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Sample records for gene gain loss

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Frequent Gain and Loss of Introns in Fungal Cytochrome b Genes

    Science.gov (United States)

    Yin, Liang-Fen; Hu, Meng-Jun; Wang, Fei; Kuang, Hanhui; Zhang, Yu; Schnabel, Guido; Li, Guo-Qing; Luo, Chao-Xi

    2012-01-01

    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. PMID:23145081

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

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    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

  4. 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

  5. progressiveMauve: multiple genome alignment with gene gain, loss and rearrangement.

    Directory of Open Access Journals (Sweden)

    Aaron E Darling

    2010-06-01

    Full Text Available Multiple genome alignment remains a challenging problem. Effects of recombination including rearrangement, segmental duplication, gain, and loss can create a mosaic pattern of homology even among closely related organisms.We describe a new method to align two or more genomes that have undergone rearrangements due to recombination and substantial amounts of segmental gain and loss (flux. We demonstrate that the new method can accurately align regions conserved in some, but not all, of the genomes, an important case not handled by our previous work. The method uses a novel alignment objective score called a sum-of-pairs breakpoint score, which facilitates accurate detection of rearrangement breakpoints when genomes have unequal gene content. We also apply a probabilistic alignment filtering method to remove erroneous alignments of unrelated sequences, which are commonly observed in other genome alignment methods. We describe new metrics for quantifying genome alignment accuracy which measure the quality of rearrangement breakpoint predictions and indel predictions. The new genome alignment algorithm demonstrates high accuracy in situations where genomes have undergone biologically feasible amounts of genome rearrangement, segmental gain and loss. We apply the new algorithm to a set of 23 genomes from the genera Escherichia, Shigella, and Salmonella. Analysis of whole-genome multiple alignments allows us to extend the previously defined concepts of core- and pan-genomes to include not only annotated genes, but also non-coding regions with potential regulatory roles. The 23 enterobacteria have an estimated core-genome of 2.46Mbp conserved among all taxa and a pan-genome of 15.2Mbp. We document substantial population-level variability among these organisms driven by segmental gain and loss. Interestingly, much variability lies in intergenic regions, suggesting that the Enterobacteriacae may exhibit regulatory divergence.The multiple genome alignments

  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. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Phylogenetic Distribution of Intron Positions in Alpha-Amylase Genes of Bilateria Suggests Numerous Gains and Losses

    Science.gov (United States)

    Da Lage, Jean-Luc; Maczkowiak, Frédérique; Cariou, Marie-Louise

    2011-01-01

    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. PMID:21611157

  10. 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.

  11. Phylogenetic Distribution of Intron Positions in Alpha-Amylase Genes of Bilateria Suggests Numerous Gains and Losses

    OpenAIRE

    Da Lage, Jean-Luc; Maczkowiak, Frédérique; Cariou, Marie-Louise

    2011-01-01

    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, al...

  12. 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

  13. Distinct Patterns of Gene Gain and Loss: Diverse Evolutionary Modes of NBS-Encoding Genes in Three Solanaceae Crop Species.

    Science.gov (United States)

    Qian, Lan-Hua; Zhou, Guang-Can; Sun, Xiao-Qin; Lei, Zhao; Zhang, Yan-Mei; Xue, Jia-Yu; Hang, Yue-Yu

    2017-05-05

    Plant resistance conferred by nucleotide binding site (NBS)-encoding resistance genes plays a key role in the defense against various pathogens throughout the entire plant life cycle. However, comparative analyses for the systematic evaluation and determination of the evolutionary modes of NBS-encoding genes among Solanaceae species are rare. In this study, 447, 255, and 306 NBS-encoding genes were identified from the genomes of potato, tomato, and pepper, respectively. These genes usually clustered as tandem arrays on chromosomes; few existed as singletons. Phylogenetic analysis indicated that three subclasses [TNLs (TIR-NBS-LRR), CNLs (CC-NBS-LRR), and RNLs (RPW8-NBS-LRR)] each formed a monophyletic clade and were distinguished by unique exon/intron structures and amino acid motif sequences. By comparing phylogenetic and systematic relationships, we inferred that the NBS-encoding genes in the present genomes of potato, tomato, and pepper were derived from 150 CNL, 22 TNL, and 4 RNL ancestral genes, and underwent independent gene loss and duplication events after speciation. The NBS-encoding genes therefore exhibit diverse and dynamic evolutionary patterns in the three Solanaceae species, giving rise to the discrepant gene numbers observed today. Potato shows a "consistent expansion" pattern, tomato exhibits a pattern of "first expansion and then contraction," and pepper presents a "shrinking" pattern. The earlier expansion of CNLs in the common ancestor led to the dominance of this subclass in gene numbers. However, RNLs remained at low copy numbers due to their specific functions. Along the evolutionary process of NBS-encoding genes in Solanaceae, species-specific tandem duplications contributed the most to gene expansions. Copyright © 2017 Qian et al.

