WorldWideScience

Sample records for gene gain loss

  1. Distinct Trajectories of Massive Recent Gene Gains and Losses in Populations of a Microbial Eukaryotic Pathogen.

    Science.gov (United States)

    Hartmann, Fanny E; Croll, Daniel

    2017-11-01

    Differences in gene content are a significant source of variability within species and have an impact on phenotypic traits. However, little is known about the mechanisms responsible for the most recent gene gains and losses. We screened the genomes of 123 worldwide isolates of the major pathogen of wheat Zymoseptoria tritici for robust evidence of gene copy number variation. Based on orthology relationships in three closely related fungi, we identified 599 gene gains and 1,024 gene losses that have not yet reached fixation within the focal species. Our analyses of gene gains and losses segregating in populations showed that gene copy number variation arose preferentially in subtelomeres and in proximity to transposable elements. Recently lost genes were enriched in virulence factors and secondary metabolite gene clusters. In contrast, recently gained genes encoded mostly secreted protein lacking a conserved domain. We analyzed the frequency spectrum at loci segregating a gene presence-absence polymorphism in four worldwide populations. Recent gene losses showed a significant excess in low-frequency variants compared with genome-wide single nucleotide polymorphism, which is indicative of strong negative selection against gene losses. Recent gene gains were either under weak negative selection or neutral. We found evidence for strong divergent selection among populations at individual loci segregating a gene presence-absence polymorphism. Hence, gene gains and losses likely contributed to local adaptation. Our study shows that microbial eukaryotes harbor extensive copy number variation within populations and that functional differences among recently gained and lost genes led to distinct evolutionary trajectories. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  2. Frequent gain and loss of introns in fungal cytochrome b genes.

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    Liang-Fen Yin

    Full Text Available In this study, all available cytochrome b (Cyt b genes from the GOBASE database were compiled and the evolutionary dynamics of the Cyt b gene introns was assessed. Cyt b gene introns were frequently present in the fungal kingdom and some lower plants, but generally absent or rare in Chromista, Protozoa, and Animalia. Fungal Cyt b introns were found at 35 positions in Cyt b genes and the number of introns varied at individual positions from a single representative to 32 different introns at position 131, showing a wide and patchy distribution. Many homologous introns were present at the same position in distantly related species but absent in closely related species, suggesting that introns of the Cyt b genes were frequently lost. On the other hand, highly similar intron sequences were observed in some distantly related species rather than in closely related species, suggesting that these introns were gained independently, likely through lateral transfers. The intron loss-and-gain events could be mediated by transpositions that might have occurred between nuclear and mitochondria. Southern hybridization analysis confirmed that some introns contained repetitive sequences and might be transposable elements. An intron gain in Botryotinia fuckeliana prevented the development of QoI fungicide resistance, suggesting that intron loss-and-gain events were not necessarily beneficial to their host organisms.

  3. Phylogenetic distribution of intron positions in alpha-amylase genes of bilateria suggests numerous gains and losses.

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    Jean-Luc Da Lage

    Full Text Available Most eukaryotes have at least some genes interrupted by introns. While it is well accepted that introns were already present at moderate density in the last eukaryote common ancestor, the conspicuous diversity of intron density among genomes suggests a complex evolutionary history, with marked differences between phyla. The question of the rates of intron gains and loss in the course of evolution and factors influencing them remains controversial. We have investigated a single gene family, alpha-amylase, in 55 species covering a variety of animal phyla. Comparison of intron positions across phyla suggests a complex history, with a likely ancestral intronless gene undergoing frequent intron loss and gain, leading to extant intron/exon structures that are highly variable, even among species from the same phylum. Because introns are known to play no regulatory role in this gene and there is no alternative splicing, the structural differences may be interpreted more easily: intron positions, sizes, losses or gains may be more likely related to factors linked to splicing mechanisms and requirements, and to recognition of introns and exons, or to more extrinsic factors, such as life cycle and population size. We have shown that intron losses outnumbered gains in recent periods, but that "resets" of intron positions occurred at the origin of several phyla, including vertebrates. Rates of gain and loss appear to be positively correlated. No phase preference was found. We also found evidence for parallel gains and for intron sliding. Presence of introns at given positions was correlated to a strong protosplice consensus sequence AG/G, which was much weaker in the absence of intron. In contrast, recent intron insertions were not associated with a specific sequence. In animal Amy genes, population size and generation time seem to have played only minor roles in shaping gene structures.

  4. Reconstruction of Ancestral Genomes in Presence of Gene Gain and Loss.

    Science.gov (United States)

    Avdeyev, Pavel; Jiang, Shuai; Aganezov, Sergey; Hu, Fei; Alekseyev, Max A

    2016-03-01

    Since most dramatic genomic changes are caused by genome rearrangements as well as gene duplications and gain/loss events, it becomes crucial to understand their mechanisms and reconstruct ancestral genomes of the given genomes. This problem was shown to be NP-complete even in the "simplest" case of three genomes, thus calling for heuristic rather than exact algorithmic solutions. At the same time, a larger number of input genomes may actually simplify the problem in practice as it was earlier illustrated with MGRA, a state-of-the-art software tool for reconstruction of ancestral genomes of multiple genomes. One of the key obstacles for MGRA and other similar tools is presence of breakpoint reuses when the same breakpoint region is broken by several different genome rearrangements in the course of evolution. Furthermore, such tools are often limited to genomes composed of the same genes with each gene present in a single copy in every genome. This limitation makes these tools inapplicable for many biological datasets and degrades the resolution of ancestral reconstructions in diverse datasets. We address these deficiencies by extending the MGRA algorithm to genomes with unequal gene contents. The developed next-generation tool MGRA2 can handle gene gain/loss events and shares the ability of MGRA to reconstruct ancestral genomes uniquely in the case of limited breakpoint reuse. Furthermore, MGRA2 employs a number of novel heuristics to cope with higher breakpoint reuse and process datasets inaccessible for MGRA. In practical experiments, MGRA2 shows superior performance for simulated and real genomes as compared to other ancestral genome reconstruction tools.

  5. Models of gene gain and gene loss for probabilistic reconstruction of gene content in the last universal common ancestor of life.

    Science.gov (United States)

    Kannan, Lavanya; Li, Hua; Rubinstein, Boris; Mushegian, Arcady

    2013-12-19

    The problem of probabilistic inference of gene content in the last common ancestor of several extant species with completely sequenced genomes is: for each gene that is conserved in all or some of the genomes, assign the probability that its ancestral gene was present in the genome of their last common ancestor. We have developed a family of models of gene gain and gene loss in evolution, and applied the maximum-likelihood approach that uses phylogenetic tree of prokaryotes and the record of orthologous relationships between their genes to infer the gene content of LUCA, the Last Universal Common Ancestor of all currently living cellular organisms. The crucial parameter, the ratio of gene losses and gene gains, was estimated from the data and was higher in models that take account of the number of in-paralogs in genomes than in models that treat gene presences and absences as a binary trait. While the numbers of genes that are placed confidently into LUCA are similar in the ML methods and in previously published methods that use various parsimony-based approaches, the identities of genes themselves are different. Most of the models of either kind treat the genes found in many existing genomes in a similar way, assigning to them high probabilities of being ancestral ("high ancestrality"). The ML models are more likely than others to assign high ancestrality to the genes that are relatively rare in the present-day genomes.

  6. Models of gene gain and gene loss for probabilistic reconstruction of gene content in the last universal common ancestor of life

    OpenAIRE

    Kannan, Lavanya; Li, Hua; Rubinstein, Boris; Mushegian, Arcady

    2013-01-01

    Background The problem of probabilistic inference of gene content in the last common ancestor of several extant species with completely sequenced genomes is: for each gene that is conserved in all or some of the genomes, assign the probability that its ancestral gene was present in the genome of their last common ancestor. Results We have developed a family of models of gene gain and gene loss in evolution, and applied the maximum-likelihood approach that uses phylogenetic tree of prokaryotes...

  7. Models of gene gain and gene loss for probabilistic reconstruction of gene content in the last universal common ancestor of life

    Science.gov (United States)

    2013-01-01

    Background The problem of probabilistic inference of gene content in the last common ancestor of several extant species with completely sequenced genomes is: for each gene that is conserved in all or some of the genomes, assign the probability that its ancestral gene was present in the genome of their last common ancestor. Results We have developed a family of models of gene gain and gene loss in evolution, and applied the maximum-likelihood approach that uses phylogenetic tree of prokaryotes and the record of orthologous relationships between their genes to infer the gene content of LUCA, the Last Universal Common Ancestor of all currently living cellular organisms. The crucial parameter, the ratio of gene losses and gene gains, was estimated from the data and was higher in models that take account of the number of in-paralogs in genomes than in models that treat gene presences and absences as a binary trait. Conclusion While the numbers of genes that are placed confidently into LUCA are similar in the ML methods and in previously published methods that use various parsimony-based approaches, the identities of genes themselves are different. Most of the models of either kind treat the genes found in many existing genomes in a similar way, assigning to them high probabilities of being ancestral (“high ancestrality”). The ML models are more likely than others to assign high ancestrality to the genes that are relatively rare in the present-day genomes. Reviewers This article was reviewed by Martijn A Huynen, Toni Gabaldón and Fyodor Kondrashov. PMID:24354654

  8. Patterns and Implications of Gene Gain and Loss in the Evolution of Prochlorococcus

    Energy Technology Data Exchange (ETDEWEB)

    Lapidus, Alla; Kettler, Gregory C.; Martiny, Adam C.; Huang, Katherine; Zucker, Jeremy; Coleman, Maureen L.; Rodrigue, Sebastien; Chen, Feng; Lapidus, Alla; Ferriera, Steven; Johnson, Justin; Steglich, Claudia; Church, George M.; Richardson, Paul; Chisholm, Sallie W.

    2007-07-30

    Prochlorococcus is a marine cyanobacterium that numerically dominates the mid-latitude oceans and is the smallest known oxygenic phototroph. Numerous isolatesfrom diverse areas of the world's oceans have been studied and shown to be physiologically and genetically distinct. All isolates described thus far can be assigned to either a tightly clustered high-light (HL)-adapted clade, or a more divergent low-light (LL)-adapted group. The 16S rRNA sequences of the entire Prochlorococcus group differ by at most 3percent, and the four initially published genomes revealed patterns of genetic differentiation that help explain physiological differences among the isolates. Here we describe the genomes of eight newly sequenced isolates and combine them with the first four genomes for a comprehensive analysis of the core (shared by all isolates) and flexible genes of the Prochlorococcus group, and the patterns of loss and gain of the flexible genes over the course of evolution. There are 1,273 genes that represent the core shared by all 12 genomes. They are apparently sufficient, according to metabolic reconstruction, to encode a functional cell. We describe a phylogeny for all 12 isolates by subjecting their complete proteomes to three different phylogenetic analyses. For each non-core gene, we used a maximum parsimony method to estimate which ancestor likely first acquired or lost each gene. Many of the genetic differences among isolates, especially for genes involved in outer membrane synthesis and nutrient transport, are found within the same clade. Nevertheless, we identified some genes defining HL and LL ecotypes, and clades within these broad ecotypes, helping to demonstrate the basis of HL and LL adaptations in Prochlorococcus. Furthermore, our estimates of gene gain events allow us to identify highly variable genomic islands that are not apparent through simple pairwise comparisons. These results emphasize the functional roles, especially those connected to outer

  9. Patterns and implications of gene gain and loss in the evolution of Prochlorococcus.

    Directory of Open Access Journals (Sweden)

    Gregory C Kettler

    2007-12-01

    Full Text Available Prochlorococcus is a marine cyanobacterium that numerically dominates the mid-latitude oceans and is the smallest known oxygenic phototroph. Numerous isolates from diverse areas of the world's oceans have been studied and shown to be physiologically and genetically distinct. All isolates described thus far can be assigned to either a tightly clustered high-light (HL-adapted clade, or a more divergent low-light (LL-adapted group. The 16S rRNA sequences of the entire Prochlorococcus group differ by at most 3%, and the four initially published genomes revealed patterns of genetic differentiation that help explain physiological differences among the isolates. Here we describe the genomes of eight newly sequenced isolates and combine them with the first four genomes for a comprehensive analysis of the core (shared by all isolates and flexible genes of the Prochlorococcus group, and the patterns of loss and gain of the flexible genes over the course of evolution. There are 1,273 genes that represent the core shared by all 12 genomes. They are apparently sufficient, according to metabolic reconstruction, to encode a functional cell. We describe a phylogeny for all 12 isolates by subjecting their complete proteomes to three different phylogenetic analyses. For each non-core gene, we used a maximum parsimony method to estimate which ancestor likely first acquired or lost each gene. Many of the genetic differences among isolates, especially for genes involved in outer membrane synthesis and nutrient transport, are found within the same clade. Nevertheless, we identified some genes defining HL and LL ecotypes, and clades within these broad ecotypes, helping to demonstrate the basis of HL and LL adaptations in Prochlorococcus. Furthermore, our estimates of gene gain events allow us to identify highly variable genomic islands that are not apparent through simple pairwise comparisons. These results emphasize the functional roles, especially those connected to

  10. Estimating gene gain and loss rates in the presence of error in genome assembly and annotation using CAFE 3.

    Science.gov (United States)

    Han, Mira V; Thomas, Gregg W C; Lugo-Martinez, Jose; Hahn, Matthew W

    2013-08-01

    Current sequencing methods produce large amounts of data, but genome assemblies constructed from these data are often fragmented and incomplete. Incomplete and error-filled assemblies result in many annotation errors, especially in the number of genes present in a genome. This means that methods attempting to estimate rates of gene duplication and loss often will be misled by such errors and that rates of gene family evolution will be consistently overestimated. Here, we present a method that takes these errors into account, allowing one to accurately infer rates of gene gain and loss among genomes even with low assembly and annotation quality. The method is implemented in the newest version of the software package CAFE, along with several other novel features. We demonstrate the accuracy of the method with extensive simulations and reanalyze several previously published data sets. Our results show that errors in genome annotation do lead to higher inferred rates of gene gain and loss but that CAFE 3 sufficiently accounts for these errors to provide accurate estimates of important evolutionary parameters.

  11. Loss restlessness and gain calmness: durable effects of losses and gains on choice switching.

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    Yechiam, Eldad; Zahavi, Gal; Arditi, Eli

    2015-08-01

    While the traditional conceptualization of the effect of losses focuses on bias in the subjective weight of losses compared with respective gains, some accounts suggest more global task-related effects of losses. Based on a recent attentional theory, we predicted a positive after-effect of losses on choice switching in later tasks. In two experimental studies, we found increased choice switching rates in tasks with losses compared to tasks with no losses. Additionally, this heightened shifting behavior was maintained in subsequent tasks that do not include losses, a phenomenon we refer to as "loss restlessness." Conversely, gains were found to have an opposite "calming" effect on choice switching. Surprisingly, the loss restlessness phenomenon was observed following an all-losses payoff regime but not after a task with symmetric mixed gains and losses. This suggests that the unresolved mental account following an all-losses regime increases search behavior. Potential implications to macro level phenomena, such as the leverage effect, are discussed.

  12. The Biology of Intron Gain and Loss

    DEFF Research Database (Denmark)

    Jeffares, Daniel C; Mourier, Tobias; Penny, David

    2006-01-01

    Intron density in eukaryote genomes varies by more than three orders of magnitude, so there must have been extensive intron gain and/or intron loss during evolution. A favored and partial explanation for this range of intron densities has been that introns have accumulated stochastically in large...... on introns depending on the biology of the organism and the gene involved....

  13. 24 CFR 3280.506 - Heat loss/heat gain.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Heat loss/heat gain. 3280.506... URBAN DEVELOPMENT MANUFACTURED HOME CONSTRUCTION AND SAFETY STANDARDS Thermal Protection § 3280.506 Heat loss/heat gain. The manufactured home heat loss/heat gain shall be determined by methods outlined in...

  14. Gain and loss of phototrophic genes revealed by comparison of two Citromicrobium bacterial genomes.

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    Qiang Zheng

    Full Text Available Proteobacteria are thought to have diverged from a phototrophic ancestor, according to the scattered distribution of phototrophy throughout the proteobacterial clade, and so the occurrence of numerous closely related phototrophic and chemotrophic microorganisms may be the result of the loss of genes for phototrophy. A widespread form of bacterial phototrophy is based on the photochemical reaction center, encoded by puf and puh operons that typically are in a 'photosynthesis gene cluster' (abbreviated as the PGC with pigment biosynthesis genes. Comparison of two closely related Citromicrobial genomes (98.1% sequence identity of complete 16S rRNA genes, Citromicrobium sp. JL354, which contains two copies of reaction center genes, and Citromicrobium strain JLT1363, which is chemotrophic, revealed evidence for the loss of phototrophic genes. However, evidence of horizontal gene transfer was found in these two bacterial genomes. An incomplete PGC (pufLMC-puhCBA in strain JL354 was located within an integrating conjugative element, which indicates a potential mechanism for the horizontal transfer of genes for phototrophy.

  15. IKs Gain- and Loss-of-Function In Early-Onset Lone Atrial Fibrillation

    DEFF Research Database (Denmark)

    Steffensen, Annette Buur; Refsgaard, Lena; Andersen, Martin Nybo

    2015-01-01

    INTRODUCTION: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. The potassium current IKs is essential for cardiac repolarization. Gain-of-function mutation in KCNQ1, the gene encoding the pore-forming α-subunit of the IKs channel (KV 7.1), was the first ion channel dysfunction...... to be associated with familial AF. We hypothesized that early-onset lone AF is associated with a high prevalence of mutations in KCNQ1. METHODS AND RESULTS: We bidirectionally sequenced the entire coding sequence of KCNQ1 in 209 unrelated patients with early-onset lone AF (...-of-function phenotype. CONCLUSIONS: Mutations in the IKs channel leading to gain-of-function have previously been described in familial AF, yet this is the first time a loss-of-function mutation in KCNQ1 is associated with early-onset lone AF. These findings suggest that both gain-of function and loss...

  16. Cleavings: Critical Losses in the Politics of Gain

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    Michael Davidson

    2016-05-01

    Full Text Available Many of Emily Dickinson's best known poems deal with the loss of sight, based on her own experiences with temporary blindness in the mid 1860s, but they are less about the absence of sight than about how she experiences the limits of consciousness: "I could not see to see." She probed the loss of sensation for what it could teach her about what is most familiar—and thus invisible. Using poems by Emily Dickinson and recent work in cultural and queer theory, this essay explores the fine line between "gain" and "loss" in disability studies. Using the author's experience of sudden hearing loss, "Cleavings" argues that recent claims for "deaf gain" have vaunted possibilities of cultural inclusiveness to the exclusion of affective realms of frustration, loss, and failure that are seldom acknowledged experiences of deaf and hard-of-hearing persons. While endorsing the general thrust of deaf gain and its implications for the larger context of disability, "Cleavings" argues for a more critical understanding of loss in the politics of gain.

  17. Patterns of intron gain and conservation in eukaryotic genes

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    Wolf Yuri I

    2007-10-01

    Full Text Available Abstract Background: The presence of introns in protein-coding genes is a universal feature of eukaryotic genome organization, and the genes of multicellular eukaryotes, typically, contain multiple introns, a substantial fraction of which share position in distant taxa, such as plants and animals. Depending on the methods and data sets used, researchers have reached opposite conclusions on the causes of the high fraction of shared introns in orthologous genes from distant eukaryotes. Some studies conclude that shared intron positions reflect, almost entirely, a remarkable evolutionary conservation, whereas others attribute it to parallel gain of introns. To resolve these contradictions, it is crucial to analyze the evolution of introns by using a model that minimally relies on arbitrary assumptions. Results: We developed a probabilistic model of evolution that allows for variability of intron gain and loss rates over branches of the phylogenetic tree, individual genes, and individual sites. Applying this model to an extended set of conserved eukaryotic genes, we find that parallel gain, on average, accounts for only ~8% of the shared intron positions. However, the distribution of parallel gains over the phylogenetic tree of eukaryotes is highly non-uniform. There are, practically, no parallel gains in closely related lineages, whereas for distant lineages, such as animals and plants, parallel gains appear to contribute up to 20% of the shared intron positions. In accord with these findings, we estimated that ancestral introns have a high probability to be retained in extant genomes, and conversely, that a substantial fraction of extant introns have retained their positions since the early stages of eukaryotic evolution. In addition, the density of sites that are available for intron insertion is estimated to be, approximately, one in seven basepairs. Conclusion: We obtained robust estimates of the contribution of parallel gain to the observed

  18. The Lepidoptera Odorant Binding Protein gene family: Gene gain and loss within the GOBP/PBP complex of moths and butterflies.

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    Vogt, Richard G; Große-Wilde, Ewald; Zhou, Jing-Jiang

    2015-07-01

    Butterflies and moths differ significantly in their daily activities: butterflies are diurnal while moths are largely nocturnal or crepuscular. This life history difference is presumably reflected in their sensory biology, and especially the balance between the use of chemical versus visual signals. Odorant Binding Proteins (OBP) are a class of insect proteins, at least some of which are thought to orchestrate the transfer of odor molecules within an olfactory sensillum (olfactory organ), between the air and odor receptor proteins (ORs) on the olfactory neurons. A Lepidoptera specific subclass of OBPs are the GOBPs and PBPs; these were the first OBPs studied and have well documented associations with olfactory sensilla. We have used the available genomes of two moths, Manduca sexta and Bombyx mori, and two butterflies, Danaus plexippus and Heliconius melpomene, to characterize the GOBP/PBP genes, attempting to identify gene orthologs and document specific gene gain and loss. First, we identified the full repertoire of OBPs in the M. sexta genome, and compared these with the full repertoire of OBPs from the other three lepidopteran genomes, the OBPs of Drosophila melanogaster and select OBPs from other Lepidoptera. We also evaluated the tissue specific expression of the M. sexta OBPs using an available RNAseq databases. In the four lepidopteran species, GOBP2 and all PBPs reside in single gene clusters; in two species GOBP1 is documented to be nearby, about 100 kb from the cluster; all GOBP/PBP genes share a common gene structure indicating a common origin. As such, the GOBP/PBP genes form a gene complex. Our findings suggest that (1) the lepidopteran GOBP/PBP complex is a monophyletic lineage with origins deep within Lepidoptera phylogeny, (2) within this lineage PBP gene evolution is much more dynamic than GOBP gene evolution, and (3) butterflies may have lost a PBP gene that plays an important role in moth pheromone detection, correlating with a shift from

  19. When gains loom larger than losses: reversed loss aversion for small amounts of money.

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    Harinck, Fieke; Van Dijk, Eric; Van Beest, Ilja; Mersmann, Paul

    2007-12-01

    Previous research has generally shown that people are loss averse; that is, they weigh losses more heavily than gains. In a series of three experiments, we found that for small outcomes, this pattern is reversed, and gains loom larger than losses. We explain this reversal on the basis of (a) the hedonic principle, which states that individuals are motivated to maximize pleasure and to minimize pain, and (b) the assumption that small losses are more easily discounted cognitively than large losses are.

  20. An EST screen from the annelid Pomatoceros lamarckii reveals patterns of gene loss and gain in animals

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    Chen Wei-Chung

    2009-09-01

    Full Text Available Abstract Background Since the drastic reorganisation of the phylogeny of the animal kingdom into three major clades of bilaterians; Ecdysozoa, Lophotrochozoa and Deuterostomia, it became glaringly obvious that the selection of model systems with extensive molecular resources was heavily biased towards only two of these three clades, namely the Ecdysozoa and Deuterostomia. Increasing efforts have been put towards redressing this imbalance in recent years, and one of the principal phyla in the vanguard of this endeavour is the Annelida. Results In the context of this effort we here report our characterisation of an Expressed Sequence Tag (EST screen in the serpulid annelid, Pomatoceros lamarckii. We have sequenced over 5,000 ESTs which consolidate into over 2,000 sequences (clusters and singletons. These sequences are used to build phylogenetic trees to estimate relative branch lengths amongst different taxa and, by comparison to genomic data from other animals, patterns of gene retention and loss are deduced. Conclusion The molecular phylogenetic trees including the P. lamarckii sequences extend early observations that polychaetes tend to have relatively short branches in such trees, and hence are useful taxa with which to reconstruct gene family evolution. Also, with the availability of lophotrochozoan data such as that of P. lamarckii, it is now possible to make much more accurate reconstructions of the gene complement of the ancestor of the bilaterians than was previously possible from comparisons of ecdysozoan and deuterostome genomes to non-bilaterian outgroups. It is clear that the traditional molecular model systems for protostomes (e.g. Drosophila melanogaster and Caenorhabditis elegans, which are restricted to the Ecdysozoa, have undergone extensive gene loss during evolution. These ecdysozoan systems, in terms of gene content, are thus more derived from the bilaterian ancestral condition than lophotrochozoan systems like the polychaetes

  1. Genes Whose Gain or Loss-Of-Function Increases Skeletal Muscle Mass in Mice: A Systematic Literature Review

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    Sander A. J. Verbrugge

    2018-05-01

    Full Text Available Skeletal muscle mass differs greatly in mice and humans and this is partially inherited. To identify muscle hypertrophy candidate genes we conducted a systematic review to identify genes whose experimental loss or gain-of-function results in significant skeletal muscle hypertrophy in mice. We found 47 genes that meet our search criteria and cause muscle hypertrophy after gene manipulation. They are from high to small effect size: Ski, Fst, Acvr2b, Akt1, Mstn, Klf10, Rheb, Igf1, Pappa, Ppard, Ikbkb, Fstl3, Atgr1a, Ucn3, Mcu, Junb, Ncor1, Gprasp1, Grb10, Mmp9, Dgkz, Ppargc1a (specifically the Ppargc1a4 isoform, Smad4, Ltbp4, Bmpr1a, Crtc2, Xiap, Dgat1, Thra, Adrb2, Asb15, Cast, Eif2b5, Bdkrb2, Tpt1, Nr3c1, Nr4a1, Gnas, Pld1, Crym, Camkk1, Yap1, Inhba, Tp53inp2, Inhbb, Nol3, Esr1. Knock out, knock down, overexpression or a higher activity of these genes causes overall muscle hypertrophy as measured by an increased muscle weight or cross sectional area. The mean effect sizes range from 5 to 345% depending on the manipulated gene as well as the muscle size variable and muscle investigated. Bioinformatical analyses reveal that Asb15, Klf10, Tpt1 are most highly expressed hypertrophy genes in human skeletal muscle when compared to other tissues. Many of the muscle hypertrophy-regulating genes are involved in transcription and ubiquitination. Especially genes belonging to three signaling pathways are able to induce hypertrophy: (a Igf1-Akt-mTOR pathway, (b myostatin-Smad signaling, and (c the angiotensin-bradykinin signaling pathway. The expression of several muscle hypertrophy-inducing genes and the phosphorylation of their protein products changes after human resistance and high intensity exercise, in maximally stimulated mouse muscle or in overloaded mouse plantaris.

  2. HD CAG-correlated gene expression changes support a simple dominant gain of function

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    Jacobsen, Jessie C.; Gregory, Gillian C.; Woda, Juliana M.; Thompson, Morgan N.; Coser, Kathryn R.; Murthy, Vidya; Kohane, Isaac S.; Gusella, James F.; Seong, Ihn Sik; MacDonald, Marcy E.; Shioda, Toshi; Lee, Jong-Min

    2011-01-01

    Huntington's disease is initiated by the expression of a CAG repeat-encoded polyglutamine region in full-length huntingtin, with dominant effects that vary continuously with CAG size. The mechanism could involve a simple gain of function or a more complex gain of function coupled to a loss of function (e.g. dominant negative-graded loss of function). To distinguish these alternatives, we compared genome-wide gene expression changes correlated with CAG size across an allelic series of heterozygous CAG knock-in mouse embryonic stem (ES) cell lines (HdhQ20/7, HdhQ50/7, HdhQ91/7, HdhQ111/7), to genes differentially expressed between Hdhex4/5/ex4/5 huntingtin null and wild-type (HdhQ7/7) parental ES cells. The set of 73 genes whose expression varied continuously with CAG length had minimal overlap with the 754-member huntingtin-null gene set but the two were not completely unconnected. Rather, the 172 CAG length-correlated pathways and 238 huntingtin-null significant pathways clustered into 13 shared categories at the network level. A closer examination of the energy metabolism and the lipid/sterol/lipoprotein metabolism categories revealed that CAG length-correlated genes and huntingtin-null-altered genes either were different members of the same pathways or were in unique, but interconnected pathways. Thus, varying the polyglutamine size in full-length huntingtin produced gene expression changes that were distinct from, but related to, the effects of lack of huntingtin. These findings support a simple gain-of-function mechanism acting through a property of the full-length huntingtin protein and point to CAG-correlative approaches to discover its effects. Moreover, for therapeutic strategies based on huntingtin suppression, our data highlight processes that may be more sensitive to the disease trigger than to decreased huntingtin levels. PMID:21536587

  3. Weight Gain and Hair Loss during Anti-TNF Therapy

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    Abdo Lutf

    2012-01-01

    Full Text Available Objectives. To investigate the incidence of weight gain and hair loss as adverse effects of anti-TNF therapy in rheumatic diseases. Methods. Patients using anti-TNF therapy, who are followed in rheumatology clinic, were interviewed using a questionnaire to investigate the side effects of anti-TNF therapy. Patients who complained of hair loss and weight gain were asked additional questions concerning the relationship of these adverse effects to anti-TNF use, whether therapy was stopped because of these adverse effects and if the adverse effects reversed after stopping therapy. The files were reviewed to follow the weight change before, during, and after discontinuation of anti-TNF. Results. One hundred fifty consecutive patients (82 RA, 34 ankylosing spondylitis, 32 psoriatic arthritis, and 4 for other indications were interviewed .Weight gain was observed in 20 patients (13.3% with average gain of 5.5 Kg. Anti-TNF was stopped in five patients because of this adverse effect. Hair loss during anti-TNf therapy was reported in five females (3.3% and anti-TNF therapy was stopped in all of them. Conclusion. Weight gain and hair loss appear to be associated with anti-TNF therapy and may be one reason for discontinuing the therapy.

  4. 26 CFR 1.643(a)-3 - Capital gains and losses.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Capital gains and losses. 1.643(a)-3 Section 1... (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.643(a)-3 Capital gains and losses. (a) In general. Except as provided in § 1.643(a)-6 and paragraph (b) of this section, gains from the sale or...

  5. Cross-cultural comparisons of delay discounting of gain and loss.

    Science.gov (United States)

    Ishii, Keiko; Gang, Lili; Takahashi, Taiki

    2016-11-01

    People generally tend to discount future outcomes in favor of smaller but immediate gains (i.e., delay discounting). The present research examined cultural similarities and differences in delay discounting of gain and loss between Chinese and Japanese, based on a q-exponential model of intertemporal choice. Using a hypothetical situation, we asked 65 Japanese participants and 51 Chinese participants to choose between receiving (or paying) a different amount of money immediately or with a specified delay (1 week, 2 weeks, 1 month, 6 months, 1 year, 5 years, and 25 years). For each delay, participants completed a series of 40 binary choices for gain or loss. Regardless of cultures, the q-exponential model was the optimal model. Both impulsivity and time-inconsistency were higher for future gains than for future losses. In addition to the cultural similarities, Chinese participants discounted future gains and losses more steeply than did Japanese. In contrast, Japanese participants were more time-inconsistent in delay discounting than were Chinese, suggesting that the reduction in their subjective value depended relatively on delay.

  6. Gain and loss learning differentially contribute to life financial outcomes.

    Directory of Open Access Journals (Sweden)

    Brian Knutson

    Full Text Available Emerging findings imply that distinct neurobehavioral systems process gains and losses. This study investigated whether individual differences in gain learning and loss learning might contribute to different life financial outcomes (i.e., assets versus debt. In a community sample of healthy adults (n = 75, rapid learners had smaller debt-to-asset ratios overall. More specific analyses, however, revealed that those who learned rapidly about gains had more assets, while those who learned rapidly about losses had less debt. These distinct associations remained strong even after controlling for potential cognitive (e.g., intelligence, memory, and risk preferences and socioeconomic (e.g., age, sex, ethnicity, income, education confounds. Self-reported measures of assets and debt were additionally validated with credit report data in a subset of subjects. These findings support the notion that different gain and loss learning systems may exert a cumulative influence on distinct life financial outcomes.

  7. Genes and Hearing Loss

    Science.gov (United States)

    ... ENTCareers Marketplace Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient ... mutation may only have dystopia canthorum. How Do Genes Work? Genes are a road map for the ...

  8. ON SOME IDEAS FOR IMPROVEMENT OF IDENTIFICATION AND RECORDING GAINS/LOSSES

    Directory of Open Access Journals (Sweden)

    Jaan Alver

    2016-09-01

    Full Text Available The aim of paper is to analyze the definitions and recording process of revenues and gains. The authors of current paper have worked out some suggestions for improving the reporting process taking into account the definitions of income, revenue, gains, losses and profit. Analyzing the inconsistency in two pairs of opposite terms (Profit and Loss and Gain and Loss the authors came to conclusion that the amount named gain/loss in disposal of property, plant and equipment is rather correction or adjustment of previous miscalculation of depreciation expense due to the formula. To make aforementioned adjustments and show them separately a Contra depreciation expense account or Depreciation adjunct account is recommended.

  9. A Neuropsychological Approach to Understanding Risk-Taking for Potential Gains and Losses

    Science.gov (United States)

    Levin, Irwin P.; Xue, Gui; Weller, Joshua A.; Reimann, Martin; Lauriola, Marco; Bechara, Antoine

    2012-01-01

    Affective neuroscience has helped guide research and theory development in judgment and decision-making by revealing the role of emotional processes in choice behavior, especially when risk is involved. Evidence is emerging that qualitatively and quantitatively different processes may be involved in risky decision-making for gains and losses. We start by reviewing behavioral work by Kahneman and Tversky (1979) and others, which shows that risk-taking differs for potential gains and potential losses. We then turn to the literature in decision neuroscience to support the gain versus loss distinction. Relying in part on data from a new task that separates risky decision-making for gains and losses, we test a neural model that assigns unique mechanisms for risky decision-making involving potential losses. Included are studies using patients with lesions to brain areas specified as important in the model and studies with healthy individuals whose brains are scanned to reveal activation in these and other areas during risky decision-making. In some cases, there is evidence that gains and losses are processed in different regions of the brain, while in other cases the same region appears to process risk in a different manner for gains and losses. At a more general level, we provide strong support for the notion that decisions involving risk-taking for gains and decisions involving risk-taking for losses represent different psychological processes. At a deeper level, we present mounting evidence that different neural structures play different roles in guiding risky choices in these different domains. Some structures are differentially activated by risky gains and risky losses while others respond uniquely in one domain or the other. Taken together, these studies support a clear functional dissociation between risk-taking for gains and risk-taking for losses, and further dissociation at the neural level. PMID:22347161

  10. Stress effects on framed decisions: there are differences for gains and losses

    Directory of Open Access Journals (Sweden)

    Stephan ePabst

    2013-10-01

    Full Text Available Recent studies have shown that acute stress can lead to riskier decision making. Yet, the underlying mechanisms of the stress effects on decisions under risk remain poorly understood. To gain a better understanding of decision-making processes and potential strategy application under stress, we investigated decision making in pure gain and loss domains with unequal expected values across alternatives. We conducted an experimental study with a 2 × 2 design (stress vs. no stress and gain domain vs. loss domain. The Trier Social Stress Test (TSST was utilized to induce acute stress. Controls performed the placebo-TSST. To validate the stress response we measured salivary cortisol and alpha amylase concentrations. We used a modified version of the Game of Dice Task (GDT to assess decision-making performance in a gain and a loss domain. Results showed that non-stressed participants of the gain domain decided less risky compared to those of the loss domain. This behavior is in accordance with previous studies and indicates the stability of the framing effect in even more complex tasks with changing expected values across alternatives. Stress did not alter risk taking behavior in the gain domain. Yet, in the loss domain stressed participants decided less risky compared to controls. Additionally, the data support earlier findings of longer reaction times in loss compared to gain domains due to higher cognitive effort for loss-framed decisions. It is discussed that stress may lead to reduced amygdala activation, which has been found to reduce riskier decisions in a loss domain. With respect to earlier results of riskier decisions in tasks that unite both gain and loss domains, it is discussed whether stress leads to a stronger evaluation of high gains and a neglect of losses.

  11. Stress effects on framed decisions: there are differences for gains and losses.

    Science.gov (United States)

    Pabst, Stephan; Brand, Matthias; Wolf, Oliver T

    2013-01-01

    Recent studies have shown that acute stress can lead to riskier decision making. Yet, the underlying mechanisms of the stress effects on decisions under risk remain poorly understood. To gain a better understanding of decision-making processes and potential strategy application under stress, we investigated decision making in pure gain and loss domains with unequal expected values (EVs) across alternatives. We conducted an experimental study with a 2 × 2 design (stress vs. no stress and gain domain vs. loss domain). The Trier Social Stress Test (TSST) was utilized to induce acute stress. Controls performed the placebo-TSST (p-TSST). To validate the stress response we measured salivary cortisol and alpha-amylase concentrations. We used a modified version of the Game of Dice Task (GDT) to assess decision-making performance in a gain and a loss domain. Results showed that non-stressed participants made less risky decisions in the gain domain compared to those of the loss domain. This behavior is in accordance with previous studies and indicates the stability of the framing effect in even more complex tasks with changing EVs across alternatives. Stress did not alter risk taking behavior in the gain domain. Yet, in the loss domain stressed participants made less risky decisions compared to controls. Additionally, the data support earlier findings of longer reaction times in loss compared to gain domains due to higher cognitive effort for loss-framed decisions. It is discussed that stress may lead to reduced amygdala activation, which has been found to reduce riskier decisions in a loss domain. With respect to earlier results of riskier decisions in tasks that unite both gain and loss domains, it is discussed whether stress leads to a stronger evaluation of high gains and a neglect of losses.

  12. Terrestrial Ecosystem Responses to Species Gains and Losses

    NARCIS (Netherlands)

    Wardle, D.A.; Bardgett, R.D.; Callaway, R.; Putten, van der W.H.

    2011-01-01

    Ecosystems worldwide are losing some species and gaining others, resulting in an interchange of species that is having profound impacts on how these ecosystems function. However, research on the effects of species gains and losses has developed largely independently of one another. Recent conceptual

  13. Terrestrial ecosystem responses to species gains and losses

    NARCIS (Netherlands)

    Wardle, D.A.; Bardgett, R.D.; Callaway, R.M.; Van der Putten, W.H.

    2011-01-01

    Ecosystems worldwide are losing some species and gaining others, resulting in an interchange of species that is having profound impacts on how these ecosystems function. However, research on the effects of species gains and losses has developed largely independently of one another. Recent conceptual

  14. Loss and gain of cone types in vertebrate ciliary photoreceptor evolution.

    Science.gov (United States)

    Musser, Jacob M; Arendt, Detlev

    2017-11-01

    Ciliary photoreceptors are a diverse cell type family that comprises the rods and cones of the retina and other related cell types such as pineal photoreceptors. Ciliary photoreceptor evolution has been dynamic during vertebrate evolution with numerous gains and losses of opsin and phototransduction genes, and changes in their expression. For example, early mammals lost all but two cone opsins, indicating loss of cone receptor types in response to nocturnal lifestyle. Our review focuses on the comparison of specifying transcription factors and cell type-specific transcriptome data in vertebrate retinae to build and test hypotheses on ciliary photoreceptor evolution. Regarding cones, recent data reveal that a combination of factors specific for long-wavelength sensitive opsin (Lws)- cones in non-mammalian vertebrates (Thrb and Rxrg) is found across all differentiating cone photoreceptors in mice. This suggests that mammalian ancestors lost all but one ancestral cone type, the Lws-cone. We test this hypothesis by a correlation analysis of cone transcriptomes in mouse and chick, and find that, indeed, transcriptomes of all mouse cones are most highly correlated to avian Lws-cones. These findings underscore the importance of specifying transcription factors in tracking cell type evolution, and shed new light on the mechanisms of cell type loss and gain in retina evolution. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Targeting the maximum heat recovery for systems with heat losses and heat gains

    International Nuclear Information System (INIS)

    Wan Alwi, Sharifah Rafidah; Lee, Carmen Kar Mun; Lee, Kim Yau; Abd Manan, Zainuddin; Fraser, Duncan M.

    2014-01-01

    Graphical abstract: Illustration of heat gains and losses from process streams. - Highlights: • Maximising energy savings through heat losses or gains. • Identifying location where insulation can be avoided. • Heuristics to maximise heat losses or gains. • Targeting heat losses or gains using the extended STEP technique and HEAT diagram. - Abstract: Process Integration using the Pinch Analysis technique has been widely used as a tool for the optimal design of heat exchanger networks (HENs). The Composite Curves and the Stream Temperature versus Enthalpy Plot (STEP) are among the graphical tools used to target the maximum heat recovery for a HEN. However, these tools assume that heat losses and heat gains are negligible. This work presents an approach that considers heat losses and heat gains during the establishment of the minimum utility targets. The STEP method, which is plotted based on the individual, as opposed to the composite streams, has been extended to consider the effect of heat losses and heat gains during stream matching. Several rules to guide the proper location of pipe insulation, and the appropriate procedure for stream shifting have been introduced in order to minimise the heat losses and maximise the heat gains. Application of the method on two case studies shows that considering heat losses and heat gains yield more realistic utility targets and help reduce both the insulation capital cost and utility cost of a HEN

  16. On the relation between gene flow theory and genetic gain

    Directory of Open Access Journals (Sweden)

    Woolliams John A

    2000-01-01

    Full Text Available Abstract In conventional gene flow theory the rate of genetic gain is calculated as the summed products of genetic selection differential and asymptotic proportion of genes deriving from sex-age groups. Recent studies have shown that asymptotic proportions of genes predicted from conventional gene flow theory may deviate considerably from true proportions. However, the rate of genetic gain predicted from conventional gene flow theory was accurate. The current note shows that the connection between asymptotic proportions of genes and rate of genetic gain that is embodied in conventional gene flow theory is invalid, even though genetic gain may be predicted correctly from it.

  17. 26 CFR 1.453-9 - Gain or loss on disposition of installment obligations.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Gain or loss on disposition of installment...-9 Gain or loss on disposition of installment obligations. (a) In general. Subject to the exceptions contained in section 453(d)(4) and paragraph (c) of this section, the entire amount of gain or loss...

  18. 26 CFR 1.382-7 - Built-in gains and losses. [Reserved

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Built-in gains and losses. [Reserved] 1.382-7 Section 1.382-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.382-7 Built-in gains and losses. [Reserved] ...

  19. The Neural Responses to Social Cooperation in Gain and Loss Context.

    Directory of Open Access Journals (Sweden)

    Peng Sun

    Full Text Available Cooperation is pervasive and constitutes the core behavioral principle of human social life. Previous studies have revealed that mutual cooperation was reliably correlated with two reward-related brain regions, the ventral striatum and the orbitofrontal cortex. Using functional magnetic resonance imaging (fMRI, this study sought to investigate how the loss and gain contexts modulated the neural responses to mutual cooperation. Twenty-five female participants were scanned when they played a series of one-shot prisoner's dilemma games in the loss and gain contexts. Specifically, participants and partners independently chose to either cooperate with each other or not, and each was awarded or deprived of (in the gain context or the loss context, respectively a sum of money which depended upon the interaction of their choices. Behavioral results indicated that participants cooperated in nearly half of the experiment trials and reported higher level of positive emotions for mutual cooperation in both contexts, but they cooperated more in the gain than in the loss context. At the neural level, stronger activities in the orbitofrontal cortex were observed for mutual cooperation compared with the other three outcomes in both contexts, while stronger activation in ventral striatum associated with mutual cooperation was observed in the gain context only. Together, our data indicated that, even in the one-shot interaction under loss context, participants still exhibited preference for cooperation and the rewarding experience from a mutually cooperative social interaction activated the ventral striatum and the orbitofrontal cortex, but the loss context weakened the association between the ventral striatum activation and mutual cooperation.

  20. Gains and losses in nonadditive expected utility

    NARCIS (Netherlands)

    Rakesh, S.; Wakker, P.P.; Machina, M.J.; Munier, B.R.

    1995-01-01

    This paper provides a simple approach for deriving cumulative prospect theory. The key axiom is a cumulative dominance axiom which requires that a prospect be judged more attractive if in it greater gains are more likely and greater losses are less likely. In the presence of this cumulative

  1. Herbivores rescue diversity in warming tundra by modulating trait-dependent species losses and gains.

    Science.gov (United States)

    Kaarlejärvi, Elina; Eskelinen, Anu; Olofsson, Johan

    2017-09-04

    Climate warming is altering the diversity of plant communities but it remains unknown which species will be lost or gained under warming, especially considering interactions with other factors such as herbivory and nutrient availability. Here, we experimentally test effects of warming, mammalian herbivory and fertilization on tundra species richness and investigate how plant functional traits affect losses and gains. We show that herbivory reverses the impact of warming on diversity: in the presence of herbivores warming increases species richness through higher species gains and lower losses, while in the absence of herbivores warming causes higher species losses and thus decreases species richness. Herbivores promote gains of short-statured species under warming, while herbivore removal and fertilization increase losses of short-statured and resource-conservative species through light limitation. Our results demonstrate that both rarity and traits forecast species losses and gains, and mammalian herbivores are essential for preventing trait-dependent extinctions and mitigate diversity loss under warming and eutrophication.Warming can reduce plant diversity but it is unclear which species will be lost or gained under interacting global changes. Kaarlejärvi et al. manipulate temperature, herbivory and nutrients in a tundra system and find that herbivory maintains diversity under warming by reducing species losses and promoting gains.

  2. Compensation of propagation loss of surface plasmon polaritons with a finite-thickness dielectric gain layer

    International Nuclear Information System (INIS)

    Zhang, Xin; Liu, Haitao; Zhong, Ying

    2012-01-01

    We theoretically study the compensation of propagation loss of surface plasmon polaritons (SPPs) with the use of a finite-thickness dielectric layer with optical gain. The impacts of the gain coefficient, the gain-layer thickness and the wavelength on the loss compensation and the field distribution of the SPP mode are systematically explored with a fully vectorial method. Abnormal behaviors for the loss compensation as the gain-layer thickness increases are found and explained. Critical values of the gain coefficient and of the corresponding gain-layer thickness for just compensating the propagation loss are provided. Our results show that as the SPP propagation loss is fully compensated with a gain coefficient at a reasonably low level, the gain layer is still thin enough to ensure a large exterior SPP field at the gain-layer/air interface, which is important for achieving a strong light–matter interaction for applications such as bio-chemical sensing. (paper)

  3. De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy

    DEFF Research Database (Denmark)

    Syrbe, Steffen; Hedrich, Ulrike B S; Riesch, Erik

    2015-01-01

    disability, delayed speech development and sometimes ataxia. Functional studies of the two mutations associated with this phenotype showed almost complete loss of function with a dominant-negative effect. Two further individuals presented with a different and more severe epileptic encephalopathy phenotype....... They carried mutations inducing a drastic gain-of-function effect leading to permanently open channels. These results establish KCNA2 as a new gene involved in human neurodevelopmental disorders through two different mechanisms, predicting either hyperexcitability or electrical silencing of KV1.2-expressing...

  4. Resource Loss and Gain, Life Satisfaction, and Health Among Retirees in Spain.

    Science.gov (United States)

    Topa, Gabriela; Jiménez, Irene; Valero, Encarna; Ovejero, Anastasio

    2017-04-01

    This article focuses on retirement transition from the Conservation of Resources (COR) perspective to better understand how aged participants' perceptions of retirement losses and gains significantly explain retirement well-being. In this article, the mediation of social support in the losses-well-being relationship is explored. The study was conducted with a two-wave longitudinal design. Participants at T1 were aged Spanish workers (>64 years) and at T2 were retirees, with a final sample of 275, who had retired during the previous 6 months. Findings supported the assertion that losses better explain well-being than gains. In addition, specific losses revealed a higher explaining power of life satisfaction and health complaints depending on their content. Social support mediated between perceived losses and well-being. This study suggests that both perceived losses and gains associated with retirement and social support during retirement should be taken into account when addressing postretirement well-being.

  5. 76 FR 65634 - Redetermination of the Consolidated Net Unrealized Built-In Gain and Loss

    Science.gov (United States)

    2011-10-24

    ... Redetermination of the Consolidated Net Unrealized Built-In Gain and Loss AGENCY: Internal Revenue Service (IRS... consolidated net unrealized built-in gain and loss in certain circumstances. This document also invites... gain (NUBIG) at the time of its ownership change, recognized built-in gains will increase the section...

  6. Unconventional modes in lasers with spatially varying gain and loss

    International Nuclear Information System (INIS)

    Ge Li; Tuereci, H. E.; Chong, Y. D.; Stone, A. D.; Rotter, S.

    2011-01-01

    We discuss a class of lasing modes created by a spatially inhomogeneous gain profile. These lasing modes are ''extra modes,'' in addition to, and very different from, conventional lasing modes, which arise from the passive cavity resonances. These new modes do not have high intensity across the entire gain region, but instead are localized at the gain boundary and throughout the gain-free region. They are surface modes, originating from the transmission resonances of the gain-free region. Using an S-matrix description we connect these surface modes to the lasing modes in PT-symmetric (balanced gain-loss) cavities.

  7. Preference for gain- or loss-framed electronic cigarette prevention messages.

    Science.gov (United States)

    Kong, Grace; Cavallo, Dana A; Camenga, Deepa R; Morean, Meghan E; Krishnan-Sarin, Suchitra

    2016-11-01

    Effective electronic cigarette (e-cigarette) prevention messages are needed to combat the rising popularity/uptake of e-cigarettes among youth. We examined preferences for e-cigarette prevention messages that either emphasized gains (e.g., You save money by not using e-cigarettes) or losses (e.g., You spend money by using e-cigarettes) among adolescents and young adults. Using surveys in two middle schools, four high schools, and one college in CT (N=5405), we assessed students' preferences for gain- or loss-framed e-cigarette prevention messages related to four themes: financial cost, health risks, addiction potential, and social labeling as a smoker. We also assessed whether preferences for each message framing theme differed by sex, school level, cigarette-use status, and e-cigarette use-status. We also examined whether preference for message framing differed by cigarette and e-cigarette susceptibility status among never e-cigarette users. Overall, loss-framing was preferred for message themes related to health risks, addiction potential, and social labeling as a smoker, whereas gain-framing was preferred for message themes related to financial cost. Logistic regression analyses showed that 1) females preferred loss-framed messages for all themes relative to males, 2) lifetime e-cigarette users preferred loss-framed health risks and social labeling messages relative to never users, and 3) high school students preferred gain-framed social labeling messages relative to college students. The preference for message framing did not differ by cigarette or e-cigarette susceptibility. Preference for message framing differed by themes and individual characteristics. This formative research could inform the construction of persuasive e-cigarette prevention messages. Copyright © 2016. Published by Elsevier Ltd.

  8. 26 CFR 1.731-1 - Extent of recognition of gain or loss on distribution.

    Science.gov (United States)

    2010-04-01

    ..., that is, capital gain or loss. (b) Gain or loss recognized by partnership. A distribution of property... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Distributions by A Partnership § 1.731-1 Extent of... gain. (i) Where money is distributed by a partnership to a partner, no gain shall be recognized to the...

  9. Neural responses to gains and losses in children of suicide attempters.

    Science.gov (United States)

    Tsypes, Aliona; Owens, Max; Hajcak, Greg; Gibb, Brandon E

    2017-02-01

    [Correction Notice: An Erratum for this article was reported in Vol 126(2) of Journal of Abnormal Psychology (see record 2016-56318-001). In the article, Figure 1 had incorrect axis labels. There was also an error in the abstract, which did not state that ΔFN was calculated as FN to losses minus FN to gains. All versions of this article have been corrected.] Suicidal behavior aggregates within families, yet the specific mechanisms of suicide-risk transmission are poorly understood. Despite some evidence that abnormal patterns of reward responsiveness might constitute one such potential mechanism, empirical evidence is lacking. The goal of this study was to examine neural responses to gains and losses in children of suicide attempters with no personal history of suicide attempt (SA) themselves. To objectively assess these neural responses, we used feedback negativity (FN), a psychophysiological marker of responsiveness to reward and loss. Participants were 66 parents and their 7-11-year-old children (22 with parental history of SA and 44 demographically and clinically matched children of parents with no SA history). Diagnostic interviews were used to gather information about psychiatric diagnoses, symptoms, and histories of suicidal thoughts and behaviors. Children also completed a guessing task, during which continuous electroencephalography (EEG) was recorded. The FN was scored as the mean amplitude, 275-375 ms, following gain or loss feedback at frontocentral sites (Fz and FCz). Children of suicide attempters exhibited significantly more negative ΔFN (i.e., FN to losses minus FN to gains) than children of parents with no SA history. We found that this difference in ΔFN was due specifically to children of parents with a history of SA exhibiting a stronger response to loss, and no group differences were observed for responses to gains. The results suggest that an increased neural response to loss might represent one of the potential pathways of the familial

  10. Contrasting losses and gains increases the predictability of behavior by frontal EEG asymmetry

    Science.gov (United States)

    Telpaz, Ariel; Yechiam, Eldad

    2014-01-01

    Frontal asymmetry measured at rest using EEG is considered a stable marker of approach-avoidance behaviors and risk taking. We examined whether without salient cues of attention in the form of losses, predictability is reduced. Fifty-seven participants performed an experiential decision task in a gain-only, loss-only, and mixed (gains and losses) condition. Increased risk taking on the part of individuals with relatively high left frontal activation, as denoted by the Alpha band, was only observed in the task involving both gains and losses. Event-related potential analysis sheds light on the processes leading to this pattern. Left-frontal dominant individuals had increased fronto-central P300 activation following risky compared to safe outcomes, while right-frontal dominant individuals did not show a P300 difference following safe and risky outcomes. This interaction also only emerged when losses were contrasted with gains. The findings highlight the sensitivity of behavioral predictability to cues of valence. PMID:24817845

  11. 26 CFR 1.382-7T - Built-in gains and losses (temporary).

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Built-in gains and losses (temporary). 1.382-7T Section 1.382-7T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.382-7T Built-in gains and losses...

  12. When, How and Why is Loss-Framing More Effective than Gain- and Non-Gain-Framing in the Promotion of Detection Behaviors?

    OpenAIRE

    Bosone, Lucia; Martinez, Frédéric

    2017-01-01

    This short paper aims to untangle the effect of loss-framing versus gain and non-gain; explaining when, how and why it influences individuals’ intentions to engage in cholesterol screening. We argue that framing-effects are (1) significant only when individuals perceive the issue to be highly relevant and (2) are mediated by perceived negative consequences (resulting from undergoing the test) and response-efficacy. In a 2(issue-relevance: high vs low) × 3(framing: gain vs non-gain vs loss) ex...

  13. Factors Related to Weight Gain/Loss among Emerging Adults with Obesity.

    Science.gov (United States)

    Johnson, Ping H; Annesi, James J

    2018-05-01

    We examined the reasons for weight gain and barriers to weight loss among emerging adults with obesity. Eighty-one female undergraduate students with obesity completed 4-open ended questions in 2015-2016. Qualitative responses were analyzed using NVivo 11 Pro software. Most participants experienced weight gain prior to attending college. The most commonly reported reasons for weight gain include a lack of ability to control one's behaviors or overcome barriers (ie, poor eating habits, lack of physical activity, lack of time, easy access to food), emotional/mental health issues, physical health, and influence of significant others. Nearly half reported having a weight loss goal. Most reported having used one or more weight loss methods. Few reached short-term weight loss but quickly regained the lost weight. Major reported barriers reflect a lack of self-regulation skills, negative mood and stress, and lack of self-efficacy for healthy eating or physical activity. Results suggest that the perceived ability to control one's behaviors and overcome barriers, self-efficacy, and mood are important in weight-related behaviors, weight, and weight loss success among emerging adults, especially those enrolled in college.

  14. Comparative Genomic Hybridization of Human Malignant Gliomas Reveals Multiple Amplification Sites and Nonrandom Chromosomal Gains and Losses

    Science.gov (United States)

    Schròck, Evelin; Thiel, Gundula; Lozanova, Tanka; du Manoir, Stanislas; Meffert, Marie-Christine; Jauch, Anna; Speicher, Michael R.; Nürnberg, Peter; Vogel, Siegfried; Janisch, Werner; Donis-Keller, Helen; Ried, Thomas; Witkowski, Regine; Cremer, Thomas

    1994-01-01

    Nine human malignant gliomas (2 astrocytomas grade III and 7 glioblastomas) were analyzed using comparative genomic hybridization (CGH). In addition to the amplification of the EGFR gene at 7p12 in 4 of 9 cases, six new amplification sites were mapped to 1q32, 4q12, 7q21.1, 7q21.2-3, 12p, and 22q12. Nonrandom chromosomal gains and losses were identified with overrepresentation of chromosome 7 and underrepresentation of chromosome 10 as the most frequent events (1 of 2 astrocytomas, 7 of 7 glioblastomas). Gain of a part or the whole chromosome 19 and losses of chromosome bands 9pter-23 and 22q13 were detected each in five cases. Loss of chromosome band 17p13 and gain of chromosome 20 were revealed each in three cases. The validity of the CGH data was confirmed using interphase cytogenetics with YAC clones, chromosome painting in tumor metaphase spreads, and DNA fingerprinting. A comparison of CGH data with the results of chromosome banding analyses indicates that metaphase spreads accessible in primary tumor cell cultures may not represent the clones predominant in the tumor tissue ImagesFigure 1Figure 4Figure 6 PMID:8203461

  15. 26 CFR 1.721-1 - Nonrecognition of gain or loss on contribution.

    Science.gov (United States)

    2010-04-01

    ... partnership in the process of formation or to a partnership which is already formed and operating. Section 721...) whether made at the formation of the partnership or subsequent thereto. To the extent that any of the... Nonrecognition of gain or loss on contribution. (a) No gain or loss shall be recognized either to the partnership...

  16. Toxic gain of function from mutant FUS protein is crucial to trigger cell autonomous motor neuron loss.

    Science.gov (United States)

    Scekic-Zahirovic, Jelena; Sendscheid, Oliver; El Oussini, Hajer; Jambeau, Mélanie; Sun, Ying; Mersmann, Sina; Wagner, Marina; Dieterlé, Stéphane; Sinniger, Jérome; Dirrig-Grosch, Sylvie; Drenner, Kevin; Birling, Marie-Christine; Qiu, Jinsong; Zhou, Yu; Li, Hairi; Fu, Xiang-Dong; Rouaux, Caroline; Shelkovnikova, Tatyana; Witting, Anke; Ludolph, Albert C; Kiefer, Friedemann; Storkebaum, Erik; Lagier-Tourenne, Clotilde; Dupuis, Luc

    2016-05-17

    FUS is an RNA-binding protein involved in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cytoplasmic FUS-containing aggregates are often associated with concomitant loss of nuclear FUS Whether loss of nuclear FUS function, gain of a cytoplasmic function, or a combination of both lead to neurodegeneration remains elusive. To address this question, we generated knockin mice expressing mislocalized cytoplasmic FUS and complete FUS knockout mice. Both mouse models display similar perinatal lethality with respiratory insufficiency, reduced body weight and length, and largely similar alterations in gene expression and mRNA splicing patterns, indicating that mislocalized FUS results in loss of its normal function. However, FUS knockin mice, but not FUS knockout mice, display reduced motor neuron numbers at birth, associated with enhanced motor neuron apoptosis, which can be rescued by cell-specific CRE-mediated expression of wild-type FUS within motor neurons. Together, our findings indicate that cytoplasmic FUS mislocalization not only leads to nuclear loss of function, but also triggers motor neuron death through a toxic gain of function within motor neurons. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  17. Hamiltonian formulation of systems with balanced loss-gain and exactly solvable models

    Science.gov (United States)

    Ghosh, Pijush K.; Sinha, Debdeep

    2018-01-01

    A Hamiltonian formulation of generic many-body systems with balanced loss and gain is presented. It is shown that a Hamiltonian formulation is possible only if the balancing of loss and gain terms occurs in a pairwise fashion. It is also shown that with the choice of a suitable co-ordinate, the Hamiltonian can always be reformulated in the background of a pseudo-Euclidean metric. If the equations of motion of some of the well-known many-body systems like Calogero models are generalized to include balanced loss and gain, it appears that the same may not be amenable to a Hamiltonian formulation. A few exactly solvable systems with balanced loss and gain, along with a set of integrals of motion are constructed. The examples include a coupled chain of nonlinear oscillators and a many-particle Calogero-type model with four-body inverse square plus two-body pair-wise harmonic interactions. For the case of nonlinear oscillators, stable solution exists even if the loss and gain parameter has unbounded upper range. Further, the range of the parameter for which the stable solutions are obtained is independent of the total number of the oscillators. The set of coupled nonlinear equations are solved exactly for the case when the values of all the constants of motions except the Hamiltonian are equal to zero. Exact, analytical classical solutions are presented for all the examples considered.

  18. Gain-loss framing effects in dilemmas of trust and reciprocity

    NARCIS (Netherlands)

    Evans, A.M.; van Beest, I.

    2017-01-01

    How do trust and reciprocity decisions change when outcomes are framed in terms of potential losses (vs gains)? In two studies, with 7464 trust decisions from 359 participants and 2723 reciprocity decisions from 221 participants, we find that loss framing increases mean-level trust, but has no

  19. Bacterial evolution through the selective loss of beneficial Genes. Trade-offs in expression involving two loci.

    Science.gov (United States)

    Zinser, Erik R; Schneider, Dominique; Blot, Michel; Kolter, Roberto

    2003-01-01

    The loss of preexisting genes or gene activities during evolution is a major mechanism of ecological specialization. Evolutionary processes that can account for gene loss or inactivation have so far been restricted to one of two mechanisms: direct selection for the loss of gene activities that are disadvantageous under the conditions of selection (i.e., antagonistic pleiotropy) and selection-independent genetic drift of neutral (or nearly neutral) mutations (i.e., mutation accumulation). In this study we demonstrate with an evolved strain of Escherichia coli that a third, distinct mechanism exists by which gene activities can be lost. This selection-dependent mechanism involves the expropriation of one gene's upstream regulatory element by a second gene via a homologous recombination event. Resulting from this genetic exchange is the activation of the second gene and a concomitant inactivation of the first gene. This gene-for-gene expression tradeoff provides a net fitness gain, even if the forfeited activity of the first gene can play a positive role in fitness under the conditions of selection. PMID:12930738

  20. Bacterial evolution through the selective loss of beneficial Genes. Trade-offs in expression involving two loci.

    Science.gov (United States)

    Zinser, Erik R; Schneider, Dominique; Blot, Michel; Kolter, Roberto

    2003-08-01

    The loss of preexisting genes or gene activities during evolution is a major mechanism of ecological specialization. Evolutionary processes that can account for gene loss or inactivation have so far been restricted to one of two mechanisms: direct selection for the loss of gene activities that are disadvantageous under the conditions of selection (i.e., antagonistic pleiotropy) and selection-independent genetic drift of neutral (or nearly neutral) mutations (i.e., mutation accumulation). In this study we demonstrate with an evolved strain of Escherichia coli that a third, distinct mechanism exists by which gene activities can be lost. This selection-dependent mechanism involves the expropriation of one gene's upstream regulatory element by a second gene via a homologous recombination event. Resulting from this genetic exchange is the activation of the second gene and a concomitant inactivation of the first gene. This gene-for-gene expression tradeoff provides a net fitness gain, even if the forfeited activity of the first gene can play a positive role in fitness under the conditions of selection.

  1. Critical Quality Source Diagnosis for Dam Concrete Construction Based on Quality Gain-loss Function

    Directory of Open Access Journals (Sweden)

    Bo Wang

    2014-06-01

    Full Text Available In dam concrete construction process, it not only has quality loss arising from quality fluctuation, but also gains quality compensation effect due to the mutual cooperation and adaptation coupling between working procedures (WPs. The calculation and transmission complexity of the quality loss and quality compensation affect the quality management of dam concrete construction. As the quality compensation effect existing in the production practice cannot be described by Taguchi quality loss function, the concept of quality gain-loss function was presented in this paper, which was based on endowing the constant term in the expansion of Taylor series with physical meaning—quality compensation. Based on quality gain-loss function theory, a new quality gain-loss transmission model of dam concrete construction based on GERT network was constructed and its effective algorithm was designed. WP quality gain-loss and its impact on the final product were reasonably measured, and the critical quality routes and critical quality WPs were detected and diagnosed in dam concrete construction network. Summer temperature-controlled concrete construction in the third phase of Three Gorges Project (TGP was taken as an example to carry out the study, and the calculation results showed the validity and practicability of the presented model and algorithm.

  2. Chromosomal abnormalities in human glioblastomas: gain in chromosome 7p correlating with loss in chromosome 10q.

    Science.gov (United States)

    Inda, María del Mar; Fan, Xing; Muñoz, Jorge; Perot, Christine; Fauvet, Didier; Danglot, Giselle; Palacio, Ana; Madero, Pilar; Zazpe, Idoya; Portillo, Eduardo; Tuñón, Teresa; Martínez-Peñuela, José María; Alfaro, Jorge; Eiras, José; Bernheim, Alain; Castresana, Javier S

    2003-01-01

    Various genomic alterations have been detected in glioblastoma. Chromosome 7p, with the epidermal growth factor receptor locus, together with chromosome 10q, with the phosphatase and tensin homologue deleted in chromosome 10 and deleted in malignant brain tumors-1 loci, and chromosome 9p, with the cyclin-dependent kinase inhibitor 2A locus, are among the most frequently damaged chromosomal regions in glioblastoma. In this study, we evaluated the genetic status of 32 glioblastomas by comparative genomic hybridization; the sensitivity of comparative genomic hybridization versus differential polymerase chain reaction to detect deletions at the phosphatase and tensin homologue deleted in chromosome 10, deleted in malignant brain tumors-1, and cyclin-dependent kinase inhibitor 2A loci and amplifications at the cyclin-dependent kinase 4 locus; the frequency of genetic lesions (gain or loss) at 16 different selected loci (including oncogenes, tumor-suppressor genes, and proliferation markers) mapping on 13 different chromosomes; and the possible existence of a statistical association between any pair of molecular markers studied, to subdivide the glioblastoma entity molecularly. Comparative genomic hybridization showed that the most frequent region of gain was chromosome 7p, whereas the most frequent losses occurred on chromosomes 10q and 13q. The only statistically significant association was found for 7p gain and 10q loss. Copyright 2002 Wiley-Liss, Inc.

  3. Decision-making for risky gains and losses among college students with Internet gaming disorder.

    Directory of Open Access Journals (Sweden)

    Yuan-Wei Yao

    Full Text Available Individuals with Internet gaming disorder (IGD tend to exhibit disadvantageous risky decision-making not only in their real life but also in laboratory tasks. Decision-making is a complex multifaceted function and different cognitive processes are involved in decision-making for gains and losses. However, the relationship between impaired decision-making and gain versus loss processing in the context of IGD is poorly understood. The main aim of the present study was to separately evaluate decision-making for risky gains and losses among college students with IGD using the Cups task. Additionally, we further examined the effects of outcome magnitude and probability level on decision-making related to risky gains and losses respectively. Sixty college students with IGD and 42 matched healthy controls (HCs participated. Results indicated that IGD subjects exhibited generally greater risk taking tendencies than HCs. In comparison to HCs, IGD subjects made more disadvantageous risky choices in the loss domain (but not in the gain domain. Follow-up analyses indicated that the impairment was associated to insensitivity to changes in outcome magnitude and probability level for risky losses among IGD subjects. In addition, higher Internet addiction severity scores were associated with percentage of disadvantageous risky options in the loss domain. These findings emphasize the effect of insensitivity to losses on disadvantageous decisions under risk in the context of IGD, which has implications for future intervention studies.

  4. Annual measurements of gain and loss in aboveground carbon density

    Science.gov (United States)

    Baccini, A.; Walker, W. S.; Carvalho, L.; Farina, M.; Sulla-menashe, D. J.; Houghton, R. A.

    2017-12-01

    Tropical forests hold large stores of carbon, but their net carbon balance is uncertain. Land use and land-cover change (LULCC) are believed to release between 0.81 and 1.14 PgC yr-1, while intact native forests are thought to be a net carbon sink of approximately the same magnitude. Reducing the uncertainty of these estimates is not only fundamental to the advancement of carbon cycle science but is also of increasing relevance to national and international policies designed to reduce emissions from deforestation and forest degradation (e.g., REDD+). Contemporary approaches to estimating the net carbon balance of tropical forests rely on changes in forest area between two periods, typically derived from satellite data, together with information on average biomass density. These approaches tend to capture losses in biomass due to deforestation (i.e., wholesale stand removals) but are limited in their sensitivity to forest degradation (e.g., selective logging or single-tree removals), which can account for additional biomass losses on the order of 47-75% of deforestation. Furthermore, while satellite-based estimates of forest area loss have been used successfully to estimate associated carbon losses, few such analyses have endeavored to determine the rate of carbon sequestration in growing forests. Here we use 12 years (2003-2014) of pantropical satellite data to quantify net annual changes in the aboveground carbon density of woody vegetation (MgC ha-1yr-1), providing direct, measurement-based evidence that the world's tropical forests are a net carbon source of 425.2 ± 92.0 Tg C yr-1. This net release of carbon consists of losses of 861.7 ± 80.2 Tg C yr-1 and gains of -436.5 ± 31.0 Tg C yr-1 . Gains result from forest growth; losses result from reductions in forest area due to deforestation and from reductions in biomass density within standing forests (degradation), with the latter accounting for 68.9% of overall losses. Our findings advance previous research

  5. 26 CFR 1.988-4 - Source of gain or loss realized on a section 988 transaction.

    Science.gov (United States)

    2010-04-01

    ... rate at least 10 percentage points higher than the Federal mid-term rate (as determined under section....988-5 and this section, the source of exchange gain or loss shall be determined by reference to the... characterize exchange gain or loss as capital gain or loss. This section takes precedence over section 865. (b...

  6. Divergence and Convergence of Risky Decision Making Across Prospective Gains and Losses: Preferences and Strategies

    Science.gov (United States)

    Kurnianingsih, Yoanna A.; Mullette-Gillman, O'Dhaniel A.

    2015-01-01

    People choose differently when facing potential gains than when facing potential losses. Clear gross differences in decision making between gains and losses have been empirically demonstrated in numerous studies (e.g., framing effect, risk preference, loss aversion). However, theories maintain that there are strong underlying connections (e.g., reflection effect). We investigated the relationship between gains and losses decision making, examining risk preferences, and choice strategies (the reliance on option information) using a monetary gamble task with interleaved trials. For risk preferences, participants were on average risk averse in the gains domain and risk neutral/seeking in the losses domain. We specifically tested for a theoretically hypothesized correlation between individual risk preferences across the gains and losses domains (the reflection effect), but found no significant relationship in the predicted direction. Interestingly, despite the lack of reflected risk preferences, cross-domain risk preferences were still informative of individual choice behavior. For choice strategies, in both domains participants relied more heavily on the maximizing strategy than the satisficing strategy, with increased reliance on the maximizing strategy in the losses domain. Additionally, while there is no mathematical reliance between the risk preference and strategy metrics, within both domains there were significant relationships between risk preferences and strategies—the more participants relied upon the maximizing strategy the more risk neutral they were (equating value and utility maximization). These results demonstrate the complexity of gains and losses decision making, indicating the apparent contradiction that their underlying cognitive/neural processes are both dissociable and overlapping. PMID:26733779

  7. Divergence and Convergence of Risky Decision Making Across Prospective Gains and Losses: Preferences and Strategies.

    Science.gov (United States)

    Kurnianingsih, Yoanna A; Mullette-Gillman, O'Dhaniel A

    2015-01-01

    People choose differently when facing potential gains than when facing potential losses. Clear gross differences in decision making between gains and losses have been empirically demonstrated in numerous studies (e.g., framing effect, risk preference, loss aversion). However, theories maintain that there are strong underlying connections (e.g., reflection effect). We investigated the relationship between gains and losses decision making, examining risk preferences, and choice strategies (the reliance on option information) using a monetary gamble task with interleaved trials. For risk preferences, participants were on average risk averse in the gains domain and risk neutral/seeking in the losses domain. We specifically tested for a theoretically hypothesized correlation between individual risk preferences across the gains and losses domains (the reflection effect), but found no significant relationship in the predicted direction. Interestingly, despite the lack of reflected risk preferences, cross-domain risk preferences were still informative of individual choice behavior. For choice strategies, in both domains participants relied more heavily on the maximizing strategy than the satisficing strategy, with increased reliance on the maximizing strategy in the losses domain. Additionally, while there is no mathematical reliance between the risk preference and strategy metrics, within both domains there were significant relationships between risk preferences and strategies-the more participants relied upon the maximizing strategy the more risk neutral they were (equating value and utility maximization). These results demonstrate the complexity of gains and losses decision making, indicating the apparent contradiction that their underlying cognitive/neural processes are both dissociable and overlapping.

  8. Divergence and convergence of risky decision making across prospective gains and losses: preferences and strategies

    Directory of Open Access Journals (Sweden)

    Yoanna Arlina Kurnianingsih

    2015-12-01

    Full Text Available People choose differently when facing potential gains than when facing potential losses. Clear gross differences in decision making between gains and losses have been empirically demonstrated in numerous studies (e.g. framing effect, risk preference, loss aversion. However, theories maintain that there are strong underlying connections (e.g. reflection effect. We investigated the relationship between gains and losses decision making, examining risk preferences and choice strategies (the reliance on option information using a monetary gamble task with interleaved trials. For risk preferences, participants were on average risk averse in the gains domain and risk neutral/seeking in the losses domain. We specifically tested for a theoretically hypothesized correlation between individual risk preferences across the gains and losses domains (the reflection effect, but found no significant relationship in the predicted direction. Interestingly, despite the lack of reflected risk preferences, cross-domain risk preferences were still informative of individual choice behavior. For choice strategies, in both domains participants relied more heavily on the maximizing strategy than the satisficing strategy, with increased reliance on the maximizing strategy in the losses domain. Additionally, while there is no mathematical reliance between the risk preference and strategy metrics, within both domains there were significant relationships between risk preferences and strategies – the more participants relied upon the maximizing strategy the more risk neutral they were (equating value and utility maximization. These results demonstrate the complexity of gains and losses decision making, indicating the apparent contradiction that their underlying cognitive/neural processes are both dissociable and overlapping.

  9. ROMANIA'S EU ACCESSION. GAINS AND LOSSES (I

    Directory of Open Access Journals (Sweden)

    Caba Stefan

    2012-07-01

    Full Text Available EU accession has brought, as expected, many changes in economic, social and cultural domains. An important chapter is the trade dynamics and how this dynamic has been modified over time by changes in the legal status of Romania's relations with certain trading partners. In this paper we present data on trade with countries with which Romania has concluded trade agreements before accession. Data presentation and analysis continues in "Romania's EU accession. Gains and losses (II".

  10. Money, well-being, and loss aversion: does an income loss have a greater effect on well-being than an equivalent income gain?

