life-history traits. Environmental correlations with reproductive life-history traits were tested after controlling for neutral genetic structure provided by 12 nuclear simple sequence repeat markers. Trees tended to reproduce first through their male function, at a size (height) that varied little among source populations. The transition to female reproduction was slower, showed higher levels of variability and was negatively correlated with vegetative growth traits. Several female reproductive traits were correlated with a gradient of growth conditions, even after accounting for neutral genetic structure, with populations from more unfavourable sites tending to commence female reproduction at a lower individual size. The study represents the first report of genetic

  17. The functional and anatomical dissection of somatosensory subpopulations using mouse genetics

    Directory of Open Access Journals (Sweden)

    Claire E Le Pichon

    2014-04-01

    Full Text Available The word somatosensation comes from joining the Greek word for body (soma with a word for perception (sensation. Somatosensory neurons comprise the largest sensory system in mammals and have nerve endings coursing throughout the skin, viscera, muscle, and bone. Their cell bodies reside in a chain of ganglia adjacent to the dorsal spinal cord (the dorsal root ganglia and at the base of the skull (the trigeminal ganglia. While the neuronal cell bodies are intermingled within the ganglia, the somatosensory system is in reality composed of numerous sub-systems, each specialized to detect distinct stimuli, such as temperature and touch. Historically, somatosensory neurons have been classified using a diverse host of anatomical and physiological parameters, such as the size of the cell body, degree of myelination, histological labeling with markers, specialization of the nerve endings, projection patterns in the spinal cord and brainstem, receptive tuning, and conduction velocity of their action potentials. While useful, the picture that emerged was one of heterogeneity, with many markers at least partially overlapping. More recently, by capitalizing on advances in molecular techniques, researchers have identified specific ion channels and sensory receptors expressed in subsets of sensory neurons. These studies have proved invaluable as they allow genetic access to small subsets of neurons for further molecular dissection. Data being generated from transgenic mice favor the model whereby an array of dedicated neurons is responsible for selectively encoding different modalities. Here we review the current knowledge of the different sensory neuron subtypes in the mouse, the markers used to study them, and the neurogenetic strategies used to define their anatomical projections and functional roles.

  18. Argonaute 2 and nasopharyngeal carcinoma: a genetic association study and functional analysis

    International Nuclear Information System (INIS)

    Li, Peiyao; Meng, Jinfeng; Zhai, Yun; Zhang, Hongxing; Yu, Lixia; Wang, Zhifu; Zhang, Xiaoai; Cao, Pengbo; Chen, Xi; Han, Yuqing; Zhang, Yang; Chen, Huipeng; Ling, Yan; Li, Yuxia; Cui, Ying; Bei, Jin-Xin; Zeng, Yi-Xin; He, Fuchu; Zhou, Gangqiao

    2015-01-01

    Argonaute 2 (AGO2), a central component of RNA-induced silencing complex, plays critical roles in cancer. We examined whether the single nucleotide polymorphisms (SNPs) of AGO2 were related to the risk of nasopharyngeal carcinoma (NPC). Twenty-five tag SNPs within AGO2 were genotyped in Guangxi population consisting of 855 NPC patients and 1036 controls. The SNPs significantly associated with NPC were further replicated in Guangdong population consisting of 996 NPC patients and 972 controls. Functional experiments were conducted to examine the biologic roles of AGO2 in NPC. A significantly increased risk of advanced lymph node metastasis of NPC was identified for the AGO2 rs3928672 GA + AA genotype compared with GG genotype in both the Guangxi and Guangdong populations (combined odd ratio = 2.08, 95 % confidence interval = 1.44-3.01, P = 8.60 × 10 −5 ). Moreover, the AGO2 protein expression levels of rs3928672 GA + AA genotype carriers were higher than the GG genotype carriers in the NPC tissues (P = 0.041), and AGO2 was significantly over-expressed in NPC tissues compared with non-cancerous nasopharyngeal tissues (P = 0.011). In addition, AGO2 knockdown reduced cell proliferation, induced apoptosis, and inhibited migration of NPC cells. Furthermore, gene expression microarray showed that genes altered following AGO2 knockdown were clustered in tumorigenesis and metastasis relevant pathways. Our findings suggest that the genetic polymorphism in AGO2 may be a risk factor for the advanced lymph node metastasis of NPC in Chinese populations, and AGO2 acts as an oncogene in the development of NPC. The online version of this article (doi:10.1186/s12885-015-1895-4) contains supplementary material, which is available to authorized users

  19. Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis

    Science.gov (United States)

    Colizzi, Marco; Iyegbe, Conrad; Powell, John; Ursini, Gianluca; Porcelli, Annamaria; Bonvino, Aurora; Taurisano, Paolo; Romano, Raffaella; Masellis, Rita; Blasi, Giuseppe; Morgan, Craig; Aitchison, Katherine; Mondelli, Valeria; Luzi, Sonija; Kolliakou, Anna; David, Anthony; Murray, Robin M.; Bertolino, Alessandro; Forti, Marta Di

    2015-01-01

    Both cannabis use and the dopamine receptor (DRD2) gene have been associated with schizophrenia, psychosis-like experiences, and cognition. However, there are no published data investigating whether genetically determined variation in DRD2 dopaminergic signaling might play a role in individual susceptibility to cannabis-associated psychosis. We genotyped (1) a case-control study of 272 patients with their first episode of psychosis and 234 controls, and also from (2) a sample of 252 healthy subjects, for functional variation in DRD2, rs1076560. Data on history of cannabis use were collected on all the studied subjects by administering the Cannabis Experience Questionnaire. In the healthy subjects’ sample, we also collected data on schizotypy and cognitive performance using the Schizotypal Personality Questionnaire and the N-back working memory task. In the case-control study, we found a significant interaction between the rs1076560 DRD2 genotype and cannabis use in influencing the likelihood of a psychotic disorder. Among cannabis users, carriers of the DRD2, rs1076560, T allele showed a 3-fold increased probability to suffer a psychotic disorder compared with GG carriers (OR = 3.07; 95% confidence interval [CI]: 1.22–7.63). Among daily users, T carrying subjects showed a 5-fold increase in the odds of psychosis compared to GG carriers (OR = 4.82; 95% CI: 1.39–16.71). Among the healthy subjects, T carrying cannabis users had increased schizotypy compared with T carrying cannabis-naïve subjects, GG cannabis users, and GG cannabis-naïve subjects (all P ≤ .025). T carrying cannabis users had reduced working memory accuracy compared with the other groups (all P ≤ .008). Thus, variation of the DRD2, rs1076560, genotype may modulate the psychosis-inducing effect of cannabis use. PMID:25829376

  20. Changes in skeletal muscle and tendon structure and function following genetic inactivation of myostatin in rats

    Science.gov (United States)

    Mendias, Christopher L; Lynch, Evan B; Gumucio, Jonathan P; Flood, Michael D; Rittman, Danielle S; Van Pelt, Douglas W; Roche, Stuart M; Davis, Carol S

    2015-01-01

    Myostatin is a negative regulator of skeletal muscle and tendon mass. Myostatin deficiency has been well studied in mice, but limited data are available on how myostatin regulates the structure and function of muscles and tendons of larger animals. We hypothesized that, in comparison to wild-type (MSTN+/+) rats, rats in which zinc finger nucleases were used to genetically inactivate myostatin (MSTNΔ/Δ) would exhibit an increase in muscle mass and total force production, a reduction in specific force, an accumulation of type II fibres and a decrease and stiffening of connective tissue. Overall, the muscle and tendon phenotype of myostatin-deficient rats was markedly different from that of myostatin-deficient mice, which have impaired contractility and pathological changes to fibres and their extracellular matrix. Extensor digitorum longus and soleus muscles of MSTNΔ/Δ rats demonstrated 20–33% increases in mass, 35–45% increases in fibre number, 20–57% increases in isometric force and no differences in specific force. The insulin-like growth factor-1 pathway was activated to a greater extent in MSTNΔ/Δ muscles, but no substantial differences in atrophy-related genes were observed. Tendons of MSTNΔ/Δ rats had a 20% reduction in peak strain, with no differences in mass, peak stress or stiffness. The general morphology and gene expression patterns were similar between tendons of both genotypes. This large rodent model of myostatin deficiency did not have the negative consequences to muscle fibres and extracellular matrix observed in mouse models, and suggests that the greatest impact of myostatin in the regulation of muscle mass may not be to induce atrophy directly, but rather to block hypertrophy signalling. PMID:25640143

  1. Genetic deletion of Mst1 alters T cell function and protects against autoimmunity.

    Directory of Open Access Journals (Sweden)

    Konstantin V Salojin

    Full Text Available Mammalian sterile 20-like kinase 1 (Mst1 is a MAPK kinase kinase kinase which is involved in a wide range of cellular responses, including apoptosis, lymphocyte adhesion and trafficking. The contribution of Mst1 to Ag-specific immune responses and autoimmunity has not been well defined. In this study, we provide evidence for the essential role of Mst1 in T cell differentiation and autoimmunity, using both genetic and pharmacologic approaches. Absence of Mst1 in mice reduced T cell proliferation and IL-2 production in vitro, blocked cell cycle progression, and elevated activation-induced cell death in Th1 cells. Mst1 deficiency led to a CD4+ T cell development path that was biased toward Th2 and immunoregulatory cytokine production with suppressed Th1 responses. In addition, Mst1-/- B cells showed decreased stimulation to B cell mitogens in vitro and deficient Ag-specific Ig production in vivo. Consistent with altered lymphocyte function, deletion of Mst1 reduced the severity of experimental autoimmune encephalomyelitis (EAE and protected against collagen-induced arthritis development. Mst1-/- CD4+ T cells displayed an intrinsic defect in their ability to respond to encephalitogenic antigens and deletion of Mst1 in the CD4+ T cell compartment was sufficient to alleviate CNS inflammation during EAE. These findings have prompted the discovery of novel compounds that are potent inhibitors of Mst1 and exhibit desirable pharmacokinetic properties. In conclusion, this report implicates Mst1 as a critical regulator of adaptive immune responses, Th1/Th2-dependent cytokine production, and as a potential therapeutic target for immune disorders.

  2. Genetic parameters between feed-intake-related traits and conformation in 2 separate dairy populations—the Netherlands and United States

    Science.gov (United States)

    To include feed-intake-related traits in the breeding goal, accurate estimates of genetic parameters of feed intake, and its correlations with other related traits (i.e., production, conformation) are required to compare different options. However, the correlations between feed intake and conformati...

  3. 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

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

    Science.gov (United States)

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

    2015-01-01

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

  5. A genetic variant in COL11A1 is functionally associated with lumbar ...

    Indian Academy of Sciences (India)

    Navya

    Collectively, it appears increasingly possible that there are many genetic risk ... backgrounds and environment exposures in different ethnic population may affect ... Methods. Subjects. Patients who were diagnosed as LDH at our clinic center ...

  6. The relationship between genetic risk variants with brain structure and function in bipolar disorder

    DEFF Research Database (Denmark)

    Pereira, Licia P; Köhler, Cristiano A; de Sousa, Rafael T

    2017-01-01

    Genetic-neuroimaging paradigms could provide insights regarding the pathophysiology of bipolar disorder (BD). Nevertheless, findings have been inconsistent across studies. A systematic review of gene-imaging studies involving individuals with BD was conducted across electronic major databases fro...

  7. Tandem assays of protein and glucose with functionalized core/shell particles based on magnetic separation and surface-enhanced Raman scattering.

    Science.gov (United States)

    Kong, Xianming; Yu, Qian; Lv, Zhongpeng; Du, Xuezhong

    2013-10-11

    Tandem assays of protein and glucose in combination with mannose-functionalized Fe3 O4 @SiO2 and Ag@SiO2 tag particles have promising potential in effective magnetic separation and highly sensitive and selective SERS assays of biomaterials. It is for the first time that tandem assay of glucose is developed using SERS based on the Con A-sandwiched microstructures between the functionalized magnetic and tag particles. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. A semi-supervised learning approach to predict synthetic genetic interactions by combining functional and topological properties of functional gene network

    Directory of Open Access Journals (Sweden)

    Han Kyungsook

    2010-06-01

    Full Text Available Abstract Background Genetic interaction profiles are highly informative and helpful for understanding the functional linkages between genes, and therefore have been extensively exploited for annotating gene functions and dissecting specific pathway structures. However, our understanding is rather limited to the relationship between double concurrent perturbation and various higher level phenotypic changes, e.g. those in cells, tissues or organs. Modifier screens, such as synthetic genetic arrays (SGA can help us to understand the phenotype caused by combined gene mutations. Unfortunately, exhaustive tests on all possible combined mutations in any genome are vulnerable to combinatorial explosion and are infeasible either technically or financially. Therefore, an accurate computational approach to predict genetic interaction is highly desirable, and such methods have the potential of alleviating the bottleneck on experiment design. Results In this work, we introduce a computational systems biology approach for the accurate prediction of pairwise synthetic genetic interactions (SGI. First, a high-coverage and high-precision functional gene network (FGN is constructed by integrating protein-protein interaction (PPI, protein complex and gene expression data; then, a graph-based semi-supervised learning (SSL classifier is utilized to identify SGI, where the topological properties of protein pairs in weighted FGN is used as input features of the classifier. We compare the proposed SSL method with the state-of-the-art supervised classifier, the support vector machines (SVM, on a benchmark dataset in S. cerevisiae to validate our method's ability to distinguish synthetic genetic interactions from non-interaction gene pairs. Experimental results show that the proposed method can accurately predict genetic interactions in S. cerevisiae (with a sensitivity of 92% and specificity of 91%. Noticeably, the SSL method is more efficient than SVM, especially for

  9. Development of vinylic and acetylenic functionalized structures based on high permeable glassy polymers as membrane materials for gas mixtures separation

    Science.gov (United States)

    Roizard, D.; Kiryukhina, Y.; Masalev, A.; Khotimskiy, V.; Teplyakov, V.; Barth, D.

    2013-03-01

    There are several challenging separation problems in industries which can be solved with the help of membrane technologies. It is the case for instance of the purification of gas energy carriers (i.e. H2, CH4) from CO2 as well as the CO2 recovery from flue gas. Glassy polymers containing trimethylsilyl residues like poly(1-trimethylsilyl-1-propyne) [PTMSP] and polyvinyltrimethylsilane [PVTMS] are known to exhibit good membrane properties for gas separation. This paper reports two ways of improving their performances based on the controlled introduction of selective groups - alkyl imidazomium salts (C4I) and polyethyleneglycol (M-PEG)- able to enhance CO2 selectivity. CO2 Isotherm sorption data and permeability measurements have shown that the membrane performances could be significantly improved when C4I and M-PEG were introduced as residues covalently bounded to the main polymer chain. Moreover the introduced bromine reactive centres could also be used to induce chemical crosslinking giving rise to more resistant and stable membranes to organic vapours. With the C4I groups, the CO2 sorption could be enhanced by a factor 4.4.

  10. Affinity composite cryogel discs functionalized with Reactive Red 120 and Green HE 4BD dye ligands: Application on the separation of human immunoglobulin G subclasses

    Energy Technology Data Exchange (ETDEWEB)

    Huseynli, Sabina; Baydemir, Gözde; Sarı, Esma [Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara (Turkey); Elkak, Assem [Laboraory of “Valorisation des Ressources Naturelles et Produits de Santé (VRNPS)”, Doctoral School of Sciences and Technology, Lebanese University, Rafic Hariri University Campus, Hadath (Lebanon); Denizli, Adil, E-mail: denizli@hacettepe.edu.tr [Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara (Turkey)

    2015-01-01

    Naturally produced by the human immune system, immunoglobulin nowadays is widely used for in vivo and in vitro purposes. The increased needs for pure immunoglobulin have prompted researchers to find new immunoglobulin chromatographic separation processes. Cryogels as chromatographic adsorbents, congregate several mechanical features including good compatibility, large pore structure, flexibility, short diffusion pathway and stability. These different characteristics make them a good alternative to conventional chromatographic methods and allowing their potential use in separation technology. In the present study, two sets of poly(2-hydroxyethyl methacrylate) (PHEMA) based beads were prepared and functionalized with Reactive Red 120 (RR) and Reactive Green HE 4BD (RG) dyes, and then embedded into supermacroporous cryogels. The morphology, physical and chemical features of the prepared bead embedded composite cryogel discs (CCDs) were performed by scanning electron microscopy (SEM), swelling test, elemental analysis and Fourier transform infrared spectroscopy (FTIR). The results showed that the embedded composite cryogel discs have a specific surface area of 192.0 m{sup 2}/g with maximum adsorption capacity of HIgG 239.8 mg/g for the RR functionalized CCD and 170 mg/g for RG functionalized CCD columns, both at pH 6.2. - Highlights: • Dye attached composite cryogel discs were prepared to separate HIgG subclasses. • Composite cryogels characterized by swelling, FTIR, SEM and elemental analysis. • Reactive Green HE 4B and Reactive Red 120 dyes were used as the affinity ligand. • HIgG and subclasses were separate from both aqueous solution and human plasma.

  11. Affinity composite cryogel discs functionalized with Reactive Red 120 and Green HE 4BD dye ligands: Application on the separation of human immunoglobulin G subclasses

    International Nuclear Information System (INIS)

    Huseynli, Sabina; Baydemir, Gözde; Sarı, Esma; Elkak, Assem; Denizli, Adil

    2015-01-01

    Naturally produced by the human immune system, immunoglobulin nowadays is widely used for in vivo and in vitro purposes. The increased needs for pure immunoglobulin have prompted researchers to find new immunoglobulin chromatographic separation processes. Cryogels as chromatographic adsorbents, congregate several mechanical features including good compatibility, large pore structure, flexibility, short diffusion pathway and stability. These different characteristics make them a good alternative to conventional chromatographic methods and allowing their potential use in separation technology. In the present study, two sets of poly(2-hydroxyethyl methacrylate) (PHEMA) based beads were prepared and functionalized with Reactive Red 120 (RR) and Reactive Green HE 4BD (RG) dyes, and then embedded into supermacroporous cryogels. The morphology, physical and chemical features of the prepared bead embedded composite cryogel discs (CCDs) were performed by scanning electron microscopy (SEM), swelling test, elemental analysis and Fourier transform infrared spectroscopy (FTIR). The results showed that the embedded composite cryogel discs have a specific surface area of 192.0 m 2 /g with maximum adsorption capacity of HIgG 239.8 mg/g for the RR functionalized CCD and 170 mg/g for RG functionalized CCD columns, both at pH 6.2. - Highlights: • Dye attached composite cryogel discs were prepared to separate HIgG subclasses. • Composite cryogels characterized by swelling, FTIR, SEM and elemental analysis. • Reactive Green HE 4B and Reactive Red 120 dyes were used as the affinity ligand. • HIgG and subclasses were separate from both aqueous solution and human plasma

  12. Genetic ablation of soluble TNF does not affect lesion size and functional recovery after moderate spinal cord injury in mice

    DEFF Research Database (Denmark)

    Ellman, Ditte Gry; Degn, Matilda; Lund, Minna Christiansen

    2016-01-01

    Traumatic spinal cord injury (SCI) is followed by an instant increase in expression of the microglial-derived proinflammatory cytokine tumor necrosis factor (TNF) within the lesioned cord. TNF exists both as membrane-anchored TNF (mTNF) and as cleaved soluble TNF (solTNF). We previously demonstra......, and MHCII), lesion size, and functional outcome after moderate SCI were comparable between genotypes. Collectively, our data demonstrate that genetic ablation of solTNF does not significantly modulate postlesion outcome after SCI....

  13. Genetic and molecular functional characterization of variants within TNFSF13B, a positional candidate preeclampsia susceptibility gene on 13q.

    Directory of Open Access Journals (Sweden)

    Mona H Fenstad

    Full Text Available BACKGROUND: Preeclampsia is a serious pregnancy complication, demonstrating a complex pattern of inheritance. The elucidation of genetic liability to preeclampsia remains a major challenge in obstetric medicine. We have adopted a positional cloning approach to identify maternal genetic components, with linkages previously demonstrated to chromosomes 2q, 5q and 13q in an Australian/New Zealand familial cohort. The current study aimed to identify potential functional and structural variants in the positional candidate gene TNFSF13B under the 13q linkage peak and assess their association status with maternal preeclampsia genetic susceptibility. METHODOLOGY/PRINCIPAL FINDINGS: The proximal promoter and coding regions of the positional candidate gene TNFSF13B residing within the 13q linkage region was sequenced using 48 proband or founder individuals from Australian/New Zealand families. Ten sequence variants (nine SNPs and one single base insertion were identified and seven SNPs were successfully genotyped in the total Australian/New Zealand family cohort (74 families/480 individuals. Borderline association to preeclampsia (p = 0.0153 was observed for three rare SNPs (rs16972194, rs16972197 and rs56124946 in strong linkage disequilibrium with each other. Functional evaluation by electrophoretic mobility shift assays showed differential nuclear factor binding to the minor allele of the rs16972194 SNP, residing upstream of the translation start site, making this a putative functional variant. The observed genetic associations were not replicated in a Norwegian case/control cohort (The Nord-Trøndelag Health Study (HUNT2, 851 preeclamptic and 1,440 non-preeclamptic women. CONCLUSION/SIGNIFICANCE: TNFSF13B has previously been suggested to contribute to the normal immunological adaption crucial for a successful pregnancy. Our observations support TNFSF13B as a potential novel preeclampsia susceptibility gene. We discuss a possible role for TNFSF13B in

  14. Genetic contribution to the relationship between social role function and depressive symptoms in Japanese elderly twins: a twin study.