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

    Science.gov (United States)

    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

  15. Assessment and reconstruction of novel HSP90 genes: duplications, gains and losses in fungal and animal lineages.

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    Chrysoula N Pantzartzi

    Full Text Available Hsp90s, members of the Heat Shock Protein class, protect the structure and function of proteins and play a significant task in cellular homeostasis and signal transduction. In order to determine the number of hsp90 gene copies and encoded proteins in fungal and animal lineages and through that key duplication events that this family has undergone, we collected and evaluated Hsp90 protein sequences and corresponding Expressed Sequence Tags and analyzed available genomes from various taxa. We provide evidence for duplication events affecting either single species or wider taxonomic groups. With regard to Fungi, duplicated genes have been detected in several lineages. In invertebrates, we demonstrate key duplication events in certain clades of Arthropoda and Mollusca, and a possible gene loss event in a hymenopteran family. Finally, we infer that the duplication event responsible for the two (a and b isoforms in vertebrates occurred probably shortly after the split of Hyperoartia and Gnathostomata.

  16. 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 ...

  17. Gain and Loss of Floral Scent Production through Changes in Structural Genes during Pollinator-Mediated Speciation

    NARCIS (Netherlands)

    Amrad, A.; Moser, M.; Mandel, T.; de Vries, M.; Schuurink, R.C.; Freitas, L.; Kuhlemeier, C.

    2016-01-01

    The interactions of plants with their pollinators are thought to be a driving force in the evolution of angiosperms. Adaptation to a new pollinator involves coordinated changes in multiple floral traits controlled by multiple genes. Surprisingly, such complex genetic shifts have happened numerous

  18. The Biology of Intron Gain and Loss

    DEFF Research Database (Denmark)

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

    2006-01-01

    eukaryote genomes during their evolution from an intron-poor ancestor. However, recent studies have shown that some eukaryotes lost many introns, whereas others accumulated and/or gained many introns. In this article, we discuss the growing evidence that these differences are subject to selection acting...... on introns depending on the biology of the organism and the gene involved....

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

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    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".

  20. Deep sequencing of HPV E6/E7 genes reveals loss of genotypic diversity and gain of clonal dominance in high-grade intraepithelial lesions of the cervix.

    Science.gov (United States)

    Shen-Gunther, Jane; Wang, Yufeng; Lai, Zhao; Poage, Graham M; Perez, Luis; Huang, Tim H M

    2017-03-14

    Human papillomavirus (HPV) is the carcinogen of almost all invasive cervical cancer and a major cause of oral and other anogenital malignancies. HPV genotyping by dideoxy (Sanger) sequencing is currently the reference method of choice for clinical diagnostics. However, for samples with multiple HPV infections, genotype identification is singular and occasionally imprecise or indeterminable due to overlapping chromatograms. Our aim was to explore and compare HPV metagenomes in abnormal cervical cytology by deep sequencing for correlation with disease states. Low- and high-grade intraepithelial lesion (LSIL and HSIL) cytology samples were DNA extracted for PCR-amplification of the HPV E6/E7 genes. HPV+ samples were sequenced by dideoxy and deep methods. Deep sequencing revealed ~60% of all samples (n = 72) were multi-HPV infected. Among LSIL samples (n = 43), 27 different genotypes were found. The 3 dominant (most abundant) genotypes were: HPV-39, 11/43 (26%); -16, 9/43 (21%); and -35, 4/43 (9%). Among HSIL (n = 29), 17 HPV genotypes were identified; the 3 dominant genotypes were: HPV-16, 21/29 (72%); -35, 4/29 (14%); and -39, 3/29 (10%). Phylogenetically, type-specific E6/E7 genetic distances correlated with carcinogenic potential. Species diversity analysis between LSIL and HSIL revealed loss of HPV diversity and domination by HPV-16 in HSIL samples. Deep sequencing resolves HPV genotype composition within multi-infected cervical cytology. Biodiversity analysis reveals loss of diversity and gain of dominance by carcinogenic genotypes in high-grade cytology. Metagenomic profiles may therefore serve as a biomarker of disease severity and a population surveillance tool for emerging genotypes.