    Science.gov (United States)

    Boyce, Christopher J; Wood, Alex M; Banks, James; Clark, Andrew E; Brown, Gordon D A

    2013-12-01

    Higher income is associated with greater well-being, but do income gains and losses affect well-being differently? Loss aversion, whereby losses loom larger than gains, is typically examined in relation to decisions about anticipated outcomes. Here, using subjective-well-being data from Germany (N = 28,723) and the United Kingdom (N = 20,570), we found that losses in income have a larger effect on well-being than equivalent income gains and that this effect is not explained by diminishing marginal benefits of income to well-being. Our findings show that loss aversion applies to experienced losses, challenging suggestions that loss aversion is only an affective-forecasting error. By failing to account for loss aversion, longitudinal studies of the relationship between income and well-being may have overestimated the positive effect of income on well-being. Moreover, societal well-being might best be served by small and stable income increases, even if such stability impairs long-term income growth.

  11. Extensive intron gain in the ancestor of placental mammals

    Science.gov (United States)

    2011-01-01

    Background Genome-wide studies of intron dynamics in mammalian orthologous genes have found convincing evidence for loss of introns but very little for intron turnover. Similarly, large-scale analysis of intron dynamics in a few vertebrate genomes has identified only intron losses and no gains, indicating that intron gain is an extremely rare event in vertebrate evolution. These studies suggest that the intron-rich genomes of vertebrates do not allow intron gain. The aim of this study was to search for evidence of de novo intron gain in domesticated genes from an analysis of their exon/intron structures. Results A phylogenomic approach has been used to analyse all domesticated genes in mammals and chordates that originated from the coding parts of transposable elements. Gain of introns in domesticated genes has been reconstructed on well established mammalian, vertebrate and chordate phylogenies, and examined as to where and when the gain events occurred. The locations, sizes and amounts of de novo introns gained in the domesticated genes during the evolution of mammals and chordates has been analyzed. A significant amount of intron gain was found only in domesticated genes of placental mammals, where more than 70 cases were identified. De novo gained introns show clear positional bias, since they are distributed mainly in 5' UTR and coding regions, while 3' UTR introns are very rare. In the coding regions of some domesticated genes up to 8 de novo gained introns have been found. Intron densities in Eutheria-specific domesticated genes and in older domesticated genes that originated early in vertebrates are lower than those for normal mammalian and vertebrate genes. Surprisingly, the majority of intron gains have occurred in the ancestor of placentals. Conclusions This study provides the first evidence for numerous intron gains in the ancestor of placental mammals and demonstrates that adequate taxon sampling is crucial for reconstructing intron evolution. The

  12. Gain-loss frequency and final outcome in the Soochow Gambling Task: A Reassessment

    Directory of Open Access Journals (Sweden)

    Lin Ching-Hung

    2009-11-01

    Full Text Available Abstract Background Behavioral decision making literature suggests that decision makers are guided less by final outcome than by immediate gain-loss. However, studies of the Iowa Gambling Task (IGT under dynamic and uncertain conditions reveal very different conclusions about the role of final outcome. Another research group designed a similar yet simpler game, the Soochow Gambling Task (SGT, which demonstrated that, in dynamic decision making, the effect of gain-loss frequency is more powerful than that of final outcome. Further study is needed to determine the precise effect of final outcome on decision makers. This experiment developed two modified SGTs to explore the effect of final outcome under the same gain-loss frequency context. Methods Each version of the SGT was performed by twenty-four undergraduate Soochow University students. A large-value (± $200, ± $550 and ± $1050 and a small-value (± $100, ± $150 and ± $650 contrast of SGT were conducted to investigate the final outcome effect. The computerized SGT was launched to record and analyze the choices of the participants. Results The results of both SGT versions consistently showed that the preferred decks A and B to decks C and D. Analysis of learning curves also indicated that, throughout the game, final outcome had a minimal effect on the choices of decision makers. Conclusion Experimental results indicated that, in both the frequent-gain context and the frequent-loss context, final outcome has little effect on decision makers. Most decision makers are guided by gain-loss frequency but not by final outcome.

  13. The effect of framing incentives as either losses or gains with contingency management for smoking cessation.

    Science.gov (United States)

    Romanowich, Paul; Lamb, R J

    2013-04-01

    Cumulative prospect theory predicts that losses motivate behavior more than equal gains. Contingency management procedures effectively reduce drug use by placing incentives in direct competition with the drug taking behavior. Therefore, framing incentives as losses, rather than gains should decrease drug use to a greater extent, given equivalent incentives. We examined whether contingent vouchers described as either losses or gains differentially affected smoking abstinence rates. Over 5 consecutive days, participants could either gain $75 per day for verified abstinence or lose $75 per day (initial endowment=$375) for continuing to smoke. As a result, loss-framed participants were more likely to achieve at least one day of abstinence. There was a trend towards loss-framed participants reducing the amount smoked more than gain-framed participants. However, participants in the gain-framed group were more likely to maintain abstinence, once initiated. The results partially support cumulative prospect theory and suggest additional ways to initiate behavior change using incentives, outside of using larger magnitude incentives in contingency management procedures. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Motivation by potential gains and losses affects control processes via different mechanisms in the attentional network.

    Science.gov (United States)

    Paschke, Lena M; Walter, Henrik; Steimke, Rosa; Ludwig, Vera U; Gaschler, Robert; Schubert, Torsten; Stelzel, Christine

    2015-05-01

    Attentional control in demanding cognitive tasks can be improved by manipulating the motivational state. Motivation to obtain gains and motivation to avoid losses both usually result in faster reaction times and stronger activation in relevant brain areas such as the prefrontal cortex, but little is known about differences in the underlying neurocognitive mechanisms of these types of motivation in an attentional control context. In the present functional magnetic resonance imaging (fMRI) study, we tested whether potential gain and loss as motivating incentives lead to overlapping or distinct neural effects in the attentional network, and whether one of these conditions is more effective than the other. A Flanker task with word stimuli as targets and distracters was performed by 115 healthy participants. Using a mixed blocked and event-related design allowed us to investigate transient and sustained motivation-related effects. Participants could either gain money (potential gain) or avoid losing money (potential loss) in different task blocks. Participants showed a congruency effect with increased reaction times for incongruent compared to congruent trials. Potential gain led to generally faster responses compared to the neutral condition and to stronger improvements than potential loss. Potential loss also led to shorter response times compared to the neutral condition, but participants improved mainly during incongruent and not during congruent trials. The event-related fMRI data revealed a main effect of congruency with increased activity in the left inferior frontal gyrus (IFG) and inferior frontal junction area (IFJ), the pre-supplementary motor area (pre-SMA), bilateral insula, intraparietal sulcus (IPS) and visual word form area (VWFA). While potential gain led to increased activity in a cluster of the IFJ and the VWFA only during incongruent trials, potential loss was linked to activity increases in these regions during incongruent and congruent trials. The

  15. On FEL integral equation and electron energy loss in intermediate gain regime

    International Nuclear Information System (INIS)

    Takao, Masaru

    1994-03-01

    The FEL pendulum equation in a intermediate gain small signal regime is investigated. By calculating the energy loss of the electron beam in terms of the solution of the pendulum equation, we confirm the consistency of the FEL equation in intermediate gain regime. (author)

  16. 20 CFR 404.1084 - Gain or loss from disposition of property; capital assets; timber, coal, and iron ore...

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Gain or loss from disposition of property...- ) Employment, Wages, Self-Employment, and Self-Employment Income Self-Employment Income § 404.1084 Gain or loss...-employment, exclude any gain or loss— (1) That is considered a gain or loss from the sale or exchange of a...

  17. 75 FR 33990 - Built-in Gains and Losses Under Section 382(h)

    Science.gov (United States)

    2010-06-16

    ... Gains and Losses Under Section 382(h) AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Final... section 382(h). DATES: Effective Date: These regulations are effective on June 11, 2010. Applicability...) regarding the treatment of prepaid income under the built-in gain provisions of section 382(h) were...

  18. Surface waves at the interface with an antisymmetric gain/loss profile

    International Nuclear Information System (INIS)

    Ctyroky, Jiri; Kuzmiak, Vladimir; Eyderman, Sergey

    2010-01-01

    We studied properties of strongly guiding two-mode waveguides with antisymmetric gain/loss profile which constitute photonic analogues of quantum mechanical structures with parity-time symmetry breaking. For both TE and TM polarizations, the dependences of effective indices of the guided modes vs. gain/loss coefficient exhibit a degenerate critical point that defines two regimes with profoundly different behavior. In addition, we have shown that the interface between the two media supports propagation of a strongly confined non-attenuated TM polarized surface wave. We examined the properties of the surface wave obtained by both the modal and FDTD method and discuss the differences between the results obtained by both techniques as both the material and geometrical parameters are varied.

  19. What drives sleep-dependent memory consolidation: greater gain or less loss?

    Science.gov (United States)

    Fenn, Kimberly M; Hambrick, David Z

    2013-06-01

    When memory is tested after a delay, performance is typically better if the retention interval includes sleep. However, it is unclear what accounts for this well-established effect. It is possible that sleep enhances the retrieval of information, but it is also possible that sleep protects against memory loss that normally occurs during waking activity. We developed a new research approach to investigate these possibilities. Participants learned a list of paired-associate items and were tested on the items after a 12-h interval that included waking or sleep. We analyzed the number of items gained versus the number of items lost across time. The sleep condition showed more items gained and fewer items lost than did the wake condition. Furthermore, the difference between the conditions (favoring sleep) in lost items was greater than the difference in gain, suggesting that loss prevention may primarily account for the effect of sleep on declarative memory consolidation. This finding may serve as an empirical constraint on theories of memory consolidation.

  20. History of Smoking and Postcessation Weight Gain among Weight Loss Surgery Candidates

    OpenAIRE

    Levine, Michele D.; Kalarchian, Melissa A.; Courcoulas, Anita P.; Wisinski, Meghan S.C.; Marcus, Marsha D.

    2007-01-01

    Smoking cessation often results in weight gain. Although smoking cessation frequently is recommended to patients presenting for weight loss surgery (WLS), the relationship between smoking cessation and weight gain among WLS candidates is poorly understood. Thus, we sought to document the history and prevalence of smoking and smoking-related weight gain among WLS candidates. Subjects (N = 67) presenting for bariatric surgery provided demographic information, were interviewed about smoking, and...

  1. Future Time Perspective Impacts Gain-Related but Not Loss-Related Intertemporal Choice.

    Science.gov (United States)

    Li, Tian; Tan, Yuxin; Gong, Xianmin; Yin, Shufei; Qiu, Fangshu; Hu, Xue

    2018-01-01

    Future time perspective (FTP) modulates individuals' temporal orientation in selecting their motivations and goals, which widely influences their cognitions and behaviors. However, it remains unclear how FTP exactly affects intertemporal choice. To clarify the effect of FTP on intertemporal choice, 90 college students ( M age = 21.70, SD = 1.23) were randomly assigned to the limited FTP condition (16 males, 29 females) and the open-ended FTP condition (17 males, 28 females). In the limited FTP condition, participants were instructed to imagine their states of being 70 years old, whereas in the open-ended FTP condition, they were instructed to describe their current states. All participants then completed a series of intertemporal choice tasks, in which they chose from gain- and loss-related choices occurring at various time points. Results showed that the participants who received the future-imagining manipulation had more limited FTP compared with those who did not receive the manipulation, which confirmed the validity of the FTP manipulation. A 2 (FTP: limited vs. open-ended) × 2 (type of choice: gain vs. loss) repeated measures ANOVA on discount rate revealed a significant interaction between these two factors. The participants in the limited FTP condition had higher discount rates on gain-related choices but showed no difference on loss-related choices compared with the participants under the open-ended FTP condition. The results suggest that limited FTP could lower individuals' future orientation (i.e., willingness to delay an outcome) on gain-related, but not on loss-related, intertemporal decision-making.

  2. Gains and Losses of Transcription Factor Binding Sites in Saccharomyces cerevisiae and Saccharomyces paradoxus

    Science.gov (United States)

    Schaefke, Bernhard; Wang, Tzi-Yuan; Wang, Chuen-Yi; Li, Wen-Hsiung

    2015-01-01

    Gene expression evolution occurs through changes in cis- or trans-regulatory elements or both. Interactions between transcription factors (TFs) and their binding sites (TFBSs) constitute one of the most important points where these two regulatory components intersect. In this study, we investigated the evolution of TFBSs in the promoter regions of different Saccharomyces strains and species. We divided the promoter of a gene into the proximal region and the distal region, which are defined, respectively, as the 200-bp region upstream of the transcription starting site and as the 200-bp region upstream of the proximal region. We found that the predicted TFBSs in the proximal promoter regions tend to be evolutionarily more conserved than those in the distal promoter regions. Additionally, Saccharomyces cerevisiae strains used in the fermentation of alcoholic drinks have experienced more TFBS losses than gains compared with strains from other environments (wild strains, laboratory strains, and clinical strains). We also showed that differences in TFBSs correlate with the cis component of gene expression evolution between species (comparing S. cerevisiae and its sister species Saccharomyces paradoxus) and within species (comparing two closely related S. cerevisiae strains). PMID:26220934

  3. Effects of Gain/Loss Framing in Cyber Defense Decision-Making

    Energy Technology Data Exchange (ETDEWEB)

    Bos, Nathan; Paul, Celeste; Gersh, John; Greenberg, Ariel; Piatko, Christine; Sperling, Scott; Spitaletta, Jason; Arendt, Dustin L.; Burtner, Edwin R.

    2016-10-24

    Cyber defense requires decision making under uncertainty. Yet this critical area has not been a strong focus of research in judgment and decision-making. Future defense systems, which will rely on software-defined networks and may employ ‘moving target’ defenses, will increasingly automate lower level detection and analysis, but will still require humans in the loop for higher level judgment. We studied the decision making process and outcomes of 17 experienced network defense professionals who worked through a set of realistic network defense scenarios. We manipulated gain versus loss framing in a cyber defense scenario, and found significant effects in one of two focal problems. Defenders that began with a network already in quarantine (gain framing) used a quarantine system more than those that did not (loss framing). We also found some difference in perceived workload and efficacy. Alternate explanations of these findings and implications for network defense are discussed.

  4. 26 CFR 1.735-1 - Character of gain or loss on disposition of distributed property.

    Science.gov (United States)

    2010-04-01

    ... TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Distributions by A Partnership § 1.735-1 Character... him in a distribution from a partnership shall be considered gain or loss from the sale or exchange of property other than a capital asset. (2) Inventory items. Any gain realized or loss sustained by a partner...

  5. Upon Accounting for the Impact of Isoenzyme Loss, Gene Deletion Costs Anticorrelate with Their Evolutionary Rates.

    Directory of Open Access Journals (Sweden)

    Christopher Jacobs

    Full Text Available System-level metabolic network models enable the computation of growth and metabolic phenotypes from an organism's genome. In particular, flux balance approaches have been used to estimate the contribution of individual metabolic genes to organismal fitness, offering the opportunity to test whether such contributions carry information about the evolutionary pressure on the corresponding genes. Previous failure to identify the expected negative correlation between such computed gene-loss cost and sequence-derived evolutionary rates in Saccharomyces cerevisiae has been ascribed to a real biological gap between a gene's fitness contribution to an organism "here and now" and the same gene's historical importance as evidenced by its accumulated mutations over millions of years of evolution. Here we show that this negative correlation does exist, and can be exposed by revisiting a broadly employed assumption of flux balance models. In particular, we introduce a new metric that we call "function-loss cost", which estimates the cost of a gene loss event as the total potential functional impairment caused by that loss. This new metric displays significant negative correlation with evolutionary rate, across several thousand minimal environments. We demonstrate that the improvement gained using function-loss cost over gene-loss cost is explained by replacing the base assumption that isoenzymes provide unlimited capacity for backup with the assumption that isoenzymes are completely non-redundant. We further show that this change of the assumption regarding isoenzymes increases the recall of epistatic interactions predicted by the flux balance model at the cost of a reduction in the precision of the predictions. In addition to suggesting that the gene-to-reaction mapping in genome-scale flux balance models should be used with caution, our analysis provides new evidence that evolutionary gene importance captures much more than strict essentiality.

  6. Upon Accounting for the Impact of Isoenzyme Loss, Gene Deletion Costs Anticorrelate with Their Evolutionary Rates.

    Science.gov (United States)

    Jacobs, Christopher; Lambourne, Luke; Xia, Yu; Segrè, Daniel

    2017-01-01

    System-level metabolic network models enable the computation of growth and metabolic phenotypes from an organism's genome. In particular, flux balance approaches have been used to estimate the contribution of individual metabolic genes to organismal fitness, offering the opportunity to test whether such contributions carry information about the evolutionary pressure on the corresponding genes. Previous failure to identify the expected negative correlation between such computed gene-loss cost and sequence-derived evolutionary rates in Saccharomyces cerevisiae has been ascribed to a real biological gap between a gene's fitness contribution to an organism "here and now" and the same gene's historical importance as evidenced by its accumulated mutations over millions of years of evolution. Here we show that this negative correlation does exist, and can be exposed by revisiting a broadly employed assumption of flux balance models. In particular, we introduce a new metric that we call "function-loss cost", which estimates the cost of a gene loss event as the total potential functional impairment caused by that loss. This new metric displays significant negative correlation with evolutionary rate, across several thousand minimal environments. We demonstrate that the improvement gained using function-loss cost over gene-loss cost is explained by replacing the base assumption that isoenzymes provide unlimited capacity for backup with the assumption that isoenzymes are completely non-redundant. We further show that this change of the assumption regarding isoenzymes increases the recall of epistatic interactions predicted by the flux balance model at the cost of a reduction in the precision of the predictions. In addition to suggesting that the gene-to-reaction mapping in genome-scale flux balance models should be used with caution, our analysis provides new evidence that evolutionary gene importance captures much more than strict essentiality.

  7. Gain-loss study along two streams in the upper Sabine River basin, Texas; August-September 1981

    Science.gov (United States)

    Myers, Dennis R.

    1983-01-01

    A gain-loss study was made August-September 1981 along the upper Sabine River from Lake Tawakoni to Farm Road 2517 near Carthage and along Lake Fork Creek from Lake Fork Reservoir to its junction (mouth) with the Sabine River. The hydrologic data collected during the gain-loss study indicated that during periods of low flow on the Sabine River, at least as much water as is released from Lake Tawakoni and from Lake Fork Reservoir will be available downstream at Farm Road 14 near Big Sandy and at Farm Road 2517 near Carthage. Gains from bank seepage and small tributary inflows compensate for losses due to evaporation, evapotranspiration, and loss of water into the alluvial aquifer.

  8. Kids, candy, brain and behavior: Age differences in responses to candy gains and losses

    Directory of Open Access Journals (Sweden)

    Katherine R. Luking

    2014-07-01

    Full Text Available The development of reward-related neural systems, from adolescence through adulthood, has received much recent attention in the developmental neuroimaging literature. However, few studies have investigated behavioral and neural responses to both gains and losses in pre-pubertal child populations. To address this gap in the literature, in the present study healthy children aged 7–11 years and young-adults completed an fMRI card-guessing game using candy pieces delivered post-scan as an incentive. Age differences in behavioral and neural responses to candy gains/losses were investigated. Adults and children displayed similar responses to gains, but robust age differences were observed following candy losses within the caudate, thalamus, insula, and hippocampus. Interestingly, when task behavior was included as a factor in post hoc mediation analyses, activation following loss within the caudate/thalamus related to task behavior and relationships with age were no longer significant. Conversely, relationships between response to loss and age within the hippocampus and insula remained significant even when controlling for behavior, with children showing heightened loss responses within the dorsal/posterior insula. These results suggest that both age and task behavior influence responses within the extended reward circuitry, and that children seem to be more sensitive than adults to loss feedback particularly within the dorsal/posterior insula.

  9. Age differences in gain- and loss-motivated attention.

    Science.gov (United States)

    Williams, Ryan S; Biel, Anna Lena; Dyson, Benjamin J; Spaniol, Julia

    2017-02-01

    Adaptive gain theory (Aston-Jones & Cohen, 2005) suggests that the phasic release of norepinephrine (NE) to cortical areas reflects changes in the utility of ongoing tasks. In the context of aging, this theory raises interesting questions, given that the motivations of older adults differ from those of younger adults. According to socioemotional selectivity theory (Carstensen, Isaacowitz, & Charles, 1999), aging is associated with greater emphasis on emotion-regulation goals, leading older adults to prioritize positive over negative information. This suggests that the phasic release of NE in response to threatening stimuli may be diminished in older adults. In the present study, younger adults (aged 18-34years) and older adults (60-82years) completed the Attention Network Test (ANT), modified to include an incentive manipulation. A behavioral index of attentional alerting served as a marker of phasic arousal. For younger adults, this marker correlated with the effect of both gain and loss incentives on performance. For older adults, in contrast, the correlation between phasic arousal and incentive sensitivity held for gain incentives only. These findings suggest that the enlistment of phasic NE activity may be specific to approach-oriented motivation in older adults. Copyright © 2016. Published by Elsevier Inc.

  10. Copy number of the Adenomatous Polyposis Coli gene is not always neutral in sporadic colorectal cancers with loss of heterozygosity for the gene.

    Science.gov (United States)

    Zauber, Peter; Marotta, Stephen; Sabbath-Solitare, Marlene

    2016-03-12

    Changes in the number of alleles of a chromosome may have an impact upon gene expression. Loss of heterozygosity (LOH) indicates that one allele of a gene has been lost, and knowing the exact copy number of the gene would indicate whether duplication of the remaining allele has occurred. We were interested to determine the copy number of the Adenomatous Polyposis Coli (APC) gene in sporadic colorectal cancers with LOH. We selected 38 carcinomas with LOH for the APC gene region of chromosome 5, as determined by amplification of the CA repeat region within the D5S346 loci. The copy number status of APC was ascertained using the SALSA® MLPA® P043-B1 APC Kit. LOH for the DCC gene, KRAS gene mutation, and microsatellite instability were also evaluated for each tumor, utilizing standard polymerase chain reaction methods. No tumor demonstrated microsatellite instability. LOH of the DCC gene was also present in 33 of 36 (91.7%) informative tumors. A KRAS gene mutation was present in 16 of the 38 (42.1%) tumors. Twenty-four (63.2%) of the tumors were copy number neutral, 10 (26.3%) tumors demonstrated major loss, while two (5.3%) showed partial loss. Two tumors (5.3%) had copy number gain. Results of APC and DCC LOH, KRAS and microsatellite instability indicate our colorectal cancer cases were typical of sporadic cancers following the 'chromosomal instability' pathway. The majority of our colorectal carcinomas with LOH for APC gene are copy number neutral. However, one-third of our cases showed copy number loss, suggesting that duplication of the remaining allele is not required for the development of a colorectal carcinoma.

  11. Copy number of the Adenomatous Polyposis Coli gene is not always neutral in sporadic colorectal cancers with loss of heterozygosity for the gene

    International Nuclear Information System (INIS)

    Zauber, Peter; Marotta, Stephen; Sabbath-Solitare, Marlene

    2016-01-01

    Changes in the number of alleles of a chromosome may have an impact upon gene expression. Loss of heterozygosity (LOH) indicates that one allele of a gene has been lost, and knowing the exact copy number of the gene would indicate whether duplication of the remaining allele has occurred. We were interested to determine the copy number of the Adenomatous Polyposis Coli (APC) gene in sporadic colorectal cancers with LOH. We selected 38 carcinomas with LOH for the APC gene region of chromosome 5, as determined by amplification of the CA repeat region within the D5S346 loci. The copy number status of APC was ascertained using the SALSA® MLPA® P043-B1 APC Kit. LOH for the DCC gene, KRAS gene mutation, and microsatellite instability were also evaluated for each tumor, utilizing standard polymerase chain reaction methods. No tumor demonstrated microsatellite instability. LOH of the DCC gene was also present in 33 of 36 (91.7 %) informative tumors. A KRAS gene mutation was present in 16 of the 38 (42.1 %) tumors. Twenty-four (63.2 %) of the tumors were copy number neutral, 10 (26.3 %) tumors demonstrated major loss, while two (5.3 %) showed partial loss. Two tumors (5.3 %) had copy number gain. Results of APC and DCC LOH, KRAS and microsatellite instability indicate our colorectal cancer cases were typical of sporadic cancers following the ‘chromosomal instability’ pathway. The majority of our colorectal carcinomas with LOH for APC gene are copy number neutral. However, one-third of our cases showed copy number loss, suggesting that duplication of the remaining allele is not required for the development of a colorectal carcinoma

  12. Identification of Genes that Maintain Behavioral and Structural Plasticity during Sleep Loss

    Directory of Open Access Journals (Sweden)

    Laurent Seugnet

    2017-10-01

    Full Text Available Although patients with primary insomnia experience sleep disruption, they are able to maintain normal performance on a variety of cognitive tasks. This observation suggests that insomnia may be a condition where predisposing factors simultaneously increase the risk for insomnia and also mitigate against the deleterious consequences of waking. To gain insight into processes that might regulate sleep and buffer neuronal circuits during sleep loss, we manipulated three genes, fat facet (faf, highwire (hiw and the GABA receptor Resistance to dieldrin (Rdl, that were differentially modulated in a Drosophila model of insomnia. Our results indicate that increasing faf and decreasing hiw or Rdl within wake-promoting large ventral lateral clock neurons (lLNvs induces sleep loss. As expected, sleep loss induced by decreasing hiw in the lLNvs results in deficits in short-term memory and increases of synaptic growth. However, sleep loss induced by knocking down Rdl in the lLNvs protects flies from sleep-loss induced deficits in short-term memory and increases in synaptic markers. Surprisingly, decreasing hiw and Rdl within the Mushroom Bodies (MBs protects against the negative effects of sleep deprivation (SD as indicated by the absence of a subsequent homeostatic response, or deficits in short-term memory. Together these results indicate that specific genes are able to disrupt sleep and protect against the negative consequences of waking in a circuit dependent manner.

  13. 75 FR 44138 - Build-In Gains and Losses Under Section 382(h); Correction

    Science.gov (United States)

    2010-07-28

    ... DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Part 1 [TD 9487] RIN 1545-BG03 Build-In Gains and Losses Under Section 382(h); Correction AGENCY: Internal Revenue Service (IRS), Treasury... providing guidance regarding the treatment of prepaid income under the built-in gain provisions of section...

  14. Partial Adaptation of Obtained and Observed Value Signals Preserves Information about Gains and Losses.

    Science.gov (United States)

    Burke, Christopher J; Baddeley, Michelle; Tobler, Philippe N; Schultz, Wolfram

    2016-09-28

    Given that the range of rewarding and punishing outcomes of actions is large but neural coding capacity is limited, efficient processing of outcomes by the brain is necessary. One mechanism to increase efficiency is to rescale neural output to the range of outcomes expected in the current context, and process only experienced deviations from this expectation. However, this mechanism comes at the cost of not being able to discriminate between unexpectedly low losses when times are bad versus unexpectedly high gains when times are good. Thus, too much adaptation would result in disregarding information about the nature and absolute magnitude of outcomes, preventing learning about the longer-term value structure of the environment. Here we investigate the degree of adaptation in outcome coding brain regions in humans, for directly experienced outcomes and observed outcomes. We scanned participants while they performed a social learning task in gain and loss blocks. Multivariate pattern analysis showed two distinct networks of brain regions adapt to the most likely outcomes within a block. Frontostriatal areas adapted to directly experienced outcomes, whereas lateral frontal and temporoparietal regions adapted to observed social outcomes. Critically, in both cases, adaptation was incomplete and information about whether the outcomes arose in a gain block or a loss block was retained. Univariate analysis confirmed incomplete adaptive coding in these regions but also detected nonadapting outcome signals. Thus, although neural areas rescale their responses to outcomes for efficient coding, they adapt incompletely and keep track of the longer-term incentives available in the environment. Optimal value-based choice requires that the brain precisely and efficiently represents positive and negative outcomes. One way to increase efficiency is to adapt responding to the most likely outcomes in a given context. However, too strong adaptation would result in loss of precise

  15. The Impact of Gain- and Loss-Framed Messages on Young Adults' Sexual Decision Making: An Experimental Study.

    Science.gov (United States)

    Macapagal, Kathryn; Janssen, Erick; Matson, Margaret; Finn, Peter R; Heiman, Julia R

    2017-02-01

    Messages that frame a target behavior in terms of its benefits (gain frame) or costs (loss frame) have been widely and successfully used for health promotion and risk reduction. However, the impact of framed messages on decisions to have sex and sexual risk, as well as moderators of these effects, has remained largely unexplored. We used a computerized laboratory task to test the effects of framed messages about condom use on young adults' sexual decision making. Participants (N = 127) listened to both gain- and loss-framed messages and rated their intentions to have sex with partners who posed a high and low risk for sexually transmitted infections (STIs). The effects of message frame, partner risk, participant gender, ability to adopt the messages, and message presentation order on intentions to have sex were examined. Intentions to have sex with high-risk partners significantly decreased after the loss-framed message, but not after the gain-framed message, and intentions to have sex increased for participants who received the gain-framed message first. Yet, participants found it easier to adopt the gain-framed message. Results suggest that loss-framed messages may be particularly effective in reducing intentions to have sex with partners who might pose a higher risk for STIs, and that message presentation order may alter the relative effectiveness of gain- and loss-framed messages on sexual decision making. Future studies should examine the precise conditions under which gain- and loss-framed messages can promote healthy sexual behaviors and reduce sexual risk behaviors.

  16. Individual Differences in Loss Aversion: Conscientiousness Predicts How Life Satisfaction Responds to Losses Versus Gains in Income.

    Science.gov (United States)

    Boyce, Christopher J; Wood, Alex M; Ferguson, Eamonn

    2016-04-01

    Loss aversion is considered a general pervasive bias occurring regardless of the context or the person making the decision. We hypothesized that conscientiousness would predict an aversion to losses in the financial domain. We index loss aversion by the relative impact of income losses and gains on life satisfaction. In a representative German sample (N = 105,558; replicated in a British sample, N = 33,848), with conscientiousness measured at baseline, those high on conscientiousness have the strongest reactions to income losses, suggesting a pronounced loss aversion effect, whereas for those moderately unconscientious, there is no loss aversion effect. Our research (a) provides the first evidence of personality moderation of any loss aversion phenomena, (b) supports contextual perspectives that both personality and situational factors need to be examined in combination, (c) shows that the small but robust relationship between income and life satisfaction is driven primarily by a subset of people experiencing highly impactful losses. © 2016 by the Society for Personality and Social Psychology, Inc.

  17. Gains and Losses of Transcription Factor Binding Sites in Saccharomyces cerevisiae and Saccharomyces paradoxus.

    Science.gov (United States)

    Schaefke, Bernhard; Wang, Tzi-Yuan; Wang, Chuen-Yi; Li, Wen-Hsiung

    2015-07-27

    Gene expression evolution occurs through changes in cis- or trans-regulatory elements or both. Interactions between transcription factors (TFs) and their binding sites (TFBSs) constitute one of the most important points where these two regulatory components intersect. In this study, we investigated the evolution of TFBSs in the promoter regions of different Saccharomyces strains and species. We divided the promoter of a gene into the proximal region and the distal region, which are defined, respectively, as the 200-bp region upstream of the transcription starting site and as the 200-bp region upstream of the proximal region. We found that the predicted TFBSs in the proximal promoter regions tend to be evolutionarily more conserved than those in the distal promoter regions. Additionally, Saccharomyces cerevisiae strains used in the fermentation of alcoholic drinks have experienced more TFBS losses than gains compared with strains from other environments (wild strains, laboratory strains, and clinical strains). We also showed that differences in TFBSs correlate with the cis component of gene expression evolution between species (comparing S. cerevisiae and its sister species Saccharomyces paradoxus) and within species (comparing two closely related S. cerevisiae strains). © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  18. Genes and Syndromic Hearing Loss.

    Science.gov (United States)

    Keats, Bronya J. B.

    2002-01-01

    This article provides a description of the human genome and patterns of inheritance and discusses genes that are associated with some of the syndromes for which hearing loss is a common finding, including: Waardenburg, Stickler, Jervell and Lange-Neilsen, Usher, Alport, mitochondrial encephalomyopathy, and sensorineural hearing loss. (Contains…

  19. TDP-43 Loss-of-Function Causes Neuronal Loss Due to Defective Steroid Receptor-Mediated Gene Program Switching in Drosophila

    Directory of Open Access Journals (Sweden)

    Lies Vanden Broeck

    2013-01-01

    Full Text Available TDP-43 proteinopathy is strongly implicated in the pathogenesis of amyotrophic lateral sclerosis and related neurodegenerative disorders. Whether TDP-43 neurotoxicity is caused by a novel toxic gain-of-function mechanism of the aggregates or by a loss of its normal function is unknown. We increased and decreased expression of TDP-43 (dTDP-43 in Drosophila. Although upregulation of dTDP-43 induced neuronal ubiquitin and dTDP-43-positive inclusions, both up- and downregulated dTDP-43 resulted in selective apoptosis of bursicon neurons and highly similar transcriptome alterations at the pupal-adult transition. Gene network analysis and genetic validation showed that both up- and downregulated dTDP-43 directly and dramatically increased the expression of the neuronal microtubule-associated protein Map205, resulting in cytoplasmic accumulations of the ecdysteroid receptor (EcR and a failure to switch EcR-dependent gene programs from a pupal to adult pattern. We propose that dTDP-43 neurotoxicity is caused by a loss of its normal function.

  20. Gestational Weight Gain and Post-Partum Weight Loss Among Young, Low-Income, Ethnic Minority Women

    Science.gov (United States)

    ROTHBERG, Bonnie E. Gould; MAGRIPLES, Urania; KERSHAW, Trace S.; RISING, Sharon Schindler; ICKOVICS, Jeannette R.

    2010-01-01

    Objective Document weight change trajectories that lead to gestational weight gain or postpartum weight loss outside clinical recommendations established by Institute of Medicine (IOM). Methods Women aged 14-25 receiving prenatal care and delivering singleton infants at term (N=427). Medical record review and four structured interviews conducted: second and third trimester, 6- and 12-months postpartum. Longitudinal mixed modeling to evaluate weight change trajectories. Results Only 22% of participants gained gestational weight within IOM guidelines. 62% exceeded maximum recommendations -- more common among those overweight/obese (BMI≥25.0; phypertension; breastfeeding promoted postpartum weight loss (all p<.02). BMI by race interaction suggested healthier outcomes for Latinas (p=0.02). Conclusion Excessive pregnancy weight gain and inadequate postpartum weight loss are highly prevalent among young low-income ethnic minority women. Pregnancy and postpartum are critical junctures for weight management interventions. PMID:20974459

  1. Keldysh meets Lindblad: Correlated Gain and Loss in Higher Order Perturbation Theory

    Science.gov (United States)

    Stace, Tom; Mueller, Clemens

    Motivated by correlated decay processes driving gain, loss and lasing in driven artificial quantum systems, we develop a theoretical technique using Keldysh diagrammatic perturbation theory to derive a Lindblad master equation that goes beyond the usual second order perturbation theory. We demonstrate the method on the driven dissipative Rabi model, including terms up to fourth order in the interaction between the qubit and both the resonator and environment. This results in a large class of Lindblad dissipators and associated rates which go beyond the terms that have previously been proposed to describe similar systems. All of the additional terms contribute to the system behaviour at the same order of perturbation theory. We then apply these results to analyse the phonon-assisted steady-state gain of a microwave field driving a double quantum-dot in a resonator. We show that resonator gain and loss are substantially affected by dephasing- assisted dissipative processes in the quantum-dot system. These additional processes, which go beyond recently proposed polaronic theories, are in good quantitative agreement with experimental observations.

  2. Does Weight Gain During the Operation Wait Time Have an Impact on Weight Loss After Laparoscopic Sleeve Gastrectomy?

    Science.gov (United States)

    Cayci, Haci Murat; Erdogdu, Umut Eren; Karaman, Kerem; Budak, Ersin; Taymur, İbrahim; Buyukuysal, Cagatay

    2017-02-01

    The effect of preoperative weight changes on postoperative outcomes after bariatric surgery remains inconclusive. The aim of the present study was to evaluate the effect of preoperative weight gain on postoperative weight loss outcomes after laparoscopic sleeve gastrectomy (SG). Ninety-two morbidly obese patients undergoing SG from January 2014 to April 2016 were separated into two groups according to whether they gained weight or not during the waiting time prior to surgery. Thirty-nine patients (42.4 %) gained weight during the waiting time and 53 patients (57.6 %) did not. The median body mass index (BMI; kg/m 2 ) at surgery was significantly higher in weight-gained patients (47.8 (min-max, 40-62)) compared to patients who had not gained weight (45.10 (min-max, 41-67)), (P = 0.034). No significant difference was found between the two groups regarding the distribution of age, gender, family history of obesity, existence of comorbidity, smoking, weight gain during childhood or adulthood, preoperative Beck depression and Beck anxiety scores, waiting time period, and body weight at the initial visit (P > 0.05). The ASA I score was higher in weight-gained patients whereas ASA II score was higher in those who did not gain, and the difference was significant (P = 0.046). Postoperative % BMI loss and % weight loss were not significantly different between the two groups at the first, third, sixth months, and the end of the first year (P > 0.05). Weight gain during waiting time has no negative impact on % weight loss and % BMI loss after SG.

  3. Carbon gains by conservation projects overbalance carbon losses by degradation in China's karst ecoregions

    Science.gov (United States)

    Tong, X.; Yue, Y.; Fensholt, R.; Brandt, M.

    2017-12-01

    China's ecological restoration projects are considered as "mega-engineering" activities and the most ambitious afforestation and conservation projects in human history. The highly sensitive and vulnerable karst ecosystem in Southwest China is one of the largest exposed carbonate rock areas (more than 0.54 million km2) in the world. Accelerating desertification has been reported during the last half century, caused by the increasing intensity of human exploitation of natural resources. As a result, vast karst areas (approximately 0.12 million km2) previously covered by vegetation and soil were turned into a rocky landscape. To combat this severe form of land degradation, more than 19 billion USD have been invested in mitigation initiatives since the end of the 1990s. The costs of mega-engineering as a climate change mitigation measure are however only justified if ecosystem properties can be affected at large scales. Here we study the carbon balance of the karst regions of 8 Chinese provinces over four decades, using optical and passive microwave satellite data, supported by statistical data on project implementations. We find that most areas experiencing losses in aboveground biomass carbon are located in areas with a high standing biomass ( 95 Mg C ha-1), whereas areas with a carbon gain are mostly located in regions with a low standing biomass ( 45 Mg C ha-1). However, the overall gains in carbon stocks overbalance the losses, with an average gross loss of -0.8 Pg C and a gross gain of +2.4 Pg C (1980s to 2016), resulting in a net gain of 1.6 Pg C. Areas of carbon gains are widespread and spatially coherent with conservation projects implemented after 2001, whereas areas of carbon losses show that ongoing degradation is still happening in the western parts of the karst regions. We conclude that the impact of conservation projects on the carbon balance of China's karst ecoregions is remarkable, but biomass carbon losses caused by ongoing degradation can not be

  4. The invasive MED/Q Bemisia tabaci genome: a tale of gene loss and gene gain

    Science.gov (United States)

    Whiteflies are a group of invasive crop pests that impact global agriculture. An analysis was conducted to compare draft genomes of two whitefly strains, which demonstrated the relative conserved gene order, but a number of genes were either novel (added) or omitted (deleted) between genomes. This...

  5. Validation of Tilt Gain under Realistic Path Loss Model and Network Scenario

    DEFF Research Database (Denmark)

    Nguyen, Huan Cong; Rodriguez, Ignacio; Sørensen, Troels Bundgaard

    2013-01-01

    Despite being a simple and commonly-applied radio optimization technique, the impact on practical network performance from base station antenna downtilt is not well understood. Most published studies based on empirical path loss models report tilt angles and performance gains that are far higher...... than practical experience suggests. We motivate in this paper, based on a practical LTE scenario, that the discrepancy partly lies in the path loss model, and shows that a more detailed semi-deterministic model leads to both lower gains in terms of SINR, outage probability and downlink throughput...... settings, including the use of electrical and/or mechanical antenna downtilt, and therefore it is possible to find multiple optimum tilt profiles in a practical case. A broader implication of this study is that care must be taken when using the 3GPP model to evaluate advanced adaptive antenna techniques...

  6. The transition from No Net Loss to a Net Gain of biodiversity is far from trivial

    DEFF Research Database (Denmark)

    Bull, Joseph William; Brownlie, S.

    2017-01-01

    appropriate in evaluating the ecological outcomes, depending on the principle chosen; and (4) stakeholder expectations differ considerably under the two principles. In exploring these arguments we hope to support policy-makers in choosing the more appropriate of the two objectives. We suggest that financial......The objectives of No Net Loss and Net Gain have emerged as key principles in conservation policy. Both give rise to mechanisms by which certain unavoidable biodiversity losses associated with development are quantified, and compensated with comparable gains (e.g. habitat restoration). The former...... seeks a neutral outcome for biodiversity after losses and gains are accounted for, and the latter seeks an improved outcome. Policy-makers often assume that the transition from one to the other is straightforward and essentially a question of the amount of compensation provided. Consequently, companies...

  7. History of Smoking and Postcessation Weight Gain among Weight Loss Surgery Candidates

    Science.gov (United States)

    Levine, Michele D.; Kalarchian, Melissa A.; Courcoulas, Anita P.; Wisinski, Meghan S.C.; Marcus, Marsha D.

    2007-01-01

    Smoking cessation often results in weight gain. Although smoking cessation frequently is recommended to patients presenting for weight loss surgery (WLS), the relationship between smoking cessation and weight gain among WLS candidates is poorly understood. Thus, we sought to document the history and prevalence of smoking and smoking-related weight gain among WLS candidates. Subjects (N = 67) presenting for bariatric surgery provided demographic information, were interviewed about smoking, and weighed and measured prior to operation. Sixty-seven percent of patients reported a lifetime history of smoking, and 26.9% were current smokers. Among lifetime smokers who had attempted to quit, the average maximum amount of weight gained following smoking cessation was 28.1 pounds, but there was wide variability in postcessation weight gain. These data suggest that smoking among candidates for bariatric surgery is prevalent, and that previous cessation attempts were associated with considerable weight gain. Because patients often receive recommendations to quit smoking and lose weight prior to surgery, additional information on the impact of presurgical smoking cessation on long-tem weight control in this population is needed. PMID:17408868

  8. Gain-Framed Messages Do Not Motivate Sun Protection: A Meta-Analytic Review of Randomized Trials Comparing Gain-Framed and Loss-Framed Appeals for Promoting Skin Cancer Prevention

    Science.gov (United States)

    O’Keefe, Daniel J.; Wu, Daisy

    2012-01-01

    Persuading people to undertake actions to prevent skin cancer is an important public health challenge. A number of studies have compared the effectiveness of gain-framed and loss-framed appeals in this domain, often expecting gain-framed appeals to be more persuasive. A meta-analytic review (k = 33, N = 4,168), however, finds no significant difference in the persuasiveness of gain- and loss-framed appeals for encouraging skin cancer prevention. This conclusion is unaffected by differences in the specific protective action advocated or by differences in the kind of outcomes invoked. But the results offer an intimation that men might be more susceptible to framing variations in this domain—with loss-framed appeals potentially having a persuasive advantage. PMID:22829794

  9. The order of information processing alters economic gain-loss framing effects.

    Science.gov (United States)

    Kwak, Youngbin; Huettel, Scott

    2018-01-01

    Adaptive decision making requires analysis of available information during the process of choice. In many decisions that information is presented visually - which means that variations in visual properties (e.g., salience, complexity) can potentially influence the process of choice. In the current study, we demonstrate that variation in the left-right positioning of risky and safe decision options can influence the canonical gain-loss framing effect. Two experiments were conducted using an economic framing task in which participants chose between gambles and certain outcomes. The first experiment demonstrated that the magnitude of the gain-loss framing effect was greater when the certain option signaling the current frame was presented on the left side of the visual display. Eye-tracking data during task performance showed a left-gaze bias for initial fixations, suggesting that the option presented on the left side was processed first. Combination of eye-tracking and choice data revealed that there was a significant effect of direction of first gaze (i.e. left vs. right) as well as an interaction between gaze direction and identity of the first fixated information (i.e. certain vs. gamble) regardless of frame. A second experiment presented the gamble and certain options in a random order, with a temporal delay between their presentations. We found that the magnitude of gain-loss framing was larger when the certain option was presented first, regardless of left and right positioning, only in individuals with lower risk-taking tendencies. The effect of presentation order on framing was not present in high risk-takers. These results suggest that the sequence of visual information processing as well as their left-right positioning can bias choices by changing the impact of the presented information during risky decision making. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Optimization of loss and gain multilayers for reducing the scattering of a perfect conducting cylinder

    Science.gov (United States)

    Zhen-Zhong, Yu; Guo-Shu, Zhao; Gang, Sun; Hai-Fei, Si; Zhong, Yang

    2016-07-01

    Reduction of electromagnetic scattering from a conducting cylinder could be achieved by covering it with optimized multilayers of normal dielectric and plasmonic material. The plasmonic material with intrinsic losses could degrade the cloaking effect. Using a genetic algorithm, we present the optimized design of loss and gain multilayers for reduction of the scattering from a perfect conducting cylinder. This multilayered structure is theoretically and numerically analyzed when the plasmonic material with low loss and high loss respectively is considered. We demonstrate by full-wave simulation that the optimized nonmagnetic gain-loss design can greatly compensate the decreased cloaking effect caused by loss material, which facilitates the realization of practical electromagnetic cloaking, especially in the optical range. Project supported by the Research Foundation of Jinling Institute of Technology, China (Grant No. JIT-B-201426), the Jiangsu Modern Education and Technology Key Project, China (Grant No. 2014-R-31984), the Jiangsu 333 Project Funded Research Project, China (Grant No. BRA2010004), and the University Science Research Project of Jiangsu Province, China (Grant No. 15KJB520010).

  11. Reducing Thermal Losses and Gains With Buried and Encapsulated Ducts in Hot-Humid Climates

    Energy Technology Data Exchange (ETDEWEB)

    Shapiro, C.; Magee, A.; Zoeller, W.

    2013-02-01

    The Consortium for Advanced Residential Buildings (CARB) monitored three houses in Jacksonville, FL, to investigate the effectiveness of encapsulated and encapsulated/buried ducts in reducing thermal losses and gains from ductwork in unconditioned attics. Burying ductwork beneath loose-fill insulation has been identified as an effective method of reducing thermal losses and gains from ductwork in dry climates, but it is not applicable in humid climates where condensation may occur on the outside of the duct jacket. By encapsulating the ductwork in closed cell polyurethane foam (ccSPF) before burial beneath loose-fill mineral fiber insulation, the condensation potential may be reduced while increasing the R-value of the ductwork.

  12. The value of success: acquiring gains, avoiding losses, and simply being successful.

    Directory of Open Access Journals (Sweden)

    Samantha M Mowrer

    Full Text Available A large network of spatially contiguous, yet anatomically distinct regions in medial frontal cortex is involved in reward processing. Although it is clear these regions play a role in critical aspects of reward-related learning and decision-making, the individual contributions of each component remains unclear. We explored dissociations in reward processing throughout several key regions in the reward system and aimed to clarify the nature of previously observed outcome-related activity in a portion of anterior medial orbitofrontal cortex (mOFC. Specifically, we tested whether activity in anterior mOFC was related to processing successful actions, such that this region would respond similarly to rewards with and without tangible benefits, or whether this region instead encoded only quantifiable outcome values (e.g., money. Participants performed a task where they encountered monetary gains and losses (and non-gains and non-losses during fMRI scanning. Critically, in addition to the outcomes with monetary consequences, the task included trials that provided outcomes without tangible benefits (participants were simply told that they were correct or incorrect. We found that anterior mOFC responded to all successful outcomes regardless of whether they carried tangible benefits (monetary gains and non-losses or not (controls. These results support the hypothesis that anterior mOFC processes rewards in terms of a common currency and is capable of providing reward-based signals for everything we value, whether it be primary or secondary rewards or simply a successful experience without objectively quantifiable benefits.

  13. Not all streaks are the same: Individual differences in risk preferences during runs of gains and losses

    Directory of Open Access Journals (Sweden)

    Christopher T. Ball

    2012-07-01

    Full Text Available Runs of gains and losses are particularly salient to decision makers because of their perceived departure from randomness, as well as their immediate impact on the financial status of the decision makers. Past research has focused on decision making biases that relate to faulty conceptions of chance and luck, such as the gambler's fallacy and the hot hand effect. Participants in the current study bet on the outcomes of a long sequence of simulated coin tosses. Risk preferences were found to change as a function of run valence (i.e., losses vs. gains, run length, and financial status. Individuals were found to differ in the effect of all of these factors, in their responses to runs of gains and losses in sequential risky choice.

  14. Rapid duplication and loss of nbs-encoding genes in eurosids II

    International Nuclear Information System (INIS)

    Si, W.; Gu, L.; Yang, S.; Zhang, X.; Memon, S.

    2015-01-01

    Eurosids basically evolved from the core Eudicots Rosids. The Rosids consist of two large assemblages, Eurosids I (Fabids) and Eurosids II (Malvids), which belong to the largest group of Angiosperms, comprising of >40,000 and ∼ 15,000 species, respectively. Although the evolutionary patterns of the largest class of disease resistance genes consisting of a nucleotide binding site (NBS) and leucine-rich repeats (LRRs) have been studied in many species, systemic research of NBS-encoding genes has not been performed in different orders of Eurosids II. Here, five Eurosids II species, Gossypium raimondii, Theobroma cacao, Carica papaya, Citrus clementina, and Arabidopsis thaliana, distributing in three orders, were used to gain insights into the evolutionary patterns of the NBS-encoding genes. Our data showed that frequent copy number variations of NBS-encoding genes were found among these species. Phylogenetic tree analysis and the numbers of the NBS-encoding genes in the common ancestor of these species showed that species-specific NBS clades, including multi-copy and single copy numbers are dominant among these genes. However, not a single clade was found with only five copies, which come from all of the five species, respectively, suggesting rapid turn-over with birth and death of the NBS-encoding genes among Eurosids II species. In addition, a strong positive correlation was observed between the Toll/interleukin receptor (TIR)) type NBS-encoding genes and species-specific genes, indicating rapid gene loss and duplication. Whereas, non- TIR type NBS-encoding genes in these five species showed two distinct evolutionary patterns. (author)

  15. Quantum Optical Realization of Arbitrary Linear Transformations Allowing for Loss and Gain

    Science.gov (United States)

    Tischler, N.; Rockstuhl, C.; Słowik, K.

    2018-04-01

    Unitary transformations are routinely modeled and implemented in the field of quantum optics. In contrast, nonunitary transformations, which can involve loss and gain, require a different approach. In this work, we present a universal method to deal with nonunitary networks. An input to the method is an arbitrary linear transformation matrix of optical modes that does not need to adhere to bosonic commutation relations. The method constructs a transformation that includes the network of interest and accounts for full quantum optical effects related to loss and gain. Furthermore, through a decomposition in terms of simple building blocks, it provides a step-by-step implementation recipe, in a manner similar to the decomposition by Reck et al. [Experimental Realization of Any Discrete Unitary Operator, Phys. Rev. Lett. 73, 58 (1994), 10.1103/PhysRevLett.73.58] but applicable to nonunitary transformations. Applications of the method include the implementation of positive-operator-valued measures and the design of probabilistic optical quantum information protocols.

  16. Phase and gain measurements in a distributed-loss cyclotron-resonance maser amplifier

    International Nuclear Information System (INIS)

    Kesar, Amit; Jerby, Eli

    2002-01-01

    The control of gain and phase delay in a cyclotron-resonance maser (CRM) amplifier is essential for a variety of applications. In this experiment, the gain and phase-delay variations are measured with respect to controlling parameters; the electron-beam current and the axial magnetic field. Following Chu et al. [Phys. Rev. Lett. 74, 1103 (1995)], the CRM amplifier comprises of a distributed-loss waveguide to enable high gain without oscillations. Our experiment yields an amplification up to 26 dB, and a phase-delay control range of 360 deg. In order to keep a fixed gain with the varying phase delay, the two controlling parameters (i.e., the solenoid field and the beam current) are operated together in a compensating mode. The experiment is conducted in a frequency of 7.3 GHz, with an electron beam of 18-kV voltage and 0.25-0.4-A current. The experimental results are compared with a theoretical model. Practical implementations of gain and phase control in CRM devices are discussed

  17. Complex ABCD transformations for optical ring cavities with losses and gain

    International Nuclear Information System (INIS)

    Kudashov, V N; Radin, A M; Plachenov, A B

    1999-01-01

    Complex ABCD field transformations are investigated for inhomogeneous optical ring cavities with losses and gain. It is shown that the sets of eigenfunctions, corresponding to counterpropagating waves, are really biorthogonal: the functions in each of these sets are really orthogonal relative to one another, and have a complex weighting factor independent of the mode number. Bidirectional and unidirectional stability conditions are formulated for such cavities. These conditions are qualitatively different from those for loss-free cavities. A simple algorithm is proposed for the evaluation of the ABCD matrix for a medium with an arbitrary longitudinal inhomogeneity along the beam. (laser applications and other topics in quantum electronics)

  18. Modulating the neural bases of persuasion: why/how, gain/loss, and users/non-users

    Science.gov (United States)

    Katzman, Perri L.; Ames, Daniel L.; Falk, Emily B.; Lieberman, Matthew D.

    2017-01-01

    Abstract Designing persuasive content is challenging, in part because people can be poor predictors of their actions. Medial prefrontal cortex (MPFC) activation during message exposure reliably predicts downstream behavior, but past work has been largely atheoretical. We replicated past results on this relationship and tested two additional framing effects known to alter message receptivity. First, we examined gain- vs. loss-framed reasons for a health behavior (sunscreen use). Consistent with predictions from prospect theory, we observed greater MPFC activity to gain- vs. loss-framed messages, and this activity was associated with behavior. This relationship was stronger for those who were not previously sunscreen users. Second, building on theories of action planning, we compared neural activity during messages regarding how vs. why to enact the behavior. We observed rostral inferior parietal lobule and posterior inferior frontal gyrus activity during action planning (“how” messages), and this activity was associated with behavior; this is in contrast to the relationship between MPFC activity during the “why” (i.e., gain and loss) messages and behavior. These results reinforce that persuasion occurs in part via self-value integration—seeing value and incorporating persuasive messages into one's self-concept—and extend this work to demonstrate how message framing and action planning may influence this process. PMID:27521303

  19. 26 CFR 1.1402(a)-6 - Gain or loss from disposition of property.

    Science.gov (United States)

    2010-04-01

    ... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Tax on Self-Employment Income § 1.1402(a)-6 Gain or loss from..., coal, or iron ore, even though held primarily for sale to customers, if section 631 is applicable to...

  20. High-frequency binge eating predicts weight gain among veterans receiving behavioral weight loss treatments.

    Science.gov (United States)

    Masheb, Robin M; Lutes, Lesley D; Kim, Hyungjin Myra; Holleman, Robert G; Goodrich, David E; Janney, Carol A; Kirsh, Susan; Richardson, Caroline R; Damschroder, Laura J

    2015-01-01

    To assess for the frequency of binge eating behavior and its association with weight loss in an overweight/obese sample of veterans. This study is a secondary analysis of data from the ASPIRE study, a randomized effectiveness trial of weight loss among veterans. Of the 481 enrolled veterans with overweight/obesity, binge eating frequency was obtained by survey for 392 (82%). The majority (77.6%) reported binge eating, and 6.1% reported high-frequency binge eating. Those reporting any binge eating lost 1.4% of body weight, decreased waist circumference by 2.0 cm, and had significantly worse outcomes than those reporting never binge eating who lost about double the weight (2.7%) and reduced waist circumference by twice as much (4.2 cm). The high-frequency binge group gained 1.4% of body weight and increased waist circumference by 0.3 cm. High rates of binge eating were observed in an overweight/obese sample of veterans enrolled in weight loss treatment. The presence of binge eating predicted poorer weight loss outcomes. Furthermore, high-frequency binge eating was associated with weight gain. These findings have operational and policy implications for developing effective strategies to address binge eating in the context of behavioral weight loss programs for veterans. © 2014 The Obesity Society.

  1. Gain-loss-frame in outcome-interdependence : Does it influence equality or equity considerations?

    NARCIS (Netherlands)

    deDreu, CKW

    1996-01-01

    Research suggests that framing outcomes as gains produces stronger concern for distributive justice than framing outcomes as losses. Unfortunately, however, this prior research manipulated own and other's outcomes only (and not own and other's input). Hence, it remained unclear whether framing

  2. Reason's Enemy Is Not Emotion: Engagement of Cognitive Control Networks Explains Biases in Gain/Loss Framing

    Science.gov (United States)

    2017-01-01

    In the classic gain/loss framing effect, describing a gamble as a potential gain or loss biases people to make risk-averse or risk-seeking decisions, respectively. The canonical explanation for this effect is that frames differentially modulate emotional processes, which in turn leads to irrational choice behavior. Here, we evaluate the source of framing biases by integrating functional magnetic resonance imaging data from 143 human participants performing a gain/loss framing task with meta-analytic data from >8000 neuroimaging studies. We found that activation during choices consistent with the framing effect were most correlated with activation associated with the resting or default brain, while activation during choices inconsistent with the framing effect was most correlated with the task-engaged brain. Our findings argue against the common interpretation of gain/loss framing as a competition between emotion and control. Instead, our study indicates that this effect results from differential cognitive engagement across decision frames. SIGNIFICANCE STATEMENT The biases frequently exhibited by human decision makers have often been attributed to the presence of emotion. Using a large fMRI sample and analysis of whole-brain networks defined with the meta-analytic tool Neurosynth, we find that neural activity during frame-biased decisions was more significantly associated with default behaviors (and the absence of executive control) than with emotion. These findings point to a role for neuroscience in shaping long-standing psychological theories in decision science. PMID:28264981

  3. Reason's Enemy Is Not Emotion: Engagement of Cognitive Control Networks Explains Biases in Gain/Loss Framing.

    Science.gov (United States)

    Li, Rosa; Smith, David V; Clithero, John A; Venkatraman, Vinod; Carter, R McKell; Huettel, Scott A

    2017-03-29

    In the classic gain/loss framing effect, describing a gamble as a potential gain or loss biases people to make risk-averse or risk-seeking decisions, respectively. The canonical explanation for this effect is that frames differentially modulate emotional processes, which in turn leads to irrational choice behavior. Here, we evaluate the source of framing biases by integrating functional magnetic resonance imaging data from 143 human participants performing a gain/loss framing task with meta-analytic data from >8000 neuroimaging studies. We found that activation during choices consistent with the framing effect were most correlated with activation associated with the resting or default brain, while activation during choices inconsistent with the framing effect was most correlated with the task-engaged brain. Our findings argue against the common interpretation of gain/loss framing as a competition between emotion and control. Instead, our study indicates that this effect results from differential cognitive engagement across decision frames. SIGNIFICANCE STATEMENT The biases frequently exhibited by human decision makers have often been attributed to the presence of emotion. Using a large fMRI sample and analysis of whole-brain networks defined with the meta-analytic tool Neurosynth, we find that neural activity during frame-biased decisions was more significantly associated with default behaviors (and the absence of executive control) than with emotion. These findings point to a role for neuroscience in shaping long-standing psychological theories in decision science. Copyright © 2017 the authors 0270-6474/17/373588-11$15.00/0.

  4. A Functional Model for the Integration of Gains and Losses under Risk: Implications for the Measurement of Subjective Value

    Science.gov (United States)

    Viegas, Ricardo G.; Oliveira, Armando M.; Garriga-Trillo, Ana; Grieco, Alba

    2012-01-01

    In order to be treated quantitatively, subjective gains and losses (utilities/disutilities) must be psychologically measured. If legitimate comparisons are sought between them, measurement must be at least interval level, with a common unit. If comparisons of absolute magnitudes across gains and losses are further sought, as in standard…

  5. Association between Stock Market Gains and Losses and Google Searches.

    Science.gov (United States)

    Arditi, Eli; Yechiam, Eldad; Zahavi, Gal

    2015-01-01

    Experimental studies in the area of Psychology and Behavioral Economics have suggested that people change their search pattern in response to positive and negative events. Using Internet search data provided by Google, we investigated the relationship between stock-specific events and related Google searches. We studied daily data from 13 stocks from the Dow-Jones and NASDAQ100 indices, over a period of 4 trading years. Focusing on periods in which stocks were extensively searched (Intensive Search Periods), we found a correlation between the magnitude of stock returns at the beginning of the period and the volume, peak, and duration of search generated during the period. This relation between magnitudes of stock returns and subsequent searches was considerably magnified in periods following negative stock returns. Yet, we did not find that intensive search periods following losses were associated with more Google searches than periods following gains. Thus, rather than increasing search, losses improved the fit between people's search behavior and the extent of real-world events triggering the search. The findings demonstrate the robustness of the attentional effect of losses.

  6. When good is stickier than bad: Understanding gain/loss asymmetries in sequential framing effects.

    Science.gov (United States)

    Sparks, Jehan; Ledgerwood, Alison

    2017-08-01

    Considerable research has demonstrated the power of the current positive or negative frame to shape people's current judgments. But humans must often learn about positive and negative information as they encounter that information sequentially over time. It is therefore crucial to consider the potential importance of sequencing when developing an understanding of how humans think about valenced information. Indeed, recent work looking at sequentially encountered frames suggests that some frames can linger outside the context in which they are first encountered, sticking in the mind so that subsequent frames have a muted effect. The present research builds a comprehensive account of sequential framing effects in both the loss and the gain domains. After seeing information about a potential gain or loss framed in positive terms or negative terms, participants saw the same issue reframed in the opposing way. Across 5 studies and 1566 participants, we find accumulating evidence for the notion that in the gain domain, positive frames are stickier than negative frames for novel but not familiar scenarios, whereas in the loss domain, negative frames are always stickier than positive frames. Integrating regulatory focus theory with the literatures on negativity dominance and positivity offset, we develop a new and comprehensive account of sequential framing effects that emphasizes the adaptive value of positivity and negativity biases in specific contexts. Our findings highlight the fact that research conducted solely in the loss domain risks painting an incomplete and oversimplified picture of human bias and suggest new directions for future research. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  7. The indication area of a diagnostic test. Part I--discounting gain and loss in diagnostic certainty

    NARCIS (Netherlands)

    Stalpers, Lukas J. A.; Nelemans, Patty J.; Geurts, Sandra M. E.; Jansen, Erik; de Boer, Peter; Verbeek, André L. M.

    2015-01-01

    Test performance is conventionally expressed by gain in diagnostic certainty. We propose net diagnostic gain and indication area as more appropriate measures of test performance; then, the loss in certainty due to misclassification and the information of "no test" would be performed are taken into

  8. 26 CFR 1.631-3 - Gain or loss upon the disposal of coal or domestic iron ore with a retained economic interest.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Gain or loss upon the disposal of coal or...) Sales and Exchanges § 1.631-3 Gain or loss upon the disposal of coal or domestic iron ore with a... under section 272, shall be gain or loss upon the sale of the coal or iron ore. See paragraph (b)(4) of...

  9. Processes of fungal proteome evolution and gain of function: gene duplication and domain rearrangement

    International Nuclear Information System (INIS)

    Cohen-Gihon, Inbar; Nussinov, Ruth; Sharan, Roded

    2011-01-01

    During evolution, organisms have gained functional complexity mainly by modifying and improving existing functioning systems rather than creating new ones ab initio. Here we explore the interplay between two processes which during evolution have had major roles in the acquisition of new functions: gene duplication and protein domain rearrangements. We consider four possible evolutionary scenarios: gene families that have undergone none of these event types; only gene duplication; only domain rearrangement, or both events. We characterize each of the four evolutionary scenarios by functional attributes. Our analysis of ten fungal genomes indicates that at least for the fungi clade, species significantly appear to gain complexity by gene duplication accompanied by the expansion of existing domain architectures via rearrangements. We show that paralogs gaining new domain architectures via duplication tend to adopt new functions compared to paralogs that preserve their domain architectures. We conclude that evolution of protein families through gene duplication and domain rearrangement is correlated with their functional properties. We suggest that in general, new functions are acquired via the integration of gene duplication and domain rearrangements rather than each process acting independently

  10. Gain of DNA methylation is enhanced in the absence of CTCF at the human retinoblastoma gene promoter

    International Nuclear Information System (INIS)

    Dávalos-Salas, Mercedes; Furlan-Magaril, Mayra; González-Buendía, Edgar; Valdes-Quezada, Christian; Ayala-Ortega, Erandi; Recillas-Targa, Félix

    2011-01-01

    Long-term gene silencing throughout cell division is generally achieved by DNA methylation and other epigenetic processes. Aberrant DNA methylation is now widely recognized to be associated with cancer and other human diseases. Here we addressed the contribution of the multifunctional nuclear factor CTCF to the epigenetic regulation of the human retinoblastoma (Rb) gene promoter in different tumoral cell lines. To assess the DNA methylation status of the Rb promoter, genomic DNA from stably transfected human erythroleukemic K562 cells expressing a GFP reporter transgene was transformed with sodium bisulfite, and then PCR-amplified with modified primers and sequenced. Single- and multi-copy integrants with the CTCF binding site mutated were isolated and characterized by Southern blotting. Silenced transgenes were reactivated using 5-aza-2'-deoxycytidine and Trichostatin-A, and their expression was monitored by fluorescent cytometry. Rb gene expression and protein abundance were assessed by RT-PCR and Western blotting in three different glioma cell lines, and DNA methylation of the promoter region was determined by sodium bisulfite sequencing, together with CTCF dissociation and methyl-CpG-binding protein incorporation by chromatin immunoprecipitation assays. We found that the inability of CTCF to bind to the Rb promoter causes a dramatic loss of gene expression and a progressive gain of DNA methylation. This study indicates that CTCF plays an important role in maintaining the Rb promoter in an optimal chromatin configuration. The absence of CTCF induces a rapid epigenetic silencing through a progressive gain of DNA methylation. Consequently, CTCF can now be seen as one of the epigenetic components that allows the proper configuration of tumor suppressor gene promoters. Its aberrant dissociation can then predispose key genes in cancer cells to acquire DNA methylation and epigenetic silencing

  11. Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data.

    Directory of Open Access Journals (Sweden)

    Niedzica Camacho

    2017-09-01

    Full Text Available A variety of models have been proposed to explain regions of recurrent somatic copy number alteration (SCNA in human cancer. Our study employs Whole Genome DNA Sequence (WGS data from tumor samples (n = 103 to comprehensively assess the role of the Knudson two hit genetic model in SCNA generation in prostate cancer. 64 recurrent regions of loss and gain were detected, of which 28 were novel, including regions of loss with more than 15% frequency at Chr4p15.2-p15.1 (15.53%, Chr6q27 (16.50% and Chr18q12.3 (17.48%. Comprehensive mutation screens of genes, lincRNA encoding sequences, control regions and conserved domains within SCNAs demonstrated that a two-hit genetic model was supported in only a minor proportion of recurrent SCNA losses examined (15/40. We found that recurrent breakpoints and regions of inversion often occur within Knudson model SCNAs, leading to the identification of ZNF292 as a target gene for the deletion at 6q14.3-q15 and NKX3.1 as a two-hit target at 8p21.3-p21.2. The importance of alterations of lincRNA sequences was illustrated by the identification of a novel mutational hotspot at the KCCAT42, FENDRR, CAT1886 and STCAT2 loci at the 16q23.1-q24.3 loss. Our data confirm that the burden of SCNAs is predictive of biochemical recurrence, define nine individual regions that are associated with relapse, and highlight the possible importance of ion channel and G-protein coupled-receptor (GPCR pathways in cancer development. We concluded that a two-hit genetic model accounts for about one third of SCNA indicating that mechanisms, such haploinsufficiency and epigenetic inactivation, account for the remaining SCNA losses.

  12. Resolution and reconciliation of non-binary gene trees with transfers, duplications and losses.

    Science.gov (United States)

    Jacox, Edwin; Weller, Mathias; Tannier, Eric; Scornavacca, Celine

    2017-04-01

    Gene trees reconstructed from sequence alignments contain poorly supported branches when the phylogenetic signal in the sequences is insufficient to determine them all. When a species tree is available, the signal of gains and losses of genes can be used to correctly resolve the unsupported parts of the gene history. However finding a most parsimonious binary resolution of a non-binary tree obtained by contracting the unsupported branches is NP-hard if transfer events are considered as possible gene scale events, in addition to gene origination, duplication and loss. We propose an exact, parameterized algorithm to solve this problem in single-exponential time, where the parameter is the number of connected branches of the gene tree that show low support from the sequence alignment or, equivalently, the maximum number of children of any node of the gene tree once the low-support branches have been collapsed. This improves on the best known algorithm by an exponential factor. We propose a way to choose among optimal solutions based on the available information. We show the usability of this principle on several simulated and biological datasets. The results are comparable in quality to several other tested methods having similar goals, but our approach provides a lower running time and a guarantee that the produced solution is optimal. Our algorithm has been integrated into the ecceTERA phylogeny package, available at http://mbb.univ-montp2.fr/MBB/download_sources/16__ecceTERA and which can be run online at http://mbb.univ-montp2.fr/MBB/subsection/softExec.php?soft=eccetera . celine.scornavacca@umontpellier.fr. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  13. Modulating the neural bases of persuasion: why/how, gain/loss, and users/non-users.

    Science.gov (United States)

    Vezich, I Stephanie; Katzman, Perri L; Ames, Daniel L; Falk, Emily B; Lieberman, Matthew D

    2017-02-01

    Designing persuasive content is challenging, in part because people can be poor predictors of their actions. Medial prefrontal cortex (MPFC) activation during message exposure reliably predicts downstream behavior, but past work has been largely atheoretical. We replicated past results on this relationship and tested two additional framing effects known to alter message receptivity. First, we examined gain- vs. loss-framed reasons for a health behavior (sunscreen use). Consistent with predictions from prospect theory, we observed greater MPFC activity to gain- vs. loss-framed messages, and this activity was associated with behavior. This relationship was stronger for those who were not previously sunscreen users. Second, building on theories of action planning, we compared neural activity during messages regarding how vs. why to enact the behavior. We observed rostral inferior parietal lobule and posterior inferior frontal gyrus activity during action planning ("how" messages), and this activity was associated with behavior; this is in contrast to the relationship between MPFC activity during the "why" (i.e., gain and loss) messages and behavior. These results reinforce that persuasion occurs in part via self-value integration-seeing value and incorporating persuasive messages into one's self-concept-and extend this work to demonstrate how message framing and action planning may influence this process. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  14. Reduced rates of gene loss, gene silencing, and gene mutation in Dnmt1-deficient embryonic stem cells

    NARCIS (Netherlands)

    Chan, M.F.; van Amerongen, R.; Nijjar, T.; Cuppen, E.; Jones, P.A.; Laird, P.W.

    2001-01-01

    Tumor suppressor gene inactivation is a crucial event in oncogenesis. Gene inactivation mechanisms include events resulting in loss of heterozygosity (LOH), gene mutation, and transcriptional silencing. The contribution of each of these different pathways varies among tumor suppressor genes and by

  15. Missed losses loom larger than missed gains: Electrodermal reactivity to decision choices and outcomes in a gambling task.

    Science.gov (United States)

    Wu, Yin; Van Dijk, Eric; Aitken, Mike; Clark, Luke

    2016-04-01

    Loss aversion is a defining characteristic of prospect theory, whereby responses are stronger to losses than to equivalently sized gains (Kahneman & Tversky Econometrica, 47, 263-291, 1979). By monitoring electrodermal activity (EDA) during a gambling task, in this study we examined physiological activity during risky decisions, as well as to both obtained (e.g., gains and losses) and counterfactual (e.g., narrowly missed gains and losses) outcomes. During the bet selection phase, EDA increased linearly with bet size, highlighting the role of somatic signals in decision-making under uncertainty in a task without any learning requirement. Outcome-related EDA scaled with the magnitudes of monetary wins and losses, and losses had a stronger impact on EDA than did equivalently sized wins. Narrowly missed wins (i.e., near-wins) and narrowly missed losses (i.e., near-losses) also evoked EDA responses, and the change of EDA as a function of the size of the missed outcome was modestly greater for near-losses than for near-wins, suggesting that near-losses have more impact on subjective value than do near-wins. Across individuals, the slope for choice-related EDA (as a function of bet size) correlated with the slope for outcome-related EDA as a function of both the obtained and counterfactual outcome magnitudes, and these correlations were stronger for loss and near-loss conditions than for win and near-win conditions. Taken together, these asymmetrical EDA patterns to objective wins and losses, as well as to near-wins and near-losses, provide a psychophysiological instantiation of the value function curve in prospect theory, which is steeper in the negative than in the positive domain.

  16. Estimating coastal wetland gain and losses in Galveston County and Cameron County, Texas, USA.

    Science.gov (United States)

    Entwistle, Clare; Mora, Miguel A; Knight, Robert

    2018-01-01

    Coastal wetlands serve many important ecological services. One of these important ecological services is their use as storm buffers. Coastal wetlands provide habitat for migratory birds and aquatic species and can improve water quality. In the late 1990s, the US Fish and Wildlife Service (USFWS) published a study outlining the trends of coastal wetlands from the 1950s to early 1990s. In the present study, wetland gains and losses were calculated for Galveston County and Cameron County, Texas, USA, between 2001 and 2011. Maps from the National Land Cover Database were used to determine wetland areas for the years 2001, 2006, and 2011. ArcGIS was used to compare land cover between the study periods to determine overall wetland losses and gains. A statistical analysis was performed between wetland loss and population data to determine whether increased population density led to a higher loss of wetlands. Our analysis indicates that wetland loss is still occurring, however at a lower rate of loss (0.14%-0.18% annually) than the USFWS study predicted earlier (2.7%). In addition, the majority of wetland losses were due to conversion to upland areas. We found a positive correlation between increased population density and decreased wetland area; however, the trend was not significant. The present study shows how the majority of wetland loss in Galveston and Cameron counties is occurring as a result of increased upland areas. In addition, the present study shows that the use of online mapping systems can be used as a low-cost alternative to assess land changes when field tests are not feasible. Integr Environ Assess Manag 2018;14:120-129. © 2017 SETAC. © 2017 SETAC.

  17. Tropical forests are a net carbon source based on aboveground measurements of gain and loss

    Science.gov (United States)

    Baccini, A.; Walker, W.; Carvalho, L.; Farina, M.; Sulla-Menashe, D.; Houghton, R. A.

    2017-10-01

    The carbon balance of tropical ecosystems remains uncertain, with top-down atmospheric studies suggesting an overall sink and bottom-up ecological approaches indicating a modest net source. Here we use 12 years (2003 to 2014) of MODIS pantropical satellite data to quantify net annual changes in the aboveground carbon density of tropical woody live vegetation, providing direct, measurement-based evidence that the world’s tropical forests are a net carbon source of 425.2 ± 92.0 teragrams of carbon per year (Tg C year-1). This net release of carbon consists of losses of 861.7 ± 80.2 Tg C year-1 and gains of 436.5 ± 31.0 Tg C year-1. Gains result from forest growth; losses result from deforestation and from reductions in carbon density within standing forests (degradation or disturbance), with the latter accounting for 68.9% of overall losses.

  18. Preaching to the choir? The influence of personal relevance on the effects of gain- and loss-framed health-promoting messages

    NARCIS (Netherlands)

    Riet, van 't J.P.; Ruiter, de R.; Vries, de H.