    Science.gov (United States)

    Nishihara, Reiko; Inui, Fujio; Kato, Kenji; Tomizawa, Rie; Hayakawa, Kazuo

    2011-03-01

    Social role function is the capacity to maintain interpersonal relationships and is essential for being independent in the community. Limitations in social role function often coexist with depressive symptoms, suggesting a possible common mechanistic basis. We investigated whether the observed association between these traits is mainly a result of genetic or environmental influences. In 2008, a questionnaire was sent to 745 male twins aged 65 years and older. Our sample included 397 male twins. The number of monozygotic twins was 302, and dizygotic was 95. Among the twin pairs for whom data were available for both twins, 75 twin pairs (150 individuals) were monozygotic and 28 pairs (56 individuals) were dizygotic. Social role function was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Depressive symptoms were measured by the 15-item version of the Geriatric Depression Scale. Relative importance of genes and environments for the phenotypes was calculated using structural equation analyses. Our results show that genetic influence was the major contributor to the relationship between social role function and depressive symptoms, and non-shared environmental influence was important for overall variation in each trait. We concluded that focusing on a non-shared environment is an essential approach for maintaining social role function and psychological well-being. It is suggested that treatments specific to depressive symptoms are more effective than indirect intervention targeting social role function. © 2011 The Authors. Psychogeriatrics © 2011 Japanese Psychogeriatric Society.

  15. Two-body Schrödinger wave functions in a plane-wave basis via separation of dimensions

    Science.gov (United States)

    Jerke, Jonathan; Poirier, Bill

    2018-03-01

    Using a combination of ideas, the ground and several excited electronic states of the helium atom and the hydrogen molecule are computed to chemical accuracy—i.e., to within 1-2 mhartree or better. The basic strategy is very different from the standard electronic structure approach in that the full two-electron six-dimensional (6D) problem is tackled directly, rather than starting from a single-electron Hartree-Fock approximation. Electron correlation is thus treated exactly, even though computational requirements remain modest. The method also allows for exact wave functions to be computed, as well as energy levels. From the full-dimensional 6D wave functions computed here, radial distribution functions and radial correlation functions are extracted—as well as a 2D probability density function exhibiting antisymmetry for a single Cartesian component. These calculations support a more recent interpretation of Hund's rule, which states that the lower energy of the higher spin-multiplicity states is actually due to reduced screening, rather than reduced electron-electron repulsion. Prospects for larger systems and/or electron dynamics applications appear promising.

  16. Organic electronic materials: Recent advances in the dft description of the ground and excited states using tuned range-separated hybrid functionals

    KAUST Repository

    Körzdörfer, Thomas

    2014-11-18

    Density functional theory (DFT) and its time-dependent extension (TD-DFT) are powerful tools enabling the theoretical prediction of the ground- and excited-state properties of organic electronic materials with reasonable accuracy at affordable computational costs. Due to their excellent accuracy-to-numerical-costs ratio, semilocal and global hybrid functionals such as B3LYP have become the workhorse for geometry optimizations and the prediction of vibrational spectra in modern theoretical organic chemistry. Despite the overwhelming success of these out-of-the-box functionals for such applications, the computational treatment of electronic and structural properties that are of particular interest in organic electronic materials sometimes reveals severe and qualitative failures of such functionals. Important examples include the overestimation of conjugation, torsional barriers, and electronic coupling as well as the underestimation of bond-length alternations or excited-state energies in low-band-gap polymers.In this Account, we highlight how these failures can be traced back to the delocalization error inherent to semilocal and global hybrid functionals, which leads to the spurious delocalization of electron densities and an overestimation of conjugation. The delocalization error for systems and functionals of interest can be quantified by allowing for fractional occupation of the highest occupied molecular orbital. It can be minimized by using long-range corrected hybrid functionals and a nonempirical tuning procedure for the range-separation parameter.We then review the benefits and drawbacks of using tuned long-range corrected hybrid functionals for the description of the ground and excited states of π-conjugated systems. In particular, we show that this approach provides for robust and efficient means of characterizing the electronic couplings in organic mixed-valence systems, for the calculation of accurate torsional barriers at the polymer limit, and for the

  17. Subtypes of familial hemophagocytic lymphohistiocytosis in Japan based on genetic and functional analyses of cytotoxic T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Kozo Nagai

    Full Text Available BACKGROUND: Familial hemophagocytic lymphohistiocytosis (FHL is a rare disease of infancy or early childhood. To clarify the incidence and subtypes of FHL in Japan, we performed genetic and functional analyses of cytotoxic T lymphocytes (CTLs in Japanese patients with FHL. DESIGN AND METHODS: Among the Japanese children with hemophagocytic lymphohistiocytosis (HLH registered at our laboratory, those with more than one of the following findings were eligible for study entry under a diagnosis of FHL: positive for known genetic mutations, a family history of HLH, and impaired CTL-mediated cytotoxicity. Mutations of the newly identified causative gene for FHL5, STXBP2, and the cytotoxicity and degranulation activity of CTLs in FHL patients, were analyzed. RESULTS: Among 31 FHL patients who satisfied the above criteria, PRF1 mutation was detected in 17 (FHL2 and UNC13D mutation was in 10 (FHL3. In 2 other patients, 3 novel mutations of STXBP2 gene were confirmed (FHL5. Finally, the remaining 2 were classified as having FHL with unknown genetic mutations. In all FHL patients, CTL-mediated cytotoxicity was low or deficient, and degranulation activity was also low or absent except FHL2 patients. In 2 patients with unknown genetic mutations, the cytotoxicity and degranulation activity of CTLs appeared to be deficient in one patient and moderately impaired in the other. CONCLUSIONS: FHL can be diagnosed and classified on the basis of CTL-mediated cytotoxicity, degranulation activity, and genetic analysis. Based on the data obtained from functional analysis of CTLs, other unknown gene(s responsible for FHL remain to be identified.

  18. A separator

    Energy Technology Data Exchange (ETDEWEB)

    Prokopyuk, S.G.; Dyachenko, A.Ye.; Mukhametov, M.N.; Prokopov, O.I.

    1982-01-01

    A separator is proposed which contains separating slanted plates and baffle plates installed at a distance to them at an acute angle to them. To increase the effectiveness of separating a gas and liquid stream and the throughput through reducing the secondary carry away of the liquid drops and to reduce the hydraulic resistance, as well, openings are made in the plates. The horizontal projections of each opening from the lower and upper surfaces of the plate do not overlap each other.

  19. Effect of acid- and alkaline-aided extractions on functional and rheological properties of proteins recovered from mechanically separated turkey meat (MSTM).

    Science.gov (United States)

    Hrynets, Yuliya; Omana, Dileep A; Xu, Yan; Betti, Mirko

    2010-09-01

    Functional and rheological characteristics of acid- and alkali-extracted proteins from mechanically separated turkey meat (MSTM) have been investigated. Extractions were carried out at 4 pH values (2.5, 3.5, 10.5, and 11.5). The study demonstrated that alkali and acid extractions resulted in significant (P hardness, chewiness, springiness, and cohesiveness) of recovered proteins were found to be unaffected (P > 0.05) by different extraction pH. The protein extracted at pH 3.5 formed a highly viscoelastic gel network as evidenced by storage modulus (G') values, whereas the gel formed from proteins extracted at pH 10.5 was found to be the weakest. The work also revealed that acid treatments were more effective for removal of total heme pigments from MSTM. Color characteristics of protein isolates were markedly improved compared to the initial material and tended to be better when subjected to acid extractions. Mechanically separated meat is one of the cheapest sources of protein obtained by grinding meat and bones together and forcing the mixture through a perforated drum. The use of mechanically separated turkey meat (MSTM) for the production of further processed poultry products is limited due to its undesirable color and textural properties. Recovery of proteins from MSTM using pH shifting process will help the poultry processors to get better returns and also create opportunity to produce functional food ingredients.

  20. Description of the Charge Transfer States at the Pentacene/C60 Interface: Combining Range-Separated Hybrid Functionals with the Polarizable Continuum Model

    KAUST Repository

    Zheng, Zilong

    2016-06-24

    Density functional theory (DFT) approaches based on range-separated hybrid functionals are currently methods of choice for the description of the charge-transfer (CT) states in organic donor/acceptor solar cells. However, these calculations are usually performed on small-size donor/acceptor complexes and as result do not account for electronic polarization effects. Here, using a pentacene/C60 complex as a model system, we discuss the ability of long-range corrected (LCR) hybrid functionals in combination with the polarizable continuum model (PCM) to determine the impact of the solid-state environment on the CT states. The CT energies are found to be insensitive to the interactions with the dielectric medium when a conventional time-dependent DFT/PCM (TDDFT/PCM) approach is used. However, a decrease in the energy of the CT state in the framework of LRC functionals can be obtained by using a smaller range-separated parameter when going from an isolated donor/acceptor complex to the solid-state case.

  1. Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis.

    Science.gov (United States)

    Colizzi, Marco; Iyegbe, Conrad; Powell, John; Ursini, Gianluca; Porcelli, Annamaria; Bonvino, Aurora; Taurisano, Paolo; Romano, Raffaella; Masellis, Rita; Blasi, Giuseppe; Morgan, Craig; Aitchison, Katherine; Mondelli, Valeria; Luzi, Sonija; Kolliakou, Anna; David, Anthony; Murray, Robin M; Bertolino, Alessandro; Di Forti, Marta

    2015-09-01

    Both cannabis use and the dopamine receptor (DRD2) gene have been associated with schizophrenia, psychosis-like experiences, and cognition. However, there are no published data investigating whether genetically determined variation in DRD2 dopaminergic signaling might play a role in individual susceptibility to cannabis-associated psychosis. We genotyped (1) a case-control study of 272 patients with their first episode of psychosis and 234 controls, and also from (2) a sample of 252 healthy subjects, for functional variation in DRD2, rs1076560. Data on history of cannabis use were collected on all the studied subjects by administering the Cannabis Experience Questionnaire. In the healthy subjects' sample, we also collected data on schizotypy and cognitive performance using the Schizotypal Personality Questionnaire and the N-back working memory task. In the case-control study, we found a significant interaction between the rs1076560 DRD2 genotype and cannabis use in influencing the likelihood of a psychotic disorder. Among cannabis users, carriers of the DRD2, rs1076560, T allele showed a 3-fold increased probability to suffer a psychotic disorder compared with GG carriers (OR = 3.07; 95% confidence interval [CI]: 1.22-7.63). Among daily users, T carrying subjects showed a 5-fold increase in the odds of psychosis compared to GG carriers (OR = 4.82; 95% CI: 1.39-16.71). Among the healthy subjects, T carrying cannabis users had increased schizotypy compared with T carrying cannabis-naïve subjects, GG cannabis users, and GG cannabis-naïve subjects (all P ≤ .025). T carrying cannabis users had reduced working memory accuracy compared with the other groups (all P ≤ .008). Thus, variation of the DRD2, rs1076560, genotype may modulate the psychosis-inducing effect of cannabis use. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Straight-run vs. sex separate rearing for 2 broiler genetic lines Part 1: Live production parameters, carcass yield, and feeding behavior.

    Science.gov (United States)

    Da Costa, M J; Zaragoza-Santacruz, S; Frost, T J; Halley, J; Pesti, G M

    2017-08-01

    The objective of this experiment was to evaluate the effects of raising broilers under sex separate and straight-run conditions for 2 broiler strains. Day-old Ross 308 and Ross 708 chicks (n = 1,344) were separated by sex and placed in 48 pens according to the rearing type: sex separate (28 males or 28 females) or straight-run (14 males + 14 females). There were 3 dietary phases: starter (zero to 17 d), grower (17 to 32 d), and finisher (32 to 48 d). Birds' individual BW and feed intakes were measured at 12, 17, 25, 32, 42, and 48 d to evaluate performance. At 33, 43, and 49 d, 4 birds per pen were sampled for carcass yield evaluation. Additionally, from 06:00 to 06:30, 13:00 to 13:30, and 22:00 to 22:30, video records were taken to assess behavior at 45 days. Data were analyzed as CRD with a 2 × 3 factorial arrangement of treatments over time. Throughout the experiment Ross 308 were heavier than the 708, and after 17 d, male pens had the heavier birds, followed by straight-run and then females. Straight-run pens had higher BW CV in comparison with sex separate pens. Sex separate male BW was negatively impacted from 17 to 32 days. On the other hand, females raised sex separate were heavier than females raised straight-run with lower CV from 25 to 41 days. Post 25 d, FCR was the lowest in male pens whereas feed intake was the highest for these pens after 17 days. Overall, males had total carcass cut-up weights higher than straight-run and females at the 3 processing times. The Ross 708 had higher white meat yields, whereas 308 had higher yields for dark meat. Feeding behavior results were not consistent over time. However, from 13:00 to 13:30, birds in female pens spent more time eating, followed by straight-run and then males. In conclusion, raising females in a straight-run system negatively impacted performance and CV, whereas males benefited from straight-run rearing, with the differences being possibly related to feeder space competition. © 2017

  3. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Demontis, Ditte; Castro Dias Cuyabano, Beatriz

    2016-01-01

    was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case–control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism......Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited...... genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT...

  4. Using Wearable Sensors and Machine Learning Models to Separate Functional Upper Extremity Use From Walking-Associated Arm Movements.

    Science.gov (United States)

    McLeod, Adam; Bochniewicz, Elaine M; Lum, Peter S; Holley, Rahsaan J; Emmer, Geoff; Dromerick, Alexander W

    2016-02-01

    To improve measurement of upper extremity (UE) use in the community by evaluating the feasibility of using body-worn sensor data and machine learning models to distinguish productive prehensile and bimanual UE activity use from extraneous movements associated with walking. Comparison of machine learning classification models with criterion standard of manually scored videos of performance in UE prosthesis users. Rehabilitation hospital training apartment. Convenience sample of UE prosthesis users (n=5) and controls (n=13) similar in age and hand dominance (N=18). Participants were filmed executing a series of functional activities; a trained observer annotated each frame to indicate either UE movement directed at functional activity or walking. Synchronized data from an inertial sensor attached to the dominant wrist were similarly classified as indicating either a functional use or walking. These data were used to train 3 classification models to predict the functional versus walking state given the associated sensor information. Models were trained over 4 trials: on UE amputees and controls and both within subject and across subject. Model performance was also examined with and without preprocessing (centering) in the across-subject trials. Percent correct classification. With the exception of the amputee/across-subject trial, at least 1 model classified >95% of test data correctly for all trial types. The top performer in the amputee/across-subject trial classified 85% of test examples correctly. We have demonstrated that computationally lightweight classification models can use inertial data collected from wrist-worn sensors to reliably distinguish prosthetic UE movements during functional use from walking-associated movement. This approach has promise in objectively measuring real-world UE use of prosthetic limbs and may be helpful in clinical trials and in measuring response to treatment of other UE pathologies. Copyright © 2016 American Congress of

  5. Doehlert design-desirability function multi-criteria optimal separation of 17 phenolic compounds from extra-virgin olive oil by capillary zone electrophoresis.

    Science.gov (United States)

    Ballus, Cristiano Augusto; Meinhart, Adriana Dillenburg; de Souza Campos, Francisco Alberto; Bruns, Roy Edward; Godoy, Helena Teixeira

    2014-03-01

    In Brazil, the consumption of extra-virgin olive oil (EVOO) is increasing annually, but there are no experimental studies concerning the phenolic compound contents of commercial EVOO. The aim of this work was to optimise the separation of 17 phenolic compounds already detected in EVOO. A Doehlert matrix experimental design was used, evaluating the effects of pH and electrolyte concentration. Resolution, runtime and migration time relative standard deviation values were evaluated. Derringer's desirability function was used to simultaneously optimise all 37 responses. The 17 peaks were separated in 19min using a fused-silica capillary (50μm internal diameter, 72cm of effective length) with an extended light path and 101.3mmolL(-1) of boric acid electrolyte (pH 9.15, 30kV). The method was validated and applied to 15 EVOO samples found in Brazilian supermarkets. Published by Elsevier Ltd.

  6. Human Kin Investment as a Function of Genetic Relatedness and Lineage

    Directory of Open Access Journals (Sweden)

    Gregory D. Webster

    2004-01-01

    Full Text Available Two independent samples of students were asked to allocate fictional lotteries of varying dollar amounts to their blood relatives. In both studies, a reliable genetic relatedness by lineage interaction emerged, such that the genetic effect was a more positive predictor of percent of money allocated for relatives of a direct lineage (e.g., parents, grandparents than it was for peripheral relatives (e.g., siblings, aunts and uncles. In a third study, this interaction was replicated in an archival analysis of wills. The implications of accounting for differences in relatives' lineages in studies of kin investment are discussed.

  7. Noise genetics: inferring protein function by correlating phenotype with protein levels and localization in individual human cells.

    Directory of Open Access Journals (Sweden)

    Shlomit Farkash-Amar

    2014-03-01

    Full Text Available To understand gene function, genetic analysis uses large perturbations such as gene deletion, knockdown or over-expression. Large perturbations have drawbacks: they move the cell far from its normal working point, and can thus be masked by off-target effects or compensation by other genes. Here, we offer a complementary approach, called noise genetics. We use natural cell-cell variations in protein level and localization, and correlate them to the natural variations of the phenotype of the same cells. Observing these variations is made possible by recent advances in dynamic proteomics that allow measuring proteins over time in individual living cells. Using motility of human cancer cells as a model system, and time-lapse microscopy on 566 fluorescently tagged proteins, we found 74 candidate motility genes whose level or localization strongly correlate with motility in individual cells. We recovered 30 known motility genes, and validated several novel ones by mild knockdown experiments. Noise genetics can complement standard genetics for a variety of phenotypes.

  8. Charge pattern matching as a ‘fuzzy’ mode of molecular recognition for the functional phase separations of intrinsically disordered proteins

    Science.gov (United States)

    Lin, Yi-Hsuan; Brady, Jacob P.; Forman-Kay, Julie D.; Chan, Hue Sun

    2017-11-01

    Biologically functional liquid-liquid phase separation of intrinsically disordered proteins (IDPs) is driven by interactions encoded by their amino acid sequences. Little is currently known about the molecular recognition mechanisms for distributing different IDP sequences into various cellular membraneless compartments. Pertinent physics was addressed recently by applying random-phase-approximation (RPA) polymer theory to electrostatics, which is a major energetic component governing IDP phase properties. RPA accounts for charge patterns and thus has advantages over Flory-Huggins (FH) and Overbeek-Voorn mean-field theories. To make progress toward deciphering the phase behaviors of multiple IDP sequences, the RPA formulation for one IDP species plus solvent is hereby extended to treat polyampholyte solutions containing two IDP species plus solvent. The new formulation generally allows for binary coexistence of two phases, each containing a different set of volume fractions ({φ }1,{φ }2) for the two different IDP sequences. The asymmetry between the two predicted coexisting phases with regard to their {φ }1/{φ }2 ratios for the two sequences increases with increasing mismatch between their charge patterns. This finding points to a multivalent, stochastic, ‘fuzzy’ mode of molecular recognition that helps populate various IDP sequences differentially into separate phase compartments. An intuitive illustration of this trend is provided by FH models, whereby a hypothetical case of ternary coexistence is also explored. Augmentations of the present RPA theory with a relative permittivity {ɛ }{{r}}(φ ) that depends on IDP volume fraction φ ={φ }1+{φ }2 lead to higher propensities to phase separate, in line with the case with one IDP species we studied previously. Notably, the cooperative, phase-separation-enhancing effects predicted by the prescriptions for {ɛ }{{r}}(φ ) we deem physically plausible are much more prominent than that entailed by common

  9. A functional TNFAIP2 3'-UTR rs8126 genetic polymorphism contributes to risk of esophageal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Jian Zhang

    Full Text Available BACKGROUND: Accumulated evidences demonstrated that single nucleotide polymorphisms (SNPs in mRNA 3'-untranslated region (3'-UTR may impact microRNAs (miRNAs-mediated expression regulation of oncogenes and tumor suppressors. There is a TNFAIP2 3'-UTR rs8126 T>C genetic variant which has been proved to be associated with head and neck cancer susceptibility. This SNP could disturb binding of miR-184 with TNFAIP2 mRNA and influence TNFAIP2 regulation. However, it is still unclear how this polymorphism is involved in development of esophageal squamous cell carcinoma (ESCC. Therefore, we hypothesized that the functional TNFAIP2 rs8126 SNP may affect TNFAIP2 expression and, thus, ESCC risk. METHODS: We investigated the association between the TNFAIP2 rs8126 variant and ESCC risk as well as the functional relevance on TNFAIP2 expression in vivo. Genotypes were determined in a case-control set consisted of 588 ESCC patients and 600 controls. The allele-specific regulation on TNFAIP2 expression by the rs8126 SNP was examined in normal and cancerous tissue specimens of esophagus. RESULTS: We found that individuals carrying the rs8126 CC or CT genotype had an OR of 1.89 (95%CI  = 1.23-2.85, P = 0.003 or 1.38 (95%CI  = 1.05-1.73, P = 0.017 for developing ESCC in Chinese compared with individual carrying the TT genotype. Carriers of the rs8126 CC and CT genotypes had significantly lower TNFAIP2 mRNA levels than those with the TT genotypes in normal esophagus tissues (P<0.05. CONCLUSIONS: Our data demonstrate that functional TNFAIP2 rs8126 genetic variant is a ESCC susceptibility SNP. These results support the hypothesis that genetic variants interrupting miRNA-mediated gene regulation might be important genetic modifiers of cancer risk.