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

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    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.

  2. 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...

  3. Income Gains and Losses of Mobilized Reservists

    National Research Council Canada - National Science Library

    Doyle, Colin M; Gotz, Glenn A

    2005-01-01

    .... In the absence of individual data on civilian earnings, this study sought to identify those categories of reservists by civilian occupation and military pay grade that may have the largest expected income losses...

  4. A neurochemical approach to valuation sensitivity over gains and losses

    OpenAIRE

    Zhong, Songfa; Israel, Salomon; Xue, Hong; Sham, Pak C.; Ebstein, Richard P.; Chew, Soo Hong

    2009-01-01

    Prospect theory proposes the hypothesis that people have diminishing sensitivity in valuing increases in the size of monetary outcomes, for both gains and losses. For decision-making under risk, this implies a tendency to be risk-tolerant over losses while being generally risk averse over gains. We offer a neurochemistry-based model of the diminishing valuation sensitivity hypothesis. Specifically, we propose that dopamine tone modulates the sensitivity towards valuation of gains while seroto...

  5. Cavity solitons in a microring dimer with gain and loss

    Science.gov (United States)

    Milián, Carles; Kartashov, Yaroslav V.; Skryabin, Dmitry V.; Torner, Lluis

    2018-03-01

    We address a pair of vertically coupled microring resonators with gain and loss pumped by a single-frequency field. Coupling between microrings results in a twofold splitting of the single microring resonance that increases when gain and losses decrease and that gives rise to two different cavity soliton (CS) families. We show that the existence regions of CSs are tunable and that both CS families can be stable in the presence of an imbalance between gain and losses in the two microrings. These findings enable experimental realization of frequency combs in configurations with active microrings and contribute towards the realization of compact multisoliton comb sources.

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

    Science.gov (United States)

    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.

  8. Cleavings: Critical Losses in the Politics of Gain

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Patterns of intron gain and conservation in eukaryotic genes

    Directory of Open Access Journals (Sweden)

    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

  11. Genetic gain and gene diversity of seed orchard crops

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Kyu-Suk [Swedish Univ. of Agricultural Sciences, Umeaa (Sweden). Dept. of Forest Genetics and Plant Physiology

    2001-07-01

    Seed orchards are the major tool for deploying the improvement generated by breeding programs and assuring the consistent supply of genetically improved seed. Attainment of genetic gain and monitoring of gene diversity through selection and breeding were studied considering the factors: selection intensity; genetic value; coancestry; fertility variation; and pollen contamination. The optimum goal of a seed orchard is achieved when the orchard population is under an idealized situation, i.e., panmixis, equal gamete contributions from all parental genotypes, non-relatedness and no pollen contamination. In practice, however, due to relatedness among parents, variation in clonal fertility and ramet number, and gene migration from outside, the realized genetic gain and gene diversity deviate from the expectation. In the present study, the genetic value of seed orchard crops (genetic gain, G) could be increased by selective harvest, genetic thinning and/or both. Status number (N{sub S}) was used to monitor the loss of gene diversity in the process of forest tree domestication, and calculated to be reasonably high in most seed orchards. Fertility of parents was estimated based on the assessment of flowering or seed production, which was shown to be under strong genetic control. Variation in fertility among orchard parents was a general feature and reduced the predicted gene diversity of the orchard crop. Fertility variation among parents could be described by the sibling coefficient ({psi}). {psi} was estimated to be 2 (CV = 100% for fertility). In calculating {psi}, it was possible to consider, besides fertility variation, the phenotypic correlation between maternal and parental fertilities, and pollen contamination. Status number was increased by controlling parental fertility, e.g., equal seed harvest, mixing seed in equal proportions and balancing parental contribution. By equalizing female fertility among over-represented parents, it was possible to effect a