    2012-01-01

    This article examines the moderating influence of personal relevance on the persuasive effects of gain- and loss-framed messages. We assessed current behaviour as a proxy for personal relevance, provided 169 participants with gain- and loss-framed messages advocating skin self-examination (SSE) and

  19. 26 CFR 1.988-2 - Recognition and computation of exchange gain or loss.

    Science.gov (United States)

    2010-04-01

    ... computation of exchange gain or loss. (a) Disposition of nonfunctional currency—(1) Recognition of exchange... currency shall be governed by the recognition provisions of the Internal Revenue Code which apply to the... 1092). The disposition of nonfunctional currency in settlement of a forward contract, futures contract...

  20. Casimir forces in multilayer magnetodielectrics with both gain and loss

    DEFF Research Database (Denmark)

    Amooghorban, Ehsan; Wubs, Martijn; Mortensen, N. Asger

    2011-01-01

    of the amplifying medium, with negative imaginary parts in finite frequency intervals, are identified and their relationships to microscopic coupling functions are determined. By carefully relating the two-point functions of the field theory to the optical Green functions, we calculate the Casimir energy...... and Casimir forces for a multilayer magnetodielectric medium with both gain and loss. We point out the essential differences with a purely passive layered medium. For a single layer, we find different bounds on the Casimir force for fully amplifying and for lossy media. The force is attractive in both cases...

  1. Recombination between Homeologous Chromosomes in Lager Yeasts leads to Loss of Function of the Hybrid GPH1 Gene.

    OpenAIRE

    BOND, URSULA

    2009-01-01

    PUBLISHED Yeasts used in the production of lagers contain complex allopolyploid genomes, resulting from the fusion of two different yeast species closely related to Saccharomyces cerevisiae and Saccharomyces bayanus. Recombination between the homoeologous chromosomes has generated a number of hybrid chromosomes. These recombination events provide potential for adaptive evolution through the loss or gain of gene function. We have examined the genotypic and phenotypic effects of one of the c...

  2. Dissociable effects of basolateral amygdala lesions on decision making biases in rats when loss or gain is emphasized.

    Science.gov (United States)

    Tremblay, Melanie; Cocker, Paul J; Hosking, Jay G; Zeeb, Fiona D; Rogers, Robert D; Winstanley, Catharine A

    2014-12-01

    Individuals switch from risk seeking to risk aversion when mathematically identical options are described in terms of loss versus gains, as exemplified in the reflection and framing effects. Determining the neurobiology underlying such cognitive biases could inform our understanding of decision making in health and disease. Although reports vary, data using human subjects have implicated the amygdala in such biases. Animal models enable more detailed investigation of neurobiological mechanisms. We therefore tested whether basolateral amygdala (BLA) lesions would affect risk preference for gains or losses in rats. Choices in both paradigms were always between options of equal expected value-a guaranteed outcome, or the 50:50 chance of double or nothing. In the loss-chasing task, most rats exhibited strong risk seeking preferences, gambling at the risk of incurring double the penalty, regardless of the size of the guaranteed loss. In the betting task, the majority of animals were equivocal in their choice, irrespective of bet size; however, a wager-sensitive subgroup progressively shifted away from the uncertain option as the bet size increased, which is reminiscent of risk aversion. BLA lesions increased preference for the smaller guaranteed loss in the loss-chasing task, without affecting choice on the betting task, which is indicative of reduced risk seeking for losses, but intact risk aversion for gains. These data support the hypothesis that the amygdala plays a more prominent role in choice biases related to losses. Given the importance of the amygdala in representing negative affect, the aversive emotional reaction to loss, rather than aberrant estimations of probability or loss magnitude, may underlie risk seeking for losses.

  3. Relative Gains, Losses, and Reference Points in Probabilistic Choice in Rats

    Science.gov (United States)

    Marshall, Andrew T.; Kirkpatrick, Kimberly

    2015-01-01

    Theoretical reference points have been proposed to differentiate probabilistic gains from probabilistic losses in humans, but such a phenomenon in non-human animals has yet to be thoroughly elucidated. Three experiments evaluated the effect of reward magnitude on probabilistic choice in rats, seeking to determine reference point use by examining the effect of previous outcome magnitude(s) on subsequent choice behavior. Rats were trained to choose between an outcome that always delivered reward (low-uncertainty choice) and one that probabilistically delivered reward (high-uncertainty). The probability of high-uncertainty outcome receipt and the magnitudes of low-uncertainty and high-uncertainty outcomes were manipulated within and between experiments. Both the low- and high-uncertainty outcomes involved variable reward magnitudes, so that either a smaller or larger magnitude was probabilistically delivered, as well as reward omission following high-uncertainty choices. In Experiments 1 and 2, the between groups factor was the magnitude of the high-uncertainty-smaller (H-S) and high-uncertainty-larger (H-L) outcome, respectively. The H-S magnitude manipulation differentiated the groups, while the H-L magnitude manipulation did not. Experiment 3 showed that manipulating the probability of differential losses as well as the expected value of the low-uncertainty choice produced systematic effects on choice behavior. The results suggest that the reference point for probabilistic gains and losses was the expected value of the low-uncertainty choice. Current theories of probabilistic choice behavior have difficulty accounting for the present results, so an integrated theoretical framework is proposed. Overall, the present results have implications for understanding individual differences and corresponding underlying mechanisms of probabilistic choice behavior. PMID:25658448

  4. Relative gains, losses, and reference points in probabilistic choice in rats.

    Directory of Open Access Journals (Sweden)

    Andrew T Marshall

    Full Text Available Theoretical reference points have been proposed to differentiate probabilistic gains from probabilistic losses in humans, but such a phenomenon in non-human animals has yet to be thoroughly elucidated. Three experiments evaluated the effect of reward magnitude on probabilistic choice in rats, seeking to determine reference point use by examining the effect of previous outcome magnitude(s on subsequent choice behavior. Rats were trained to choose between an outcome that always delivered reward (low-uncertainty choice and one that probabilistically delivered reward (high-uncertainty. The probability of high-uncertainty outcome receipt and the magnitudes of low-uncertainty and high-uncertainty outcomes were manipulated within and between experiments. Both the low- and high-uncertainty outcomes involved variable reward magnitudes, so that either a smaller or larger magnitude was probabilistically delivered, as well as reward omission following high-uncertainty choices. In Experiments 1 and 2, the between groups factor was the magnitude of the high-uncertainty-smaller (H-S and high-uncertainty-larger (H-L outcome, respectively. The H-S magnitude manipulation differentiated the groups, while the H-L magnitude manipulation did not. Experiment 3 showed that manipulating the probability of differential losses as well as the expected value of the low-uncertainty choice produced systematic effects on choice behavior. The results suggest that the reference point for probabilistic gains and losses was the expected value of the low-uncertainty choice. Current theories of probabilistic choice behavior have difficulty accounting for the present results, so an integrated theoretical framework is proposed. Overall, the present results have implications for understanding individual differences and corresponding underlying mechanisms of probabilistic choice behavior.

  5. Energy losses (gains) of massive coloured particles in stochastic colour medium

    International Nuclear Information System (INIS)

    Leonidov, A.; Rossijskaya Akademiya Nauk, Moscow

    1995-01-01

    The propagation of massive coloured particles in stochastic background chromoelectric field is studied using the semiclassical equations of motion. Depending on the nature of the stochastic background we obtain the formulae for the energy losses of heavy coloured projectile in nonperturbative hadronic medium and for the energy gains in the stochastic field present, e.g., in the turbulent plasma. The result appears to be significantly dependent on the form of the correlation function of stochastic external field. (orig.)

  6. Stratification of clear cell renal cell carcinoma (ccRCC) genomes by gene-directed copy number alteration (CNA) analysis.

    Science.gov (United States)

    Thiesen, H-J; Steinbeck, F; Maruschke, M; Koczan, D; Ziems, B; Hakenberg, O W

    2017-01-01

    Tumorigenic processes are understood to be driven by epi-/genetic and genomic alterations from single point mutations to chromosomal alterations such as insertions and deletions of nucleotides up to gains and losses of large chromosomal fragments including products of chromosomal rearrangements e.g. fusion genes and proteins. Overall comparisons of copy number alterations (CNAs) presented in 48 clear cell renal cell carcinoma (ccRCC) genomes resulted in ratios of gene losses versus gene gains between 26 ccRCC Fuhrman malignancy grades G1 (ratio 1.25) and 20 G3 (ratio 0.58). Gene losses and gains of 15762 CNA genes were mapped to 795 chromosomal cytoband loci including 280 KEGG pathways. CNAs were classified according to their contribution to Fuhrman tumour gradings G1 and G3. Gene gains and losses turned out to be highly structured processes in ccRCC genomes enabling the subclassification and stratification of ccRCC tumours in a genome-wide manner. CNAs of ccRCC seem to start with common tumour related gene losses flanked by CNAs specifying Fuhrman grade G1 losses and CNA gains favouring grade G3 tumours. The appearance of recurrent CNA signatures implies the presence of causal mechanisms most likely implicated in the pathogenesis and disease-outcome of ccRCC tumours distinguishing lower from higher malignant tumours. The diagnostic quality of initial 201 genes (108 genes supporting G1 and 93 genes G3 phenotypes) has been successfully validated on published Swiss data (GSE19949) leading to a restricted CNA gene set of 171 CNA genes of which 85 genes favour Fuhrman grade G1 and 86 genes Fuhrman grade G3. Regarding these gene sets overall survival decreased with the number of G3 related gene losses plus G3 related gene gains. CNA gene sets presented define an entry to a gene-directed and pathway-related functional understanding of ongoing copy number alterations within and between individual ccRCC tumours leading to CNA genes of prognostic and predictive value.

  7. Simultaneous realization of a coherent perfect absorber and laser by zero-index media with both gain and loss

    KAUST Repository

    Bai, Ping

    2016-12-20

    We investigate a unique type of zero-index medium with both gain and loss (ZIMGL), whose effective permittivity and permeability are both purely imaginary but of opposite signs. We analytically show that, by using a slab of ZIMGL with equal magnitude of loss and gain, simulation realization of a coherent perfect absorber (CPA) and laser, i.e., the so-called CPA laser, can be achieved. Previously the CPA laser was proposed in parity-time (PT) symmetric systems. However, the ZIMGL does not possess the PT symmetry and thus the underlying physics is distinctly different. By designing a photonic crystal (PC) composed of core-shell rods, with loss and gain distributed in either the core or the shell, we have realized such a ZIMGL. The CPA-laser functionality of such a PC is also confirmed in our numerical simulations. Our work provides a different approach for simultaneous realization of CPA and laser besides PT-symmetric systems.

  8. The influence of loss and gain of body mass on ovarian activity in ...

    African Journals Online (AJOL)

    Ovarian activity was studied in 36 dry, Bos taurus cows fed to achieve different rates of body mass loss and gain in a 2 x 2 factorial experiment. Cows were fed hay to supply either 70% (Treatments 1, 2) or 40% (Treatments. 3,4) of their ME requirements for maintenance until they became anoestrus. Following a 90-day ...

  9. Tropical forests are a net carbon source based on aboveground measurements of gain and loss.

    Science.gov (United States)

    Baccini, A; Walker, W; Carvalho, L; Farina, M; Sulla-Menashe, D; Houghton, R A

    2017-10-13

    The carbon balance of tropical ecosystems remains uncertain, with top-down atmospheric studies suggesting an overall sink and bottom-up ecological approaches indicating a modest net source. Here we use 12 years (2003 to 2014) of MODIS pantropical satellite data to quantify net annual changes in the aboveground carbon density of tropical woody live vegetation, providing direct, measurement-based evidence that the world's tropical forests are a net carbon source of 425.2 ± 92.0 teragrams of carbon per year (Tg C year -1 ). This net release of carbon consists of losses of 861.7 ± 80.2 Tg C year -1 and gains of 436.5 ± 31.0 Tg C year -1 Gains result from forest growth; losses result from deforestation and from reductions in carbon density within standing forests (degradation or disturbance), with the latter accounting for 68.9% of overall losses. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  10. Recurrent Fusion Genes in Gastric Cancer: CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity

    Directory of Open Access Journals (Sweden)

    Fei Yao

    2015-07-01

    Full Text Available Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET whole-genome sequencing, we analyzed 15 gastric cancers (GCs from Southeast Asians. Rearrangements were enriched in open chromatin and shaped by chromatin structure. We identified seven rearrangement hot spots and 136 gene fusions. In three out of 100 GC cases, we found recurrent fusions between CLDN18, a tight junction gene, and ARHGAP26, a gene encoding a RHOA inhibitor. Epithelial cell lines expressing CLDN18-ARHGAP26 displayed a dramatic loss of epithelial phenotype and long protrusions indicative of epithelial-mesenchymal transition (EMT. Fusion-positive cell lines showed impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, and inhibition of RHOA. Gain of invasion was seen in cancer cell lines expressing the fusion. Thus, CLDN18-ARHGAP26 mediates epithelial disintegration, possibly leading to stomach H+ leakage, and the fusion might contribute to invasiveness once a cell is transformed.

  11. Loss and Gain in Translation of Culture-Specific Items in Ahmad Tohari’s Lintang Kemukus from Indonesian Into English: A Semantic Study

    Directory of Open Access Journals (Sweden)

    Leni Tiwiyanti

    2017-05-01

    Full Text Available Culture-specific items (CSIs are difficult to translate since they are related to cultural knowledge and cultural background of the given culture. The distance and differences between two different cultures determine the extent of the gain or loss that will be exprienced by the CSIs as they are translated. The purposes of this research were to identify the translation procedures applied in translating CSIs which caused loss and gained in the translation process and to identify how the translator compensated the loss in translating CSIs. The method used was qualitative descriptive method. The result shows that loss is more prevalent than gain although the translator has enough knowledge on the source text culture as he has spent some years doing some researches in Banyumas society. There are two kinds of losses found in this study; inevitable and avertable losses. Translation procedures used which result in loss in translation are translation by a more general word (subordinate, translation by a more neutral/less expressive word and translation by cultural substitution. Gain was realized mostly through the creativity of the translator when they are able to explain the culture-specific items for effective communication. In order to compensate the loss that might have occurred, translator uses some translation procedures. They are translation by loan word with explanation, translation by paraphrase using related word, and translation by paraphrase using unrelated word. In short, gain in translation for better communication is not easy to achieve especially in the case of translating CSIs.

  12. Maintenance and Loss of Duplicated Genes by Dosage Subfunctionalization.

    Science.gov (United States)

    Gout, Jean-Francois; Lynch, Michael

    2015-08-01

    Whole-genome duplications (WGDs) have contributed to gene-repertoire enrichment in many eukaryotic lineages. However, most duplicated genes are eventually lost and it is still unclear why some duplicated genes are evolutionary successful whereas others quickly turn to pseudogenes. Here, we show that dosage constraints are major factors opposing post-WGD gene loss in several Paramecium species that share a common ancestral WGD. We propose a model where a majority of WGD-derived duplicates preserve their ancestral function and are retained to produce enough of the proteins performing this same ancestral function. Under this model, the expression level of individual duplicated genes can evolve neutrally as long as they maintain a roughly constant summed expression, and this allows random genetic drift toward uneven contributions of the two copies to total expression. Our analysis suggests that once a high level of imbalance is reached, which can require substantial lengths of time, the copy with the lowest expression level contributes a small enough fraction of the total expression that selection no longer opposes its loss. Extension of our analysis to yeast species sharing a common ancestral WGD yields similar results, suggesting that duplicated-gene retention for dosage constraints followed by divergence in expression level and eventual deterministic gene loss might be a universal feature of post-WGD evolution. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Gain- and Loss-Related Brain Activation Are Associated with Information Search Differences in Risky Gambles: An fMRI and Eye-Tracking Study.

    Science.gov (United States)

    Häusler, Alexander Niklas; Oroz Artigas, Sergio; Trautner, Peter; Weber, Bernd

    2016-01-01

    People differ in the way they approach and handle choices with unsure outcomes. In this study, we demonstrate that individual differences in the neural processing of gains and losses relates to attentional differences in the way individuals search for information in gambles. Fifty subjects participated in two independent experiments. Participants first completed an fMRI experiment involving financial gains and losses. Subsequently, they performed an eye-tracking experiment on binary choices between risky gambles, each displaying monetary outcomes and their respective probabilities. We find that individual differences in gain and loss processing relate to attention distribution. Individuals with a stronger reaction to gains in the ventromedial prefrontal cortex paid more attention to monetary amounts, while a stronger reaction in the ventral striatum to losses was correlated with an increased attention to probabilities. Reaction in the posterior cingulate cortex to losses was also found to correlate with an increased attention to probabilities. Our data show that individual differences in brain activity and differences in information search processes are closely linked.

  14. Sudden losses and sudden gains during a DBT-PTSD treatment for posttraumatic stress disorder following childhood sexual abuse

    Directory of Open Access Journals (Sweden)

    Antje Krüger

    2014-09-01

    Full Text Available Background: Exposure-based treatment approaches are first-line interventions for patients suffering from posttraumatic stress disorder (PTSD. However, the dissemination of exposure-based treatments for PTSD is challenging, as a large proportion of clinicians report being concerned about symptoms worsening as a result of this type of intervention and are therefore reluctant to offer it to patients with PTSD. However, there is only little empirical evidence to date on the pattern of symptom worsening during exposure-based treatment for PTSD. Objective: The goal of the present study was to explore the frequency of sudden losses and sudden gains in the course of an exposure-based treatment programme for female patients suffering from PTSD related to childhood sexual abuse who also show severe comorbidity. In addition, the relationship between sudden changes and treatment outcome was examined. Methods: Female participants (N=74 were randomised to either a 12-week residential DBT-PTSD programme or a treatment-as-usual wait list. The pattern of symptom change was assessed via weekly assessments using the Posttraumatic Diagnostic Scale (PDS. Sudden changes were computed as suggested by the literature on sudden gains. Results: During treatment, only one participant (3% experienced a sudden loss, whereas 25% of participants experienced sudden gains. In the waiting condition, 8% of the participants experienced sudden losses and 5% experienced sudden gains during the same time period. No symptom worsening was observed in response to exposure sessions. However, sudden gains occurred during exposure and non-exposure treatment weeks. Patients with sudden gains showed better treatment outcome in the post-treatment and follow-up assessments. Conclusions: Exposure-based treatment did not lead to PTSD symptom worsening in the study sample. Results show that sudden gains occur frequently during PTSD treatment and have a prognostic value for treatment outcome.

  15. Hearing-loss-associated gene detection in neonatal intensive care unit.

    Science.gov (United States)

    Yang, S M; Liu, Ying; Liu, C; Yin, A H; Wu, Y F; Zheng, X E; Yang, H M; Yang, J

    2018-02-01

    To investigate the frequency and mutation spectrum of hearing loss-associated gene mutation in Neonatal Intensive Care Unit (NICU). Neonates (n=2305) admitted to NICU were enrolled in this study. Nine prominent hearing loss-associated genes, GJB2 (35 del G, 176 del 16,235 del C, 299 del AT), GJB3 (538 C > T), SLC26A4 (IVS7-2A > G, 2168 A > G) and mtDNA 12S rRNA(1555 A > G, 1494 C > T), were detected. There were 73 cases hearing-loss-associated gene mutation among 2305 cases, the mutation frequency was 3.1%, with 40 cases GJB2 (235del C) mutation (54.8%), 6 cases GJB2 (299 del AT) mutation (8.2%), 21 cases SLC26A4 (IVS 7-2 A > G) mutation (28.7%), 4 cases SLC26A4 (2168 A > G) mutation (5.5%), 2 cases of GJB2 (235del C) combined SLC26A4 (IVS 7-2 A > G, 2168 A > G) mutation (2.8%). Among 73 gene mutation cases, preterm neonates presented in 18 cases, accounting for 24.7% (18/73); hyperbilirubinemia in 13 cases, accounting for 17.8% (13/73); Torch Syndrome in 15 cases, with 12 cases CMV, 2 cases rubella, 1 case toxoplasm, respectively, totally accounting for 20.54% (15/73); neonatal pneumonia in 12 cases, accounting for 16.4% (12/73); birth asphyxia in 5 cases, accounting for 6.9% (5/73); sepsis in 5 cases, accounting for 6.9% (5/73); others in 5 cases, accounting for 6.8% (5/73) . The frequency of hearing loss-associated gene mutation was higher in NICU.There were hearing loss-associated gene mutations in the NICU, suggesting this mutation may complicate with perinatal high-risk factors.

  16. The molecular evolution of cytochrome P450 genes within and between drosophila species.

    Science.gov (United States)

    Good, Robert T; Gramzow, Lydia; Battlay, Paul; Sztal, Tamar; Batterham, Philip; Robin, Charles

    2014-04-20

    We map 114 gene gains and 74 gene losses in the P450 gene family across the phylogeny of 12 Drosophila species by examining the congruence of gene trees and species trees. Although the number of P450 genes varies from 74 to 94 in the species examined, we infer that there were at least 77 P450 genes in the ancestral Drosophila genome. One of the most striking observations in the data set is the elevated loss of P450 genes in the Drosophila sechellia lineage. The gain and loss events are not evenly distributed among the P450 genes-with 30 genes showing no gene gains or losses whereas others show as many as 20 copy number changes among the species examined. The P450 gene clades showing the fewest number of gene gain and loss events tend to be those evolving with the most purifying selection acting on the protein sequences, although there are exceptions, such as the rapid rate of amino acid replacement observed in the single copy phantom (Cyp306a1) gene. Within D. melanogaster, we observe gene copy number polymorphism in ten P450 genes including multiple cases of interparalog chimeras. Nonallelic homologous recombination (NAHR) has been associated with deleterious mutations in humans, but here we provide a second possible example of an NAHR event in insect P450s being adaptive. Specifically, we find that a polymorphic Cyp12a4/Cyp12a5 chimera correlates with resistance to an insecticide. Although we observe such interparalog exchange in our within-species data sets, we have little evidence of it between species, raising the possibility that such events may occur more frequently than appreciated but are masked by subsequent sequence change. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  17. Displaying Voter Gains and Losses: Local Government Elections in South Africa for 2011 and 2016

    CSIR Research Space (South Africa)

    Schmitz, Peter MU

    2017-05-01

    Full Text Available of voter behavior between two subsequent local government elections from 2011 and 2016. The percentage voter gains and losses for the top three political parties in South Africa are shown. In the election of 2016, the ruling African National Congress (ANC...

  18. Genetic Variation in the Leptin Receptor Gene, Leptin, and Weight Gain in Young Dutch Adults

    NARCIS (Netherlands)

    Rossum, van C.T.M.; Hoebee, B.; Baak, van M.A.; Mars, M.; Saris, W.H.M.; Seidell, J.C.

    2003-01-01

    Objective: To investigate the association between leptin levels, polymorphisms in the leptin receptor (LEPR) gene, and weight gain. Research Methods and Procedures: From two large prospective cohorts in The Netherlands (n = 17, 500), we compared the baseline leptin of 259 subjects who had gained an

  19. Algorithms for computing parsimonious evolutionary scenarios for genome evolution, the last universal common ancestor and dominance of horizontal gene transfer in the evolution of prokaryotes

    Directory of Open Access Journals (Sweden)

    Galperin Michael Y

    2003-01-01

    Full Text Available Abstract Background Comparative analysis of sequenced genomes reveals numerous instances of apparent horizontal gene transfer (HGT, at least in prokaryotes, and indicates that lineage-specific gene loss might have been even more common in evolution. This complicates the notion of a species tree, which needs to be re-interpreted as a prevailing evolutionary trend, rather than the full depiction of evolution, and makes reconstruction of ancestral genomes a non-trivial task. Results We addressed the problem of constructing parsimonious scenarios for individual sets of orthologous genes given a species tree. The orthologous sets were taken from the database of Clusters of Orthologous Groups of proteins (COGs. We show that the phyletic patterns (patterns of presence-absence in completely sequenced genomes of almost 90% of the COGs are inconsistent with the hypothetical species tree. Algorithms were developed to reconcile the phyletic patterns with the species tree by postulating gene loss, COG emergence and HGT (the latter two classes of events were collectively treated as gene gains. We prove that each of these algorithms produces a parsimonious evolutionary scenario, which can be represented as mapping of loss and gain events on the species tree. The distribution of the evolutionary events among the tree nodes substantially depends on the underlying assumptions of the reconciliation algorithm, e.g. whether or not independent gene gains (gain after loss after gain are permitted. Biological considerations suggest that, on average, gene loss might be a more likely event than gene gain. Therefore different gain penalties were used and the resulting series of reconstructed gene sets for the last universal common ancestor (LUCA of the extant life forms were analysed. The number of genes in the reconstructed LUCA gene sets grows as the gain penalty increases. However, qualitative examination of the LUCA versions reconstructed with different gain penalties

  20. Dominant Drop mutants are gain-of-function alleles of the muscle segment homeobox gene (msh) whose overexpression leads to the arrest of eye development.

    Science.gov (United States)

    Mozer, B A

    2001-05-15

    Dominant Drop (Dr) mutations are nearly eyeless and have additional recessive phenotypes including lethality and patterning defects in eye and sensory bristles due to cis-regulatory lesions in the cell cycle regulator string (stg). Genetic analysis demonstrates that the dominant small eye phenotype is the result of separate gain-of-function mutations in the closely linked muscle segment homeobox (msh) gene, encoding a homeodomain transcription factor required for patterning of muscle and nervous system. Reversion of the Dr(Mio) allele was coincident with the generation of lethal loss-of-function mutations in msh in cis, suggesting that the dominant eye phenotype is the result of ectopic expression. Molecular genetic analysis revealed that two dominant Dr alleles contain lesions upstream of the msh transcription start site. In the Dr(Mio) mutant, a 3S18 retrotransposon insertion is the target of second-site mutations (P-element insertions or deletions) which suppress the dominant eye phenotype following reversion. The pattern of 3S18 expression and the absence of msh in eye imaginal discs suggest that transcriptional activation of the msh promoter accounts for ectopic expression. Dr dominant mutations arrest eye development by blocking the progression of the morphogenetic furrow leading to photoreceptor cell loss via apoptosis. Gal4-mediated ubiquitous expression of msh in third-instar larvae was sufficient to arrest the morphogenetic furrow in the eye imaginal disc and resulted in lethality prior to eclosion. Dominant mutations in the human msx2 gene, one of the vertebrate homologs of msh, are associated with craniosynostosis, a disease affecting cranial development. The Dr mutations are the first example of gain-of-function mutations in the msh/msx gene family identified in a genetically tractible model organism and may serve as a useful tool to identify additional genes that regulate this class of homeodomain proteins. Copyright 2001 Academic Press.

  1. Metformin and berberine prevent olanzapine-induced weight gain in rats.

    Directory of Open Access Journals (Sweden)

    Yueshan Hu

    Full Text Available Olanzapine is a first line medication for the treatment of schizophrenia, but it is also one of the atypical antipsychotics carrying the highest risk of weight gain. Metformin was reported to produce significant attenuation of antipsychotic-induced weight gain in patients, while the study of preventing olanzapine-induced weight gain in an animal model is absent. Berberine, an herbal alkaloid, was shown in our previous studies to prevent fat accumulation in vitro and in vivo. Utilizing a well-replicated rat model of olanzapine-induced weight gain, here we demonstrated that two weeks of metformin or berberine treatment significantly prevented the olanzapine-induced weight gain and white fat accumulation. Neither metformin nor berberine treatment demonstrated a significant inhibition of olanzapine-increased food intake. But interestingly, a significant loss of brown adipose tissue caused by olanzapine treatment was prevented by the addition of metformin or berberine. Our gene expression analysis also demonstrated that the weight gain prevention efficacy of metformin or berberine treatment was associated with changes in the expression of multiple key genes controlling energy expenditure. This study not only demonstrates a significant preventive efficacy of metformin and berberine treatment on olanzapine-induced weight gain in rats, but also suggests a potential mechanism of action for preventing olanzapine-reduced energy expenditure.

  2. Gain of chromosomal region 20q and loss of 18 discriminates between Lynch syndrome and familial colorectal cancer

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Jönsson, Göran; Dominguez-Valentin, Mev

    2013-01-01

    Lynch syndrome and familial colorectal cancer type X, FCCTX, represent the two predominant colorectal cancer syndromes. Whereas Lynch syndrome is clinically and genetically well defined, the genetic cause of FCCTX is unknown and genomic differences between Lynch syndrome and FCCTX tumours...... are largely unknown. We applied array-based comparative genomic hybridisation to 23 colorectal cancers from FCCTX with comparison to 23 Lynch syndrome tumours and to 45 sporadic colorectal cancers. FCCTX tumours showed genomic complexity with frequent gains on chromosomes 20q, 19 and 17 and losses of 18, 8p...... and 15. Gain of genetic material in two separate regions encompassing, 20q12-13.12 and 20q13.2-13.32, was identified in 65% of the FCCTX tumours. Gain of material on chromosome 20q and loss on chromosome 18 significantly discriminated colorectal cancers associated with FCCTX from Lynch syndrome, which...

  3. Recurrent loss of specific introns during angiosperm evolution.

    Directory of Open Access Journals (Sweden)

    Hao Wang

    2014-12-01

    Full Text Available Numerous instances of presence/absence variations for introns have been documented in eukaryotes, and some cases of recurrent loss of the same intron have been suggested. However, there has been no comprehensive or phylogenetically deep analysis of recurrent intron loss. Of 883 cases of intron presence/absence variation that we detected in five sequenced grass genomes, 93 were confirmed as recurrent losses and the rest could be explained by single losses (652 or single gains (118. No case of recurrent intron gain was observed. Deep phylogenetic analysis often indicated that apparent intron gains were actually numerous independent losses of the same intron. Recurrent loss exhibited extreme non-randomness, in that some introns were removed independently in many lineages. The two larger genomes, maize and sorghum, were found to have a higher rate of both recurrent loss and overall loss and/or gain than foxtail millet, rice or Brachypodium. Adjacent introns and small introns were found to be preferentially lost. Intron loss genes exhibited a high frequency of germ line or early embryogenesis expression. In addition, flanking exon A+T-richness and intron TG/CG ratios were higher in retained introns. This last result suggests that epigenetic status, as evidenced by a loss of methylated CG dinucleotides, may play a role in the process of intron loss. This study provides the first comprehensive analysis of recurrent intron loss, makes a series of novel findings on the patterns of recurrent intron loss during the evolution of the grass family, and provides insight into the molecular mechanism(s underlying intron loss.

  4. PT -symmetric gain and loss in a rotating Bose-Einstein condensate

    Science.gov (United States)

    Haag, Daniel; Dast, Dennis; Cartarius, Holger; Wunner, Günter

    2018-03-01

    PT -symmetric quantum mechanics allows finding stationary states in mean-field systems with balanced gain and loss of particles. In this work we apply this method to rotating Bose-Einstein condensates with contact interaction which are known to support ground states with vortices. Due to the particle exchange with the environment transport phenomena through ultracold gases with vortices can be studied. We find that even strongly interacting rotating systems support stable PT -symmetric ground states, sustaining a current parallel and perpendicular to the vortex cores. The vortices move through the nonuniform particle density and leave or enter the condensate through its borders creating the required net current.

  5. Loss of the NKX3.1 tumorsuppressor promotes the TMPRSS2-ERG fusion gene expression in prostate cancer

    International Nuclear Information System (INIS)

    Thangapazham, Rajesh; Saenz, Francisco; Katta, Shilpa; Mohamed, Ahmed A; Tan, Shyh-Han; Petrovics, Gyorgy; Srivastava, Shiv; Dobi, Albert

    2014-01-01

    In normal prostate epithelium the TMPRSS2 gene encoding a type II serine protease is directly regulated by male hormones through the androgen receptor. In prostate cancer ERG protooncogene frequently gains hormonal control by seizing gene regulatory elements of TMPRSS2 through genomic fusion events. Although, the androgenic activation of TMPRSS2 gene has been established, little is known about other elements that may interact with TMPRSS2 promoter sequences to modulate ERG expression in TMPRSS2-ERG gene fusion context. Comparative genomic analyses of the TMPRSS2 promoter upstream sequences and pathway analyses were performed by the Genomatix Software. NKX3.1 and ERG genes expressions were evaluated by immunoblot or by quantitative Real-Time PCR (qRT-PCR) assays in response to siRNA knockdown or heterologous expression. QRT-PCR assay was used for monitoring the gene expression levels of NKX3.1-regulated genes. Transcriptional regulatory function of NKX3.1 was assessed by luciferase assay. Recruitment of NKX3.1 to its cognate elements was monitored by Chromatin Immunoprecipitation assay. Comparative analysis of the TMPRSS2 promoter upstream sequences among different species revealed the conservation of binding sites for the androgen inducible NKX3.1 tumor suppressor. Defects of NKX3.1, such as, allelic loss, haploinsufficiency, attenuated expression or decreased protein stability represent established pathways in prostate tumorigenesis. We found that NKX3.1 directly binds to TMPRSS2 upstream sequences and negatively regulates the expression of the ERG protooncogene through the TMPRSS2-ERG gene fusion. These observations imply that the frequently noted loss-of-function of NKX3.1 cooperates with the activation of TMPRSS2-ERG fusions in prostate tumorigenesis

  6. Gain, loss and divergence in primate zinc-finger genes: a rich resource for evolution of gene regulatory differences between species.

    Directory of Open Access Journals (Sweden)

    Katja Nowick

    Full Text Available The molecular changes underlying major phenotypic differences between humans and other primates are not well understood, but alterations in gene regulation are likely to play a major role. Here we performed a thorough evolutionary analysis of the largest family of primate transcription factors, the Krüppel-type zinc finger (KZNF gene family. We identified and curated gene and pseudogene models for KZNFs in three primate species, chimpanzee, orangutan and rhesus macaque, to allow for a comparison with the curated set of human KZNFs. We show that the recent evolutionary history of primate KZNFs has been complex, including many lineage-specific duplications and deletions. We found 213 species-specific KZNFs, among them 7 human-specific and 23 chimpanzee-specific genes. Two human-specific genes were validated experimentally. Ten genes have been lost in humans and 13 in chimpanzees, either through deletion or pseudogenization. We also identified 30 KZNF orthologs with human-specific and 42 with chimpanzee-specific sequence changes that are predicted to affect DNA binding properties of the proteins. Eleven of these genes show signatures of accelerated evolution, suggesting positive selection between humans and chimpanzees. During primate evolution the most extensive re-shaping of the KZNF repertoire, including most gene additions, pseudogenizations, and structural changes occurred within the subfamily homininae. Using zinc finger (ZNF binding predictions, we suggest potential impact these changes have had on human gene regulatory networks. The large species differences in this family of TFs stands in stark contrast to the overall high conservation of primate genomes and potentially represents a potent driver of primate evolution.

  7. Uncovering the Best Skill Multimap by Constraining the Error Probabilities of the Gain-Loss Model

    Science.gov (United States)

    Anselmi, Pasquale; Robusto, Egidio; Stefanutti, Luca

    2012-01-01

    The Gain-Loss model is a probabilistic skill multimap model for assessing learning processes. In practical applications, more than one skill multimap could be plausible, while none corresponds to the true one. The article investigates whether constraining the error probabilities is a way of uncovering the best skill assignment among a number of…

  8. Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes.

    Science.gov (United States)

    Bridge, Julia A; Liu, Jian; Qualman, Stephen J; Suijkerbuijk, Ron; Wenger, Gail; Zhang, Ji; Wan, Xiaoying; Baker, K Scott; Sorensen, Poul; Barr, Frederic G

    2002-03-01

    In this investigation, we selected PAX3/FKHR and PAX7/FKHR fusion transcript-positive and -negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS fusion transcript subtypes, providing evidence for a genetic kinship despite the absence of a fusion transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGF1R) gene. Amplification of IGF1R was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is

  9. Just Add a Verse from the Quran: Effects of Religious Rhetoric in Gain- and Loss-Framed Anti-Alcohol Messages with a Palestinian Sample.

    Science.gov (United States)

    Alhabash, Saleem; Almutairi, Nasser; Rub, Mohammad Abu

    2017-10-01

    This experiment investigated the effects of message framing (gain vs. loss) and religious rhetoric (religious vs. non-religious) on the expression of anti-alcohol civic intentions with a sample (N = 80) of Palestinian young adults. Results showed that the main effects of message framing (gain > loss) and religious rhetoric (non-religious > religious) on anti-alcohol civic intentions were significant. Furthermore, the study showed that viral behavioral intentions were strongly and significantly associated with expressing anti-alcohol civic intentions, with larger explanatory power for gain-framed PSAs that used a religious rhetoric. Additionally, a serial mediation model showed that the effect of religious rhetoric on anti-alcohol civic intentions was successfully mediated by the serial combination of attitudes toward the PSA and viral behavioral intention for gain-framed PSAs, but not for loss-framed PSAs. Findings are discussed within the framework of persuasion models.

  10. Time-scale effects on the gain-loss asymmetry in stock indices

    Science.gov (United States)

    Sándor, Bulcsú; Simonsen, Ingve; Nagy, Bálint Zsolt; Néda, Zoltán

    2016-08-01

    The gain-loss asymmetry, observed in the inverse statistics of stock indices is present for logarithmic return levels that are over 2 % , and it is the result of the non-Pearson-type autocorrelations in the index. These non-Pearson-type correlations can be viewed also as functionally dependent daily volatilities, extending for a finite time interval. A generalized time-window shuffling method is used to show the existence of such autocorrelations. Their characteristic time scale proves to be smaller (less than 25 trading days) than what was previously believed. It is also found that this characteristic time scale has decreased with the appearance of program trading in the stock market transactions. Connections with the leverage effect are also established.

  11. 48 CFR 31.205-16 - Gains and losses on disposition or impairment of depreciable property or other capital assets.

    Science.gov (United States)

    2010-10-01

    ... identifiable intangible assets held for use, no loss shall be allowed for a write-down from carrying value to... disposition or impairment of depreciable property or other capital assets. 31.205-16 Section 31.205-16 Federal... or impairment of depreciable property or other capital assets. (a) Gains and losses from the sale...

  12. Association Study of 60 Candidate Genes with Antipsychotic-induced Weight Gain in Schizophrenia Patients.

    Science.gov (United States)

    Ryu, S; Huh, I-S; Cho, E-Y; Cho, Y; Park, T; Yoon, S C; Joo, Y H; Hong, K S

    2016-03-01

    This study aimed to investigate the association of multiple candidate genes with weight gain and appetite change during antipsychotic treatment. A total of 233 single nucleotide polymorphisms (SNPs) within 60 candidate genes were genotyped. BMI changes for up to 8 weeks in 84 schizophrenia patients receiving antipsychotic medication were analyzed using a linear mixed model. In addition, we assessed appetite change during antipsychotic treatment in a different group of 46 schizophrenia patients using the Drug-Related Eating Behavior Questionnaire. No SNP showed a statistically significant association with BMI or appetite change after correction for multiple testing. We observed trends of association (PGHRL showed suggestive evidence of association with not only weight gain (P=0.001) but also appetite change (P=0.042). Patients carrying the GG genotype of rs696217 exhibited higher increase in both BMI and appetite compared to patients carrying the GT/TT genotype. Our findings suggested the involvement of a GHRL polymorphism in weight gain, which was specifically mediated by appetite change, during antipsychotic treatment in schizophrenia patients. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Loss aversion and 5HTT gene variants in adolescent anxiety

    Directory of Open Access Journals (Sweden)

    Monique Ernst

    2014-04-01

    Full Text Available Loss aversion, a well-documented behavioral phenomenon, characterizes decisions under risk in adult populations. As such, loss aversion may provide a reliable measure of risky behavior. Surprisingly, little is known about loss aversion in adolescents, a group who manifests risk-taking behavior, or in anxiety disorders, which are associated with risk-avoidance. Finally, loss aversion is expected to be modulated by genotype, particularly the serotonin transporter (SERT gene variant, based on its role in anxiety and impulsivity. This genetic modulation may also differ between anxious and healthy adolescents, given their distinct propensities for risk taking. The present work examines the modulation of loss aversion, an index of risk-taking, and reaction-time to decision, an index of impulsivity, by the serotonin-transporter-gene-linked polymorphisms (5HTTLPR in healthy and clinically anxious adolescents. Findings show that loss aversion (1 does manifest in adolescents, (2 does not differ between healthy and clinically anxious participants, and (3, when stratified by SERT genotype, identifies a subset of anxious adolescents who are high SERT-expressers, and show excessively low loss-aversion and high impulsivity. This last finding may serve as preliminary evidence for 5HTTLPR as a risk factor for the development of comorbid disorders associated with risk-taking and impulsivity in clinically anxious adolescents.

  14. On the Complexity of Duplication-Transfer-Loss Reconciliation with Non-Binary Gene Trees.

    Science.gov (United States)

    Kordi, Misagh; Bansal, Mukul S

    2017-01-01

    Duplication-Transfer-Loss (DTL) reconciliation has emerged as a powerful technique for studying gene family evolution in the presence of horizontal gene transfer. DTL reconciliation takes as input a gene family phylogeny and the corresponding species phylogeny, and reconciles the two by postulating speciation, gene duplication, horizontal gene transfer, and gene loss events. Efficient algorithms exist for finding optimal DTL reconciliations when the gene tree is binary. However, gene trees are frequently non-binary. With such non-binary gene trees, the reconciliation problem seeks to find a binary resolution of the gene tree that minimizes the reconciliation cost. Given the prevalence of non-binary gene trees, many efficient algorithms have been developed for this problem in the context of the simpler Duplication-Loss (DL) reconciliation model. Yet, no efficient algorithms exist for DTL reconciliation with non-binary gene trees and the complexity of the problem remains unknown. In this work, we resolve this open question by showing that the problem is, in fact, NP-hard. Our reduction applies to both the dated and undated formulations of DTL reconciliation. By resolving this long-standing open problem, this work will spur the development of both exact and heuristic algorithms for this important problem.

  15. Gain and loss mechanisms for neutral species in low pressure fluorocarbon plasmas by infrared spectroscopy

    International Nuclear Information System (INIS)

    Nelson, Caleb T.; Overzet, Lawrence J.; Goeckner, Matthew J.

    2012-01-01

    This article examines the chemical reaction pathways of stable neutral species in fluorocarbon plasmas. Octafluorocyclobutane (c-C 4 F 8 ) inductively coupled plasma discharges were found to primarily produce stable and metastable products downstream from the discharge, including c-C 4 F 8 , C 2 F 4 , C 2 F 6 , CF 4 , C 3 F 8 , C 4 F 10 , C 3 F 6 , and CF 2 . A novel analysis technique allows the estimation of gain and loss rates for neutral species in the steady state as functions of residence time, pressure, and discharge power. The gain and loss rates show that CF 4 , C 2 F 6 , C 3 F 8 , and C 4 F 10 share related gain mechanisms, speculated to occur at the surface. Further analysis confirms that CF 2 is predominantly produced at the chamber walls through electron impact dissociation of C 2 F 4 and lost through gas-phase addition reactions to form C 2 F 4 . Additionally, time-resolved FTIR spectra provide a second-order rate coefficient of 1.8 × 10 −14 cm 3 /s for the gas-phase addition of CF 2 to form C 2 F 4 . Finally, C 2 F 4, which is much more abundant than CF 2 in the discharge, is shown to be dominantly produced through electron impact dissociation of c-C 4 F 8 and lost through either surface or gas-phase addition reactions.

  16. Mechanisms of stable lipid loss in a social insect

    Science.gov (United States)

    Ament, Seth A.; Chan, Queenie W.; Wheeler, Marsha M.; Nixon, Scott E.; Johnson, S. Peir; Rodriguez-Zas, Sandra L.; Foster, Leonard J.; Robinson, Gene E.

    2011-01-01

    SUMMARY Worker honey bees undergo a socially regulated, highly stable lipid loss as part of their behavioral maturation. We used large-scale transcriptomic and proteomic experiments, physiological experiments and RNA interference to explore the mechanistic basis for this lipid loss. Lipid loss was associated with thousands of gene expression changes in abdominal fat bodies. Many of these genes were also regulated in young bees by nutrition during an initial period of lipid gain. Surprisingly, in older bees, which is when maximum lipid loss occurs, diet played less of a role in regulating fat body gene expression for components of evolutionarily conserved nutrition-related endocrine systems involving insulin and juvenile hormone signaling. By contrast, fat body gene expression in older bees was regulated more strongly by evolutionarily novel regulatory factors, queen mandibular pheromone (a honey bee-specific social signal) and vitellogenin (a conserved yolk protein that has evolved novel, maturation-related functions in the bee), independent of nutrition. These results demonstrate that conserved molecular pathways can be manipulated to achieve stable lipid loss through evolutionarily novel regulatory processes. PMID:22031746

  17. Mechanisms of stable lipid loss in a social insect.

    Science.gov (United States)

    Ament, Seth A; Chan, Queenie W; Wheeler, Marsha M; Nixon, Scott E; Johnson, S Peir; Rodriguez-Zas, Sandra L; Foster, Leonard J; Robinson, Gene E

    2011-11-15

    Worker honey bees undergo a socially regulated, highly stable lipid loss as part of their behavioral maturation. We used large-scale transcriptomic and proteomic experiments, physiological experiments and RNA interference to explore the mechanistic basis for this lipid loss. Lipid loss was associated with thousands of gene expression changes in abdominal fat bodies. Many of these genes were also regulated in young bees by nutrition during an initial period of lipid gain. Surprisingly, in older bees, which is when maximum lipid loss occurs, diet played less of a role in regulating fat body gene expression for components of evolutionarily conserved nutrition-related endocrine systems involving insulin and juvenile hormone signaling. By contrast, fat body gene expression in older bees was regulated more strongly by evolutionarily novel regulatory factors, queen mandibular pheromone (a honey bee-specific social signal) and vitellogenin (a conserved yolk protein that has evolved novel, maturation-related functions in the bee), independent of nutrition. These results demonstrate that conserved molecular pathways can be manipulated to achieve stable lipid loss through evolutionarily novel regulatory processes.

  18. Gain versus loss-framed messaging and colorectal cancer screening among African Americans: A preliminary examination of perceived racism and culturally targeted dual messaging.

    Science.gov (United States)

    Lucas, Todd; Hayman, Lenwood W; Blessman, James E; Asabigi, Kanzoni; Novak, Julie M

    2016-05-01

    This preliminary study examined the effect of gain versus loss-framed messaging as well as culturally targeted personal prevention messaging on African Americans' receptivity to colorectal cancer (CRC) screening. This research also examined mechanistic functions of perceived racism in response to message framing. Community samples of African Americans (N = 132) and White Americans (N = 50) who were non-compliant with recommended CRC screening completed an online education module about CRC, and were either exposed to a gain-framed or loss-framed message about CRC screening. Half of African Americans were exposed to an additional and culturally targeted self-control message about personal prevention of CRC. Theory of planned behavior measures of attitudes, normative beliefs, perceived behavioural control, and intentions to obtain a CRC screen served as primary outcomes. The effect of messaging on perceived racism was also measured as an outcome. Consistent with prior research, White Americans were more receptive to CRC screening when exposed to a loss-framed message. However, African Americans were more receptive when exposed to a gain-framed message. The contrary effect of loss-framed messaging on receptivity to screening among African Americans was mediated by an increase in perceived racism. However, including an additional and culturally targeted prevention message mitigated the adverse effect of a loss-framed message. This study identifies an important potential cultural difference in the effect of message framing on illness screening among African Americans, while also suggesting a culturally relevant linking mechanism. This study also suggests the potential for simultaneously presented and culturally targeted messaging to alter the effects of gain and loss-framed messaging on African Americans. What is already known on this subject? African Americans are at an increased risk of both developing and dying from colorectal cancer (CRC). These disparities can be

  19. Mitochondrial genome evolution in Alismatales: Size reduction and extensive loss of ribosomal protein genes

    DEFF Research Database (Denmark)

    Petersen, Gitte; Cuenca, Argelia; Zervas, Athanasios

    2017-01-01

    The order Alismatales is a hotspot for evolution of plant mitochondrial genomes characterized by remarkable differences in genome size, substitution rates, RNA editing, retrotranscription, gene loss and intron loss. Here we have sequenced the complete mitogenomes of Zostera marina and Stratiotes...... aloides, which together with previously sequenced mitogenomes from Butomus and Spirodela, provide new evolutionary evidence of genome size reduction, gene loss and transfer to the nucleus. The Zostera mitogenome includes a large portion of DNA transferred from the plastome, yet it is the smallest known...... mitogenome from a non-parasitic plant. Using a broad sample of the Alismatales, the evolutionary history of ribosomal protein gene loss is analyzed. In Zostera almost all ribosomal protein genes are lost from the mitogenome, but only some can be found in the nucleus....

  20. Loss aversion and 5HTT gene variants in adolescent anxiety.

    Science.gov (United States)

    Ernst, Monique; Plate, Rista C; Carlisi, Christina O; Gorodetsky, Elena; Goldman, David; Pine, Daniel S

    2014-04-01

    Loss aversion, a well-documented behavioral phenomenon, characterizes decisions under risk in adult populations. As such, loss aversion may provide a reliable measure of risky behavior. Surprisingly, little is known about loss aversion in adolescents, a group who manifests risk-taking behavior, or in anxiety disorders, which are associated with risk-avoidance. Finally, loss aversion is expected to be modulated by genotype, particularly the serotonin transporter (SERT) gene variant, based on its role in anxiety and impulsivity. This genetic modulation may also differ between anxious and healthy adolescents, given their distinct propensities for risk taking. The present work examines the modulation of loss aversion, an index of risk-taking, and reaction-time to decision, an index of impulsivity, by the serotonin-transporter-gene-linked polymorphisms (5HTTLPR) in healthy and clinically anxious adolescents. Findings show that loss aversion (1) does manifest in adolescents, (2) does not differ between healthy and clinically anxious participants, and (3), when stratified by SERT genotype, identifies a subset of anxious adolescents who are high SERT-expressers, and show excessively low loss-aversion and high impulsivity. This last finding may serve as preliminary evidence for 5HTTLPR as a risk factor for the development of comorbid disorders associated with risk-taking and impulsivity in clinically anxious adolescents. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. FROM BEHAVIORAL FINANCE TO ECCLESIASTES FINANCE: THE PAIN OF GAIN AND THE GLORY OF AN INVESTMENT LOSS

    Directory of Open Access Journals (Sweden)

    ADRIAN MITROI

    2016-12-01

    Full Text Available Academic and practitioner’s literature has a plethora of evidence that active investment management is futile economically and underperforming financially, - more preponderant for large, blue chips. For smaller capitalization companies, purchased at discount there is an attractive, sustainable return promise, a long-term outperformance. We introduce a terminology that encapsulates this capitulation against this apparently overwhelming forces of tangible underperformance of active investment, inefficient asset allocation and high risk - low return portfolios, the era of Ecclesiastes Finance. Investors loathe to make decisions for fear of loss and discount all negative subtle announcement of the fragility of our gains and futility of our investment arrogance. And ignoring them can lead investors to make less fortunate financial decisions that can affect portfolio for decades. Investing with an Ecclesiastes attitude - the fragility of human condition in context of financial affairs - temporary gains and losses are less significant when framed in a larger perspective.

  2. Exact Algorithms for Duplication-Transfer-Loss Reconciliation with Non-Binary Gene Trees.

    Science.gov (United States)

    Kordi, Misagh; Bansal, Mukul S

    2017-06-01

    Duplication-Transfer-Loss (DTL) reconciliation is a powerful method for studying gene family evolution in the presence of horizontal gene transfer. DTL reconciliation seeks to reconcile gene trees with species trees by postulating speciation, duplication, transfer, and loss events. Efficient algorithms exist for finding optimal DTL reconciliations when the gene tree is binary. In practice, however, gene trees are often non-binary due to uncertainty in the gene tree topologies, and DTL reconciliation with non-binary gene trees is known to be NP-hard. In this paper, we present the first exact algorithms for DTL reconciliation with non-binary gene trees. Specifically, we (i) show that the DTL reconciliation problem for non-binary gene trees is fixed-parameter tractable in the maximum degree of the gene tree, (ii) present an exponential-time, but in-practice efficient, algorithm to track and enumerate all optimal binary resolutions of a non-binary input gene tree, and (iii) apply our algorithms to a large empirical data set of over 4700 gene trees from 100 species to study the impact of gene tree uncertainty on DTL-reconciliation and to demonstrate the applicability and utility of our algorithms. The new techniques and algorithms introduced in this paper will help biologists avoid incorrect evolutionary inferences caused by gene tree uncertainty.

  3. Seagrass blue carbon dynamics in the Gulf of Mexico: Stocks, losses from anthropogenic disturbance, and gains through seagrass restoration.

    Science.gov (United States)

    Thorhaug, Anitra; Poulos, Helen M; López-Portillo, Jorge; Ku, Timothy C W; Berlyn, Graeme P

    2017-12-15

    Seagrasses comprise a substantive North American and Caribbean Sea blue carbon sink. Yet fine-scale estimates of seagrass carbon stocks, fluxes from anthropogenic disturbances, and potential gains in sedimentary carbon from seagrass restoration are lacking for most of the Western Hemisphere. To begin to fill this knowledge gap in the subtropics and tropics, we quantified organic carbon (C org ) stocks, losses, and gains from restorations at 8 previously-disturbed seagrass sites around the Gulf of Mexico (GoM) (n=128 cores). Mean natural seagrass C org stocks were 25.7±6.7MgC org ha -1 around the GoM, while mean C org stocks at adjacent barren sites that had previously hosted seagrass were 17.8MgC org ha -1 . Restored seagrass beds contained a mean of 38.7±13.1MgC org ha -1 . Mean C org losses differed by anthropogenic impact type, but averaged 20.98±7.14MgC org ha -1 . C org gains from seagrass restoration averaged 20.96±8.59Mgha -1 . These results, when combined with the similarity between natural and restored C org content, highlight the potential of seagrass restoration for mitigating seagrass C org losses from prior impact events. Our GoM basin-wide estimates of natural C org totaled ~36.4Tg for the 947,327ha for the USA-GoM. Including Mexico, the total basin contained an estimated 37.2-37.5Tg C org . Regional US-GoM losses totaled 21.69Tg C org . C org losses differed significantly among anthropogenic impacts. Yet, seagrass restoration appears to be an important climate change mitigation strategy that could be implemented elsewhere throughout the tropics and subtropics. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Gene Overexpression Resources in Cereals for Functional Genomics and Discovery of Useful Genes

    Directory of Open Access Journals (Sweden)

    Kiyomi Abe

    2016-09-01

    Full Text Available Identification and elucidation of functions of plant genes is valuable for both basic and applied research. In addition to natural variation in model plants, numerous loss-of-function resources have been produced by mutagenesis with chemicals, irradiation, or insertions of transposable elements or T-DNA. However, we may be unable to observe loss-of-function phenotypes for genes with functionally redundant homologs, and for those essential for growth and development. To offset such disadvantages, gain-of-function transgenic resources have been exploited. Activation-tagged lines have been generated using obligatory overexpression of endogenous genes by random insertion of an enhancer. Recent progress in DNA sequencing technology and bioinformatics has enabled the preparation of genomewide collections of full-length cDNAs (fl-cDNAs in some model species. Using the fl-cDNA clones, a novel gain-of-function strategy, Fl-cDNA OvereXpressor gene (FOX-hunting system, has been developed. A mutant phenotype in a FOX line can be directly attributed to the overexpressed fl-cDNA. Investigating a large population of FOX lines could reveal important genes conferring favorable phenotypes for crop breeding. Alternatively, a unique loss-of-function approach Chimeric REpressor gene Silencing Technology (CRES-T has been developed. In CRES-T, overexpression of a chimeric repressor, composed of the coding sequence of a transcription factor (TF and short peptide designated as the repression domain, could interfere with the action of endogenous TF in plants. Although plant TFs usually consist of gene families, CRES-T is effective, in principle, even for the TFs with functional redundancy. In this review, we focus on the current status of the gene-overexpression strategies and resources for identifying and elucidating novel functions of cereal genes. We discuss the potential of these research tools for identifying useful genes and phenotypes for application in crop

  5. Genetic variation in the leptin receptor gene, leptin, and weight gain in young Dutch adults.

    Science.gov (United States)

    van Rossum, Caroline T M; Hoebee, Barbara; van Baak, Marleen A; Mars, Monica; Saris, Wim H M; Seidell, Jacob C

    2003-03-01

    To investigate the association between leptin levels, polymorphisms in the leptin receptor (LEPR) gene, and weight gain. From two large prospective cohorts in The Netherlands (n = 17,500), we compared the baseline leptin of 259 subjects who had gained an average of 12.6 kg (range 5.5 to 33 kg) with 277 subjects who kept stable weight (range -2.6 to 3.1 kg) after a mean follow-up of 6.8 years. Three polymorphisms in the LEPR gene (Lys109Arg, Gln223Arg, and Lys656Asn) were determined. Weight gainers had significantly higher baseline leptin levels than those who kept stable weight (odds ratio = 1.27, 95% confidence interval 1.1 to 1.5, per SD increase in log(e)-transformed leptin). Weight gainers with the Arg109 or the Arg223 alleles had higher leptin levels compared with the noncarriers of these alleles. Only among men, the association between leptin and weight gain tended to be stronger among those with an Arg223 allele compared with those without this mutation. Relatively high leptin levels predict weight gain, suggesting that leptin resistance plays a role in the development of obesity in the general population. Higher leptin levels for those with a Lys109Arg or Gln223Arg mutation (or a linked other marker) may imply that these subjects have a modified functional leptin receptor. However, the role of these mutations on weight gain is limited.

  6. Functional Connectivity with Distinct Neural Networks Tracks Fluctuations in Gain/Loss Framing Susceptibility

    Science.gov (United States)

    Smith, David V.; Sip, Kamila E.; Delgado, Mauricio R.

    2016-01-01

    Multiple large-scale neural networks orchestrate a wide range of cognitive processes. For example, interoceptive processes related to self-referential thinking have been linked to the default-mode network (DMN); whereas exteroceptive processes related to cognitive control have been linked to the executive-control network (ECN). Although the DMN and ECN have been postulated to exert opposing effects on cognition, it remains unclear how connectivity with these spatially overlapping networks contribute to fluctuations in behavior. While previous work has suggested the medial prefrontal cortex (MPFC) is involved in behavioral change following feedback, these observations could be linked to interoceptive processes tied to DMN or exteroceptive processes tied to ECN because MPFC is positioned in both networks. To address this problem, we employed independent component analysis combined with dual-regression functional connectivity analysis. Participants made a series of financial decisions framed as monetary gains or losses. In some sessions, participants received feedback from a peer observing their choices; in other sessions, feedback was not provided. Following feedback, framing susceptibility—indexed as the increase in gambling behavior in loss frames compared to gain frames—was heightened in some participants and diminished in others. We examined whether these individual differences were linked to differences in connectivity by contrasting sessions containing feedback against those that did not contain feedback. We found two key results. As framing susceptibility increased, the MPFC increased connectivity with DMN; in contrast, temporal-parietal junction decreased connectivity with the ECN. Our results highlight how functional connectivity patterns with distinct neural networks contribute to idiosyncratic behavioral changes. PMID:25858445

  7. Simultaneous realization of a coherent perfect absorber and laser by zero-index media with both gain and loss

    KAUST Repository

    Bai, Ping; Ding, Kun; Wang, Gang; Luo, Jie; Zhang, Zhao Qing; Chan, C. T.; Wu, Ying; Lai, Yun

    2016-01-01

    We investigate a unique type of zero-index medium with both gain and loss (ZIMGL), whose effective permittivity and permeability are both purely imaginary but of opposite signs. We analytically show that, by using a slab of ZIMGL with equal

  8. Designing Skin Cancer Prevention Messages: Should We Emphasize Gains or Losses? Message Framing, Risk Type, and Prior Experience.

    Science.gov (United States)

    Lee, Moon J; Kang, Hannah

    2018-05-01

    To test whether message framing (ie, gain vs. loss) and risk type (ie, health vs appearance risk) in skin cancer prevention messages interact with one's prior experience. Two experiments with a 2 (message framing: gain vs loss) × 2 (risk type: health vs appearance risk) factorial design were conducted. The participants were given a URL to the experiment website via e-mail. On the first page of the website, the participants were told that they would be asked to evaluate a skin cancer print public service announcement (PSA): Online experiments. A total of 397 individuals participated (236 for experiment 1 and 161 for experiment 2). Apparatus: Four versions of the skin cancer print PSAs were developed. Four PSAs were identical except for the 2 manipulated components: message framing and risk type. Measures were adopted from Cho and Boster (message framing), Jones and Leary and Kiene et al. (risk type), De Vries, Mesters, van't Riet, Willems, and Reubsaet and Knight, Kirincich, Farmer, and Hood (prior experience), and Hammond, Fong, Zanna, Thrasher, and Borland and Hoffner and Ye (behavioral intent). General linear models were used to test hypotheses. Three-way interactions among message framing, risk type, and prior experience were found: When the intent of the message was to encourage sunscreen use, the effects of message framing and risk type were shown to be the exact opposite directions from when the intent was to discourage indoor/outdoor tanning. To discourage tanning among those with prior experience, messages emphasizing losses in terms of one's health will work better. For those with no prior experience, messages emphasizing potential appearance losses will work better for discouraging tanning while messages emphasizing gains like improving appearance will do a better job in encouraging sunscreen use.

  9. Loss of activating EGFR mutant gene contributes to acquired resistance to EGFR tyrosine kinase inhibitors in lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Keisuke Tabara

    Full Text Available Non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR mutations attains a meaningful response to EGFR-tyrosine kinase inhibitors (TKIs. However, acquired resistance to EGFR-TKIs could affect long-term outcome in almost all patients. To identify the potential mechanisms of resistance, we established cell lines resistant to EGFR-TKIs from the human lung cancer cell lines PC9 and11-18, which harbored activating EGFR mutations. One erlotinib-resistant cell line from PC9 and two erlotinib-resistant cell lines and two gefitinib-resistant cell lines from 11-18 were independently established. Almost complete loss of mutant delE746-A750 EGFR gene was observed in the erlotinib-resistant cells isolated from PC9, and partial loss of the mutant L858R EGFR gene copy was specifically observed in the erlotinib- and gefitinib-resistant cells from 11-18. However, constitutive activation of EGFR downstream signaling, PI3K/Akt, was observed even after loss of the mutated EGFR gene in all resistant cell lines even in the presence of the drug. In the erlotinib-resistant cells from PC9, constitutive PI3K/Akt activation was effectively inhibited by lapatinib (a dual TKI of EGFR and HER2 or BIBW2992 (pan-TKI of EGFR family proteins. Furthermore, erlotinib with either HER2 or HER3 knockdown by their cognate siRNAs also inhibited PI3K/Akt activation. Transfection of activating mutant EGFR complementary DNA restored drug sensitivity in the erlotinib-resistant cell line. Our study indicates that loss of addiction to mutant EGFR resulted in gain of addiction to both HER2/HER3 and PI3K/Akt signaling to acquire EGFR-TKI resistance.

  10. Rapid genome reshaping by multiple-gene loss after whole-genome duplication in teleost fish suggested by mathematical modeling

    Science.gov (United States)

    Sato, Yukuto; Tsukamoto, Katsumi; Nishida, Mutsumi

    2015-01-01

    Whole-genome duplication (WGD) is believed to be a significant source of major evolutionary innovation. Redundant genes resulting from WGD are thought to be lost or acquire new functions. However, the rates of gene loss and thus temporal process of genome reshaping after WGD remain unclear. The WGD shared by all teleost fish, one-half of all jawed vertebrates, was more recent than the two ancient WGDs that occurred before the origin of jawed vertebrates, and thus lends itself to analysis of gene loss and genome reshaping. Using a newly developed orthology identification pipeline, we inferred the post–teleost-specific WGD evolutionary histories of 6,892 protein-coding genes from nine phylogenetically representative teleost genomes on a time-calibrated tree. We found that rapid gene loss did occur in the first 60 My, with a loss of more than 70–80% of duplicated genes, and produced similar genomic gene arrangements within teleosts in that relatively short time. Mathematical modeling suggests that rapid gene loss occurred mainly by events involving simultaneous loss of multiple genes. We found that the subsequent 250 My were characterized by slow and steady loss of individual genes. Our pipeline also identified about 1,100 shared single-copy genes that are inferred to have become singletons before the divergence of clupeocephalan teleosts. Therefore, our comparative genome analysis suggests that rapid gene loss just after the WGD reshaped teleost genomes before the major divergence, and provides a useful set of marker genes for future phylogenetic analysis. PMID:26578810

  11. Matching Message Design and Depressed Cognition: An Exploration of Attention Patterns for Gain- and Loss-Framed Depression Help-Seeking Messages.

    Science.gov (United States)

    Lueck, Jennifer A

    2017-07-01

    Although disproportionally affected by depression, most depressed college students do not seek the help they need. Research has recently uncovered the potential negative effects of depression help-seeking messages if depressed cognition is not considered in the health message design process. It is unclear if depression determines whether and how individuals pay attention to gain- and loss-framed depression help-seeking messages-a mechanism that has significant implications for the strategic planning of health communication interventions. In order to enable the effective matching of message design and audience features, this study investigated attention patterns for gain (n = 75)- and loss (n = 78)-framed depression help-seeking messages using eye-tracking technology and self-report measures. The results confirmed that depression is a characteristic of risk avoidance and negative cognition. Depressed participants tended to pay more attention to disease information that was placed in a loss-framed rather than a gain-framed depression help-seeking message. Using negative message framing strategies for health messages seeking to educate about depression symptoms might therefore be a useful persuasive strategy-particularly when disseminated to vulnerable populations affected by depression. Furthermore, the present study emphasizes the effective use of eye-tracking technology in communication research.

  12. P300 amplitude variation is related to ventral striatum BOLD response during gain and loss anticipation: an EEG and fMRI experiment.

    Science.gov (United States)

    Pfabigan, Daniela M; Seidel, Eva-Maria; Sladky, Ronald; Hahn, Andreas; Paul, Katharina; Grahl, Arvina; Küblböck, Martin; Kraus, Christoph; Hummer, Allan; Kranz, Georg S; Windischberger, Christian; Lanzenberger, Rupert; Lamm, Claus

    2014-08-01

    The anticipation of favourable or unfavourable events is a key component in our daily life. However, the temporal dynamics of anticipation processes in relation to brain activation are still not fully understood. A modified version of the monetary incentive delay task was administered during separate functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) sessions in the same 25 participants to assess anticipatory processes with a multi-modal neuroimaging set-up. During fMRI, gain and loss anticipation were both associated with heightened activation in ventral striatum and reward-related areas. EEG revealed most pronounced P300 amplitudes for gain anticipation, whereas CNV amplitudes distinguished neutral from gain and loss anticipation. Importantly, P300, but not CNV amplitudes, were correlated to neural activation in the ventral striatum for both gain and loss anticipation. Larger P300 amplitudes indicated higher ventral striatum blood oxygen level dependent (BOLD) response. Early stimulus evaluation processes indexed by EEG seem to be positively related to higher activation levels in the ventral striatum, indexed by fMRI, which are usually associated with reward processing. The current results, however, point towards a more general motivational mechanism processing salient stimuli during anticipation. Copyright © 2014. Published by Elsevier Inc.

  13. Decisions for Others Are Less Risk-Averse in the Gain Frame and Less Risk-Seeking in the Loss Frame Than Decisions for the Self.

    Science.gov (United States)

    Zhang, Xiangyi; Liu, Yi; Chen, Xiyou; Shang, Xuesong; Liu, Yongfang

    2017-01-01

    Despite the fact that people make decisions for others as often as they make decisions for themselves, little is known about how decisions for others are different from those made for the self. In two experiments, we investigated the effect of social distance (i.e., making decisions for oneself, a friend, or a stranger) on risk preferences in both gain and loss situations. We found that people were more risk averse in gain situations when they made decisions for themselves than for a stranger (Studies 1 and 2), but were equally risk averse for themselves and their friends (Study 2). However, people were more risk seeking in loss situations when they made decisions for themselves than for their friends as well as for a stranger, and were more risk seeking for their friends than for a stranger (Study 2). Furthermore, the effect of social distance on risk preferences was stronger in loss than in gain situations. Mediation analysis indicated that outcome-induced loss aversion was responsible for effects of social distance on risk preferences. These findings demonstrate that social distance influences risk preferences via perceived loss aversion, which sheds new light on self-other differences in decision making.

  14. My loss is your loss ... Sometimes: loss aversion and the effect of motivational biases.

    Science.gov (United States)

    Wilson, Robyn S; Arvai, Joseph L; Arkes, Hal R

    2008-08-01

    Findings from previous studies of individual decision-making behavior predict that losses will loom larger than gains. It is less clear, however, if this loss aversion applies to the way in which individuals attribute value to the gains and losses of others, or if it is robust across a broad spectrum of policy and management decision contexts. Consistent with previous work, the results from a series of experiments reported here revealed that subjects exhibited loss aversion when evaluating their own financial gains and losses. The presence of loss aversion was also confirmed for the way in which individuals attribute value to the financial gains and losses of others. However, similar evaluations within social and environmental contexts did not exhibit loss aversion. In addition, research subjects expected that individuals who were unknown to them would significantly undervalue the subjects' own losses across all contexts. The implications of these findings for risk-based policy and management are many. Specifically, they warrant caution when relying upon loss aversion to explain or predict the reaction of affected individuals to risk-based decisions that involve moral or protected values. The findings also suggest that motivational biases may lead decisionmakers to assume that their attitudes and beliefs are common among those affected by a decision, while those affected may expect unfamiliar others to be unable to identify and act in accordance with shared values.

  15. Gene-gene interactions and gene polymorphisms of VEGFA and EG-VEGF gene systems in recurrent pregnancy loss.

    Science.gov (United States)

    Su, Mei-Tsz; Lin, Sheng-Hsiang; Chen, Yi-Chi; Kuo, Pao-Lin

    2014-06-01

    Both vascular endothelial growth factor A (VEGFA) and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) systems play major roles in angiogenesis. A body of evidence suggests VEGFs regulate critical processes during pregnancy and have been associated with recurrent pregnancy loss (RPL). However, little information is available regarding the interaction of these two major major angiogenesis-related systems in early human pregnancy. This study was conducted to investigate the association of gene polymorphisms and gene-gene interaction among genes in VEGFA and EG-VEGF systems and idiopathic RPL. A total of 98 women with history of idiopathic RPL and 142 controls were included, and 5 functional SNPs selected from VEGFA, KDR, EG-VEGF (PROK1), PROKR1 and PROKR2 were genotyped. We used multifactor dimensionality reduction (MDR) analysis to choose a best model and evaluate gene-gene interactions. Ingenuity pathways analysis (IPA) was introduced to explore possible complex interactions. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL (P<0.01). The MDR test revealed that the KDR (Q472H) polymorphism was the best loci to be associated with RPL (P=0.02). IPA revealed EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3 signaling pathways. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL. EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3.

  16. 26 CFR 1.864-6 - Income, gain, or loss attributable to an office or other fixed place of business in the United...

    Science.gov (United States)

    2010-04-01

    ... INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES... attributable to an office or other fixed place of business in the United States. (a) In general. Income, gain... if the income, gain, or loss is attributable under paragraphs (b) and (c) of this section to an...

  17. Gain-of-function mutations in the ALS8 causative gene VAPB have detrimental effects on neurons and muscles

    Directory of Open Access Journals (Sweden)

    Mario Sanhueza

    2013-12-01

    Amyotrophic Lateral Sclerosis (ALS is a motor neuron degenerative disease characterized by a progressive, and ultimately fatal, muscle paralysis. The human VAMP-Associated Protein B (hVAPB is the causative gene of ALS type 8. Previous studies have shown that a loss-of-function mechanism is responsible for VAPB-induced ALS. Recently, a novel mutation in hVAPB (V234I has been identified but its pathogenic potential has not been assessed. We found that neuronal expression of the V234I mutant allele in Drosophila (DVAP-V260I induces defects in synaptic structure and microtubule architecture that are opposite to those associated with DVAP mutants and transgenic expression of other ALS-linked alleles. Expression of DVAP-V260I also induces aggregate formation, reduced viability, wing postural defects, abnormal locomotion behavior, nuclear abnormalities, neurodegeneration and upregulation of the heat-shock-mediated stress response. Similar, albeit milder, phenotypes are associated with the overexpression of the wild-type protein. These data show that overexpressing the wild-type DVAP is sufficient to induce the disease and that DVAP-V260I is a pathogenic allele with increased wild-type activity. We propose that a combination of gain- and loss-of-function mechanisms is responsible for VAPB-induced ALS.

  18. Transgenic mice display hair loss and regrowth overexpressing mutant Hr gene.

    Science.gov (United States)

    Zhu, Kuicheng; Xu, Cunshuan; Zhang, Jintao; Chen, Yingying; Liu, Mengduan

    2017-10-30

    Mutations in the hairless (Hr) gene in both mice and humans have been implicated in the development of congenital atrichia, but the role of Hr in skin and hair follicle (HF) biology remains unknown. Here, we established transgenic mice (TG) overexpressing mutant Hr to investigate its specific role in the development of HF. Three transgenic lines were successfully constructed, and two of them (TG3 and TG8) displayed a pattern of hair loss and regrowth with alternation in the expression of HR protein. The mutant Hr gene inhibited the expression of the endogenous gene in transgenic individuals, which led to the development of alopecia. Interestingly, the hair regrew with the increase in the endogenous expression levels resulting from decreased mutant Hr expression. The findings of our study indicate that the changes in the expression of Hr result in hair loss or regrowth.

  19. Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis

    Directory of Open Access Journals (Sweden)

    Eilers Paul HC

    2008-10-01

    Full Text Available Abstract Background Accurate staging of rectal tumors is essential for making the correct treatment choice. In a previous study, we found that loss of 17p, 18q and gain of 8q, 13q and 20q could distinguish adenoma from carcinoma tissue and that gain of 1q was related to lymph node metastasis. In order to find markers for tumor staging, we searched for candidate genes on these specific chromosomes. Methods We performed gene expression microarray analysis on 79 rectal tumors and integrated these data with genomic data from the same sample series. We performed supervised analysis to find candidate genes on affected chromosomes and validated the results with qRT-PCR and immunohistochemistry. Results Integration of gene expression and chromosomal instability data revealed similarity between these two data types. Supervised analysis identified up-regulation of EFNA1 in cases with 1q gain, and EFNA1 expression was correlated with the expression of a target gene (VEGF. The BOP1 gene, involved in ribosome biogenesis and related to chromosomal instability, was over-expressed in cases with 8q gain. SMAD2 was the most down-regulated gene on 18q, and on 20q, STMN3 and TGIF2 were highly up-regulated. Immunohistochemistry for SMAD4 correlated with SMAD2 gene expression and 18q loss. Conclusion On basis of integrative analysis this study identified one well known CRC gene (SMAD2 and several other genes (EFNA1, BOP1, TGIF2 and STMN3 that possibly could be used for rectal cancer characterization.

  20. A Mathematical Model Of Ageing In Man Due To Gene Loss | Mbah ...

    African Journals Online (AJOL)

    Aging is as a result of dysfunction of the body mechanisms due to failure of one organelle, tissue, component or the other. In man there is a pointer towards gene loss as a primary cause of ageing. In this paper we develop a mathematical model describing changes in gene efficiency or gene failure. This model is used to ...