  10. Enhanced propylene/propane separation by thermal annealing of an intrinsically microporous Hydroxyl-functionalized polyimide membrane

    KAUST Repository

    Swaidan, Ramy J.; Ma, Xiaohua; Litwiller, Eric; Pinnau, Ingo

    2015-01-01

    Effective separation of propylene/propane is vital to the chemical industry where C3H6 is used as feedstock for a variety of important chemicals. The purity requirements are currently met with cryogenic distillation, which is an extremely energy-intensive process. Hybrid arrangements incorporating highly selective membranes (α>20) have been proposed to “debottleneck” the process and potentially improve the economics. Selective and permeable membranes can be obtained by the design of polymers of intrinsic microporosity (PIMs). In this work, a 250 °C annealed polyimide (PIM-6FDA-OH) membrane produced among the highest reported pure-gas C3H6/C3H8 selectivity of 30 for a solution-processable polymer to date. The high selectivity resulted from enhanced diffusivity selectivity due to the formation of inter-chain charge-transfer-complexes. Although there were some inevitable losses in selectivity under 50:50 mixed-gas feed conditions due to competitive sorption, relatively high selectivities were preserved due to enhanced plasticization resistance.

  11. Functional properties of meat by-products and mechanically separated chicken (MSC) in a high-moisture model petfood system.

    Science.gov (United States)

    Rivera, J A; Sebranek, J G; Rust, R E

    2000-05-01

    Contributions to water retention capacity (% WRC) and texture changes were determined for pork by-products (lung lobes, kidneys), chicken viscera (head, feet and viscera) and mechanically separated chicken (MSC) as affected by pH and various salts in a high-moisture model system. The % WRC for meat by-products and MSC was increased by increased pH (4.5-6.8). Pork lungs and MSC had the highest % WRC (pmeat by-products. Meat by-product % WRC was not signifcantly (p>0.05) affected by salt (2%), phosphate (0.3%) or NaOH (0.075%). Chicken viscera had the lowest (pmeat by-products and MSC. Strong negative correlations (p<0.05) were obtained for texture with total collagen, soluble collagen and high ionic strength soluble (HIS) proteins. These results should be considered for product quality changes when these by-products are used in formulation of high moisture pet food products.

  12. Enhanced propylene/propane separation by thermal annealing of an intrinsically microporous Hydroxyl-functionalized polyimide membrane

    KAUST Repository

    Swaidan, Ramy Jawdat

    2015-08-06

    Effective separation of propylene/propane is vital to the chemical industry where C3H6 is used as feedstock for a variety of important chemicals. The purity requirements are currently met with cryogenic distillation, which is an extremely energy-intensive process. Hybrid arrangements incorporating highly selective membranes (α>20) have been proposed to “debottleneck” the process and potentially improve the economics. Selective and permeable membranes can be obtained by the design of polymers of intrinsic microporosity (PIMs). In this work, a 250 °C annealed polyimide (PIM-6FDA-OH) membrane produced among the highest reported pure-gas C3H6/C3H8 selectivity of 30 for a solution-processable polymer to date. The high selectivity resulted from enhanced diffusivity selectivity due to the formation of inter-chain charge-transfer-complexes. Although there were some inevitable losses in selectivity under 50:50 mixed-gas feed conditions due to competitive sorption, relatively high selectivities were preserved due to enhanced plasticization resistance.

  13. Phase separation in biopolymer gels: a low- to high-solid exploration of structural morphology and functionality.

    Science.gov (United States)

    Kasapis, Stefan

    2008-04-01

    Phase separation in protein and polysaccharide gels remains one of the basic tools of achieving the required structural properties and textural profile in food product formulations. As ever, the industrialist is faced with the challenge of innovation in an increasingly competitive market in terms of ingredient cost, product added-value, and expectations of a healthy life-style to mention but a few. It appears, however, that a gap persists between the fundamental knowledge and a direct application to food related concepts with a growing need for scientific input. Furthermore, within the context of materials science, there is a tendency to examine research findings in either low- or high-solid systems without considering synergistic insights/benefits to contemporary needs, spanning the full range of relevant time-, length-, and concentration scales. This review highlights the latest attempts made to utilize and further develop fundamental protocols from the advanced synthetic polymer research as a source of inspiration for contemporary bio-related applications in low- and intermediate-solid composite gels. Then, it takes advantage of this school of thought to "force a passage" through the phase topology and molecular dynamics of binary biopolymer mixtures at high levels of co-solute. It is hoped that these phenomenological and fundamental tools should be able to bridge the divide in the analysis of the two "types" of composite materials (from low to high solids) thus dealing effectively with the specific and often intricate problems of their science and applications.

  14. Modes of interaction between nanostructured metal and a conducting mirror as a function of separation and incident polarization

    Science.gov (United States)

    Bonnie, F.; Arnold, M. D.; Smith, G. B.; Gentle, A. R.

    2013-09-01

    The optical resonances that occur in nanostructured metal layers are modulated in thin film stacks if the nanostructured layer is separated from a reflecting conducting layer by various thicknesses of thin dielectric. We have measured and modeled the optical response of interacting silver layers, with alumina spacer thickness ranging from a few nm to 50 nm, for s- and p-polarized incident light, and a range of incident angles. Standard thin film models, including standard effective medium models for the nanostructured layer, will break down for spacer thickness below a critical threshold. For example, with polarisation in the film plane and some nano-islands, it may occur at around 10 nm depending on spacer refractive index. Of particular interest here are novel effects observed with the onset of percolation in the nanolayer. Hot spot effects can be modified by nearby mirrors. Other modes to consider include (a) a two-particle mode involving a particle and its mirror image (b) A Fano resonance from hybridisation of localized and de-localised plasmon modes (c) a Babinet's core-(partial) shell particle with metal core-dielectric shell in metal (d) spacing dependent phase modulation (e) the impact of field gradients induced by the mirror at the nano-layer.

  15. [Effect of medicinal-cake-separated moxibustion on functional activity of back-leg and plasma substance P level in patients with lumbar disc herniation].

    Science.gov (United States)

    Yang, Shuo; Yang, Xiao-fang; Jiang, Yu; Xiang, Kai-wei; Li, Hai-yu

    2014-12-01

    To observe the effect of medicinal-cake-separated moxibustion combined with acupuncture on back-leg activities and plasma substance P (SP) levels in patients with lumbar disc herniation, so as to reveal its mechanism underlying pain relief. A total of 114 patients with lumbar disc herniation were randomly divided into control group (n=56) and treatment group (n=58) according to a random digits table. Patients of the control group were treated by manual acupuncture stimulation of main acupoints Jiaji (EX-B 2), Huantiao (GB 30, affected side), Chengshan (BL 57, affected side), Kunlun (BL 60, affected side), and supplemented acupoints Yanglingquan (GB 34), Weizhong (BL 40) and Zusanli (ST 36) in combination with wheat-flour-cake separated moxibustion at the main acupoints, and patients of the treatment group were treated by medicinal-cake [Chuanwu (Radix Aconiti), Caowu (Radix Aconiti Kusnezoffii), Ruxiang (Olibanum), etc. ]-separated moxibustion in combination with manual acupuncture stimulation of the same acupoints mentioned above. Acupuncture treatment was conducted for 30 min, followed by moxibustion for 15 min. The treatment was given once daily for 10 days. The patients' back-leg functional activity ability was assessed using straight-leg raising test, and the pain state assessed using visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) scores, respectively. The therapeutic effect was evaluated by using "Crite- ria for Diagnosis and Outcome Evaluation of Clinical Disorders or Syndromes of Chinese Medicine" issued in 1994 and plasma SP content was detected by radioimmunoassay. After the therapy, the back-leg activity score and JOA score of both groups were significantly higher than those of pre-treatment in the same one group (Pcake-separated moxibustion therapy can ame- liorate pain severity and functional activity of the back-leg pain patients with lumbar disc hernia, which may be related to its effect in reducing blood SP level.

  16. Isotope separation

    International Nuclear Information System (INIS)

    Eerkens, J.W.

    1979-01-01

    A method of isotope separation is described which involves the use of a laser photon beam to selectively induce energy level transitions of an isotope molecule containing the isotope to be separated. The use of the technique for 235 U enrichment is demonstrated. (UK)

  17. Genetic modifiers of comatose mutations in Drosophila: insights into neuronal NSF (N-ethylmaleimide-sensitive fusion factor) functions.

    Science.gov (United States)

    Sanyal, Subhabrata; Krishnan, K S

    2012-09-01

    By the middle of the 20th century, development of powerful genetic approaches had ensured that the fruit fly would remain a model organism of choice for genetic and developmental studies. But in the 1970s, a few pioneering groups turned their attention to the prospect of using the fly for neurophysiological experiments. They proposed that in a poikilothermic organism such as Drosophila, temperature-sensitive or "ts" mutations in proteins that controlled nerve function would translate to a "ts" paralytic phenotype. This was by no means an obvious or even a likely assumption. However, following directed screens these groups soon reported dramatic demonstrations of reversible ts paralysis in fly mutants. Resultantly, these "simple" experiments led to the isolation of a number of conditional mutations including shibire, paralytic, and comatose. All have since been cloned and have enabled deep mechanistic insights into synaptic transmission and nerve conduction. comatose (comt) mutations, for example, were found to map to missense changes in dNSF1, a neuron-specific fly homolog of mammalian NSF (N-ethylmaleimide-sensitive fusion factor). Studies on comt were also some of the first to discriminate between nuanced models of NSF function during presynaptic transmitter release that have since been borne out by experiments in multiple preparations. Here, the authors present an overview of NSF function as it is understood today, with an emphasis on contributions from Drosophila beginning with experiments carried out by Obaid Siddiqi in the Benzer laboratory. The authors also outline initial results from a genetic screen for phenotypic modifiers of comt that hold the promise of further elucidating NSF function at the synapse. Over the years, the neuromuscular system of Drosophila has served as a uniquely accessible model to unravel mechanisms underlying synaptic transmission. To this day, ts paralysis remains one of the most emphatic demonstrations of nerve function in an

  18. Glacial vicariance in the Pacific Northwest: evidence from a lodgepole pine mitochondrial DNA minisatellite for multiple genetically distinct and widely separated refugia.

    Science.gov (United States)

    Godbout, Julie; Fazekas, Aron; Newton, Craig H; Yeh, Francis C; Bousquet, Jean

    2008-05-01

    The Canadian side of the Pacific Northwest was almost entirely covered by ice during the last glacial maximum, which has induced vicariance and genetic population structure for several plant and animal taxa. Lodgepole pine (Pinus contorta Dougl. ex. Loud.) has a wide latitudinal and longitudinal distribution in the Pacific Northwest. Our main objective was to identify relictual signatures of glacial vicariance in the population structure of the species and search for evidence of distinct glacial refugia in the Pacific Northwest. A maternally inherited mitochondrial DNA minisatellite-like marker was used to decipher haplotype diversity in 91 populations of lodgepole pine located across the natural range. Overall population differentiation was sizeable (G(ST) = 0.365 and R(ST) = 0.568). Four relatively homogeneous groups of populations, possibly representative of as many genetically distinct glacial populations, were identified for the two main subspecies, ssp. latifolia and ssp. contorta. For ssp. contorta, one glacial lineage is suggested to have been located at high latitudes and possibly off the coast of mainland British Columbia (BC), while the other is considered to have been located south of the ice sheet along the Pacific coast. For ssp. latifolia, two genetically distinct glacial populations probably occurred south of the ice sheet: in the area bounded by the Cascades and Rocky Mountains ranges, and on the eastern side of the Rockies. A possible fifth refugium located in the Yukon may have also been present for ssp. latifolia. Zones of contact between these ancestral lineages were also apparent in interior and northern BC. These results indicate the role of the Queen Charlotte Islands and the Alexander Archipelago as a refugial zone for some Pacific Northwest species and the vicariant role played by the Cascades and the American Rocky Mountains during glaciation.

  19. Influence of Hypothyroidism on Separate Links of Metabolism, Structure and Function of the Heart in Insulin Resistance

    Directory of Open Access Journals (Sweden)

    T.Yu. Yuzvenko

    2014-05-01

    Full Text Available The article presents research findings of reduced thyroid function impact on the background of insulin resistance on the specific links of metabolism, structure and function of the heart. It is found that in thyroid dysfunction, the main nosological form of myocardial lesion in female patients without concomitant cardiovascular disease is the development of metabolic endocrine cardiomyopathy. Feature of cardiac lesion is the absence of cardiosclerotic, myocardial and ischemic processes in hypothyroidism. Obscure clinical symptoms of the heart both in apparent and subclinical hypothyroidism are detected. Features of clinical, instrumental and laboratory changes in female patients with impaired thyroid function are a trend to systolic blood pressure increase, the absence of significant dyslipidemia, dysglycemia, and cardiocytolysis and hepatocytolysis. Thyroid hormone deficiency is associated with increased myocardial repolarization heterogeneity: subclinical hypothyroidism is accompanied by violation of repolarization processes and the development of electrical heterogeneity of ventricular myocardium, and in the apparent hypothyroidism changes are more linked with the violation of the homogeneity of the electrical impulse to the atria.

  20. Functional Dysconnection of the Inferior Frontal Gyrus in Young People With Bipolar Disorder or at Genetic High Risk.

    Science.gov (United States)

    Roberts, Gloria; Lord, Anton; Frankland, Andrew; Wright, Adam; Lau, Phoebe; Levy, Florence; Lenroot, Rhoshel K; Mitchell, Philip B; Breakspear, Michael

    2017-04-15

    Bipolar disorder (BD) is characterized by a dysregulation of affect and impaired integration of emotion with cognition. These traits are also expressed in probands at high genetic risk of BD. The inferior frontal gyrus (IFG) is a key cortical hub in the circuits of emotion and cognitive control, and it has been frequently associated with BD. Here, we studied resting-state functional connectivity of the left IFG in participants with BD and in those at increased genetic risk. Using resting-state functional magnetic resonance imaging we compared 49 young BD participants, 71 individuals with at least one first-degree relative with BD (at-risk), and 80 control subjects. We performed between-group analyses of the functional connectivity of the left IFG and used graph theory to study its local functional network topology. We also used machine learning to study classification based solely on the functional connectivity of the IFG. In BD, the left IFG was functionally dysconnected from a network of regions, including bilateral insulae, ventrolateral prefrontal gyri, superior temporal gyri, and the putamen (p < .001). A small network incorporating neighboring insular regions and the anterior cingulate cortex showed weaker functional connectivity in at-risk than control participants (p < .006). These constellations of regions overlapped with frontolimbic regions that a machine learning classifier selected as predicting group membership with an accuracy significantly greater than chance. Functional dysconnectivity of the IFG from regions involved in emotional regulation may represent a trait abnormality for BD and could potentially aid clinical diagnosis. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Endogenous network states predict gain or loss of functions for genetic mutations in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Gaowei; Su, Hang; Yu, Helin; Yuan, Ruoshi; Zhu, Xiaomei; Ao, Ping

    2016-02-01

    Cancers have been typically characterized by genetic mutations. Patterns of such mutations have traditionally been analysed by posteriori statistical association approaches. One may ponder the possibility of a priori determination of any mutation regularity. Here by exploring biological processes implied in a mechanistic theory recently developed (the endogenous molecular-cellular network theory), we found that the features of genetic mutations in cancers may be predicted without any prior knowledge of mutation propensities. With hepatocellular carcinoma (HCC) as an example, we found that the normal hepatocyte and cancerous hepatocyte can be represented by robust stable states of one single endogenous network. These stable states, specified by distinct patterns of expressions or activities of proteins in the network, provide means to directly identify a set of most probable genetic mutations and their effects in HCC. As the key proteins and main interactions in the network are conserved through cell types in an organism, similar mutational features may also be found in other cancers. This analysis yielded straightforward and testable predictions on accumulated and preferred mutation spectra in normal tissue. The validation of predicted cancer state mutation patterns demonstrates the usefulness and potential of a causal dynamical framework to understand and predict genetic mutations in cancer. © 2016 The Author(s).

  2. Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation

    DEFF Research Database (Denmark)

    Sinner, Moritz F; Tucker, Nathan R; Lunetta, Kathryn L

    2014-01-01

    BACKGROUND: Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. METHODS AND RESULTS: To identify new AF-re...

  3. The genetic variation in Monocarboxylic acid transporter 2 (MCT2 has functional and clinical relevance with male infertility

    Directory of Open Access Journals (Sweden)

    Jinu Lee

    2014-10-01

    Full Text Available Monocarboxylic acid transporter 2 (MCT2 transports pyruvate and lactate outside and inside of sperms, mainly as energy sources and plays roles in the regulation of spermatogenesis. We investigated the association among genetic variations in the MCT2 gene, male infertility and MCT2 expression levels in sperm. The functional and genetic significance of the intron 2 (+28201A > G, rs10506398 and 3' untranslated region (UTR single nucleotide polymorphism (SNP (+2626G > A, rs10506399 of MCT2 variants were investigated. Two MCT2 polymorphisms were associated with male infertility (n = 471, P A had a strong association with the oligoasthenoteratozoospermia (OAT group. The +2626GG type had an almost 2.4-fold higher sperm count than that of the +2626AA type (+2626GG; 66 × 10 6 vs +2626AA; 27 × 10 6 , P < 0.0001. The MCT2-3' UTR SNP may be important for expression, as it is located at the MCT2 3' UTR. The average MCT2 protein amount in sperm of the +2626GG type was about two times higher than that of the +2626AA type. The results suggest that genetic variation in MCT2 has functional and clinical relevance with male infertility.

  4. Range-separated time-dependent density-functional theory with a frequency-dependent second-order Bethe-Salpeter correlation kernel

    Energy Technology Data Exchange (ETDEWEB)

    Rebolini, Elisa, E-mail: elisa.rebolini@kjemi.uio.no; Toulouse, Julien, E-mail: julien.toulouse@upmc.fr [Laboratoire de Chimie Théorique, Sorbonne Universités, UPMC Univ Paris 06, CNRS, 4 place Jussieu, F-75005 Paris (France)

    2016-03-07

    We present a range-separated linear-response time-dependent density-functional theory (TDDFT) which combines a density-functional approximation for the short-range response kernel and a frequency-dependent second-order Bethe-Salpeter approximation for the long-range response kernel. This approach goes beyond the adiabatic approximation usually used in linear-response TDDFT and aims at improving the accuracy of calculations of electronic excitation energies of molecular systems. A detailed derivation of the frequency-dependent second-order Bethe-Salpeter correlation kernel is given using many-body Green-function theory. Preliminary tests of this range-separated TDDFT method are presented for the calculation of excitation energies of the He and Be atoms and small molecules (H{sub 2}, N{sub 2}, CO{sub 2}, H{sub 2}CO, and C{sub 2}H{sub 4}). The results suggest that the addition of the long-range second-order Bethe-Salpeter correlation kernel overall slightly improves the excitation energies.

  5. Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms

    Directory of Open Access Journals (Sweden)

    Kirk I Erickson

    2008-09-01

    Full Text Available Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT and brain-derived neurotrophic factor (BDNF were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single-nucleotide polymorphism (SNP in the COMT (Val158/108Met gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age.

  6. Effects of mercury contamination on the culturable heterotrophic, functional and genetic diversity of the bacterial community in soil

    DEFF Research Database (Denmark)

    Rasmussen, Lasse Dam; Sørensen, S. J.

    2001-01-01

    This study investigates the effect of mercury contamination on the culturable heterotrophic, functional and genetic diversity of the bacterial community in soil. The changes in diversity were monitored in soil microcosms, enriched with 25 mug Hg(II) g(-1) soil, over a period of 3 months...... by purification of total soil DNA and amplification of bacterial 16S rDNA fragments by polymerase chain reaction. Concentrations of bioavailable and total mercury were measured throughout the experiment. The effect on the culturable heterotrophic and genetic diversity was very similar, showing an immediate...... decrease after mercury addition but then slowly increasing throughout the entire experimental period. Pre-exposure levels were not reached within the time span of this investigation. The DGGE band pattern indicated that a shift in the community structure was responsible for recovered diversity. When...

  7. Genetic covariance functioners for live weight, condition score, and dry-matter intake measured at different lactations stages of Holstein-Friesian heifers

    NARCIS (Netherlands)

    Koenen, E.P.C.; Veerkamp, R.F.

    1998-01-01

    Genetic parameters for live weight, body condition score and dry-matter intake of dairy heifers were estimated using covariance function methodology. Data were from 469 heifers of the Langhill Dairy Cattle Research Centre and included observations during the first 25 weeks in lactation. Genetic

  8. CENTRIFUGAL SEPARATORS

    Science.gov (United States)

    Skarstrom, C.

    1959-03-10

    A centrifugal separator is described for separating gaseous mixtures where the temperature gradients both longitudinally and radially of the centrifuge may be controlled effectively to produce a maximum separation of the process gases flowing through. Tbe invention provides for the balancing of increases and decreases in temperature in various zones of the centrifuge chamber as the result of compression and expansions respectively, of process gases and may be employed effectively both to neutralize harmful temperature gradients and to utilize beneficial temperaturc gradients within the centrifuge.