  12. 76 FR 65634 - Redetermination of the Consolidated Net Unrealized Built-In Gain and Loss

    Science.gov (United States)

    2011-10-24

    .... Under this rule, unrealized gain or loss with respect to the stock of a member of the loss group (an... unrecognized gain or loss on included subsidiary stock generally reflects the same economic gain or loss... eliminates the duplicative gain or loss reflected in stock basis. Conversely, if a member first recognizes...

  13. 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…

  14. 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.

  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

    were found in genes previously associated with AF. The mutations A46T, R195W, and A302V have previously been associated with long-QT syndrome. In line with previous reports, we found A302V to display a pronounced loss-of-function of the IKs current, while the other mutants exhibited a gain...

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Eli Arditi

    Full Text Available 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.

  18. Gene losses during human origins.

    Directory of Open Access Journals (Sweden)

    Xiaoxia Wang

    2006-03-01

    Full Text Available Pseudogenization is a widespread phenomenon in genome evolution, and it has been proposed to serve as an engine of evolutionary change, especially during human origins (the "less-is-more" hypothesis. However, there has been no comprehensive analysis of human-specific pseudogenes. Furthermore, it is unclear whether pseudogenization itself can be selectively favored and thus play an active role in human evolution. Here we conduct a comparative genomic analysis and a literature survey to identify 80 nonprocessed pseudogenes that were inactivated in the human lineage after its separation from the chimpanzee lineage. Many functions are involved among these genes, with chemoreception and immune response being outstandingly overrepresented, suggesting potential species-specific features in these aspects of human physiology. To explore the possibility of adaptive pseudogenization, we focus on CASPASE12, a cysteinyl aspartate proteinase participating in inflammatory and innate immune response to endotoxins. We provide population genetic evidence that the nearly complete fixation of a null allele at CASPASE12 has been driven by positive selection, probably because the null allele confers protection from severe sepsis. We estimate that the selective advantage of the null allele is about 0.9% and the pseudogenization started shortly before the out-of-Africa migration of modern humans. Interestingly, two other genes related to sepsis were also pseudogenized in humans, possibly by selection. These adaptive gene losses might have occurred because of changes in our environment or genetic background that altered the threat from or response to sepsis. The identification and analysis of human-specific pseudogenes open the door for understanding the roles of gene losses in human origins, and the demonstration that gene loss itself can be adaptive supports and extends the "less-is-more" hypothesis.

  19. 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...

  20. 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...

  1. 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

  2. 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.

  3. 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.

  4. Loss compensation symmetry in dimers made of gain and lossy nanoparticles

    Science.gov (United States)

    Klimov, V. V.; Zabkov, I. V.; Guzatov, D. V.; Vinogradov, A. P.

    2018-03-01

    The eigenmodes in a two-dimensional dimer made of gain and lossy nanoparticles have been investigated within an exact analytical approach. It has been shown that there are eigenmodes for which all Joule losses are exactly compensated by the gain. Among such solutions there are solutions with a new type of symmetry, which we refer to as loss compensation symmetry, as well as well-known parity–time (PT) symmetric solutions. Unlike PT symmetric ones, the modes with loss compensation symmetry allow one to achieve full loss compensation with significantly less gain that in the case of PT symmetry. This effect paves the way to new loss compensation methods in optics.

  5. 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.

  6. 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....

  7. 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...

  8. 26 CFR 1.1233-1 - Gains and losses from short sales.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Gains and losses from short sales. 1.1233-1... and losses from short sales. (a) General. (1) For income tax purposes, a short sale is not deemed to be consummated until delivery of property to close the short sale. Whether the recognized gain or...

  9. 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...