  1. Streamflow gain and loss and water quality in the upper Nueces River Basin, south-central Texas, 2008-10

    Science.gov (United States)

    Banta, J. Ryan; Lambert, Rebecca B.; Slattery, Richard N.; Ockerman, Darwin J.

    2012-01-01

    The U.S. Geological Survey-in cooperation with the U.S. Army Corps of Engineers, The Nature Conservancy, the Real Edwards Conservation and Reclamation District, and the Texas Parks and Wildlife Department-investigated streamflow gain and loss and water quality in the upper Nueces River Basin, south-central Texas, specifically in the watersheds of the West Nueces, Nueces, Dry Frio, Frio, and Sabinal Rivers upstream from the Edwards aquifer outcrop. Streamflow in these rivers is sustained by groundwater contributions (for example, from springs) and storm runoff from rainfall events. To date (2012), there are few data available that describe streamflow and water-quality conditions of the rivers within the upper Nueces River Basin. This report describes streamflow gain-loss characteristics from three reconnaissance-level synoptic measurement surveys (hereinafter referred to as "surveys") during 2008-10 in the upper Nueces River Basin. To help characterize the hydrology, groundwater-level measurements were made, and water-quality samples were collected from both surface-water and groundwater sites in the study area from two surveys during 2009-10. The hydrologic (streamflow, springflow, and groundwater) measurements were made during three reconnaissance-level synoptic measurement surveys occurring in July 21-23, 2008; August 8-18, 2009; and March 22-24, 2010. These survey periods were selected to represent different hydrologic conditions. Streamflow gains and losses were based on streamflow and springflow measurements made at 74 sites in the study area, although not all sites were measured during each survey. Possible water chemistry relations among sample types (streamflow, springflow, or groundwater), between surveys, and among watersheds were examined using water-quality samples collected from as many as 20 sites in the study area.

  2. Mutations in Cancer Cause Gain of Cysteine, Histidine, and Tryptophan at the Expense of a Net Loss of Arginine on the Proteome Level

    Directory of Open Access Journals (Sweden)

    Viktoriia Tsuber

    2017-07-01

    Full Text Available Accumulation of somatic mutations is critical for the transition of a normal cell to become cancerous. Mutations cause amino acid substitutions that change properties of proteins. However, it has not been studied as to what extent the composition and accordingly chemical properties of the cell proteome is altered as a result of the increased mutation load in cancer. Here, we analyzed data on amino acid substitutions caused by mutations in about 2000 protein coding genes from the Cancer Cell Line Encyclopedia that contains information on nucleotide and amino acid alterations in 782 cancer cell lines, and validated the analysis with information on amino acid substitutions for the same set of proteins in the Catalogue of Somatic Mutations in Cancer (COSMIC; v78 in circa 18,000 tumor samples. We found that nonsynonymous single nucleotide substitutions in the analyzed proteome subset ultimately result in a net gain of cysteine, histidine, and tryptophan at the expense of a net loss of arginine. The extraordinary loss of arginine may be attributed to some extent to composition of its codons as well as to the importance of arginine in the functioning of prominent tumor suppressor proteins like p53.

  3. Decisions for Others Are Less Risk-Averse in the Gain Frame and Less Risk-Seeking in the Loss Frame Than Decisions for the Self

    Science.gov (United States)

    Zhang, Xiangyi; Liu, Yi; Chen, Xiyou; Shang, Xuesong; Liu, Yongfang

    2017-01-01

    Despite the fact that people make decisions for others as often as they make decisions for themselves, little is known about how decisions for others are different from those made for the self. In two experiments, we investigated the effect of social distance (i.e., making decisions for oneself, a friend, or a stranger) on risk preferences in both gain and loss situations. We found that people were more risk averse in gain situations when they made decisions for themselves than for a stranger (Studies 1 and 2), but were equally risk averse for themselves and their friends (Study 2). However, people were more risk seeking in loss situations when they made decisions for themselves than for their friends as well as for a stranger, and were more risk seeking for their friends than for a stranger (Study 2). Furthermore, the effect of social distance on risk preferences was stronger in loss than in gain situations. Mediation analysis indicated that outcome-induced loss aversion was responsible for effects of social distance on risk preferences. These findings demonstrate that social distance influences risk preferences via perceived loss aversion, which sheds new light on self-other differences in decision making. PMID:28966604

  4. Beyond gains and losses: the effect of need on risky choice in framed decisions.

    Science.gov (United States)

    Mishra, Sandeep; Fiddick, Laurence

    2012-06-01

    Substantial evidence suggests people are risk-averse when making decisions described in terms of gains and risk-prone when making decisions described in terms of losses, a phenomenon known as the framing effect. Little research, however, has examined whether framing effects are a product of normative risk-sensitive cognitive processes. In 5 experiments, it is demonstrated that framing effects in the Asian disease problem can be explained by risk-sensitivity theory, which predicts that decision makers adjust risk acceptance on the basis of minimal acceptable thresholds, or need. Both explicit and self-determined need requirements eliminated framing effects and affected risk acceptance consistent with risk-sensitivity theory. Furthermore, negative language choice in loss frames conferred the perception of high need and led to the construction of higher minimal acceptable thresholds. The results of this study suggest that risk-sensitivity theory provides a normative rationale for framing effects based on sensitivity to minimal acceptable thresholds, or needs. 2012 APA, all rights reserved

  5. Omnidirectional mirror based on Bragg stacks with a periodic gain-loss modulation

    International Nuclear Information System (INIS)

    Manzanares-Martinez, Jesus; Ham-Rodriguez, Carlos Ivan; Moctezuma-Enriquez, Damian; Manzanares-Martinez, Betsabe

    2014-01-01

    In this work we demonstrate that a Bragg Stack with a periodic gain-loss modulation can function as an Omnidirectional Mirror (OM) with complete reflection at any angle of incidence irrespective of the light polarization. The Bragg Stack is composed by the periodic variation of two layers with the same value of the real part of the refractive index (n r ) and a periodic modulation in the imaginary part (n i ). The origin of the band gaps is due to the interference of complex waves with propagating and evanescent fields in each layer. It is found that the band gaps are wider as the contrast n i /n r increases. We have found the ambient conditions to obtain an OM considering an auxiliary medium n ′ external to the Bragg Stack

  6. Cone dystrophy with "supernormal" rod ERG: psychophysical testing shows comparable rod and cone temporal sensitivity losses with no gain in rod function.

    Science.gov (United States)

    Stockman, Andrew; Henning, G Bruce; Michaelides, Michel; Moore, Anthony T; Webster, Andrew R; Cammack, Jocelyn; Ripamonti, Caterina

    2014-02-10

    We report a psychophysical investigation of 5 observers with the retinal disorder "cone dystrophy with supernormal rod ERG," caused by mutations in the gene KCNV2 that encodes a voltage-gated potassium channel found in rod and cone photoreceptors. We compared losses for rod- and for cone-mediated vision to further investigate the disorder and to assess whether the supernormal ERG is associated with any visual benefit. L-cone, S-cone, and rod temporal acuity (critical flicker fusion frequency) were measured as a function of target irradiance; L-cone temporal contrast sensitivity was measured as a function of temporal frequency. Temporal acuity measures revealed that losses for vision mediated by rods, S-cones, and L-cones are roughly equivalent. Further, the gain in rod function implied by the supernormal ERG provides no apparent benefit to near-threshold rod-mediated visual performance. The L-cone temporal contrast sensitivity function in affected observers was similar in shape to the mean normal function but only after the mean function was compressed by halving the logarithmic sensitivities. The name of this disorder is potentially misleading because the comparable losses found across rod and cone vision suggest that the disorder is a generalized cone-rod dystrophy. Temporal acuity and temporal contrast sensitivity measures are broadly consistent with the defect in the voltage-gated potassium channel producing a nonlinear distortion of the photoreceptor response but after otherwise normal transduction processes.

  7. Adult onset global loss of the fto gene alters body composition and metabolism in the mouse.

    Directory of Open Access Journals (Sweden)

    Fiona McMurray

    Full Text Available The strongest BMI-associated GWAS locus in humans is the FTO gene. Rodent studies demonstrate a role for FTO in energy homeostasis and body composition. The phenotypes observed in loss of expression studies are complex with perinatal lethality, stunted growth from weaning, and significant alterations in body composition. Thus understanding how and where Fto regulates food intake, energy expenditure, and body composition is a challenge. To address this we generated a series of mice with distinct temporal and spatial loss of Fto expression. Global germline loss of Fto resulted in high perinatal lethality and a reduction in body length, fat mass, and lean mass. When ratio corrected for lean mass, mice had a significant increase in energy expenditure, but more appropriate multiple linear regression normalisation showed no difference in energy expenditure. Global deletion of Fto after the in utero and perinatal period, at 6 weeks of age, removed the high lethality of germline loss. However, there was a reduction in weight by 9 weeks, primarily as loss of lean mass. Over the subsequent 10 weeks, weight converged, driven by an increase in fat mass. There was a switch to a lower RER with no overall change in food intake or energy expenditure. To test if the phenotype can be explained by loss of Fto in the mediobasal hypothalamus, we sterotactically injected adeno-associated viral vectors encoding Cre recombinase to cause regional deletion. We observed a small reduction in food intake and weight gain with no effect on energy expenditure or body composition. Thus, although hypothalamic Fto can impact feeding, the effect of loss of Fto on body composition is brought about by its actions at sites elsewhere. Our data suggest that Fto may have a critical role in the control of lean mass, independent of its effect on food intake.

  8. Attribution of Causes of Weight Loss and Weight Gain to 3-Year Mortality in Older Adults: Results From the Longitudinal Aging Study Amsterdam

    NARCIS (Netherlands)

    Wijnhoven, H.A.H.; van Zon, S.K.R.; Twisk, J.; Visser, M.

    2014-01-01

    Background: Weight loss is associated with a higher mortality risk in old age, but the underlying cause may impact this association. We examined associations between causes of intentional and unintentional weight loss and weight gain and mortality. Methods: We used data of five triannual examination

  9. Attribution of Causes of Weight Loss and Weight Gain to 3-Year Mortality in Older Adults : Results From the Longitudinal Aging Study Amsterdam

    NARCIS (Netherlands)

    Wijnhoven, Hanneke A. H.; van Zon, Sander K. R.; Twisk, Jos; Visser, Marjolein

    2014-01-01

    Background. Weight loss is associated with a higher mortality risk in old age, but the underlying cause may impact this association. We examined associations between causes of intentional and unintentional weight loss and weight gain and mortality. Methods. We used data of five triannual examination

  10. 26 CFR 1.582-1 - Bad debts, losses, and gains with respect to securities held by financial institutions.

    Science.gov (United States)

    2010-04-01

    ... securities held by financial institutions. 1.582-1 Section 1.582-1 Internal Revenue INTERNAL REVENUE SERVICE... § 1.582-1 Bad debts, losses, and gains with respect to securities held by financial institutions. (a... financial institutions. For taxable years beginning after July 11, 1969, the sale or exchange of a security...

  11. Constraints on genome dynamics revealed from gene distribution among the Ralstonia solanacearum species.

    Directory of Open Access Journals (Sweden)

    Pierre Lefeuvre

    Full Text Available Because it is suspected that gene content may partly explain host adaptation and ecology of pathogenic bacteria, it is important to study factors affecting genome composition and its evolution. While recent genomic advances have revealed extremely large pan-genomes for some bacterial species, it remains difficult to predict to what extent gene pool is accessible within or transferable between populations. As genomes bear imprints of the history of the organisms, gene distribution pattern analyses should provide insights into the forces and factors at play in the shaping and maintaining of bacterial genomes. In this study, we revisited the data obtained from a previous CGH microarrays analysis in order to assess the genomic plasticity of the R. solanacearum species complex. Gene distribution analyses demonstrated the remarkably dispersed genome of R. solanacearum with more than half of the genes being accessory. From the reconstruction of the ancestral genomes compositions, we were able to infer the number of gene gain and loss events along the phylogeny. Analyses of gene movement patterns reveal that factors associated with gene function, genomic localization and ecology delineate gene flow patterns. While the chromosome displayed lower rates of movement, the megaplasmid was clearly associated with hot-spots of gene gain and loss. Gene function was also confirmed to be an essential factor in gene gain and loss dynamics with significant differences in movement patterns between different COG categories. Finally, analyses of gene distribution highlighted possible highways of horizontal gene transfer. Due to sampling and design bias, we can only speculate on factors at play in this gene movement dynamic. Further studies examining precise conditions that favor gene transfer would provide invaluable insights in the fate of bacteria, species delineation and the emergence of successful pathogens.

  12. Plastid genome evolution across the genus Cuscuta (Convolvulaceae): two clades within subgenus Grammica exhibit extensive gene loss.

    Science.gov (United States)

    Braukmann, Thomas; Kuzmina, Maria; Stefanovic, Sasa

    2013-02-01

    The genus Cuscuta (Convolvulaceae, the morning glory family) is one of the most intensely studied lineages of parasitic plants. Whole plastome sequencing of four Cuscuta species has demonstrated changes to both plastid gene content and structure. The presence of photosynthetic genes under purifying selection indicates that Cuscuta is cryptically photosynthetic. However, the tempo and mode of plastid genome evolution across the diversity of this group (~200 species) remain largely unknown. A comparative investigation of plastid genome content, grounded within a phylogenetic framework, was conducted using a slot-blot Southern hybridization approach. Cuscuta was extensively sampled (~56% of species), including groups previously suggested to possess more altered plastomes compared with other members of this genus. A total of 56 probes derived from all categories of protein-coding genes, typically found within the plastomes of flowering plants, were used. The results indicate that two clades within subgenus Grammica (clades 'O' and 'K') exhibit substantially more plastid gene loss relative to other members of Cuscuta. All surveyed members of the 'O' clade show extensive losses of plastid genes from every category of genes typically found in the plastome, including otherwise highly conserved small and large ribosomal subunits. The extent of plastid gene losses within this clade is similar in magnitude to that observed previously in some non-asterid holoparasites, in which the very presence of a plastome has been questioned. The 'K' clade also exhibits considerable loss of plastid genes. Unlike in the 'O' clade, in which all species seem to be affected, the losses in clade 'K' progress phylogenetically, following a pattern consistent with the Evolutionary Transition Series hypothesis. This clade presents an ideal opportunity to study the reduction of the plastome of parasites 'in action'. The widespread plastid gene loss in these two clades is hypothesized to be a

  13. Dual gain of HER2 and EGFR gene copy numbers impacts the prognosis of carcinoma ex pleomorphic adenoma.

    Science.gov (United States)

    Nishijima, Toshimitsu; Yamamoto, Hidetaka; Nakano, Takafumi; Nakashima, Torahiko; Taguchi, Ken-ichi; Masuda, Muneyuki; Motoshita, Jun-ichi; Komune, Shizuo; Oda, Yoshinao

    2015-11-01

    We investigated the potential roles of HER2 and EGFR and evaluated their prognostic significance in carcinoma ex pleomorphic adenoma (CXPA). We analyzed HER2 and EGFR overexpression status using immunohistochemistry (IHC) and gene copy number gain by chromogenic in situ hybridization (CISH) in 50 cases of CXPA (40 ductal-type and 10 myoepithelial-type CXPAs). Salivary duct carcinoma was the most common histologic subtype of malignant component (n = 21). Immunohistochemistry positivity and chromogenic in situ hybridization positivity were closely correlated in both HER2 and EGFR. HER2 CISH positivity (mostly gene amplification) and EGFR CISH positivity (mostly gene high polysomy) were present in 19 (40%) and 21 (44%) cases, respectively, and were each significantly correlated with poor outcome (P = .0009 and P = .0032, respectively). Dual gain of HER2 and EGFR gene copy numbers was present in 11 cases (23%) and was the most aggressive genotype. HER2 CISH positivity was more frequently present in ductal-type CXPAs (47%) than in myoepithelial-type CXPAs (10%), whereas the prevalence of EGFR CISH positivity was similar in both histologic subtypes (42% and 50%, respectively). Our results suggest that HER2 and EGFR gene copy number gains may play an important role in the progression of CXPA, in particular ductal-type CXPAs. HER2 CISH-positive/EGFR CISH-positive tumors may be the most aggressive subgroup in CXPA. The molecular subclassification of CXPA based on the HER2 and EGFR status may be helpful for prognostic prediction and decisions regarding the choice of therapeutic strategy. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women

    DEFF Research Database (Denmark)

    Gartland, Alison; Skarratt, Kristen K; Hocking, Lynne J

    2012-01-01

    The P2X7 receptor gene (P2RX7) is highly polymorphic with five previously described loss-of-function (LOF) single-nucleotide polymorphisms (SNP; c.151+1G>T, c.946G>A, c.1096C>G, c.1513A>C and c.1729T>A) and one gain-of-function SNP (c.489C>T). The purpose of this study was to determine whether th...... publication, 11 January 2012; doi:10.1038/ejhg.2011.245....

  15. Cell-to-module optical loss/gain analysis for various photovoltaic module materials through systematic characterization

    Science.gov (United States)

    Hsian Saw, Min; Khoo, Yong Sheng; Singh, Jai Prakash; Wang, Yan

    2017-08-01

    Reducing levelized cost of electricity (LCOE) is important for solar photovoltaics to compete against other energy sources. Thus, the focus should not only be on improving the solar cell efficiency, but also on continuously reducing the losses (or achieving gain) in the cell-to-module process. This can be achieved by choosing the appropriate module material and design. This paper presents a detailed and systematic characterization of various photovoltaic (PV) module materials (encapsulants, tabbing ribbons, and backsheets) and an evaluation of their impact on the output power of silicon wafer-based PV modules. Various characterization tools/techniques, such as UV-vis (reflectance) measurement, external quantum efficiency (EQE) measurement and EQE line-scan are used. Based on the characterization results, we use module materials with the best-evaluated optical performance to build “optimized modules”. Compared to the standard mini-module, an optical gain of more than 5% is achievable for the “optimized module” with selected module materials.

  16. Omnidirectional mirror based on Bragg stacks with a periodic gain-loss modulation

    Energy Technology Data Exchange (ETDEWEB)

    Manzanares-Martinez, Jesus; Ham-Rodriguez, Carlos Ivan [Departamento de Investigacion en Fisica, Universidad de Sonora, Apartado Postal 5-088, Hermosillo, Sonora 83000 (Mexico); Moctezuma-Enriquez, Damian, E-mail: foxonicos@gmail.com [Centro de Investigacion en Materiales Avanzados (CIMAV), Miguel de Cervantes 120, Chihuahua 31109 (Mexico); Manzanares-Martinez, Betsabe [Departamento de Fisica, Universidad de Sonora, Blvd. Luis Encinas y Rosales, Hermosillo, Sonora 83000 (Mexico)

    2014-01-15

    In this work we demonstrate that a Bragg Stack with a periodic gain-loss modulation can function as an Omnidirectional Mirror (OM) with complete reflection at any angle of incidence irrespective of the light polarization. The Bragg Stack is composed by the periodic variation of two layers with the same value of the real part of the refractive index (n{sub r}) and a periodic modulation in the imaginary part (n{sub i}). The origin of the band gaps is due to the interference of complex waves with propagating and evanescent fields in each layer. It is found that the band gaps are wider as the contrast n{sub i}/n{sub r} increases. We have found the ambient conditions to obtain an OM considering an auxiliary medium n{sup ′} external to the Bragg Stack.

  17. Evolution of stress-regulated gene expression in duplicate genes of Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Cheng Zou

    2009-07-01

    Full Text Available Due to the selection pressure imposed by highly variable environmental conditions, stress sensing and regulatory response mechanisms in plants are expected to evolve rapidly. One potential source of innovation in plant stress response mechanisms is gene duplication. In this study, we examined the evolution of stress-regulated gene expression among duplicated genes in the model plant Arabidopsis thaliana. Key to this analysis was reconstructing the putative ancestral stress regulation pattern. By comparing the expression patterns of duplicated genes with the patterns of their ancestors, duplicated genes likely lost and gained stress responses at a rapid rate initially, but the rate is close to zero when the synonymous substitution rate (a proxy for time is > approximately 0.8. When considering duplicated gene pairs, we found that partitioning of putative ancestral stress responses occurred more frequently compared to cases of parallel retention and loss. Furthermore, the pattern of stress response partitioning was extremely asymmetric. An analysis of putative cis-acting DNA regulatory elements in the promoters of the duplicated stress-regulated genes indicated that the asymmetric partitioning of ancestral stress responses are likely due, at least in part, to differential loss of DNA regulatory elements; the duplicated genes losing most of their stress responses were those that had lost more of the putative cis-acting elements. Finally, duplicate genes that lost most or all of the ancestral responses are more likely to have gained responses to other stresses. Therefore, the retention of duplicates that inherit few or no functions seems to be coupled to neofunctionalization. Taken together, our findings provide new insight into the patterns of evolutionary changes in gene stress responses after duplication and lay the foundation for testing the adaptive significance of stress regulatory changes under highly variable biotic and abiotic environments.

  18. The Black Queen Hypothesis: evolution of dependencies through adaptive gene loss.

    Science.gov (United States)

    Morris, J Jeffrey; Lenski, Richard E; Zinser, Erik R

    2012-01-01

    Reductive genomic evolution, driven by genetic drift, is common in endosymbiotic bacteria. Genome reduction is less common in free-living organisms, but it has occurred in the numerically dominant open-ocean bacterioplankton Prochlorococcus and "Candidatus Pelagibacter," and in these cases the reduction appears to be driven by natural selection rather than drift. Gene loss in free-living organisms may leave them dependent on cooccurring microbes for lost metabolic functions. We present the Black Queen Hypothesis (BQH), a novel theory of reductive evolution that explains how selection leads to such dependencies; its name refers to the queen of spades in the game Hearts, where the usual strategy is to avoid taking this card. Gene loss can provide a selective advantage by conserving an organism's limiting resources, provided the gene's function is dispensable. Many vital genetic functions are leaky, thereby unavoidably producing public goods that are available to the entire community. Such leaky functions are thus dispensable for individuals, provided they are not lost entirely from the community. The BQH predicts that the loss of a costly, leaky function is selectively favored at the individual level and will proceed until the production of public goods is just sufficient to support the equilibrium community; at that point, the benefit of any further loss would be offset by the cost. Evolution in accordance with the BQH thus generates "beneficiaries" of reduced genomic content that are dependent on leaky "helpers," and it may explain the observed nonuniversality of prototrophy, stress resistance, and other cellular functions in the microbial world.

  19. Loss of ACTH expression in cultured human corticotroph macroadenoma cells is consistent with loss of the POMC gene signal sequence.

    Science.gov (United States)

    Rees, D A; Hepburn, P J; McNicol, A M; Francis, K; Jasani, B; Lewis, M D; Farrell, W E; Lewis, B M; Scanlon, M F; Ham, J

    2002-03-28

    The proopiomelanocortin (POMC) gene is highly expressed in the pituitary gland where the resulting mRNA of 1200 base pairs (bp) gives rise to a full-length protein sequence. In peripheral tissues however both shorter and longer POMC variants have been described, these include for example placental tissue which contain 800 (truncated at the 5' end) and 1500 as well as the 1200 bp transcripts. The importance of the 800 bp transcript is unclear as the lack of a signal sequence renders the molecule to be non-functional. This transcript has not been previously demonstrated in the pituitary gland. In this report we show evidence of a 5' truncated POMC gene in human pituitary corticotroph macroadenoma cells (JE) maintained in primary culture for >1 year. The original tumour tissue and the derived cells during early passage (up to passage 4-5) immunostained for ACTH and in situ hybridisation confirmed the presence of the POMC gene in the cultured cells. These cells also secreted 15-40 pg/10(5) cells/24 h ACTH. In addition, as expected RT-PCR demonstrated the presence of all three POMC gene exons and is thus indicative of a full-length POMC gene. In late culture passages (passages 8-15) JE cells ceased to express ACTH and cell growth became very slow due presumably to cells reaching their Hayflick limit. ACTH immunostaining in these cells was undetectable and ACTH secretion was also at the detection limits of the assay and no greater than 10 pg/10(5) cells/24 h. ACTH precursor molecules were also undetectable. RT-PCR for the POMC gene in these late passage cells showed that only exon 3 was detectable, in contrast to early passage cells where all three exons were present. In summary we isolated in culture, human pituitary cells that possessed initially all three exons of the POMC gene and immunostained for ACTH. On further passaging these cells showed a loss of exons 1 and 2 in the POMC gene and a loss of ACTH immunostaining and secretion. We would like to suggest that the

  20. Loss and gain cycles? A longitudinal study about burnout, engagement and self-efficacy

    Directory of Open Access Journals (Sweden)

    Susana Llorens-Gumbau

    2014-06-01

    Full Text Available The present longitudinal study (two waves, conducted on a population of 274 secondary-school teachers, expands on previous research on burnout and work engagement. Accordingly, the effect of organizational factors (obstacles, facilitators as well as personal resources (self-efficacy on burnout and engagement is tested longitudinally following the Social Cognitive Theory. More specifically, we test the loss and gain cycles, and reciprocal relationships concerning burnout, engagement, and self-efficacy over time. Four questions are addressed: (1 Are obstacles positively related to burnout and work self-efficacy over time? (2 Are facilitators positively related to engagement and self-efficacy over time? (3 Is work self-efficacy negatively related to burnout and obstacles over time? and (4 Is work self-efficacy positively related to engagement and facilitators over time? The results of a hard-copy survey carried out at two waves (8 months between the two times, which were computed on Structural Equation Modeling show that obstacles are positively related to burnout, which in turn is positively related to self-efficacy over time. Likewise, facilitators are positively related to engagement and self-efficacy, which in turn is positively related to facilitators over time. These findings suggest a positive gain cycle in which self-efficacy plays a central role.

  1. Different gain/loss sensitivity and social adaptation ability in gifted adolescents during a public goods game.

    Directory of Open Access Journals (Sweden)

    Dongil Chung

    Full Text Available Gifted adolescents are considered to have high IQs with advanced mathematical and logical performances, but are often thought to suffer from social isolation or emotional mal-adaptation to the social group. The underlying mechanisms that cause stereotypic portrayals of gifted adolescents are not well known. We aimed to investigate behavioral performance of gifted adolescents during social decision-making tasks to assess their affective and social/non-social cognitive abilities. We examined cooperation behaviors of 22 gifted and 26 average adolescents during an iterative binary public goods (PG game, a multi-player social interaction game, and analyzed strategic decision processes that include cooperation and free-riding. We found that the gifted adolescents were more cooperative than average adolescents. Particularly, comparing the strategies for the PG game between the two groups, gifted adolescents were less sensitive to loss, yet were more sensitive to gain. Additionally, the behavioral characteristics of average adolescents, such as low trust of the group and herding behavior, were not found in gifted adolescents. These results imply that gifted adolescents have a high cognitive ability but a low ability to process affective information or to adapt in social groups compared with average adolescents. We conclude that gain/loss sensitivity and the ability to adapt in social groups develop to different degrees in average and gifted adolescents.

  2. Different Gain/Loss Sensitivity and Social Adaptation Ability in Gifted Adolescents during a Public Goods Game

    Science.gov (United States)

    Chung, Dongil; Yun, Kyongsik; Kim, Jin Ho; Jang, Bosun; Jeong, Jaeseung

    2011-01-01

    Gifted adolescents are considered to have high IQs with advanced mathematical and logical performances, but are often thought to suffer from social isolation or emotional mal-adaptation to the social group. The underlying mechanisms that cause stereotypic portrayals of gifted adolescents are not well known. We aimed to investigate behavioral performance of gifted adolescents during social decision-making tasks to assess their affective and social/non-social cognitive abilities. We examined cooperation behaviors of 22 gifted and 26 average adolescents during an iterative binary public goods (PG) game, a multi-player social interaction game, and analyzed strategic decision processes that include cooperation and free-riding. We found that the gifted adolescents were more cooperative than average adolescents. Particularly, comparing the strategies for the PG game between the two groups, gifted adolescents were less sensitive to loss, yet were more sensitive to gain. Additionally, the behavioral characteristics of average adolescents, such as low trust of the group and herding behavior, were not found in gifted adolescents. These results imply that gifted adolescents have a high cognitive ability but a low ability to process affective information or to adapt in social groups compared with average adolescents. We conclude that gain/loss sensitivity and the ability to adapt in social groups develop to different degrees in average and gifted adolescents. PMID:21359224

  3. Quantifying the mechanisms of domain gain in animal proteins.

    Science.gov (United States)

    Buljan, Marija; Frankish, Adam; Bateman, Alex

    2010-01-01

    Protein domains are protein regions that are shared among different proteins and are frequently functionally and structurally independent from the rest of the protein. Novel domain combinations have a major role in evolutionary innovation. However, the relative contributions of the different molecular mechanisms that underlie domain gains in animals are still unknown. By using animal gene phylogenies we were able to identify a set of high confidence domain gain events and by looking at their coding DNA investigate the causative mechanisms. Here we show that the major mechanism for gains of new domains in metazoan proteins is likely to be gene fusion through joining of exons from adjacent genes, possibly mediated by non-allelic homologous recombination. Retroposition and insertion of exons into ancestral introns through intronic recombination are, in contrast to previous expectations, only minor contributors to domain gains and have accounted for less than 1% and 10% of high confidence domain gain events, respectively. Additionally, exonization of previously non-coding regions appears to be an important mechanism for addition of disordered segments to proteins. We observe that gene duplication has preceded domain gain in at least 80% of the gain events. The interplay of gene duplication and domain gain demonstrates an important mechanism for fast neofunctionalization of genes.

  4. Modulating activity in the prefrontal cortex changes decision-making for risky gains and losses: a transcranial direct current stimulation study.

    Science.gov (United States)

    Ye, Hang; Chen, Shu; Huang, Daqiang; Wang, Siqi; Luo, Jun

    2015-06-01

    When making choices under uncertainty, people usually consider both the risks and benefits of each option. Previous studies have found that weighing of risks and benefits during decision-making involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC), but the causal effect of this network on risk decision-making has remained unclear. This experiment was based on a risk-measurement table designed to provide a direct measure of risk preference, with a weighted value of the choices (denoted as weighted risk aversion, WRA) as an index of the participant's degree of risk aversion. We studied whether bifrontal transcranial direct current stimulation (tDCS) applied over the right and left prefrontal cortex can change the balance of risky vs. safe responses under both gain frame and loss frame. A total of 60 volunteers performed risk tasks while receiving either anodal over the right with cathodal over the left DLPFC, anodal over the left with cathodal over the right DLPFC, or sham stimulation. The participants tended to choose more risky options in the gain frame and more safe options in the loss frame after the right anodal/left cathodal tDCS. We also found that right anodal/left cathodal tDCS significantly decreased the WRA values compared with those associated with sham stimulation. These findings extend the notion that DLPFC activity is critical for risk decision-making, indicating an asymmetric role of the right DLPFC in the gain frame vs. the loss frame of risk decision-making. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. The Association between Obesity-Risk Genes and Gestational Weight Gain Is Modified by Dietary Intake in African American Women

    Directory of Open Access Journals (Sweden)

    Ying Meng

    2018-01-01

    Full Text Available Obesity-risk genes have been associated with dietary intake, appetite regulation, and gestational weight gain (GWG. The purpose of this study was to examine whether dietary intake including total energy intake and macronutrients modify or mediate the association between obesity-risk genes and GWG. An observational study was conducted with 85 African American pregnant women. Sociodemographic, medical, and lifestyle factors and dietary recalls were collected during pregnancy. Seven obesity-risk genetic variants were genotyped. Regression analyses with bootstrapping methods were used to examine the moderation and mediation effects of dietary intake. The mean GWG was 14.2 kg, and 55.3% of the women gained above the Institute of Medicine GWG guidelines. A nominally significant association was found between rs17782313 (close to MC4R and percentage of energy intake from fat P=0.043. A variant downstream of KCTD15 (rs11084753 was nominally significantly related to GWG P=0.023. There was a significant interaction between the KCTD15 polymorphism and dietary fat intake P=0.048. Women with the AG genotype gained more weight during pregnancy with more dietary fat consumption. In conclusion, our results indicate that dietary macronutrients, especially fat intake, may modify the effect of the KCTD15 gene on GWG. Improved knowledge of gene-diet interactions can facilitate the development of personalized interventions.

  6. Somatic loss of function mutations in neurofibromin 1 and MYC associated factor X genes identified by exome-wide sequencing in a wild-type GIST case

    International Nuclear Information System (INIS)

    Belinsky, Martin G.; Rink, Lori; Cai, Kathy Q.; Capuzzi, Stephen J.; Hoang, Yen; Chien, Jeremy; Godwin, Andrew K.; Mehren, Margaret von

    2015-01-01

    Approximately 10–15 % of gastrointestinal stromal tumors (GISTs) lack gain of function mutations in the KIT and platelet-derived growth factor receptor alpha (PDGFRA) genes. An alternate mechanism of oncogenesis through loss of function of the succinate-dehydrogenase (SDH) enzyme complex has been identified for a subset of these “wild type” GISTs. Paired tumor and normal DNA from an SDH-intact wild-type GIST case was subjected to whole exome sequencing to identify the pathogenic mechanism(s) in this tumor. Selected findings were further investigated in panels of GIST tumors through Sanger DNA sequencing, quantitative real-time PCR, and immunohistochemical approaches. A hemizygous frameshift mutation (p.His2261Leufs*4), in the neurofibromin 1 (NF1) gene was identified in the patient’s GIST; however, no germline NF1 mutation was found. A somatic frameshift mutation (p.Lys54Argfs*31) in the MYC associated factor X (MAX) gene was also identified. Immunohistochemical analysis for MAX on a large panel of GISTs identified loss of MAX expression in the MAX-mutated GIST and in a subset of mainly KIT-mutated tumors. This study suggests that inactivating NF1 mutations outside the context of neurofibromatosis may be the oncogenic mechanism for a subset of sporadic GIST. In addition, loss of function mutation of the MAX gene was identified for the first time in GIST, and a broader role for MAX in GIST progression was suggested. The online version of this article (doi:10.1186/s12885-015-1872-y) contains supplementary material, which is available to authorized users

  7. Role of 5-HT2C receptor gene variants in antipsychotic-induced weight gain

    Directory of Open Access Journals (Sweden)

    Brandl EJ

    2011-08-01

    Full Text Available Tessa JM Wallace, Clement C Zai, Eva J Brandl, Daniel J MüllerNeurogenetics Section, Center for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, CanadaAbstract: Antipsychotic-induced weight gain is a serious side effect of antipsychotic medication that can lead to increased morbidity, mortality, and non-compliance in patients. Numerous single nucleotide polymorphisms have been studied for association with antipsychotic-induced weight gain in an attempt to find genetic predictors of this side effect. An ability to predict this side effect could lead to personalized treatment plans for predisposed individuals, which could significantly decrease the prevalence and severity of weight gain. Variations in the serotonin receptor 2c gene (HTR2C have emerged as promising candidates for prediction of antipsychotic-induced weight gain. Specifically, the well-studied -759C/T promoter polymorphism has been associated with weight gain in diverse populations, although some studies have reported no association. This discrepancy is likely due to heterogeneity in study design with respect to ethnicity, treatment duration, and other variables. Notably, the association between HTR2C and antipsychotic-induced weight gain appears strongest in short-term studies on patients with limited or no previous antipsychotic treatment. Other, less extensively studied promoter polymorphisms (-697C/G, -997G/A, and -1165A/G have also emerged as potential predictors of antipsychotic-induced weight gain. Conversely, the well-studied intronic polymorphism Cys23Ser does not appear to be associated. With further research on both HTR2C and other genetic and environmental predictors of antipsychotic-induced weight gain, a predictive test could one day be created to screen patients and provide preventative or alternative treatment for those who are predisposed to this serious side effect.Keywords: HTR2C, pharmacogenomics, promoter polymorphism

  8. 26 CFR 1.312-7 - Effect on earnings and profits of gain or loss realized after February 28, 1913.

    Science.gov (United States)

    2010-04-01

    ... in determining invested capital; and (2) The computation of earnings and profits of the corporation... stock in the hands of Corporation R for purposes of computing earnings and profits, however, will be... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Effect on earnings and profits of gain or loss...

  9. Gene loss and horizontal gene transfer contributed to the genome evolution of the extreme acidophile Ferrovum

    Directory of Open Access Journals (Sweden)

    Sophie Roxana Ullrich

    2016-05-01

    Full Text Available Acid mine drainage (AMD, associated with active and abandoned mining sites, is a habitat for acidophilic microorganisms that gain energy from the oxidation of reduced sulfur compounds and ferrous iron and that thrive at pH below 4. Members of the recently proposed genus Ferrovum are the first acidophilic iron oxidizers to be described within the Betaproteobacteria. Although they have been detected as typical community members in AMD habitats worldwide, knowledge of their phylogenetic and metabolic diversity is scarce. Genomics approaches appear to be most promising in addressing this lacuna since isolation and cultivation of Ferrovum has proven to be extremely difficult and has so far only been successful for the designated type strain Ferrovum myxofaciens P3G. In this study, the genomes of two novel strains of Ferrovum (PN-J185 and Z-31 derived from water samples of a mine water treatment plant were sequenced. These genomes were compared with those of Ferrovum sp. JA12 that also originated from the mine water treatment plant, and of the type strain (P3G. Phylogenomic scrutiny suggests that the four strains represent three Ferrovum species that cluster in two groups (1 and 2. Comprehensive analysis of their predicted metabolic pathways revealed that these groups harbor characteristic metabolic profiles, notably with respect to motility, chemotaxis, nitrogen metabolism, biofilm formation and their potential strategies to cope with the acidic environment. For example, while the F. myxofaciens strains (group 1 appear to be motile and diazotrophic, the non-motile group 2 strains have the predicted potential to use a greater variety of fixed nitrogen sources. Furthermore, analysis of their genome synteny provides first insights into their genome evolution, suggesting that horizontal gene transfer and genome reduction in the group 2 strains by loss of genes encoding complete metabolic pathways or physiological features contributed to the observed

  10. Parity-Time Symmetry and the Toy Models of Gain-Loss Dynamics near the Real Kato’s Exceptional Points

    Directory of Open Access Journals (Sweden)

    Miloslav Znojil

    2016-06-01

    Full Text Available For a given operator D ( t of an observable in theoretical parity-time symmetric quantum physics (or for its evolution-generator analogues in the experimental gain-loss classical optics, etc. the instant t c r i t i c a l of a spontaneous breakdown of the parity-time alias gain-loss symmetry should be given, in the rigorous language of mathematics, the Kato’s name of an “exceptional point”, t c r i t i c a l = t ( E P . In the majority of conventional applications the exceptional point (EP values are not real. In our paper, we pay attention to several exactly tractable toy-model evolutions for which at least some of the values of t ( E P become real. These values are interpreted as “instants of a catastrophe”, be it classical or quantum. In the classical optical setting the discrete nature of our toy models might make them amenable to simulations. In the latter context the instant of Big Bang is mentioned as an illustrative sample of possible physical meaning of such an EP catastrophe in quantum cosmology.

  11. Loss-Aversion or Loss-Attention: The Impact of Losses on Cognitive Performance

    Science.gov (United States)

    Yechiam, Eldad; Hochman, Guy

    2013-01-01

    Losses were found to improve cognitive performance, and this has been commonly explained by increased weighting of losses compared to gains (i.e., loss aversion). We examine whether effects of losses on performance could be modulated by two alternative processes: an attentional effect leading to increased sensitivity to task incentives; and a…

  12. Individual Responsiveness to Exercise-Induced Fat Loss and Improvement of Metabolic Profile in Young Women is Associated with Polymorphisms of Adrenergic Receptor Genes

    Directory of Open Access Journals (Sweden)

    Agata Leońska-Duniec, Zbigniew Jastrzębski, Aleksandra Jażdżewska, Waldemar Moska, Ewelina Lulińska-Kuklik, Marek Sawczuk, Svetlana I. Gubaydullina, Alsu T. Shakirova, Pawel Cięszczyk, Adam Maszczyk, Ildus I. Ahmetov

    2018-03-01

    Full Text Available The effectiveness of physical exercise on fat loss and improvement of aerobic capacity varies considerably between individuals. A strong linkage exists between common allelic variants of the adrenergic receptor genes and weight gain, as well as changes in body composition. Therefore we aimed to check if body composition and metabolic variables were modulated by the ADRB2 (Gly16Arg and Glu27Gln, ADRB3 (Trp64Arg and ADRA2A (rs553668 G/A gene polymorphisms in 163 Polish sedentary women (age 19-24; body mass index (BMI 21.7 ± 0.2 kg·m-2 involved in a 12-week aerobic training program. Only 74.8% of participants lost fat mass. On average, participants lost 5.8 (10.4% of their relative fat mass with training (range: +28.3 to -63.6%. The improvement of VO2max was significantly greater in women who could lose their fat mass compared to women who were unsuccessful in fat loss (4.5 (5.6% vs. 1.5 (3.8%; p = 0.0045. The carriers of a low number (0-3 of obesity-related risk alleles (ADRB2 Gly16, ADRB2 Glu27, ADRA2A rs553668 G were more successful in fat mass loss compared to the carriers of a high number (5-6 of risk alleles (7.7 (9.8 vs 4.0 (9.4%, p = 0.0362. The presented results support the assumption that variation within adrenergic receptor genes contributes to interindividual changes of body composition in response to physical exercise.

  13. Gain versus loss framing in adherence-promoting communication targeting patients with chronic diseases: the moderating effect of individual time perspective.

    Science.gov (United States)

    Zhao, Xiaoquan; Villagran, Melinda M; Kreps, Gary L; McHorney, Colleen

    2012-01-01

    This study investigated the joint effect of message framing and time perspective in adherence-promoting communication targeting patients with chronic diseases. Based on previous framing and time perspective research, it was hypothesized that the gain frame would show an advantage over the loss frame among future-oriented patients; for present-oriented patients, it was hypothesized that the framing effect would be relatively indistinct. In total, 1,108 currently nonadherent patients with chronic disease participated in an experiment where they were randomly assigned to either gain- or loss-framed messages addressing key beliefs underlying their nonadherence or a no-message control condition. Intention and attitude regarding future adherence as well as message perceptions were measured after message presentation. Results of this study generally supported the hypotheses. Message topics-whether the messages addressed patients' perceived need for medications or concerns about side effects-did not moderate the effect of framing or the interaction between framing and time perspective. Theoretical and practical implications are discussed.

  14. Do you want the good news or the bad news? Gain- versus loss-framed messages following health risk information: The effects on leisure time physical activity beliefs and cognitions.

    Science.gov (United States)

    Bassett-Gunter, Rebecca L; Martin Ginis, Kathleen A; Latimer-Cheung, Amy E

    2013-12-01

    The primary purpose was to examine the relative effectiveness of chronic disease and psychological health risk information combined with gain- versus loss-framed leisure time physical activity (LTPA) messages for changing perceived personal risk, LTPA response efficacy (i.e., the belief that LTPA can effectively reduce risk), and LTPA intentions. A secondary purpose was to explore the relationship between message framing and cognitive processing. Baseline assessments of perceived risk for inactivity-related disease and psychological health problems, LTPA response efficacy, and intentions were measured among 96 individuals with spinal cord injury (SCI). Participants read population-specific information about the risk for inactivity-related disease and psychological health problems following SCI, and perceived risk was reassessed. Participants were then randomized to read LTPA response efficacy messages emphasizing the benefits of LTPA (gain framed) or the risks of inactivity (loss framed). Immediately following message exposure, cognitive processing (i.e., thought listing and message recall), LTPA response efficacy, and LTPA intentions were assessed. Changes in perceived risk were observed following exposure to health risk information. Changes in LTPA response efficacy and intentions were greater following loss-framed messages targeting psychological health compared with gain-framed messages. Greater cognitive processing was observed following loss-framed messages compared with gain-framed messages. Following exposure to psychological health risk information, loss-framed messages may be more effective than gain-framed messages for eliciting cognitive processing and changing LTPA beliefs and intentions.

  15. Transitioning hearing aid users with severe and profound loss to a new gain/frequency response: benefit, perception, and acceptance.

    Science.gov (United States)

    Convery, Elizabeth; Keidser, Gitte

    2011-03-01

    Adults with severe and profound hearing loss tend to be long-term, full-time users of amplification who are highly reliant on their hearing aids. As a result of these characteristics, they are often reluctant to update their hearing aids when new features or signal-processing algorithms become available. Due to the electroacoustic constraints of older devices, many severely and profoundly hearing-impaired adults continue to wear hearing aids that provide more low- and mid-frequency gain and less high-frequency gain than would be prescribed by the National Acoustic Laboratories' revised formula with profound correction factor (NAL-RP). To investigate the effect of a gradual change in gain/frequency response on experienced hearing-aid wearers with moderately severe to profound hearing loss. Double-blind, randomized controlled trial. Twenty-three experienced adult hearing-aid users with severe and profound hearing loss participated in the study. Participants were selected for inclusion in the study if the gain/frequency response of their own hearing aids differed significantly from their NAL-RP prescription. Participants were assigned either to a control or to an experimental group balanced for aided ear three-frequency pure-tone average (PTA) and age. Participants were fitted with Siemens Artis 2 SP behind-the-ear (BTE) hearing aids that were matched to the gain/frequency response of their own hearing aids for a 65 dB SPL input level. The experimental group progressed incrementally to their NAL-RP targets over the course of 15 wk, while the control group maintained their initial settings throughout the study. Aided speech discrimination testing, loudness scaling, and structured questionnaires were completed at 3, 6, 9, 12, and 15 wk postfitting. A paired comparison between the old and new gain/frequency responses was completed at 1 and 15 wk postfitting. Statistical analysis was conducted to examine differences between the experimental and control groups and changes

  16. Molecular genetic approach to human meningioma: loss of genes on chromosome 22

    International Nuclear Information System (INIS)

    Seizinger, B.R.; De La Monte, S.; Atkins, L.; Gusella, J.F.; Martuza, R.L.

    1987-01-01

    A molecular genetic approach employing polymorphic DNA markers has been used to investigate the role of chromosomal aberrations in meningioma, one of the most common tumors of the human nervous system. Comparison of the alleles detected by DNA markers in tumor DNA versus DNA from normal tissue revealed chromosomal alterations present in primary surgical specimens. In agreement with cytogenetic studies of cultured meningiomas, the most frequent alteration detected was loss of heterozygosity on chromosome 22. Forty of 51 patients were constitutionally heterozygous for at least one chromosome 22 DNA marker. Seventeen of the 40 constitutionally heterozygotic patients (43%) displayed hemizygosity for the corresponding marker in their meningioma tumor tissues. Loss of heterozygosity was also detected at a significantly lower frequency for markers on several other autosomes. In view of the striking association between acoustic neuroma and meningioma in bilateral acoustic neurofibromatosis and the discovery that acoustic neuromas display specific loss of genes on chromosome 22, the authors propose that a common mechanism involving chromosome 22 is operative in the development of both tumor types. Fine-structure mapping to reveal partial deletions in meningiomas may provide the means to clone and characterize a gene (or genes) of importance for tumorigenesis in this and possibly other clinically associated tumors of the human nervous system

  17. Loss of Sfpq Causes Long-Gene Transcriptopathy in the Brain

    Directory of Open Access Journals (Sweden)

    Akihide Takeuchi

    2018-05-01

    Full Text Available Summary: Genes specifically expressed in neurons contain members with extended long introns. Longer genes present a problem with respect to fulfilment of gene length transcription, and evidence suggests that dysregulation of long genes is a mechanism underlying neurodegenerative and psychiatric disorders. Here, we report the discovery that RNA-binding protein Sfpq is a critical factor for maintaining transcriptional elongation of long genes. We demonstrate that Sfpq co-transcriptionally binds to long introns and is required for sustaining long-gene transcription by RNA polymerase II through mediating the interaction of cyclin-dependent kinase 9 with the elongation complex. Phenotypically, Sfpq disruption caused neuronal apoptosis in developing mouse brains. Expression analysis of Sfpq-regulated genes revealed specific downregulation of developmentally essential neuronal genes longer than 100 kb in Sfpq-disrupted brains; those genes are enriched in associations with neurodegenerative and psychiatric diseases. The identified molecular machinery yields directions for targeted investigations of the association between long-gene transcriptopathy and neuronal diseases. : It has been a long-standing question how mammalian neuronal cells achieve full gene length transcription of extra-long genes. Takeuchi et al. show that RNA-binding protein Sfpq sustains long-gene transcription through Pol II-CTD activation. Loss of Sfpq caused long-gene transcriptopathy, which could be the cause of neurodegenerative and psychiatric disorders. Keywords: RNA-binding protein, transcriptional regulation, RNA polymerase II, cyclin-dependent kinase 9, RBP/transcript-dependent elongation, long-gene transcriptotherapy, neuronal development, neurological and psychiatric diseases, long-gene diseases, long genopathies

  18. Physical training prevents body weight gain but does not modify adipose tissue gene expression

    Science.gov (United States)

    Higa, T.S.; Bergamo, F.C.; Mazzucatto, F.; Fonseca-Alaniz, M.H.; Evangelista, F.S.

    2012-01-01

    The relationship of body weight (BW) with white adipose tissue (WAT) mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT). Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18), 5 days/week for 4 weeks or maintained sedentary (S, N = 15). Citrate synthase activity increased significantly in the T group (P weight gain compared to T mice (4.06 ± 0.43 vs 0.38 ± 0.28 g, P weights of gastrocnemius and soleus muscles, lung, kidney, and adrenal gland were not different. Liver and heart were larger and the spleen was smaller in T compared to S mice (P < 0.05). Food intake was higher in T than S mice (4.7 ± 0.2 vs 4.0 ± 0.3 g/animal, P < 0.05) but oxygen consumption at rest did not differ between groups. T animals showed higher serum leptin concentration compared to S animals (6.37 ± 0.5 vs 3.11 ± 0.12 ng/mL). WAT gene expression pattern obtained by transcription factor adipocyte determination and differentiation-dependent factor 1, fatty acid synthase, malic enzyme, hormone-sensitive lipase, adipocyte lipid binding protein, leptin, and adiponectin did not differ significantly between groups. Collectively, our results showed that PT prevents BW gain and maintains WAT mass due to an increase in food intake and unchanged resting metabolic rate. These responses are closely related to unchanged WAT gene expression patterns. PMID:22666778

  19. Adipose gene expression prior to weight loss can differentiate and weakly predict dietary responders.

    Directory of Open Access Journals (Sweden)

    David M Mutch

    Full Text Available BACKGROUND: The ability to identify obese individuals who will successfully lose weight in response to dietary intervention will revolutionize disease management. Therefore, we asked whether it is possible to identify subjects who will lose weight during dietary intervention using only a single gene expression snapshot. METHODOLOGY/PRINCIPAL FINDINGS: The present study involved 54 female subjects from the Nutrient-Gene Interactions in Human Obesity-Implications for Dietary Guidelines (NUGENOB trial to determine whether subcutaneous adipose tissue gene expression could be used to predict weight loss prior to the 10-week consumption of a low-fat hypocaloric diet. Using several statistical tests revealed that the gene expression profiles of responders (8-12 kgs weight loss could always be differentiated from non-responders (<4 kgs weight loss. We also assessed whether this differentiation was sufficient for prediction. Using a bottom-up (i.e. black-box approach, standard class prediction algorithms were able to predict dietary responders with up to 61.1%+/-8.1% accuracy. Using a top-down approach (i.e. using differentially expressed genes to build a classifier improved prediction accuracy to 80.9%+/-2.2%. CONCLUSION: Adipose gene expression profiling prior to the consumption of a low-fat diet is able to differentiate responders from non-responders as well as serve as a weak predictor of subjects destined to lose weight. While the degree of prediction accuracy currently achieved with a gene expression snapshot is perhaps insufficient for clinical use, this work reveals that the comprehensive molecular signature of adipose tissue paves the way for the future of personalized nutrition.

  20. Textural gain and subsequent loss in irradiated apples, carrots and potatoes with increase in dose from 0.03 to 1.0 kGy

    International Nuclear Information System (INIS)

    Cathalin, J.; McNulty, P.

    1996-01-01

    Cored samples (16mm X 15mm diameter) of apples, carrots and potatoes were irradiated in an Isomedix Gammacell 1000 irradiator at a dose rate of approximately 9Gy/min. Texture was measured using unrestrained uniaxial compression to microrupture on the JJ Universal Testing Machine. The loading rate was 6mm/min. Texture or firmness was assessed as the force to microrupture; the force required for various microrupture sample deformations (25%, 50% and 75%); the apparent Young's Modulus (ratio of the average stress to the average strain to microrupture); and the microrupture energy (area under the force-deformation curve). As the dose increased from 0.03 up to about 0.1 kGy, a gain in texture generally occurred in all products ranging from 3% to 16%. A transition area from gain to loss occurred within the 0.1 to 0.3 kGy range. Loss of texture occurred in all products as the dose increased from 0.3 to 1.0kGy, the loss ranging from 4% to 30%. The greatest loss of texture occurred in apples and the least loss in carrots. There textural trends may have commercial significance in low dose irradiation processes such as sprout inhibition, senescence delay and disinfestation

  1. How to make loss aversion disappear and reverse: tests of the decision by sampling origin of loss aversion.

    Science.gov (United States)

    Walasek, Lukasz; Stewart, Neil

    2015-02-01

    One of the most robust empirical findings in the behavioral sciences is loss aversion--the finding that losses loom larger than gains. We offer a new psychological explanation of the origins of loss aversion in which loss aversion emerges from differences in the distribution of gains and losses people experience. In 4 experiments, we tested this proposition by manipulating the range of gains and losses that individuals saw during the process of eliciting their loss aversion. We were able to find loss aversion, loss neutrality, and even the reverse of loss aversion.

  2. Updated clusters of orthologous genes for Archaea: a complex ancestor of the Archaea and the byways of horizontal gene transfer

    Directory of Open Access Journals (Sweden)

    Wolf Yuri I

    2012-12-01

    Full Text Available Abstract Background Collections of Clusters of Orthologous Genes (COGs provide indispensable tools for comparative genomic analysis, evolutionary reconstruction and functional annotation of new genomes. Initially, COGs were made for all complete genomes of cellular life forms that were available at the time. However, with the accumulation of thousands of complete genomes, construction of a comprehensive COG set has become extremely computationally demanding and prone to error propagation, necessitating the switch to taxon-specific COG collections. Previously, we reported the collection of COGs for 41 genomes of Archaea (arCOGs. Here we present a major update of the arCOGs and describe evolutionary reconstructions to reveal general trends in the evolution of Archaea. Results The updated version of the arCOG database incorporates 91% of the pangenome of 120 archaea (251,032 protein-coding genes altogether into 10,335 arCOGs. Using this new set of arCOGs, we performed maximum likelihood reconstruction of the genome content of archaeal ancestral forms and gene gain and loss events in archaeal evolution. This reconstruction shows that the last Common Ancestor of the extant Archaea was an organism of greater complexity than most of the extant archaea, probably with over 2,500 protein-coding genes. The subsequent evolution of almost all archaeal lineages was apparently dominated by gene loss resulting in genome streamlining. Overall, in the evolution of Archaea as well as a representative set of bacteria that was similarly analyzed for comparison, gene losses are estimated to outnumber gene gains at least 4 to 1. Analysis of specific patterns of gene gain in Archaea shows that, although some groups, in particular Halobacteria, acquire substantially more genes than others, on the whole, gene exchange between major groups of Archaea appears to be largely random, with no major ‘highways’ of horizontal gene transfer. Conclusions The updated collection

  3. High gene flow in epiphytic ferns despite habitat loss and fragmentation.

    Science.gov (United States)

    Winkler, Manuela; Koch, Marcus; Hietz, Peter

    2011-01-01

    Tropical montane forests suffer from increasing fragmentation and replacement by other types of land-use such as coffee plantations. These processes are known to affect gene flow and genetic structure of plant populations. Epiphytes are particularly vulnerable because they depend on their supporting trees for their entire life-cycle. We compared population genetic structure and genetic diversity derived from AFLP markers of two epiphytic fern species differing in their ability to colonize secondary habitats. One species, Pleopeltis crassinervata , is a successful colonizer of shade trees and isolated trees whereas the other species, Polypodium rhodopleuron , is restricted to forests with anthropogenic separation leading to significant isolation between populations. By far most genetic variation was distributed within rather than among populations in both species, and a genetic admixture analysis did not reveal any clustering. Gene flow exceeded by far the benchmark of one migrant per generation to prevent genetic divergence between populations in both species. Though populations are threatened by habitat loss, long-distance dispersal is likely to support gene flow even between distant populations, which efficiently delays genetic isolation. Consequently, populations may rather be threatened by ecological consequences of habitat loss and fragmentation.

  4. Duplications and losses in gene families of rust pathogens highlight putative effectors.

    Science.gov (United States)

    Pendleton, Amanda L; Smith, Katherine E; Feau, Nicolas; Martin, Francis M; Grigoriev, Igor V; Hamelin, Richard; Nelson, C Dana; Burleigh, J Gordon; Davis, John M

    2014-01-01

    Rust fungi are a group of fungal pathogens that cause some of the world's most destructive diseases of trees and crops. A shared characteristic among rust fungi is obligate biotrophy, the inability to complete a lifecycle without a host. This dependence on a host species likely affects patterns of gene expansion, contraction, and innovation within rust pathogen genomes. The establishment of disease by biotrophic pathogens is reliant upon effector proteins that are encoded in the fungal genome and secreted from the pathogen into the host's cell apoplast or within the cells. This study uses a comparative genomic approach to elucidate putative effectors and determine their evolutionary histories. We used OrthoMCL to identify nearly 20,000 gene families in proteomes of 16 diverse fungal species, which include 15 basidiomycetes and one ascomycete. We inferred patterns of duplication and loss for each gene family and identified families with distinctive patterns of expansion/contraction associated with the evolution of rust fungal genomes. To recognize potential contributors for the unique features of rust pathogens, we identified families harboring secreted proteins that: (i) arose or expanded in rust pathogens relative to other fungi, or (ii) contracted or were lost in rust fungal genomes. While the origin of rust fungi appears to be associated with considerable gene loss, there are many gene duplications associated with each sampled rust fungal genome. We also highlight two putative effector gene families that have expanded in Cqf that we hypothesize have roles in pathogenicity.

  5. Array-based gene expression, CGH and tissue data defines a 12q24 gain in neuroblastic tumors with prognostic implication

    Directory of Open Access Journals (Sweden)

    Kilpinen Sami

    2010-05-01

    Full Text Available Abstract Background Neuroblastoma has successfully served as a model system for the identification of neuroectoderm-derived oncogenes. However, in spite of various efforts, only a few clinically useful prognostic markers have been found. Here, we present a framework, which integrates DNA, RNA and tissue data to identify and prioritize genetic events that represent clinically relevant new therapeutic targets and prognostic biomarkers for neuroblastoma. Methods A single-gene resolution aCGH profiling was integrated with microarray-based gene expression profiling data to distinguish genetic copy number alterations that were strongly associated with transcriptional changes in two neuroblastoma cell lines. FISH analysis using a hotspot tumor tissue microarray of 37 paraffin-embedded neuroblastoma samples and in silico data mining for gene expression information obtained from previously published studies including up to 445 healthy nervous system samples and 123 neuroblastoma samples were used to evaluate the clinical significance and transcriptional consequences of the detected alterations and to identify subsequently activated gene(s. Results In addition to the anticipated high-level amplification and subsequent overexpression of MYCN, MEIS1, CDK4 and MDM2 oncogenes, the aCGH analysis revealed numerous other genetic alterations, including microamplifications at 2p and 12q24.11. Most interestingly, we identified and investigated the clinical relevance of a previously poorly characterized amplicon at 12q24.31. FISH analysis showed low-level gain of 12q24.31 in 14 of 33 (42% neuroblastomas. Patients with the low-level gain had an intermediate prognosis in comparison to patients with MYCN amplification (poor prognosis and to those with no MYCN amplification or 12q24.31 gain (good prognosis (P = 0.001. Using the in silico data mining approach, we identified elevated expression of five genes located at the 12q24.31 amplicon in neuroblastoma (DIABLO, ZCCHC

  6. Disentangling the effects of selection and loss bias on gene dynamics

    NARCIS (Netherlands)

    Iranzo, J.; Cuesta, J.A.; Manrubia, S.; Katsnelson, M.I.; Koonin, E.V.

    2017-01-01

    We combine mathematical modeling of genome evolution with comparative analysis of prokaryotic genomes to estimate the relative contributions of selection and intrinsic loss bias to the evolution of different functional classes of genes and mobile genetic elements (MGE). An exact solution for the

  7. Genome-wide loss of heterozygosity and copy number alteration in esophageal squamous cell carcinoma using the Affymetrix GeneChip Mapping 10 K array

    Directory of Open Access Journals (Sweden)

    Goldstein Alisa M

    2006-11-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is a common malignancy worldwide. Comprehensive genomic characterization of ESCC will further our understanding of the carcinogenesis process in this disease. Results Genome-wide detection of chromosomal changes was performed using the Affymetrix GeneChip 10 K single nucleotide polymorphism (SNP array, including loss of heterozygosity (LOH and copy number alterations (CNA, for 26 pairs of matched germ-line and micro-dissected tumor DNA samples. LOH regions were identified by two methods – using Affymetrix's genotype call software and using Affymetrix's copy number alteration tool (CNAT software – and both approaches yielded similar results. Non-random LOH regions were found on 10 chromosomal arms (in decreasing order of frequency: 17p, 9p, 9q, 13q, 17q, 4q, 4p, 3p, 15q, and 5q, including 20 novel LOH regions (10 kb to 4.26 Mb. Fifteen CNA-loss regions (200 kb to 4.3 Mb and 36 CNA-gain regions (200 kb to 9.3 Mb were also identified. Conclusion These studies demonstrate that the Affymetrix 10 K SNP chip is a valid platform to integrate analyses of LOH and CNA. The comprehensive knowledge gained from this analysis will enable improved strategies to prevent, diagnose, and treat ESCC.

  8. Clinical attachment level gain and three-year maintenance of a maxillary incisor with 100% bone loss: A case report.

    Science.gov (United States)

    Tirone, Federico; Salzano, Stefano

    2016-01-01

    This case report discusses a patient suffering from chronic periodontal disease and diagnosed with a hopeless central incisor. The intention was to show the possibility of gaining new clinical attachment via regenerative surgery in a tooth with 100% bone loss around the root. Treatment of hopeless and questionable teeth in periodontal patients has become an ideological matter. On the one hand, dental implants have proved to be a reliable solution to replace lost teeth; on the other hand, newly emerging evidence suggests that successful periodontal treatment of teeth diagnosed as hopeless is possible. Here we describe surgical, orthodontic, and restorative treatments that led to clinical attachment gain and achieved clinical success over a three-year follow-up period.

  9. How to Make Loss Aversion Disappear and Reverse: Tests of the Decision by Sampling Origin of Loss Aversion

    OpenAIRE

    Walasek, Lukasz; Stewart, Neil

    2014-01-01

    One of the most robust empirical findings in the behavioral sciences is loss aversion—the finding that losses loom larger than gains. We offer a new psychological explanation of the origins of loss aversion in which loss aversion emerges from differences in the distribution of gains and losses people experience. In 4 experiments, we tested this proposition by manipulating the range of gains and losses that individuals saw during the process of eliciting their loss aversion. We were able to fi...

  10. Physical training prevents body weight gain but does not modify adipose tissue gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Higa, T.S. [Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, SP (Brazil); Bergamo, F.C. [Escola de Educação Física e Esporte, Universidade de São Paulo, São Paulo, SP (Brazil); Mazzucatto, F. [Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, SP (Brazil); Fonseca-Alaniz, M.H. [Instituto do Coração, Departamento de Medicina-LIM13, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Evangelista, F.S. [Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, SP (Brazil); Escola de Educação Física e Esporte, Universidade de São Paulo, São Paulo, SP (Brazil); Instituto do Coração, Departamento de Medicina-LIM13, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2012-06-08

    The relationship of body weight (BW) with white adipose tissue (WAT) mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT). Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18), 5 days/week for 4 weeks or maintained sedentary (S, N = 15). Citrate synthase activity increased significantly in the T group (P < 0.05). S mice had a substantial weight gain compared to T mice (4.06 ± 0.43 vs 0.38 ± 0.28 g, P < 0.01). WAT mass, adipocyte size, and the weights of gastrocnemius and soleus muscles, lung, kidney, and adrenal gland were not different. Liver and heart were larger and the spleen was smaller in T compared to S mice (P < 0.05). Food intake was higher in T than S mice (4.7 ± 0.2 vs 4.0 ± 0.3 g/animal, P < 0.05) but oxygen consumption at rest did not differ between groups. T animals showed higher serum leptin concentration compared to S animals (6.37 ± 0.5 vs 3.11 ± 0.12 ng/mL). WAT gene expression pattern obtained by transcription factor adipocyte determination and differentiation-dependent factor 1, fatty acid synthase, malic enzyme, hormone-sensitive lipase, adipocyte lipid binding protein, leptin, and adiponectin did not differ significantly between groups. Collectively, our results showed that PT prevents BW gain and maintains WAT mass due to an increase in food intake and unchanged resting metabolic rate. These responses are closely related to unchanged WAT gene expression patterns.

  11. Physical training prevents body weight gain but does not modify adipose tissue gene expression

    International Nuclear Information System (INIS)

    Higa, T.S.; Bergamo, F.C.; Mazzucatto, F.; Fonseca-Alaniz, M.H.; Evangelista, F.S.

    2012-01-01

    The relationship of body weight (BW) with white adipose tissue (WAT) mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT). Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18), 5 days/week for 4 weeks or maintained sedentary (S, N = 15). Citrate synthase activity increased significantly in the T group (P < 0.05). S mice had a substantial weight gain compared to T mice (4.06 ± 0.43 vs 0.38 ± 0.28 g, P < 0.01). WAT mass, adipocyte size, and the weights of gastrocnemius and soleus muscles, lung, kidney, and adrenal gland were not different. Liver and heart were larger and the spleen was smaller in T compared to S mice (P < 0.05). Food intake was higher in T than S mice (4.7 ± 0.2 vs 4.0 ± 0.3 g/animal, P < 0.05) but oxygen consumption at rest did not differ between groups. T animals showed higher serum leptin concentration compared to S animals (6.37 ± 0.5 vs 3.11 ± 0.12 ng/mL). WAT gene expression pattern obtained by transcription factor adipocyte determination and differentiation-dependent factor 1, fatty acid synthase, malic enzyme, hormone-sensitive lipase, adipocyte lipid binding protein, leptin, and adiponectin did not differ significantly between groups. Collectively, our results showed that PT prevents BW gain and maintains WAT mass due to an increase in food intake and unchanged resting metabolic rate. These responses are closely related to unchanged WAT gene expression patterns

  12. Physical training prevents body weight gain but does not modify adipose tissue gene expression

    Directory of Open Access Journals (Sweden)

    T.S. Higa

    2012-10-01

    Full Text Available The relationship of body weight (BW with white adipose tissue (WAT mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT. Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18, 5 days/week for 4 weeks or maintained sedentary (S, N = 15. Citrate synthase activity increased significantly in the T group (P < 0.05. S mice had a substantial weight gain compared to T mice (4.06 ± 0.43 vs 0.38 ± 0.28 g, P < 0.01. WAT mass, adipocyte size, and the weights of gastrocnemius and soleus muscles, lung, kidney, and adrenal gland were not different. Liver and heart were larger and the spleen was smaller in T compared to S mice (P < 0.05. Food intake was higher in T than S mice (4.7 ± 0.2 vs 4.0 ± 0.3 g/animal, P < 0.05 but oxygen consumption at rest did not differ between groups. T animals showed higher serum leptin concentration compared to S animals (6.37 ± 0.5 vs 3.11 ± 0.12 ng/mL. WAT gene expression pattern obtained by transcription factor adipocyte determination and differentiation-dependent factor 1, fatty acid synthase, malic enzyme, hormone-sensitive lipase, adipocyte lipid binding protein, leptin, and adiponectin did not differ significantly between groups. Collectively, our results showed that PT prevents BW gain and maintains WAT mass due to an increase in food intake and unchanged resting metabolic rate. These responses are closely related to unchanged WAT gene expression patterns.

  13. Gains and losses of exclusivity in grocery retailing

    NARCIS (Netherlands)

    Gielens, K.J.P.; Gijsbrechts, E.; Dekimpe, M.G.

    Conventional wisdom dictates that convenience goods should be distributed as intensively as possible. Still, exclusivity arrangements are rapidly gaining way in grocery retailing. We discuss the possible performance outcomes of exclusivity deals, and propose a unified framework (i) to quantify the

  14. Remarkable interkingdom conservation of intron positions and massive, lineage-specific intron loss and gain in eukaryotic evolution.

    Science.gov (United States)

    Rogozin, Igor B; Wolf, Yuri I; Sorokin, Alexander V; Mirkin, Boris G; Koonin, Eugene V

    2003-09-02

    Sequencing of eukaryotic genomes allows one to address major evolutionary problems, such as the evolution of gene structure. We compared the intron positions in 684 orthologous gene sets from 8 complete genomes of animals, plants, fungi, and protists and constructed parsimonious scenarios of evolution of the exon-intron structure for the respective genes. Approximately one-third of the introns in the malaria parasite Plasmodium falciparum are shared with at least one crown group eukaryote; this number indicates that these introns have been conserved through >1.5 billion years of evolution that separate Plasmodium from the crown group. Paradoxically, humans share many more introns with the plant Arabidopsis thaliana than with the fly or nematode. The inferred evolutionary scenario holds that the common ancestor of Plasmodium and the crown group and, especially, the common ancestor of animals, plants, and fungi had numerous introns. Most of these ancestral introns, which are retained in the genomes of vertebrates and plants, have been lost in fungi, nematodes, arthropods, and probably Plasmodium. In addition, numerous introns have been inserted into vertebrate and plant genes, whereas, in other lineages, intron gain was much less prominent.

  15. Loss aversion and hypoxia: less loss aversion in oxygen-depleted environment.

    Science.gov (United States)

    Pighin, Stefania; Bonini, Nicolao; Savadori, Lucia; Hadjichristidis, Constantinos; Schena, Federico

    2014-03-01

    Hypoxia, the deprivation of adequate oxygen supply, constitutes a direct threat to survival by disrupting cardiovascular or respiratory homeostasis and eliciting a respiratory distress. Although hypoxia has been shown to increase brain vulnerability and impair basic cognitive functions, only one study has examined its effect on decision-making. The present study examined the effect of mild hypoxia on individual's loss aversion, that is, the tendency to be more affected by losses than equal sized gains. A sample of 26 participants were asked to either accept or reject a series of mixed gambles once in an oxygen-depleted environment (14.1% oxygen concentration) and once in a normoxic environment (20.9% oxygen concentration). Each gamble involved a 50-50 chance of winning or losing specified amounts of money. Mild hypoxia decreased loss aversion: on average in the normoxic condition participants accepted gambles if the gain was at least 2.4 times as large as the loss, whereas in the oxygen-depleted condition participants accepted gambles if the gain was at least 1.7 times as large as the loss. Mild hypoxia may push individuals to be less cautious in daily decisions that involve a trade-off between a gain and a loss.

  16. Duplications and losses in gene families of rust pathogens highlight putative effectors

    Directory of Open Access Journals (Sweden)

    Amanda L. Pendleton

    2014-06-01

    Full Text Available Rust fungi are a group of fungal pathogens that cause some of the world’s most destructive diseases of trees and crops. A shared characteristic among rust fungi is obligate biotrophy, the inability to complete a lifecycle without a host. This dependence on a host species likely affects patterns of gene expansion, contraction, and innovation within rust pathogen genomes. The establishment of disease by biotrophic pathogens is reliant upon effector proteins that are encoded in the fungal genome and secreted from the pathogen into the host’s cell apoplast or within the cells. This study uses a comparative genomic approach to elucidate putative effectors and determine their evolutionary histories. We used OrthoMCL to identify nearly 20,000 gene families in proteomes of sixteen diverse fungal species, which include fifteen basidiomycetes and one ascomycete. We inferred patterns of duplication and loss for each gene family and identified families with distinctive patterns of expansion/contraction associated with the evolution of rust fungal genomes. To recognize potential contributors for the unique features of rust pathogens, we identified families harboring secreted proteins that: i arose or expanded in rust pathogens relative to other fungi, or ii contracted or were lost in rust fungal genomes. While the origin of rust fungi appears to be associated with considerable gene loss, there are many gene duplications associated with each sampled rust fungal genome. We also highlight two putative effector gene families that have expanded in Cqf that we hypothesize have roles in pathogenicity.

  17. Association Between Human Hair Loss and the Expression Levels of Nucleolin, Nucleophosmin, and UBTF Genes.

    Science.gov (United States)

    Tasdemir, Sener; Eroz, Recep; Dogan, Hasan; Erdem, Haktan Bagis; Sahin, Ibrahim; Kara, Murat; Engin, Ragip Ismail; Turkez, Hasan

    2016-04-01

    Nucleolar organizer regions, also known as argyrophilic nucleolar organizer regions, are associated with ribosomal genes. The main function of the nucleolus is the rapid production of ribosomal subunits, a process that must be highly regulated to provide the appropriate levels for cellular proliferation and cell growth. There are no studies in the literature addressing the expression and function of nucleolar component proteins, including nucleophosmin, nucleolin and the upstream binding transcription factor (UBTF), in human follicular hair cells. Nineteen healthy males who had normal and sufficient hair follicles on the back of the head, but exhibited hair loss on the frontal/vertex portions of the head and 14 healthy males without hair loss were included in the current study. Gene expression levels were measured by relative quantitative real time polymerase chain reaction. In the individuals suffering from alopecia, the total expression levels of nucleolin, nucleophosmin, and UBTF were lower in normal sites than in hair loss sites. Strong expression level correlations were detected between: nucleophosmin and nucleolin; nucleophosmin and UBTF, and nucleolin and UBTF for both groups. There was an association between human hair loss and the expression levels of nucleolin, nucleophosmin, and UBTF genes.

  18. Exercise decreases lipogenic gene expression in adipose tissue and alters adipocyte cellularity during weight regain after weight loss.

    Directory of Open Access Journals (Sweden)

    Erin Danielle Giles

    2016-02-01

    Full Text Available Exercise is a potent strategy to facilitate long-term weight maintenance. In addition to increasing energy expenditure and reducing appetite, exercise also favors the oxidation of dietary fat, which likely helps prevent weight re-gain. It is unclear whether this exercise-induced metabolic shift is due to changes in energy balance, or whether exercise imparts additional adaptations in the periphery that limit the storage and favor the oxidation of dietary fat. To answer this question, adipose tissue lipid metabolism and related gene expression were studied in obese rats following weight loss and during the first day of relapse to obesity. Mature, obese rats were weight-reduced for 2 weeks with or without daily treadmill exercise (EX. Rats were weight maintained for 6 weeks, followed by relapse on: a ad libitum low fat diet (LFD, b ad libitum LFD plus EX, or c a provision of LFD to match the positive energy imbalance of exercised, relapsing animals. 24h retention of dietary- and de novo-derived fat were assessed directly using 14C palmitate/oleate and 3H20, respectively. Exercise decreased the size, but increased the number of adipocytes in both retroperitoneal (RP and subcutaneous (SC adipose depots, and prevented the relapse-induced increase in adipocyte size. Further, exercise decreased the expression of genes involved in lipid uptake (CD36 & LPL, de novo lipogenesis (FAS, ACC1, and triacylglycerol synthesis (MGAT & DGAT in RP adipose during relapse following weight loss. This was consistent with the metabolic data, whereby exercise reduced retention of de novo-derived fat even when controlling for the positive energy imbalance. The decreased trafficking of dietary fat to adipose tissue with exercise was explained by reduced energy intake which attenuated energy imbalance during refeeding. Despite having decreased expression of lipogenic genes, the net retention of de novo-derived lipid was higher in both the RP and SC adipose of exercising

  19. Phenylpropanolamine appears not to promote weight loss in patients with schizophrenia who have gained weight during clozapine treatment.