  9. Microparticle Separation by Cyclonic Separation

    Science.gov (United States)

    Karback, Keegan; Leith, Alexander

    2017-11-01

    The ability to separate particles based on their size has wide ranging applications from the industrial to the medical. Currently, cyclonic separators are primarily used in agriculture and manufacturing to syphon out contaminates or products from an air supply. This has led us to believe that cyclonic separation has more applications than the agricultural and industrial. Using the OpenFoam computational package, we were able to determine the flow parameters of a vortex in a cyclonic separator in order to segregate dust particles to a cutoff size of tens of nanometers. To test the model, we constructed an experiment to separate a test dust of various sized particles. We filled a chamber with Arizona test dust and utilized an acoustic suspension technique to segregate particles finer than a coarse cutoff size and introduce them into the cyclonic separation apparatus where they were further separated via a vortex following our computational model. The size of the particles separated from this experiment will be used to further refine our model. Metropolitan State University of Denver, Colorado University of Denver, Dr. Randall Tagg, Dr. Richard Krantz.

  10. Dispersive solid-phase microextraction and capillary electrophoresis separation of food colorants in beverages using diamino moiety functionalized silica nanoparticles as both extractant and pseudostationary phase.

    Science.gov (United States)

    Liu, Feng-Jie; Liu, Chuan-Ting; Li, Wei; Tang, An-Na

    2015-01-01

    In this work, a new method for the determination of food colorants in beverage samples is developed, using diamino moiety functionalized silica nanoparticles (dASNPs) as both adsorbents in dispersive solid-phase microextraction (dSPME) and pseudostationary phases (PSPs) in capillary electrophoresis (CE) separation. dASNPs were firstly used as adsorbents for the preconcentration of four colorants by the dSPME process. After that, colorants were efficiently separated by CE using 30 mM phosphate buffer (pH 6.0) containing 2 mM β-CD and 0.9 mg/mL dASNPs as additives. All factors influencing dSPME and CE separations were optimized in detail. The investigated analytes showed good linearities with correlation coefficients (R(2)) higher than 0.9932. The limits of detection for the four food colorants were between 0.030 and 0.36 mg/L, which are lower than those reported previously. The established method was also used to analyze four colorants in beverage samples with recoveries ranging from 82.7% to 114.6%. To the best of our knowledge, this is the first time to use NPs both as extractants in dSPME and pseudostationary phases in CE for the analytical purpose. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Pristine and thermally-rearranged gas separation membranes from novel o-hydroxyl-functionalized spirobifluorene-based polyimides

    KAUST Repository

    Ma, Xiaohua

    2014-01-01

    A novel o-hydroxyl-functionalized spirobifluorene-based diamine monomer, 2,2′-dihydroxyl-9,9′-spiro-bifluorene- 3,3′-diamine (HSBF), was successfully prepared by a universal synthetic method. Two o-hydroxyl-containing polyimides, denoted as 6FDA-HSBF and SPDA-HSBF, were synthesized and characterized. The BET surface areas of 6FDA-HSBF and SPDA-HSBF are 70 and 464 m2 g-1, respectively. To date, SPDA-HSBF exhibits the highest CO2 permeability (568 Barrer) among all hydroxyl-containing polyimides. The HSBF-based polyimides exhibited higher CO2/CH4 selectivity than their spirobifluorene (SBF) analogues (42 for 6FDA-HSBF vs. 27 for 6FDA-SBF) due to an increase in their diffusivity selectivity. Polybenzoxazole (PBO) membranes obtained from HSBF-based polyimide precursors by thermal rearrangement showed enhanced permeability but at the cost of significantly decreased selectivity.

  12. Liking is not the opposite of disliking: the functional separability of positive and negative attitudes toward minority groups.

    Science.gov (United States)

    Pittinsky, Todd L; Rosenthal, Seth A; Montoya, R Matthew

    2011-04-01

    Two studies tested the hypotheses that positive and negative attitudes toward minority groups are not interchangeable in predicting positive versus negative behaviors toward those groups. In Study 1, positive attitudes about Latinos were a better predictor of a positive behavior toward Latinos than were negative attitudes or stereotyped positive attitudes. In Study 2, positive attitudes about African Americans were a better predictor of positive behavioral intentions toward that group than were negative attitudes, whereas negative attitudes were better predictors of negative behavioral intentions than were positive attitudes. Taken together, the studies support the perspective that positive and negative attitudes toward minority groups are theoretically and functionally distinct constructs. We conclude that it is important to measure both positive and negative attitudes to understand and predict behaviors toward minority groups.

  13. Genetic method for separation of males and females of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann, 1824) (Diptera: Tephritidae), based on pupal color dimorphisms

    International Nuclear Information System (INIS)

    Barrios, C.E.C.

    1990-06-01

    Pupae of Ceratitis capitata (Wiedemann, 1824) were irradiated with 60 Gy gamma radiation and subsequently the emergent males were crossed with females of recessive mutants on white pupa color (w p/w p). A strain with a translocation between autosomal chromosome number 5, carrier of w p+ dominant gene, and Y chromosome was isolated. By this way the T:Y (w p+) 70 strain with sexual dimorphism based on pupal color was obtained. Cytological examination of the males was carried out to confirm the translocation. The genetic stability was monitored under laboratory conditions during 21 generations. The rates of contaminant females emerged from brown pupae were 0,96 to 4,5% and for males from white pupae these rates were 0,26 to 0,66%. These values presented no definite increase tendency. The origin of contaminant genotypes and the potential for utilization of the sterile male techniques are discussed. (author)

  14. Isotopic separation

    International Nuclear Information System (INIS)

    Castle, P.M.

    1979-01-01

    This invention relates to molecular and atomic isotope separation and is particularly applicable to the separation of 235 U from other uranium isotopes including 238 U. In the method described a desired isotope is separated mechanically from an atomic or molecular beam formed from an isotope mixture utilising the isotropic recoil momenta resulting from selective excitation of the desired isotope species by radiation, followed by ionization or dissociation by radiation or electron attachment. By forming a matrix of UF 6 molecules in HBr molecules so as to collapse the V 3 vibrational mode of the UF 6 molecule the 235 UF 6 molecules are selectively excited to promote reduction of UF 6 molecules containing 235 U and facilitate separation. (UK)

  15. Isotopic separation

    International Nuclear Information System (INIS)

    Chen, C.L.

    1979-01-01

    Isotopic species in an isotopic mixture including a first species having a first isotope and a second species having a second isotope are separated by selectively exciting the first species in preference to the second species and then reacting the selectively excited first species with an additional preselected radiation, an electron or another chemical species so as to form a product having a mass different from the original species and separating the product from the balance of the mixture in a centrifugal separating device such as centrifuge or aerodynamic nozzle. In the centrifuge the isotopic mixture is passed into a rotor where it is irradiated through a window. Heavier and lighter components can be withdrawn. The irradiated mixture experiences a large centrifugal force and is separated in a deflection area into lighter and heavier components. (UK)

  16. Genetic differences in hemoglobin function between highland and lowland deer mice

    DEFF Research Database (Denmark)

    Storz, Jay F.; Runck, Amy M.; Moriyama, Hideaki

    2010-01-01

    In high-altitude vertebrates, adaptive changes in blood–O2 affinity may be mediated by modifications of hemoglobin (Hb) structure that affect intrinsic O2 affinity and/or responsiveness to allosteric effectors that modulate Hb–O2 affinity. This mode of genotypic specialization is considered typical...... of mammalian species that are high-altitude natives. Here we investigated genetically based differences in Hb–O2 affinity between highland and lowland populations of the deer mouse (Peromyscus maniculatus), a generalist species that has the broadest altitudinal distribution of any North American mammal....... The results of a combined genetic and proteomic analysis revealed that deer mice harbor a high level of Hb isoform diversity that is attributable to allelic polymorphism at two tandemly duplicated -globin genes and two tandemly duplicated β-globin genes. This high level of isoHb diversity translates...

  17. Separations chemistry

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Results of studies on the photochemistry of aqueous Pu solutions and the stability of iodine in liquid and gaseous CO 2 are reported. Progress is reported in studies on: the preparation of macroporous bodies filled with oxides and sulfides to be used as adsorbents; the beneficiation of photographic wastes; the anion exchange adsorption of transition elements from thiosulfate solutions; advanced filtration applications of energy significance; high-resolution separations; and, the examination of the separation agents, octylphenylphosphoric acid (OPPA) and trihexyl phosphate (THP)

  18. Isotopic separation

    International Nuclear Information System (INIS)

    Chen, C.L.

    1982-01-01

    A method is described for separating isotopes in which photo-excitation of selected isotope species is used together with the reaction of the excited species with postive ions of predetermined ionization energy, other excited species, or free electrons to produce ions or ion fragments of the selected species. Ions and electrons are produced by an electrical discharge, and separation is achieved through radial ambipolar diffusion, electrostatic techniques, or magnetohydrodynamic methods

  19. Genetics of susceptibility to leishmaniasis in mice: four novel loci and functional heterogeneity of gene effects

    Czech Academy of Sciences Publication Activity Database

    Havelková, Helena; Badalová, Jana; Svobodová, M.; Vojtíšková, Jarmila; Kurey, Irina; Vladimirov, Vladimir; Demant, P.; Lipoldová, Marie

    2006-01-01

    Roč. 7, č. 3 (2006), s. 220-233 ISSN 1466-4879 R&D Projects: GA ČR(CZ) GA310/03/1381; GA ČR(CZ) GD310/03/H147 Grant - others:HHMI(US) 55000323 Institutional research plan: CEZ:AV0Z50520514 Keywords : leishmania sis * host response * gene effect Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.533, year: 2006

  20. Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Desler, Claus; Boggild, Sisse

    2013-01-01

    Helicobacter pylori infection is an important factor for the development of atrophic gastritis and gastric carcinogenesis. However, the mechanisms explaining the effects of H. pylori infection are not fully elucidated. H. pylori infection is known to induce genetic instability in both nuclear and....... pylori infection, furthermore, the results demonstrate that multiple DNA repair activities are involved in protecting mtDNA during infection. (C) 2013 Elsevier Ireland Ltd. All rights reserved....

  1. Comparative epigenetic and genetic spatial structure of the perennial herb Helleborus foetidus: Isolation by environment, isolation by distance, and functional trait divergence.

    Science.gov (United States)

    Herrera, Carlos M; Medrano, Mónica; Bazaga, Pilar

    2017-08-16

    Epigenetic variation can play a role in local adaptation; thus, there should be associations among epigenetic variation, environmental variation, and functional trait variation across populations. This study examines these relationships in the perennial herb Helleborus foetidus (Ranunculaceae). Plants from 10 subpopulations were characterized genetically (AFLP, SSR markers), epigenetically (MSAP markers), and phenotypically (20 functional traits). Habitats were characterized using six environmental variables. Isolation-by-distance (IBD) and isolation-by-environment (IBE) patterns of genetic and epigenetic divergence were assessed, as was the comparative explanatory value of geographical and environmental distance as predictors of epigenetic, genetic, and functional differentiation. Subpopulations were differentiated genetically, epigenetically, and phenotypically. Genetic differentiation was best explained by geographical distance, while epigenetic differentiation was best explained by environmental distance. Divergence in functional traits was correlated with environmental and epigenetic distances, but not with geographical and genetic distances. Results are compatible with the hypothesis that epigenetic IBE and functional divergence reflected responses to environmental variation. Spatial analyses simultaneously considering epigenetic, genetic, phenotypic and environmental information provide a useful tool to evaluate the role of environmental features as drivers of natural epigenetic variation between populations. © 2017 Botanical Society of America.

  2. Unique battery with an active membrane separator having uniform physico-chemically functionalized ion channels and a method making the same

    Science.gov (United States)

    Gerald, II, Rex E.; Ruscic, Katarina J [Chicago, IL; Sears, Devin N [Spruce Grove, CA; Smith, Luis J [Natick, MA; Klingler, Robert J [Glenview, IL; Rathke, Jerome W [Homer Glen, IL

    2012-02-21

    The invention relates to a unique battery having an active, porous membrane and method of making the same. More specifically the invention relates to a sealed battery system having a porous, metal oxide membrane with uniform, physicochemically functionalized ion channels capable of adjustable ionic interaction. The physicochemically-active porous membrane purports dual functions: an electronic insulator (separator) and a unidirectional ion-transporter (electrolyte). The electrochemical cell membrane is activated for the transport of ions by contiguous ion coordination sites on the interior two-dimensional surfaces of the trans-membrane unidirectional pores. The membrane material is designed to have physicochemical interaction with ions. Control of the extent of the interactions between the ions and the interior pore walls of the membrane and other materials, chemicals, or structures contained within the pores provides adjustability of the ionic conductivity of the membrane.

  3. Catechol functionalized aminopropyl silica gel: synthesis, characterization and preconcentrative separation of uranium(VI) from thorium(IV)

    International Nuclear Information System (INIS)

    Metilda, P.; Mary Gladis, J.; Prasada Rao, T.P.

    2005-01-01

    A novel solid phase extractant is prepared by chemically immobilizing catechol with diazotized aminopropyl silica gel. The resulting catechol functionalized silica gel (CASG) was characterized by FTIR, and microanalysis and was used for selective enrichment of uranium(VI) from other inorganic ions. The optimum pH range for maximum sorption of uranium(VI) and thorium(IV) was found to be in the range 3.5-6.0. The above actinides were eluted with 10 cm 3 of 1.0 mol dm -3 HCl and determined by using an Arsenazo III spectrophotometric procedure. The calibration graph was rectilinear over the uranium(VI) concentration in the range 2-100 μg dm -3 with a relative standard deviation of 2.15% (for 25 μg of uranium(VI) present in 1.0 dm 3 of sample). The validation of the developed preconcentration procedure was carried out by analyzing marine sediment (MESS-3, NRC, Canada) and soil (IAEA soil-7, Austria) reference materials. The developed preconcentration method enables a simple instruments like a spectrophotometer gave comparable values of uranium(VI) to that of standard inductively coupled plasma-mass spectrometric values during the analysis of real soil and sediment samples. (orig.)

  4. Catechol functionalized aminopropyl silica gel: synthesis, characterization and preconcentrative separation of uranium(VI) from thorium(IV)

    Energy Technology Data Exchange (ETDEWEB)

    Metilda, P.; Mary Gladis, J.; Prasada Rao, T.P. [Regional Research Lab. (CSIR), Trivandrum (India)

    2005-07-01

    A novel solid phase extractant is prepared by chemically immobilizing catechol with diazotized aminopropyl silica gel. The resulting catechol functionalized silica gel (CASG) was characterized by FTIR, and microanalysis and was used for selective enrichment of uranium(VI) from other inorganic ions. The optimum pH range for maximum sorption of uranium(VI) and thorium(IV) was found to be in the range 3.5-6.0. The above actinides were eluted with 10 cm{sup 3} of 1.0 mol dm{sup -3} HCl and determined by using an Arsenazo III spectrophotometric procedure. The calibration graph was rectilinear over the uranium(VI) concentration in the range 2-100 {mu}g dm{sup -3} with a relative standard deviation of 2.15% (for 25 {mu}g of uranium(VI) present in 1.0 dm{sup 3} of sample). The validation of the developed preconcentration procedure was carried out by analyzing marine sediment (MESS-3, NRC, Canada) and soil (IAEA soil-7, Austria) reference materials. The developed preconcentration method enables a simple instruments like a spectrophotometer gave comparable values of uranium(VI) to that of standard inductively coupled plasma-mass spectrometric values during the analysis of real soil and sediment samples. (orig.)

  5. Two separate interfaces between the voltage sensor and pore are required for the function of voltage-dependent K(+ channels.

    Directory of Open Access Journals (Sweden)

    Seok-Yong Lee

    2009-03-01

    Full Text Available Voltage-dependent K(+ (Kv channels gate open in response to the membrane voltage. To further our understanding of how cell membrane voltage regulates the opening of a Kv channel, we have studied the protein interfaces that attach the voltage-sensor domains to the pore. In the crystal structure, three physical interfaces exist. Only two of these consist of amino acids that are co-evolved across the interface between voltage sensor and pore according to statistical coupling analysis of 360 Kv channel sequences. A first co-evolved interface is formed by the S4-S5 linkers (one from each of four voltage sensors, which form a cuff surrounding the S6-lined pore opening at the intracellular surface. The crystal structure and published mutational studies support the hypothesis that the S4-S5 linkers convert voltage-sensor motions directly into gate opening and closing. A second co-evolved interface forms a small contact surface between S1 of the voltage sensor and the pore helix near the extracellular surface. We demonstrate through mutagenesis that this interface is necessary for the function and/or structure of two different Kv channels. This second interface is well positioned to act as a second anchor point between the voltage sensor and the pore, thus allowing efficient transmission of conformational changes to the pore's gate.

  6. Synthesis and Characterization of a Novel Microporous Dihydroxyl-Functionalized Triptycene-Diamine-Based Polyimide for Natural Gas Membrane Separation.

    Science.gov (United States)

    Alaslai, Nasser; Ma, Xiaohua; Ghanem, Bader; Wang, Yingge; Alghunaimi, Fahd; Pinnau, Ingo

    2017-09-01

    An intrinsically microporous polyimide is synthesized in m-cresol by a one-pot high-temperature condensation reaction of 4,4'-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) and newly designed 2,6 (7)-dihydroxy-3,7(6)-diaminotriptycene (DAT1-OH). The 6FDA-DAT1-OH polyimide is thermally stable up to 440 °C, shows excellent solubility in polar solvents, and has moderately high Brunauer-Teller-Emmett (BET) surface area of 160 m 2 g -1 , as determined by nitrogen adsorption at -196 °C. Hydroxyl functionalization applied to the rigid 3D triptycene-based diamine building block results in a polyimide that exhibits moderate pure-gas CO 2 permeability of 70 Barrer combined with high CO 2 /CH 4 selectivity of 50. Mixed-gas permeation studies demonstrate excellent plasticization resistance of 6FDA-DAT1-OH with impressive performance as potential membrane material for natural gas sweetening with a CO 2 permeability of 50 Barrer and CO 2 /CH 4 selectivity of 40 at a typical natural gas well partial pressure of 10 atm. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Synthesis and Characterization of a Novel Microporous Dihydroxyl-Functionalized Triptycene-Diamine-Based Polyimide for Natural Gas Membrane Separation

    KAUST Repository

    Alaslai, Nasser Y.

    2017-07-10

    An intrinsically microporous polyimide is synthesized in m-cresol by a one-pot high-temperature condensation reaction of 4,4\\'-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) and newly designed 2,6 (7)-dihydroxy-3,7(6)-diaminotriptycene (DAT1-OH). The 6FDA-DAT1-OH polyimide is thermally stable up to 440 °C, shows excellent solubility in polar solvents, and has moderately high Brunauer-Teller-Emmett (BET) surface area of 160 m2 g-1 , as determined by nitrogen adsorption at -196 °C. Hydroxyl functionalization applied to the rigid 3D triptycene-based diamine building block results in a polyimide that exhibits moderate pure-gas CO2 permeability of 70 Barrer combined with high CO2 /CH4 selectivity of 50. Mixed-gas permeation studies demonstrate excellent plasticization resistance of 6FDA-DAT1-OH with impressive performance as potential membrane material for natural gas sweetening with a CO2 permeability of 50 Barrer and CO2 /CH4 selectivity of 40 at a typical natural gas well partial pressure of 10 atm.

  8. Separation optimization of aniline and seven 4-substituted anilines in high-submicellar liquid chromatography using empirical retention modeling and Derringer's desirability function.

    Science.gov (United States)

    Hadjmohammadi, Mohammad Reza; S J Nazari, S Saman

    2013-08-01

    The separation optimization of aniline and seven 4-substituted derivatives in high-submicellar LC was performed using an interpretive optimization strategy and Derringer's desirability function. Description of the retention of solutes was carried out through several hyperbolic and logarithmic retention models using the retention data of five mobile phases of SDS (0.06-0.12 M) and methanol (50-70% v/v) at pH 3. Among the investigated models, a logarithmic retention model logk=c0+c1φ+c2[S]+c12φ[S]+d12(φ[S])0.5 showed the best prediction capability and was used to predict the solute retention factors. A grid search program was used to calculate the retention times of each solute, based on the best retention model, for all combinations of SDS and methanol concentrations in the factor space. Two different chromatographic goals, analysis time and retention differences between adjacent peaks, were evaluated simultaneously using Derringer's desirability function for each mobile phase conditions in the grid search. Optimal mobile phase composition for separation of eight anilines was found to be 0.119 M SDS and 53% v/v methanol. Under these conditions, full resolutions with a reasonable analysis time (22 min) were obtained. At the optimal condition, a good agreement was observed between predicted and experimental values of the retention times. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Functional separation of oxidation–reduction reactions and electron transport in PtRu/ND and conductive additive hybrid electrocatalysts during methanol oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yan; Wang, Yanhui [State Key Laboratory of Metastable Materials Science and Technology, College of Materials Science and Engineering, Yanshan University, Qinhuangdao 066004 (China); Bian, Linyan [College of Physics and Chemistry, Henan Polytechnic University, Jiaozuo, Henan 454000 (China); Lu, Rui [State Key Laboratory of Metastable Materials Science and Technology, College of Materials Science and Engineering, Yanshan University, Qinhuangdao 066004 (China); Zang, Jianbing, E-mail: jbzang@ysu.edu.cn [State Key Laboratory of Metastable Materials Science and Technology, College of Materials Science and Engineering, Yanshan University, Qinhuangdao 066004 (China)

    2016-02-28

    Graphical abstract: - Highlights: • Functional separation of reactions and electron transport in PtRu/ND + AB (or CNT). • A conductive network was formed after the addition of AB or CNT. • PtRu/ND + AB (or CNT) exhibited enhanced activity and stability than PtRu/ND. - Abstract: Undoped nanodiamond (ND) supported PtRu (PtRu/ND) electrocatalyst for methanol oxidation reactions (MOR) in direct methanol fuel cells was prepared by a microwave-assisted polyol reduction method. Sp{sup 3}-bonded ND possesses high electrochemical stability but low conductivity, while sp{sup 2}-bonded carbon nanomaterials with high conductivity are prone to oxidation. Therefore, the functions of the supporting material were separated in this study. ND (sp{sup 3}), as a support, and AB or CNTs (sp{sup 2}), as a conductive additive, were combined to form the hybrid electrocatalysts PtRu/ND + AB and PtRu/ND + CNT for MOR. The morphology of the electrocatalysts was characterized by scanning electron microscopy and electrochemical measurements were performed using an electrochemical workstation. The results indicated that the electrocatalytic activity of PtRu/ND for MOR was improved with the addition of AB or CNTs as a conductive additive. Moreover, adding CNTs to PtRu/ND as a conductive additive showed better electrocatalytic activities than adding AB, which can be ascribed to the better electron-transfer ability of CNTs.

  10. Investigation and functional characterization of rare genetic variants in the adipose triglyceride lipase in a large healthy working population.

    Directory of Open Access Journals (Sweden)

    Stefan Coassin

    2010-12-01

    Full Text Available Recent studies demonstrated a strong influence of rare genetic variants on several lipid-related traits. However, their impact on free fatty acid (FFA plasma concentrations, as well as the role of rare variants in a general population, has not yet been thoroughly addressed. The adipose triglyceride lipase (ATGL is encoded by the PNPLA2 gene and catalyzes the rate-limiting step of lipolysis. It represents a prominent candidate gene affecting FFA concentrations. We therefore screened the full genomic region of ATGL for mutations in 1,473 randomly selected individuals from the SAPHIR (Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk Study using a combined Ecotilling and sequencing approach and functionally investigated all detected protein variants by in-vitro studies. We observed 55 novel mostly rare genetic variants in this general population sample. Biochemical evaluation of all non-synonymous variants demonstrated the presence of several mutated but mostly still functional ATGL alleles with largely varying residual lipolytic activity. About one-quarter (3 out of 13 of the investigated variants presented a marked decrease or total loss of catalytic function. Genetic association studies using both continuous and dichotomous approaches showed a shift towards lower plasma FFA concentrations for rare variant carriers and an accumulation of variants in the lower 10%-quantile of the FFA distribution. However, the generally rather small effects suggest either only a secondary role of rare ATGL variants on the FFA levels in the SAPHIR population or a recessive action of ATGL variants. In contrast to these rather small effects, we describe here also the first patient with "neutral lipid storage disease with myopathy" (NLSDM with a point mutation in the catalytic dyad, but otherwise intact protein.

  11. FY 1999 project on the development of new industry support type international standards. Standardization of evaluation method of the genetic testing system (Separate volume); 1999 nendo shinki sangyo shiengata kokusai hyojunka kaihatsu jigyo seika hokokusho. Idenshi kensa system no hyoka hoho no hyojunka (bessatsu)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    The separate volume included the proceedings of the re-consignee joint meeting on the standardization of evaluation method of the genetic testing system, the proceedings/data of the meeting of the committee of the standardization of evaluation method of the genetic testing system, etc. The data of the meeting are about a plan to execute the standardization of evaluation method of the genetic testing system, standardization of forms for reporting the results of the genetic test, a trial guideline for standardization of the genetic testing, standardization of evaluation method of the genetic testing system, etc. Moreover, the volume included 11 literature papers overseas on the above-mentioned themes, 'reports on the surveys in Europe and the U.S. on the standardization of evaluation method of the genetic testing system,' etc. (NEDO)

  12. FY 1999 project on the development of new industry support type international standards. Standardization of evaluation method of the genetic testing system (Separate volume); 1999 nendo shinki sangyo shiengata kokusai hyojunka kaihatsu jigyo seika hokokusho. Idenshi kensa system no hyoka hoho no hyojunka (bessatsu)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    The separate volume included the proceedings of the re-consignee joint meeting on the standardization of evaluation method of the genetic testing system, the proceedings/data of the meeting of the committee of the standardization of evaluation method of the genetic testing system, etc. The data of the meeting are about a plan to execute the standardization of evaluation method of the genetic testing system, standardization of forms for reporting the results of the genetic test, a trial guideline for standardization of the genetic testing, standardization of evaluation method of the genetic testing system, etc. Moreover, the volume included 11 literature papers overseas on the above-mentioned themes, 'reports on the surveys in Europe and the U.S. on the standardization of evaluation method of the genetic testing system,' etc. (NEDO)

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

    Directory of Open Access Journals (Sweden)

    Aaron R Wolen

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

  14. The role of zebrafish (Danio rerio in dissecting the genetics and neural circuits of executive function

    Directory of Open Access Journals (Sweden)

    Matthew O Parker

    2013-04-01

    Full Text Available Zebrafish have great potential to contribute to our understanding of behavioural genetics and thus to contribute to our understanding of the aetiology of psychiatric disease. However, progress is dependent upon the rate at which behavioural assays addressing complex behavioural phenotypes are designed, reported and validated. Here we critically review existing behavioural assays with particular focus on the use of adult zebrafish to explore executive processes and phenotypes associated with human psychiatric disease. We outline the case for using zebrafish as models to study impulse control and attention, discussing the validity of applying extant rodent assays to zebrafish and evidence for the conservation of relevant neural circuits.

  15. Designing mixed metal halide ammines for ammonia storage using density functional theory and genetic algorithms

    DEFF Research Database (Denmark)

    Jensen, Peter Bjerre; Lysgaard, Steen; Quaade, Ulrich J.

    2014-01-01

    electrolyte membrane fuel cells (PEMFC). We use genetic algorithms (GAs) to search for materials containing up to three different metals (alkaline-earth, 3d and 4d) and two different halides (Cl, Br and I) – almost 27000 combinations, and have identified novel mixtures, with significantly improved storage......Metal halide ammines have great potential as a future, high-density energy carrier in vehicles. So far known materials, e.g. Mg(NH3)6Cl2 and Sr(NH3)8Cl2, are not suitable for automotive, fuel cell applications, because the release of ammonia is a multi-step reaction, requiring too much heat...

  16. Functional, genetic and epigenetic aspects of base and nucleotide excision repair in colorectal carcinomas

    Czech Academy of Sciences Publication Activity Database

    Slyšková, Jana; Korenková, Vlasta; Collins, A. R.; Procházka, Pavel; Vodičková, Ludmila; Švec, Jiří; Lipská, L.; Levý, M.; Schneiderová, M.; Liška, V.; Holubec, L.; Kumar, R.; Souček, P.; Naccarati, Alessio; Vodička, Pavel

    2012-01-01

    Roč. 18, č. 21 (2012), s. 5878-5887 ISSN 1078-0432 R&D Projects: GA ČR GAP304/12/1585; GA ČR(CZ) GAP304/10/1286; GA MZd NT12025 Grant - others:UICC(XE) ICR/11/068/2011; EEA-research fund:(NO) B/CZ0046/40031 Institutional research plan: CEZ:AV0Z50390512 Institutional support: RVO:68378041 ; RVO:86652036 Keywords : DNA repair capacity * DNA repair gene expression * methylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.837, year: 2012

  17. Toxic stress history and hypothalamic-pituitary-adrenal axis function in a social stress task: Genetic and epigenetic factors.

    Science.gov (United States)

    Lapp, Hannah E; Ahmed, Sarah; Moore, Celia L; Hunter, Richard G

    2018-02-21

    Histories of early life stress (ELS) or social discrimination can reach levels of severity characterized as toxic to mental and physical health. Such toxic social stress during development has been linked to altered acute hypothalamic-pituitary-adrenal (HPA) response to social stress in adulthood. However, there are important individual differences in the size and direction of these effects. We explored developmental, genetic, epigenetic, and contextual sources of individual differences in the relationship between ELS, discrimination, and adult responses to acute social stress in a standard laboratory test. Additional measures included perceived status, social support, background activity of HPA axis, and genetic variants in aspects of the stress response system. Participants (n = 90) answered questions about historical and ongoing stress, provided a DNA sample to examine genetic polymorphisms and epigenetic marks, and underwent the Trier Social Stress Test (TSST) during which three saliva samples were collected to assess HPA function. Individuals who reported high levels of childhood adversity had a blunted salivary cortisol response to the TSST. Childhood adversity, discrimination experiences, and FKBP5 genotype were found to predict pretest cortisol levels. Following up on recent observations that the glucocorticoid receptor directly interacts with the mitochondrial genome, particularly the NADH dehydrogenase 6 (MT-ND6) gene, individuals who reported high childhood adversity were also found to have higher percent methylation across six CpG sites upstream of MT-ND6. These findings suggest multiple contributions across psychological, genetic, epigenetic, and social domains to vulnerability and resilience in hypothalamic-pituitary-adrenal axis regulation. Further study to examine how these multiple contributors affect developmental endpoints through integrated or independent pathways will be of use. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Genetic susceptibility to pancreatic cancer and its functional characterisation: The PANcreatic Disease ReseArch (PANDoRA) consortium

    Czech Academy of Sciences Publication Activity Database

    Campa, D.; Rizzato, C.; Capurso, G.; Giese, N.; Funel, N.; Greenhalf, W.; Souček, P.; Gazouli, M.; Pezzilli, R.; Pasquali, C.; Talar-Wojnarowska, R.; Cantore, M.; Andriulli, A.; Scarpa, A.; Jamroziak, K.; Delle Fave, G.; Costello, E.; Khaw, K. T.; Heller, A.; Key, T. K.; Theodoropoulos, G.; Malecka-Panas, E.; Mambrini, A.; Bambi, F.; Landi, S.; Pedrazzoli, S.; Bassi, C.; Pacetti, P.; Piepoli, A.; Tavano, F.; di Sebastiano, P.; Vodičková, Ludmila; Basso, D.; Plebani, M.; Fogar, P.; Buechler, M. W.; Bugert, P.; Vodička, Pavel; Boggi, U.; Neoptolemos, J. P.; Werner, J.; Canzian, F.

    2013-01-01

    Roč. 45, č. 2 (2013), s. 95-99 ISSN 1590-8658 Institutional support: RVO:68378041 Keywords : cancer susceptibility * genetic polymorphisms * genetic susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.889, year: 2013

  19. Reliable Prediction with Tuned Range-Separated Functionals of the Singlet-Triplet Gap in Organic Emitters for Thermally Activated Delayed Fluorescence (TADF)

    KAUST Repository

    Sun, Haitao

    2015-07-09

    The thermally activated delayed fluorescence (TADF) mechanism has recently attracted much interest in the field of organic light-emitting diodes (OLEDs). TADF relies on the presence of a very small energy gap between the lowest singlet and triplet excited states. Here, we demonstrate that time-dependent density functional theory (TD-DFT) in the Tamm-Dancoff Approximation can be very successful in the calculations of the lowest singlet and triplet excitation energies and the corresponding singlet-triplet gap when using nonempirically tuned range-separated functionals. Such functionals provide very good estimates in a series of 17 molecules used in TADF-based OLED devices, with mean absolute deviations of 0.15 eV for the vertical singlet excitation energies and 0.09 eV [0.07 eV] for the adiabatic [vertical] singlet-triplet energy gaps as well as low relative errors and high correlation coefficients compared to the corresponding experimental values. They significantly outperform conventional functionals, a feature which is rationalized on the basis of the amount of exact-exchange included and the delocalization error. The present work provides a reliable theoretical tool for the prediction and development of novel TADF-based materials with low singlet-triplet energetic splittings.

  20. Separation system

    International Nuclear Information System (INIS)

    Rubin, L.S.

    1986-01-01

    A disposal container is described for use in disposal of radioactive waste materials consisting of: top wall structure, bottom wall structure, and circumferential side wall structure interconnecting the top and bottom wall structures to define an enclosed container, separation structure in the container adjacent the inner surface of the side wall structure for allowing passage of liquid and retention of solids, inlet port structure in the top wall structure, discharge port structure at the periphery of the container in communication with the outer surface of the separation structure for receiving liquid that passes through the separation structure, first centrifugally actuated valve structure having a normal position closing the inlet port structure and a centrifugally actuated position opening the inlet port structure, second centrifugally actuated valve structure having a normal position closing the discharge port structure and a centrifugally actuated position opening the discharge port structure, and coupling structure integral with wall structure of the container for releasable engagement with centrifugal drive structure

  1. Separable algebras

    CERN Document Server

    Ford, Timothy J

    2017-01-01

    This book presents a comprehensive introduction to the theory of separable algebras over commutative rings. After a thorough introduction to the general theory, the fundamental roles played by separable algebras are explored. For example, Azumaya algebras, the henselization of local rings, and Galois theory are rigorously introduced and treated. Interwoven throughout these applications is the important notion of étale algebras. Essential connections are drawn between the theory of separable algebras and Morita theory, the theory of faithfully flat descent, cohomology, derivations, differentials, reflexive lattices, maximal orders, and class groups. The text is accessible to graduate students who have finished a first course in algebra, and it includes necessary foundational material, useful exercises, and many nontrivial examples.

  2. Fine-scale genetic mapping of a hybrid sterility factor between Drosophila simulans and D. mauritiana: the varied and elusive functions of "speciation genes"

    Directory of Open Access Journals (Sweden)

    Lemos Bernardo

    2010-12-01

    Full Text Available Abstract Background Hybrid male sterility (HMS is a usual outcome of hybridization between closely related animal species. It arises because interactions between alleles that are functional within one species may be disrupted in hybrids. The identification of genes leading to hybrid sterility is of great interest for understanding the evolutionary process of speciation. In the current work we used marked P-element insertions as dominant markers to efficiently locate one genetic factor causing a severe reduction in fertility in hybrid males of Drosophila simulans and D. mauritiana. Results Our mapping effort identified a region of 9 kb on chromosome 3, containing three complete and one partial coding sequences. Within this region, two annotated genes are suggested as candidates for the HMS factor, based on the comparative molecular characterization and public-source information. Gene Taf1 is partially contained in the region, but yet shows high polymorphism with four fixed non-synonymous substitutions between the two species. Its molecular functions involve sequence-specific DNA binding and transcription factor activity. Gene agt is a small, intronless gene, whose molecular function is annotated as methylated-DNA-protein-cysteine S-methyltransferase activity. High polymorphism and one fixed non-synonymous substitution suggest this is a fast evolving gene. The gene trees of both genes perfectly separate D. simulans and D. mauritiana into monophyletic groups. Analysis of gene expression using microarray revealed trends that were similar to those previously found in comparisons between whole-genome hybrids and parental species. Conclusions The identification following confirmation of the HMS candidate gene will add another case study leading to understanding the evolutionary process of hybrid incompatibility.

  3. Fine-scale genetic mapping of a hybrid sterility factor between Drosophila simulans and D. mauritiana: the varied and elusive functions of "speciation genes".

    Science.gov (United States)

    Araripe, Luciana O; Montenegro, Horácio; Lemos, Bernardo; Hartl, Daniel L

    2010-12-14

    Hybrid male sterility (HMS) is a usual outcome of hybridization between closely related animal species. It arises because interactions between alleles that are functional within one species may be disrupted in hybrids. The identification of genes leading to hybrid sterility is of great interest for understanding the evolutionary process of speciation. In the current work we used marked P-element insertions as dominant markers to efficiently locate one genetic factor causing a severe reduction in fertility in hybrid males of Drosophila simulans and D. mauritiana. Our mapping effort identified a region of 9 kb on chromosome 3, containing three complete and one partial coding sequences. Within this region, two annotated genes are suggested as candidates for the HMS factor, based on the comparative molecular characterization and public-source information. Gene Taf1 is partially contained in the region, but yet shows high polymorphism with four fixed non-synonymous substitutions between the two species. Its molecular functions involve sequence-specific DNA binding and transcription factor activity. Gene agt is a small, intronless gene, whose molecular function is annotated as methylated-DNA-protein-cysteine S-methyltransferase activity. High polymorphism and one fixed non-synonymous substitution suggest this is a fast evolving gene. The gene trees of both genes perfectly separate D. simulans and D. mauritiana into monophyletic groups. Analysis of gene expression using microarray revealed trends that were similar to those previously found in comparisons between whole-genome hybrids and parental species. The identification following confirmation of the HMS candidate gene will add another case study leading to understanding the evolutionary process of hybrid incompatibility.

  4. Isotope separation

    International Nuclear Information System (INIS)

    Bartlett, R.J.; Morrey, J.R.

    1978-01-01

    A method and apparatus is described for separating gas molecules containing one isotope of an element from gas molecules containing other isotopes of the same element in which all of the molecules of the gas are at the same electronic state in their ground state. Gas molecules in a gas stream containing one of the isotopes are selectively excited to a different electronic state while leaving the other gas molecules in their original ground state. Gas molecules containing one of the isotopes are then deflected from the other gas molecules in the stream and thus physically separated

  5. Converging evidence for the association of functional genetic variation in the serotonin receptor 2a gene with prefrontal function and olanzapine treatment.

    Science.gov (United States)

    Blasi, Giuseppe; De Virgilio, Caterina; Papazacharias, Apostolos; Taurisano, Paolo; Gelao, Barbara; Fazio, Leonardo; Ursini, Gianluca; Sinibaldi, Lorenzo; Andriola, Ileana; Masellis, Rita; Romano, Raffaella; Rampino, Antonio; Di Giorgio, Annabella; Lo Bianco, Luciana; Caforio, Grazia; Piva, Francesco; Popolizio, Teresa; Bellantuono, Cesario; Todarello, Orlando; Kleinman, Joel E; Gadaleta, Gemma; Weinberger, Daniel R; Bertolino, Alessandro

    2013-09-01

    Serotonin (5-hydroxytryptamine) receptor 2a (5-HT2AR) signaling is important for modulation of corticostriatal pathways and prefrontal activity during cognition. Furthermore, newer antipsychotic drugs target 5-HT2AR. A single-nucleotide polymorphism in the 5-HT2AR gene (HTR2A rs6314, C>T; OMIM 182135) has been weakly associated with differential 5-HT2AR signaling and with physiologic as well as behavioral effects. To use a hierarchical approach to determine the functional effects of this single-nucleotide polymorphism on 5-HT2AR messenger RNA and protein expression, on prefrontal phenotypes linked with genetic risk for schizophrenia, and on treatment with olanzapine. In silico predictions, in vitro, and case-control investigations. Academic and clinical facilities. The postmortem study included 112 brains from healthy individuals; the in vivo investigation included a total sample of 371 healthy individuals and patients with schizophrenia. EXPOSURES Patients received olanzapine monotherapy for 8 weeks. In silico predictions, messenger RNA, and protein expression in postmortem human prefrontal cortex and HeLa cells, functional magnetic resonance imaging prefrontal activity and behavior during working memory and attention in healthy individuals, and response to an 8-week trial of olanzapine treatment in patients with schizophrenia. Bioinformatic analysis predicted that rs6314 alters patterns of splicing, with possible effects on HTR2A expression. Moreover, the T allele was associated with reduced prefrontal messenger RNA expression in postmortem prefrontal cortex, with reduced protein expression in vitro, inefficient prefrontal blood oxygen level-dependent functional magnetic resonance imaging response during working memory and attentional control processing, and impaired working memory and attention behavior, as well as with attenuated improvement in negative symptoms after olanzapine treatment. Our results suggest that HTR2A rs6314 affects 5-HT2AR expression and

  6. Constitutional and functional genetics of human alcohol-related hepatocellular carcinoma.

    Science.gov (United States)

    Nahon, Pierre; Nault, Jean-Charles

    2017-11-01

    Exploration of the constitutional genetics of hepatocellular carcinoma (HCC) has identified numerous variants associated with a higher risk of liver cancer in alcoholic cirrhotic patients. Although Genome-Wide Association studies have not been carried out in the field of alcohol-related HCC, common single nucleotide polymorphisms conferring a small increase in the risk of liver cancer risk have been identified and shown to modulate ethanol metabolism, inflammation, oxidative stress, iron or lipid metabolism. Specific patterns of gene mutations including CTNNB1, TERT, ARID1A and SMARCA2 exist in alcohol-related HCC. Moreover, a specific mutational process observed at the nucleotide level by next generation sequencing has revealed cooperation between alcohol and tobacco in the development of HCC. Combining this genetic information with epidemiological and clinical data that might define specific HCC risk classes and refine surveillance strategies needs to be assessed in large prospective cohorts of patients with alcoholic cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Stinchcombe, John R; Kirkpatrick, Mark

    2012-11-01

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

  8. Genetic Diversity Underlying the Envelope Glycoproteins of Hepatitis C Virus: Structural and Functional Consequences and the Implications for Vaccine Design

    Directory of Open Access Journals (Sweden)

    Alexander W. Tarr

    2015-07-01

    Full Text Available In the 26 years since the discovery of Hepatitis C virus (HCV a major global research effort has illuminated many aspects of the viral life cycle, facilitating the development of targeted antivirals. Recently, effective direct-acting antiviral (DAA regimens with >90% cure rates have become available for treatment of chronic HCV infection in developed nations, representing a significant advance towards global eradication. However, the high cost of these treatments results in highly restricted access in developing nations, where the disease burden is greatest. Additionally, the largely asymptomatic nature of infection facilitates continued transmission in at risk groups and resource constrained settings due to limited surveillance. Consequently a prophylactic vaccine is much needed. The HCV envelope glycoproteins E1 and E2 are located on the surface of viral lipid envelope, facilitate viral entry and are the targets for host immunity, in addition to other functions. Unfortunately, the extreme global genetic and antigenic diversity exhibited by the HCV glycoproteins represents a significant obstacle to vaccine development. Here we review current knowledge of HCV envelope protein structure, integrating knowledge of genetic, antigenic and functional diversity to inform rational immunogen design.