    Science.gov (United States)

    Borovicka, Mary C; Fuller, Matthew A; Konicki, P Eric; White, John C; Steele, Vickie M; Jaskiw, George E

    2002-04-01

    Weight gain is a common side effect of clozapine treatment and may expose patients to obesity-associated health risks. We proposed that concomitant treatment with an appetite suppressant such as phenylpropanolamine (PPA) would lead to a decrease in appetite and therefore loss of weight. This was a 12-week, double-blind, randomized, placebo-controlled trial of PPA, 75 mg/day, in outpatients with treatment-refractory schizophrenia (DSM-IV) who were stable on clozapine treatment for at least 4 months and had gained > 10% of their baseline body weight since starting clozapine. Patients were evaluated for adverse effects and weighed weekly. A Positive and Negative Syndrome Scale (PANSS) assessment, a short dietary quiz, and blood indices were completed monthly. Sixteen patients were equally randomly assigned to receive PPA or placebo. The groups did not differ in mean age, baseline weight, dose of clozapine, baseline PANSS scores, or the percent of weight gained since the start of clozapine. There was no significant effect of treatment on weight (t = 0.219, df = 10, p = .831). There was no significant change in either the total PANSS scores (t = -0.755, df = 10, p = .468), the positive or negative symptom cluster scores, or any of the remaining variables. Phenylpropanolamine 75 mg/day was well tolerated but was not effective in reversing established weight gain associated with clozapine treatment in stable outpatients with schizophrenia.

  20. 24 CFR 3280.507 - Comfort heat gain.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Comfort heat gain. 3280.507 Section... gain. Information necessary to calculate the home cooling load shall be provided as specified in this part. (a) Transmission heat gains. Homes complying with this section shall meet the minimum heat loss...

  1. Loss of 5-hydroxymethylcytosine is linked to gene body hypermethylation in kidney cancer.

    Science.gov (United States)

    Chen, Ke; Zhang, Jing; Guo, Zhongqiang; Ma, Qin; Xu, Zhengzheng; Zhou, Yuanyuan; Xu, Ziying; Li, Zhongwu; Liu, Yiqiang; Ye, Xiongjun; Li, Xuesong; Yuan, Bifeng; Ke, Yuwen; He, Chuan; Zhou, Liqun; Liu, Jiang; Ci, Weimin

    2016-01-01

    Both 5-methylcytosine (5mC) and its oxidized form 5-hydroxymethylcytosine (5hmC) have been proposed to be involved in tumorigenesis. Because the readout of the broadly used 5mC mapping method, bisulfite sequencing (BS-seq), is the sum of 5mC and 5hmC levels, the 5mC/5hmC patterns and relationship of these two modifications remain poorly understood. By profiling real 5mC (BS-seq corrected by Tet-assisted BS-seq, TAB-seq) and 5hmC (TAB-seq) levels simultaneously at single-nucleotide resolution, we here demonstrate that there is no global loss of 5mC in kidney tumors compared with matched normal tissues. Conversely, 5hmC was globally lost in virtually all kidney tumor tissues. The 5hmC level in tumor tissues is an independent prognostic marker for kidney cancer, with lower levels of 5hmC associated with shorter overall survival. Furthermore, we demonstrated that loss of 5hmC is linked to hypermethylation in tumors compared with matched normal tissues, particularly in gene body regions. Strikingly, gene body hypermethylation was significantly associated with silencing of the tumor-related genes. Downregulation of IDH1 was identified as a mechanism underlying 5hmC loss in kidney cancer. Restoring 5hmC levels attenuated the invasion capacity of tumor cells and suppressed tumor growth in a xenograft model. Collectively, our results demonstrate that loss of 5hmC is both a prognostic marker and an oncogenic event in kidney cancer by remodeling the DNA methylation pattern.

  2. Loss aversion is an affective forecasting error.

    Science.gov (United States)

    Kermer, Deborah A; Driver-Linn, Erin; Wilson, Timothy D; Gilbert, Daniel T

    2006-08-01

    Loss aversion occurs because people expect losses to have greater hedonic impact than gains of equal magnitude. In two studies, people predicted that losses in a gambling task would have greater hedonic impact than would gains of equal magnitude, but when people actually gambled, losses did not have as much of an emotional impact as they predicted. People overestimated the hedonic impact of losses because they underestimated their tendency to rationalize losses and overestimated their tendency to dwell on losses. The asymmetrical impact of losses and gains was thus more a property of affective forecasts than a property of affective experience.

  3. Public and health professionals’ misconceptions about the dynamics of body weight gain/loss

    Science.gov (United States)

    Abdel-Hamid, Tarek; Ankel, Felix; Battle-Fisher, Michele; Gibson, Bryan; Gonzalez-Parra, Gilberto; Jalali, Mohammad; Kaipainen, Kirsikka; Kalupahana, Nishan; Karanfil, Ozge; Marathe, Achla; Martinson, Brian; McKelvey, Karma; Sarbadhikari, Suptendra Nath; Pintauro, Stephen; Poucheret, Patrick; Pronk, Nicolaas; Qian, Ying; Sazonov, Edward; Van Oorschot, Kim; Venkitasubramanian, Akshay; Murphy, Philip

    2014-01-01

    Human body energy storage operates as a stock-and-flow system with inflow (food intake) and outflow (energy expenditure). In spite of the ubiquity of stock-and-flow structures, evidence suggests that human beings fail to understand stock accumulation and rates of change, a difficulty called the stock–flow failure. This study examines the influence of health care training and cultural background in overcoming stock–flow failure. A standardized protocol assessed lay people’s and health care professionals’ ability to apply stock-and-flow reasoning to infer the dynamics of weight gain/loss during the holiday season (621 subjects from seven countries). Our results indicate that both types of subjects exhibited systematic errors indicative of use of erroneous heuristics. Stock–flow failure was found across cultures and was not improved by professional health training. The problem of stock–flow failure as a transcultural global issue with education and policy implications is discussed. PMID:25620843

  4. Effects of loss aversion on neural responses to loss outcomes: An event-related potential study.

    Science.gov (United States)

    Kokmotou, Katerina; Cook, Stephanie; Xie, Yuxin; Wright, Hazel; Soto, Vicente; Fallon, Nicholas; Giesbrecht, Timo; Pantelous, Athanasios; Stancak, Andrej

    2017-05-01

    Loss aversion is the tendency to prefer avoiding losses over acquiring gains of the same amount. To shed light on the spatio-temporal processes underlying loss aversion, we analysed the associations between individual loss aversion and electrophysiological responses to loss and gain outcomes in a monetary gamble task. Electroencephalographic feedback-related negativity (FRN) was computed in 29 healthy participants as the difference in electrical potentials between losses and gains. Loss aversion was evaluated using non-linear parametric fitting of choices in a separate gamble task. Loss aversion correlated positively with FRN amplitude (233-263ms) at electrodes covering the lower face. Feedback related potentials were modelled by five equivalent source dipoles. From these dipoles, stronger activity in a source located in the orbitofrontal cortex was associated with loss aversion. The results suggest that loss aversion implemented during risky decision making is related to a valuation process in the orbitofrontal cortex, which manifests during learning choice outcomes. Copyright © 2017. Published by Elsevier B.V.

  5. Adipose Gene Expression Prior to Weight Loss Can Differentiate and Weakly Predict Dietary Responders

    Science.gov (United States)

    Mutch, David M.; Temanni, M. Ramzi; Henegar, Corneliu; Combes, Florence; Pelloux, Véronique; Holst, Claus; Sørensen, Thorkild I. A.; Astrup, Arne; Martinez, J. Alfredo; Saris, Wim H. M.; Viguerie, Nathalie; Langin, Dominique; Zucker, Jean-Daniel; Clément, Karine

    2007-01-01

    Background The ability to identify obese individuals who will successfully lose weight in response to dietary intervention will revolutionize disease management. Therefore, we asked whether it is possible to identify subjects who will lose weight during dietary intervention using only a single gene expression snapshot. Methodology/Principal Findings The present study involved 54 female subjects from the Nutrient-Gene Interactions in Human Obesity-Implications for Dietary Guidelines (NUGENOB) trial to determine whether subcutaneous adipose tissue gene expression could be used to predict weight loss prior to the 10-week consumption of a low-fat hypocaloric diet. Using several statistical tests revealed that the gene expression profiles of responders (8–12 kgs weight loss) could always be differentiated from non-responders (diet is able to differentiate responders from non-responders as well as serve as a weak predictor of subjects destined to lose weight. While the degree of prediction accuracy currently achieved with a gene expression snapshot is perhaps insufficient for clinical use, this work reveals that the comprehensive molecular signature of adipose tissue paves the way for the future of personalized nutrition. PMID:18094752

  6. Propagation properties of silver nanowires embedded in a substrate with gain

    DEFF Research Database (Denmark)

    Isidio de Lima, Joaquim Junior; Adam, Jost; Rego, Davi

    2016-01-01

    The transmittance, reflectance and absorption of silver nanowires metamaterial embedded into a semiconductor matrix with optical gain are numerically investigated. Metamaterials may suffer from appreciable dissipative losses which are inherent for all plasmonic structures. The losses can signific......The transmittance, reflectance and absorption of silver nanowires metamaterial embedded into a semiconductor matrix with optical gain are numerically investigated. Metamaterials may suffer from appreciable dissipative losses which are inherent for all plasmonic structures. The losses can...... significantly be reduced by introducing optical gain in the dielectric matrix by placing atomic or molecular impurities which are pumped by an external light source to create a population inversion. We numerically analyzed the optical properties when the semiconductor host material represents a gain medium. We...

  7. 26 CFR 1.1502-21 - Net operating losses.

    Science.gov (United States)

    2010-04-01

    ..., gain, deduction, and loss, including the member's losses and deductions actually absorbed by the group... income, gain, deduction, and loss. For this purpose— (A) Consolidated taxable income is computed without... the group has no Year 2 capital gain, it cannot absorb any capital losses in Year 2. T's Year 1 net...

  8. Phylogenetics and Gene Structure Dynamics of Polygalacturonase Genes in Aspergillus and Neurospora crassa

    Directory of Open Access Journals (Sweden)

    Jin-Sung Hong

    2013-09-01

    Full Text Available Polygalacturonase (PG gene is a typical gene family present in eukaryotes. Forty-nine PGs were mined from the genomes of Neurospora crassa and five Aspergillus species. The PGs were classified into 3 clades such as clade 1 for rhamno-PGs, clade 2 for exo-PGs and clade 3 for exo- and endo-PGs, which were further grouped into 13 sub-clades based on the polypeptide sequence similarity. In gene structure analysis, a total of 124 introns were present in 44 genes and five genes lacked introns to give an average of 2.5 introns per gene. Intron phase distribution was 64.5% for phase 0, 21.8% for phase 1, and 13.7% for phase 2, respectively. The introns varied in their sequences and their lengths ranged from 20 bp to 424 bp with an average of 65.9 bp, which is approximately half the size of introns in other fungal genes. There were 29 homologous intron blocks and 26 of those were sub-clade specific. Intron losses were counted in 18 introns in which no obvious phase preference for intron loss was observed. Eighteen introns were placed at novel positions, which is considerably higher than those of plant PGs. In an evolutionary sense both intron loss and gain must have taken place for shaping the current PGs in these fungi. Together with the small intron size, low conservation of homologous intron blocks and higher number of novel introns, PGs of fungal species seem to have recently undergone highly dynamic evolution.

  9. Molecular profiling reveals frequent gain of MYCN and anaplasia-specific loss of 4q and 14q in Wilms tumor.

    Science.gov (United States)

    Williams, Richard D; Al-Saadi, Reem; Natrajan, Rachael; Mackay, Alan; Chagtai, Tasnim; Little, Suzanne; Hing, Sandra N; Fenwick, Kerry; Ashworth, Alan; Grundy, Paul; Anderson, James R; Dome, Jeffrey S; Perlman, Elizabeth J; Jones, Chris; Pritchard-Jones, Kathy

    2011-12-01

    Anaplasia in Wilms tumor, a distinctive histology characterized by abnormal mitoses, is associated with poor patient outcome. While anaplastic tumors frequently harbour TP53 mutations, little is otherwise known about their molecular biology. We have used array comparative genomic hybridization (aCGH) and cDNA microarray expression profiling to compare anaplastic and favorable histology Wilms tumors to determine their common and differentiating features. In addition to changes on 17p, consistent with TP53 deletion, recurrent anaplasia-specific genomic loss and under-expression were noted in several other regions, most strikingly 4q and 14q. Further aberrations, including gain of 1q and loss of 16q were common to both histologies. Focal gain of MYCN, initially detected by high resolution aCGH profiling in 6/61 anaplastic samples, was confirmed in a significant proportion of both tumor types by a genomic quantitative PCR survey of over 400 tumors. Overall, these results are consistent with a model where anaplasia, rather than forming an entirely distinct molecular entity, arises from the general continuum of Wilms tumor by the acquisition of additional genomic changes at multiple loci. Copyright © 2011 Wiley Periodicals, Inc.

  10. Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo.

    Science.gov (United States)

    Kabashi, Edor; Lin, Li; Tradewell, Miranda L; Dion, Patrick A; Bercier, Valérie; Bourgouin, Patrick; Rochefort, Daniel; Bel Hadj, Samar; Durham, Heather D; Vande Velde, Christine; Rouleau, Guy A; Drapeau, Pierre

    2010-02-15

    TDP-43 has been found in inclusion bodies of multiple neurological disorders, including amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson's disease and Alzheimer's disease. Mutations in the TDP-43 encoding gene, TARDBP, have been subsequently reported in sporadic and familial ALS patients. In order to investigate the pathogenic nature of these mutants, the effects of three consistently reported TARDBP mutations (A315T, G348C and A382T) were tested in cell lines, primary cultured motor neurons and living zebrafish embryos. Each of the three mutants and wild-type (WT) human TDP-43 localized to nuclei when expressed in COS1 and Neuro2A cells by transient transfection. However, when expressed in motor neurons from dissociated spinal cord cultures these mutant TARDBP alleles, but less so for WT TARDBP, were neurotoxic, concomitant with perinuclear localization and aggregation of TDP-43. Finally, overexpression of mutant, but less so of WT, human TARDBP caused a motor phenotype in zebrafish (Danio rerio) embryos consisting of shorter motor neuronal axons, premature and excessive branching as well as swimming deficits. Interestingly, knock-down of zebrafisfh tardbp led to a similar phenotype, which was rescued by co-expressing WT but not mutant human TARDBP. Together these approaches showed that TARDBP mutations cause motor neuron defects and toxicity, suggesting that both a toxic gain of function as well as a novel loss of function may be involved in the molecular mechanism by which mutant TDP-43 contributes to disease pathogenesis.

  11. Basic modelling of transport in 2D wave-mechanical nanodots and billiards with balanced gain and loss mediated by complex potentials

    Science.gov (United States)

    Berggren, Karl-Fredrik; Tellander, Felix; Yakimenko, Irina

    2018-05-01

    Non-Hermitian quantum mechanics with parity-time (PT) symmetry is presently gaining great interest, especially within the fields of photonics and optics. Here, we give a brief overview of low-dimensional semiconductor nanodevices using the example of a quantum dot with input and output leads, which are mimicked by imaginary potentials for gain and loss, and how wave functions, particle flow, coalescence of levels and associated breaking of PT symmetry may be analysed within such a framework. Special attention is given to the presence of exceptional points and symmetry breaking. Related features for musical string instruments and ‘wolf-notes’ are outlined briefly with suggestions for further experiments.

  12. High-fat-diet-induced weight gain ameliorates bone loss without exacerbating AβPP processing and cognition in female APP/PS1 mice

    Directory of Open Access Journals (Sweden)

    Yunhua ePeng

    2014-08-01

    Full Text Available Osteoporosis is negatively correlated with body mass, whereas both osteoporosis and weight loss occur at higher incidence during the progression of Alzheimer’s disease (AD than the age-matched non-dementia individuals. Given that there is no evidence that overweight associated with AD-type cognitive dysfunction, we hypothesized that moderate weight gain might have a protective effect on the bone loss in AD without exacerbating cognitive dysfunction. In the present study, feeding a high-fat-diet (HFD, 45% calorie from fat to female APP/PS1 transgenic mice, an AD animal model, induced weight gain. The bone mineral density, microarchitecture, and biomechanical properties of the femurs were then evaluated. The results showed that the middle-aged female APP/PS1 transgenic mice were susceptible to osteoporosis of the femoral bones and that weight gain significantly enhanced bone mass and mechanical properties. Notably, HFD was not detrimental to brain insulin signaling and AβPP processing, as well as to exploration ability and working, learning and memory performance of the transgenic mice measured by T maze and water maze, compared with the mice fed a normal fat diet (10% calorie from fat. In addition, the circulating levels of leptin but not estradiol were remarkably elevated in HFD-treated mice. These results suggest that a body weight gain induced by the HFD feeding regimen significantly improved bone mass in female APP/PS1 mice with no detriments to exploration ability and spatial memory, most likely via the action of elevated circulating leptin.

  13. Characterization of hairless (Hr) and FGF5 genes provides insights into the molecular basis of hair loss in cetaceans.

    Science.gov (United States)

    Chen, Zhuo; Wang, Zhengfei; Xu, Shixia; Zhou, Kaiya; Yang, Guang

    2013-02-09

    Hair is one of the main distinguishing characteristics of mammals and it has many important biological functions. Cetaceans originated from terrestrial mammals and they have evolved a series of adaptations to aquatic environments, which are of evolutionary significance. However, the molecular mechanisms underlying their aquatic adaptations have not been well explored. This study provided insights into the evolution of hair loss during the transition from land to water by investigating and comparing two essential regulators of hair follicle development and hair follicle cycling, i.e., the Hairless (Hr) and FGF5 genes, in representative cetaceans and their terrestrial relatives. The full open reading frame sequences of the Hr and FGF5 genes were characterized in seven cetaceans. The sequence characteristics and evolutionary analyses suggested the functional loss of the Hr gene in cetaceans, which supports the loss of hair during their full adaptation to aquatic habitats. By contrast, positive selection for the FGF5 gene was found in cetaceans where a series of positively selected amino acid residues were identified. This is the first study to investigate the molecular basis of the hair loss in cetaceans. Our investigation of Hr and FGF5, two indispensable regulators of the hair cycle, provide some new insights into the molecular basis of hair loss in cetaceans. The results suggest that positive selection for the FGF5 gene might have promoted the termination of hair growth and early entry into the catagen stage of hair follicle cycling. Consequently, the hair follicle cycle was disrupted and the hair was lost completely due to the loss of the Hr gene function in cetaceans. This suggests that cetaceans have evolved an effective and complex mechanism for hair loss.

  14. Emotion regulation reduces loss aversion and decreases amygdala responses to losses.

    Science.gov (United States)

    Sokol-Hessner, Peter; Camerer, Colin F; Phelps, Elizabeth A

    2013-03-01

    Emotion regulation strategies can alter behavioral and physiological responses to emotional stimuli and the neural correlates of those responses in regions such as the amygdala or striatum. The current study investigates the brain systems engaged when using an emotion regulation technique during financial decisions. In decision making, regulating emotion with reappraisal-focused strategies that encourage taking a different perspective has been shown to reduce loss aversion as observed both in choices and in the relative arousal responses to actual loss and gain outcomes. In the current study, we find using fMRI that behavioral loss aversion correlates with amygdala activity in response to losses relative to gains. Success in regulating loss aversion also correlates with the reduction in amygdala responses to losses but not to gains. Furthermore, across both decisions and outcomes, we find the reappraisal strategy increases baseline activity in dorsolateral and ventromedial prefrontal cortex and the striatum. The similarity of the neural circuitry observed to that seen in emotion regulation, despite divergent tasks, serves as further evidence for a role of emotion in decision making, and for the power of reappraisal to change assessments of value and thereby choices.

  15. Revisiting the missing protein-coding gene catalog of the domestic dog

    Directory of Open Access Journals (Sweden)

    Galibert Francis

    2009-02-01

    Full Text Available Abstract Background Among mammals for which there is a high sequence coverage, the whole genome assembly of the dog is unique in that it predicts a low number of protein-coding genes, ~19,000, compared to the over 20,000 reported for other mammalian species. Of particular interest are the more than 400 of genes annotated in primates and rodent genomes, but missing in dog. Results Using over 14,000 orthologous genes between human, chimpanzee, mouse rat and dog, we built multiple pairwise synteny maps to infer short orthologous intervals that were targeted for characterizing the canine missing genes. Based on gene prediction and a functionality test using the ratio of replacement to silent nucleotide substitution rates (dN/dS, we provide compelling structural and functional evidence for the identification of 232 new protein-coding genes in the canine genome and 69 gene losses, characterized as undetected gene or pseudogenes. Gene loss phyletic pattern analysis using ten species from chicken to human allowed us to characterize 28 canine-specific gene losses that have functional orthologs continuously from chicken or marsupials through human, and 10 genes that arose specifically in the evolutionary lineage leading to rodent and primates. Conclusion This study demonstrates the central role of comparative genomics for refining gene catalogs and exploring the evolutionary history of gene repertoires, particularly as applied for the characterization of species-specific gene gains and losses.

  16. Lack of association of TNFalpha gene polymorphisms and recurrent pregnancy loss in Caucasian women.

    Science.gov (United States)

    Pietrowski, Detlef; Bettendorf, Herta; Keck, Christoph; Bürkle, Bernd; Unfried, Gertrud; Riener, Eva-Katrin; Hefler, Lukas A; Tempfer, Clemens

    2004-02-01

    The tumor necrosis factor alpha (TNFalpha) gene plays an important role in immunology and inflammation. Variant alleles of TNFalpha are associated with altered RNA and serum protein levels in humans. Conflicting results have been obtained regarding the role of TNFalpha during pregnancy and recurrent pregnancy loss (RPL). This study investigated the relationship between RPL and two polymorphisms in the promoter of the TNFalpha gene (TNFalpha -308 and -863). Genotyping was performed in 168 RPL women and 212 ethnically matched healthy individuals. In addition, we performed analysis of TNFalpha serum protein levels. We demonstrate that neither the polymorphism -308 nor the polymorphism -863 of the TNFalpha gene is associated with RPL in Caucasian women. In addition, we did not find any association between TNFalpha serum levels and the occurrence of RPL in a subset of 36 RPL women and 36 healthy individuals. We conclude that TNFalpha polymorphisms and resting blood TNFalpha levels do not correlate with the propensity to recurrent pregnancy loss in Caucasian women.

  17. Weight gain following treatment of hyperthyroidism.

    Science.gov (United States)

    Dale, J; Daykin, J; Holder, R; Sheppard, M C; Franklyn, J A

    2001-08-01

    Patients frequently express concern that treating hyperthyroidism will lead to excessive weight gain. This study aimed to determine the extent of, and risk factors for, weight gain in an unselected group of hyperthyroid patients. We investigated 162 consecutive hyperthyroid patients followed for at least 6 months. Height, weight, clinical features, biochemistry and management were recorded at each clinic visit. Documented weight gain was 5.42 +/- 0.46 kg (mean +/- SE) and increase in BMI was 8.49 +/- 0.71%, over a mean 24.2 +/- 1.6 months. Pre-existing obesity, Graves' disease causing hyperthyroidism, weight loss before presentation and length of follow-up each independently predicted weight gain. Patients treated with thionamides or radioiodine gained a similar amount of weight (thionamides, n = 87, 5.16 +/- 0.63 kg vs. radioiodine, n = 62, 4.75 +/- 0.57 kg, P = 0.645), but patients who underwent thyroidectomy (n = 13) gained more weight (10.27 +/- 2.56 kg vs. others, P = 0.007). Development of hypothyroidism (even transiently) was associated with weight gain (never hypothyroid, n = 102, 4.57 +/- 0.52 kg, transiently hypothyroid, n = 29, 5.37 +/- 0.85 kg, on T4, n = 31, 8.06 +/- 1.42 kg, P = 0.014). This difference remained after correcting for length of follow-up. In the whole cohort, weight increased by 3.95 +/- 0.40 kg at 1 year (n = 144) to 9.91 +/- 1.62 kg after 4 years (n = 27) (P = 0.008), representing a mean weight gain of 3.66 +/- 0.44 kg/year. We have demonstrated marked weight gain after treatment of hyperthyroidism. Pre-existing obesity, a diagnosis of Graves' disease and prior weight loss independently predicted weight gain and weight continued to rise with time. Patients who became hypothyroid, despite T4 replacement, gained most weight.

  18. NDH expression marks major transitions in plant evolution and reveals coordinate intracellular gene loss.

    Science.gov (United States)

    Ruhlman, Tracey A; Chang, Wan-Jung; Chen, Jeremy J W; Huang, Yao-Ting; Chan, Ming-Tsair; Zhang, Jin; Liao, De-Chih; Blazier, John C; Jin, Xiaohua; Shih, Ming-Che; Jansen, Robert K; Lin, Choun-Sea

    2015-04-11

    Key innovations have facilitated novel niche utilization, such as the movement of the algal predecessors of land plants into terrestrial habitats where drastic fluctuations in light intensity, ultraviolet radiation and water limitation required a number of adaptations. The NDH (NADH dehydrogenase-like) complex of Viridiplantae plastids participates in adapting the photosynthetic response to environmental stress, suggesting its involvement in the transition to terrestrial habitats. Although relatively rare, the loss or pseudogenization of plastid NDH genes is widely distributed across diverse lineages of photoautotrophic seed plants and mutants/transgenics lacking NDH function demonstrate little difference from wild type under non-stressed conditions. This study analyzes large transcriptomic and genomic datasets to evaluate the persistence and loss of NDH expression across plants. Nuclear expression profiles showed accretion of the NDH gene complement at key transitions in land plant evolution, such as the transition to land and at the base of the angiosperm lineage. While detection of transcripts for a selection of non-NDH, photosynthesis related proteins was independent of the state of NDH, coordinate, lineage-specific loss of plastid NDH genes and expression of nuclear-encoded NDH subunits was documented in Pinaceae, gnetophytes, Orchidaceae and Geraniales confirming the independent and complete loss of NDH in these diverse seed plant taxa. The broad phylogenetic distribution of NDH loss and the subtle phenotypes of mutants suggest that the NDH complex is of limited biological significance in contemporary plants. While NDH activity appears dispensable under favorable conditions, there were likely sufficiently frequent episodes of abiotic stress affecting terrestrial habitats to allow the retention of NDH activity. These findings reveal genetic factors influencing plant/environment interactions in a changing climate through 450 million years of land plant

  19. Central gain control in tinnitus and hyperacusis

    Directory of Open Access Journals (Sweden)

    Benjamin D Auerbach

    2014-10-01

    Full Text Available Sensorineural hearing loss induced by noise or ototoxic drug exposure reduces the neural activity transmitted from the cochlea to the central auditory system. Despite a reduced cochlear output, neural activity from more central auditory structures is paradoxically enhanced at suprathreshold intensities. This compensatory increase in the central auditory activity in response to the loss of sensory input is referred to as central gain enhancement. Enhanced central gain is hypothesized to be a potential mechanism that gives rise to hyperacusis and tinnitus, two debilitating auditory perceptual disorders that afflict millions of individuals. This review will examine the evidence for gain enhancement in the central auditory system in response to cochlear damage. Further, it will address the potential cellular and molecular mechanisms underlying this enhancement and discuss the contribution of central gain enhancement to tinnitus and hyperacusis. Current evidence suggests that multiple mechanisms with distinct temporal and spectral profiles are likely to contribute to central gain enhancement. Dissecting the contributions of these different mechanisms at different levels of the central auditory system is essential for elucidating the role of central gain enhancement in tinnitus and hyperacusis and, most importantly, the development of novel treatments for these disorders.

  20. Central Gain Control in Tinnitus and Hyperacusis

    Science.gov (United States)

    Auerbach, Benjamin D.; Rodrigues, Paulo V.; Salvi, Richard J.

    2014-01-01

    Sensorineural hearing loss induced by noise or ototoxic drug exposure reduces the neural activity transmitted from the cochlea to the central auditory system. Despite a reduced cochlear output, neural activity from more central auditory structures is paradoxically enhanced at suprathreshold intensities. This compensatory increase in the central auditory activity in response to the loss of sensory input is referred to as central gain enhancement. Enhanced central gain is hypothesized to be a potential mechanism that gives rise to hyperacusis and tinnitus, two debilitating auditory perceptual disorders that afflict millions of individuals. This review will examine the evidence for gain enhancement in the central auditory system in response to cochlear damage. Further, it will address the potential cellular and molecular mechanisms underlying this enhancement and discuss the contribution of central gain enhancement to tinnitus and hyperacusis. Current evidence suggests that multiple mechanisms with distinct temporal and spectral profiles are likely to contribute to central gain enhancement. Dissecting the contributions of these different mechanisms at different levels of the central auditory system is essential for elucidating the role of central gain enhancement in tinnitus and hyperacusis and, most importantly, the development of novel treatments for these disorders. PMID:25386157

  1. Like or dislike? Affective preference modulates neural response to others' gains and losses.

    Directory of Open Access Journals (Sweden)

    Yang Wang

    Full Text Available Previous studies have demonstrated that the brain responds differentially to others' gains and losses relative to one's own, moderated by social context factors such as competition and interpersonal relationships. In the current study, we tested the hypothesis that the neural response to others' outcomes could be modulated by a short-term induced affective preference. We engaged 17 men and 18 women in a social-exchange game, in which two confederates played fairly or unfairly. Both men and women rated the fair player as likable and the unfair players as unlikable. Afterwards, ERPs were recorded while participants observed each confederates playing a gambling game individually. This study examines feedback related negativity (FRN, an ERP component sensitive to negative feedback. ANOVA showed a significant interaction in which females but not males displayed stronger FRNs when observing likable players' outcomes compared to unlikable ones'. However, males did not respond differently under either circumstance. These findings suggest that, at least in females, the neural response is influenced by a short-term induced affective preference.

  2. The Effects of Gain- versus Loss-Framed Messages Following Health Risk Information on Physical Activity in Individuals With Multiple Sclerosis.

    Science.gov (United States)

    Lithopoulos, Alexander; Bassett-Gunter, Rebecca L; Martin Ginis, Kathleen A; Latimer-Cheung, Amy E

    2017-06-01

    Few people with multiple sclerosis engage in physical activity. Messaging interventions may motivate more physical activity among these individuals. The purpose of this online study was to evaluate an intervention presenting participants with multiple sclerosis (N = 237) with risk information (i.e., information demonstrating people with multiple sclerosis are more likely to experience certain health issues) or no risk information followed by gain- or loss-framed physical activity messages. Participants completed questionnaires on Days 1, 6, and 28 and received information material on Days 2-5. The dependent variables were as follows: physical activity intentions and behavior, response and task efficacy, perceived threat (i.e., perception of threat to health issues relevant to people with multiple sclerosis), and avoidance (i.e., avoiding thinking about/doing something about the health issues presented in the messages). Analyses indicated physical activity and response efficacy increased over time. Also, participants receiving risk information had higher levels of physical activity and perceived threat. However, manipulation checks showed no differences between participants regarding perceptions of risk information or gain/loss-framed messages. Despite the lack of impact of the framing intervention, this study suggests that a brief informational intervention can positively influence physical activity and certain correlates of physical activity among people with multiple sclerosis.

  3. Clonal and Widespread Gene Transfer by Proviral Electroporation for Analysis of Brain Laminar Formation

    Science.gov (United States)

    Sugiyama, Sayaka; Nakamura, Harukazu

    An essential approach to understanding the mechanisms of development is to alter a gene function/expression. In vivo electroporation has been adapted as one such technique (Muramatsu et al., 1997). It is a very useful tool to achieve a gain- and loss-of-function (by using RNAi or morpholinos) of a gene of interest (Funahashi et al., 1999; Fukuchi-Shimogori and Grove, 2001; Kos et al., 2001; Katahira and Nakamura, 2003; Sugiyama and Nakamura, 2003). The technique has allowed the altering of gene expression temporally and spatially. Pulse-labeling technique is an approach to manipulate a specific cell population temporally, depending on its birthday, as this chapter describes. This technique is more advantageous over the BrdU application, as it can reveal cell lineage; it also has the ability to manipulate a gain- and loss-of-function into specific precursor cells (Tabata and Nakajima, 2001; Sugiyama and Nakamura, 2003; Huber et al., 2008).

  4. Target genes of myostatin loss-of-function in muscles of late bovine fetuses

    Directory of Open Access Journals (Sweden)

    Hocquette Jean-François

    2007-03-01

    Full Text Available Abstract Background Myostatin, a muscle-specific member of the Transforming Growth Factor beta family, negatively regulates muscle development. Double-muscled (DM cattle have a loss-of-function mutation in their myostatin gene responsible for the hypermuscular phenotype. Thus, these animals are a good model for understanding the mechanisms underpinning muscular hypertrophy. In order to identify individual genes or networks that may be myostatin targets, we looked for genes that were differentially expressed between DM and normal (NM animals (n = 3 per group in the semitendinosus muscle (hypertrophied in DM animals at 260 days of fetal development (when the biochemical differentiation of muscle is intensive. A heterologous microarray (human and murine oligonucleotide sequences of around 6,000 genes expressed in muscle was used. Results Many genes were found to be differentially expressed according to genetic type (some with a more than 5-fold change, and according to the presence of one or two functional myostatin allele(s. They belonged to various functional categories. The genes down-regulated in DM fetuses were mainly those encoding extracellular matrix proteins, slow contractile proteins and ribosomal proteins. The genes up-regulated in DM fetuses were mainly involved in the regulation of transcription, cell cycle/apoptosis, translation or DNA metabolism. These data highlight features indicating that DM muscle is shifted towards a more glycolytic metabolism, and has an altered extracellular matrix composition (e.g. down-regulation of COL1A1 and COL1A2, and up-regulation of COL4A2 and decreased adipocyte differentiation (down-regulation of C1QTNF3. The altered gene expression in the three major muscle compartments (fibers, connective tissue and intramuscular adipose tissue is consistent with the well-known characteristics of DM cattle. In addition, novel potential targets of the myostatin gene were identified (MB, PLN, troponins, ZFHX1B

  5. Gain attenuation of gated framing camera

    International Nuclear Information System (INIS)

    Xiao Shali; Liu Shenye; Cao Zhurong; Li Hang; Zhang Haiying; Yuan Zheng; Wang Liwei

    2009-01-01

    The theoretic model of framing camera's gain attenuation is analyzed. The exponential attenuation curve of the gain along the pulse propagation time is simulated. An experiment to measure the coefficient of gain attenuation based on the gain attenuation theory is designed. Experiment result shows that the gain follows an exponential attenuation rule with a quotient of 0.0249 nm -1 , the attenuation coefficient of the pulse is 0.00356 mm -1 . The loss of the pulse propagation along the MCP stripline is the leading reason of gain attenuation. But in the figure of a single stripline, the gain dose not follow the rule of exponential attenuation completely, instead, there is a gain increase at the stripline bottom. That is caused by the reflection of the pulse. The reflectance is about 24.2%. Combining the experiment and theory, which design of the stripline MCP can improved the gain attenuation. (authors)

  6. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy

    NARCIS (Netherlands)

    Brown, Sara J.; Asai, Yuka; Cordell, Heather J.; Campbell, Linda E.; Zhao, Yiwei; Liao, Haihui; Northstone, Kate; Henderson, John; Alizadehfar, Reza; Ben-Shoshan, Moshe; Morgan, Kenneth; Roberts, Graham; Masthoff, Laury J. N.; Pasmans, Suzanne G. M. A.; van den Akker, Peter C.; Wijmenga, Cisca; Hourihane, Jonathan O'B.; Palmer, Colin N. A.; Lack, Gideon; Clarke, Ann; Hull, Peter R.; Irvine, Alan D.; McLean, W. H. Irwin

    Background: IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the

  7. Energy Gaining Windows for Residental Buildings

    DEFF Research Database (Denmark)

    Kragh, Jesper; Laustsen, Jacob Birck; Svendsen, Svend

    2008-01-01

    window is made of fiber-reinforced plastic (plastic reinforced by fine fibers made of glass). This composite material is a weatherproof material with very low thermal conductivity and high mechanical strength. These properties make the material very suitable for frame profiles due to lower heat loss...... minus the heat loss integrated over the heating season. It is assumed that in northern cold climates all of the solar gain during the heating season can be utilized for space heating. Problems with overheating in the summer period must be solved with overhang or moveable solar shading devices. Two...... and longer durability of the window. The glazing in these fiber reinforced polyester windows is both unsealed and sealed triple glazing units. To increase the net energy gain slim frame profiles have been developed to increase the glazing area and thereby the solar gain. The challenge when developing slim...

  8. Online technology for teaching and learning-gains and losses.

    Science.gov (United States)

    Cann, Alan

    2015-07-01

    This commentary describes recent developments in the use of online technologies, in particular social media and mobile devices, for teaching and learning and considers what has been gained and lost. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Missense mutation in the USH2A gene: association with recessive retinitis pigmentosa without hearing loss.

    Science.gov (United States)

    Rivolta, C; Sweklo, E A; Berson, E L; Dryja, T P

    2000-06-01

    Microdeletions Glu767(1-bp del), Thr967(1-bp del), and Leu1446(2-bp del) in the human USH2A gene have been reported to cause Usher syndrome type II, a disorder characterized by retinitis pigmentosa (RP) and mild-to-severe hearing loss. Each of these three frameshift mutations is predicted to lead to an unstable mRNA transcript that, if translated, would result in a truncated protein lacking the carboxy terminus. Here, we report Cys759Phe, a novel missense mutation in this gene that changes an amino-acid residue within the fifth laminin-epidermal growth factor-like domain of the USH2A gene and that is associated with recessive RP without hearing loss. This single mutation was found in 4.5% of 224 patients with recessive RP, suggesting that USH2A could cause more cases of nonsyndromic recessive RP than does any other gene identified to date.

  10. Optimal weight gain in obese and overweight pregnant Japanese women.

    Science.gov (United States)

    Hirooka-Nakama, Junko; Enomoto, Kimiko; Sakamaki, Kentaro; Kurasawa, Kentaro; Miyagi, Etsuko; Aoki, Shigeru

    2018-03-20

    We aimed to determine the optimal gestational weight gain (GWG) in Japanese women with a Body Mass Index (BMI) ≥25 kg/m 2 . The present retrospective study investigated singleton pregnancies in 6,781 Japanese women registered in the Japan Society of Obstetrics and Gynecology system in 2013. We divided overweight and obese women into four GWG categories based on the Institute of Medicine (IOM) recommended: weight loss, small weight gain, within IOM criteria, and above IOM criteria. The adjusted odds ratios and predicted probabilities of maternal and neonatal outcomes of interest with weight change were calculated. In overweight women, GWG was associated with neonatal birth weight. In the loss and small gain subgroups, there was a significant increase in small for gestational age (SGA) and low birth weight neonates (LBW). Predicted probabilities showed the lowest risk was observed in a weight gain of 0 kg; the risk sharply increased at a gain of 11.5 kg. In obese women, weight gain increased the prevalence of large for gestational age (LGA) neonates; however; SGA was not associated with GWG. Predicted probabilities showed an increase in the risk with weight gain. The observed optimal GWG was 0 to 11.5 kg in overweight, and weight loss in obese, pregnant Japanese women.

  11. Overview of recurrent chromosomal losses in retinoblastoma detected by low coverage next generation sequencing

    Science.gov (United States)

    García-Chequer, A.J.; Méndez-Tenorio, A.; Olguín-Ruiz, G.; Sánchez-Vallejo, C.; Isa, P.; Arias, C.F.; Torres, J.; Hernández-Angeles, A.; Ramírez-Ortiz, M.A.; Lara, C.; Cabrera-Muñoz, M.L.; Sadowinski-Pine, S.; Bravo-Ortiz, J.C.; Ramón-García, G.; Diegopérez-Ramírez, J.; Ramírez-Reyes, G.; Casarrubias-Islas, R.; Ramírez, J.; Orjuela, M.A.; Ponce-Castañeda, M.V.

    2016-01-01

    Genes are frequently lost or gained in malignant tumors and the analysis of these changes can be informative about the underlying tumor biology. Retinoblastoma is a pediatric intraocular malignancy, and since deletions in chromosome 13 have been described in this tumor, we performed genome wide sequencing with the Illumina platform to test whether recurrent losses could be detected in low coverage data from DNA pools of Rb cases. An in silico reference profile for each pool was created from the human genome sequence GRCh37p5; a chromosome integrity score and a graphics 40 Kb window analysis approach, allowed us to identify with high resolution previously reported non random recurrent losses in all chromosomes of these tumors. We also found a pattern of gains and losses associated to clear and dark cytogenetic bands respectively. We further analyze a pool of medulloblastoma and found a more stable genomic profile and previously reported losses in this tumor. This approach facilitates identification of recurrent deletions from many patients that may be biological relevant for tumor development. PMID:26883451

  12. A therapeutic gain model for brachytherapy

    International Nuclear Information System (INIS)

    Wigg, D.R.

    2003-01-01

    When treating with continuous irradiation the potential therapeutic gain or loss depends on several treatment, normal tissue and tumour variables. There are similarities between equations defining tissue effects with fractionated treatment and brachytherapy. The former is sensitive to dose per fraction (and incomplete repair for short intervals between treatments) and the later is sensitive to dose rate and continuous repair factors. Because of these similarities, for typical tumours and normal tissues, dose per fraction and dose rates generally work in similar directions. As the dose per fraction or dose rate increases the therapeutic gain falls. With continuous irradiation the dose rates effects are determined by Beta cell kill and hence the absolute value of Beta . Minimal sensitivity occurs at very low and very high dose rates. The magnitude of cell kill also depends on the Continuous Repair Factor (g) which is a function of the treatment time and the Repair Half Time (in hours) of the tissues (Repair Half Time T 1/2Ln(2)/h, when h the Repair Constant). An interactive optimising model has been written to predict the therapeutic gain or loss as the parameter values are varied. This model includes the tumour and normal tissue parameters alpha and beta Gy (or individual values), their Repair Half Times, dose rates and overall treatment time. The model is based on the Linear-Quadratic equation and the Total Effect (TE) method of Thames and Hendry although the Extrapolated Response Dose (ERD) method of Barendsen produces the same results. The model is written so that the gain or loss may be seen when treatment is always to normal tissue tolerance doses. The magnitude of the therapeutic loss as the dose rate increases and its sensitivity to changes in normal tissue and tumour parameter values is clearly demonstrated

  13. 26 CFR 1.1374-2 - Net recognized built-in gain.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Net recognized built-in gain. 1.1374-2 Section 1...-in gain. (a) In general. An S corporation's net recognized built-in gain for any taxable year is the... considering only its recognized built-in gain, recognized built-in loss, and recognized built-in gain...

  14. Antarctic sea ice losses drive gains in benthic carbon drawdown.

    Science.gov (United States)

    Barnes, D K A

    2015-09-21

    Climate forcing of sea-ice losses from the Arctic and West Antarctic are blueing the poles. These losses are accelerating, reducing Earth's albedo and increasing heat absorption. Subarctic forest (area expansion and increased growth) and ice-shelf losses (resulting in new phytoplankton blooms which are eaten by benthos) are the only significant described negative feedbacks acting to counteract the effects of increasing CO2 on a warming planet, together accounting for uptake of ∼10(7) tonnes of carbon per year. Most sea-ice loss to date has occurred over polar continental shelves, which are richly, but patchily, colonised by benthic animals. Most polar benthos feeds on microscopic algae (phytoplankton), which has shown increased blooms coincident with sea-ice losses. Here, growth responses of Antarctic shelf benthos to sea-ice losses and phytoplankton increases were investigated. Analysis of two decades of benthic collections showed strong increases in annual production of shelf seabed carbon in West Antarctic bryozoans. These were calculated to have nearly doubled to >2x10(5) tonnes of carbon per year since the 1980s. Annual production of bryozoans is median within wider Antarctic benthos, so upscaling to include other benthos (combined study species typically constitute ∼3% benthic biomass) suggests an increased drawdown of ∼2.9x10(6) tonnes of carbon per year. This drawdown could become sequestration because polar continental shelves are typically deeper than most modern iceberg scouring, bacterial breakdown rates are slow, and benthos is easily buried. To date, most sea-ice losses have been Arctic, so, if hyperboreal benthos shows a similar increase in drawdown, polar continental shelves would represent Earth's largest negative feedback to climate change. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. The natural history of class I primate alcohol dehydrogenases includes gene duplication, gene loss, and gene conversion.

    Directory of Open Access Journals (Sweden)

    Matthew A Carrigan

    Full Text Available Gene duplication is a source of molecular innovation throughout evolution. However, even with massive amounts of genome sequence data, correlating gene duplication with speciation and other events in natural history can be difficult. This is especially true in its most interesting cases, where rapid and multiple duplications are likely to reflect adaptation to rapidly changing environments and life styles. This may be so for Class I of alcohol dehydrogenases (ADH1s, where multiple duplications occurred in primate lineages in Old and New World monkeys (OWMs and NWMs and hominoids.To build a preferred model for the natural history of ADH1s, we determined the sequences of nine new ADH1 genes, finding for the first time multiple paralogs in various prosimians (lemurs, strepsirhines. Database mining then identified novel ADH1 paralogs in both macaque (an OWM and marmoset (a NWM. These were used with the previously identified human paralogs to resolve controversies relating to dates of duplication and gene conversion in the ADH1 family. Central to these controversies are differences in the topologies of trees generated from exonic (coding sequences and intronic sequences.We provide evidence that gene conversions are the primary source of difference, using molecular clock dating of duplications and analyses of microinsertions and deletions (micro-indels. The tree topology inferred from intron sequences appear to more correctly represent the natural history of ADH1s, with the ADH1 paralogs in platyrrhines (NWMs and catarrhines (OWMs and hominoids having arisen by duplications shortly predating the divergence of OWMs and NWMs. We also conclude that paralogs in lemurs arose independently. Finally, we identify errors in database interpretation as the source of controversies concerning gene conversion. These analyses provide a model for the natural history of ADH1s that posits four ADH1 paralogs in the ancestor of Catarrhine and Platyrrhine primates

  16. 26 CFR 1.1231-1 - Gains and losses from the sale or exchange of certain property used in the trade or business.

    Science.gov (United States)

    2010-04-01

    ... having a fair market value of $1,000 at the time of the storm 1,000 8. Total gains 12,500 ___ 9. Total.... During 1970 furniture used in his business and held for more than 6 months was destroyed by fire. The... business, as defined in section 1231(b). The $2,000 loss upon the destruction of the furniture is not a...

  17. Reducing the losses of optical metamaterials

    International Nuclear Information System (INIS)

    Fang, Anan

    2010-01-01

    The field of metamaterials is driven by fascinating and far-reaching theoretical visions, such as perfect lenses, invisibility cloaking, and enhanced optical nonlinearities. However, losses have become the major obstacle towards real world applications in the optical regime. Reducing the losses of optical metamaterials becomes necessary and extremely important. In this thesis, two approaches are taken to reduce the losses. One is to construct an indefinite medium. Indefinite media are materials where not all the principal components of the permittivity and permeability tensors have the same sign. They do not need the resonances to achieve negative permittivity, (var e psilon). So, the losses can be comparatively small. To obtain indefinite media, three-dimensional (3D) optical metallic nanowire media with different structures are designed. They are numerically demonstrated that they are homogeneous effective indefinite anisotropic media by showing that their dispersion relations are hyperbolic. Negative group refraction and pseudo focusing are observed. Another approach is to incorporate gain into metamaterial nanostructures. The nonlinearity of gain is included by a generic four-level atomic model. A computational scheme is presented, which allows for a self-consistent treatment of a dispersive metallic photonic metamaterial coupled to a gain material incorporated into the nanostructure using the finite-difference time-domain (FDTD) method. The loss compensations with gain are done for various structures, from 2D simplified models to 3D realistic structures. Results show the losses of optical metamaterials can be effectively compensated by gain. The effective gain coefficient of the combined system can be much larger than the bulk gain counterpart, due to the strong local-field enhancement.

  18. Reducing the losses of optical metamaterials

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Anan [Iowa State Univ., Ames, IA (United States)

    2010-01-01

    The field of metamaterials is driven by fascinating and far-reaching theoretical visions, such as perfect lenses, invisibility cloaking, and enhanced optical nonlinearities. However, losses have become the major obstacle towards real world applications in the optical regime. Reducing the losses of optical metamaterials becomes necessary and extremely important. In this thesis, two approaches are taken to reduce the losses. One is to construct an indefinite medium. Indefinite media are materials where not all the principal components of the permittivity and permeability tensors have the same sign. They do not need the resonances to achieve negative permittivity, ε. So, the losses can be comparatively small. To obtain indefinite media, three-dimensional (3D) optical metallic nanowire media with different structures are designed. They are numerically demonstrated that they are homogeneous effective indefinite anisotropic media by showing that their dispersion relations are hyperbolic. Negative group refraction and pseudo focusing are observed. Another approach is to incorporate gain into metamaterial nanostructures. The nonlinearity of gain is included by a generic four-level atomic model. A computational scheme is presented, which allows for a self-consistent treatment of a dispersive metallic photonic metamaterial coupled to a gain material incorporated into the nanostructure using the finite-difference time-domain (FDTD) method. The loss compensations with gain are done for various structures, from 2D simplified models to 3D realistic structures. Results show the losses of optical metamaterials can be effectively compensated by gain. The effective gain coefficient of the combined system can be much larger than the bulk gain counterpart, due to the strong local-field enhancement.

  19. Investigating the contribution of VAPB/ALS8 loss of function in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kabashi, Edor; El Oussini, Hajer; Bercier, Valérie; Gros-Louis, François; Valdmanis, Paul N; McDearmid, Jonathan; Mejier, Inge A; Dion, Patrick A; Dupre, Nicolas; Hollinger, David; Sinniger, Jérome; Dirrig-Grosch, Sylvie; Camu, William; Meininger, Vincent; Loeffler, Jean-Philippe; René, Frédérique; Drapeau, Pierre; Rouleau, Guy A; Dupuis, Luc

    2013-06-15

    The mutations P56S and T46I in the gene encoding vesicle-associated membrane protein-associated protein B/C (VAPB) cause ALS8, a familial form of amyotrophic lateral sclerosis (ALS). Overexpression of mutant forms of VAPB leads to cytosolic aggregates, suggesting a gain of function of the mutant protein. However, recent work suggested that the loss of VAPB function could be the major mechanism leading to ALS8. Here, we used multiple genetic and experimental approaches to study whether VAPB loss of function might be sufficient to trigger motor neuron degeneration. In order to identify additional ALS-associated VAPB mutations, we screened the entire VAPB gene in a cohort of ALS patients and detected two mutations (A145V and S160Δ). To directly address the contribution of VAPB loss of function in ALS, we generated zebrafish and mouse models with either a decreased or a complete loss of Vapb expression. Vapb knockdown in zebrafish led to swimming deficits. Mice knocked-out for Vapb showed mild motor deficits after 18 months of age yet had innervated neuromuscular junctions (NMJs). Importantly, overexpression of VAPB mutations were unable to rescue the motor deficit caused by Vapb knockdown in zebrafish and failed to cause a toxic gain-of-function defect on their own. Thus, Vapb loss of function weakens the motor system of vertebrate animal models but is on its own unable to lead to a complete ALS phenotype. Our findings are consistent with the notion that VAPB mutations constitute a risk factor for motor neuron disease through a loss of VAPB function.

  20. Sudden Sensorineural Hearing Loss and Polymorphisms in Iron Homeostasis Genes: New Insights from a Case-Control Study

    Directory of Open Access Journals (Sweden)

    Alessandro Castiglione

    2015-01-01

    Full Text Available Background. Even if various pathophysiological events have been proposed as explanations, the putative cause of sudden hearing loss remains unclear. Objectives. To investigate and to reveal associations (if any between the main iron-related gene variants and idiopathic sudden sensorineural hearing loss. Study Design. Case-control study. Materials and Methods. A total of 200 sudden sensorineural hearing loss patients (median age 63.65 years; range 10–92 were compared with 400 healthy control subjects. The following genetic variants were investigated: the polymorphism c.−8CG in the promoter of the ferroportin gene (FPN1; SLC40A1, the two isoforms C1 and C2 (p.P570S of the transferrin protein (TF, the amino acidic substitutions p.H63D and p.C282Y in the hereditary hemochromatosis protein (HFE, and the polymorphism c.–582AG in the promoter of the HEPC gene, which encodes the protein hepcidin (HAMP. Results. The homozygous genotype c.−8GG of the SLC40A1 gene revealed an OR for ISSNHL risk of 4.27 (CI 95%, 2.65–6.89; P=0.001, being overrepresented among cases. Conclusions. Our study indicates that the homozygous genotype FPN1 −8GG was significantly associated with increased risk of developing sudden hearing loss. These findings suggest new research should be conducted in the field of iron homeostasis in the inner ear.

  1. Parent-Reported Patterns of Loss and Gain in Communication in 1- to 2-Year-Old Children Are Not Unique to Autism Spectrum Disorder

    Science.gov (United States)

    Brignell, Amanda; Williams, Katrina; Prior, Margot; Donath, Susan; Reilly, Sheena; Bavin, Edith L.; Eadie, Patricia; Morgan, Angela T.

    2017-01-01

    We compared loss and gain in communication from 1 to 2 years in children later diagnosed with autism spectrum disorder (n = 41), language impairment (n = 110) and in children with typical language development at 7 years (n = 831). Participants were selected from a prospective population cohort study of child language (the Early Language in…

  2. Interleukin-1β gene polymorphism and hearing loss related to the history of occupational noise exposure in Brazilian elderly.

    Science.gov (United States)

    Carvalho, Luiz C L; Marchiori, Luciana L M; Melo, Juliana J; Maciel, Sandra M; Poli-Frederico, Regina C

    2013-01-01

    Hearing loss is the most common sensory impairment in older people, and may have social and psychological consequences, such as social isolation, frustration and depression. Noise-induced hearing loss (NIHL) is an interaction of both genetic and environmental factors. Some studies have led to the identification of possible NIHL susceptibility genes. The aim of the present study was to investigate whether the polymorphism of the interleukin (IL)-1β gene at position + 3954 was associated with complaints of hearing loss due to occupational exposure. The sample was composed of elderly people with hearing loss (age ≥ 60 years) divided into two groups: 99 with occupational exposure to noise and 193 without exposure. Information on occupational exposure to noise was obtained through interviews using a semi-structured questionnaire. Hearing acuity was measured from 500 to 6000 Hz and the IL-1β genotype was obtained by the polymerase chain reaction- restriction fragment length polymorphism technique. Differences in allelic and genotypic frequencies, and the association between genotypic frequencies and complaints of hearing loss due to occupational exposure, were analyzed by the Chi-square test at the 5% significance level. Fifty-one percent of the elderly were homozygous for the ancestral allele (C), 17.2% were homozygous for the polymorphic allele (T) and 31.8% were heterozygous. The frequency was found to be 67-33% C to allele T. There was no significant association between polymorphism in gene IL-1β and hearing loss associated with occupational exposure (χ2 = 0.538; P = 0.676). No association was found with the polymorphism of the IL-1β +3954 C/T gene and hearing loss associated with the occupational noise exposure history.

  3. Association between loss-of-function mutations in the filaggrin gene and self-reported food allergy and alcohol sensitivity

    DEFF Research Database (Denmark)

    Linneberg, Allan René; Fenger, Runa V; Husemoen, Lise Lotte Nystrup

    2013-01-01

    Loss-of-function mutations of the filaggrin (FLG) gene cause an impaired skin barrier and increase the risk of atopic dermatitis. Interestingly, FLG mutations have also been found to be associated with a high risk of peanut allergy.......Loss-of-function mutations of the filaggrin (FLG) gene cause an impaired skin barrier and increase the risk of atopic dermatitis. Interestingly, FLG mutations have also been found to be associated with a high risk of peanut allergy....

  4. Evolution of gremlin 2 in cetartiodactyl mammals: gene loss coincides with lack of upper jaw incisors in ruminants

    Directory of Open Access Journals (Sweden)

    Juan C. Opazo

    2017-01-01

    Full Text Available Understanding the processes that give rise to genomic variability in extant species is an active area of research within evolutionary biology. With the availability of whole genome sequences, it is possible to quantify different forms of variability such as variation in gene copy number, which has been described as an important source of genetic variability and in consequence of phenotypic variability. Most of the research on this topic has been focused on understanding the biological significance of gene duplication, and less attention has been given to the evolutionary role of gene loss. Gremlin 2 is a member of the DAN gene family and plays a significant role in tooth development by blocking the ligand-signaling pathway of BMP2 and BMP4. The goal of this study was to investigate the evolutionary history of gremlin 2 in cetartiodactyl mammals, a group that possesses highly divergent teeth morphology. Results from our analyses indicate that gremlin 2 has experienced a mixture of gene loss, gene duplication, and rate acceleration. Although the last common ancestor of cetartiodactyls possessed a single gene copy, pigs and camels are the only cetartiodactyl groups that have retained gremlin 2. According to the phyletic distribution of this gene and synteny analyses, we propose that gremlin 2 was lost in the common ancestor of ruminants and cetaceans between 56.3 and 63.5 million years ago as a product of a chromosomal rearrangement. Our analyses also indicate that the rate of evolution of gremlin 2 has been accelerated in the two groups that have retained this gene. Additionally, the lack of this gene could explain the high diversity of teeth among cetartiodactyl mammals; specifically, the presence of this gene could act as a biological constraint. Thus, our results support the notions that gene loss is a way to increase phenotypic diversity and that gremlin 2 is a dispensable gene, at least in cetartiodactyl mammals.

  5. A randomized controlled trial to prevent excessive gestational weight gain and promote postpartum weight loss in overweight and obese women: Health In Pregnancy and Postpartum (HIPP).

    Science.gov (United States)

    Wilcox, Sara; Liu, Jihong; Addy, Cheryl L; Turner-McGrievy, Gabrielle; Burgis, Judith T; Wingard, Ellen; Dahl, Alicia A; Whitaker, Kara M; Schneider, Lara; Boutté, Alycia K

    2018-03-01

    Interventions to prevent excessive gestational weight gain and promote postpartum weight loss have yielded modest results, particularly in overweight and obese women. To examine the impact of a theory-based lifestyle intervention on gestational weight gain, postpartum weight loss, and related maternal and child outcomes and to examine race differences in these outcomes. A randomized controlled trial (target N=400; 200 intervention, 200 standard care; 200 African American, 200 white). Overweight and obese African American and white women ≤16weeks gestation are recruited from obstetrics and gynecology clinics in South Carolina. Intervention participants receive two in-depth counseling sessions (early pregnancy and postpartum), telephone counseling, behavioral podcasts, and social media support that target weight self-monitoring and increasing physical activity and healthy dietary behavior practices, guided by Social Cognitive Theory. Standard care participants receive monthly mailings and a matched number of podcasts on non-weight related topics. All intervention activities last from ≤18weeks gestation to 6months after delivery. Gestational weight gain is the primary outcome. Secondary outcomes are meeting gestational weight gain guidelines (inadequate, adequate, excessive), weekly rate of gestational weight gain, postpartum weight retention, physical activity and dietary behaviors, health-related quality of life, and offspring adiposity. Participants are assessed at baseline (≤16weeks gestation), 32weeks gestation, and 6 and 12months postpartum, and offspring are assessed at 6 and 12months. HIPP is an innovative study that addresses significant gaps in the literature. Primary outcome results are expected in 2019. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Employment, work hours and weight gain among middle-aged women.

    Science.gov (United States)

    Au, N; Hauck, K; Hollingsworth, B

    2013-05-01

    To investigate the influence of employment and work hours on weight gain and weight loss among middle-aged women. Quantile regression techniques were used to estimate the influence of employment and hours worked on percentage weight change over 2 years across the entire distribution of weight change in a cohort of middle-aged women. A range of controls was included in the models to isolate the effect of work status. A total of 9276 women aged 45-50 years at baseline who were present in both the 1996 and 1998 surveys of the Australian Longitudinal Study of Women's Health. The women were a representative sample of the Australian population. Being out of the labour force or unemployed was associated with lower weight gain and higher weight loss than being employed. The association was stronger at low to moderate levels of weight gain. Among employed women, working regular (35-40), long (41-48) or very long (49+) hours was associated with increasingly higher levels of weight gain compared with working part-time hours. The association was stronger for women with greater weight gain overall. The association between unemployment and weight change became insignificant when health status was controlled for. Employment was associated with more weight gain and less weight loss. Among the employed, working longer hours was associated with more weight gain, especially at the higher levels of weight gain where the health consequences are more serious. These findings suggest that as women work longer hours they are more likely to make lifestyle choices that are associated with weight gain.

  7. The assessment of knowledge and learning in competence spaces: The gain-loss model for dependent skills.

    Science.gov (United States)

    Anselmi, Pasquale; Stefanutti, Luca; de Chiusole, Debora; Robusto, Egidio

    2017-11-01

    The gain-loss model (GaLoM) is a formal model for assessing knowledge and learning. In its original formulation, the GaLoM assumes independence among the skills. Such an assumption is not reasonable in several domains, in which some preliminary knowledge is the foundation for other knowledge. This paper presents an extension of the GaLoM to the case in which the skills are not independent, and the dependence relation among them is described by a well-graded competence space. The probability of mastering skill s at the pretest is conditional on the presence of all skills on which s depends. The probabilities of gaining or losing skill s when moving from pretest to posttest are conditional on the mastery of s at the pretest, and on the presence at the posttest of all skills on which s depends. Two formulations of the model are presented, in which the learning path is allowed to change from pretest to posttest or not. A simulation study shows that models based on the true competence space obtain a better fit than models based on false competence spaces, and are also characterized by a higher assessment accuracy. An empirical application shows that models based on pedagogically sound assumptions about the dependencies among the skills obtain a better fit than models assuming independence among the skills. © 2017 The British Psychological Society.

  8. Richer histories for more relevant policies: 42 years of tree cover loss and gain in Southeast Sulawesi, Indonesia.

    Science.gov (United States)

    Kelley, Lisa C; Evans, Samuel G; Potts, Matthew D

    2017-02-01

    Understandings of contemporary forest cover loss are critical for policy but have come at the expense of long-term, multidirectional analyses of land cover change. This is a critical gap given (i) profound reconfigurations in land use and land control over the past several decades and (ii) evidence of widespread 'woodland resurgence' throughout the tropics. In this study, we argue that recent advancements within the field of land change science provide new opportunities to address this gap. In turn, we suggest that multidecadal and multidirectional analyses of land cover change can facilitate richer social analyses of land cover change and more relevant conservation policies and practice. Our argument is grounded in a case study from Southeast Sulawesi, Indonesia. Using a novel analytical platform, Google Earth Engine, and open access to high-quality Landsat data, we map land cover change in Southeast Sulawesi, Indonesia, from 1972 to 2014. We find that tree cover loss constitutes the single largest net change over the period 1972-2014 but that gross rates of tree cover gain were three times higher than gross loss rates from 1972 to 1995 and equivalent to loss rates from 1995 to 2014. We suggest the smallholder tree crop economy likely produced both forest loss and Imperata grassland restoration in this region. This case points to the need to expand rather than collapse the baselines used to study carbon and biodiversity change in tropical regions. It also demonstrates the possible utility of applying such methods to other regions. © 2016 John Wiley & Sons Ltd.

  9. 26 CFR 1.1247-3 - Treatment of capital gains.

    Science.gov (United States)

    2010-04-01

    ... portion of the excess capital gains were designated. The amount so includible by the partnership shall be... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Treatment of capital gains. 1.1247-3 Section 1... (CONTINUED) INCOME TAXES Special Rules for Determining Capital Gains and Losses § 1.1247-3 Treatment of...

  10. Interleukin-1β gene polymorphism and hearing loss related to the history of occupational noise exposure in Brazilian elderly

    Directory of Open Access Journals (Sweden)

    Luiz C. L. Carvalho

    2013-01-01

    Full Text Available Hearing loss is the most common sensory impairment in older people, and may have social and psychological consequences, such as social isolation, frustration and depression. Noise-induced hearing loss (NIHL is an interaction of both genetic and environmental factors. Some studies have led to the identification of possible NIHL susceptibility genes. The aim of the present study was to investigate whether the polymorphism of the interleukin (IL-1β gene at position + 3954 was associated with complaints of hearing loss due to occupational exposure. The sample was composed of elderly people with hearing loss (age ≥ 60 years divided into two groups: 99 with occupational exposure to noise and 193 without exposure. Information on occupational exposure to noise was obtained through interviews using a semi-structured questionnaire. Hearing acuity was measured from 500 to 6000 Hz and the IL-1β genotype was obtained by the polymerase chain reaction- restriction fragment length polymorphism technique. Differences in allelic and genotypic frequencies, and the association between genotypic frequencies and complaints of hearing loss due to occupational exposure, were analyzed by the Chi-square test at the 5% significance level. Fifty-one percent of the elderly were homozygous for the ancestral allele (C, 17.2% were homozygous for the polymorphic allele (T and 31.8% were heterozygous. The frequency was found to be 67-33% C to allele T. There was no significant association between polymorphism in gene IL-1β and hearing loss associated with occupational exposure (χ2 = 0.538; P = 0.676. No association was found with the polymorphism of the IL-1β +3954 C/T gene and hearing loss associated with the occupational noise exposure history.

  11. Over-expression of histone H3K4 demethylase gene JMJ15 enhances salt tolerance in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Yuan eShen

    2014-06-01

    Full Text Available Histone H3 lysine 4 trimethylation (H3K4me3 has been shown to be involved in stress-responsive gene expression and gene priming in plants. However, the role of H3K4me3 resetting in the processes is not clear. In this work we studied the expression and function of Arabidopsis H3K4 demethylase gene JMJ15. We show that the expression of JMJ15 was relatively low and was limited to a number of tissues during vegetative growth but was higher in young floral organs. Over-expression of the gene in gain-of-function mutants reduced the plant height with accumulation of lignin in stems, while the loss-of-function mutation did not produce any visible phenotype. The gain-of-function mutants showed enhanced salt tolerance, whereas the loss-of-function mutant was more sensitive to salt compared to the wild type. Transcriptomic analysis revealed that over-expression of JMJ15 down-regulated many genes which are preferentially marked by H3K4me3 and H3K4me2. Many of the down-regulated genes encode transcription regulators involved in stress responses. The data suggest that increased JMJ15 levels may regulate the gene expression program that enhances stress tolerance.

  12. Energy Gaining Windows for Residental Buildings

    DEFF Research Database (Denmark)

    Kragh, Jesper; Laustsen, Jacob Birck; Svendsen, Svend

    2008-01-01

    This paper presents some of the research done during the last 8 years at the Technical University of Denmark developing improved low-energy window solutions. The focus has been on maximizing the net energy gain of windows for residential buildings. The net energy gain of windows is the solar gain...... minus the heat loss integrated over the heating season. It is assumed that in northern cold climates all of the solar gain during the heating season can be utilized for space heating. Problems with overheating in the summer period must be solved with overhang or moveable solar shading devices. Two...... and longer durability of the window. The glazing in these fiber reinforced polyester windows is both unsealed and sealed triple glazing units. To increase the net energy gain slim frame profiles have been developed to increase the glazing area and thereby the solar gain. The challenge when developing slim...

  13. Heavy inertial particles in turbulent flows gain energy slowly but lose it rapidly.

    Science.gov (United States)

    Bhatnagar, Akshay; Gupta, Anupam; Mitra, Dhrubaditya; Pandit, Rahul

    2018-03-01

    We present an extensive numerical study of the time irreversibility of the dynamics of heavy inertial particles in three-dimensional, statistically homogeneous, and isotropic turbulent flows. We show that the probability density function (PDF) of the increment, W(τ), of a particle's energy over a time scale τ is non-Gaussian, and skewed toward negative values. This implies that, on average, particles gain energy over a period of time that is longer than the duration over which they lose energy. We call this slow gain and fast loss. We find that the third moment of W(τ) scales as τ^{3} for small values of τ. We show that the PDF of power-input p is negatively skewed too; we use this skewness Ir as a measure of the time irreversibility and we demonstrate that it increases sharply with the Stokes number St for small St; this increase slows down at St≃1. Furthermore, we obtain the PDFs of t^{+} and t^{-}, the times over which p has, respectively, positive or negative signs, i.e., the particle gains or loses energy. We obtain from these PDFs a direct and natural quantification of the slow gain and fast loss of the energy of the particles, because these PDFs possess exponential tails from which we infer the characteristic loss and gain times t_{loss} and t_{gain}, respectively, and we obtain t_{loss}} for all the cases we have considered. Finally, we show that the fast loss of energy occurs with greater probability in the strain-dominated region than in the vortical one; in contrast, the slow gain in the energy of the particles is equally likely in vortical or strain-dominated regions of the flow.

  14. [Plasma levels of insulin and leptin in patients with morbid obesity and anorexia nervosa after weight loss or gain, respectively].

    Science.gov (United States)

    Escobar, L; Freire, J M; Girón, J A; Vázquez, J M; Pajares, M; Ortego, J; Gavilán, I; Chover, A J; Carrasco, M; Epinosa, R; Marín, F; Aguilar, M

    2000-06-01

    patients after drastic weight loss; 3) in anorexic patients after weight gain; and that hyper- or normoinsulinemia do not seem to have any influence on the leptin changes caused by weight loss or gain.

  15. Strikes in the public sector in Denmark – assessing the economic gains and losses of collective action

    DEFF Research Database (Denmark)

    Scheuer, Steen; Ibsen, Flemming; Høgedahl, Laust Kristian

    2016-01-01

    and losses, ranging from a slightly positive result to a negative result from which it will take eight to ten years to recover. This is of great importance because the challenge facing public sector unions is different from that of their counterparts: private sector unions struggle with the owners of capital......This article looks at strikes by employees in the public sector, discusses the theoretical background to these conflicts and shows – based on a case study of three strikes in the Danish public sector – how different union strategies lead to very different outcomes in terms of economic gains......, while public sector unions trying to move up the wage hierarchy cannot expect much help from fellow public sector unions, often quite the reverse....

  16. Plasmon enhanced light amplification in metal–insulator–metal waveguides with gain

    International Nuclear Information System (INIS)

    Zhong, Xiao-Lan; Li, Zhi-Yuan

    2012-01-01

    In this paper we study the loss compensation and light amplification properties of metal–insulator–metal (MIM) waveguides that are doped with gain material in the dielectric core. An analytical approach based on Maxwell’s equations is developed to evaluate quantitatively the influence of the gain coefficient on the loss compensation and light amplification efficiencies of the waveguide under different values of the waveguide width and working wavelengths. The analytical results agree excellently with all-numerical calculations that directly solve Maxwell’s equations. The results show that the light amplification efficiency obeys a strict linear relationship with the gain coefficient, and MIM waveguides with narrower widths and under shorter wavelengths have better efficiencies. In addition, the MIM waveguides have higher light amplification efficiencies than usual dielectric waveguides, which suggests a very positive role of the plasmonic structure in enhancing the light amplification when gain is introduced. These loss and gain behaviors can be well explained by looking at the modal profile of each transport mode and the corresponding light energy confinement effect and slow light effect. (paper)

  17. Pendred syndrome (goitre and sensorineural hearing loss) maps to chromosome 7 in the region containing the nonsyndromic deafness gene DFNB4.

    Science.gov (United States)

    Coyle, B; Coffey, R; Armour, J A; Gausden, E; Hochberg, Z; Grossman, A; Britton, K; Pembrey, M; Reardon, W; Trembath, R

    1996-04-01

    Inherited causes account for about 50% of individuals presenting with childhood (prelingual) hearing loss, of which 70% are due to mutation in numerous single genes which impair auditory function alone (non-syndromic). The remainder are associated with other developmental anomalies termed syndromic deafness. Genes responsible for syndromic forms of hearing loss include the COL4A5 gene in Alport syndrome and the PAX3 and MITF genes in Waardenburg syndrome. Pendred syndrome is an autosomal recessive disorder associated with developmental abnormalities of the cochlea, sensorineural hearing loss and diffuse thyroid enlargement (goitre). Pendred syndrome is the most common syndromal form of deafness, yet the primary defect remains unknown. We have established a panel of 12 families with two or more affected individuals and used them to search for the location of the Pendred gene by linkage analysis. We excluded localization to four previously mapped nonsyndromic deafness loci but obtained conclusive evidence for linkage of the Pendred syndrome gene to microsatellite markers on chromosome 7q31 (D7S495 Zmax 7.32, Qmax = 0). This region contains a gene, DFNBL, for autosomal recessive non-syndromic sensorineural hearing loss. Multipoint analysis indicates that DFNB4 and Pendred syndrome co-localize to the same 5.5 centiMorgan (cM) interval flanked by D7S501 and D7S523. These data raise the possibility that Pendred syndrome is either allelic with DFNB4 or may represent an inherited contiguous gene disorder, not clinically manifest in the heterozygote.

  18. Social Health Insurance-Based Simultaneous Screening for 154 Mutations in 19 Deafness Genes Efficiently Identified Causative Mutations in Japanese Hearing Loss Patients.

    Directory of Open Access Journals (Sweden)

    Kentaro Mori

    Full Text Available Sensorineural hearing loss is one of the most common neurosensory disorders in humans. The incidence of SNHL is estimated to be 1 in 500-1000 newborns. In more than half of these patients, the hearing loss is associated with genetic causes. In Japan, genetic testing for the patients with SNHL using the Invader assay to screen for 46 mutations in 13 deafness genes was approved by the Ministry of Health, Labour and Welfare for inclusion in social health insurance coverage in 2012. Furthermore, from August 2015, this genetic testing has been expanded to screen for 154 mutations in 19 deafness genes using targeted genomic enrichment with massively parallel DNA sequencing combined with the Invader assay and TaqMan genotyping. For this study we analyzed 717 unrelated Japanese hearing loss patients. The total allele frequency of 154 mutations in 19 deafness genes was 32.64% (468/1434 and the total numbers of cases associated with at least one mutation was 44.07% (316/717. Among these, we were able to diagnose 212 (30% patients, indicating that the present screening could efficiently identify causative mutations in hearing loss patients. It is noteworthy that 27 patients (3.8% had coexistent multiple mutations in different genes. Five of these 27 patients (0.7%, 5/717 overall were diagnosed with genetic hearing loss affected by concomitant with responsible mutations in more than two different genes. For patients identified with multiple mutations in different genes, it is necessary to consider that several genes might have an impact on their phenotypes.

  19. Deletions in cox2 mRNA result in loss of splicing and RNA editing and gain of novel RNA editing sites.

    Directory of Open Access Journals (Sweden)

    Stefanie Grüttner

    Full Text Available As previously demonstrated, the maize cox2 RNA is fully edited in cauliflower mitochondria. Use of constructs with a deleted cox2 intron, however, led to a loss of RNA editing at almost all editing sites, with only a few sites still partially edited. Likewise, one deletion in exon 1 and three in exon 2 abolish RNA editing at all cox2 sites analyzed. Furthermore, intron splicing is abolished using these deletions. Mutation of a cytosine residue, which is normally edited and localized directly adjacent to the intron, to thymidine did not result in restoration of splicing, indicating that the loss of splicing was not due to loss of RNA editing. One deletion in exon 2 did not lead to loss of splicing. Instead, most editing sites were found to be edited, only three were not edited. Unexpectedly, we observed additional RNA editing events at new sites. Thus it appears that deletions in the cox2 RNA sequence can have a strong effect on RNA processing, leading to loss of splicing, loss of editing at all sites, or even to a gain of new editing sites. As these effects are not limited to the vicinity of the respective deletions, but appear to be widespread or even affect all editing sites, they may not be explained by the loss of PPR binding sites. Instead, it appears that several parts of the cox2 transcript are required for proper RNA processing. This indicates the roles of the RNA sequence and structural elements in the recognition of the editing sites.

  20. Genome evolution in an ancient bacteria-ant symbiosis: parallel gene loss among Blochmannia spanning the origin of the ant tribe Camponotini

    Directory of Open Access Journals (Sweden)

    Laura E. Williams

    2015-04-01

    Full Text Available Stable associations between bacterial endosymbionts and insect hosts provide opportunities to explore genome evolution in the context of established mutualisms and assess the roles of selection and genetic drift across host lineages and habitats. Blochmannia, obligate endosymbionts of ants of the tribe Camponotini, have coevolved with their ant hosts for ∼40 MY. To investigate early events in Blochmannia genome evolution across this ant host tribe, we sequenced Blochmannia from two divergent host lineages, Colobopsis obliquus and Polyrhachis turneri, and compared them with four published genomes from Blochmannia of Camponotus sensu stricto. Reconstructed gene content of the last common ancestor (LCA of these six Blochmannia genomes is reduced (690 protein coding genes, consistent with rapid gene loss soon after establishment of the symbiosis. Differential gene loss among Blochmannia lineages has affected cellular functions and metabolic pathways, including DNA replication and repair, vitamin biosynthesis and membrane proteins. Blochmannia of P. turneri (i.e., B. turneri encodes an intact DnaA chromosomal replication initiation protein, demonstrating that loss of dnaA was not essential for establishment of the symbiosis. Based on gene content, B. obliquus and B. turneri are unable to provision hosts with riboflavin. Of the six sequenced Blochmannia, B. obliquus is the earliest diverging lineage (i.e., the sister group of other Blochmannia sampled and encodes the fewest protein-coding genes and the most pseudogenes. We identified 55 genes involved in parallel gene loss, including glutamine synthetase, which may participate in nitrogen recycling. Pathways for biosynthesis of coenzyme A, terpenoids and riboflavin were lost in multiple lineages, suggesting relaxed selection on the pathway after inactivation of one component. Analysis of Illumina read datasets did not detect evidence of plasmids encoding missing functions, nor the presence of

  1. Fundamental Limitations to Gain Enhancement in Periodic Media and Waveguides

    DEFF Research Database (Denmark)

    Grgic, Jure; Ott, Johan Raunkjær; Wang, Fengwen

    2012-01-01

    A common strategy to compensate for losses in optical nanostructures is to add gain material in the system. By exploiting slow-light effects it is expected that the gain may be enhanced beyond its bulk value. Here we show that this route cannot be followed uncritically: inclusion of gain inevitably...

  2. Hereditary Hearing Loss.

    Science.gov (United States)

    Tran, LenhAnh P.; Grundfast, Kenneth M.

    1997-01-01

    This article discusses inheritance patterns in hearing loss, epidemiology, clues to genetic causes, locating genes that cause hereditary disorders, genes related to hearing loss disorders in individuals with Usher syndrome, Waardenburg syndrome, Treacher-Collins syndrome, Branchio-oto-renal and Pendred syndromes, and the significance of finding…

  3. Novel compound heterozygous mutations in MYO7A gene associated with autosomal recessive sensorineural hearing loss in a Chinese family.

    Science.gov (United States)

    Ma, Yalin; Xiao, Yun; Zhang, Fengguo; Han, Yuechen; Li, Jianfeng; Xu, Lei; Bai, Xiaohui; Wang, Haibo

    2016-04-01

    Mutations in MYO7A gene have been reported to be associated with Usher Syndrome type 1B (USH1B) and nonsyndromic hearing loss (DFNB2, DFNA11). Most mutations in MYO7A gene caused USH1B, whereas only a few reported mutations led to DFNB2 and DFNA11. The current study was designed to investigate the mutations among a Chinese family with autosomal recessive hearing loss. In this study, we present the clinical, genetic and molecular characteristics of a Chinese family. Targeted capture of 127 known deafness genes and next-generation sequencing were employed to study the genetic causes of two siblings in the Chinese family. Sanger sequencing was employed to examine those variant mutations in the members of this family and other ethnicity-matched controls. We identified the novel compound heterozygous mutant alleles of MYO7A gene: a novel missense mutation c.3671C>A (p.A1224D) and a reported insert mutation c.390_391insC (p.P131PfsX9). Variants were further confirmed by Sanger sequencing. These two compound heterozygous variants were co-segregated with autosomal recessive hearing loss phenotype. The gene mutation analysis and protein sequence alignment further supported that the novel compound heterozygous mutations were pathogenic. The novel compound heterozygous mutations (c.3671C>A and c.390_391insC) in MYO7A gene identified in this study were responsible for the autosomal recessive sensorineural hearing loss of this Chinese family. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Complete Chloroplast Genome of Pinus massoniana (Pinaceae): Gene Rearrangements, Loss of ndh Genes, and Short Inverted Repeats Contraction, Expansion.

    Science.gov (United States)

    Ni, ZhouXian; Ye, YouJu; Bai, Tiandao; Xu, Meng; Xu, Li-An

    2017-09-11

    The chloroplast genome (CPG) of Pinus massoniana belonging to the genus Pinus (Pinaceae), which is a primary source of turpentine, was sequenced and analyzed in terms of gene rearrangements, ndh genes loss, and the contraction and expansion of short inverted repeats (IRs). P. massoniana CPG has a typical quadripartite structure that includes large single copy (LSC) (65,563 bp), small single copy (SSC) (53,230 bp) and two IRs (IRa and IRb, 485 bp). The 108 unique genes were identified, including 73 protein-coding genes, 31 tRNAs, and 4 rRNAs. Most of the 81 simple sequence repeats (SSRs) identified in CPG were mononucleotides motifs of A/T types and located in non-coding regions. Comparisons with related species revealed an inversion (21,556 bp) in the LSC region; P. massoniana CPG lacks all 11 intact ndh genes (four ndh genes lost completely; the five remained truncated as pseudogenes; and the other two ndh genes remain as pseudogenes because of short insertions or deletions). A pair of short IRs was found instead of large IRs, and size variations among pine species were observed, which resulted from short insertions or deletions and non-synchronized variations between "IRa" and "IRb". The results of phylogenetic analyses based on whole CPG sequences of 16 conifers indicated that the whole CPG sequences could be used as a powerful tool in phylogenetic analyses.

  5. The neural basis of loss aversion in decision-making under risk.

    Science.gov (United States)

    Tom, Sabrina M; Fox, Craig R; Trepel, Christopher; Poldrack, Russell A

    2007-01-26

    People typically exhibit greater sensitivity to losses than to equivalent gains when making decisions. We investigated neural correlates of loss aversion while individuals decided whether to accept or reject gambles that offered a 50/50 chance of gaining or losing money. A broad set of areas (including midbrain dopaminergic regions and their targets) showed increasing activity as potential gains increased. Potential losses were represented by decreasing activity in several of these same gain-sensitive areas. Finally, individual differences in behavioral loss aversion were predicted by a measure of neural loss aversion in several regions, including the ventral striatum and prefrontal cortex.

  6. Electricity-price arbitrage with plug-in hybrid electric vehicle: Gain or loss?

    International Nuclear Information System (INIS)

    Shang, Duo; Sun, Guodong

    2016-01-01

    Customers, utilities, and society can gain many benefits from distributed energy resources (DERs), including plug-in hybrid electric vehicles (PHEVs). Using battery on PHEV to arbitrage electricity price is one of the potential benefits to PHEV owners. There is, however, disagreement on the magnitude of such profit. This study uses a stochastic optimization model to estimate the potential profit from electricity price arbitrage of two types of PHEVs (PHEV-10, and PHEV-40) under three scenarios with variant electricity tariff and PHEV owners over a five-year period. The simulation results indicate that under current market structure, even with significant improvement in battery technologies (e.g., higher efficiency, lower cost), the PHEV owners can't achieve a positive arbitrage profit. This finding implies that expected arbitrage profit solely is not a viable option to engage PHEVs larger adoption. Subsidy and combining PHEV arbitraging with alternative PHEV services are required. - Highlights: •A stochastic optimization model is proposed to assess the arbitrage value of plug-in hybrid electric vehicle (PHEV). •Under current market condition, PHEV owners lose money from conducting PHEV arbitrage if counting battery degradation cost. •PHEV owner loses more money at real time pricing (RTP) than at time of use (TOU) scheme. •Battery improvement will reduce but can't even the arbitrage loss. •Expected arbitrage profit is not a viable option to engage PHEVs in dispatching and in providing ancillary services.

  7. Upregulation of gene expression in reward-modulatory striatal opioid systems by sleep loss.

    Science.gov (United States)

    Baldo, Brian A; Hanlon, Erin C; Obermeyer, William; Bremer, Quentin; Paletz, Elliott; Benca, Ruth M

    2013-12-01

    Epidemiological studies have shown a link between sleep loss and the obesity 'epidemic,' and several observations indicate that sleep curtailment engenders positive energy balance via increased palatable-food 'snacking.' These effects suggest alterations in reward-modulatory brain systems. We explored the effects of 10 days of sleep deprivation in rats on the expression of striatal opioid peptide (OP) genes that subserve food motivation and hedonic reward, and compared effects with those seen in hypothalamic energy balance-regulatory systems. Sleep-deprived (Sleep-Dep) rats were compared with yoked forced-locomotion apparatus controls (App-Controls), food-restricted rats (Food-Restrict), and unmanipulated controls (Home-Cage). Detection of mRNA levels with in situ hybridization revealed a subregion-specific upregulation of striatal preproenkephalin and prodynorhin gene expression in the Sleep-Dep group relative to all other groups. Neuropeptide Y (NPY) gene expression in the hippocampal dentate gyrus and throughout neocortex was also robustly upregulated selectively in the Sleep-Dep group. In contrast, parallel gene expression changes were observed in the Sleep-Dep and Food-Restrict groups in hypothalamic energy-sensing systems (arcuate nucleus NPY was upregulated, and cocaine- and amphetamine-regulated transcript was downregulated), in alignment with leptin suppression in both groups. Together, these results reveal a novel set of sleep deprivation-induced transcriptional changes in reward-modulatory peptide systems, which are dissociable from the energy-balance perturbations of sleep loss or the potentially stressful effects of the forced-locomotion procedure. The recruitment of telencephalic food-reward systems may provide a feeding drive highly resistant to feedback control, which could engender obesity through the enhancement of palatable feeding.

  8. Acceptable losses: the debatable origins of loss aversion.

    Science.gov (United States)

    Yechiam, Eldad

    2018-04-16

    It is often claimed that negative events carry a larger weight than positive events. Loss aversion is the manifestation of this argument in monetary outcomes. In this review, we examine early studies of the utility function of gains and losses, and in particular the original evidence for loss aversion reported by Kahneman and Tversky (Econometrica  47:263-291, 1979). We suggest that loss aversion proponents have over-interpreted these findings. Specifically, the early studies of utility functions have shown that while very large losses are overweighted, smaller losses are often not. In addition, the findings of some of these studies have been systematically misrepresented to reflect loss aversion, though they did not find it. These findings shed light both on the inability of modern studies to reproduce loss aversion as well as a second literature arguing strongly for it.

  9. A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation

    DEFF Research Database (Denmark)

    Xia, Min; Jin, Qingfeng; Bendahhou, Saïd

    2005-01-01

    that KCNJ2 was associated with familial AF. Thirty Chinese AF kindreds were evaluated for mutations in KCNJ2 gene. A valine-to-isoleucine mutation at position 93 (V93I) of Kir2.1 was found in all affected members in one kindred. This valine and its flanking sequence is highly conserved in Kir2.1 proteins...... among different species. Functional analysis of the V93I mutant demonstrated a gain-of-function consequence on the Kir2.1 current. This effect is opposed to the loss-of-function effect of previously reported mutations in Andersen's syndrome. Kir2.1 V93I mutation may play a role in initiating and...

  10. Loss of microRNA-22 prevents high-fat diet induced dyslipidemia and increases energy expenditure without affecting cardiac hypertrophy.

    Science.gov (United States)

    Diniz, Gabriela Placoná; Huang, Zhan-Peng; Liu, Jianming; Chen, Jinghai; Ding, Jian; Fonseca, Renata Inzinna; Barreto-Chaves, Maria Luiza; Donato, Jose; Hu, Xiaoyun; Wang, Da-Zhi

    2017-12-15

    Obesity is associated with development of diverse diseases, including cardiovascular diseases and dyslipidemia. MiRNA-22 (miR-22) is a critical regulator of cardiac function and targets genes involved in metabolic processes. Previously, we generated miR-22 null mice and we showed that loss of miR-22 blunted cardiac hypertrophy induced by mechanohormornal stress. In the present study, we examined the role of miR-22 in the cardiac and metabolic alterations promoted by high-fat (HF) diet. We found that loss of miR-22 attenuated the gain of fat mass and prevented dyslipidemia induced by HF diet, although the body weight gain, or glucose intolerance and insulin resistance did not seem to be affected. Mechanistically, loss of miR-22 attenuated the increased expression of genes involved in lipogenesis and inflammation mediated by HF diet. Similarly, we found that miR-22 mediates metabolic alterations and inflammation induced by obesity in the liver. However, loss of miR-22 did not appear to alter HF diet induced cardiac hypertrophy or fibrosis in the heart. Our study therefore establishes miR-22 as an important regulator of dyslipidemia and suggests it may serve as a potential candidate in the treatment of dyslipidemia associated with obesity. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  11. Introducing Upfront Money Can Decrease Discounting in Intertemporal Choices with Losses.

    Science.gov (United States)

    Jiang, Cheng-Ming; Sun, Hong-Yue; Zheng, Sheng-Hua; Wang, Liang-Jun; Qin, Yu

    2016-01-01

    People generally tend to advance gains and postpone losses in intertemporal choice. Jiang et al. (2014) recently showed that adding upfront losses or gains to both smaller and sooner (SS) and larger and later (LL) rewards can decrease people's discounting. To account for this decrease, they proposed the salience hypothesis, which states that introducing upfront losses or gains makes the money dimension more salient than not, thus increasing people's preference for LL rewards. Considering that decreasing the discounting of delayed losses is imperative and that most previous studies have focused on intertemporal choices with gains, in the current paper we conducted two experiments and used hypothetical money outcomes to examine whether the effect of upfront money could be extended to intertemporal choices with losses. The results showed that when both SS and LL intertemporal losses were combined with an upfront loss or gain, people's discounting rate decreased and the preference for the SS option increased. This finding further supports the salience account.

  12. Active Microwave Metamaterials Incorporating Ideal Gain Devices

    Directory of Open Access Journals (Sweden)

    Hao Xin

    2010-12-01

    Full Text Available Incorporation of active devices/media such as transistors for microwave and gain media for optics may be very attractive for enabling desired low loss and broadband metamaterials. Such metamaterials can even have gain which may very well lead to new and exciting physical phenomena. We investigate microwave composite right/left-handed transmission lines (CRLH-TL incorporating ideal gain devices such as constant negative resistance. With realistic lumped element values, we have shown that the negative phase constant of this kind of transmission lines is maintained (i.e., left-handedness kept while gain can be obtained (negative attenuation constant of transmission line simultaneously. Possible implementation and challenging issues of the proposed active CRLH-TL are also discussed.

  13. Interventions to reduce weight gain in schizophrenia.

    Science.gov (United States)

    Faulkner, G; Cohn, T; Remington, G

    2007-01-24

    Weight gain is common for people with schizophrenia and this has serious implications for health and well being. To determine the effects of both pharmacological (excluding medication switching) and non pharmacological strategies for reducing or preventing weight gain in people with schizophrenia. We searched key databases and the Cochrane Schizophrenia Group's trials register (April 2006), reference sections within relevant papers, hand searched key journals, and contacted the first author of each relevant study and other experts to collect further information. We included all clinical randomised controlled trials comparing any pharmacological or non pharmacological intervention for weight gain (diet and exercise counselling) with standard care or other treatments for people with schizophrenia or schizophrenia-like illnesses. We reliably selected, quality assessed and extracted data from studies. As weight is a continuous outcome measurement, weighted mean differences (WMD) of the change from baseline were calculated. The primary outcome measure was weight loss. Twenty-three randomised controlled trials met the inclusion criteria for this review. Five trials assessed a cognitive/behavioural intervention and eighteen assessed a pharmacological adjunct. In terms of prevention, two cognitive/behavioural trials showed significant treatment effect (mean weight change) at end of treatment (n=104, 2 RCTs, WMD -3.38 kg CI -4.2 to -2.0). Pharmacological adjunct treatments were significant with a modest prevention of weight gain (n=274, 6 RCTs, WMD - 1.16 kg CI -1.9 to -0.4). In terms of treatments for weight loss, we found significantly greater weight reduction in the cognitive behavioural intervention group (n=129, 3 RCTs, WMD -1.69 kg CI -2.8 to -0.6) compared with standard care. Modest weight loss can be achieved with selective pharmacological and non pharmacological interventions. However, interpretation is limited by the small number of studies, small sample size

  14. Life after unsuccessful IVF treatment in an assisted reproduction unit: a qualitative analysis of gains through loss among Chinese persons in Hong Kong.

    Science.gov (United States)

    Lee, Geok Ling; Hui Choi, W H; Chan, Celia H Y; Chan, Cecilia L W; Ng, Ernest H Y

    2009-08-01

    Previous studies examining experiences of infertility focused mainly on the aspect of loss but neglected the possible gains realized through surviving the experience of infertility. The success rate of IVF remains relatively low, and we used the strengths perspective to examine adjustment after unsuccessful treatment. This study aims to provide an in-depth description of the gains perceived by Chinese men and women and how they re-constructed their lives after unsuccessful IVF treatment. Four couples and another six women who experienced unsuccessful IVF treatment were recruited from an assisted reproduction clinic. Data were collected through in-depth interviews, using a grounded theory constructivist approach. Of the 10 women and 4 men interviewed, 9 remained childless, 3 had adopted a child and 2 had conceived naturally. They reported gains on a personal level, interpersonal level and transpersonal level through surviving the experience of infertility. All, regardless of the eventual outcome, reported at least one form of personal gain: in personality or knowledge gain. Interpersonal gains were perceived in relationships with their spouses, children, parents, friends, colleagues and fellow IVF service users. More than half of them reported spiritual growth and a change in identity through integrating their experiences and offering help to others. Despite the small sample size, this study makes a significant contribution by suggesting that while negative feelings provoked by the failure to conceive should be acknowledged, people in this situation should also be enabled to consolidate their negative experiences of IVF constructively, helping them to move on with their lives.

  15. Finding new genes for non-syndromic hearing loss through an in silico prioritization study.

    Directory of Open Access Journals (Sweden)

    Matteo Accetturo

    Full Text Available At present, 51 genes are already known to be responsible for Non-Syndromic hereditary Hearing Loss (NSHL, but the knowledge of 121 NSHL-linked chromosomal regions brings to the hypothesis that a number of disease genes have still to be uncovered. To help scientists to find new NSHL genes, we built a gene-scoring system, integrating Gene Ontology, NCBI Gene and Map Viewer databases, which prioritizes the candidate genes according to their probability to cause NSHL. We defined a set of candidates and measured their functional similarity with respect to the disease gene set, computing a score ( S S M avg that relies on the assumption that functionally related genes might contribute to the same (disease phenotype. A Kolmogorov-Smirnov test, comparing the pair-wise distribution on the disease gene set with the distribution on the remaining human genes, provided a statistical assessment of this assumption. We found at a p-value 0.99. The twenty top-scored genes were finally examined to evaluate their possible involvement in NSHL. We found that half of them are known to be expressed in human inner ear or cochlea and are mainly involved in remodeling and organization of actin formation and maintenance of the cilia and the endocochlear potential. These findings strongly indicate that our metric was able to suggest excellent NSHL candidates to be screened in patients and controls for causative mutations.

  16. Gene dosage, expression, and ontology analysis identifies driver genes in the carcinogenesis and chemoradioresistance of cervical cancer.

    Directory of Open Access Journals (Sweden)

    Malin Lando

    2009-11-01

    Full Text Available Integrative analysis of gene dosage, expression, and ontology (GO data was performed to discover driver genes in the carcinogenesis and chemoradioresistance of cervical cancers. Gene dosage and expression profiles of 102 locally advanced cervical cancers were generated by microarray techniques. Fifty-two of these patients were also analyzed with the Illumina expression method to confirm the gene expression results. An independent cohort of 41 patients was used for validation of gene expressions associated with clinical outcome. Statistical analysis identified 29 recurrent gains and losses and 3 losses (on 3p, 13q, 21q associated with poor outcome after chemoradiotherapy. The intratumor heterogeneity, assessed from the gene dosage profiles, was low for these alterations, showing that they had emerged prior to many other alterations and probably were early events in carcinogenesis. Integration of the alterations with gene expression and GO data identified genes that were regulated by the alterations and revealed five biological processes that were significantly overrepresented among the affected genes: apoptosis, metabolism, macromolecule localization, translation, and transcription. Four genes on 3p (RYBP, GBE1 and 13q (FAM48A, MED4 correlated with outcome at both the gene dosage and expression level and were satisfactorily validated in the independent cohort. These integrated analyses yielded 57 candidate drivers of 24 genetic events, including novel loci responsible for chemoradioresistance. Further mapping of the connections among genetic events, drivers, and biological processes suggested that each individual event stimulates specific processes in carcinogenesis through the coordinated control of multiple genes. The present results may provide novel therapeutic opportunities of both early and advanced stage cervical cancers.

  17. Regulation of Nuclear Receptor Interacting Protein 1 (NRIP1) Gene Expression in Response to Weight Loss and Exercise in Humans

    DEFF Research Database (Denmark)

    De Marinis, Yang Z; Sun, Jiangming; Bompada, Pradeep

    2017-01-01

    Objective: Nuclear receptor interacting protein 1 (NRIP1) is an important energy regulator, but few studies have addressed its role in humans. This study investigated adipose tissue and skeletal muscle NRIP1 gene expression and serum levels in response to weight loss and exercise in humans. Methods...... network/module. Conclusions: NRIP1 gene expression and serum levels are strongly associated with metabolic states such as obesity, weight loss, different types of exercise, and peripheral tissue insulin resistance, potentially as a mediator of sedentary effects.......: In patients with obesity, adipose tissue NRIP1 mRNA expression increased during weight loss and weight maintenance and showed strong associations with metabolic markers and anthropometric parameters. Serum NRIP1 protein levels also increased after weight loss. In skeletal muscle, imposed rest increased NRIP1...

  18. 78 FR 54156 - Limitations on Duplication of Net Built-in Losses

    Science.gov (United States)

    2013-09-03

    ... it is not a transfer of net built-in loss property under section 362(e)(1); that gain recognized by... transferor distributes the stock received in the transaction and, in the distribution, no gain or loss was... the transaction. 3. Securities Received Without the Recognition of Gain or Loss Section 362(e)(2) is...

  19. [Application of MALDI-TOF-MS in gene testing for non-syndromic hearing loss].

    Science.gov (United States)

    Zeng, Yun; Jiang, Dan; Feng, Da-fei; Jin, Dong-dong; Wu, Xiao-hui; Ding, Yan-li; Zou, Jing

    2013-12-01

    To investigate the feasibility of Matrix-Assisted Laser Desorption-Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) , according to the genetic test of non-syndromic hearing loss (NSHL), and check using the direct sequencing. Peripheral blood was collected from 454 NSHL patients. DNA samples were extracted and 20 loci of the four common disease-causing genes were analysed by MALDI-TOF-MS, including GJB2 (35delG, 167delT, 176_191del16, 235delC, 299_300delAT ), GJB3 (538C→T, 547G→A), SLC26A4 (281C→T, 589G→A, IVS7-2A→G, 1174A→T, 1226G→A, 1229C→T, IVS15+5G→A, 1975G→C, 2027T→A, 2162C→T, 2168A→G), and mitochondrial 12S rRNA (1494C→T, 1555A→G). Direct sequencing was also used to analyse the aforementioned 20 loci in order to validate the accuracy of MALDI-TOF-MS. Among the 454 patients, 166 cases (36.56%) of disease-causing mutations were detected, which included 69 cases (21.15%) of GJB2 gene mutation, four cases (0.88%) of GJB3 gene mutation, 64 cases (14.10%) of SLC26A4 gene mutation, and three cases (0.66%) of mitochondrial 12S rRNA gene mutation. Moreover, the results obtained from direct sequencing and MALDI-TOF-MS were consistent, and the results showed that the two methods were consistent. The MALDI-TOF-MS detection method was designed based on the hearing loss-related mutation hotspots seen in the Chinese population, and it has a high detection rate for NSHL related mutations. In comparison to the conventional detection methods, MALDI-TOF-MS has the following advantages: more detection sites, greater coverage, accurate, high throughput and low cost. Therefore, this method is capable of satisfying the needs of clinical detection for hearing impairment and it is suitable for large-scale implementation.

  20. AUDIOME: a tiered exome sequencing-based comprehensive gene panel for the diagnosis of heterogeneous nonsyndromic sensorineural hearing loss.

    Science.gov (United States)

    Guan, Qiaoning; Balciuniene, Jorune; Cao, Kajia; Fan, Zhiqian; Biswas, Sawona; Wilkens, Alisha; Gallo, Daniel J; Bedoukian, Emma; Tarpinian, Jennifer; Jayaraman, Pushkala; Sarmady, Mahdi; Dulik, Matthew; Santani, Avni; Spinner, Nancy; Abou Tayoun, Ahmad N; Krantz, Ian D; Conlin, Laura K; Luo, Minjie

    2018-03-29

    PurposeHereditary hearing loss is highly heterogeneous. To keep up with rapidly emerging disease-causing genes, we developed the AUDIOME test for nonsyndromic hearing loss (NSHL) using an exome sequencing (ES) platform and targeted analysis for the curated genes.MethodsA tiered strategy was implemented for this test. Tier 1 includes combined Sanger and targeted deletion analyses of the two most common NSHL genes and two mitochondrial genes. Nondiagnostic tier 1 cases are subjected to ES and array followed by targeted analysis of the remaining AUDIOME genes.ResultsES resulted in good coverage of the selected genes with 98.24% of targeted bases at >15 ×. A fill-in strategy was developed for the poorly covered regions, which generally fell within GC-rich or highly homologous regions. Prospective testing of 33 patients with NSHL revealed a diagnosis in 11 (33%) and a possible diagnosis in 8 cases (24.2%). Among those, 10 individuals had variants in tier 1 genes. The ES data in the remaining nondiagnostic cases are readily available for further analysis.ConclusionThe tiered and ES-based test provides an efficient and cost-effective diagnostic strategy for NSHL, with the potential to reflex to full exome to identify causal changes outside of the AUDIOME test.Genetics in Medicine advance online publication, 29 March 2018; doi:10.1038/gim.2018.48.

  1. Listening to music in a risk-reward context: The roles of the temporoparietal junction and the orbitofrontal/insular cortices in reward-anticipation, reward-gain, and reward-loss.

    Science.gov (United States)

    Li, Chia-Wei; Chen, Jyh-Horng; Tsai, Chen-Gia

    2015-12-10

    Artificial rewards, such as visual arts and music, produce pleasurable feelings. Popular songs in the verse-chorus form provide a useful model for understanding the neural mechanisms underlying the processing of artificial rewards, because the chorus is usually the most rewarding element of a song. In this functional magnetic resonance imaging (fMRI) study, the stimuli were excerpts of 10 popular songs with a tensioned verse-to-chorus transition. We examined the neural correlates of three phases of reward processing: (1) reward-anticipation during the verse-to-chorus transition, (2) reward-gain during the first phrase of the chorus, and (3) reward-loss during the unexpected noise followed by the verse-to-chorus transition. Participants listened to these excerpts in a risk-reward context because the verse was followed by either the chorus or noise with equal probability. The results showed that reward-gain and reward-loss were associated with left- and right-biased temporoparietal junction activation, respectively. The bilateral temporoparietal junctions were active during reward-anticipation. Moreover, we observed left-biased lateral orbitofrontal activation during reward-anticipation, whereas the medial orbitofrontal cortex was activated during reward-gain. The findings are discussed in relation to the cognitive and emotional aspects of reward processing. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Co-regulation analysis of closely linked genes identifies a highly recurrent gain on chromosome 17q25.3 in prostate cancer

    International Nuclear Information System (INIS)

    Bermudo, Raquel; Martínez-A, Carlos; Ortiz, Ángel R; Fernández, Pedro L; Thomson, Timothy M; Abia, David; Ferrer, Berta; Nayach, Iracema; Benguria, Alberto; Zaballos, Ángel; Rey, Javier del; Miró, Rosa; Campo, Elías

    2008-01-01

    Transcriptional profiling of prostate cancer (PC) has unveiled new markers of neoplasia and allowed insights into mechanisms underlying this disease. Genomewide analyses have also identified new chromosomal abnormalities associated with PC. The combination of both classes of data for the same sample cohort might provide better criteria for identifying relevant factors involved in neoplasia. Here we describe transcriptional signatures identifying distinct normal and tumoral prostate tissue compartments, and the inference and demonstration of a new, highly recurrent copy number gain on chromosome 17q25.3. We have applied transcriptional profiling to tumoral and non-tumoral prostate samples with relatively homogeneous epithelial representations as well as pure stromal tissue from peripheral prostate and cultured cell lines, followed by quantitative RT-PCR validations and immunohistochemical analysis. In addition, we have performed in silico colocalization analysis of co-regulated genes and validation by fluorescent in situ hybridization (FISH). The transcriptomic analysis has allowed us to identify signatures corresponding to non-tumoral luminal and tumoral epithelium, basal epithelial cells, and prostate stromal tissue. In addition, in silico analysis of co-regulated expression of physically linked genes has allowed us to predict the occurrence of a copy number gain at chromosomal region 17q25.3. This computational inference was validated by fluorescent in situ hybridization, which showed gains in this region in over 65% of primary and metastatic tumoral samples. Our approach permits to directly link gene copy number variations with transcript co-regulation in association with neoplastic states. Therefore, transcriptomic studies of carefully selected samples can unveil new diagnostic markers and transcriptional signatures highly specific of PC, and lead to the discovery of novel genomic abnormalities that may provide additional insights into the causes and mechanisms

  3. CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23

    International Nuclear Information System (INIS)

    Michels, Evi; Speleman, Frank; Hoebeeck, Jasmien; De Preter, Katleen; Schramm, Alexander; Brichard, Bénédicte; De Paepe, Anne; Eggert, Angelika; Laureys, Geneviève; Vandesompele, Jo

    2008-01-01

    Recurrent loss of part of the long arm of chromosome 11 is a well established hallmark of a subtype of aggressive neuroblastomas. Despite intensive mapping efforts to localize the culprit 11q tumour suppressor gene, this search has been unsuccessful thus far as no sufficiently small critical region could be delineated for selection of candidate genes. To refine the critical region of 11q loss, the chromosome 11 status of 100 primary neuroblastoma tumours and 29 cell lines was analyzed using a BAC array containing a chromosome 11 tiling path. For the genes mapping within our refined region of loss, meta-analysis on published neuroblastoma mRNA gene expression datasets was performed for candidate gene selection. The DNA methylation status of the resulting candidate gene was determined using re-expression experiments by treatment of neuroblastoma cells with the demethylating agent 5-aza-2'-deoxycytidine and bisulphite sequencing. Two small critical regions of loss within 11q23 at chromosomal band 11q23.1-q23.2 (1.79 Mb) and 11q23.2-q23.3 (3.72 Mb) were identified. In a first step towards further selection of candidate neuroblastoma tumour suppressor genes, we performed a meta-analysis on published expression profiles of 692 neuroblastoma tumours. Integration of the resulting candidate gene list with expression data of neuroblastoma progenitor cells pinpointed CADM1 as a compelling candidate gene. Meta-analysis indicated that CADM1 expression has prognostic significance and differential expression for the gene was noted in unfavourable neuroblastoma versus normal neuroblasts. Methylation analysis provided no evidence for a two-hit mechanism in 11q deleted cell lines. Our study puts CADM1 forward as a strong candidate neuroblastoma suppressor gene. Further functional studies are warranted to elucidate the role of CADM1 in neuroblastoma development and to investigate the possibility of CADM1 haploinsufficiency in neuroblastoma

  4. 26 CFR 1.1233-1 - Gains and losses from short sales.

    Science.gov (United States)

    2010-04-01

    ... makes a short sale of shares of stock and covers the short sale by purchasing and delivering shares...) Treatment of losses. The third rule, which is set forth in section 1233(d), is applicable whenever property... loss attributable to so much of the property sold short as exceeds in quantity the substantially...

  5. Quantifying the impact on navigation performance in visually impaired: Auditory information loss versus information gain enabled through electronic travel aids.

    Directory of Open Access Journals (Sweden)

    Alex Kreilinger

    Full Text Available This study's purpose was to analyze and quantify the impact of auditory information loss versus information gain provided by electronic travel aids (ETAs on navigation performance in people with low vision. Navigation performance of ten subjects (age: 54.9±11.2 years with visual acuities >1.0 LogMAR was assessed via the Graz Mobility Test (GMT. Subjects passed through a maze in three different modalities: 'Normal' with visual and auditory information available, 'Auditory Information Loss' with artificially reduced hearing (leaving only visual information, and 'ETA' with a vibrating ETA based on ultrasonic waves, thereby facilitating visual, auditory, and tactile information. Main performance measures comprised passage time and number of contacts. Additionally, head tracking was used to relate head movements to motion direction. When comparing 'Auditory Information Loss' to 'Normal', subjects needed significantly more time (p<0.001, made more contacts (p<0.001, had higher relative viewing angles (p = 0.002, and a higher percentage of orientation losses (p = 0.011. The only significant difference when comparing 'ETA' to 'Normal' was a reduced number of contacts (p<0.001. Our study provides objective, quantifiable measures of the impact of reduced hearing on the navigation performance in low vision subjects. Significant effects of 'Auditory Information Loss' were found for all measures; for example, passage time increased by 17.4%. These findings show that low vision subjects rely on auditory information for navigation. In contrast, the impact of the ETA was not significant but further analysis of head movements revealed two different coping strategies: half of the subjects used the ETA to increase speed, whereas the other half aimed at avoiding contacts.

  6. Progressive hearing loss and degeneration of hair cell stereocilia in taperin gene knockout mice

    International Nuclear Information System (INIS)

    Chen, Mo; Wang, Qin; Zhu, Gang-Hua; Hu, Peng; Zhou, Yuan; Wang, Tian; Lai, Ruo-Sha; Xiao, Zi-An; Xie, Ding-Hua

    2016-01-01

    The TPRN gene encodes taperin, which is prominently present at the taper region of hair cell stereocilia. Mutations in TPRN have been reported to cause autosomal recessive nonsyndromic deafness 79(DFNB 79). To investigate the role of taperin in pathogenesis of hearing loss, we generated TPRN knockout mice using TALEN technique. Sanger sequencing confirmed an 11 bp deletion at nucleotide 177–187 in exon 1 of TPRN, which results in a truncated form of taperin protein. Heterozygous TPRN +/− mice showed apparently normal auditory phenotypes to their wide-type (WT) littermates. Homozygous TPRN −/− mice exhibited progressive sensorineural hearing loss as reflected by auditory brainstem response to both click and tone burst stimuli at postnatal days 15 (P15), 30 (P30), and 60 (P60). Alex Fluor-594 phalloidin labeling showed no obvious difference in hair cell numbers in the cochlea between TPRN −/− mice and WT mice under light microscope. However, scanning electronic microscopy revealed progressive degeneration of inner hair cell stereocilia, from apparently normal at postnatal days 3 (P3) to scattered absence at P15 and further to substantial loss at P30. The outer hair cell stereocilia also showed progressive degeneration, though much less severe, Collectively, we conclude that taperin plays an important role in maintenance of hair cell stereocilia. Establishment of TPRN knockout mice enables further investigation into the function of this gene. - Highlights: • TPRN −/− mice were generated using TALEN technique. • TPRN −/− mice presented progressive hearing loss. • WT and TPRN −/− mice showed no difference in hair cell numbers. • TPRN −/− mice showed progressive degeneration of hair cell stereocilia.

  7. Amygdala damage eliminates monetary loss aversion.

    Science.gov (United States)

    De Martino, Benedetto; Camerer, Colin F; Adolphs, Ralph

    2010-02-23

    Losses are a possibility in many risky decisions, and organisms have evolved mechanisms to evaluate and avoid them. Laboratory and field evidence suggests that people often avoid risks with losses even when they might earn a substantially larger gain, a behavioral preference termed "loss aversion." The cautionary brake on behavior known to rely on the amygdala is a plausible candidate mechanism for loss aversion, yet evidence for this idea has so far not been found. We studied two rare individuals with focal bilateral amygdala lesions using a series of experimental economics tasks. To measure individual sensitivity to financial losses we asked participants to play a variety of monetary gambles with possible gains and losses. Although both participants retained a normal ability to respond to changes in the gambles' expected value and risk, they showed a dramatic reduction in loss aversion compared to matched controls. The findings suggest that the amygdala plays a key role in generating loss aversion by inhibiting actions with potentially deleterious outcomes.

  8. The retinoblastoma gene is frequently altered leading to loss of expression in primary breast tumours.

    Science.gov (United States)

    Varley, J M; Armour, J; Swallow, J E; Jeffreys, A J; Ponder, B A; T'Ang, A; Fung, Y K; Brammar, W J; Walker, R A

    1989-06-01

    We have analysed the organisation of the retinoblastoma (RB1) gene in 77 primary breast carcinomas, in metastatic tissue derived from 16 of those primary tumours, and in a variety of benign breast lesions. Expression of RB1 was also assessed in most samples by immunohistochemical detection of the RB1 protein in tissue sections. Structural abnormalities to RB1 were detected in DNA from 15/77 (19%) of primary breast carcinomas examined. Where DNA was available from metastatic tissue derived from such primary tumours, the same aberration could be detected. No alterations were seen in benign breast lesions. 16/56 (29%) of tumours examined for expression by immunohistochemical methods showed a proportion of tumour cells to be completely negative for the RB1 protein. All tumours in which a structural alteration to RB1 was detected had a proportion of negative cells, except for one case where all cells were positive. Several primary tumour samples were identified where there was no detectable structural change to the gene, but there was loss of expression in some tumour cells. The data presented here demonstrate that changes to the RB1 gene leading to loss of expression of both alleles are frequent in primary human breast tumours.

  9. Molecular diagnostics for congenital hearing loss including 15 deafness genes using a next generation sequencing platform

    Directory of Open Access Journals (Sweden)

    De Keulenaer Sarah

    2012-05-01

    Full Text Available Abstract Background Hereditary hearing loss (HL can originate from mutations in one of many genes involved in the complex process of hearing. Identification of the genetic defects in patients is currently labor intensive and expensive. While screening with Sanger sequencing for GJB2 mutations is common, this is not the case for the other known deafness genes (> 60. Next generation sequencing technology (NGS has the potential to be much more cost efficient. Published methods mainly use hybridization based target enrichment procedures that are time saving and efficient, but lead to loss in sensitivity. In this study we used a semi-automated PCR amplification and NGS in order to combine high sensitivity, speed and cost efficiency. Results In this proof of concept study, we screened 15 autosomal recessive deafness genes in 5 patients with congenital genetic deafness. 646 specific primer pairs for all exons and most of the UTR of the 15 selected genes were designed using primerXL. Using patient specific identifiers, all amplicons were pooled and analyzed using the Roche 454 NGS technology. Three of these patients are members of families in which a region of interest has previously been characterized by linkage studies. In these, we were able to identify two new mutations in CDH23 and OTOF. For another patient, the etiology of deafness was unclear, and no causal mutation was found. In a fifth patient, included as a positive control, we could confirm a known mutation in TMC1. Conclusions We have developed an assay that holds great promise as a tool for screening patients with familial autosomal recessive nonsyndromal hearing loss (ARNSHL. For the first time, an efficient, reliable and cost effective genetic test, based on PCR enrichment, for newborns with undiagnosed deafness is available.

  10. Global loss of bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism.

    Directory of Open Access Journals (Sweden)

    David John Kennaway

    Full Text Available The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood. Here we investigated adipocyte function and the metabolic status of mice with a global loss of the core clock gene Bmal1 fed either a normal or a high fat diet (22% by weight. Bmal1 null mice aged 2 months were killed across 24 hours and plasma adiponectin and leptin, and adipose tissue expression of Adipoq, Lep, Retn and Nampt mRNA measured. Glucose, insulin and pyruvate tolerance tests were conducted and the expression of liver glycolytic and gluconeogenic enzyme mRNA determined. Bmal1 null mice displayed a pattern of increased plasma adiponectin and plasma leptin concentrations on both control and high fat diets. Bmal1 null male and female mice displayed increased adiposity (1.8 fold and 2.3 fold respectively on the normal diet, but the high fat diet did not exaggerate these differences. Despite normal glucose and insulin tolerance, Bmal1 null mice had increased production of glucose from pyruvate, implying increased liver gluconeogenesis. The Bmal1 null mice had arrhythmic clock gene expression in epigonadal fat and liver, and loss of rhythmic transcription of a range of metabolic genes. Furthermore, the expression of epigonadal fat Adipoq, Retn, Nampt, AdipoR1 and AdipoR2 and liver Pfkfb3 mRNA were down-regulated. These results show for the first time that global loss of Bmal1, and the consequent arrhythmicity, results in compensatory changes in adipokines involved in the cellular control of glucose metabolism.

  11. Selector genes display tumor cooperation and inhibition in Drosophila epithelium in a developmental context-dependent manner

    Directory of Open Access Journals (Sweden)

    Ram Prakash Gupta

    2017-11-01

    Full Text Available During animal development, selector genes determine identities of body segments and those of individual organs. Selector genes are also misexpressed in cancers, although their contributions to tumor progression per se remain poorly understood. Using a model of cooperative tumorigenesis, we show that gain of selector genes results in tumor cooperation, but in only select developmental domains of the wing, haltere and eye-antennal imaginal discs of Drosophila larva. Thus, the field selector, Eyeless (Ey, and the segment selector, Ultrabithorax (Ubx, readily cooperate to bring about neoplastic transformation of cells displaying somatic loss of the tumor suppressor, Lgl, but in only those developmental domains that express the homeo-box protein, Homothorax (Hth, and/or the Zinc-finger protein, Teashirt (Tsh. In non-Hth/Tsh-expressing domains of these imaginal discs, however, gain of Ey in lgl− somatic clones induces neoplastic transformation in the distal wing disc and haltere, but not in the eye imaginal disc. Likewise, gain of Ubx in lgl− somatic clones induces transformation in the eye imaginal disc but not in its endogenous domain, namely, the haltere imaginal disc. Our results reveal that selector genes could behave as tumor drivers or inhibitors depending on the tissue contexts of their gains.

  12. 26 CFR 2.1-12 - Election as to nonrecognition of gain.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Election as to nonrecognition of gain. 2.1-12... TAX (CONTINUED) MARITIME CONSTRUCTION RESERVE FUND § 2.1-12 Election as to nonrecognition of gain. (a) Election requirements. As a prerequisite to the nonrecognition of gain on the sale or loss of a vessel (or...

  13. PAX3 gene deletion detected by microarray analysis in a girl with hearing loss.

    Science.gov (United States)

    Drozniewska, Malgorzata; Haus, Olga

    2014-01-01

    Deletions of the PAX3 gene have been rarely reported in the literature. Mutations of this gene are a common cause of Waardenburg syndrome type 1 and 3. We report a 16 year old female presenting hearing loss and normal intellectual development, without major features of Waardenburg syndrome type 1, and without family history of the syndrome. Her phenotype, however, overlaps with features of craniofacial-deafness-hand syndrome. Microarray analysis showed ~862 kb de novo deletion at 2q36.1 including PAX3. The above findings suggest that the rearrangement found in our patient appeared de novo and with high probability is a cause of her phenotype.

  14. Energy performance of windows based on the net energy gain

    DEFF Research Database (Denmark)

    Svendsen, Svend; Kragh, Jesper; Laustsen, Jacob Birck

    2005-01-01

    The paper presents a new method to set up energy performance requirements and energy classes for windows of all dimensions and configurations. The net energy gain of windows is the solar gain minus the heat loss integrated over the heating season. The net energy gain can be calculated for one...... be expressed as a function of two parameters representing the energy performance and two parameters representing the geometry of the window. The two energy performance parameters are the net energy gain per area of the glazing unit and the sum of the heat losses through the frame and the assembly per length...... of the frame. The two geometry numbers are the area of the glazing unit relative to the window area and the length of the frame profiles relative to the window area. Requirements and classes for the energy performance of the window can be given by assigning values to the two energy performance parameters...

  15. Three gangliogliomas: results of GTG-banding, SKY, genome-wide high resolution SNP-array, gene expression and review of the literature.

    Science.gov (United States)

    Xu, Li-Xin; Holland, Heidrun; Kirsten, Holger; Ahnert, Peter; Krupp, Wolfgang; Bauer, Manfred; Schober, Ralf; Mueller, Wolf; Fritzsch, Dominik; Meixensberger, Jürgen; Koschny, Ronald

    2015-04-01

    According to the World Health Organization gangliogliomas are classified as well-differentiated and slowly growing neuroepithelial tumors, composed of neoplastic mature ganglion and glial cells. It is the most frequent tumor entity observed in patients with long-term epilepsy. Comprehensive cytogenetic and molecular cytogenetic data including high-resolution genomic profiling (single nucleotide polymorphism (SNP)-array) of gangliogliomas are scarce but necessary for a better oncological understanding of this tumor entity. For a detailed characterization at the single cell and cell population levels, we analyzed genomic alterations of three gangliogliomas using trypsin-Giemsa banding (GTG-banding) and by spectral karyotyping (SKY) in combination with SNP-array and gene expression array experiments. By GTG and SKY, we could confirm frequently detected chromosomal aberrations (losses within chromosomes 10, 13 and 22; gains within chromosomes 5, 7, 8 and 12), and identify so far unknown genetic aberrations like the unbalanced non-reciprocal translocation t(1;18)(q21;q21). Interestingly, we report on the second so far detected ganglioglioma with ring chromosome 1. Analyses of SNP-array data from two of the tumors and respective germline DNA (peripheral blood) identified few small gains and losses and a number of copy-neutral regions with loss of heterozygosity (LOH) in germline and in tumor tissue. In comparison to germline DNA, tumor tissues did not show substantial regions with significant loss or gain or with newly developed LOH. Gene expression analyses of tumor-specific genes revealed similarities in the profile of the analyzed samples regarding different relevant pathways. Taken together, we describe overlapping but also distinct and novel genetic aberrations of three gangliogliomas. © 2014 Japanese Society of Neuropathology.

  16. Interventions to reduce weight gain in schizophrenia

    Science.gov (United States)

    Faulkner, Guy; Cohn, Tony; Remington, Gary

    2014-01-01

    Background Weight gain is common for people with schizophrenia and this has serious implications for health and well being. Objectives To determine the effects of both pharmacological (excluding medication switching) and non pharmacological strategies for reducing or preventing weight gain in people with schizophrenia. Search methods We searched key databases and the Cochrane Schizophrenia Group’s trials register (April 2006), reference sections within relevant papers, hand searched key journals, and contacted the first author of each relevant study and other experts to collect further information. Selection criteria We included all clinical randomised controlled trials comparing any pharmacological or non pharmacological intervention for weight gain (diet and exercise counselling) with standard care or other treatments for people with schizophrenia or schizophrenia-like illnesses. Data collection and analysis We reliably selected, quality assessed and extracted data from studies. As weight is a continuous outcome measurement, weighted mean differences (WMD) of the change from baseline were calculated. The primary outcome measure was weight loss. Main results Twenty-three randomised controlled trials met the inclusion criteria for this review. Five trials assessed a cognitive/behavioural intervention and eighteen assessed a pharmacological adjunct. In terms of prevention, two cognitive/behavioural trials showed significant treatment effect (mean weight change) at end of treatment (n=104, 2 RCTs, WMD −3.38 kg CI −4.2 to −2.0). Pharmacological adjunct treatments were significant with a modest prevention of weight gain (n=274, 6 RCTs, WMD − 1.16 kg CI −1.9 to −0.4). In terms of treatments for weight loss, we found significantly greater weight reduction in the cognitive behavioural intervention group (n=129, 3 RCTs, WMD −1.69 kg CI −2.8 to −0.6) compared with standard care. Authors’ conclusions Modest weight loss can be achieved with selective

  17. Gains or Losses of Ultratrace Elements in Polyethylene Containers

    DEFF Research Database (Denmark)

    Heydorn, Kaj; Damsgaard, Else

    1982-01-01

    The extent of elimination of losses and reduction of blank values in ultratrace elemental analysis can only be ascertained by comprehensive investigations for each element separately. Different, and partially conflicting precautions are found to be needed in the determination of manganese, copper......, selenium, and mercury by neutron-activation analysis when polyethylene irradiation containers are used....

  18. The association between gestational weight gain and risk of stillbirth: a population-based cohort study.

    Science.gov (United States)

    Yao, Ruofan; Park, Bo Y; Foster, Sarah E; Caughey, Aaron B

    2017-10-01

    To estimate the risk of stillbirth associated with excessive and inadequate weight gain during pregnancy. Retrospective cohort study using the Texas vital records database between 2006 and 2011, with 2,230,310 births (5502 stillbirths) was included for analysis. Pregnancies were categorized as adequate weight gain, excessive weight gain, inadequate weight gain, or weight loss based on the Institute of Medicine 2009 recommendations. Hazard ratios (HRs) for stillbirth were estimated for each gestational weight-gain stratum using adequate weight gain as the comparison group. The analysis was performed separately for each body mass index (BMI) class. Both inadequate weight gain and weight loss were associated with an increased risk of stillbirth for all BMI classes except the morbidly obese group. Highest risk was seen in weight-loss groups after 36 completed weeks (normal weight: HR = 18.85 [8.25-43.09]; overweight: HR = 5.87 [2.99-11.55]; obese: HR = 3.44 [2.34-5.05]). Weight loss was associated with reduced stillbirth risk in morbidly obese women between 24 and 28 weeks (HR = 0.56 [0.34-0.95]). Excess weight gain was associated with an increased risk of stillbirth among obese and morbidly obese women, with highest risk after 36 completed weeks (obese: HR = 2.00 [1.55-2.58]; morbidly obese: HR = 3.16 [2.17-4.62]). In contrast, excess weight gain was associated with reduced risk of stillbirth in normal-weight women between 24 and 28 weeks (HR = 0.57 [0.44-0.70]) and in overweight women between 29 and 33 weeks (HR = 0.62 [0.45-0.85]). Analysis for the underweight group was limited by sample size. Both excessive weight gain and inadequate weight gain were not associated with stillbirth in this group. Stillbirth risk increased with inadequate weight gain and weight loss in all BMI classes except the morbidly obese group, where weight demonstrated a protective effect. Conversely, excessive weight gain was associated with higher risk of stillbirth among

  19. Optical properties of nanowire metamaterials with gain

    DEFF Research Database (Denmark)

    Isidio de Lima, Joaquim Junior; Adam, Jost; Rego, Davi

    2016-01-01

    The transmittance, reflectance and absorption of a nanowire metamaterial with optical gain are numerically simulated and investigated. It is assumed that the metamaterial is represented by aligned silver nanowires embedded into a semiconductor matrix, made of either silicon or gallium phosphide....... The gain in the matrix is modeled by adding a negative imaginary part to the dielectric function of the semiconductor. It is found that the optical coefficients of the metamaterial depend on the gain magnitude in a non-trivial way: they can both increase and decrease with gain depending on the lattice...... constant of the metamaterial. This peculiar behavior is explained by the field redistribution between the lossy metal nanowires and the amplifying matrix material. These findings are significant for a proper design of nanowire metamaterials with low optical losses for diverse applications....

  20. RANGER-DTL 2.0: Rigorous Reconstruction of Gene-Family Evolution by Duplication, Transfer, and Loss.

    Science.gov (United States)

    Bansal, Mukul S; Kellis, Manolis; Kordi, Misagh; Kundu, Soumya

    2018-04-24

    RANGER-DTL 2.0 is a software program for inferring gene family evolution using Duplication-Transfer-Loss reconciliation. This new software is highly scalable and easy to use, and offers many new features not currently available in any other reconciliation program. RANGER-DTL 2.0 has a particular focus on reconciliation accuracy and can account for many sources of reconciliation uncertainty including uncertain gene tree rooting, gene tree topological uncertainty, multiple optimal reconciliations, and alternative event cost assignments. RANGER-DTL 2.0 is open-source and written in C ++ and Python. Pre-compiled executables, source code (open-source under GNU GPL), and a detailed manual are freely available from http://compbio.engr.uconn.edu/software/RANGER-DTL/. mukul.bansal@uconn.edu.

  1. Genetic factors as predictors of weight gain in young adult Dutch men and women

    NARCIS (Netherlands)

    Rossum, van C.T.M.; Hoebee, B.; Seidell, J.C.; Bouchard, C.; Baak, van M.A.; Groot, de C.P.G.M.; Chagnon, M.; Graaf, de C.; Saris, W.H.M.

    2002-01-01

    OBJECTIVE: To investigate the association between DNA polymorphisms in several candidate genes for obesity and weight gain. Polymorphisms in these genes may contribute to weight gain through effects on energy intake, energy expenditure or adipogenesis. DESIGN AND METHODS: From two large cohorts in

  2. Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn H; Knop, Filip K; Ishøy, Pelle L

    2012-01-01

    between schizophrenia and overweight patients. DISCUSSION: Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogues used in the treatment of type 2 diabetes are associated with significant and sustained weight loss...... are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes...... in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogues are discussed. CONCLUSIONS: We propose that adjunctive treatment with GLP-1 analogues may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies...

  3. Corona helps curb losses

    Energy Technology Data Exchange (ETDEWEB)

    Laasonen, M.; Lahtinen, M.; Lustre, L.

    1996-11-01

    The greatest power losses in electricity transmission arise through a phenomenon called load losses. Corona losses caused by the surface discharge of electricity also constitute a considerable cost item. IVS, the nationwide network company, is investigating corona- induced losses, and has also commissioned similar research from IVO International, the Technical Research Centre of Finland (VTT) and from Tampere University of Technology. The research work strives to gain more in-depth knowledge on the phenomenon of frosting and its impact on corona losses. The correct prediction of frost helps reduce corona losses, while also cutting costs considerably. (orig.)

  4. The evolution of pepsinogen C genes in vertebrates: duplication, loss and functional diversification.

    Directory of Open Access Journals (Sweden)

    Luís Filipe Costa Castro

    Full Text Available BACKGROUND: Aspartic proteases comprise a large group of enzymes involved in peptide proteolysis. This collection includes prominent enzymes globally categorized as pepsins, which are derived from pepsinogen precursors. Pepsins are involved in gastric digestion, a hallmark of vertebrate physiology. An important member among the pepsinogens is pepsinogen C (Pgc. A particular aspect of Pgc is its apparent single copy status, which contrasts with the numerous gene copies found for example in pepsinogen A (Pga. Although gene sequences with similarity to Pgc have been described in some vertebrate groups, no exhaustive evolutionary framework has been considered so far. METHODOLOGY/PRINCIPAL FINDINGS: By combining phylogenetics and genomic analysis, we find an unexpected Pgc diversity in the vertebrate sub-phylum. We were able to reconstruct gene duplication timings relative to the divergence of major vertebrate clades. Before tetrapod divergence, a single Pgc gene tandemly expanded to produce two gene lineages (Pgbc and Pgc2. These have been differentially retained in various classes. Accordingly, we find Pgc2 in sauropsids, amphibians and marsupials, but not in eutherian mammals. Pgbc was retained in amphibians, but duplicated in the ancestor of amniotes giving rise to Pgb and Pgc1. The latter was retained in mammals and probably in reptiles and marsupials but not in birds. Pgb was kept in all of the amniote clade with independent episodes of loss in some mammalian species. Lineage specific expansions of Pgc2 and Pgbc have also occurred in marsupials and amphibians respectively. We find that teleost and tetrapod Pgc genes reside in distinct genomic regions hinting at a possible translocation. CONCLUSIONS: We conclude that the repertoire of Pgc genes is larger than previously reported, and that tandem duplications have modelled the history of Pgc genes. We hypothesize that gene expansion lead to functional divergence in tetrapods, coincident with the

  5. Optimal portfolio choice under loss aversion

    NARCIS (Netherlands)

    A.B. Berkelaar (Arjan); R.R.P. Kouwenberg (Roy)

    2000-01-01

    textabstractProspect theory and loss aversion play a dominant role in behavioral finance. In this paper we derive closed-form solutions for optimal portfolio choice under loss aversion. When confronted with gains a loss averse investor behaves similar to a portfolio insurer. When confronted with

  6. Almost all antipsychotics result in weight gain: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Maarten Bak

    Full Text Available INTRODUCTION: Antipsychotics (AP induce weight gain. However, reviews and meta-analyses generally are restricted to second generation antipsychotics (SGA and do not stratify for duration of AP use. It is hypothesised that patients gain more weight if duration of AP use is longer. METHOD: A meta-analysis was conducted of clinical trials of AP that reported weight change. Outcome measures were body weight change, change in BMI and clinically relevant weight change (7% weight gain or loss. Duration of AP-use was stratified as follows: ≤6 weeks, 6-16 weeks, 16-38 weeks and >38 weeks. Forest plots stratified by AP as well as by duration of use were generated and results were summarised in figures. RESULTS: 307 articles met inclusion criteria. The majority were AP switch studies. Almost all AP showed a degree of weight gain after prolonged use, except for amisulpride, aripiprazole and ziprasidone, for which prolonged exposure resulted in negligible weight change. The level of weight gain per AP varied from discrete to severe. Contrary to expectations, switch of AP did not result in weight loss for amisulpride, aripiprazole or ziprasidone. In AP-naive patients, weight gain was much more pronounced for all AP. CONCLUSION: Given prolonged exposure, virtually all AP are associated with weight gain. The rational of switching AP to achieve weight reduction may be overrated. In AP-naive patients, weight gain is more pronounced.

  7. Insights gained from the reverse engineering of gene networks in keloid fibroblasts

    Directory of Open Access Journals (Sweden)

    Phan Toan

    2011-05-01

    Full Text Available Abstract Background Keloids are protrusive claw-like scars that have a propensity to recur even after surgery, and its molecular etiology remains elusive. The goal of reverse engineering is to infer gene networks from observational data, thus providing insight into the inner workings of a cell. However, most attempts at modeling biological networks have been done using simulated data. This study aims to highlight some of the issues involved in working with experimental data, and at the same time gain some insights into the transcriptional regulatory mechanism present in keloid fibroblasts. Methods Microarray data from our previous study was combined with microarray data obtained from the literature as well as new microarray data generated by our group. For the physical approach, we used the fREDUCE algorithm for correlating expression values to binding motifs. For the influence approach, we compared the Bayesian algorithm BANJO with the information theoretic method ARACNE in terms of performance in recovering known influence networks obtained from the KEGG database. In addition, we also compared the performance of different normalization methods as well as different types of gene networks. Results Using the physical approach, we found consensus sequences that were active in the keloid condition, as well as some sequences that were responsive to steroids, a commonly used treatment for keloids. From the influence approach, we found that BANJO was better at recovering the gene networks compared to ARACNE and that transcriptional networks were better suited for network recovery compared to cytokine-receptor interaction networks and intracellular signaling networks. We also found that the NFKB transcriptional network that was inferred from normal fibroblast data was more accurate compared to that inferred from keloid data, suggesting a more robust network in the keloid condition. Conclusions Consensus sequences that were found from this study are

  8. Allelic variants of melanocortin 3 receptor gene (MC3R) and weight loss in obesity

    DEFF Research Database (Denmark)

    L. Santos, José; De la Cruz, Rolando; Holst, Claus

    2011-01-01

    receptor gene (MC3R) have been associated with childhood obesity, higher BMI Z-score and elevated body fat percentage compared to non-carriers. The aim of this study is to assess the association in adults between allelic variants of MC3R with weight loss induced by energy-restricted diets.......The melanocortin system plays an important role in energy homeostasis. Mice genetically deficient in the melanocortin-3 receptor gene have a normal body weight with increased body fat, mild hypophagia compared to wild-type mice. In humans, Thr6Lys and Val81Ile variants of the melanocortin-3...

  9. Data for occupancy internal heat gain calculation in main building categories

    Directory of Open Access Journals (Sweden)

    Kaiser Ahmed

    2017-12-01

    Full Text Available Heat losses from occupant body by means of convection, radiation, vapor, and sweat are essential data for indoor climate and energy simulations. Heat losses depend on the metabolic activity and body surface area. Higher variations of body surface area of occupants are observed in day care centers, kinder gardens and schools compared to other building categories (Tables 2 and 3 and these variations need to be accounted, otherwise in these building categories heat gains, CO2 and humidity generation are overestimated. Indoor temperature, humidity level, air velocity, and clothing insulation have significant influences on dry and total heat losses from occupant body leading to typical values for summer and winter. The data presented in this article are related to the research article entitled Occupancy schedules for energy simulation in new prEN16798-1 and ISO/FDIS 17772-1 standards (Ahmed et al., 2017 [1]. Keywords: Body surface area, Metabolic rate, Dry heat loss, Total heat loss, Internal heat gain

  10. Variation in extracellular matrix genes is associated with weight regain after weight loss in a sex-specific manner

    DEFF Research Database (Denmark)

    Roumans, Nadia J T; Vink, Roel G; Gielen, Marij

    2015-01-01

    The extracellular matrix (ECM) of adipocytes is important for body weight regulation. Here, we investigated whether genetic variation in ECM-related genes is associated with weight regain among participants of the European DiOGenes study. Overweight and obese subjects (n = 469, 310 females, 159 m.......40-5.63). Concluding, variants of ECM genes are associated with weight regain after weight loss in a sex-specific manner....

  11. Anyalysis of Msx1 and Msx2 Transactivation Function in the Context of the Heat Shock 70 (Hspa1b) Gene Promoter

    OpenAIRE

    Zhuang, Fengfeng; Nguyen, Manuel P.; Shuler, Charles; Liu, Yi-Hsin

    2009-01-01

    Previous studies have shown that Msx proteins control gene transcription predominantly through repression mechanisms. However, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression require functional Msx proteins. To date, investigations into the mechanisms of Msx-dependent trans-activation have been hindered by the lack of a responsive promoter. Here, we demonstrated the usefulness of the mouse Hspa1b promoter in...

  12. Ion Channel Genes and Epilepsy: Functional Alteration, Pathogenic Potential, and Mechanism of Epilepsy.

    Science.gov (United States)

    Wei, Feng; Yan, Li-Min; Su, Tao; He, Na; Lin, Zhi-Jian; Wang, Jie; Shi, Yi-Wu; Yi, Yong-Hong; Liao, Wei-Ping

    2017-08-01

    Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsy-associated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations (funotypes), and phenotypes of these mutations. Eleven genes featured loss-of-function mutations and six had gain-of-function mutations. Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.

  13. Loss-of-function of neuroplasticity-related genes confers risk for human neurodevelopmental disorders.

    Science.gov (United States)

    Smith, Milo R; Glicksberg, Benjamin S; Li, Li; Chen, Rong; Morishita, Hirofumi; Dudley, Joel T

    2018-01-01

    High and increasing prevalence of neurodevelopmental disorders place enormous personal and economic burdens on society. Given the growing realization that the roots of neurodevelopmental disorders often lie in early childhood, there is an urgent need to identify childhood risk factors. Neurodevelopment is marked by periods of heightened experience-dependent neuroplasticity wherein neural circuitry is optimized by the environment. If these critical periods are disrupted, development of normal brain function can be permanently altered, leading to neurodevelopmental disorders. Here, we aim to systematically identify human variants in neuroplasticity-related genes that confer risk for neurodevelopmental disorders. Historically, this knowledge has been limited by a lack of techniques to identify genes related to neurodevelopmental plasticity in a high-throughput manner and a lack of methods to systematically identify mutations in these genes that confer risk for neurodevelopmental disorders. Using an integrative genomics approach, we determined loss-of-function (LOF) variants in putative plasticity genes, identified from transcriptional profiles of brain from mice with elevated plasticity, that were associated with neurodevelopmental disorders. From five shared differentially expressed genes found in two mouse models of juvenile-like elevated plasticity (juvenile wild-type or adult Lynx1-/- relative to adult wild-type) that were also genotyped in the Mount Sinai BioMe Biobank we identified multiple associations between LOF genes and increased risk for neurodevelopmental disorders across 10,510 patients linked to the Mount Sinai Electronic Medical Records (EMR), including epilepsy and schizophrenia. This work demonstrates a novel approach to identify neurodevelopmental risk genes and points toward a promising avenue to discover new drug targets to address the unmet therapeutic needs of neurodevelopmental disease.

  14. Missense Mutation in the USH2A Gene: Association with Recessive Retinitis Pigmentosa without Hearing Loss

    OpenAIRE

    Rivolta, Carlo; Sweklo, Elizabeth A.; Berson, Eliot L.; Dryja, Thaddeus P.

    2000-01-01

    Microdeletions Glu767(1-bp del), Thr967(1-bp del), and Leu1446(2-bp del) in the human USH2A gene have been reported to cause Usher syndrome type II, a disorder characterized by retinitis pigmentosa (RP) and mild-to-severe hearing loss. Each of these three frameshift mutations is predicted to lead to an unstable mRNA transcript that, if translated, would result in a truncated protein lacking the carboxy terminus. Here, we report Cys759Phe, a novel missense mutation in this gene that changes an...

  15. Gene loss, adaptive evolution and the co-evolution of plumage coloration genes with opsins in birds.

    Science.gov (United States)

    Borges, Rui; Khan, Imran; Johnson, Warren E; Gilbert, M Thomas P; Zhang, Guojie; Jarvis, Erich D; O'Brien, Stephen J; Antunes, Agostinho

    2015-10-06

    The wide range of complex photic systems observed in birds exemplifies one of their key evolutionary adaptions, a well-developed visual system. However, genomic approaches have yet to be used to disentangle the evolutionary mechanisms that govern evolution of avian visual systems. We performed comparative genomic analyses across 48 avian genomes that span extant bird phylogenetic diversity to assess evolutionary changes in the 17 representatives of the opsin gene family and five plumage coloration genes. Our analyses suggest modern birds have maintained a repertoire of up to 15 opsins. Synteny analyses indicate that PARA and PARIE pineal opsins were lost, probably in conjunction with the degeneration of the parietal organ. Eleven of the 15 avian opsins evolved in a non-neutral pattern, confirming the adaptive importance of vision in birds. Visual conopsins sw1, sw2 and lw evolved under negative selection, while the dim-light RH1 photopigment diversified. The evolutionary patterns of sw1 and of violet/ultraviolet sensitivity in birds suggest that avian ancestors had violet-sensitive vision. Additionally, we demonstrate an adaptive association between the RH2 opsin and the MC1R plumage color gene, suggesting that plumage coloration has been photic mediated. At the intra-avian level we observed some unique adaptive patterns. For example, barn owl showed early signs of pseudogenization in RH2, perhaps in response to nocturnal behavior, and penguins had amino acid deletions in RH2 sites responsible for the red shift and retinal binding. These patterns in the barn owl and penguins were convergent with adaptive strategies in nocturnal and aquatic mammals, respectively. We conclude that birds have evolved diverse opsin adaptations through gene loss, adaptive selection and coevolution with plumage coloration, and that differentiated selective patterns at the species level suggest novel photic pressures to influence evolutionary patterns of more-recent lineages.

  16. Age, Loss Minimization, and the Role of Probability for Decision-Making.

    Science.gov (United States)

    Best, Ryan; Freund, Alexandra M

    2018-04-05

    Older adults are stereotypically considered to be risk averse compared to younger age groups, although meta-analyses on age and the influence of gain/loss framing on risky choices have not found empirical evidence for age differences in risk-taking. The current study extends the investigation of age differences in risk preference by including analyses on the effect of the probability of a risky option on choices in gain versus loss situations. Participants (n = 130 adults aged 19-80 years) chose between a certain option and a risky option of varying probability in gain- and loss-framed gambles with actual monetary outcomes. Only younger adults displayed an overall framing effect. Younger and older adults responded differently to probability fluctuations depending on the framing condition. Older adults were more likely to choose the risky option as the likelihood of avoiding a larger loss increased and as the likelihood of a larger gain decreased. Younger adults responded with the opposite pattern: they were more likely to choose the risky option as the likelihood of a larger gain increased and as the likelihood of avoiding a (slightly) larger loss decreased. Results suggest that older adults are more willing to select a risky option when it increases the likelihood that larger losses be avoided, whereas younger adults are more willing to select a risky option when it allows for slightly larger gains. This finding supports expectations based on theoretical accounts of goal orientation shifting away from securing gains in younger adulthood towards maintenance and avoiding losses in older adulthood. Findings are also discussed in respect to the affective enhancement perspective and socioemotional selectivity theory. © 2018 S. Karger AG, Basel.

  17. Global alteration in gene expression profiles of deciduas from women with idiopathic recurrent pregnancy loss.

    Science.gov (United States)

    Krieg, S A; Fan, X; Hong, Y; Sang, Q-X; Giaccia, A; Westphal, L M; Lathi, R B; Krieg, A J; Nayak, N R

    2012-09-01

    Recurrent pregnancy loss (RPL) occurs in ∼5% of women. However, the etiology is still poorly understood. Defects in decidualization of the endometrium during early pregnancy contribute to several pregnancy complications, such as pre-eclampsia and intrauterine growth restriction (IUGR), and are believed to be important in the pathogenesis of idiopathic RPL. We performed microarray analysis to identify gene expression alterations in the deciduas of idiopathic RPL patients. Control patients had one antecedent term delivery, but were undergoing dilation and curettage for current aneuploid miscarriage. Gene expression differences were evaluated using both pathway and gene ontology (GO) analysis. Selected genes were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A total of 155 genes were found to be significantly dysregulated in the deciduas of RPL patients (>2-fold change, P genes up-regulated and 133 genes down-regulated. GO analysis linked a large percentage of genes to discrete biological functions, including immune response (23%), cell signaling (18%) and cell invasion (17.1%), and pathway analysis revealed consistent changes in both the interleukin 1 (IL-1) and IL-8 pathways. All genes in the IL-8 pathway were up-regulated while genes in the IL-1 pathway were down-regulated. Although both pathways can promote inflammation, IL-1 pathway activity is important for normal implantation. Additionally, genes known to be critical for degradation of the extracellular matrix, including matrix metalloproteinase 26 and serine peptidase inhibitor Kazal-type 1, were also highly up-regulated. In this first microarray approach to decidual gene expression in RPL patients, our data suggest that dysregulation of genes associated with cell invasion and immunity may contribute significantly to idiopathic recurrent miscarriage.

  18. 38 CFR 4.112 - Weight loss.

    Science.gov (United States)

    2010-07-01

    .... The term “inability to gain weight” means that there has been substantial weight loss with inability... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Weight loss. 4.112... DISABILITIES Disability Ratings The Digestive System § 4.112 Weight loss. For purposes of evaluating conditions...

  19. Thinking like a trader selectively reduces individuals' loss aversion.

    Science.gov (United States)

    Sokol-Hessner, Peter; Hsu, Ming; Curley, Nina G; Delgado, Mauricio R; Camerer, Colin F; Phelps, Elizabeth A

    2009-03-31

    Research on emotion regulation has focused upon observers' ability to regulate their emotional reaction to stimuli such as affective pictures, but many other aspects of our affective experience are also potentially amenable to intentional cognitive regulation. In the domain of decision-making, recent work has demonstrated a role for emotions in choice, although such work has generally remained agnostic about the specific role of emotion. Combining psychologically-derived cognitive strategies, physiological measurements of arousal, and an economic model of behavior, this study examined changes in choices (specifically, loss aversion) and physiological correlates of behavior as the result of an intentional cognitive regulation strategy. Participants were on average more aroused per dollar to losses relative to gains, as measured with skin conductance response, and the difference in arousal to losses versus gains correlated with behavioral loss aversion across subjects. These results suggest a specific role for arousal responses in loss aversion. Most importantly, the intentional cognitive regulation strategy, which emphasized "perspective-taking," uniquely reduced both behavioral loss aversion and arousal to losses relative to gains, largely by influencing arousal to losses. Our results confirm previous research demonstrating loss aversion while providing new evidence characterizing individual differences and arousal correlates and illustrating the effectiveness of intentional regulation strategies in reducing loss aversion both behaviorally and physiologically.

  20. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies.

    Science.gov (United States)

    Platt, Adam; Morten, John; Ji, Qunsheng; Elvin, Paul; Womack, Chris; Su, Xinying; Donald, Emma; Gray, Neil; Read, Jessica; Bigley, Graham; Blockley, Laura; Cresswell, Carl; Dale, Angela; Davies, Amanda; Zhang, Tianwei; Fan, Shuqiong; Fu, Haihua; Gladwin, Amanda; Harrod, Grace; Stevens, James; Williams, Victoria; Ye, Qingqing; Zheng, Li; de Boer, Richard; Herbst, Roy S; Lee, Jin-Soo; Vasselli, James

    2015-03-23

    To determine the prevalence of RET rearrangement genes, RET copy number gains and expression in tumor samples from four Phase III non-small-cell lung cancer (NSCLC) trials of vandetanib, a selective inhibitor of VEGFR, RET and EGFR signaling, and to determine any association with outcome to vandetanib treatment. Archival tumor samples from the ZODIAC ( NCT00312377 , vandetanib ± docetaxel), ZEAL ( NCT00418886 , vandetanib ± pemetrexed), ZEPHYR ( NCT00404924 , vandetanib vs placebo) and ZEST ( NCT00364351 , vandetanib vs erlotinib) studies were evaluated by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in 944 and 1102 patients. The prevalence of RET rearrangements by FISH was 0.7% (95% CI 0.3-1.5%) among patients with a known result. Seven tumor samples were positive for RET rearrangements (vandetanib, n = 3; comparator, n = 4). 2.8% (n = 26) of samples had RET amplification (innumerable RET clusters, or ≥7 copies in > 10% of tumor cells), 8.1% (n = 76) had low RET gene copy number gain (4-6 copies in ≥40% of tumor cells) and 8.3% (n = 92) were RET expression positive (signal intensity ++ or +++ in >10% of tumor cells). Of RET-rearrangement-positive patients, none had an objective response in the vandetanib arm and one patient responded in the comparator arm. Radiologic evidence of tumor shrinkage was observed in two patients treated with vandetanib and one treated with comparator drug. The objective response rate was similar in the vandetanib and comparator arms for patients positive for RET copy number gains or RET protein expression. We have identified prevalence for three RET biomarkers in a population predominated by non-Asians and smokers. RET rearrangement prevalence was lower than previously reported. We found no evidence of a differential benefit for efficacy by IHC and RET gene copy number gains. The low prevalence of RET rearrangements (0.7%) prevents firm conclusions regarding association of vandetanib treatment with

  1. Utilizing wideband AMC structures for high-gain inkjet-printed antennas on lossy paper substrate

    KAUST Repository

    Cook, Benjamin Stassen

    2013-01-01

    Significant gain and bandwidth improvement of inkjet-printed antennas with integrated artificial magnetic conductor (AMC) is achieved by utilizing wideband ground-backed frequency selective surfaces (FSSs) to overcome the high losses of organic substrates such as paper. A microstrip-fed monopole mounted on an artificial magnetic conductor is demonstrated to improve the gain by 5 dB over previous works and exhibit much wider impedance bandwidth while maintaining a thin antenna profile and a 20% electrical size reduction. The effect of AMC bandwidth on substrate losses and the gain reduction caused by finite AMC array effects are investigated in an effort to produce high-gain, miniaturized, low-cost wearable and structure mount antennas. © 2013 IEEE.