  9. Characterization of macular structure and function in two Swedish families with genetically identified autosomal dominant retinitis pigmentosa

    Science.gov (United States)

    Abdulridha-Aboud, Wissam; Kjellström, Ulrika; Andréasson, Sten

    2016-01-01

    Purpose To study the phenotype in two families with genetically identified autosomal dominant retinitis pigmentosa (adRP) focusing on macular structure and function. Methods Clinical data were collected at the Department of Ophthalmology, Lund University, Sweden, for affected and unaffected family members from two pedigrees with adRP. Examinations included optical coherence tomography (OCT), full-field electroretinography (ffERG), and multifocal electroretinography (mfERG). Molecular genetic screening was performed for known mutations associated with adRP. Results The mode of inheritance was autosomal dominant in both families. The members of the family with a mutation in the PRPF31 (p.IVS6+1G>T) gene had clinical features characteristic of RP, with severely reduced retinal rod and cone function. The degree of deterioration correlated well with increasing age. The mfERG showed only centrally preserved macular function that correlated well with retinal thinning on OCT. The family with a mutation in the RHO (p.R135W) gene had an extreme intrafamilial variability of the phenotype, with more severe disease in the younger generations. OCT showed pathology, but the degree of morphological changes was not correlated with age or with the mfERG results. The mother, with a de novo mutation in the RHO (p.R135W) gene, had a normal ffERG, and her retinal degeneration was detected merely with the reduced mfERG. Conclusions These two families demonstrate the extreme inter- and intrafamilial variability in the clinical phenotype of adRP. This is the first Swedish report of the clinical phenotype associated with a mutation in the PRPF31 (p.IVS6+1G>T) gene. Our results indicate that methods for assessment of the central retinal structure and function may improve the detection and characterization of the RP phenotype. PMID:27212874

  10. Genetic predictor of working memory and prefrontal function in women with HIV.

    Science.gov (United States)

    Sundermann, Erin E; Bishop, Jeffrey R; Rubin, Leah H; Little, Deborah M; Meyer, Vanessa J; Martin, Eileen; Weber, Kathleen; Cohen, Mardge; Maki, Pauline M

    2015-02-01

    The Val158Met (rs4680) single-nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1-, and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared with HIV-uninfected women (p women performed significantly worse than HIV-uninfected controls across N-back conditions (p working memory deficits and altered prefrontal function in HIV-infected individuals.

  11. Incorporating Data Link Features into a Multi-Function Display to Support Self-Separation and Spacing Tasks for General Aviation Pilots

    Science.gov (United States)

    Adams, Catherine A.; Murdoch, Jennifer L.; Consiglio, Maria C.; WIlliams, Daniel M.

    2005-01-01

    One objective of the Small Aircraft Transportation System (SATS) Higher Volume Operations (HVO) project is to increase the capacity and utilization of small non-towered, non-radar equipped airports by transferring traffic management activities to an automated Airport Management Module (AMM) and separation responsibilities to general aviation (GA) pilots. Implementation of this concept required the development of a research Multi-Function Display (MFD) to support the interactive communications between pilots and the AMM. The interface also had to accommodate traffic awareness, self-separation, and spacing tasks through dynamic messaging and symbology for flight path conformance and conflict detection and alerting (CDA). The display served as the mechanism to support the examination of the viability of executing instrument operations designed for SATS designated airports. Results of simulation and flight experiments conducted at the National Aeronautics and Space Administration's (NASA) Langley Research Center indicate that the concept, as facilitated by the research MFD, did not increase pilots subjective workload levels or reduce their situation awareness (SA). Post-test usability assessments revealed that pilots preferred using the enhanced MFD to execute flight procedures, reporting improved SA over conventional instrument flight rules (IFR) procedures.

  12. Preparation of 1-(2-pyridylazo)-2-naphthol functionalized benzophenone/naphthalene and their uses in solid phase extractive preconcentration/separation of uranium(VI)

    International Nuclear Information System (INIS)

    Preetha, C.R.; Prasada Rao, T.

    2003-01-01

    The preparation of solid reagent 1-(2-pyridylazo)-2-naphthol functionalized benzophenone/naphthalene for preconcentration/separation of uranium(VI) is described. These reagents enriches uranium(VI) quantitatively from dilute aqueous solutions in the pH range 10.5-11.0. The solid mixture consisting of the enriched metal ion along with solid phase extractant were dissolved in 2 ml of acetone and uranium(VI) content was established spectrophotometrically by using Arsenazo III procedure. Calibration graphs were rectilinear over the uranium(VI) concentration in the range 0.002-0.1 μg cm -3 . Five replicate determinations of 40 μg of uranium present in 1 dm 3 of sample solution gave a mean absorbance of 0.185 with a relative standard deviation of 1.4%. The detection limit (corresponding to 3 times the standard deviation of the blank) and the enrichment factor were found to be 2 μg dm -3 and 500 respectively. Further the possible separation of uranium(VI) from several bivalent, trivalent and tetravalent elements was also established. In addition to validating the developed method by successfully analysing marine sediment reference material (MESS-3), uranium content was established in soil, river and marine sediment samples by the developed method and compared with standard inductively coupled plasma mass spectrometry (ICP-MS) values. (orig.)

  13. Functional and genetic deconstruction of the cellular origin in liver cancer

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Andersen, Jesper B; Thorgeirsson, Snorri S

    2015-01-01

    During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation......, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance...... of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution...

  14. Genetic and Functional Evidence Supports LPAR1 as a Susceptibility Gene for Hypertension.

    Science.gov (United States)

    Xu, Ke; Ma, Lu; Li, Yang; Wang, Fang; Zheng, Gu-Yan; Sun, Zhijun; Jiang, Feng; Chen, Yundai; Liu, Huirong; Dang, Aimin; Chen, Xi; Chun, Jerold; Tian, Xiao-Li

    2015-09-01

    Essential hypertension is a complex disease affected by genetic and environmental factors and serves as a major risk factor for cardiovascular diseases. Serum lysophosphatidic acid correlates with an elevated blood pressure in rats, and lysophosphatidic acid interacts with 6 subtypes of receptors. In this study, we assessed the genetic association of lysophosphatidic acid receptors with essential hypertension by genotyping 28 single-nucleotide polymorphisms from genes encoding for lysophosphatidic acid receptors, LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, and LPAR6 and their flanking sequences, in 3 Han Chinese cohorts consisting of 2630 patients and 3171 controls in total. We identified a single-nucleotide polymorphism, rs531003 in the 3'-flanking genomic region of LPAR1, associated with hypertension (the Bonferroni corrected P=1.09×10(-5), odds ratio [95% confidence interval]=1.23 [1.13-1.33]). The risk allele C of rs531003 is associated with the increased expression of LPAR1 and the susceptibility of hypertension, particularly in those with a shortage of sleep (P=4.73×10(-5), odds ratio [95% confidence interval]=1.75 [1.34-2.28]). We further demonstrated that blood pressure elevation caused by sleep deprivation and phenylephrine-induced vasoconstriction was both diminished in LPAR1-deficient mice. Together, we show that LPAR1 is a novel susceptibility gene for human essential hypertension and that stress, such as shortage of sleep, increases the susceptibility of patients with risk allele to essential hypertension. © 2015 American Heart Association, Inc.

  15. Ion distributions, exclusion coefficients, and separation factors of electrolytes in a charged cylindrical nanopore: a partially perturbative density functional theory study.

    Science.gov (United States)

    Peng, Bo; Yu, Yang-Xin

    2009-10-07

    The structural and thermodynamic properties for charge symmetric and asymmetric electrolytes as well as mixed electrolyte system inside a charged cylindrical nanopore are investigated using a partially perturbative density functional theory. The electrolytes are treated in the restricted primitive model and the internal surface of the cylindrical nanopore is considered to have a uniform charge density. The proposed theory is directly applicable to the arbitrary mixed electrolyte solution containing ions with the equal diameter and different valences. Large amount of simulation data for ion density distributions, separation factors, and exclusion coefficients are used to determine the range of validity of the partially perturbative density functional theory for monovalent and multivalent counterion systems. The proposed theory is found to be in good agreement with the simulations for both mono- and multivalent counterion systems. In contrast, the classical Poisson-Boltzmann equation only provides reasonable descriptions of monovalent counterion system at low bulk density, and is qualitatively and quantitatively wrong in the prediction for the multivalent counterion systems due to its neglect of the strong interionic correlations in these systems. The proposed density functional theory has also been applied to an electrolyte absorbed into a pore that is a model of the filter of a physiological calcium channel.

  16. Ionization Energies, Electron Affinities, and Polarization Energies of Organic Molecular Crystals: Quantitative Estimations from a Polarizable Continuum Model (PCM)–Tuned Range-Separated Density Functional Approach

    KAUST Repository

    Sun, Haitao

    2016-05-16

    We propose a new methodology for the first-principles description of the electronic properties relevant for charge transport in organic molecular crystals. This methodology, which is based on the combination of a non-empirical, optimally tuned range-separated hybrid functional with the polarizable continuum model, is applied to a series of eight representative molecular semiconductor crystals. We show that it provides ionization energies, electron affinities, and transport gaps in very good agreement with experimental values as well as with the results of many-body perturbation theory within the GW approximation at a fraction of the computational costs. Hence, this approach represents an easily applicable and computationally efficient tool to estimate the gas-to-crystal-phase shifts of the frontier-orbital quasiparticle energies in organic electronic materials.

  17. Dynamic density functional theory with hydrodynamic interactions: Theoretical development and application in the study of phase separation in gas-liquid systems

    International Nuclear Information System (INIS)

    Kikkinides, E. S.; Monson, P. A.

    2015-01-01

    Building on recent developments in dynamic density functional theory, we have developed a version of the theory that includes hydrodynamic interactions. This is achieved by combining the continuity and momentum equations eliminating velocity fields, so the resulting model equation contains only terms related to the fluid density and its time and spatial derivatives. The new model satisfies simultaneously continuity and momentum equations under the assumptions of constant dynamic or kinematic viscosity and small velocities and/or density gradients. We present applications of the theory to spinodal decomposition of subcritical temperatures for one-dimensional and three-dimensional density perturbations for both a van der Waals fluid and for a lattice gas model in mean field theory. In the latter case, the theory provides a hydrodynamic extension to the recently studied dynamic mean field theory. We find that the theory correctly describes the transition from diffusive phase separation at short times to hydrodynamic behaviour at long times

  18. Genetic Variants in KLOTHO Associate With Cognitive Function in the Oldest Old Group

    DEFF Research Database (Denmark)

    Mengel-From, Jonas; Sørensen, Mette; Nygaard, Marianne

    2016-01-01

    , for example, growth factor signaling. In the present study, 19 tagging gene variants in KL were studied in relation to 2 measures of cognitive function, a 5-item cognitive composite score and the Mini Mental State Examination, in 1,480 Danes 92-100 years of age. We found that heterozygotes for the previously......Decline in cognitive abilities is a major concern in aging individuals. A potential important factor for functioning of the central nervous system in late-life stages is the KLOTHO (KL) gene. KL is expressed in various organs including the brain and is involved in multiple biological processes...... reported KL-VS had poorer cognitive function than noncarriers. Two other variants positioned in the 5' end of the gene, rs398655 and rs562020, were associated with better cognitive function independently of KL-VS, and the common haplotype AG was associated with poorer cognition, consistently across two...

  19. Multifunctional G-rich and RRM-containing domains of TbRGG2 perform separate yet essential functions in trypanosome RNA editing.

    Science.gov (United States)

    Foda, Bardees M; Downey, Kurtis M; Fisk, John C; Read, Laurie K

    2012-09-01

    Efficient editing of Trypanosoma brucei mitochondrial RNAs involves the actions of multiple accessory factors. T. brucei RGG2 (TbRGG2) is an essential protein crucial for initiation and 3'-to-5' progression of editing. TbRGG2 comprises an N-terminal G-rich region containing GWG and RG repeats and a C-terminal RNA recognition motif (RRM)-containing domain. Here, we perform in vitro and in vivo separation-of-function studies to interrogate the mechanism of TbRGG2 action in RNA editing. TbRGG2 preferentially binds preedited mRNA in vitro with high affinity attributable to its G-rich region. RNA-annealing and -melting activities are separable, carried out primarily by the G-rich and RRM domains, respectively. In vivo, the G-rich domain partially complements TbRGG2 knockdown, but the RRM domain is also required. Notably, TbRGG2's RNA-melting activity is dispensable for RNA editing in vivo. Interactions between TbRGG2 and MRB1 complex proteins are mediated by both G-rich and RRM-containing domains, depending on the binding partner. Overall, our results are consistent with a model in which the high-affinity RNA binding and RNA-annealing activities of the G-rich domain are essential for RNA editing in vivo. The RRM domain may have key functions involving interactions with the MRB1 complex and/or regulation of the activities of the G-rich domain.

  20. Dual-Functional Superhydrophobic Textiles with Asymmetric Roll-Down/Pinned States for Water Droplet Transportation and Oil-Water Separation.

    Science.gov (United States)

    Su, Xiaojing; Li, Hongqiang; Lai, Xuejun; Zhang, Lin; Liao, Xiaofeng; Wang, Jing; Chen, Zhonghua; He, Jie; Zeng, Xingrong

    2018-01-31

    Superhydrophobic surfaces with tunable adhesion from lotus-leaf to rose-petal states have generated much attention for their potential applications in self-cleaning, anti-icing, oil-water separation, microdroplet transportation, and microfluidic devices. Herein we report a facile magnetic-field-manipulation strategy to fabricate dual-functional superhydrophobic textiles with asymmetric roll-down/pinned states on the two surfaces of the textile simultaneously. Upon exposure to a static magnetic field, fluoroalkylsilane-modified iron oxide (F-Fe 3 O 4 ) nanoparticles in polydimethylsiloxane (PDMS) moved along the magnetic field to construct discrepant hierarchical structures and roughnesses on the two sides of the textile. The positive surface (closer to the magnet, or P-surface) showed a water contact angle up to 165°, and the opposite surface (or O-surface) had a water contact angle of 152.5°. The P-surface where water droplets easily slid off with a sliding angle of 7.5° appeared in the "roll-down" state as Cassie mode, while the O-surface was in the "pinned" state as Wenzel mode, where water droplets firmly adhered even at vertical (90°) and inverted (180°) angles. The surface morphology and wetting mode were adjustable by varying the ratios of F-Fe 3 O 4 nanoparticles and PDMS. By taking advantage of the asymmetric adhesion behaviors, the as-fabricated superhydrophobic textile was successfully applied in no-loss microdroplet transportation and oil-water separation. Our method is simple and cost-effective. The fabricated textile has the characteristics of superhydrophobicity, magnetic responsiveness, excellent chemical stability, adjustable surface morphology, and controllable adhesion. Our findings conceivably stand out as a new tool to fabricate functional superhydrophobic materials with asymmetric surface properties for various potential applications.

  1. Functional variant in complement C3 gene promoter and genetic susceptibility to temporal lobe epilepsy and febrile seizures.

    Directory of Open Access Journals (Sweden)

    Sarah Jamali

    Full Text Available BACKGROUND: Human mesial temporal lobe epilepsies (MTLE represent the most frequent form of partial epilepsies and are frequently preceded by febrile seizures (FS in infancy and early childhood. Genetic associations of several complement genes including its central component C3 with disorders of the central nervous system, and the existence of C3 dysregulation in the epilepsies and in the MTLE particularly, make it the C3 gene a good candidate for human MTLE. METHODOLOGY/PRINCIPAL FINDINGS: A case-control association study of the C3 gene was performed in a first series of 122 patients with MTLE and 196 controls. Four haplotypes (HAP1 to 4 comprising GF100472, a newly discovered dinucleotide repeat polymorphism [(CA8 to (CA15] in the C3 promoter region showed significant association after Bonferroni correction, in the subgroup of MTLE patients having a personal history of FS (MTLE-FS+. Replication analysis in independent patients and controls confirmed that the rare HAP4 haplotype comprising the minimal length allele of GF100472 [(CA8], protected against MTLE-FS+. A fifth haplotype (HAP5 with medium-size (CA11 allele of GF100472 displayed four times higher frequency in controls than in the first cohort of MTLE-FS+ and showed a protective effect against FS through a high statistical significance in an independent population of 97 pure FS. Consistently, (CA11 allele by its own protected against pure FS in a second group of 148 FS patients. Reporter gene assays showed that GF100472 significantly influenced C3 promoter activity (the higher the number of repeats, the lower the transcriptional activity. Taken together, the consistent genetic data and the functional analysis presented here indicate that a newly-identified and functional polymorphism in the promoter of the complement C3 gene might participate in the genetic susceptibility to human MTLE with a history of FS, and to pure FS. CONCLUSIONS/SIGNIFICANCE: The present study provides important

  2. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin.

    Science.gov (United States)

    Clark, Ira E; Dodson, Mark W; Jiang, Changan; Cao, Joseph H; Huh, Jun R; Seol, Jae Hong; Yoo, Soon Ji; Hay, Bruce A; Guo, Ming

    2006-06-29

    Parkinson's disease is the second most common neurodegenerative disorder and is characterized by the degeneration of dopaminergic neurons in the substantia nigra. Mitochondrial dysfunction has been implicated as an important trigger for Parkinson's disease-like pathogenesis because exposure to environmental mitochondrial toxins leads to Parkinson's disease-like pathology. Recently, multiple genes mediating familial forms of Parkinson's disease have been identified, including PTEN-induced kinase 1 (PINK1; PARK6) and parkin (PARK2), which are also associated with sporadic forms of Parkinson's disease. PINK1 encodes a putative serine/threonine kinase with a mitochondrial targeting sequence. So far, no in vivo studies have been reported for pink1 in any model system. Here we show that removal of Drosophila PINK1 homologue (CG4523; hereafter called pink1) function results in male sterility, apoptotic muscle degeneration, defects in mitochondrial morphology and increased sensitivity to multiple stresses including oxidative stress. Pink1 localizes to mitochondria, and mitochondrial cristae are fragmented in pink1 mutants. Expression of human PINK1 in the Drosophila testes restores male fertility and normal mitochondrial morphology in a portion of pink1 mutants, demonstrating functional conservation between human and Drosophila Pink1. Loss of Drosophila parkin shows phenotypes similar to loss of pink1 function. Notably, overexpression of parkin rescues the male sterility and mitochondrial morphology defects of pink1 mutants, whereas double mutants removing both pink1 and parkin function show muscle phenotypes identical to those observed in either mutant alone. These observations suggest that pink1 and parkin function, at least in part, in the same pathway, with pink1 functioning upstream of parkin. The role of the pink1-parkin pathway in regulating mitochondrial function underscores the importance of mitochondrial dysfunction as a central mechanism of Parkinson's disease

  3. Association of genetic variation in cannabinoid mechanisms and gastric motor functions and satiation in overweight and obesity.

    Science.gov (United States)

    Vazquez-Roque, M I; Camilleri, M; Vella, A; Carlson, P; Laugen, J; Zinsmeister, A R

    2011-07-01

    The endocannabinoid system is associated with food intake. We hypothesized that genes regulating cannabinoids are associated with obesity. Genetic variations in fatty acid amide hydroxylase (FAAH) and cannabinoid receptor 1 (CNR1) are associated with satiation and gastric motor function. In 62 overweight or obese adults of European ancestry, single nucleotide polymorphisms of rs806378 (nearest gene CNR1) and rs324420 (nearest gene FAAH) were genotyped and the associations with gastric emptying (GE) of solids and liquids, gastric volume (GV), and satiation [maximum tolerated volume (MTV) and symptoms after Ensure(®) nutrient drink test] were explored using a dominant genetic model, with gender and BMI as covariates. rs806378 CC genotype was associated with reduced fasting GV (210.2±11.0mL for CC group compared to 242.5±11.3mL for CT/TT group, P=0.031) and a modest, non-significant association with GE of solids (P=0.17). rs324420 genotype was not associated with alterations in gastric motor functions; however, there was a difference in the Ensure(®) MTV (1174.6±37.2mL for CC group compared to 1395.0±123.1mL for CA/AA group, P=0.046) suggesting higher satiation with CC genotype. Our data suggest that CNR1 and FAAH are associated with altered gastric functions or satiation that may predispose to obesity. © 2011 Blackwell Publishing Ltd.

  4. Regulators Involved in Dickeya solani Virulence, Genetic Conservation and Functional Variability.

    Science.gov (United States)

    Potrykus, Marta; Golanowska, Małgorzata; Hugouvieux-Cotte-Pattat, Nicole; Lojkowska, Ewa

    2015-01-01

    Bacteria from the genus Dickeya (formerly Erwinia chrysanthemi) are plant pathogens causing severe diseases in many economically important crops. A majority of the strains responsible for potato disease in Europe belong to a newly identified Dickeya solani species. Although some ecological and epidemiological studies have been carried out, little is known about the regulation of D. solani virulence. The characterization of four D. solani strains indicates significant differences in their virulence on potato although they are genetically similar based on genomic fingerprinting profiles. A phenotypic examination included an analysis of virulence on potato, growth rate in culture, motility, Fe 3+ chelation, and pectate lyase, cellulase, protease, biosurfactant and blue pigment production. Mutants of four D. solani strains were constructed by inactivating the genes coding either for one of the main negative regulators of D. dadantii virulence (kdgR, pecS and pecT) or for the synthesis and perception of signaling molecules (expI and expR). Analysis of these mutants indicated that PecS, PecT and KdgR play a similar role in both species, repressing to different degrees the synthesis of virulence factors. The thermoregulator PecT seems to be a major regulator of D. solani virulence. This work also reveals the role of quorum sensing mediated by ExpI and ExpR in D. solani virulence on potato.

  5. The genetic basis for altered blood vessel function in disease: large artery stiffening

    Directory of Open Access Journals (Sweden)

    Alex Agrotis

    2005-12-01

    Full Text Available Alex AgrotisThe Cell Biology Laboratory, Baker Heart Research Institute, Melbourne, Victoria, AustraliaAbstract: The progressive stiffening of the large arteries in humans that occurs during aging constitutes a potential risk factor for increased cardiovascular morbidity and mortality, and is accompanied by an elevation in systolic blood pressure and pulse pressure. While the underlying basis for these changes remains to be fully elucidated, factors that are able to influence the structure and composition of the extracellular matrix and the way it interacts with arterial smooth muscle cells could profoundly affect the properties of the large arteries. Thus, while age and sex represent important factors contributing to large artery stiffening, the variation in growth-stimulating factors and those that modulate extracellular production and homeostasis are also being increasingly recognized to play a key role in the process. Therefore, elucidating the contribution that genetic variation makes to large artery stiffening could ultimately provide the basis for clinical strategies designed to regulate the process for therapeutic benefit.Keywords: arterial stiffness, genes, polymorphism, extracellular matrix proteins

  6. Cumulative role of rare and common putative functional genetic variants at NPAS3 in schizophrenia susceptibility.

    Science.gov (United States)

    González-Peñas, Javier; Arrojo, Manuel; Paz, Eduardo; Brenlla, Julio; Páramo, Mario; Costas, Javier

    2015-10-01

    Schizophrenia may be considered a human-specific disorder arisen as a maladaptive by-product of human-specific brain evolution. Therefore, genetic variants involved in susceptibility to schizophrenia may be identified among those genes related to acquisition of human-specific traits. NPAS3, a transcription factor involved in central nervous system development and neurogenesis, seems to be implicated in the evolution of human brain, as it is the human gene with most human-specific accelerated elements (HAEs), i.e., .mammalian conserved regulatory sequences with accelerated evolution in the lineage leading to humans after human-chimpanzee split. We hypothesize that any nucleotide variant at the NPAS3 HAEs may lead to altered susceptibility to schizophrenia. Twenty-one variants at these HAEs detected by the 1000 genomes Project, as well as five additional variants taken from psychiatric genome-wide association studies, were genotyped in 538 schizophrenic patients and 539 controls from Galicia. Analyses at the haplotype level or based on the cumulative role of the variants assuming different susceptibility models did not find any significant association in spite of enough power under several plausible scenarios regarding direction of effect and the specific role of rare and common variants. These results suggest that, contrary to our hypothesis, the special evolution of the NPAS3 HAEs in Homo relaxed the strong constraint on sequence that characterized these regions during mammalian evolution, allowing some sequence changes without any effect on schizophrenia risk. © 2015 Wiley Periodicals, Inc.

  7. Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study

    Science.gov (United States)

    Rowe, James B.; Winder-Rhodes, Sophie E.; Hampshire, Adam; Owen, Adrian M.; Breen, David P.; Duncan, Gordon W.; Khoo, Tien K.; Yarnall, Alison J.; Firbank, Michael J.; Chinnery, Patrick F.; Robbins, Trevor W.; O’Brien, John T.; Brooks, David J.; Burn, David J.; Barker, Roger A.

    2014-01-01

    Parkinson’s disease is associated with multiple cognitive impairments and increased risk of dementia, but the extent of these deficits varies widely among patients. The ICICLE-PD study was established to define the characteristics and prevalence of cognitive change soon after diagnosis, in a representative cohort of patients, using a multimodal approach. Specifically, we tested the ‘Dual Syndrome’ hypothesis for cognitive impairment in Parkinson’s disease, which distinguishes an executive syndrome (affecting the frontostriatal regions due to dopaminergic deficits) from a posterior cortical syndrome (affecting visuospatial, mnemonic and semantic functions related to Lewy body pathology and secondary cholinergic loss). An incident Parkinson’s disease cohort (n = 168, median 8 months from diagnosis to participation) and matched control group (n = 85) were recruited to a neuroimaging study at two sites in the UK. All participants underwent clinical, neuropsychological and functional magnetic resonance imaging assessments. The three neuroimaging tasks (Tower of London, Spatial Rotations and Memory Encoding Tasks) were designed to probe executive, visuospatial and memory encoding domains, respectively. Patients were also genotyped for three polymorphisms associated with cognitive change in Parkinson’s disease and related disorders: (i) rs4680 for COMT Val158Met polymorphism; (ii) rs9468 for MAPT H1 versus H2 haplotype; and (iii) rs429358 for APOE-ε2, 3, 4. We identified performance deficits in all three cognitive domains, which were associated with regionally specific changes in cortical activation. Task-specific regional activations in Parkinson’s disease were linked with genetic variation: the rs4680 polymorphism modulated the effect of levodopa therapy on planning-related activations in the frontoparietal network; the MAPT haplotype modulated parietal activations associated with spatial rotations; and APOE allelic variation influenced the magnitude of

  8. Conservation and Divergence in the Candida Species Biofilm Matrix Mannan-Glucan Complex Structure, Function, and Genetic Control.

    Science.gov (United States)

    Dominguez, Eddie; Zarnowski, Robert; Sanchez, Hiram; Covelli, Antonio S; Westler, William M; Azadi, Parastoo; Nett, Jeniel; Mitchell, Aaron P; Andes, David R

    2018-04-03

    Candida biofilms resist the effects of available antifungal therapies. Prior studies with Candida albicans biofilms show that an extracellular matrix mannan-glucan complex (MGCx) contributes to antifungal sequestration, leading to drug resistance. Here we implement biochemical, pharmacological, and genetic approaches to explore a similar mechanism of resistance for the three most common clinically encountered non- albicans Candida species (NAC). Our findings reveal that each Candida species biofilm synthesizes a mannan-glucan complex and that the antifungal-protective function of this complex is conserved. Structural similarities extended primarily to the polysaccharide backbone (α-1,6-mannan and β-1,6-glucan). Surprisingly, biochemical analysis uncovered stark differences in the branching side chains of the MGCx among the species. Consistent with the structural analysis, similarities in the genetic control of MGCx production for each Candida species also appeared limited to the synthesis of the polysaccharide backbone. Each species appears to employ a unique subset of modification enzymes for MGCx synthesis, likely accounting for the observed side chain diversity. Our results argue for the conservation of matrix function among Candida spp. While biogenesis is preserved at the level of the mannan-glucan complex backbone, divergence emerges for construction of branching side chains. Thus, the MGCx backbone represents an ideal drug target for effective pan- Candida species biofilm therapy. IMPORTANCE Candida species, the most common fungal pathogens, frequently grow as a biofilm. These adherent communities tolerate extremely high concentrations of antifungal agents, due in large part, to a protective extracellular matrix. The present studies define the structural, functional, and genetic similarities and differences in the biofilm matrix from the four most common Candida species. Each species synthesizes an extracellular mannan-glucan complex (MGCx) which

  9. Genetic manipulation in Sulfolobus islandicus and functional analysis of DNA repair genes

    DEFF Research Database (Denmark)

    Zhang, Changyi; Tian, Bin; Li, Suming

    2013-01-01

    Recently, a novel gene-deletion method was developed for the crenarchaeal model Sulfolobus islandicus, which is a suitable tool for addressing gene essentiality in depth. Using this technique, we have investigated functions of putative DNA repair genes by constructing deletion mutants and studying...

  10. Genetic Fuzzy Prediction of Mass Perception in Non-Functional 3D Shapes

    DEFF Research Database (Denmark)

    Achiche, Sofiane

    2010-01-01

    and it is argued that human attributes originate from three different levels of the brain: the visceral level; the behavioral level and the reflective level. This paper focuses upon the visceral level of reaction by automatically building a link between geometric properties of non-functional 3D shapes...

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

    Directory of Open Access Journals (Sweden)

    Tia DiTommaso

    2014-10-01

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

  12. Transcriptional and functional characterization of genetic elements involved in galacto-oligosaccharide utilization by Bifidobacterium breve UCC2003.

    Science.gov (United States)

    O'Connell Motherway, Mary; Kinsella, Michael; Fitzgerald, Gerald F; van Sinderen, Douwe

    2013-01-01

    Several prebiotics, such as inulin, fructo-oligosaccharides and galacto-oligosaccharides, are widely used commercially in foods and there is convincing evidence, in particular for galacto-oligosaccharides, that prebiotics can modulate the microbiota and promote bifidobacterial growth in the intestinal tract of infants and adults. In this study we describe the identification and functional characterization of the genetic loci responsible for the transport and metabolism of purified galacto-oligosaccharides (PGOS) by Bifidobacterium breve UCC2003. We further demonstrate that an extracellular endogalactanase specified by several B. breve strains, including B. breve UCC2003, is essential for partial degradation of PGOS components with a high degree of polymerization. These partially hydrolysed PGOS components are presumed to be transported into the bifidobacterial cell via various ABC transport systems and sugar permeases where they are further degraded to galactose and glucose monomers that feed into the bifid shunt. This work significantly advances our molecular understanding of bifidobacterial PGOS metabolism and its associated genetic machinery to utilize this prebiotic. © 2012 The Authors. Published by Society for Applied Microbiology and Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  13. Transcriptional and functional characterization of genetic elements involved in galacto-oligosaccharide utilization by Bifidobacterium breve UCC2003

    Science.gov (United States)

    O'Connell Motherway, Mary; Kinsella, Michael; Fitzgerald, Gerald F; Sinderen, Douwe

    2013-01-01

    Several prebiotics, such as inulin, fructo-oligosaccharides and galacto-oligosaccharides, are widely used commercially in foods and there is convincing evidence, in particular for galacto-oligosaccharides, that prebiotics can modulate the microbiota and promote bifidobacterial growth in the intestinal tract of infants and adults. In this study we describe the identification and functional characterization of the genetic loci responsible for the transport and metabolism of purified galacto-oligosaccharides (PGOS) by Bifidobacterium breve UCC2003. We further demonstrate that an extracellular endogalactanase specified by several B. breve strains, including B. breve UCC2003, is essential for partial degradation of PGOS components with a high degree of polymerization. These partially hydrolysed PGOS components are presumed to be transported into the bifidobacterial cell via various ABC transport systems and sugar permeases where they are further degraded to galactose and glucose monomers that feed into the bifid shunt. This work significantly advances our molecular understanding of bifidobacterial PGOS metabolism and its associated genetic machinery to utilize this prebiotic. PMID:23199239

  14. Charge Separation in Intermixed Polymer:PC70BM Photovoltaic Blends: Correlating Structural and Photophysical Length Scales as a Function of Blend Composition

    KAUST Repository

    Utzat, Hendrik; Dimitrov, Stoichko D.; Wheeler, Scot; Collado-Fregoso, Elisa; Tuladhar, Pabitra Shakya; Schroeder, Bob C.; McCulloch, Iain; Durrant, James R.

    2017-01-01

    A key challenge in achieving control over photocurrent generation by bulk-heterojunction organic solar cells is understanding how the morphology of the active layer impacts charge separation and in particular the separation dynamics within

  15. Fast evaluation of solid harmonic Gaussian integrals for local resolution-of-the-identity methods and range-separated hybrid functionals

    Science.gov (United States)

    Golze, Dorothea; Benedikter, Niels; Iannuzzi, Marcella; Wilhelm, Jan; Hutter, Jürg

    2017-01-01

    An integral scheme for the efficient evaluation of two-center integrals over contracted solid harmonic Gaussian functions is presented. Integral expressions are derived for local operators that depend on the position vector of one of the two Gaussian centers. These expressions are then used to derive the formula for three-index overlap integrals where two of the three Gaussians are located at the same center. The efficient evaluation of the latter is essential for local resolution-of-the-identity techniques that employ an overlap metric. We compare the performance of our integral scheme to the widely used Cartesian Gaussian-based method of Obara and Saika (OS). Non-local interaction potentials such as standard Coulomb, modified Coulomb, and Gaussian-type operators, which occur in range-separated hybrid functionals, are also included in the performance tests. The speed-up with respect to the OS scheme is up to three orders of magnitude for both integrals and their derivatives. In particular, our method is increasingly efficient for large angular momenta and highly contracted basis sets.

  16. Neuropsychological and social cognitive function in young people at genetic risk of bipolar disorder.

    Science.gov (United States)

    McCormack, C; Green, M J; Rowland, J E; Roberts, G; Frankland, A; Hadzi-Pavlovic, D; Joslyn, C; Lau, P; Wright, A; Levy, F; Lenroot, R K; Mitchell, P B

    2016-03-01

    Impairments in key neuropsychological domains (e.g. working memory, attention) and social cognitive deficits have been implicated as intermediate (endo) phenotypes for bipolar disorder (BD), and should therefore be evident in unaffected relatives. Neurocognitive and social cognitive ability was examined in 99 young people (age range 16-30 years) with a biological parent or sibling diagnosed with the disorder [thus deemed to be at risk (AR) of developing BD], compared with 78 healthy control (HC) subjects, and 52 people with a confirmed diagnosis of BD. Only verbal intelligence and affective response inhibition were significantly impaired in AR relative to HC participants; the BD participants showed significant deficits in attention tasks compared with HCs. Neither AR nor BD patients showed impairments in general intellectual ability, working memory, visuospatial or language ability, relative to HC participants. Analysis of BD-I and BD-II cases separately revealed deficits in attention and immediate memory in BD-I patients (only), relative to HCs. Only the BD (but not AR) participants showed impaired emotion recognition, relative to HCs. Selective cognitive deficits in the capacity to inhibit negative affective information, and general verbal ability may be intermediate markers of risk for BD; however, the extent and severity of impairment in this sample was less pronounced than has been reported in previous studies of older family members and BD cases. These findings highlight distinctions in the cognitive profiles of AR and BD participants, and provide limited support for progressive cognitive decline in association with illness development in BD.

  17. Gas separating

    Science.gov (United States)

    Gollan, A.

    1988-03-29

    Feed gas is directed tangentially along the non-skin surface of gas separation membrane modules comprising a cylindrical bundle of parallel contiguous hollow fibers supported to allow feed gas to flow from an inlet at one end of a cylindrical housing through the bores of the bundled fibers to an outlet at the other end while a component of the feed gas permeates through the fibers, each having the skin side on the outside, through a permeate outlet in the cylindrical casing. 3 figs.

  18. Isotope separation

    International Nuclear Information System (INIS)

    Rosevear, A.; Sims, H.E.

    1985-01-01

    sup(195m)Au for medical usage is separated from sup(195m)Hg in a solution containing ions of sup(195m)Hg by contacting the solution with an adsorbing agent to adsorb 195 Hgsup(H) thereon, followed by selective elution of sup(195m)Au generated by radioactive decay of the sup(195m)Hg. The adsorbing agent comprises a composite material in the form of an inert porous inorganic substrate (e.g. Kieselguhr),the pores of which are occupied by a hydrogel of a polysaccharide (e.g. agarose) carrying terminal thiol groups for binding Hgsup(H) ions. (author)

  19. Functional, genetic and chemical characterization of biosurfactants produced by plant growth-promoting Pseudomonas putida 267.

    Science.gov (United States)

    Kruijt, Marco; Tran, Ha; Raaijmakers, Jos M

    2009-08-01

    Plant growth-promoting Pseudomonas putida strain 267, originally isolated from the rhizosphere of black pepper, produces biosurfactants that cause lysis of zoospores of the oomycete pathogen Phytophthora capsici. The biosurfactants were characterized, the biosynthesis gene(s) partially identified, and their role in control of Phytophthora damping-off of cucumber evaluated. The biosurfactants were shown to lyse zoospores of Phy. capsici and inhibit growth of the fungal pathogens Botrytis cinerea and Rhizoctonia solani. In vitro assays further showed that the biosurfactants of strain 267 are essential in swarming motility and biofilm formation. In spite of the zoosporicidal activity, the biosurfactants did not play a significant role in control of Phytophthora damping-off of cucumber, since both wild type strain 267 and its biosurfactant-deficient mutant were equally effective, and addition of the biosurfactants did not provide control. Genetic characterization revealed that surfactant biosynthesis in strain 267 is governed by homologues of PsoA and PsoB, two nonribosomal peptide synthetases involved in production of the cyclic lipopeptides (CLPs) putisolvin I and II. The structural relatedness of the biosurfactants of strain 267 to putisolvins I and II was supported by LC-MS and MS-MS analyses. The biosurfactants produced by Ps. putida 267 were identified as putisolvin-like CLPs; they are essential in swarming motility and biofilm formation, and have zoosporicidal and antifungal activities. Strain 267 provides excellent biocontrol activity against Phytophthora damping-off of cucumber, but the lipopeptide surfactants are not involved in disease suppression. Pseudomonas putida 267 suppresses Phy. capsici damping-off of cucumber and provides a potential supplementary strategy to control this economically important oomycete pathogen. The putisolvin-like biosurfactants exhibit zoosporicidal and antifungal activities, yet they do not contribute to biocontrol of Phy

  20. Contribution of genetic polymorphisms on functional status at very old age

    DEFF Research Database (Denmark)

    Dato, S.; Sørensen, Mette; Lagani, V.

    2014-01-01

    Preservation of functional ability is a well-recognized marker of longevity. At a molecular level, a major determinant of the physiological decline occurring with aging is the imbalance between production and accumulation of oxidative damage to macromolecules, together with a decreased efficiency...... observations reported in the same cohort. Overall, our work supports the evidence that genes belonging to the pro-anti-oxidant pathway are able to modulate physical and cognitive performance after the ninth decade of life, finally influencing extreme survival.......Preservation of functional ability is a well-recognized marker of longevity. At a molecular level, a major determinant of the physiological decline occurring with aging is the imbalance between production and accumulation of oxidative damage to macromolecules, together with a decreased efficiency...

  1. Functional properties and synaptic integration of genetically labelled dopaminergic neurons in intrastriatal grafts

    DEFF Research Database (Denmark)

    Sørensen, Andreas Toft; Thompson, Lachlan; Kirik, Deniz

    2005-01-01

    in the dopamine-depleted striatum than of those in the intact striatum. Our findings define specific electrophysiological characteristics of transplanted fetal dopaminergic neurons, and we provide the first direct evidence of functional synaptic integration of these neurons into host neural circuitries......., the electrophysiological properties grafted cells need to have in order to induce substantial functional recovery are poorly defined. It has not been possible to prospectively identify and record from dopaminergic neurons in fetal transplants. Here we used transgenic mice expressing green fluorescent protein under control...... of the rat tyrosine hydroxylase promoter for whole-cell patch-clamp recordings of endogenous and grafted dopaminergic neurons. We transplanted ventral mesencephalic tissue from E12.5 transgenic mice into striatum of neonatal rats with or without lesions of the nigrostriatal dopamine system. The transplanted...

  2. Pancreatic non-functioning neuroendocrine tumor: a new entity genetically related to Lynch syndrome

    OpenAIRE

    Serracant Barrera, Anna; Serra Pla, Sheila; Blázquez Maña, Carmen María; Salas, Rubén Carrera; García Monforte, Neus; Bejarano González, Natalia; Romaguera Monzonis, Andreu; Andreu Navarro, Francisco Javier; Bella Cueto, Maria Rosa; Borobia, Francisco G.

    2017-01-01

    Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary syndromes. An association between Lynch syndrome (LS) and P-NETs has been suggested, however it has not been confirmed to date. We describe the first case associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20 years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC), infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non-functioning P-NETs and seboma...

  3. Genetic and Diagnostic Biomarker Development in ASD Toddlers Using Resting State Functional MRI

    Science.gov (United States)

    2016-09-01

    temporal lobe and partial volumes of sulcal CSF at this early stage in brain development when white matter tracts are not yet robust enough to be...ages 3 to 4 years. 2. KEYWORDS Autism spectrum disorder, ASD, early brain development , intrinsic functional brain networks, fMRI, infants, toddlers...TD in bottom left triangle and ASD in top right triangle. Figure 4. Within-network ( left ) and Between-Network (Out-of-Network) ( right ) connectivity

  4. Assessing the Effectiveness of Functional Genetic Screens for the Identification of Bioactive Metabolites

    Directory of Open Access Journals (Sweden)

    Staffan Kjelleberg

    2012-12-01

    Full Text Available A common limitation for the identification of novel activities from functional (meta genomic screens is the low number of active clones detected relative to the number of clones screened. Here we demonstrate that constructing libraries with strains known to produce bioactives can greatly enhance the screening efficiency, by increasing the “hit-rate” and unmasking multiple activities from the same bacterial source.

  5. Multi-objective optimization strategy based on desirability functions used for electrophoratic separation and quantification of rosiglitazone and glimepiride in plasma and formulations.