  2. Changes in job strain and subsequent weight gain

    DEFF Research Database (Denmark)

    Vesterlund, Gitte Kingo; Keller, Amélie Cléo; Heitmann, Berit Lilienthal

    2018-01-01

    in 1999 between those who were rarely v. sometimes v. often busy in 1993 (P=0·03), with the largest weight gain in individuals with sustained high busyness in both years. Loss of influence between 1993 and 1999 was associated with larger subsequent weight gain than sustained high influence (P=0......Objective: Obesity as well as job strain is increasing, and job strain might contribute to weight gain. The objective of the current study was to examine associations between longitudinal alterations in the components of job strain and subsequent weight gain. Design: The study was designed...... as a prospective cohort study with three questionnaire surveys enabling measurement of job-strain alterations over 6 years and subsequent measurements of weight gain after further 10 years of follow-up. ANCOVA and trend analyses were conducted. Job demands were measured as job busyness and speed, and control...

  3. Immunohistochemical loss of 5-hydroxymethylcytosine expression in acute myeloid leukaemia: relationship to somatic gene mutations affecting epigenetic pathways.

    Science.gov (United States)

    Magotra, Minoti; Sakhdari, Ali; Lee, Paul J; Tomaszewicz, Keith; Dresser, Karen; Hutchinson, Lloyd M; Woda, Bruce A; Chen, Benjamin J

    2016-12-01

    Genes affecting epigenetic pathways are frequently mutated in myeloid malignancies, including acute myeloid leukaemia (AML). The genes encoding TET2, IDH1 and IDH2 are among the most commonly mutated genes, and cause defective conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5hmC), impairing demethylation of DNA, and presumably serving as driver mutations in leukaemogenesis. The aim of this study was to correlate 5hmC immunohistochemical loss with the mutation status of genes involved in epigenetic pathways in AML. Immunohistochemical staining with an anti-5hmC antibody was performed on 41 decalcified, formalin-fixed paraffin-embedded (FFPE) bone marrow biopsies from patients with AML. Archived DNA was subjected to next-generation sequencing for analysis of a panel of genes, including TET2, IDH1, IDH2, WT1 and DNMT3A. TET2, IDH1, IDH2, WT1 and DNMT3A mutations were found in 46% (19/41) of the cases. Ten of 15 cases (67%) with TET2, IDH1, IDH2 or WT1 mutations showed deficient 5hmC staining, whereas nine of 26 cases (35%) without a mutation in these genes showed loss of 5hmC. It is of note that all four cases with TET2 mutations showed deficient 5hmC staining. Overall, somatic mutations in TET2, IDH1, IDH2, WT1 and DNMT3A were common in our cohort of AML cases. Immunohistochemical staining for 5hmC was lost in the majority of cases harbouring mutations in these genes, reflecting the proposed relationship between dysfunctional epigenetic pathways and leukaemogenesis. © 2016 John Wiley & Sons Ltd.

  4. Predicting losing and gaining river reaches in lowland New Zealand based on a statistical methodology

    Science.gov (United States)

    Yang, Jing; Zammit, Christian; Dudley, Bruce

    2017-04-01

    The phenomenon of losing and gaining in rivers normally takes place in lowland where often there are various, sometimes conflicting uses for water resources, e.g., agriculture, industry, recreation, and maintenance of ecosystem function. To better support water allocation decisions, it is crucial to understand the location and seasonal dynamics of these losses and gains. We present a statistical methodology to predict losing and gaining river reaches in New Zealand based on 1) information surveys with surface water and groundwater experts from regional government, 2) A collection of river/watershed characteristics, including climate, soil and hydrogeologic information, and 3) the random forests technique. The surveys on losing and gaining reaches were conducted face-to-face at 16 New Zealand regional government authorities, and climate, soil, river geometry, and hydrogeologic data from various sources were collected and compiled to represent river/watershed characteristics. The random forests technique was used to build up the statistical relationship between river reach status (gain and loss) and river/watershed characteristics, and then to predict for river reaches at Strahler order one without prior losing and gaining information. Results show that the model has a classification error of around 10% for "gain" and "loss". The results will assist further research, and water allocation decisions in lowland New Zealand.

  5. The influence of loss aversion on mountain bikers' behavioral intentions.

    Science.gov (United States)

    Purrington, Andrew; Zinn, Harry

    2011-09-01

    Public involvement in management decision making has received increased attention from researchers in recent years. These studies, however, have rarely considered differences in behavior resulting from gains and losses, despite ample evidence that individuals' behavior is not the same across situations. Individuals are often more sensitive to losses than gains, which research suggests is related to ownership (real or perceived) of the item lost. We present evidence from a within-subjects quasi-experimental design to test whether mountain bikers' reported intentions differ between gain based and loss based conditions. These data were analyzed using a multi-step repeated measures analysis of variance and repeated measures analysis of covariance. The results suggest that losses are more powerful than gains in motivating public engagement in management decision making. Further, the type of action was also shown to influence behavioral intentions. Additional analyses provide support to the claim that, centrality, used as a proximate measure of ownership, moderates the contextual effects on behavioral intentions. Thus, loss aversion, moderated by ownership, is a plausible explanation of stakeholder involvement.

  6. Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women

    OpenAIRE

    Saliba,Louise F.; Reis,Rodrigo S.; Brownson,Ross C.; Hino,Adriano A.; Tureck,Luciane V.; Valko,Cheryl; Souza,Ricardo L.R. de; Furtado-Alle,Lupe

    2014-01-01

    The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713), ADRB3 (Trp64Arg, rs4994) and GHRL (Leu72Met, rs696217) polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109). The body mass index (BMI) was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (...

  7. Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting | Office of Cancer Genomics

    Science.gov (United States)

    The CRISPR/Cas9 system enables genome editing and somatic cell genetic screens in mammalian cells. We performed genome-scale loss-of-function screens in 33 cancer cell lines to identify genes essential for proliferation/survival and found a strong correlation between increased gene copy number and decreased cell viability after genome editing. Within regions of copy-number gain, CRISPR/Cas9 targeting of both expressed and unexpressed genes, as well as intergenic loci, led to significantly decreased cell proliferation through induction of a G2 cell-cycle arrest.

  8. Sensitivity of the brain to loss aversion during risky gambles.

    Science.gov (United States)

    Dreher, Jean-Claude

    2007-07-01

    Little is known about the neural systems that subserve human loss aversion. A recent neuroimaging study by Tom, Poldrack and colleagues reports that this pattern of behaviour is directly tied to the greater sensitivity of the brain to potential losses compared with potential gains and uncovers a brain network whose activity increases with potential gains and decreases with potential losses. These results challenge the common view that loss aversion engages a distinct emotion-related brain network (e.g. amygdala and insula).

  9. Comparison of effects of p53 null and gain-of-function mutations on salivary tumors in MMTV-Hras transgenic mice.

    Directory of Open Access Journals (Sweden)

    Dadi Jiang

    Full Text Available p53 is an important tumor suppressor gene which is mutated in ~50% of all human cancers. Some of these mutants appear to have acquired novel functions beyond merely losing wild-type functions. To investigate these gain-of-function effects in vivo, we generated mice of three different genotypes: MMTV-Hras/p53(+/+, MMTV-Hras/p53(-/-, and MMTV-Hras/p53R172H/R172H. Salivary tumors from these mice were characterized with regard to age of tumor onset, tumor growth rates, cell cycle distribution, apoptotic levels, tumor histopathology, as well as response to doxorubicin treatment. Microarray analysis was also performed to profile gene expression. The MMTV-Hras/p53(-/- and MMTV-Hras/p53R172H/R172H mice displayed similar properties with regard to age of tumor onset, tumor growth rates, tumor histopathology, and response to doxorubicin, while both groups were clearly distinct from the MMTV-Hras/p53(+/+ mice by these measurements. In addition, the gene expression profiles of the MMTV-Hras/p53(-/- and MMTV-Hras/p53(R172H/R172H tumors were tightly clustered, and clearly distinct from the profiles of the MMTV-Hras/p53(+/+ tumors. Only a small group of genes showing differential expression between the MMTV-Hras/p53(-/- and MMTV-Hras/p53(R172H/R172H tumors, that did not appear to be regulated by wild-type p53, were identified. Taken together, these results indicate that in this MMTV-Hras-driven salivary tumor model, the major effect of the p53 R172H mutant is due to the loss of wild-type p53 function, with little or no gain-of-function effect on tumorigenesis, which may be explained by the tissue- and tumor type-specific properties of this gain-of-function mutant of p53.

  10. Selection and Neutral Mutations Drive Pervasive Mutability Losses in Long-Lived Anti-HIV B-Cell Lineages

    Science.gov (United States)

    Vieira, Marcos C; Zinder, Daniel; Cobey, Sarah

    2018-01-01

    Abstract High-affinity antibodies arise within weeks of infection from the evolution of B-cell receptors under selection to improve antigen recognition. This rapid adaptation is enabled by the distribution of highly mutable “hotspot” motifs in B-cell receptor genes. High mutability in antigen-binding regions (complementarity determining regions [CDRs]) creates variation in binding affinity, whereas low mutability in structurally important regions (framework regions [FRs]) may reduce the frequency of destabilizing mutations. During the response, loss of mutational hotspots and changes in their distribution across CDRs and FRs are predicted to compromise the adaptability of B-cell receptors, yet the contributions of different mechanisms to gains and losses of hotspots remain unclear. We reconstructed changes in anti-HIV B-cell receptor sequences and show that mutability losses were ∼56% more frequent than gains in both CDRs and FRs, with the higher relative mutability of CDRs maintained throughout the response. At least 21% of the total mutability loss was caused by synonymous mutations. However, nonsynonymous substitutions caused most (79%) of the mutability loss in CDRs. Because CDRs also show strong positive selection, this result suggests that selection for mutations that increase binding affinity contributed to loss of mutability in antigen-binding regions. Although recurrent adaptation to evolving viruses could indirectly select for high mutation rates, we found no evidence of indirect selection to increase or retain hotspots. Our results suggest mutability losses are intrinsic to both the neutral and adaptive evolution of B-cell populations and might constrain their adaptation to rapidly evolving pathogens such as HIV and influenza. PMID:29688540

  11. A comprehensive dataset of genes with a loss-of-function mutant phenotype in Arabidopsis.

    Science.gov (United States)

    Lloyd, Johnny; Meinke, David

    2012-03-01

    Despite the widespread use of Arabidopsis (Arabidopsis thaliana) as a model plant, a curated dataset of Arabidopsis genes with mutant phenotypes remains to be established. A preliminary list published nine years ago in Plant Physiology is outdated, and genome-wide phenotype information remains difficult to obtain. We describe here a comprehensive dataset of 2,400 genes with a loss-of-function mutant phenotype in Arabidopsis. Phenotype descriptions were gathered primarily from manual curation of the scientific literature. Genes were placed into prioritized groups (essential, morphological, cellular-biochemical, and conditional) based on the documented phenotypes of putative knockout alleles. Phenotype classes (e.g. vegetative, reproductive, and timing, for the morphological group) and subsets (e.g. flowering time, senescence, circadian rhythms, and miscellaneous, for the timing class) were also established. Gene identities were classified as confirmed (through molecular complementation or multiple alleles) or not confirmed. Relationships between mutant phenotype and protein function, genetic redundancy, protein connectivity, and subcellular protein localization were explored. A complementary dataset of 401 genes that exhibit a mutant phenotype only when disrupted in combination with a putative paralog was also compiled. The importance of these genes in confirming functional redundancy and enhancing the value of single gene datasets is discussed. With further input and curation from the Arabidopsis community, these datasets should help to address a variety of important biological questions, provide a foundation for exploring the relationship between genotype and phenotype in angiosperms, enhance the utility of Arabidopsis as a reference plant, and facilitate comparative studies with model genetic organisms.

  12. An evaluation of seepage gains and losses in Indian Creek Reservoir, Ada County, Idaho, April 2010–November 2011

    Science.gov (United States)

    Williams, Marshall L.; Etheridge, Alexandra B.

    2013-01-01

    of flow. The reservoir tended to gain water from seepage of groundwater in the early spring months (March–May), while seepage losses to groundwater from the reservoir occurred in the drier months (June–October). Net monthly seepage rates, as computed by the water-budget method, varied greatly. Reservoir gains from seepage ranged from 0.2 to 59.4 acre-feet per month, while reservoir losses to seepage ranged from 1.6 and 26.8 acre-feet per month. An analysis of seepage meter estimates and segmented-Darcy estimates qualitatively supports the seasonal patterns in seepage provided by the water-budget calculations, except that they tended to be much smaller in magnitude. This suggests that actual seepage might be smaller than those estimates made by the water-budget method. Although the results of all three methods indicate that there is some water loss from the reservoir to groundwater, the seepage losses may be due to rewetting of unsaturated near-shore soils, possible replenishment of a perched aquifer, or both, rather than through percolation to the local aquifer that lies 130 feet below the reservoir. A lithologic log from an adjacent well indicates the existence of a clay lithology that is well correlated to the original reservoir’s base elevation. If the clay lithologic unit extends beneath the reservoir basin underlying the fine-grain reservoir bed sediments, the clay layer should act as an effective barrier to reservoir seepage to the local aquifer, which would explain the low seepage loss estimates calculated in this study.

  13. MTOR signaling and ubiquitin-proteosome gene expression in the preservation of fat free mass following high protein, calorie restricted weight loss

    Directory of Open Access Journals (Sweden)

    McIver Cassandra M

    2012-09-01

    Full Text Available Abstract Caloric restriction is one of the most efficient ways to promote weight loss and is known to activate protective metabolic pathways. Frequently reported with weight loss is the undesirable consequence of fat free (lean muscle mass loss. Weight loss diets with increased dietary protein intake are popular and may provide additional benefits through preservation of fat free mass compared to a standard protein, high carbohydrate diet. However, the precise mechanism by which a high protein diet may mitigate dietary weight loss induced reductions in fat free mass has not been fully elucidated. Maintenance of fat free mass is dependent upon nutrient stimulation of protein synthesis via the mTOR complex, although during caloric restriction a decrease (atrophy in skeletal muscle may be driven by a homeostatic shift favouring protein catabolism. This review evaluates the relationship between the macronutrient composition of calorie restricted diets and weight loss using metabolic indicators. Specifically we evaluate the effect of increased dietary protein intake and caloric restricted diets on gene expression in skeletal muscle, particularly focusing on biosynthesis, degradation and the expression of genes in the ubiquitin-proteosome (UPP and mTOR signaling pathways, including MuRF-1, MAFbx/atrogin-1, mTORC1, and S6K1.

  14. Injured workers' perception of loss and gain in the return to work process.

    Science.gov (United States)

    Lai, Hon Sun; Szeto, Grace Py; Chan, Chetwyn Ch

    2017-01-01

    When a worker is injured at work, he has to face a tough decision-making process about when and how to return to work (RTW). This study tests how the prospect theory can be applied to influence the injured workers' perceptions about this important choice. One hundred forty-one injured workers were presented with wage- and pain-related information in four different message framing (negatively or positively) and precision (smaller or larger number) conditions. After exposure to the specific combination of this wage and pain information, the participants were asked to express intentions to RTW in terms of perceived chance, confidence, and anticipated sick leave duration. When asked to predict their RTW outcome, 101 participants (72.3%) responded favorably, whereas only 40 (27.7%) indicated an expectation for staying on sick leave. The present results did not show significant differences in the participants' responses to the positively and negatively framed information about wage and pain. However, it was noted that the control group that was presented with positive framing for both "wage" and "pain" information showed higher scores in expectation and confidence for RTW, whereas the Ambivalent Group that had both negative messages showed lower scores. Seventy-nine participants who had ≥60% perceived improvement in condition were selected for further analysis, and those who were presented with "wage loss" information rated significantly higher perceived chance of RTW than those in the "pain gain" group. More in-depth investigation is warranted on this topic, with a larger sample of injured workers to investigate the effects of message framing on the decision-making process about RTW.

  15. New polymorphic mtDNA restriction site in the 12S rRNA gene detected in Tunisian patients with non-syndromic hearing loss

    International Nuclear Information System (INIS)

    Mkaouar-Rebai, Emna; Tlili, Abdelaziz; Masmoudi, Saber; Charfeddine, Ilhem; Fakhfakh, Faiza

    2008-01-01

    The 12S rRNA gene was shown to be a hot spot for aminoglycoside-induced and non-syndromic hearing loss since several deafness-associated mtDNA mutations were identified in this gene. Among them, we distinguished the A1555G, the C1494T and the T1095C mutations and C-insertion or deletion at position 961. One hundred Tunisian patients with non-syndromic hearing loss and 100 hearing individuals were analysed in this study. A PCR-RFLP analysis with HaeIII restriction enzyme showed the presence of the A1555G mutation in the 12S rRNA gene in only one out of the 100 patients. In addition, PCR-RFLP and radioactive PCR revealed the presence of a new HaeIII polymorphic restriction site in the same gene of 12S rRNA site in 4 patients with non-syndromic hearing loss. UVIDOC-008-XD analyses showed the presence of this new polymorphic restriction site with a variable heteroplasmic rates at position +1517 of the human mitochondrial genome. On the other hand, direct sequencing of the entire mitochondrial 12S rRNA gene in the 100 patients and in 100 hearing individuals revealed the presence of the A750G and A1438G polymorphisms and the absence of the C1494T, T1095C and 961insC mutations in all the tested individuals. Sequencing of the whole mitochondrial genome in the 4 patients showing the new HaeIII polymorphic restriction site revealed only the presence of the A8860G transition in the MT-ATP6 gene and the A4769G polymorphism in the ND2 gene

  16. The contribution of fat component to gestational weight gain

    Directory of Open Access Journals (Sweden)

    2013-12-01

    Full Text Available Objective: to estimate the role of adipose tissue in gestational weight gain (GWG and preferential fat deposition among normal-weight women. Subjects and methods: prospective cohort study of 84 pregnancies: maternal body mass index 18,5–24,9 kg/m2, singleton term pregnancy, nondiabetic women, somatically well. GWG and skinfold thickness were evaluated in the 1st, 2nd, 3d trimesters, on the 3d day after delivery. Results: fat mass gain in low GWG was similar to recommended GWG and in the high-GWG group was greater one. Women with recommended and low GWG returned to their initial fat level on the 3d day after delivery, in excessive weight gain fat significantly increased (р=0,025. Compared to initial recommended GWG resulted in triceps skinfold thicknesses loss (р=0,001, in abdominal skinfold gained nothing and in thighs skinfold thicknesses increasing (р=0,021. Inadequate GWG leads to fat loss in arms (р=0,017, fat of abdominal area and thighs return to initial level. In excessive GWG fat in the upper trunk and arms not changed, in the lower area (thighs significantly increased compared to initial level (р=0,001 or other groups (р=0,001. Conclusion: excessive GWG was associated with greater adipose tissue cumulation and its deposition preferentially over the thighs. Inadequate GWG was clearly linked to low fat-free mass gain.

  17. Rapid Generation of Human Genetic Loss-of-Function iPSC Lines by Simultaneous Reprogramming and Gene Editing

    Directory of Open Access Journals (Sweden)

    Andrew M. Tidball

    2017-09-01

    Full Text Available Specifically ablating genes in human induced pluripotent stem cells (iPSCs allows for studies of gene function as well as disease mechanisms in disorders caused by loss-of-function (LOF mutations. While techniques exist for engineering such lines, we have developed and rigorously validated a method of simultaneous iPSC reprogramming while generating CRISPR/Cas9-dependent insertions/deletions (indels. This approach allows for the efficient and rapid formation of genetic LOF human disease cell models with isogenic controls. The rate of mutagenized lines was strikingly consistent across experiments targeting four different human epileptic encephalopathy genes and a metabolic enzyme-encoding gene, and was more efficient and consistent than using CRISPR gene editing of established iPSC lines. The ability of our streamlined method to reproducibly generate heterozygous and homozygous LOF iPSC lines with passage-matched isogenic controls in a single step provides for the rapid development of LOF disease models with ideal control lines, even in the absence of patient tissue.

  18. Frequency of intron loss correlates with processed pseudogene abundance: a novel strategy to test the reverse transcriptase model of intron loss.

    Science.gov (United States)

    Zhu, Tao; Niu, Deng-Ke

    2013-03-05

    Although intron loss in evolution has been described, the mechanism involved is still unclear. Three models have been proposed, the reverse transcriptase (RT) model, genomic deletion model and double-strand-break repair model. The RT model, also termed mRNA-mediated intron loss, suggests that cDNA molecules reverse transcribed from spliced mRNA recombine with genomic DNA causing intron loss. Many studies have attempted to test this model based on its predictions, such as simultaneous loss of adjacent introns, 3'-side bias of intron loss, and germline expression of intron-lost genes. Evidence either supporting or opposing the model has been reported. The mechanism of intron loss proposed in the RT model shares the process of reverse transcription with the formation of processed pseudogenes. If the RT model is correct, genes that have produced more processed pseudogenes are more likely to undergo intron loss. In the present study, we observed that the frequency of intron loss is correlated with processed pseudogene abundance by analyzing a new dataset of intron loss obtained in mice and rats. Furthermore, we found that mRNA molecules of intron-lost genes are mostly translated on free cytoplasmic ribosomes, a feature shared by mRNA molecules of the parental genes of processed pseudogenes and long interspersed elements. This feature is likely convenient for intron-lost gene mRNA molecules to be reverse transcribed. Analyses of adjacent intron loss, 3'-side bias of intron loss, and germline expression of intron-lost genes also support the RT model. Compared with previous evidence, the correlation between the abundance of processed pseudogenes and intron loss frequency more directly supports the RT model of intron loss. Exploring such a correlation is a new strategy to test the RT model in organisms with abundant processed pseudogenes.

  19. Molecular Analysis: Microsatellite Instability and Loss of Heterozygosity of Tumor Suppressor Gene in Hereditary Non-Polyposis Colorectal Cancer (HNPCC

    Directory of Open Access Journals (Sweden)

    Vesna Hadžiavdić

    2009-02-01

    Full Text Available HNPCC (Hereditary non-polyposis colorectal cancer development is caused by mutation of genes included in system of mismatch repair genes. The mutation exists at 60% of patients in hMSH2 gene, 30% in hMLH1 and 10% both in hPMS1and hPMS2 genes. RER+ exists in about 90% in hereditary non-polyposis colorectal cancer and about 15-28% in sporadic cancers.The purpose of the study was to determine highly sensitive microsatellite markers which can be fast and efficient way of microsatellite screening for detection of HNPCC patients. Moreover, we have analysed the loss of heterozygosity of tumour suppressor genes which could have the diagnostic value in detection of HPNCC patients.

  20. Loss or gain? Invasive aliens and biodiversity in the Mediterranean Sea

    International Nuclear Information System (INIS)

    Galil, B.S.

    2007-01-01

    More than 500 alien species were listed from the Mediterranean Sea. Though no extinction of a native species is known, sudden decline in abundance, and even local extirpations, concurrent with proliferation of aliens, had been recorded. Examination of the profound ecological impacts of some of the most conspicuous invasive alien species underscores their role, among multiple anthropogenic stressors, in altering the infralittoral communities. Local population losses and niche contraction of native species may not induce immediate extirpation, but they augur reduction of genetic diversity, loss of functions, processes, and habitat structure, increase the risk of decline and extinction, and lead to biotic homogenization. The relevant environmental policy and management framework is discussed

  1. Loss or gain? Invasive aliens and biodiversity in the Mediterranean Sea

    Energy Technology Data Exchange (ETDEWEB)

    Galil, B.S. [National Institute of Oceanography, Israel Oceanographic and Limnological Research, POB 8030, Haifa 31080 (Israel)]. E-mail: galil@post.tau.ac.il

    2007-07-01

    More than 500 alien species were listed from the Mediterranean Sea. Though no extinction of a native species is known, sudden decline in abundance, and even local extirpations, concurrent with proliferation of aliens, had been recorded. Examination of the profound ecological impacts of some of the most conspicuous invasive alien species underscores their role, among multiple anthropogenic stressors, in altering the infralittoral communities. Local population losses and niche contraction of native species may not induce immediate extirpation, but they augur reduction of genetic diversity, loss of functions, processes, and habitat structure, increase the risk of decline and extinction, and lead to biotic homogenization. The relevant environmental policy and management framework is discussed.

  2. Analytical study of optimal design and gain parameters of double-slot plasmonic waveguides

    International Nuclear Information System (INIS)

    Handapangoda, Dayan; Rukhlenko, Ivan D; Premaratne, Malin

    2013-01-01

    We theoretically analyze guided modes in optically active and passive double-slot plasmonic waveguides. We show that for one of the two different mode symmetries supported by the waveguide, a most productive guiding condition can be realized by adjusting the thicknesses of the layers to optimal values. We also derive approximate analytic expressions to calculate the optimal geometrical parameters of the waveguide. Interestingly, our analysis shows that the propagation losses associated with the inverse mode symmetry of the double-slot waveguide are comparatively low, regardless of the dimensions of the waveguide. We further show that the propagation losses become the smallest in the limiting case of a single-slot (metal–dielectric–metal (MDM)) waveguide. For both double- and single-slot waveguides, we show that the gain required to overcome the losses can be reduced by choosing a dielectric with a low refractive index. We also derive accurate analytical expressions to readily estimate the critical gain and modal gain of the waveguides. (paper)

  3. Disruption of the petal identity gene APETALA3-3 is highly correlated with loss of petals within the buttercup family (Ranunculaceae).

    Science.gov (United States)

    Zhang, Rui; Guo, Chunce; Zhang, Wengen; Wang, Peipei; Li, Lin; Duan, Xiaoshan; Du, Qinggao; Zhao, Liang; Shan, Hongyan; Hodges, Scott A; Kramer, Elena M; Ren, Yi; Kong, Hongzhi

    2013-03-26

    Absence of petals, or being apetalous, is usually one of the most important features that characterizes a group of flowering plants at high taxonomic ranks (i.e., family and above). The apetalous condition, however, appears to be the result of parallel or convergent evolution with unknown genetic causes. Here we show that within the buttercup family (Ranunculaceae), apetalous genera in at least seven different lineages were all derived from petalous ancestors, indicative of parallel petal losses. We also show that independent petal losses within this family were strongly associated with decreased or eliminated expression of a single floral organ identity gene, APETALA3-3 (AP3-3), apparently owing to species-specific molecular lesions. In an apetalous mutant of Nigella, insertion of a transposable element into the second intron has led to silencing of the gene and transformation of petals into sepals. In several naturally occurring apetalous genera, such as Thalictrum, Beesia, and Enemion, the gene has either been lost altogether or disrupted by deletions in coding or regulatory regions. In Clematis, a large genus in which petalous species evolved secondarily from apetalous ones, the gene exhibits hallmarks of a pseudogene. These results suggest that, as a petal identity gene, AP3-3 has been silenced or down-regulated by different mechanisms in different evolutionary lineages. This also suggests that petal identity did not evolve many times independently across the Ranunculaceae but was lost in numerous instances. The genetic mechanisms underlying the independent petal losses, however, may be complex, with disruption of AP3-3 being either cause or effect.

  4. Relationship between perilipin gene polymorphisms and body weight and body composition during weight loss and weight maintenance.

    Science.gov (United States)

    Soenen, Stijn; Mariman, Edwin C M; Vogels, Neeltje; Bouwman, Freek G; den Hoed, Marcel; Brown, Louise; Westerterp-Plantenga, Margriet S

    2009-03-23

    Genetic variation in the perilipin (PLIN) gene may play a role in the etiology and treatment of obesity. To examine different polymorphisms in the PLIN gene in relation to body-weight regulation. 118 subjects followed a 6 wk VLCD, followed by 1 year weight maintenance. Body-weight (BW), body composition, leptin concentration, and polymorphisms of the PLIN gene: PLIN1:rs2289487, PLIN4:rs894160, PLIN6:rs1052700, PLIN5:rs2304795 and PLIN7:rs 2304796 were determined. BW loss during VLCD was 7.0+/-3.1 kg (p0.9, r2=0.72; PLIN5 and PLIN7: D' >0.9, r2=0.85. In men, body weight, BMI, waist circumference, body fat, leptin concentrations were significantly lower for the haplotype of PLIN1 (C-alleles) and PLIN4 (A-alleles). In women weight loss and loss of fat mass were larger for the haplotype of PLIN1 (C-alleles) and PLIN4 (A-alleles). For PLIN6 genotypes body weight and body fat were lower for homozygotes of the minor allele (T/T) in the men; in the women leptin concentrations were lower. The haplotype of PLIN5 and PLIN7 consisting of A/G and G/G of PLIN5 and A/A of PLIN7 showed a reduction in FM: 5.9+/-0.6 kg vs 3.1+/-0.4 kg, % body fat: 5.5+/-0.6% vs 2.2+/-0.2%, and leptin: 20.5+/-10.8 ng/ml vs 12.9+/-6.7 ng/ml over time in the women (pinfluencer of obesity risk in humans.

  5. Multi-platform whole-genome microarray analyses refine the epigenetic signature of breast cancer metastasis with gene expression and copy number.

    Directory of Open Access Journals (Sweden)

    Joseph Andrews

    2010-01-01

    Full Text Available We have previously identified genome-wide DNA methylation changes in a cell line model of breast cancer metastasis. These complex epigenetic changes that we observed, along with concurrent karyotype analyses, have led us to hypothesize that complex genomic alterations in cancer cells (deletions, translocations and ploidy are superimposed over promoter-specific methylation events that are responsible for gene-specific expression changes observed in breast cancer metastasis.We undertook simultaneous high-resolution, whole-genome analyses of MDA-MB-468GFP and MDA-MB-468GFP-LN human breast cancer cell lines (an isogenic, paired lymphatic metastasis cell line model using Affymetrix gene expression (U133, promoter (1.0R, and SNP/CNV (SNP 6.0 microarray platforms to correlate data from gene expression, epigenetic (DNA methylation, and combination copy number variant/single nucleotide polymorphism microarrays. Using Partek Software and Ingenuity Pathway Analysis we integrated datasets from these three platforms and detected multiple hypomethylation and hypermethylation events. Many of these epigenetic alterations correlated with gene expression changes. In addition, gene dosage events correlated with the karyotypic differences observed between the cell lines and were reflected in specific promoter methylation patterns. Gene subsets were identified that correlated hyper (and hypo methylation with the loss (or gain of gene expression and in parallel, with gene dosage losses and gains, respectively. Individual gene targets from these subsets were also validated for their methylation, expression and copy number status, and susceptible gene pathways were identified that may indicate how selective advantage drives the processes of tumourigenesis and metastasis.Our approach allows more precisely profiling of functionally relevant epigenetic signatures that are associated with cancer progression and metastasis.

  6. Expression loss and revivification of RhoB gene in ovary carcinoma carcinogenesis and development.

    Science.gov (United States)

    Liu, Yingwei; Song, Na; Ren, Kexing; Meng, Shenglan; Xie, Yao; Long, Qida; Chen, Xiancheng; Zhao, Xia

    2013-01-01

    RhoB, a member of small GTPases belonging to the Ras protein superfamily, might have a suppressive activity in cancer progression. Here, expression of RhoB gene was evaluated in human benign, borderline and malignant ovary tumors by immunostaining, with normal ovary tissue as control. Malignant tumors were assessed according to Federation Internationale de Gynecologie Obstetrique (FIGO) guidelines and classified in stage I-IV. Revivification of RhoB gene was investigated by analyzing the effect of histone deacetylase (HDAC) inhibitor trichostatin (TSA) and methyltransferase inhibitor 5-azacytidine (5-Aza) on ovarian cancer cells via RT-PCR and western blot. Apoptosis of ovary cancer cells was detected using flowcytometry and fluorescence microscopy. Subsequently, RhoB expression is detected in normal ovary epithelium, borderline tumors, and decreases significantly or lost in the majority of ovarian cancer specimen (Pcancer cells, but 5-Aza couldn't. Interference into Revivification of RhoB gene results in reduction of ovary carcinoma cell apoptosis. It is proposed that loss of RhoB expression occurs frequently in ovary carcinogenesis and progression and its expression could be regulated by histone deacetylation but not by promoter hypermethylation, which may serve as a prospective gene treatment target for the patients with ovarian malignancy not responding to standard therapies.

  7. Evolution of hepatic glucose metabolism: liver-specific glucokinase deficiency explained by parallel loss of the gene for glucokinase regulatory protein (GCKR.

    Directory of Open Access Journals (Sweden)

    Zhao Yang Wang

    Full Text Available Glucokinase (GCK plays an important role in the regulation of carbohydrate metabolism. In the liver, phosphorylation of glucose to glucose-6-phosphate by GCK is the first step for both glycolysis and glycogen synthesis. However, some vertebrate species are deficient in GCK activity in the liver, despite containing GCK genes that appear to be compatible with function in their genomes. Glucokinase regulatory protein (GCKR is the most important post-transcriptional regulator of GCK in the liver; it participates in the modulation of GCK activity and location depending upon changes in glucose levels. In experimental models, loss of GCKR has been shown to associate with reduced hepatic GCK protein levels and activity.GCKR genes and GCKR-like sequences were identified in the genomes of all vertebrate species with available genome sequences. The coding sequences of GCKR and GCKR-like genes were identified and aligned; base changes likely to disrupt coding potential or splicing were also identified.GCKR genes could not be found in the genomes of 9 vertebrate species, including all birds. In addition, in multiple mammalian genomes, whereas GCKR-like gene sequences could be identified, these genes could not predict a functional protein. Vertebrate species that were previously reported to be deficient in hepatic GCK activity were found to have deleted (birds and lizard or mutated (mammals GCKR genes. Our results suggest that mutation of the GCKR gene leads to hepatic GCK deficiency due to the loss of the stabilizing effect of GCKR.

  8. Genomes in turmoil: quantification of genome dynamics in prokaryote supergenomes.

    Science.gov (United States)

    Puigbò, Pere; Lobkovsky, Alexander E; Kristensen, David M; Wolf, Yuri I; Koonin, Eugene V

    2014-08-21

    Genomes of bacteria and archaea (collectively, prokaryotes) appear to exist in incessant flux, expanding via horizontal gene transfer and gene duplication, and contracting via gene loss. However, the actual rates of genome dynamics and relative contributions of different types of event across the diversity of prokaryotes are largely unknown, as are the sizes of microbial supergenomes, i.e. pools of genes that are accessible to the given microbial species. We performed a comprehensive analysis of the genome dynamics in 35 groups (34 bacterial and one archaeal) of closely related microbial genomes using a phylogenetic birth-and-death maximum likelihood model to quantify the rates of gene family gain and loss, as well as expansion and reduction. The results show that loss of gene families dominates the evolution of prokaryotes, occurring at approximately three times the rate of gain. The rates of gene family expansion and reduction are typically seven and twenty times less than the gain and loss rates, respectively. Thus, the prevailing mode of evolution in bacteria and archaea is genome contraction, which is partially compensated by the gain of new gene families via horizontal gene transfer. However, the rates of gene family gain, loss, expansion and reduction vary within wide ranges, with the most stable genomes showing rates about 25 times lower than the most dynamic genomes. For many groups, the supergenome estimated from the fraction of repetitive gene family gains includes about tenfold more gene families than the typical genome in the group although some groups appear to have vast, 'open' supergenomes. Reconstruction of evolution for groups of closely related bacteria and archaea reveals an extremely rapid and highly variable flux of genes in evolving microbial genomes, demonstrates that extensive gene loss and horizontal gene transfer leading to innovation are the two dominant evolutionary processes, and yields robust estimates of the supergenome size.

  9. Projected gains and losses of wildlife habitat from bioenergy-induced landscape change

    Science.gov (United States)

    Tarr, Nathan M.; Rubino, Matthew J.; Costanza, Jennifer K.; McKerrow, Alexa; Collazo, Jaime A.; Abt, Robert C.

    2016-01-01

    Domestic and foreign renewable energy targets and financial incentives have increased demand for woody biomass and bioenergy in the southeastern United States. This demand is expected to be met through purpose-grown agricultural bioenergy crops, short-rotation tree plantations, thinning and harvest of planted and natural forests, and forest harvest residues. With results from a forest economics model, spatially explicit state-and-transition simulation models, and species–habitat models, we projected change in habitat amount for 16 wildlife species caused by meeting a renewable fuel target and expected demand for wood pellets in North Carolina, USA. We projected changes over 40 years under a baseline ‘business-as-usual’ scenario without bioenergy production and five scenarios with unique feedstock portfolios. Bioenergy demand had potential to influence trends in habitat availability for some species in our study area. We found variation in impacts among species, and no scenario was the ‘best’ or ‘worst’ across all species. Our models projected that shrub-associated species would gain habitat under some scenarios because of increases in the amount of regenerating forests on the landscape, while species restricted to mature forests would lose habitat. Some forest species could also lose habitat from the conversion of forests on marginal soils to purpose-grown feedstocks. The conversion of agricultural lands on marginal soils to purpose-grown feedstocks increased habitat losses for one species with strong associations with pasture, which is being lost to urbanization in our study region. Our results indicate that landscape-scale impacts on wildlife habitat will vary among species and depend upon the bioenergy feedstock portfolio. Therefore, decisions about bioenergy and wildlife will likely involve trade-offs among wildlife species, and the choice of focal species is likely to affect the results of landscape-scale assessments. We offer general principals

  10. Habitat loss and gain: Influence on habitat attractiveness for estuarine fish communities

    Science.gov (United States)

    Amorim, Eva; Ramos, Sandra; Elliott, Michael; Franco, Anita; Bordalo, Adriano A.

    2017-10-01

    Habitat structure and complexity influence the structuring and functioning of fish communities. Habitat changes are one of the main pressures affecting estuarine systems worldwide, yet the degree and rate of change and its impact on fish communities is still poorly understood. In order to quantify historical modifications in habitat structure, an ecohydrological classification system using physiotopes, i.e. units with homogenous abiotic characteristics, was developed for the lower Lima estuary (NW Portugal). Field data, aerial imagery, historical maps and interpolation methods were used to map input variables, including bathymetry, substratum (hard/soft), sediment composition, hydrodynamics (current velocity) and vegetation coverage. Physiotopes were then mapped for the years of 1933 and 2013 and the areas lost and gained over the 80 years were quantified. The implications of changes for the benthic and demersal fish communities using the lower estuary were estimated using the attractiveness to those communities of each physiotope, while considering the main estuarine habitat functions for fish, namely spawning, nursery, feeding and refuge areas and migratory routes. The lower estuary was highly affected due to urbanisation and development and, following a port/harbour expansion, its boundary moved seaward causing an increase in total area. Modifications led to the loss of most of its sandy and saltmarsh intertidal physiotopes, which were replaced by deeper subtidal physiotopes. The most attractive physiotopes for fish (defined as the way in which they supported the fish ecological features) decreased in area while less attractive ones increased, producing an overall lower attractiveness of the studied area in 2013 compared to 1933. The implications of habitat alterations for the fish using the estuary include potential changes in the nursery carrying capacity and the functioning of the fish community. The study also highlighted the poor knowledge of the impacts of

  11. Hyper-responsivity to losses in the anterior insula during economic choice scales with depression severity.

    Science.gov (United States)

    Engelmann, J B; Berns, G S; Dunlop, B W

    2017-12-01

    Commonly observed distortions in decision-making among patients with major depressive disorder (MDD) may emerge from impaired reward processing and cognitive biases toward negative events. There is substantial theoretical support for the hypothesis that MDD patients overweight potential losses compared with gains, though the neurobiological underpinnings of this bias are uncertain. Twenty-one unmedicated patients with MDD were compared with 25 healthy controls (HC) using functional magnetic resonance imaging (fMRI) together with an economic decision-making task over mixed lotteries involving probabilistic gains and losses. Region-of-interest analyses evaluated neural signatures of gain and loss coding within a core network of brain areas known to be involved in valuation (anterior insula, caudate nucleus, ventromedial prefrontal cortex). Usable fMRI data were available for 19 MDD and 23 HC subjects. Anterior insula signal showed negative coding of losses (gain > loss) in HC subjects consistent with previous findings, whereas MDD subjects demonstrated significant reversals in these associations (loss > gain). Moreover, depression severity further enhanced the positive coding of losses in anterior insula, ventromedial prefrontal cortex, and caudate nucleus. The hyper-responsivity to losses displayed by the anterior insula of MDD patients was paralleled by a reduced influence of gain, but not loss, stake size on choice latencies. Patients with MDD demonstrate a significant shift from negative to positive coding of losses in the anterior insula, revealing the importance of this structure in value-based decision-making in the context of emotional disturbances.

  12. DNA Hypermethylation of the Serotonin Receptor Type-2A Gene Is Associated with a Worse Response to a Weight Loss Intervention in Subjects with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Aurora Perez-Cornago

    2014-06-01

    Full Text Available Understanding the regulation of gene activities depending on DNA methylation has been the subject of much recent study. However, although polymorphisms of the HTR2A gene have been associated with both obesity and psychiatric disorders, the role of HTR2A gene methylation in these illnesses remains uncertain. The aim of this study was to evaluate the association of HTR2A gene promoter methylation levels in white blood cells (WBC with obesity traits and depressive symptoms in individuals with metabolic syndrome (MetS enrolled in a behavioural weight loss programme. Analyses were based on 41 volunteers (mean age 49 ± 1 year recruited within the RESMENA study. Depressive symptoms (as determined using the Beck Depression Inventory, anthropometric and biochemical measurements were analysed at the beginning and after six months of weight loss treatment. At baseline, DNA from WBC was isolated and cytosine methylation in the HTR2A gene promoter was quantified by a microarray approach. In the whole-study sample, a positive association of HTR2A gene methylation with waist circumference and insulin levels was detected at baseline. Obesity measures significantly improved after six months of dietary treatment, where a lower mean HTR2A gene methylation at baseline was associated with major reductions in body weight, BMI and fat mass after the treatment. Moreover, mean HTR2A gene methylation at baseline significantly predicted the decrease in depressive symptoms after the weight loss treatment. In conclusion, this study provides newer evidence that hypermethylation of the HTR2A gene in WBC at baseline is significantly associated with a worse response to a weight-loss intervention and with a lower decrease in depressive symptoms after the dietary treatment in subjects with MetS.

  13. Establishment of a model of cochlear lesions in rats to study potential gene therapy for sensorineural hearing loss.

    Science.gov (United States)

    Wang, Ye; Qiao, Li; Chen, Yang; Wen, Liting; Yue, Bo; Qiu, Jianhua; Wu, Shengxi

    2015-12-01

    Sensorineural hearing loss seriously influences a patient's daily life, and no effective treatments exist to date. Gene therapy is a potential treatment for regenerating hair cells to restore hearing. In this study, we established a cochlear lesions model to study hair cell regeneration by co-administration of kanamycin and furosemide. After the injections, we assessed the survival of outer hair cells (OHC), inner hair cells (IHC), supporting cells (SC), spiral ganglion neurons (SGN) and peripheral axons. Moreover, we used two viral vectors to detect the transgene distribution. Our results showed at 12h post-treatment, numerous OHC were missing in the basal turn. At 24h post-treatment, all OHCs in basal half of the cochlea were lost, and by 48h, OHC loss had spread to the apical coil. Four days after the injections, all OHCs were absent. At 1mo post-treatment, the organ of Corti had collapsed. In contrast, most of the SC remained 4d after the injections. The loss of SGN and peripheral axons was consistent with this time course post-treatment. The results of transgene distribution suggested the correlative gene can be transferred into the organ of Corti using adenoviruses (AdV) vectors and lentiviruses (LV) vectors in our cochlear lesion model. We assessed the details of HC death at more time point and chosen the time point for gene transfer in this model. We conclude that this cochlear lesion model would be suitable for the study of hair cell regeneration. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Heavy inertial particles in turbulent flows gain energy slowly but lose it rapidly

    Science.gov (United States)

    Bhatnagar, Akshay; Gupta, Anupam; Mitra, Dhrubaditya; Pandit, Rahul

    2018-03-01

    We present an extensive numerical study of the time irreversibility of the dynamics of heavy inertial particles in three-dimensional, statistically homogeneous, and isotropic turbulent flows. We show that the probability density function (PDF) of the increment, W (τ ) , of a particle's energy over a time scale τ is non-Gaussian, and skewed toward negative values. This implies that, on average, particles gain energy over a period of time that is longer than the duration over which they lose energy. We call this slow gain and fast loss. We find that the third moment of W (τ ) scales as τ3 for small values of τ . We show that the PDF of power-input p is negatively skewed too; we use this skewness Ir as a measure of the time irreversibility and we demonstrate that it increases sharply with the Stokes number St for small St; this increase slows down at St≃1 . Furthermore, we obtain the PDFs of t+ and t-, the times over which p has, respectively, positive or negative signs, i.e., the particle gains or loses energy. We obtain from these PDFs a direct and natural quantification of the slow gain and fast loss of the energy of the particles, because these PDFs possess exponential tails from which we infer the characteristic loss and gain times tloss and tgain, respectively, and we obtain tlossprobability in the strain-dominated region than in the vortical one; in contrast, the slow gain in the energy of the particles is equally likely in vortical or strain-dominated regions of the flow.

  15. Gains Based Remedies: the misguided search for a doctrine

    Directory of Open Access Journals (Sweden)

    Tom Stafford

    2016-12-01

    Full Text Available ADVANCE ACCESSIn this article Tom Stafford (Paralegal at Clyde & Co LLP examines the phenomenon of “Gains Based Remedies”. These are awards that, unlike classical damage awards which are calculated by reference to the loss suffered by the claimant, correlate to the gain made by the defendant. A couple of common examples include an account of profits for breach of trust claims, or the “disgorgement” damages that were awarded in AG v Blake. These awards are however available for a spectrum of varied wrongs. Their seeming lack of unity has often baffled commentators who have tried to search for an underpinning doctrine. One particularly renowned commentary is that of Professor Edelman’s, who suggests that these wrongs can be understood by being broken down into one of two categories: awards which seek to deter wrongdoing, and awards which reverse a wrongful transfer of value. The purpose of this article is to discuss the flaws of this view of the law, and to suggest that in fact, any search for a doctrinal underpinning to Gains Based Remedies is misguided. The cases in which these awards are granted have only one feature common to all: the claimant’s loss is, for whatever reason, difficult or impossible to assess. For that reason, the courts use the only other measure of the wrong available: the defendant’s gain.

  16. Enhancing optical gains in Si nanocrystals via hydrogenation and cerium ion doping

    International Nuclear Information System (INIS)

    Wang, Dong-Chen; Li, Yan-Li; Song, Sheng-Chi; Guo, Wen-Ping; Lu, Ming; Chen, Jia-Rong

    2014-01-01

    We report optical gain enhancements in Si nanocrystals (Si-NCs) via hydrogenation and Ce 3+ ion doping. Variable stripe length technique was used to obtain gains. At 0.3 W/cm 2 pumping power density of pulsed laser, net gains were observed together with gain enhancements after hydrogenation and/or Ce 3+ ion doping; gains after loss corrections were between 89.52 and 341.95 cm −1 ; and the photoluminescence (PL) lifetime was found to decrease with the increasing gain enhancement. At 0.04 W/cm 2 power density, however, no net gain was found and the PL lifetime increased with the increasing PL enhancement. The results were discussed according to stimulated and spontaneous excitation and de-excitation mechanisms of Si-NCs.

  17. Glutathione S-transferase (GSTM1, GSTT1) gene polymorphisms, maternal gestational weight gain, bioimpedance factors and their relationship with birth weight: a cross-sectional study in Romanian mothers and their newborns.

    Science.gov (United States)

    Mărginean, Claudiu; Bănescu, Claudia Violeta; Mărginean, Cristina Oana; Tripon, Florin; Meliţ, Lorena Elena; Iancu, Mihaela

    2017-01-01

    The aim of this study was to assess the relationship between mother-child GSTM1, GSTT1 gene polymorphisms, maternal weight gain, maternal bioimpedance parameters and newborn's weight, in order to identify the factors that influence birth weight. We performed a cross-sectional study on 405 mothers and their newborns, evaluated in an Obstetrics and Gynecology Tertiary Hospital from Romania. Newborns whose mothers had the null genotype of GSTT1 gene polymorphism were more likely to gain a birth weight of >3 kg, compared to newborns whose mothers had the T1 genotype (odds ratio - OR: 2.14, 95% confidence interval - CI: [1.03; 4.44]). Also, the null genotype of GSTM1 gene polymorphism in both mothers and newborns was associated with a higher birth weight. Gestational weight gain was positively associated with newborn's birth weight (pmother's fat mass (%) and basal metabolism rate were also independent factors for a birth weight of more than 3 kg (p=0.006 and p=0.037). The null genotype of GSTT1 gene polymorphism in mothers and the null genotype of GSTM1 in mothers and newborns had a positive effect on birth weight. Also, increased maternal fat mass and basal metabolism rate were associated with increased birth weight. We conclude that maternal GSTM1÷GSTT1 gene polymorphisms present an impact on birth weight, being involved in the neonatal nutritional status. The clinical relevance of our study is sustained by the importance of identifying the factors that influence birth weight, which can be triggers for childhood obesity.

  18. Hearing impairment caused by mutations in two different genes responsible for nonsyndromic and syndromic hearing loss within a single family.

    Science.gov (United States)

    Niepokój, Katarzyna; Rygiel, Agnieszka M; Jurczak, Piotr; Kujko, Aleksandra A; Śniegórska, Dominika; Sawicka, Justyna; Grabarczyk, Alicja; Bal, Jerzy; Wertheim-Tysarowska, Katarzyna

    2018-02-01

    Usher syndrome is rare genetic disorder impairing two human senses, hearing and vision, with the characteristic late onset of vision loss. This syndrome is divided into three types. In all cases, the vision loss is postlingual, while loss of hearing is usually prelingual. The vestibular functions may also be disturbed in Usher type 1 and sometimes in type 3. Vestibular areflexia is helpful in making a proper diagnosis of the syndrome, but, often, the syndrome is misdiagnosed as a nonsyndromic hearing loss. Here, we present a Polish family with hearing loss, which was clinically classified as nonsyndromic. After excluding mutations in the DFNB1 locus, we implemented the next-generation sequencing method and revealed that hearing loss was syndromic and mutations in the USH2A gene indicate Usher syndrome. This research highlights the importance of molecular analysis in establishing a clinical diagnosis of congenital hearing loss.

  19. The consequences of chromosomal aneuploidy on gene expression profiles in a cell line model for prostate carcinogenesis.

    Science.gov (United States)

    Phillips, J L; Hayward, S W; Wang, Y; Vasselli, J; Pavlovich, C; Padilla-Nash, H; Pezullo, J R; Ghadimi, B M; Grossfeld, G D; Rivera, A; Linehan, W M; Cunha, G R; Ried, T

    2001-11-15

    Here we report the genetic characterization of immortalized prostate epithelial cells before and after conversion to tumorigenicity using molecular cytogenetics and microarray technology. We were particularly interested to analyze the consequences of acquired chromosomal aneuploidies with respect to modifications of gene expression profiles. Compared with nontumorigenic but immortalized prostate epithelium, prostate tumor cell lines showed high levels of chromosomal rearrangements that led to gains of 1p, 5, 11q, 12p, 16q, and 20q and losses of 1pter, 11p, 17, 20p, 21, 22, and Y. Of 5700 unique targets on a 6.5K cDNA microarray, approximately 3% were subject to modification in expression levels; these included GRO-1, -2, IAP-1,- 2, MMP-9, and cyclin D1, which showed increased expression, and TRAIL, BRCA1, and CTNNA, which showed decreased expression. Thirty % of expression changes occurred in regions the genomic copy number of which remained balanced. Of the remainder, 42% of down-regulated and 51% of up-regulated genes mapped to regions present in decreased or increased genomic copy numbers, respectively. A relative gain or loss of a chromosome or chromosomal arm usually resulted in a statistically significant increase or decrease, respectively, in the average expression level of all of the genes on the chromosome. However, of these genes, very few (e.g., 5 of 101 genes on chromosome 11q), and in some instances only two genes (MMP-9 and PROCR on chromosome 20q), were overexpressed by > or =1.7-fold when scored individually. Cluster analysis by gene function suggests that prostate tumorigenesis in these cell line models involves alterations in gene expression that may favor invasion, prevent apoptosis, and promote growth.

  20. Effect of the common -866G/A polymorphism of the uncoupling protein 2 gene on weight loss and body composition under sibutramine therapy in an obese Taiwanese population.

    Science.gov (United States)

    Hsiao, Tun-Jen; Wu, Lawrence Shih-Hsin; Hwang, Yuchi; Huang, Shih-Yi; Lin, Eugene

    2010-04-01

    Sibutramine, a serotonin and norepinephrine reuptake inhibitor, is used as an anti-obesity drug. Several pharmacogenetic studies have shown correlations between sibutramine effects and genetic variants, such as the 825C/T (rs5443) single nucleotide polymorphism (SNP) in the guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene. In this study, our goal was to investigate whether a common SNP, -866G/A (rs659366), in the uncoupling protein 2 (UCP2) gene could influence weight reduction and body composition under sibutramine therapy in an obese Taiwanese population. The study included 131 obese patients, 44 in the placebo group and 87 in the sibutramine group. We assessed the measures of weight loss and body fat reduction at the end of a 12-week treatment period by analysis of covariance (ANCOVA) models using gender, baseline weight, and body fat percentage at baseline as covariates. By comparing the placebo and sibutramine groups with ANCOVA, our data showed a strong effect of sibutramine on weight loss in the combined UCP2 -866 AA + GA genotype groups (p sibutramine on body fat percentage loss was found for individuals with the AA or GA genotypes (p sibutramine had no significant effect on weight loss (p = 0.063) or body fat percentage loss (p = 0.194) for individuals with the wild-type GG genotype, compared with the placebo group of the same genotype. Moreover, a potential gene-gene interaction between UCP2 and GNB3 was identified by multiple linear regression models for the weight loss (p sibutramine. The results suggest that the UCP2 gene may contribute to weight loss and fat change in response to sibutramine therapy in obese Taiwanese patients.

  1. Age-related hearing loss

    Science.gov (United States)

    ... grow older. Your genes and loud noise (from rock concerts or music headphones) may play a large role. The following factors contribute to age-related hearing loss: Family history (age-related hearing loss tends to run in ...

  2. Increased Loss Aversion in Unmedicated Patients with Obsessive–Compulsive Disorder

    Directory of Open Access Journals (Sweden)

    Kamila E. Sip

    2018-01-01

    Full Text Available IntroductionObsessive–compulsive disorder (OCD patients show abnormalities in decision-making and, clinically, appear to show heightened sensitivity to potential negative outcomes. Despite the importance of these cognitive processes in OCD, few studies have examined the disorder within an economic decision-making framework. Here, we investigated loss aversion, a key construct in the prospect theory that describes the tendency for individuals to be more sensitive to potential losses than gains when making decisions.MethodsAcross two study sites, groups of unmedicated OCD patients (n = 14, medicated OCD patients (n = 29, and healthy controls (n = 34 accepted or rejected a series of 50/50 gambles containing varying loss/gain values. Loss aversion was calculated as the ratio of the likelihood of rejecting a gamble with increasing potential losses to the likelihood of accepting a gamble with increasing potential gains. Decision times to accept or reject were also examined and correlated with loss aversion.ResultsUnmedicated OCD patients exhibited significantly more loss aversion compared to medicated OCD or controls, an effect that was replicated across both sites and remained significant even after controlling for OCD symptom severity, trait anxiety, and sex. Post hoc analyses further indicated that unmedicated patients’ increased likelihood to reject a gamble as its loss value increased could not be explained solely by greater risk aversion among patients. Unmedicated patients were also slower to accept than reject gambles, effects that were not found in the other two groups. Loss aversion was correlated with decision times in unmedicated patients but not in the other two groups.DiscussionThese data identify abnormalities of decision-making in a subgroup of OCD patients not taking psychotropic medication. The findings help elucidate the cognitive mechanisms of the disorder and suggest that future treatments could aim to target

  3. Biodiversity offsets and the challenge of achieving no net loss.

    Science.gov (United States)

    Gardner, Toby A; VON Hase, Amrei; Brownlie, Susie; Ekstrom, Jonathan M M; Pilgrim, John D; Savy, Conrad E; Stephens, R T Theo; Treweek, Jo; Ussher, Graham T; Ward, Gerri; Ten Kate, Kerry

    2013-12-01

    Businesses, governments, and financial institutions are increasingly adopting a policy of no net loss of biodiversity for development activities. The goal of no net loss is intended to help relieve tension between conservation and development by enabling economic gains to be achieved without concomitant biodiversity losses. biodiversity offsets represent a necessary component of a much broader mitigation strategy for achieving no net loss following prior application of avoidance, minimization, and remediation measures. However, doubts have been raised about the appropriate use of biodiversity offsets. We examined what no net loss means as a desirable conservation outcome and reviewed the conditions that determine whether, and under what circumstances, biodiversity offsets can help achieve such a goal. We propose a conceptual framework to substitute the often ad hoc approaches evident in many biodiversity offset initiatives. The relevance of biodiversity offsets to no net loss rests on 2 fundamental premises. First, offsets are rarely adequate for achieving no net loss of biodiversity alone. Second, some development effects may be too difficult or risky, or even impossible, to offset. To help to deliver no net loss through biodiversity offsets, biodiversity gains must be comparable to losses, be in addition to conservation gains that may have occurred in absence of the offset, and be lasting and protected from risk of failure. Adherence to these conditions requires consideration of the wider landscape context of development and offset activities, timing of offset delivery, measurement of biodiversity, accounting procedures and rule sets used to calculate biodiversity losses and gains and guide offset design, and approaches to managing risk. Adoption of this framework will strengthen the potential for offsets to provide an ecologically defensible mechanism that can help reconcile conservation and development. Balances de Biodiversidad y el Reto de No Obtener P

  4. Increased Loss Aversion in Unmedicated Patients with Obsessive-Compulsive Disorder.

    Science.gov (United States)

    Sip, Kamila E; Gonzalez, Richard; Taylor, Stephan F; Stern, Emily R

    2017-01-01

    Obsessive-compulsive disorder (OCD) patients show abnormalities in decision-making and, clinically, appear to show heightened sensitivity to potential negative outcomes. Despite the importance of these cognitive processes in OCD, few studies have examined the disorder within an economic decision-making framework. Here, we investigated loss aversion, a key construct in the prospect theory that describes the tendency for individuals to be more sensitive to potential losses than gains when making decisions. Across two study sites, groups of unmedicated OCD patients ( n  = 14), medicated OCD patients ( n  = 29), and healthy controls ( n  = 34) accepted or rejected a series of 50/50 gambles containing varying loss/gain values. Loss aversion was calculated as the ratio of the likelihood of rejecting a gamble with increasing potential losses to the likelihood of accepting a gamble with increasing potential gains. Decision times to accept or reject were also examined and correlated with loss aversion. Unmedicated OCD patients exhibited significantly more loss aversion compared to medicated OCD or controls, an effect that was replicated across both sites and remained significant even after controlling for OCD symptom severity, trait anxiety, and sex. Post hoc analyses further indicated that unmedicated patients' increased likelihood to reject a gamble as its loss value increased could not be explained solely by greater risk aversion among patients. Unmedicated patients were also slower to accept than reject gambles, effects that were not found in the other two groups. Loss aversion was correlated with decision times in unmedicated patients but not in the other two groups. These data identify abnormalities of decision-making in a subgroup of OCD patients not taking psychotropic medication. The findings help elucidate the cognitive mechanisms of the disorder and suggest that future treatments could aim to target abnormalities of loss/gain processing during

  5. A high-fat diet induces bone loss in mice lacking the Alox5 gene.

    Science.gov (United States)

    Le, Phuong; Kawai, Masanobu; Bornstein, Sheila; DeMambro, Victoria E; Horowitz, Mark C; Rosen, Clifford J

    2012-01-01

    5-Lipoxygenase catalyzes leukotriene generation from arachidonic acid. The gene that encodes 5-lipoxygenase, Alox5, has been identified in genome-wide association and mouse Quantitative Trait Locus studies as a candidate gene for obesity and low bone mass. Thus, we tested the hypothesis that Alox5(-/-) mice would exhibit metabolic and skeletal changes when challenged by a high-fat diet (HFD). On a regular diet, Alox5(-/-) mice did not differ in total body weight, percent fat mass, or bone mineral density compared with wild-type (WT) controls (P < 0.05). However, when placed on a HFD, Alox5(-/-) gained more fat mass and lost greater areal bone mass vs. WT (P < 0.05). Microarchitectural analyses revealed that on a HFD, WT showed increases in cortical area (P < 0.01) and trabecular thickness (P < 0.01), whereas Alox5(-/-) showed no change in cortical parameters but a decrease in trabecular number (P < 0.05) and bone volume fraction compared with WT controls (P < 0.05). By histomorphometry, a HFD did not change bone formation rates of either strain but produced an increase in osteoclast number per bone perimeter in Alox5(-/-) mice (P < 0.03). In vitro, osteoclastogenesis of marrow stromal cells was enhanced in mutant but not WT mice fed a HFD. Gene expression for Rankl, Pparg, and Cox-2 was greater in the femur of Alox5(-/-) than WT mice on a HFD (P < 0.01), but these increases were suppressed in the Alox5(-/-) mice after 8 wk of treatment with celecoxib, a cyclooxygenase-2 inhibitor. In sum, there is a strong gene by environmental interaction for bone mass when mice lacking the Alox5 gene are fed a HFD.

  6. Communicating Earthquake Preparedness: The Influence of Induced Mood, Perceived Risk, and Gain or Loss Frames on Homeowners' Attitudes Toward General Precautionary Measures for Earthquakes.

    Science.gov (United States)

    Marti, Michèle; Stauffacher, Michael; Matthes, Jörg; Wiemer, Stefan

    2018-04-01

    Despite global efforts to reduce seismic risk, actual preparedness levels remain universally low. Although earthquake-resistant building design is the most efficient way to decrease potential losses, its application is not a legal requirement across all earthquake-prone countries and even if, often not strictly enforced. Risk communication encouraging homeowners to take precautionary measures is therefore an important means to enhance a country's earthquake resilience. Our study illustrates that specific interactions of mood, perceived risk, and frame type significantly affect homeowners' attitudes toward general precautionary measures for earthquakes. The interdependencies of the variables mood, risk information, and frame type were tested in an experimental 2 × 2 × 2 design (N = 156). Only in combination and not on their own, these variables effectively influence attitudes toward general precautionary measures for earthquakes. The control variables gender, "trait anxiety" index, and alteration of perceived risk adjust the effect. Overall, the group with the strongest attitudes toward general precautionary actions for earthquakes are homeowners with induced negative mood who process high-risk information and gain-framed messages. However, the conditions comprising induced negative mood, low-risk information and loss-frame and induced positive mood, low-risk information and gain-framed messages both also significantly influence homeowners' attitudes toward general precautionary measures for earthquakes. These results mostly confirm previous findings in the field of health communication. For practitioners, our study emphasizes that carefully compiled communication measures are a powerful means to encourage precautionary attitudes among homeowners, especially for those with an elevated perceived risk. © 2017 Society for Risk Analysis.

  7. On the genetics of loss aversion: An interaction effect of BDNF Val66Met and DRD2/ANKK1 Taq1a.

    Science.gov (United States)

    Voigt, Gesine; Montag, Christian; Markett, Sebastian; Reuter, Martin

    2015-12-01

    Loss aversion is the tendency to overweight losses compared with gains in decision situations. Several studies have investigated the neurobiological background of this phenomenon and it was found that activation in the mesolimbic-mesocortical dopamine system during a gambling decision correlates with loss aversion. In a behavioral experiment with N = 143 subjects, the present study investigates the influence of 2 functional single-nucleotide polymorphisms on the BDNF gene (BDNF Val66Met polymorphism) and ANKK1 gene (DRD2 Taq1a/ANKK1 polymorphism), that are known to affect the dopamine system, on loss aversion. Additionally, associations of alexithymia, a personality construct describing the disability to consciously experience emotions in the self, with loss aversion and with the mentioned polymorphisms were assessed using the TAS-20 questionnaire, to replicate associations that have been reported before. Results revealed a significant interaction effect of the 2 polymorphisms on loss aversion. Carriers of the genetic constellation 66Met+/A1+ had the lowest loss aversion scores, compared with all other allelic groups. According to the literature this allelic configuration is characterized by a relatively low D2/3 receptor binding in the striatum and an impaired activity-dependent secretion of BDNF. This is the first study showing that loss aversion is related to naturally occurring differences in dopamine function. (c) 2015 APA, all rights reserved).

  8. Molecular evolution of the odorant and gustatory receptor genes in lepidopteran insects: implications for their adaptation and speciation.

    Science.gov (United States)

    Engsontia, Patamarerk; Sangket, Unitsa; Chotigeat, Wilaiwan; Satasook, Chutamas

    2014-08-01

    Lepidoptera (comprised of butterflies and moths) is one of the largest groups of insects, including more than 160,000 described species. Chemoreception plays important roles in the adaptation of these species to a wide range of niches, e.g., plant hosts, egg-laying sites, and mates. This study investigated the molecular evolution of the lepidopteran odorant (Or) and gustatory receptor (Gr) genes using recently identified genes from Bombyx mori, Danaus plexippus, Heliconius melpomene, Plutella xylostella, Heliothis virescens, Manduca sexta, Cydia pomonella, and Spodoptera littoralis. A limited number of cases of large lineage-specific gene expansion are observed (except in the P. xylostella lineage), possibly due to selection against tandem gene duplication. There has been strong purifying selection during the evolution of both lepidopteran odorant and gustatory genes, as shown by the low ω values estimated through CodeML analysis, ranging from 0.0093 to 0.3926. However, purifying selection has been relaxed on some amino acid sites in these receptors, leading to sequence divergence, which is a precursor of positive selection on these sequences. Signatures of positive selection were detected only in a few loci from the lineage-specific analysis. Estimation of gene gains and losses suggests that the common ancestor of the Lepidoptera had fewer Or genes compared to extant species and an even more reduced number of Gr genes, particularly within the bitter receptor clade. Multiple gene gains and a few gene losses occurred during the evolution of Lepidoptera. Gene family expansion may be associated with the adaptation of lepidopteran species to plant hosts, especially after angiosperm radiation. Phylogenetic analysis of the moth sex pheromone receptor genes suggested that chromosomal translocations have occurred several times. New sex pheromone receptors have arisen through tandem gene duplication. Positive selection was detected at some amino acid sites predicted to be

  9. Utilizing wideband AMC structures for high-gain inkjet-printed antennas on lossy paper substrate

    KAUST Repository

    Cook, Benjamin Stassen; Shamim, Atif

    2013-01-01

    % electrical size reduction. The effect of AMC bandwidth on substrate losses and the gain reduction caused by finite AMC array effects are investigated in an effort to produce high-gain, miniaturized, low-cost wearable and structure mount antennas. © 2013 IEEE.

  10. CNVs affecting cancer predisposing genes (CPGs) detected as incidental findings in routine germline diagnostic chromosomal microarray (CMA) testing.

    Science.gov (United States)

    Innes, Josie; Reali, Lisa; Clayton-Smith, Jill; Hall, Georgina; Lim, Derek Hk; Burghel, George J; French, Kim; Khan, Unzela; Walker, Daniel; Lalloo, Fiona; Evans, D Gareth R; McMullan, Dominic; Maher, Eamonn R; Woodward, Emma R

    2018-02-01

    Identification of CNVs through chromosomal microarray (CMA) testing is the first-line investigation in individuals with learning difficulties/congenital abnormalities. Although recognised that CMA testing may identify CNVs encompassing a cancer predisposition gene (CPG), limited information is available on the frequency and nature of such results. We investigated CNV gains and losses affecting 39 CPGs in 3366 pilot index case individuals undergoing CMA testing, and then studied an extended cohort (n=10 454) for CNV losses at 105 CPGs and CNV gains at 9 proto-oncogenes implicated in inherited cancer susceptibility. In the pilot cohort, 31/3366 (0.92%) individuals had a CNV involving one or more of 16/39 CPGs. 30/31 CNVs involved a tumour suppressor gene (TSG), and 1/30 a proto-oncogene (gain of MET ). BMPR1A , TSC2 and TMEM127 were affected in multiple cases. In the second stage analysis, 49/10 454 (0.47%) individuals in the extended cohort had 50 CNVs involving 24/105 CPGs. 43/50 CNVs involved a TSG and 7/50 a proto-oncogene (4 gains, 3 deletions). The most frequently involved genes, FLCN (n=10) and SDHA (n=7), map to the Smith-Magenis and cri-du-chat regions, respectively. Incidental identification of a CNV involving a CPG is not rare and poses challenges for future cancer risk estimation. Prospective data collection from CPG-CNV cohorts ascertained incidentally and through syndromic presentations is required to determine the risks posed by specific CNVs. In particular, ascertainment and investigation of adults with CPG-CNVs and adults with learning disability and cancer, could provide important information to guide clinical management and surveillance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Loss of lager specific genes and subtelomeric regions define two different Saccharomyces cerevisiae lineages for Saccharomyces pastorianus Group I and II strains.

    Science.gov (United States)

    Monerawela, Chandre; James, Tharappel C; Wolfe, Kenneth H; Bond, Ursula

    2015-03-01

    Lager yeasts, Saccharomyces pastorianus, are interspecies hybrids between S. cerevisiae and S. eubayanus and are classified into Group I and Group II clades. The genome of the Group II strain, Weihenstephan 34/70, contains eight so-called 'lager-specific' genes that are located in subtelomeric regions. We evaluated the origins of these genes through bioinformatic and PCR analyses of Saccharomyces genomes. We determined that four are of cerevisiae origin while four originate from S. eubayanus. The Group I yeasts contain all four S. eubayanus genes but individual strains contain only a subset of the cerevisiae genes. We identified S. cerevisiae strains that contain all four cerevisiae 'lager-specific' genes, and distinct patterns of loss of these genes in other strains. Analysis of the subtelomeric regions uncovered patterns of loss in different S. cerevisiae strains. We identify two classes of S. cerevisiae strains: ale yeasts (Foster O) and stout yeasts with patterns of 'lager-specific' genes and subtelomeric regions identical to Group I and II S. pastorianus yeasts, respectively. These findings lead us to propose that Group I and II S. pastorianus strains originate from separate hybridization events involving different S. cerevisiae lineages. Using the combined bioinformatic and PCR data, we describe a potential classification map for industrial yeasts. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

  12. Microarray analysis of subcutaneous adipose tissue from mature cows with divergent body weight gain after feed restriction and realimentation

    Directory of Open Access Journals (Sweden)

    H.C. Cunningham

    2018-02-01

    Full Text Available Body weight response to periods of feed restriction and realimentation is critical and relevant to the agricultural industry. The purpose of this study was to evaluate differentially expressed genes identified in subcutaneous adipose tissue collected from cows divergent in body weight (BW gain after feed restriction and realimentation. We compared adipose samples from cows with greater gain based on average daily gain (ADG during realimentation with samples from cows with lesser gain. Specifically, there were four comparisons including two comparing the high and low gain animals across each feeding period (feed restriction and realimentation and two that compared differences in feed restriction and realimentation across high or low gain classifications. Using microarray analysis, we provide a set of differentially expressed genes identified between the high and low gain at both periods of nutrient restriction and realimentation. These data identify multiple differentially expressed genes between these two phenotypes across both nutritional environments. Keywords: Beef cows, Subcutaneous fat, Transcriptome

  13. Capacity gains of buffer-aided moving relays

    KAUST Repository

    Zafar, Ammar

    2017-03-14

    This work investigates the gain due to reduction in path loss by deploying buffer-aided moving relaying. In particular, the increase in gain due to moving relays is studied for dual-hop broadcast channels and the bidirectional relay channel. It is shown that the exploited gains in these channels due to buffer-aided relaying can be enhanced by utilizing the fact that a moving relay can communicate with the terminal closest to it and store the data in the buffer and then forward the data to the intended destination when it comes in close proximity with the destination. Numerical results show that for both the considered channels the achievable rates are increased as compared to the case of stationary relays. Numerical results also show that more significant increase in performance is seen when the relay moves to-and-fro between the source and the relay.

  14. Capacity gains of buffer-aided moving relays

    KAUST Repository

    Zafar, Ammar; Shaqfeh, Mohammad; Alnuweiri, Hussein; Alouini, Mohamed-Slim

    2017-01-01

    This work investigates the gain due to reduction in path loss by deploying buffer-aided moving relaying. In particular, the increase in gain due to moving relays is studied for dual-hop broadcast channels and the bidirectional relay channel. It is shown that the exploited gains in these channels due to buffer-aided relaying can be enhanced by utilizing the fact that a moving relay can communicate with the terminal closest to it and store the data in the buffer and then forward the data to the intended destination when it comes in close proximity with the destination. Numerical results show that for both the considered channels the achievable rates are increased as compared to the case of stationary relays. Numerical results also show that more significant increase in performance is seen when the relay moves to-and-fro between the source and the relay.

  15. Shifts of heat availability and stressful temperatures in Russian Federation result in gains and losses of wheat thermal suitability

    Science.gov (United States)

    Di Paola, Arianna; Caporaso, Luca; Santini, Monia; Di Paola, Francesco; Vasenev, Ivan; Valentini, Riccardo

    2017-04-01

    Climate changes are likely to shift the suitability of lands devoted to cropping systems. We explored the past-to-future thermal suitability of Russian Federation for wheat (Triticum aestivum) culture through an ensemble of bias corrected CMIP5-GCMs outputs considering two representative concentration pathways (RCP 4.5 and 8.5). Thermal suitability assesses where wheat heat requirement, counted from suggested sowing dates, is satisfied without the occurrence of stressful hot and frost temperatures. Thermal requirement was estimated by means of phenological observations on soft wheat involving different wheat cultivar collected in different regions of Russian Federation, Azerbaidhan, Kazakhstan and Tadzhikistan, whilst stressful temperatures were taken from a literature survey. Results showed projected geographical shift of heat resource toward the north-eastern regions, currently mainly covered by forests and croplands, but also an increase of very hot temperatures in the most productive areas of the southern regions. Gains and losses were then quantified and discussed from both agronomical and climatic perspective.

  16. An overview of hereditary hearing loss.

    Science.gov (United States)

    Bayazit, Yildirim A; Yilmaz, Metin

    2006-01-01

    Understanding the genetic basis of hearing loss is important because almost 50% of profound hearing loss are caused by genetic factors and more than 120 independent genes have been identified. In this review, after a brief explanation of some genetic terms (allele, heterozygosis, homozygosis, polymorphism, genotype and phenotype), classification of genetic hearing loss (syndromic versus nonsyndromic, and recessive dominant, X-linked and mitochondrial) was performed. Some of the most common syndromes (Usher, Pendred, Jervell and Lange-Nielsen, Waardenburg, branchio-oto-renal, Stickler, Treacher Collins and Alport syndromes, biotinidase deficiency and Norrie disease) causing genetic hearing loss were also explained briefly. The genes involved in hearing loss and genetic heterogeneity were presented. Copyright 2006 S. Karger AG, Basel.

  17. The combined effect of side-coupled gain cavity and lossy cavity on the plasmonic response of metal-dielectric-metal surface plasmon polariton waveguide

    International Nuclear Information System (INIS)

    Zhu, Qiong-gan; Wang, Zhi-guo; Tan, Wei

    2014-01-01

    The combined effect of side-coupled gain cavity and lossy cavity on the plasmonic response of metal-dielectric-metal (MDM) surface plasmon polariton (SPP) waveguide is investigated theoretically using Green's function method. Our result suggests that the gain and loss parameters influence the amplitude and phase of the fields localized in the two cavities. For the case of balanced gain and loss, the fields of the two cavities are always of equi-amplitude but out of phase. A plasmon induced transparency (PIT)-like transmission peak can be achieved by the destructive interference of two fields with anti-phase. For the case of unbalanced gain and loss, some unexpected responses of structure are generated. When the gain is more than the loss, the system response is dissipative at around the resonant frequency of the two cavities, where the sum of reflectance and transmittance becomes less than one. This is because the lossy cavity, with a stronger localized field, makes the main contribution to the system response. When the gain is less than the loss, the reverse is true. It is found that the metal loss dissipates the system energy but facilitates the gain cavity to make a dominant effect on the system response. This mechanism may have a potential application for optical amplification and for a plasmonic waveguide switch. (paper)

  18. Weight gain following breast cancer diagnosis: Implication and proposed mechanisms

    Science.gov (United States)

    Makari-Judson, Grace; Braun, Barry; Jerry, D Joseph; Mertens, Wilson C

    2014-01-01

    Weight gain occurs in the majority of women following breast cancer treatment. An overview of studies describing weight gain amongst women treated with early to modern chemotherapy regimens is included. Populations at higher risk include women who are younger, closer to ideal body weight and who have been treated with chemotherapy. Weight gain ranges between 1 to 5 kg, and may be associated with change in body composition with gain in fat mass and loss in lean body mass. Women are unlikely to return to pre-diagnosis weight. Possible mechanisms including inactivity and metabolic changes are explored. Potential interventions are reviewed including exercise, dietary changes and pharmacologic agents. Although breast cancer prognosis does not appear to be significantly impacted, weight gain has negative consequences on quality of life and overall health. Future studies should explore change in body composition, metabolism and insulin resistance. Avoiding weight gain in breast cancer survivors following initial diagnosis and treatment should be encouraged. PMID:25114844

  19. Loss-of-function and gain-of-function phenotypes of stomatocytosis mutant RhAG F65S

    Science.gov (United States)

    Stewart, Andrew K.; Shmukler, Boris E.; Vandorpe, David H.; Rivera, Alicia; Heneghan, John F.; Li, Xiaojin; Hsu, Ann; Karpatkin, Margaret; O'Neill, Allison F.; Bauer, Daniel E.; Heeney, Matthew M.; John, Kathryn; Kuypers, Frans A.; Gallagher, Patrick G.; Lux, Samuel E.; Brugnara, Carlo; Westhoff, Connie M.

    2011-01-01

    Four patients with overhydrated cation leak stomatocytosis (OHSt) exhibited the heterozygous RhAG missense mutation F65S. OHSt erythrocytes were osmotically fragile, with elevated Na and decreased K contents and increased cation channel-like activity. Xenopus oocytes expressing wild-type RhAG and RhAG F65S exhibited increased ouabain and bumetanide-resistant uptake of Li+ and 86Rb+, with secondarily increased 86Rb+ influx sensitive to ouabain and to bumetanide. Increased RhAG-associated 14C-methylammonium (MA) influx was severely reduced in RhAG F65S-expressing oocytes. RhAG-associated influxes of Li+, 86Rb+, and 14C-MA were pharmacologically distinct, and Li+ uptakes associated with RhAG and RhAG F65S were differentially inhibited by NH4+ and Gd3+. RhAG-expressing oocytes were acidified and depolarized by 5 mM bath NH3/NH4+, but alkalinized and depolarized by subsequent bath exposure to 5 mM methylammonium chloride (MA/MA+). RhAG F65S-expressing oocytes exhibited near-wild-type responses to NH4Cl, but MA/MA+ elicited attenuated alkalinization and strong hyperpolarization. Expression of RhAG or RhAG F65S increased steady-state cation currents unaltered by bath Li+ substitution or bath addition of 5 mM NH4Cl or MA/MA+. These oocyte studies suggest that 1) RhAG expression increases oocyte transport of NH3/NH4+ and MA/MA+; 2) RhAG F65S exhibits gain-of-function phenotypes of increased cation conductance/permeability, and loss-of-function phenotypes of decreased and modified MA/MA+ transport, and decreased NH3/NH4+-associated depolarization; and 3) RhAG transports NH3/NH4+ and MA/MA+ by distinct mechanisms, and/or the substrates elicit distinct cellular responses. Thus, RhAG F65S is a loss-of-function mutation for amine transport. The altered oocyte intracellular pH, membrane potential, and currents associated with RhAG or RhAG F65S expression may reflect distinct transport mechanisms. PMID:21849667

  20. A Review of Gene Delivery and Stem Cell Based Therapies for Regenerating Inner Ear Hair Cells

    Directory of Open Access Journals (Sweden)

    Michael S. Detamore

    2011-09-01

    Full Text Available Sensory neural hearing loss and vestibular dysfunction have become the most common forms of sensory defects, affecting millions of people worldwide. Developing effective therapies to restore hearing loss is challenging, owing to the limited regenerative capacity of the inner ear hair cells. With recent advances in understanding the developmental biology of mammalian and non-mammalian hair cells a variety of strategies have emerged to restore lost hair cells are being developed. Two predominant strategies have developed to restore hair cells: transfer of genes responsible for hair cell genesis and replacement of missing cells via transfer of stem cells. In this review article, we evaluate the use of several genes involved in hair cell regeneration, the advantages and disadvantages of the different viral vectors employed in inner ear gene delivery and the insights gained from the use of embryonic, adult and induced pluripotent stem cells in generating inner ear hair cells. Understanding the role of genes, vectors and stem cells in therapeutic strategies led us to explore potential solutions to overcome the limitations associated with their use in hair cell regeneration.

  1. A review of gene delivery and stem cell based therapies for regenerating inner ear hair cells.

    Science.gov (United States)

    Devarajan, Keerthana; Staecker, Hinrich; Detamore, Michael S

    2011-09-13

    Sensory neural hearing loss and vestibular dysfunction have become the most common forms of sensory defects, affecting millions of people worldwide. Developing effective therapies to restore hearing loss is challenging, owing to the limited regenerative capacity of the inner ear hair cells. With recent advances in understanding the developmental biology of mammalian and non-mammalian hair cells a variety of strategies have emerged to restore lost hair cells are being developed. Two predominant strategies have developed to restore hair cells: transfer of genes responsible for hair cell genesis and replacement of missing cells via transfer of stem cells. In this review article, we evaluate the use of several genes involved in hair cell regeneration, the advantages and disadvantages of the different viral vectors employed in inner ear gene delivery and the insights gained from the use of embryonic, adult and induced pluripotent stem cells in generating inner ear hair cells. Understanding the role of genes, vectors and stem cells in therapeutic strategies led us to explore potential solutions to overcome the limitations associated with their use in hair cell regeneration.

  2. Cocaine dependent individuals discount future rewards more than future losses for both cocaine and monetary outcomes.

    Science.gov (United States)

    Johnson, Matthew W; Bruner, Natalie R; Johnson, Patrick S

    2015-01-01

    Cocaine dependence and other forms of drug dependence are associated with steeper devaluation of future outcomes (delay discounting). Although studies in this domain have typically assessed choices between monetary gains (e.g., receive less money now versus receive more money after a delay), delay discounting is also applicable to decisions involving losses (e.g., small loss now versus larger delayed loss), with gains typically discounted more than losses (the "sign effect"). It is also known that drugs are discounted more than equivalently valued money. In the context of drug dependence, however, relatively little is known about the discounting of delayed monetary and drug losses and the presence of the sign effect. In this within-subject, laboratory study, delay discounting for gains and losses was assessed for cocaine and money outcomes in cocaine-dependent individuals (n=89). Both cocaine and monetary gains were discounted at significantly greater rates than cocaine and monetary losses, respectively (i.e., the sign effect). Cocaine gains were discounted significantly more than monetary gains, but cocaine and monetary losses were discounted similarly. Results suggest that cocaine is discounted by cocaine-dependent individuals in a systematic manner similar to other rewards. Because the sign effect was shown for both cocaine and money, delayed aversive outcomes may generally have greater impact than delayed rewards in shaping present behavior in this population. Copyright © 2014. Published by Elsevier Ltd.

  3. The functional and structural neural basis of individual differences in loss aversion.

    Science.gov (United States)

    Canessa, Nicola; Crespi, Chiara; Motterlini, Matteo; Baud-Bovy, Gabriel; Chierchia, Gabriele; Pantaleo, Giuseppe; Tettamanti, Marco; Cappa, Stefano F

    2013-09-04

    Decision making under risk entails the anticipation of prospective outcomes, typically leading to the greater sensitivity to losses than gains known as loss aversion. Previous studies on the neural bases of choice-outcome anticipation and loss aversion provided inconsistent results, showing either bidirectional mesolimbic responses of activation for gains and deactivation for losses, or a specific amygdala involvement in processing losses. Here we focused on loss aversion with the aim to address interindividual differences in the neural bases of choice-outcome anticipation. Fifty-six healthy human participants accepted or rejected 104 mixed gambles offering equal (50%) chances of gaining or losing different amounts of money while their brain activity was measured with functional magnetic resonance imaging (fMRI). We report both bidirectional and gain/loss-specific responses while evaluating risky gambles, with amygdala and posterior insula specifically tracking the magnitude of potential losses. At the individual level, loss aversion was reflected both in limbic fMRI responses and in gray matter volume in a structural amygdala-thalamus-striatum network, in which the volume of the "output" centromedial amygdala nuclei mediating avoidance behavior was negatively correlated with monetary performance. We conclude that outcome anticipation and ensuing loss aversion involve multiple neural systems, showing functional and structural individual variability directly related to the actual financial outcomes of choices. By supporting the simultaneous involvement of both appetitive and aversive processing in economic decision making, these results contribute to the interpretation of existing inconsistencies on the neural bases of anticipating choice outcomes.

  4. Antipsychotic-associated weight gain: management strategies and impact on treatment adherence

    Directory of Open Access Journals (Sweden)

    Dayabandara M

    2017-08-01

    Full Text Available Madhubhashinee Dayabandara, Raveen Hanwella, Suhashini Ratnatunga, Sudarshi Seneviratne, Chathurie Suraweera, Varuni A de Silva Department of Psychiatry, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka Abstract: Antipsychotic-induced weight gain is a major management problem for clinicians. It has been shown that weight gain and obesity lead to increased cardiovascular and cerebrovascular morbidity and mortality, reduced quality of life and poor drug compliance. This narrative review discusses the propensity of various antipsychotics to cause weight gain, the pharmacologic and nonpharmacologic interventions available to counteract this effect and its impact on adherence. Most antipsychotics cause weight gain. The risk appears to be highest with olanzapine and clozapine. Weight increases rapidly in the initial period after starting antipsychotics. Patients continue to gain weight in the long term. Children appear to be particularly vulnerable to antipsychotic-induced weight gain. Tailoring antipsychotics according to the needs of the individual and close monitoring of weight and other metabolic parameters are the best preventive strategies at the outset. Switching to an agent with lesser tendency to cause weight gain is an option, but carries the risk of relapse of the illness. Nonpharmacologic interventions of dietary counseling, exercise programs and cognitive and behavioral strategies appear to be equally effective in individual and group therapy formats. Both nonpharmacologic prevention and intervention strategies have shown modest effects on weight. Multiple compounds have been investigated as add-on medications to cause weight loss. Metformin has the best evidence in this respect. Burden of side effects needs to be considered when prescribing weight loss medications. There is no strong evidence to recommend routine prescription of add-on medication for weight reduction. Heterogeneity of study methodologies and other

  5. A novel solution to the gated x-ray detector gain droop problem

    International Nuclear Information System (INIS)

    Oertel, J. A.; Archuleta, T. N.

    2014-01-01

    Microchannel plate (MCP), microstrip transmission line based, gated x-ray detectors used at the premier ICF laser facilities have a drop in gain as a function of mircostrip length that can be greater than 50% over 40 mm. These losses are due to ohmic losses in a microstrip coating that is less than the optimum electrical skin depth. The electrical skin depth for a copper transmission line at 3 GHz is 1.2 μm while the standard microstrip coating thickness is roughly half a single skin depth. Simply increasing the copper coating thickness would begin filling the MCP pores and limit the number of secondary electrons created in the MCP. The current coating thickness represents a compromise between gain and ohmic loss. We suggest a novel solution to the loss problem by overcoating the copper transmission line with five electrical skin depths (∼6 μm) of Beryllium. Beryllium is reasonably transparent to x-rays above 800 eV and would improve the carrier current on the transmission line. The net result should be an optically flat photocathode response with almost no measurable loss in voltage along the transmission line

  6. Monetary Losses Do Not Loom Large in Later Life: Age Differences in the Framing Effect

    OpenAIRE

    Joseph A. Mikels; Andrew E. Reed

    2009-01-01

    Studies of the framing effect indicate that individuals are risk averse for decisions framed as gains but risk seeking for decisions framed as losses. However, findings regarding age-related changes in susceptibility to framing are mixed. Recent work demonstrating age-related decreases in reactivity to anticipated monetary losses, but not gains, suggests that older and younger adults might show equivalent risk aversion for gains but discrepant risk seeking for losses. In the current study, ol...

  7. 76 FR 22336 - Controlled Groups; Deferral of Losses

    Science.gov (United States)

    2011-04-21

    ... intercompany loss when B recognizes a corresponding gain. For example, if S sells 30 percent of T's stock to B... occurrence of either of two events. The deferred loss is taken into account to the extent of any... Controlled Groups; Deferral of Losses AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of...

  8. Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

    Science.gov (United States)

    2012-01-01

    Background Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes between schizophrenia and overweight patients. Discussion Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogs used in the treatment of type 2 diabetes are associated with significant and sustained weight loss in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogs are discussed. Conclusions We propose that adjunctive treatment with GLP-1 analogs may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies in schizophrenia patients with antipsychotic-induced weight gain. Clinical research to support this idea is highly warranted. PMID:22891821

  9. Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

    Directory of Open Access Journals (Sweden)

    Ebdrup Bjørn H

    2012-08-01

    Full Text Available Abstract Background Antipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1. Moreover, we account for similarities in brain changes between schizophrenia and overweight patients. Discussion Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogs used in the treatment of type 2 diabetes are associated with significant and sustained weight loss in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogs are discussed. Conclusions We propose that adjunctive treatment with GLP-1 analogs may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies in schizophrenia patients with antipsychotic-induced weight gain. Clinical research to support this idea is highly warranted.

  10. 26 CFR 1.1249-1 - Gain from certain sales or exchanges of patents, etc., to foreign corporations.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Gain from certain sales or exchanges of patents... Capital Gains and Losses § 1.1249-1 Gain from certain sales or exchanges of patents, etc., to foreign corporations. (a) General rule. Section 1249 provides that if gain is recognized from the sale or exchange...

  11. Evolution of plastid gene rps2 in a lineage of hemiparasitic and holoparasitic plants: Many losses of photosynthesis and complex patterns of rate variation

    Science.gov (United States)

    dePamphilis, Claude W.; Young, Nelson D.; Wolfe, Andrea D.

    1997-01-01

    The plastid genomes of some nonphotosynthetic parasitic plants have experienced an extreme reduction in gene content and an increase in evolutionary rate of remaining genes. Nothing is known of the dynamics of these events or whether either is a direct outcome of the loss of photosynthesis. The parasitic Scrophulariaceae and Orobanchaceae, representing a continuum of heterotrophic ability ranging from photosynthetic hemiparasites to nonphotosynthetic holoparasites, are used to investigate these issues. We present a phylogenetic hypothesis for parasitic Scrophulariaceae and Orobanchaceae based on sequences of the plastid gene rps2, encoding the S2 subunit of the plastid ribosome. Parasitic Scrophulariaceae and Orobanchaceae form a monophyletic group in which parasitism can be inferred to have evolved once. Holoparasitism has evolved independently at least five times, with certain holoparasitic lineages representing single species, genera, and collections of nonphotosynthetic genera. Evolutionary loss of the photosynthetic gene rbcL is limited to a subset of holoparasitic lineages, with several holoparasites retaining a full length rbcL sequence. In contrast, the translational gene rps2 is retained in all plants investigated but has experienced rate accelerations in several hemi- as well as holoparasitic lineages, suggesting that there may be substantial molecular evolutionary changes to the plastid genome of parasites before the loss of photosynthesis. Independent patterns of synonymous and nonsynonymous rate acceleration in rps2 point to distinct mechanisms underlying rate variation in different lineages. Parasitic Scrophulariaceae (including the traditional Orobanchaceae) provide a rich platform for the investigation of molecular evolutionary process, gene function, and the evolution of parasitism. PMID:9207097

  12. Unpleasant odors increase aversion to monetary losses.

    Science.gov (United States)

    Stancak, Andrej; Xie, Yuxin; Fallon, Nicholas; Bulsing, Patricia; Giesbrecht, Timo; Thomas, Anna; Pantelous, Athanasios A

    2015-04-01

    Loss aversion is the tendency to prefer avoiding losses over acquiring gains of equal nominal values. Unpleasant odors not only influence affective state but have also been shown to activate brain regions similar to those mediating loss aversion. Therefore, we hypothesized a stronger loss aversion in a monetary gamble task if gambles were associated with an unpleasant as opposed to pleasant odor. In thirty human subjects, unpleasant (methylmercaptan), pleasant (jasmine), and neutral (clean air) odors were presented for 4 s. At the same time, uncertain gambles offering an equal chance of gain or loss of a variable amount of money, or a prospect of an assured win were displayed. One hundred different gambles were presented three times, each time paired with a different odor. Loss aversion, risk aversion, and logit sensitivity were evaluated using non-linear fitting of individual gamble decisions. Loss aversion was larger when prospects were displayed in the presence of methylmercaptan compared to jasmine or clean air. Moreover, individual differences in changes in loss aversion to the unpleasant as compared to pleasant odor correlated with odor pleasantness but not with odor intensity. Skin conductance responses to losses during the outcome period were larger when gambles were associated with methylmercaptan compared to jasmine. Increased loss aversion while perceiving an unpleasant odor suggests a dynamic adjustment of loss aversion toward greater sensitivity to losses. Given that odors are biological signals of hazards, such adjustment of loss aversion may have adaptive value in situations entailing threat or danger. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Monetary losses do not loom large in later life: age differences in the framing effect.

    Science.gov (United States)

    Mikels, Joseph A; Reed, Andrew E

    2009-06-01

    Studies of the framing effect indicate that individuals are risk averse for decisions framed as gains but risk seeking for decisions framed as losses. However, findings regarding age-related changes in susceptibility to framing are mixed. Recent work demonstrating age-related decreases in reactivity to anticipated monetary losses, but not gains, suggests that older and younger adults might show equivalent risk aversion for gains but discrepant risk seeking for losses. In the current study, older and younger adults completed a monetary gambling task in which they chose between sure options and risky gambles (the expected outcomes of which were equated). Although both groups demonstrated risk aversion in the gain frame, only younger adults showed risk seeking in the loss frame.

  14. Exploiting orthologue diversity for systematic detection of gain-of-function phenotypes

    Directory of Open Access Journals (Sweden)

    Cantarella Daniela

    2008-05-01

    Full Text Available Abstract Background Systematic search for genes whose gain-of-function by exogenous expression confers an advantage in cell-based selective screenings is a powerful method for unbiased functional exploration of the genome, and has the potential to disclose new targets for cancer therapy. A major limit of this approach resides in the labor-intensive cloning of resistant cells, identification of the integrated genes and validation of their ability to confer a selective advantage. Moreover, the selection has to be drastic and genes conferring a limited advantage are typically missed. Results We developed a new functional screening strategy based on transduction of mammalian cells of a given species with an expression library from another species, followed by one-shot quantitative tracing with DNA microarrays of all library-derived transcripts before and after selection. In this way, exogenous transcripts enriched after selection, and therefore likely to confer resistance, are readily detected. We transduced a retroviral cDNA expression library from mouse testis into human and canine cells, and optimized the use of commercial murine gene expression arrays for species-specific detection of library-derived transcripts. We then conducted a functional screening by growing library-transduced canine MDCK cells in suspension, to enrich for cDNAs conferring anchorage independence. Notably, these cells show partial resistance to loss of anchorage, and the selection can be of limited stringency, compromising approaches based on clonal selection or anyway requiring high stringency. Microarray analysis revealed reproducible enrichment after three weeks of growth on polyhema for seven genes, among which the Hras proto-oncogene and Sox5. When individually transduced into MDCK cells, Sox5 specifically promoted anchorage-independent growth, thereby confirming the validity and specificity of the approach. Conclusion The procedure described here brings substantial

  15. Up-regulation of HOXB cluster genes are epigenetically regulated in tamoxifen-resistant MCF7 breast cancer cells.

    Science.gov (United States)

    Yang, Seoyeon; Lee, Ji-Yeon; Hur, Ho; Oh, Ji Hoon; Kim, Myoung Hee

    2018-05-28

    Tamoxifen (TAM) is commonly used to treat estrogen receptor (ER)-positive breast cancer. Despite the remarkable benefits, resistance to TAM presents a serious therapeutic challenge. Since several HOX transcription factors have been proposed as strong candidates in the development of resistance to TAM therapy in breast cancer, we generated an in vitro model of acquired TAM resistance using ER-positive MCF7 breast cancer cells (MCF7-TAMR), and analyzed the expression pattern and epigenetic states of HOX genes. HOXB cluster genes were uniquely up-regulated in MCF7-TAMR cells. Survival analysis of in slico data showed the correlation of high expression of HOXB genes with poor response to TAM in ER-positive breast cancer patients treated with TAM. Gain- and loss-of-function experiments showed that the overexpression of multi HOXB genes in MCF7 renders cancer cells more resistant to TAM, whereas the knockdown restores TAM sensitivity. Furthermore, activation of HOXB genes in MCF7-TAMR was associated with histone modifications, particularly the gain of H3K9ac. These findings imply that the activation of HOXB genes mediate the development of TAM resistance, and represent a target for development of new strategies to prevent or reverse TAM resistance.

  16. [From gene to disease; genetic causes of hearing loss and visual impairment sometimes accompanied by vestibular problems (Usher syndrome)].

    Science.gov (United States)

    Pennings, R J E; Kremer, H; Deutman, A F; Kimberling, W J; Cremers, C W R J

    2002-12-07

    Usher syndrome is an autosomal recessively inherited disease, characterised by sensorineural hearing loss, tapetoretinal degeneration and in some cases vestibular problems. Based on the clinical heterogeneity, the disease can be classified into three clinical types (I, II and III), which have their own genetic subtypes (Usher 1A-Usher IG, Usher 2A-Usher 2C and Usher 3). The majority of the Usher type I cases are caused by mutations in the MYO7A gene (Usher 1B) while mutations in the USH2A gene (Usher 2A) are the cause of most cases of type II. Usher syndrome type III, caused by mutations in the USH3 gene, is frequently seen only in Finland.

  17. Utility of barium studies for patients with recurrent weight gain after Roux-en-Y gastric bypass

    International Nuclear Information System (INIS)

    Wang, B.; Levine, M.S.; Rubesin, S.E.; Williams, N.N.; Dumon, K.; Raper, S.

    2015-01-01

    Aim: To determine the utility of barium studies for detecting abnormalities responsible for recurrent weight gain after gastric bypass surgery. Methods: A computerized search identified 42 patients who had undergone barium studies for recurrent weight gain after gastric bypass and 42 controls. The images were reviewed to determine the frequency of staple-line breakdown and measure the length/width of the pouch and gastrojejunal anastomosis. A large pouch exceeded 6 cm in length or 5 cm in width and a wide anastomosis exceeded 2 cm. Records were reviewed for the amount of recurrent weight gain and subsequent weight loss after additional treatment. Results: Staple-line breakdown was present in 6/42 patients (14%) with recurrent weight gain. When measurements were obtained, 13/35 patients (37%) with recurrent weight gain had a large pouch, three (9%) had a wide anastomosis, and four (11%) had both, whereas 22/42 controls (52%) had a large pouch, one (2%) had a wide anastomosis, and two (5%) had both. Ten patients (24%) with recurrent weight gain underwent staple-line repair (n = 3) or pouch/anastomosis revision (n = 7). These 10 patients had a mean weight loss of 38.1 lbs versus a mean loss of 8.6 lbs in 19 patients managed medically. Conclusion: Only 14% of patients with recurrent weight gain after gastric bypass had staple-line breakdown, whereas 57% had a large pouch, wide anastomosis, or both. Not all patients with abnormal anatomy had recurrent weight gain, but those who did were more likely to benefit from surgical intervention than from medical management. - Highlights: • Only 14% of patients with recurrent weight gain after gastric bypass had GGFs. • The majority of patients with recurrent weight gain had a large pouch/wide GJA. • Many patients without recurrent weight gain also had a large pouch/wide GJA. • Those with weight gain and a large pouch/wide GJA are likely to benefit from surgery

  18. Receiver gain function: the actual NMR receiver gain

    OpenAIRE

    Mo, Huaping; Harwood, John S.; Raftery, Daniel

    2010-01-01

    The observed NMR signal size depends on the receiver gain parameter. We propose a receiver gain function to characterize how much the raw FID is amplified by the receiver as a function of the receiver gain setting. Although the receiver is linear for a fixed gain setting, the actual gain of the receiver may differ from what the gain setting suggests. Nevertheless, for a given receiver, we demonstrate that the receiver gain function can be calibrated. Such a calibration enables accurate compar...

  19. No major effect of estrogen receptor gene polymorphisms on bone mineral density or bone loss in postmenopausal Danish women

    DEFF Research Database (Denmark)

    Bagger, Y Z; Jørgensen, H L; Heegaard, Anne-Marie

    2000-01-01

    The polymorphisms of the estrogen receptor (ER) gene defined by the restriction enodonucleases PvuII and XbaI have recently been reported to be associated with bone mineral density (BMD) in postmenopausal women. To investigate the possible relation of the PvuII and XbaI restriction fragment......-length polymorphisms of the ER gene with BMD in Danish postmenopausal women, two studies were undertaken: 1) a cross-sectional study of 499 postmenopausal women, where the ER genotypes and alleles were related to BMD of the hip, spine, and lower forearm; and 2) a longitudinal study of 101 postmenopausal women followed...... up for 18 years. In the latter study, late postmenopausal bone loss in the hip and spine was determined over a period of 6 years in women (mean age of 63 to 69 years), and long-term postmenopausal bone loss in the lower forearm was determined over a period of 18 years in women (mean age of 51 to 69...

  20. Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women.

    Science.gov (United States)

    Saliba, Louise F; Reis, Rodrigo S; Brownson, Ross C; Hino, Adriano A; Tureck, Luciane V; Valko, Cheryl; de Souza, Ricardo L R; Furtado-Alle, Lupe

    2014-03-01

    The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713), ADRB3 (Trp64Arg, rs4994) and GHRL (Leu72Met, rs696217) polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109). The body mass index (BMI) was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (2 × 2) were used to analyze the intervention effect between polymorphisms and BMI over the period and after stratification for age and socioeconomic status (SES). The weight loss intervention resulted in decreased BMI over the seven-week period (p polymorphism carriers and non-carriers, and although, the ADRB2, ADRB3 and GHRL polymorphisms did not moderate weight loss, the Gln27Glu polymorphism carriers showed a lower BMI compared to non-carriers in the low SES (p = 0.018) and the 30-39 y (p = 0.036) groups, suggesting a role for this polymorphism related to BMI control.

  1. The restriction-modification genes of Escherichia coli K-12 may not be selfish: they do not resist loss and are readily replaced by alleles conferring different specificities.

    Science.gov (United States)

    O'Neill, M; Chen, A; Murray, N E

    1997-12-23

    Type II restriction and modification (R-M) genes have been described as selfish because they have been shown to impose selection for the maintenance of the plasmid that encodes them. In our experiments, the type I R-M system EcoKI does not behave in the same way. The genes specifying EcoKI are, however, normally residents of the chromosome and therefore our analyses were extended to monitor the deletion of chromosomal genes rather than loss of plasmid vector. If EcoKI were to behave in the same way as the plasmid-encoded type II R-M systems, the loss of the relevant chromosomal genes by mutation or recombination should lead to cell death because the cell would become deficient in modification enzyme and the bacterial chromosome would be vulnerable to the restriction endonuclease. Our data contradict this prediction; they reveal that functional type I R-M genes in the chromosome are readily replaced by mutant alleles and by alleles encoding a type I R-M system of different specificity. The acquisition of allelic genes conferring a new sequence specificity, but not the loss of the resident genes, is dependent on the product of an unlinked gene, one predicted [Prakash-Cheng, A., Chung, S. S. & Ryu, J. (1993) Mol. Gen. Genet. 241, 491-496] to be relevant to control of expression of the genes that encode EcoKI. Our evidence suggests that not all R-M systems are evolving as "selfish" units; rather, the diversity and distribution of the family of type I enzymes we have investigated require an alternative selective pressure.

  2. Gain-assisted broadband ring cavity enhanced spectroscopy

    Science.gov (United States)

    Selim, Mahmoud A.; Adib, George A.; Sabry, Yasser M.; Khalil, Diaa

    2017-02-01

    Incoherent broadband cavity enhanced spectroscopy can significantly increase the effective path length of light-matter interaction to detect weak absorption lines over broad spectral range, for instance to detect gases in confined environments. Broadband cavity enhancement can be based on the decay time or the intensity drop technique. Decay time measurement is based on using tunable laser source that is expensive and suffers from long scan time. Intensity dependent measurement is usually reported based on broadband source using Fabry-Perot cavity, enabling short measurement time but suffers from the alignment tolerance of the cavity and the cavity insertion loss. In this work we overcome these challenges by using an alignment-free ring cavity made of an optical fiber loop and a directional coupler, while having a gain medium pumped below the lasing threshold to improve the finesse and reduce the insertion loss. Acetylene (C2H2) gas absorption is measured around 1535 nm wavelength using a semiconductor optical amplifier (SOA) gain medium. The system is analyzed for different ring resonator forward coupling coefficient and loses, including the 3-cm long gas cell insertion loss and fiber connector losses used in the experimental verification. The experimental results are obtained for a coupler ratio of 90/10 and a fiber length of 4 m. The broadband source is the amplified spontaneous emission of another SOA and the output is measured using a 70pm-resolution optical spectrum analyzer. The absorption depth and the effective interaction length are improved about an order of magnitude compared to the direct absorption of the gas cell. The presented technique provides an engineering method to improve the finesse and, consequently the effective length, while relaxing the technological constraints on the high reflectivity mirrors and free-space cavity alignment.

  3. Gain optimization in fiber optical parametric amplifiers by combining standard and high-SBS threshold highly nonlinear fibers

    DEFF Research Database (Denmark)

    Da Ros, Francesco; Rottwitt, Karsten; Peucheret, Christophe

    2012-01-01

    Combining Al-doped and Ge-doped HNLFs as gain media in FOPAs is proposed and optimized, resulting in efficient SBS mitigation while circumventing the additional loss of the high SBS threshold Al-doped fiber.......Combining Al-doped and Ge-doped HNLFs as gain media in FOPAs is proposed and optimized, resulting in efficient SBS mitigation while circumventing the additional loss of the high SBS threshold Al-doped fiber....

  4. The α1,6-fucosyltransferase gene (fut8 from the Sf9 lepidopteran insect cell line: insights into fut8 evolution.

    Directory of Open Access Journals (Sweden)

    Sylvie Juliant

    Full Text Available The core alpha1,6-fucosyltransferase (FUT8 catalyzes the transfer of a fucosyl moiety from GDP-fucose to the innermost asparagine-linked N-acetylglucosamine residue of glycoproteins. In mammals, this glycosylation has an important function in many fundamental biological processes and although no essential role has been demonstrated yet in all animals, FUT8 amino acid (aa sequence and FUT8 activity are very well conserved throughout the animal kingdom. We have cloned the cDNA and the complete gene encoding the FUT8 in the Sf9 (Spodoptera frugiperda lepidopteran cell line. As in most animal genomes, fut8 is a single-copy gene organized in different exons. The open reading frame contains 12 exons, a characteristic that seems to be shared by all lepidopteran fut8 genes. We chose to study the gene structure as a way to characterize the evolutionary relationships of the fut8 genes in metazoans. Analysis of the intron-exon organization in 56 fut8 orthologs allowed us to propose a model for fut8 evolution in metazoans. The presence of a highly variable number of exons in metazoan fut8 genes suggests a complex evolutionary history with many intron gain and loss events, particularly in arthropods, but not in chordata. Moreover, despite the high conservation of lepidoptera FUT8 sequences also in vertebrates and hymenoptera, the exon-intron organization of hymenoptera fut8 genes is order-specific with no shared exons. This feature suggests that the observed intron losses and gains may be linked to evolutionary innovations, such as the appearance of new orders.

  5. Allelic variants of melanocortin 3 receptor gene (MC3R and weight loss in obesity: a randomised trial of hypo-energetic high- versus low-fat diets.

    Directory of Open Access Journals (Sweden)

    José L Santos

    Full Text Available INTRODUCTION: The melanocortin system plays an important role in energy homeostasis. Mice genetically deficient in the melanocortin-3 receptor gene have a normal body weight with increased body fat, mild hypophagia compared to wild-type mice. In humans, Thr6Lys and Val81Ile variants of the melanocortin-3 receptor gene (MC3R have been associated with childhood obesity, higher BMI Z-score and elevated body fat percentage compared to non-carriers. The aim of this study is to assess the association in adults between allelic variants of MC3R with weight loss induced by energy-restricted diets. SUBJECTS AND METHODS: This research is based on the NUGENOB study, a trial conducted to assess weight loss during a 10-week dietary intervention involving two different hypo-energetic (high-fat and low-fat diets. A total of 760 obese patients were genotyped for 10 single nucleotide polymorphisms covering the single exon of MC3R gene and its flanking regions, including the missense variants Thr6Lys and Val81Ile. Linear mixed models and haplotype-based analysis were carried out to assess the potential association between genetic polymorphisms and differential weight loss, fat mass loss, waist change and resting energy expenditure changes. RESULTS: No differences in drop-out rate were found by MC3R genotypes. The rs6014646 polymorphism was significantly associated with weight loss using co-dominant (p = 0.04 and dominant models (p = 0.03. These p-values were not statistically significant after strict control for multiple testing. Haplotype-based multivariate analysis using permutations showed that rs3827103-rs1543873 (p = 0.06, rs6014646-rs6024730 (p = 0.05 and rs3746619-rs3827103 (p = 0.10 displayed near-statistical significant results in relation to weight loss. No other significant associations or gene*diet interactions were detected for weight loss, fat mass loss, waist change and resting energy expenditure changes. CONCLUSION: The study

  6. Stacked Transformer for Driver Gain and Receive Signal Splitting

    Science.gov (United States)

    Driscoll, Kevin R.

    2013-01-01

    In a high-speed signal transmission system that uses transformer coupling, there is a need to provide increased transmitted signal strength without adding active components. This invention uses additional transformers to achieve the needed gain. The prior art uses stronger drivers (which require an IC redesign and a higher power supply voltage), or the addition of another active component (which can decrease reliability, increase power consumption, reduce the beneficial effect of serializer/deserializer preemphasis or deemphasis, and/or interfere with fault containment mechanisms), or uses a different transformer winding ratio (which requires redesign of the transformer and may not be feasible with high-speed signals that require a 1:1 winding ratio). This invention achieves the required gain by connecting the secondaries of multiple transformers in series. The primaries of these transformers are currently either connected in parallel or are connected to multiple drivers. There is also a need to split a receive signal to multiple destinations with minimal signal loss. Additional transformers can achieve the split. The prior art uses impedance-matching series resistors that cause a loss of signal. Instead of causing a loss, most instantiations of this invention would actually provide gain. Multiple transformers are used instead of multiple windings on a single transformer because multiple windings on the same transformer would require a redesign of the transformer, and may not be feasible with high-speed transformers that usually require a bifilar winding with a 1:1 ratio. This invention creates the split by connecting the primaries of multiple transformers in series. The secondary of each transformer is connected to one of the intended destinations without the use of impedance-matching series resistors.

  7. Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease

    International Nuclear Information System (INIS)

    Skirnisdottir, Ingiridur; Mayrhofer, Markus; Rydåker, Maria; Åkerud, Helena; Isaksson, Anders

    2012-01-01

    Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II) serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome. Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified. The most significant differences (p < 0.01) in Loss-of-heterozygosity (LOH) were identified in two relatively small regions of chromosome 19; 8.0-8,8 Mbp (19 genes) and 51.5-53.0 Mbp (37 genes). Thus, 56 genes on chromosome 19 were potential candidate genes associated with clinical outcome. LOH at 19q (51-56 Mbp) was associated with shorter disease-free survival and was an independent prognostic factor for survival in a multivariate Cox regression analysis. In particular LOH on chromosome 19q (51-56 Mbp) was significantly (p < 0.01) associated with loss of TP53 function. The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome

  8. Ejector-Enhanced, Pulsed, Pressure-Gain Combustor

    Science.gov (United States)

    Paxson, Daniel E.; Dougherty, Kevin T.

    2009-01-01

    An experimental combination of an off-the-shelf valved pulsejet combustor and an aerodynamically optimized ejector has shown promise as a prototype of improved combustors for gas turbine engines. Despite their name, the constant pressure combustors heretofore used in gas turbine engines exhibit typical pressure losses ranging from 4 to 8 percent of the total pressures delivered by upstream compressors. In contrast, the present ejector-enhanced pulsejet combustor exhibits a pressure rise of about 3.5 percent at overall enthalpy and temperature ratios compatible with those of modern turbomachines. The modest pressure rise translates to a comparable increase in overall engine efficiency and, consequently, a comparable decrease in specific fuel consumption. The ejector-enhanced pulsejet combustor may also offer potential for reducing the emission of harmful exhaust compounds by making it practical to employ a low-loss rich-burn/quench/lean-burn sequence. Like all prior concepts for pressure-gain combustion, the present concept involves an approximation of constant-volume combustion, which is inherently unsteady (in this case, more specifically, cyclic). The consequent unsteadiness in combustor exit flow is generally regarded as detrimental to the performance of downstream turbomachinery. Among other adverse effects, this unsteadiness tends to detract from the thermodynamic benefits of pressure gain. Therefore, it is desirable in any intermittent combustion process to minimize unsteadiness in the exhaust path.

  9. Popular Weight Loss Strategies: a Review of Four Weight Loss Techniques.

    Science.gov (United States)

    Obert, Jonathan; Pearlman, Michelle; Obert, Lois; Chapin, Sarah

    2017-11-09

    The purpose of this paper is to review the epidemiology of obesity and the most recent literature on popular fad diets and exercise regimens that are used for weight loss. The weight loss plans that will be discussed in this article include juicing or detoxification diets, intermittent fasting, the paleo diet, and high intensity training. Despite the growing popularity of fad diets and exercise plans for weight loss, there are limited studies that actually suggest these particular regimens are beneficial and lead to long-term weight loss. Juicing or detoxification diets tend to work because they lead to extremely low caloric intake for short periods of time, however tend to lead to weight gain once a normal diet is resumed. Both intermittent fasting and the paleo diet lead to weight loss because of overall decreased caloric intake as well. Lastly, studies on short bursts of high intensity training have shown remarkable weight loss and improvements in cardiovascular health. Review of the literature does suggest that some fad diets and exercise plans do lead to weight loss; however, the studies are quite limited and are all based on the concept of caloric restriction.

  10. Beam depolarization and gain saturation in neodymium rods with a diameter of 85 mm

    Energy Technology Data Exchange (ETDEWEB)

    Sukhanov, V N; Ugodenko, A A

    1990-04-01

    Depolarization and gain saturation were investigated in rod amplifiers using phosphate and silicate Nd glasses 85 mm in diameter and 300 mm in length at a pulse duration of 35 ns. Total depolarization losses over the rod cross section were measured for various radial distributions of the small-signal gain. For the phosphate glass the losses amounted to 3-6 percent; for the silicate glass, they amounted to 4-7 percent. Saturation energy densities of 4.5 + or - 0.4 and 8.0 + or - 0.7 J/sq cm were obtained for the phosphate and silicate glass, respectively. 8 refs.

  11. Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women

    Directory of Open Access Journals (Sweden)

    Louise F. Saliba

    2014-01-01

    Full Text Available The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713, ADRB3 (Trp64Arg, rs4994 and GHRL (Leu72Met, rs696217 polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109. The body mass index (BMI was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (2 x 2 were used to analyze the intervention effect between polymorphisms and BMI over the period and after stratification for age and socioeconomic status (SES. The weight loss intervention resulted in decreased BMI over the seven-week period (p < 0.001, for high and low SES (p < 0.05 and mainly for participants with 30-49 y. The intervention did not result in a statistically significant difference in weight loss between polymorphism carriers and non-carriers, and although, the ADRB2, ADRB3 and GHRL polymorphisms did not moderate weight loss, the Gln27Glu polymorphism carriers showed a lower BMI compared to non-carriers in the low SES (p = 0.018 and the 30-39 y (p = 0.036 groups, suggesting a role for this polymorphism related to BMI control.

  12. Critical coupling and coherent perfect absorption for ranges of energies due to a complex gain and loss symmetric system

    International Nuclear Information System (INIS)

    Hasan, Mohammad; Ghatak, Ananya; Mandal, Bhabani Prasad

    2014-01-01

    We consider a non-Hermitian medium with a gain and loss symmetric, exponentially damped potential distribution to demonstrate different scattering features analytically. The condition for critical coupling (CC) for unidirectional wave and coherent perfect absorption (CPA) for bidirectional waves are obtained analytically for this system. The energy points at which total absorption occurs are shown to be the spectral singular points for the time reversed system. The possible energies at which CC occurs for left and right incidence are different. We further obtain periodic intervals with increasing periodicity of energy for CC and CPA to occur in this system. -- Highlights: •Energy ranges for CC and CPA are obtained explicitly for complex WS potential. •Analytical conditions for CC and CPA for PT symmetric WS potential are obtained. •Conditions for left and right CC are shown to be different. •Conditions for CC and CPA are shown to be that of SS for the time reversed system. •Our model shows the great flexibility of frequencies for CC and CPA

  13. Recurring DNA copy number gain at chromosome 9p13 plays a role in the activation of multiple candidate oncogenes in progressing oral premalignant lesions

    International Nuclear Information System (INIS)

    Towle, Rebecca; Tsui, Ivy F L; Zhu, Yuqi; MacLellan, Sara; Poh, Catherine F; Garnis, Cathie

    2014-01-01

    Genomic alteration at chromosome 9p has been previously reported as a frequent and critical event in oral premalignancy. While this alteration is typically reported as a loss driven by selection for CDKN2A deactivation (at 9p21.3), we detect a recurrent DNA copy number gain of ∼2.49 Mbp at chromosome 9p13 in oral premalignant lesions (OPLs) that later progressed to invasive lesions. This recurrent alteration event has been validated using fluorescence in situ hybridization in an independent set of OPLs. Analysis of publicly available gene expression datasets aided in identifying three oncogene candidates that may have driven selection for DNA copy number increases in this region (VCP, DCTN3, and STOML2). We performed in vitro silencing and activation experiments for each of these genes in oral cancer cell lines and found that each gene is independently capable of upregulating proliferation and anchorage-independent growth. We next analyzed the activity of each of these genes in biopsies of varying histological grades that were obtained from a diseased oral tissue field in a single patient, finding further molecular evidence of parallel activation of VCP, DCTN3, and STOML2 during progression from normal healthy tissue to invasive oral carcinoma. Our results support the conclusion that DNA gain at 9p13 is important to the earliest stages of oral tumorigenesis and that this alteration event likely contributes to the activation of multiple oncogene candidates capable of governing oral cancer phenotypes

  14. Loss and gain of function in SERPINB11: an example of a gene under selection on standing variation, with implications for host-pathogen interactions.

    Directory of Open Access Journals (Sweden)

    Susana Seixas

    Full Text Available Serine protease inhibitors (SERPINs are crucial in the regulation of diverse biological processes including inflammation and immune response. SERPINB11, located in the 18q21 gene cluster, is a polymorphic gene/pseudogene coding for a non-inhibitory SERPIN. In a genome-wide scan for recent selection, SERPINB11 was identified as a potential candidate gene for adaptive evolution in Yoruba. The present study sought a better understanding of the evolutionary history of SERPINB11, with special focus on evaluating its selective signature. Through the resequencing of coding and noncoding regions of SERPINB11 in 20 Yorubans and analyzing primate orthologous sequences, we identified a full-length SERPINB11 variant encoding a non-inhibitory SERPIN as the putative candidate of selection--probably driven to higher frequencies by an adaptive response using preexisting variation. In addition, we detected contrasting evolutionary features of SERPINB11 in primates: While primate phylogeny as a whole is under purifying selection, the human lineage shows evidence of positive selection in a few codons, all associated with the active SERPINB11. Comparative modeling studies suggest that positively selected codons reduce SERPINB11's ability to undergo the conformational changes typical of inhibitory SERPINs--suggesting that it is evolving towards a new non-inhibitory function in humans. Significant correlations between SERPINB11 variants and the environmental variables, pastoralism and pathogen richness, have led us to propose a selective advantage through host-pathogen interactions, possibly linked to an adaptive response combating the emergence of infectious diseases in recent human evolution. This work represents the first description of a resurrected gene in humans, and may well exemplify selection on standing variation triggered by drastic ecological shifts.

  15. Finding all sorting tandem duplication random loss operations

    DEFF Research Database (Denmark)

    Bernt, Matthias; Chen, Kuan Yu; Chen, Ming Chiang

    2011-01-01

    A tandem duplication random loss (TDRL) operation duplicates a contiguous segment of genes, followed by the random loss of one copy of each of the duplicated genes. Although the importance of this operation is founded by several recent biological studies, it has been investigated only rarely from...

  16. Massive gene losses in Asian cultivated rice unveiled by comparative genome analysis

    Directory of Open Access Journals (Sweden)

    Itoh Takeshi

    2010-02-01

    Full Text Available Abstract Background Rice is one of the most important food crops in the world. With increasing world demand for food crops, there is an urgent need to develop new cultivars that have enhanced performance with regard to yield, disease resistance, and so on. Wild rice is expected to provide useful genetic resources that could improve the present cultivated species. However, the quantity and quality of these unexplored resources remain unclear. Recent accumulation of the genomic information of both cultivated and wild rice species allows for their comparison at the molecular level. Here, we compared the genome sequence of Oryza sativa ssp. japonica with sets of bacterial artificial chromosome end sequences (BESs from two wild rice species, O. rufipogon and O. nivara, and an African rice species, O. glaberrima. Results We found that about four to five percent of the BESs of the two wild rice species and about seven percent of the African rice could not be mapped to the japonica genome, suggesting that a substantial number of genes have been lost in the japonica rice lineage; however, their close relatives still possess their counterpart genes. We estimated that during evolution, O. sativa has lost at least one thousand genes that are still preserved in the genomes of the other species. In addition, our BLASTX searches against the non-redundant protein sequence database showed that disease resistance-related proteins were significantly overrepresented in the close relative-specific genomic portions. In total, 235 unmapped BESs of the three relatives matched 83 non-redundant proteins that contained a disease resistance protein domain, most of which corresponded to an NBS-LRR domain. Conclusion We found that the O. sativa lineage appears to have recently experienced massive gene losses following divergence from its wild ancestor. Our results imply that the domestication process accelerated large-scale genomic deletions in the lineage of Asian

  17. Ovarian carcinomas with genetic and epigenetic BRCA1 loss havedistinct molecular abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E.; Blood, Katherine A.; Smith, Margaret; Spellman, Paul T.; Wang, Yuker; Miller, Dianne M.; Horsman, Doug; Faham, Malek; Gilks, C. Blake; Gray,Joe; Huntsman, David G.

    2007-07-23

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.

  18. Streamflow gains and losses and selected water-quality observations in five subreaches of the Rio Grande/Rio Bravo del Norte from near Presidio to Langtry, Texas, Big Bend area, United States and Mexico, 2006

    Science.gov (United States)

    Raines, Timothy H.; Turco, Michael J.; Connor, Patrick J.; Bennett, Jeffery B.

    2012-01-01

    Few historical streamflow and water-quality data are available to characterize the segment of the Rio Grande/Rio Bravo del Norte (hereinafter Rio Grande) extending from near Presidio to near Langtry, Texas. The U.S. Geological Survey, in cooperation with the National Park Service and the Texas Commission on Environmental Quality, collected water-quality and streamflow data from the Rio Grande from near Presidio to near Langtry, Texas, to characterize the streamflow gain and loss and selected constituent concentrations in a 336.3-mile reach of the Rio Grande from near Presidio to near Langtry, Texas. Streamflow was measured at 38 sites and water-quality samples were collected at 20 sites along the Rio Grande in February, March, and June 2006. Streamflow gains and losses over the course of the stream were measured indirectly by computing the differences in measured streamflow between sites along the stream. Water-quality data were collected and analyzed for salinity, dissolved solids, major ions, nutrients, trace elements, and stable isotopes. Selected properties and constituents were compared to available Texas Commission on Environmental Quality general use protection criteria or screening levels. Summary statistics of selected water-quality data were computed for each of the five designated subreaches. Streamflow gain and loss and water-quality constituent concentration were compared for each subreach, rather than the entire segment because of the temporal variation in sample collection caused by controlled releases upstream. Subreach A was determined to be a losing reach, and subreaches B, C, D, and E were determined to be gaining reaches. Compared to concentrations measured in upstream subreaches, downstream subreaches exhibited evidence of dilution of selected constituent concentrations. Subreaches A and B had measured total dissolved solids, chloride, and sulfate exceeding the Texas Commission on Environmental Quality general use protection criteria

  19. Sex differences in the composition of weight gain and loss in overweight and obese adults.

    Science.gov (United States)

    Millward, D Joe; Truby, Helen; Fox, Kenneth R; Livingstone, M Barbara E; Macdonald, Ian A; Tothill, Peter

    2014-03-14

    Sex differences in the ratio of fat mass (FM):fat-free mass (FFM) during weight change should differentially affect the extent of weight change during energy imbalance in men and women. In the present study, we determined FM and FFM contents by dual-energy X-ray absorptiometry and calculated the P-ratios (protein energy/total energy) of excess weight and weight loss during a randomised controlled trial of four commercial weight loss regimens. Overweight and obese women (n 210) and men (n 77) were studied at baseline and at 2 and 6 months during weight loss on four dietary regimens: Dr Atkins' New Diet Revolution; The Slim-Fast Plan; Weight-Watchers programme; Rosemary Conley's Diet and Fitness Plan. At baseline, the percentage of FFM (%FFM) and P-ratios of excess weight were 40 % and 0·071 for men and 27 % and 0·039 for women. At 2 months, men had lost twice as much weight as women and three times more FFM than women, indicating higher FFM content and P-ratios of weight loss for men, 0·052, than for women, 0·029, with no dietary effects. Between 2 and 6 months, the rate at which weight was lost decreased and the %FFM of weight loss decreased to similar low levels in men (7 %) and women (5 %): i.e. P-ratios of 0·009 and 0·006, respectively, with no dietary effects. Thus, for men compared with women, there were greater FFM content and P-ratios of weight change, which could partly, but not completely, explain their greater weight loss at 2 months. However, protein-conserving adaptations occur with increasing weight loss and over time, more extensively in men, eventually eliminating any sex difference in the composition of weight loss.

  20. Loss of the homologous recombination gene rad51 leads to Fanconi anemia-like symptoms in zebrafish.

    Science.gov (United States)

    Botthof, Jan Gregor; Bielczyk-Maczyńska, Ewa; Ferreira, Lauren; Cvejic, Ana

    2017-05-30

    RAD51 is an indispensable homologous recombination protein, necessary for strand invasion and crossing over. It has recently been designated as a Fanconi anemia (FA) gene, following the discovery of two patients carrying dominant-negative mutations. FA is a hereditary DNA-repair disorder characterized by various congenital abnormalities, progressive bone marrow failure, and cancer predisposition. In this report, we describe a viable vertebrate model of RAD51 loss. Zebrafish rad51 loss-of-function mutants developed key features of FA, including hypocellular kidney marrow, sensitivity to cross-linking agents, and decreased size. We show that some of these symptoms stem from both decreased proliferation and increased apoptosis of embryonic hematopoietic stem and progenitor cells. Comutation of p53 was able to rescue the hematopoietic defects seen in the single mutants, but led to tumor development. We further demonstrate that prolonged inflammatory stress can exacerbate the hematological impairment, leading to an additional decrease in kidney marrow cell numbers. These findings strengthen the assignment of RAD51 as a Fanconi gene and provide more evidence for the notion that aberrant p53 signaling during embryogenesis leads to the hematological defects seen later in life in FA. Further research on this zebrafish FA model will lead to a deeper understanding of the molecular basis of bone marrow failure in FA and the cellular role of RAD51.

  1. Physical training and weight loss in dogs lead to transcriptional changes in genes involved in the glucose-transport pathway in muscle and adipose tissues

    DEFF Research Database (Denmark)

    Herrera Uribe, Juber; Vitger, Anne Désiré; Ritz, Christian

    2016-01-01

    little attention. The aim of the present study was to investigate changes in the transcriptome of key energy metabolism genes in muscle and adipose tissues in response to diet-induced weight loss alone, or combined with exercise in dogs. Overweight pet dogs were enrolled on a weight loss programme, based...... on calorie restriction and physical training (FD group, n = 5) or calorie restriction alone (DO group, n = 7). mRNA expression of 12 genes and six microRNAs were investigated using quantitative real-time PCR (qPCR). In the FD group, FOXO1 and RAC1 were expressed at lower levels in adipose tissue, whereas...

  2. A bHLH gene from Tamarix hispida improves abiotic stress tolerance by enhancing osmotic potential and decreasing reactive oxygen species accumulation.

    Science.gov (United States)

    Ji, Xiaoyu; Nie, Xianguang; Liu, Yujia; Zheng, Lei; Zhao, Huimin; Zhang, Bing; Huo, Lin; Wang, Yucheng

    2016-02-01

    Basic helix-loop-helix (bHLH) leucine-zipper transcription factors play important roles in abiotic stress responses. However, their specific roles in abiotic stress tolerance are not fully known. Here, we functionally characterized a bHLH gene, ThbHLH1, from Tamarix hispida in abiotic stress tolerance. ThbHLH1 specifically binds to G-box motif with the sequence of 'CACGTG'. Transiently transfected T. hispida plantlets with transiently overexpressed ThbHLH1 and RNAi-silenced ThbHLH1 were generated for gain- and loss-of-function analysis. Transgenic Arabidopsis thaliana lines overexpressing ThbHLH1 were generated to confirm the gain- and loss-of-function analysis. Overexpression of ThbHLH1 significantly elevates glycine betaine and proline levels, increases Ca(2+) concentration and enhances peroxidase (POD) and superoxide dismutase (SOD) activities to decrease reactive oxygen species (ROS) accumulation. Additionally, ThbHLH1 regulates the expression of the genes including P5CS, BADH, CaM, POD and SOD, to activate the above physiological changes, and also induces the expression of stress tolerance-related genes LEAs and HSPs. These data suggest that ThbHLH1 induces the expression of stress tolerance-related genes to improve abiotic stress tolerance by increasing osmotic potential, improving ROS scavenging capability and enhancing second messenger in stress signaling cascades. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Cytokine gene polymorphism associations with congenital cytomegalovirus infection and sensorineural hearing loss.

    Science.gov (United States)

    Kasztelewicz, B; Czech-Kowalska, J; Lipka, B; Milewska-Bobula, B; Borszewska-Kornacka, M K; Romańska, J; Dzierżanowska-Fangrat, K

    2017-10-01

    Cytomegalovirus (CMV) is the most common viral agent of congenital infections and a leading nongenetic cause of sensorineural hearing loss (SNHL). The host immunologic factors that render a developing foetus prone to intrauterine CMV infection and development of hearing loss are unknown. The aim of this study was to assess the potential associations between the polymorphisms within cytokine and cytokine receptors genes, and the risk of congenital CMV infection, and the hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs): TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634, IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900, CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV infection and 398 uninfected controls), and related to congenital CMV infection, and the outcome. In multivariate analysis, the IL1B rs16944 TT and TNF rs1799964 TC genotypes were significantly associated with intrauterine CMV infection (aOR = 2.32; 95% CI, 1.11-4.89; p = 0.032, and aOR = 2.17, 95% CI, 1.25-3.77; p = 0.007, respectively). Twenty-two out of 72 congenitally infected newborns had confirmed SNHL. Carriers of CT or TT genotype of CCL2 rs13900 had increased risk of hearing loss at birth and at 6 months of age (aOR = 3.59; p = 0.028 and aOR = 4.10; p = 0.039, respectively). This is the first study to report an association between SNPs in IL1B, TNF, and CCL2, and susceptibility to congenital CMV infection (IL1B and TNF) and SNHL (CCL2).

  4. Optimal Tax-Timing and Asset Allocation when Tax Rebates on Capital Losses are Limited

    DEFF Research Database (Denmark)

    Marekwica, Marcel

    2012-01-01

    to realize capital gains immediately and pay capital gain taxes to regain the option to use potential future losses against a higher tax rate. This incentive adds an entirely new and as yet unstudied dimension to the portfolio problem. It causes risk averse investors to hold more equity and attain higher......This article studies the portfolio problem with realization-based capital gain taxation when limited amounts of losses qualify for tax rebate payments, as is the case under current US tax law. When the tax rate applicable to realized losses exceeds that on realized capital gains, it can be optimal...... welfare levels than is the case when trading under a tax system that seeks to collect the same amount of taxes, but does not allow for tax rebate payments. This is because the benefit to these investors from having their losses subsidized is greater than the suffering from having profits taxed at a higher...

  5. A Bidirectional Resonant DC-DC Converter Suitable for Wide Voltage Gain Range

    DEFF Research Database (Denmark)

    Shen, Yanfeng; Wang, Huai; Al-Durra, Ahmed

    2018-01-01

    This paper proposes a new bidirectional resonant dc-dc converter suitable for wide voltage gain range applications (e.g., energy storage systems). The proposed converter overcomes the narrow voltage gain range of conventional resonant dc-dc converters, and meanwhile achieves high efficiency...... losses. The operation principles and characteristics of the proposed converter are firstly analyzed in this paper. Then the analytical solutions for the voltage gain, soft-switching, and rms currents are derived, which facilitates the parameters design and optimization. Finally, the proposed topology...... and analysis are verified with experimental results obtained from a 1-kW converter prototype....

  6. Progressive thalamocortical neuron loss in Cln5 deficient mice: Distinct effects in Finnish variant late infantile NCL.

    Science.gov (United States)

    von Schantz, Carina; Kielar, Catherine; Hansen, Stine N; Pontikis, Charlie C; Alexander, Noreen A; Kopra, Outi; Jalanko, Anu; Cooper, Jonathan D

    2009-05-01

    Finnish variant LINCL (vLINCL(Fin)) is the result of mutations in the CLN5 gene. To gain insights into the pathological staging of this fatal pediatric disorder, we have undertaken a stereological analysis of the CNS of Cln5 deficient mice (Cln5-/-) at different stages of disease progression. Consistent with human vLINCL(Fin), these Cln5-/- mice displayed a relatively late onset regional atrophy and generalized cortical thinning and synaptic pathology, preceded by early and localized glial responses within the thalamocortical system. However, in marked contrast to other forms of NCL, neuron loss in Cln5-/- mice began in the cortex and only subsequently occurred within thalamic relay nuclei. Nevertheless, as in other NCL mouse models, this progressive thalamocortical neuron loss was still most pronounced within the visual system. These data provide unexpected evidence for a distinctive sequence of neuron loss in the thalamocortical system of Cln5-/- mice, diametrically opposed to that seen in other forms of NCL.

  7. Active Enhancement of Slow Light Based on Plasmon-Induced Transparency with Gain Materials.

    Science.gov (United States)

    Zhang, Zhaojian; Yang, Junbo; He, Xin; Han, Yunxin; Zhang, Jingjing; Huang, Jie; Chen, Dingbo; Xu, Siyu

    2018-06-03

    As a plasmonic analogue of electromagnetically induced transparency (EIT), plasmon-induced transparency (PIT) has drawn more attention due to its potential of realizing on-chip sensing, slow light and nonlinear effect enhancement. However, the performance of a plasmonic system is always limited by the metal ohmic loss. Here, we numerically report a PIT system with gain materials based on plasmonic metal-insulator-metal waveguide. The corresponding phenomenon can be theoretically analyzed by coupled mode theory (CMT). After filling gain material into a disk cavity, the system intrinsic loss can be compensated by external pump beam, and the PIT can be greatly fueled to achieve a dramatic enhancement of slow light performance. Finally, a double-channel enhanced slow light is introduced by adding a second gain disk cavity. This work paves way for a potential new high-performance slow light device, which can have significant applications for high-compact plasmonic circuits and optical communication.

  8. Coordinating a Supply Chain with a Loss-Averse Retailer and Effort Dependent Demand

    Science.gov (United States)

    Li, Liying

    2014-01-01

    This study investigates the channel coordination issue of a supply chain with a risk-neutral manufacturer and a loss-averse retailer facing stochastic demand that is sensitive to sales effort. Under the loss-averse newsvendor setting, a distribution-free gain/loss-sharing-and-buyback (GLB) contract has been shown to be able to coordinate the supply chain. However, we find that a GLB contract remains ineffective in managing the supply chain when retailer sales efforts influence the demand. To effectively coordinate the channel, we propose to combine a GLB contract with sales rebate and penalty (SRP) contract. In addition, we discover a special class of gain/loss contracts that can coordinate the supply chain and arbitrarily allocate the expected supply chain profit between the manufacturer and the retailer. We then analyze the effect of loss aversion on the retailer's decision-making behavior and supply chain performance. Finally, we perform a numerical study to illustrate the findings and gain additional insights. PMID:25197696

  9. Coordinating a supply chain with a loss-averse retailer and effort dependent demand.

    Science.gov (United States)

    Li, Liying; Wang, Yong

    2014-01-01

    This study investigates the channel coordination issue of a supply chain with a risk-neutral manufacturer and a loss-averse retailer facing stochastic demand that is sensitive to sales effort. Under the loss-averse newsvendor setting, a distribution-free gain/loss-sharing-and-buyback (GLB) contract has been shown to be able to coordinate the supply chain. However, we find that a GLB contract remains ineffective in managing the supply chain when retailer sales efforts influence the demand. To effectively coordinate the channel, we propose to combine a GLB contract with sales rebate and penalty (SRP) contract. In addition, we discover a special class of gain/loss contracts that can coordinate the supply chain and arbitrarily allocate the expected supply chain profit between the manufacturer and the retailer. We then analyze the effect of loss aversion on the retailer's decision-making behavior and supply chain performance. Finally, we perform a numerical study to illustrate the findings and gain additional insights.

  10. MOSFET-Only Mixer/IIR Filter with Gain using Parametric Amplification

    DEFF Research Database (Denmark)

    Custódio, José R.; Oliveira, J.; Oliveira, L. B.

    2010-01-01

    This paper describes the design of a discrete-time passive Mixer/IIR filter. The use of an improved MOS Parametric Amplification leads to a moderate gain in the signal path and improved noise performance, instead of the conversion loss inherent to passive mixers. Simulation results demonstrate th...

  11. Independent losses of visual perception genes Gja10 and Rbp3 in echolocating bats (Order: Chiroptera.

    Directory of Open Access Journals (Sweden)

    Bin Shen

    Full Text Available A trade-off between the sensory modalities of vision and hearing is likely to have occurred in echolocating bats as the sophisticated mechanism of laryngeal echolocation requires considerable neural processing and has reduced the reliance of echolocating bats on vision for perceiving the environment. If such a trade-off exists, it is reasonable to hypothesize that some genes involved in visual function may have undergone relaxed selection or even functional loss in echolocating bats. The Gap junction protein, alpha 10 (Gja10, encoded by Gja10 gene is expressed abundantly in mammal retinal horizontal cells and plays an important role in horizontal cell coupling. The interphotoreceptor retinoid-binding protein (Irbp, encoded by the Rbp3 gene is mainly expressed in interphotoreceptor matrix and is known to be critical for normal functioning of the visual cycle. We sequenced Gja10 and Rbp3 genes in a taxonomically wide range of bats with divergent auditory characteristics (35 and 18 species for Gja10 and Rbp3, respectively. Both genes have became pseudogenes in species from the families Hipposideridae and Rhinolophidae that emit constant frequency echolocation calls with Doppler shift compensation at high-duty-cycles (the most sophisticated form of biosonar known, and in some bat species that emit echolocation calls at low-duty-cycles. Our study thus provides further evidence for the hypothesis that a trade-off occurs at the genetic level between vision and echolocation in bats.

  12. Independent losses of visual perception genes Gja10 and Rbp3 in echolocating bats (Order: Chiroptera).

    Science.gov (United States)

    Shen, Bin; Fang, Tao; Dai, Mengyao; Jones, Gareth; Zhang, Shuyi

    2013-01-01

    A trade-off between the sensory modalities of vision and hearing is likely to have occurred in echolocating bats as the sophisticated mechanism of laryngeal echolocation requires considerable neural processing and has reduced the reliance of echolocating bats on vision for perceiving the environment. If such a trade-off exists, it is reasonable to hypothesize that some genes involved in visual function may have undergone relaxed selection or even functional loss in echolocating bats. The Gap junction protein, alpha 10 (Gja10, encoded by Gja10 gene) is expressed abundantly in mammal retinal horizontal cells and plays an important role in horizontal cell coupling. The interphotoreceptor retinoid-binding protein (Irbp, encoded by the Rbp3 gene) is mainly expressed in interphotoreceptor matrix and is known to be critical for normal functioning of the visual cycle. We sequenced Gja10 and Rbp3 genes in a taxonomically wide range of bats with divergent auditory characteristics (35 and 18 species for Gja10 and Rbp3, respectively). Both genes have became pseudogenes in species from the families Hipposideridae and Rhinolophidae that emit constant frequency echolocation calls with Doppler shift compensation at high-duty-cycles (the most sophisticated form of biosonar known), and in some bat species that emit echolocation calls at low-duty-cycles. Our study thus provides further evidence for the hypothesis that a trade-off occurs at the genetic level between vision and echolocation in bats.

  13. Opportunities for biodiversity gains under the world's largest reforestation programme

    Science.gov (United States)

    Hua, Fangyuan; Wang, Xiaoyang; Zheng, Xinlei; Fisher, Brendan; Wang, Lin; Zhu, Jianguo; Tang, Ya; Yu, Douglas W.; Wilcove, David S.

    2016-01-01

    Reforestation is a critical means of addressing the environmental and social problems of deforestation. China's Grain-for-Green Program (GFGP) is the world's largest reforestation scheme. Here we provide the first nationwide assessment of the tree composition of GFGP forests and the first combined ecological and economic study aimed at understanding GFGP's biodiversity implications. Across China, GFGP forests are overwhelmingly monocultures or compositionally simple mixed forests. Focusing on birds and bees in Sichuan Province, we find that GFGP reforestation results in modest gains (via mixed forest) and losses (via monocultures) of bird diversity, along with major losses of bee diversity. Moreover, all current modes of GFGP reforestation fall short of restoring biodiversity to levels approximating native forests. However, even within existing modes of reforestation, GFGP can achieve greater biodiversity gains by promoting mixed forests over monocultures; doing so is unlikely to entail major opportunity costs or pose unforeseen economic risks to households. PMID:27598524

  14. How closely does stem growth of adult beech (Fagus sylvatica) relate to net carbon gain under experimentally enhanced ozone stress?

    International Nuclear Information System (INIS)

    Kitao, Mitsutoshi; Winkler, J. Barbro; Löw, Markus; Nunn, Angela J.; Kuptz, Daniel; Häberle, Karl-Heinz; Reiter, Ilja M.; Matyssek, Rainer

    2012-01-01

    The hypothesis was tested that O 3 -induced changes in leaf-level photosynthetic parameters have the capacity of limiting the seasonal photosynthetic carbon gain of adult beech trees. To this end, canopy-level photosynthetic carbon gain and respiratory carbon loss were assessed in European beech (Fagus sylvatica) by using a physiologically based model, integrating environmental and photosynthetic parameters. The latter were derived from leaves at various canopy positions under the ambient O 3 regime, as prevailing at the forest site (control), or under an experimental twice-ambient O 3 regime (elevated O 3 ), as released through a free-air canopy O 3 fumigation system. Gross carbon gain at the canopy-level declined by 1.7%, while respiratory carbon loss increased by 4.6% under elevated O 3 . As this outcome only partly accounts for the decline in stem growth, O 3 -induced changes in allocation are referred to and discussed as crucial in quantitatively linking carbon gain with stem growth. - Highlights: ► We model O 3 -induced changes in the photosynthetic carbon gain of adult beech trees. ► Elevated O 3 decreases gross carbon gain but increases respiratory carbon loss. ► Reduction in net carbon gain only partly accounts for the decline in stem growth. ► O 3 effects on the whole-tree allocation is crucial in addition to carbon gains. - Reduction in net carbon gain at the canopy level only partly accounts for the decline in stem growth under elevated ozone.

  15. Weight Gain, Schizophrenia and Antipsychotics: New Findings from Animal Model and Pharmacogenomic Studies

    Directory of Open Access Journals (Sweden)

    Fabio Panariello

    2011-01-01

    Full Text Available Excess body weight is one of the most common physical health problems among patients with schizophrenia that increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, and hypertension, and accounts in part for 20% shorter life expectancy than in general population. Among patients with severe mental illness, obesity can be attributed to an unhealthy lifestyle, personal genetic profile, as well as the effects of psychotropic medications, above all antipsychotic drugs. Novel “atypical” antipsychotic drugs represent a substantial improvement on older “typical” drugs. However, clinical experience has shown that some, but not all, of these drugs can induce substantial weight gain. Animal models of antipsychotic-related weight gain and animal transgenic models of knockout or overexpressed genes of antipsychotic receptors have been largely evaluated by scientific community for changes in obesity-related gene expression or phenotypes. Moreover, pharmacogenomic approaches have allowed to detect more than 300 possible candidate genes for antipsychotics-induced body weight gain. In this paper, we summarize current thinking on: (1 the role of polymorphisms in several candidate genes, (2 the possible roles of various neurotransmitters and neuropeptides in this adverse drug reaction, and (3 the state of development of animal models in this matter. We also outline major areas for future research.

  16. A Comprehensive Dataset of Genes with a Loss-of-Function Mutant Phenotype in Arabidopsis1[W][OA

    Science.gov (United States)

    Lloyd, Johnny; Meinke, David

    2012-01-01

    Despite the widespread use of Arabidopsis (Arabidopsis thaliana) as a model plant, a curated dataset of Arabidopsis genes with mutant phenotypes remains to be established. A preliminary list published nine years ago in Plant Physiology is outdated, and genome-wide phenotype information remains difficult to obtain. We describe here a comprehensive dataset of 2,400 genes with a loss-of-function mutant phenotype in Arabidopsis. Phenotype descriptions were gathered primarily from manual curation of the scientific literature. Genes were placed into prioritized groups (essential, morphological, cellular-biochemical, and conditional) based on the documented phenotypes of putative knockout alleles. Phenotype classes (e.g. vegetative, reproductive, and timing, for the morphological group) and subsets (e.g. flowering time, senescence, circadian rhythms, and miscellaneous, for the timing class) were also established. Gene identities were classified as confirmed (through molecular complementation or multiple alleles) or not confirmed. Relationships between mutant phenotype and protein function, genetic redundancy, protein connectivity, and subcellular protein localization were explored. A complementary dataset of 401 genes that exhibit a mutant phenotype only when disrupted in combination with a putative paralog was also compiled. The importance of these genes in confirming functional redundancy and enhancing the value of single gene datasets is discussed. With further input and curation from the Arabidopsis community, these datasets should help to address a variety of important biological questions, provide a foundation for exploring the relationship between genotype and phenotype in angiosperms, enhance the utility of Arabidopsis as a reference plant, and facilitate comparative studies with model genetic organisms. PMID:22247268

  17. Analysis of Msx1 and Msx2 transactivation function in the context of the heat shock 70 (Hspa1b) gene promoter.

    Science.gov (United States)

    Zhuang, Fengfeng; Nguyen, Manuel P; Shuler, Charles; Liu, Yi-Hsin

    2009-04-03

    Previous studies have shown that Msx proteins control gene transcription predominantly through repression mechanisms. However, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression require functional Msx proteins. To date, investigations into the mechanisms of Msx-dependent transactivation have been hindered by the lack of a responsive promoter. Here, we demonstrated the usefulness of the mouse Hspa1b promoter in probing Msx-dependent mechanisms of gene activation. We showed that Msx protein activates Hspa1b promoter via its C-terminal domain. The activation absolutely depends on the HSEs and physical interactions between Msx proteins and heat shock factors may play a contributing role.

  18. Altered neural reward and loss processing and prediction error signalling in depression

    Science.gov (United States)

    Ubl, Bettina; Kuehner, Christine; Kirsch, Peter; Ruttorf, Michaela

    2015-01-01

    Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression. PMID:25567763

  19. Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

    International Nuclear Information System (INIS)

    Press, Joshua Z; Smith, Margaret; Spellman, Paul T; Wang, Yuker; Miller, Dianne M; Horsman, Doug; Faham, Malek; Gilks, C Blake; Gray, Joe; Huntsman, David G; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E; Blood, Katherine A

    2008-01-01

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumours were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumours with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways

  20. Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Gilks, C. Blake; Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E.; Blood, Katherine A.; Smith, Margaret; Spellman, Paul T.; Wang, Yuker; Miller, Dianne M.; Horsman, Doug; Faham, Malek; Gilks, C. Blake; Gray, Joe; Huntsman, David G.

    2008-05-02

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n=5), clear cell (n=4), or low grade serous (n=2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.