    Science.gov (United States)

    Hefnawy, Mohamed M; Sultan, Maha A; Al-Johar, Haya I; Kassem, Mohamed G; Aboul-Enein, Hassan Y

    2012-01-01

    Multiple response simultaneous optimization employing Derringer's desirability function was used for the development of a capillary electrophoresis method for the simultaneous determination of rosiglitazone (RSG) and glimepiride (GLM) in plasma and formulations. Twenty experiments, taking the two resolutions, the analysis time, and the capillary current as the responses with three important factors--buffer morality, volte and column temperature--were used to design mathematical models. The experimental responses were fitted into a second order polynomial and the six responses were simultaneously optimized to predict the optimum conditions for the effective separation of the studied compounds. The separation was carried out by using capillary zone electrophoresis (CZE) with a silica capillary column and diode array detector at 210 nm. The optimum assay conditions were 52 mmol l⁻¹ phosphate buffer, pH 7, and voltage of 22 kV at 29 °C. The method showed good agreement between the experimental data and predictive value throughout the studied parameter space. The assay limit of detection was 0.02 µg ml⁻¹ and the effective working range at relative standard deviation (RSD) of ≤ 5% was 0.05-16 µg ml⁻¹ (r = 0.999) for both drugs. Analytical recoveries of the studied drugs from spiked plasma were 97.2-101.9 ± 0.31-3.0%. The precision of the assay was satisfactory; RSD was 1.07 and 1.14 for intra- and inter-assay precision, respectively. The proposed method has a great value in routine analysis of RSG and GLM for its therapeutic monitoring and pharmacokinetic studies. Copyright © 2011 John Wiley & Sons, Ltd.

  6. Separation of BSA through FAU-type zeolite ceramic composite membrane formed on tubular ceramic support: Optimization of process parameters by hybrid response surface methodology and biobjective genetic algorithm.

    Science.gov (United States)

    Vinoth Kumar, R; Ganesh Moorthy, I; Pugazhenthi, G

    2017-08-09

    In this study, Faujasite (FAU) zeolite was coated on low-cost tubular ceramic support as a separating layer through hydrothermal route. The mixture of silicate and aluminate solutions was used to create a zeolitic separation layer on the support. The prepared zeolite ceramic composite membrane was characterized using X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), particle size distribution (PSD), field emission scanning electron microscopy (FESEM), and zeta potential measurements. The porosity of ceramic support (53%) was reduced by the deposition of FAU (43%) zeolite layer. The pore size and water permeability of the membrane were evaluated as 0.179 µm and 1.62 × 10 -7  m 3 /m 2  s kPa, respectively, which are lower than that of the support (pore size of 0.309 µm and water permeability of 5.93 × 10 -7  m 3 /m 2  s kPa). The permeate flux and rejection potential of the prepared membrane were evaluated by microfiltration of bovine serum albumin (BSA). To study the influences of three independent variables such as operating pressure (68.94-275.79 kPa), concentration of BSA (100-500 ppm), and solution pH (2-4) on permeate flux and percentage of rejection, the response surface methodology (RSM) was used. The predicted models for permeate flux and rejection were further subjected to biobjective genetic algorithm (GA). The hybrid RSM-GA approach resulted in a maximum permeate flux of 2.66 × 10 -5  m 3 /m 2  s and BSA rejection of 88.02%, at which the optimum conditions were attained as 100 ppm BSA concentration, 2 pH solution, and 275.79 kPa applied pressure. In addition, the separation efficiency was compared with other membranes applied for BSA separation to know the potential of the fabricated FAU zeolite ceramic composite membrane.

  7. A functional genetic variant in fragile-site gene FATS modulates the risk of breast cancer in triparous women

    International Nuclear Information System (INIS)

    Song, Fangfang; Zhang, Jun; Qiu, Li; Zhao, Yawen; Xing, Pan; Lu, Jiachun; Chen, Kexin; Li, Zheng

    2015-01-01

    The fragile-site associated tumor suppressor (FATS, formerly known as C10orf90), a regulator of p53-p21 pathway has been involved in the onset of breast cancer. Recent data support the idea that the crosstalk between FATS and p53 may be of physiological importance for reproduction during evolution. The aim of the current study was to test the hypothesis that FATS genetic polymorphism can influence the risk of breast cancer. We conducted population-based studies in two independent cohorts comprising 1 532 cases and 1 573 controls in Tianjin of North China, and 804 cases and 835 controls in Guangzhou of South China, coupled with functional validation methods, to investigate the role of FATS genetic variant in breast cancer risk. We identified a functional variant rs11245007 (905C > T, 262D/N) in fragile-site gene FATS that modulates p53 activation. FATS-262 N exhibited stronger E3 activity to polyubiquitinate p53 than did FATS-262D, leading to the stronger transcriptional activity of p53 and more pronounced stabilization of p53 protein and its activation in response to DNA damage. Case–control studies found that CT or TT genotype was significantly associated with a protective effect on breast cancer risk in women with parity ≥ 3, which was not affected by family history. Our findings suggest the role of FATS-p53 signaling cascade in suppressing pregnancy-related carcinogenesis and potential application of FATS genotyping in breast cancer prevention. The online version of this article (doi:10.1186/s12885-015-1570-9) contains supplementary material, which is available to authorized users

  8. Genetic Ablation of Soluble TNF Does Not Affect Lesion Size and Functional Recovery after Moderate Spinal Cord Injury in Mice

    Directory of Open Access Journals (Sweden)

    Ditte Gry Ellman

    2016-01-01

    Full Text Available Traumatic spinal cord injury (SCI is followed by an instant increase in expression of the microglial-derived proinflammatory cytokine tumor necrosis factor (TNF within the lesioned cord. TNF exists both as membrane-anchored TNF (mTNF and as cleaved soluble TNF (solTNF. We previously demonstrated that epidural administration of a dominant-negative inhibitor of solTNF, XPro1595, to the contused spinal cord resulted in changes in Iba1 protein expression in microglia/macrophages, decreased lesion volume, and improved locomotor function. Here, we extend our studies using mice expressing mTNF, but no solTNF (mTNFΔ/Δ, to study the effect of genetic ablation of solTNF on SCI. We demonstrate that TNF levels were significantly decreased within the lesioned spinal cord 3 days after SCI in mTNFΔ/Δ mice compared to littermates. This decrease did, however, not translate into significant changes in other pro- and anti-inflammatory cytokines (IL-10, IL-1β, IL-6, IL-5, IL-2, CXCL1, CCL2, or CCL5, despite a tendency towards increased IL-10 and decreased IL-1β, TNFR1, and TNFR2 levels in mTNFΔ/Δ mice. In addition, microglial and leukocyte infiltration, activation state (Iba1, CD11b, CD11c, CD45, and MHCII, lesion size, and functional outcome after moderate SCI were comparable between genotypes. Collectively, our data demonstrate that genetic ablation of solTNF does not significantly modulate postlesion outcome after SCI.

  9. Aminotryptophan-containing barstar: structure--function tradeoff in protein design and engineering with an expanded genetic code.

    Science.gov (United States)

    Rubini, Marina; Lepthien, Sandra; Golbik, Ralph; Budisa, Nediljko

    2006-07-01

    The indole ring of the canonical amino acid tryptophan (Trp) possesses distinguished features, such as sterical bulk, hydrophobicity and the nitrogen atom which is capable of acting as a hydrogen bond donor. The introduction of an amino group into the indole moiety of Trp yields the structural analogs 4-aminotryptophan ((4-NH(2))Trp) and 5-aminotryptophan ((5-NH(2))Trp). Their hydrophobicity and spectral properties are substantially different when compared to those of Trp. They resemble the purine bases of DNA and share their capacity for pH-sensitive intramolecular charge transfer. The Trp --> aminotryptophan substitution in proteins during ribosomal translation is expected to result in related protein variants that acquire these features. These expectations have been fulfilled by incorporating (4-NH(2))Trp and (5-NH(2))Trp into barstar, an intracellular inhibitor of the ribonuclease barnase from Bacillus amyloliquefaciens. The crystal structure of (4-NH(2))Trp-barstar is similar to that of the parent protein, whereas its spectral and thermodynamic behavior is found to be remarkably different. The T(m) value of (4-NH(2))Trp- and (5-NH(2))Trp-barstar is lowered by about 20 degrees Celsius, and they exhibit a strongly reduced unfolding cooperativity and substantial loss of free energy in folding. Furthermore, folding kinetic study of (4-NH(2))Trp-barstar revealed that the denatured state is even preferred over native one. The combination of structural and thermodynamic analyses clearly shows how structures of substituted barstar display a typical structure-function tradeoff: the acquirement of unique pH-sensitive charge transfer as a novel function is achieved at the expense of protein stability. These findings provide a new insight into the evolution of the amino acid repertoire of the universal genetic code and highlight possible problems regarding protein engineering and design by using an expanded genetic code.

  10. Association of functional MMP-2 gene variant with intracranial aneurysms: case-control genetic association study and meta-analysis.

    Science.gov (United States)

    Alg, Varinder S; Ke, Xiayi; Grieve, Joan; Bonner, Stephen; Walsh, Daniel C; Bulters, Diederik; Kitchen, Neil; Houlden, Henry; Werring, David J

    2018-01-15

    Abnormalities in Matrix Metalloproteinase (MMP) genes, which are important in extracellular matrix (ECM) maintenance and therefore arterial wall integrity are a plausible underlying mechanism of intracranial aneurysm (IA) formation, growth and subsequent rupture. We investigated whether the rs243865 C > T SNP (single nucleotide polymorphism) within the MMP-2 gene (which influences gene transcription) is associated with IA compared to matched controls. We conducted a case-control genetic association study, adjusted for known IA risk factors (smoking and hypertension), in a UK Caucasian population of 1409 patients with intracranial aneurysms (IA), and 1290 matched controls, to determine the association of the rs243865 C > T functional MMP-2 gene SNP with IA (overall, and classified as ruptured and unruptured). We also undertook a meta-analysis of two previous studies examining this SNP. The rs243865 T allele was associated with IA presence in univariate (OR 1.18 [95% CI 1.04-1.33], p = .01) and in multi-variable analyses adjusted for smoking and hypertension status (OR 1.16 [95% CI 1.01-1.35], p = .042). Subgroup analysis demonstrated an association of the rs243865 SNP with ruptured IA (OR 1.18 [95% CI 1.03-1.34] p = .017), but, not unruptured IA (OR 1.17 [95% CI 0.97-1.42], p = .11). Our study demonstrated an association between the functional MMP-2 rs243865 variant and IAs. Our findings suggest a genetic role for altered extracellular matrix integrity in the pathogenesis of IA development and rupture.

  11. Characterization of genetically engineered mouse hepatoma cells with inducible liver functions by overexpression of liver-enriched transcription factors.

    Science.gov (United States)

    Yamamoto, Hideaki; Tonello, Jane Marie; Sambuichi, Takanori; Kawabe, Yoshinori; Ito, Akira; Kamihira, Masamichi

    2018-01-01

    New cell sources for the research and therapy of organ failure could significantly alleviate the shortage of donor livers that are available to patients who suffer from liver disease. Liver carcinoma derived cells, or hepatoma cells, are the ideal cells for developing bioartificial liver systems. Such cancerous liver cells are easy to prepare in large quantities and can be maintained over long periods under standard culture conditions, unlike primary hepatocytes. However, hepatoma cells possess only a fraction of the functions of primary hepatocytes. In a previous study, by transducing cells with liver-enriched transcription factors that could be inducibly overexpressed-hepatocyte nuclear factor (HNF)1α, HNF1β, HNF3β [FOXA2], HNF4α, HNF6, CCAAT/enhancer binding protein (C/EBP)α, C/EBPβ and C/EBPγ-we created mouse hepatoma cells with high liver-specific gene expression called the Hepa/8F5 cell line. In the present study, we performed functional and genetic analyses to characterize the Hepa/8F5 cell line. Further, in three-dimensional cultures, the function of these cells improved significantly compared to parental cells. Ultimately, these cells might become a new resource that can be used in basic and applied hepatic research. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  12. Fyn kinase genetic ablation causes structural abnormalities in mature retina and defective Müller cell function.

    Science.gov (United States)

    Chavez-Solano, Marbella; Ibarra-Sanchez, Alfredo; Treviño, Mario; Gonzalez-Espinosa, Claudia; Lamas, Monica

    2016-04-01

    Fyn kinase is widely expressed in neuronal and glial cells of the brain, where it exerts multiple functional roles that affect fundamental physiological processes. The aim of our study was to investigate the, so far unknown, functional role of Fyn in the retina. We report that Fyn is expressed, in vivo, in a subpopulation of Müller glia. We used a mouse model of Fyn genetic ablation and Müller-enriched primary cultures to demonstrate that Fyn deficiency induces morphological alterations in the mature retina, a reduction in the thickness of the outer and inner nuclear layers and alterations in postnatal Müller cell physiology. These include shortening of Müller cell processes, a decrease in cell proliferation, inactivation of the Akt signal transduction pathway, a reduced number of focal adhesions points and decreased adhesion of these cells to the ECM. As abnormalities in Müller cell physiology have been previously associated to a compromised retinal function we evaluated behavioral responses to visual stimulation. Our results associate Fyn deficiency with impaired visual optokinetic responses under scotopic and photopic light conditions. Our study reveals novel roles for Fyn kinase in retinal morphology and Müller cell physiology and suggests that Fyn is required for optimal visual processing. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Source-based neurofeedback methods using EEG recordings: training altered brain activity in a functional brain source derived from blind source separation

    Science.gov (United States)

    White, David J.; Congedo, Marco; Ciorciari, Joseph

    2014-01-01

    A developing literature explores the use of neurofeedback in the treatment of a range of clinical conditions, particularly ADHD and epilepsy, whilst neurofeedback also provides an experimental tool for studying the functional significance of endogenous brain activity. A critical component of any neurofeedback method is the underlying physiological signal which forms the basis for the feedback. While the past decade has seen the emergence of fMRI-based protocols training spatially confined BOLD activity, traditional neurofeedback has utilized a small number of electrode sites on the scalp. As scalp EEG at a given electrode site reflects a linear mixture of activity from multiple brain sources and artifacts, efforts to successfully acquire some level of control over the signal may be confounded by these extraneous sources. Further, in the event of successful training, these traditional neurofeedback methods are likely influencing multiple brain regions and processes. The present work describes the use of source-based signal processing methods in EEG neurofeedback. The feasibility and potential utility of such methods were explored in an experiment training increased theta oscillatory activity in a source derived from Blind Source Separation (BSS) of EEG data obtained during completion of a complex cognitive task (spatial navigation). Learned increases in theta activity were observed in two of the four participants to complete 20 sessions of neurofeedback targeting this individually defined functional brain source. Source-based EEG neurofeedback methods using BSS may offer important advantages over traditional neurofeedback, by targeting the desired physiological signal in a more functionally and spatially specific manner. Having provided preliminary evidence of the feasibility of these methods, future work may study a range of clinically and experimentally relevant brain processes where individual brain sources may be targeted by source-based EEG neurofeedback. PMID

  14. Functional characterization of an alkaline exonuclease and single strand annealing protein from the SXT genetic element of Vibrio cholerae

    Directory of Open Access Journals (Sweden)

    Huang Jian-dong

    2011-04-01

    Full Text Available Abstract Background SXT is an integrating conjugative element (ICE originally isolated from Vibrio cholerae, the bacterial pathogen that causes cholera. It houses multiple antibiotic and heavy metal resistance genes on its ca. 100 kb circular double stranded DNA (dsDNA genome, and functions as an effective vehicle for the horizontal transfer of resistance genes within susceptible bacterial populations. Here, we characterize the activities of an alkaline exonuclease (S066, SXT-Exo and single strand annealing protein (S065, SXT-Bet encoded on the SXT genetic element, which share significant sequence homology with Exo and Bet from bacteriophage lambda, respectively. Results SXT-Exo has the ability to degrade both linear dsDNA and single stranded DNA (ssDNA molecules, but has no detectable endonuclease or nicking activities. Adopting a stable trimeric arrangement in solution, the exonuclease activities of SXT-Exo are optimal at pH 8.2 and essentially require Mn2+ or Mg2+ ions. Similar to lambda-Exo, SXT-Exo hydrolyzes dsDNA with 5'- to 3'-polarity in a highly processive manner, and digests DNA substrates with 5'-phosphorylated termini significantly more effectively than those lacking 5'-phosphate groups. Notably, the dsDNA exonuclease activities of both SXT-Exo and lambda-Exo are stimulated by the addition of lambda-Bet, SXT-Bet or a single strand DNA binding protein encoded on the SXT genetic element (S064, SXT-Ssb. When co-expressed in E. coli cells, SXT-Bet and SXT-Exo mediate homologous recombination between a PCR-generated dsDNA fragment and the chromosome, analogous to RecET and lambda-Bet/Exo. Conclusions The activities of the SXT-Exo protein are consistent with it having the ability to resect the ends of linearized dsDNA molecules, forming partially ssDNA substrates for the partnering SXT-Bet single strand annealing protein. As such, SXT-Exo and SXT-Bet may function together to repair or process SXT genetic elements within infected V

  15. Cancer resistance of SR/CR mice in the genetic knockout backgrounds of leukocyte effector mechanisms: determinations for functional requirements.

    Science.gov (United States)

    Sanders, Anne M; Stehle, John R; Blanks, Michael J; Riedlinger, Gregory; Kim-Shapiro, Jung W; Monjazeb, Arta M; Adams, Jonathan M; Willingham, Mark C; Cui, Zheng

    2010-03-31

    Spontaneous Regression/Complete Resistant (SR/CR) mice are a colony of cancer-resistant mice that can detect and rapidly destroy malignant cells with innate cellular immunity, predominately mediated by granulocytes. Our previous studies suggest that several effector mechanisms, such as perforin, granzymes, or complements, may be involved in the killing of cancer cells. However, none of these effector mechanisms is known as critical for granulocytes. Additionally, it is unclear which effector mechanisms are required for the cancer killing activity of specific leukocyte populations and the survival of SR/CR mice against the challenges of lethal cancer cells. We hypothesized that if any of these effector mechanisms was required for the resistance to cancer cells, its functional knockout in SR/CR mice should render them sensitive to cancer challenges. This was tested by cross breeding SR/CR mice into the individual genetic knockout backgrounds of perforin (Prf-/-), superoxide (Cybb-/), or inducible nitric oxide (Nos2-/). SR/CR mice were bred into individual Prf-/-, Cybb-/-, or Nos2-/- genetic backgrounds and then challenged with sarcoma 180 (S180). Their overall survival was compared to controls. The cancer killing efficiency of purified populations of macrophages and neutrophils from these immunodeficient mice was also examined. When these genetically engineered mice were challenged with cancer cells, the knockout backgrounds of Prf-/-, Cybb-/-, or Nos2-/- did not completely abolish the SR/CR cancer resistant phenotype. However, the Nos2-/- background did appear to weaken the resistance. Incidentally, it was also observed that the male mice in these immunocompromised backgrounds tended to be less cancer-resistant than SR/CR controls. Despite the previously known roles of perforin, superoxide or nitric oxide in the effector mechanisms of innate immune responses, these effector mechanisms were not required for cancer-resistance in SR/CR mice. The resistance was

  16. Partially separable t matrix

    International Nuclear Information System (INIS)

    Sasakawa, T.; Okuno, H.; Ishikawa, S.; Sawada, T.

    1982-01-01

    The off-shell t matrix is expressed as a sum of one nonseparable and one separable terms so that it is useful for applications to more-than-two body problems. All poles are involved in this one separable term. Both the nonseparable and the separable terms of the kernel G 0 t are regular at the origin. The nonseparable term of this kernel vanishes at large distances, while the separable term behaves asymptotically as the spherical Hankel function. These properties make our expression free from defects inherent in the Jost or the K-matrix expressions, and many applications are anticipated. As the application, a compact expression of the many-level formula is presented. Also the application is suggested to the breakup threebody problem based on the Faddeev equation. It is demonstrated that the breakup amplitude is expressed in a simple and physically interesting form and we can calculate it in coordinate space

  17. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Wenna Gleyce Araújo do Nascimento

    2014-06-01

    Full Text Available Interleukin 18 (IL-18 is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL 18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL 18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL 18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518 and -137C/G (rs187238 variant alleles in the 18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL 18 variants and creatinine clearance (p > 0.05. Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45-4.55, p = 0.0014. Finally, we found that IL 18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients.

  18. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients.

    Science.gov (United States)

    do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; de Oliveira Crispim, Janaina Cristiana

    2014-06-01

    Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45-4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients.

  19. Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism

    International Nuclear Information System (INIS)

    Umezu, K.; Sugawara, N.; Chen, C.; Haber, J.E.; Kolodner, R.D.

    1998-01-01

    Replication protein A (RPA) is a single-stranded DNA-binding protein identified as an essential factor for SV40 DNA replication in vitro. To understand the in vivo functions of RPA, we mutagenized the Saccharomyces cerevisiae RFA1 gene and identified 19 ultraviolet light (UV) irradiation- and methyl methane sulfonate (MMS)-sensitive mutants and 5 temperature-sensitive mutants. The UV- and MMS-sensitive mutants showed up to 10 4 to 10 5 times increased sensitivity to these agents. Some of the UV- and MMSsensitive mutants were killed by an HO-induced double-strand break atMAT. Physical analysis of recombination in one UV- and MMS-sensitive rfa1 mutant demonstrated that it was defective for mating type switching and single-strand annealing recombination. Two temperature-sensitive mutants were characterized in detail, and at the restrictive temperature were found to have an arrest phenotype and DNA content indicative of incomplete DNA replication. DNA sequence analysis indicated that most of the mutations altered amino acids that were conserved between yeast, human, and Xenopus RPA1. Taken together, we conclude that RPA1 has multiple roles in vivo and functions in DNA replication, repair, and recombination, like the single-stranded DNA-binding proteins of bacteria and phages. (author)

  20. Simultaneous genome-wide inference of physical,