  10. Predominant gain of promoter TATA box after gene duplication associated with stress responses.

    Science.gov (United States)

    Zou, Yangyun; Huang, Wei; Gu, Zhenglong; Gu, Xun

    2011-10-01

    TATA box, the core promoter element, exists in a broad range of eukaryotes, and the expression of TATA-containing genes usually responds to various environmental stresses. Hence, the evolution of TATA-box in duplicate genes may provide some clues for the interrelationship among environmental stress, expression differentiation, and duplicate gene preservation. In the present study, we observed that the TATA box is significantly overrepresented in duplicate genes compared with singletons in human, worm, Arabidopsis, and yeast genomes. We then conducted an extensive functional genomic analysis to investigate the evolution of TATA box along over 700 yeast gene family phylogenies. After reconstructing the ancestral TATA-box states (presence or absence), we found that significantly higher numbers of TATA box gain events than loss events had occurred after yeast gene duplications-the overall gain-loss ratio is about 3-4 to 1. Interestingly, these TATA-gain duplicate genes on average have experienced greater expression divergence from the ancestral expression states than their most closely related TATA-less duplicate partners, but only under environmental stress conditions (asymmetric evolution); indeed, under normal physiological conditions, they have similar expression divergence (symmetric evolution). Moreover, we showed that TATA-gain duplicates are enriched in stress-associated functional categories but that is not the case for TATA-ancestral duplicates (those inherited from their ancestors prior to duplication). Together, we conclude that after the gene duplication, gain of the TATA box in duplicate promoters may have played an important role in yeast duplicate preservation by accelerating expression divergence that may facilitate the adaptive evolution of the organism in response to environmental changes.

  11. Gains and losses on the road to understanding Alzheimer's disease.

    Science.gov (United States)

    Konietzko, Uwe

    2015-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause for dementia, which affects approximately 120 thousand people in Switzerland and 35 million worldwide. Aging is a major risk factor for developing AD and thus, as our societies are growing older, we face great challenges to find treatment strategies. The disease is characterised by loss of memory, deposition of extracellular amyloid plaques containing Aβ peptides and intraneuronal tangles of the tau protein. To date, there is no effective treatment and the cause of the disease is still debated. The Schweizerische Alzheimervereinigung states that we need "continuous manifold research" into all possible causes of AD to find a cure for this disease. Fitting this proposition, a recent publication by Xia et al. (2015) described a novel mouse model that for the first time reproduces cortical neuron death as observed in human AD cases. At the same time, this publication questions the major theory of AD pathogenesis and points towards different treatment avenues that should be followed to find a cure for AD.

  12. 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.

  13. 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.

  14. 26 CFR 1.267(d)-1 - Amount of gain where loss previously disallowed.

    Science.gov (United States)

    2010-04-01

    ... corporate stock with an adjusted basis for determining loss to him of $800. The loss of $300 is not... transaction 1,600 Less: Loss sustained by H on sale of class A stock to W not allowable as a deduction: Basis... Unallowable loss to H on sale of class A stock 200 Recognized gain on sale of class A stock by W 1,400 Example...

  15. 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.

  16. 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...

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

    Science.gov (United States)

    Yao, Yuan-Wei; Chen, Pin-Ru; Li, Song; Wang, Ling-Jiao; Zhang, Jin-Tao; Yip, Sarah W; Chen, Gang; Deng, Lin-Yuan; Liu, Qin-Xue; Fang, Xiao-Yi

    2015-01-01

    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.

  18. 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.

  19. 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

  20. Decision-Making for Risky Gains and Losses among College Students with Internet Gaming Disorder

    OpenAIRE

    Yao, Yuan-Wei; Chen, Pin-Ru; Li, Song; Wang, Ling-Jiao; Zhang, Jin-Tao; Yip, Sarah W.; Chen, Gang; Deng, Lin-Yuan; Liu, Qin-Xue; Fang, Xiao-Yi

    2015-01-01

    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 de...

  1. Temporal structure and gain/loss asymmetry for real and artificial stock indices

    OpenAIRE

    Siven, Johannes Vitalis; Lins, Jeffrey Todd

    2009-01-01

    We demonstrate that the gain/loss asymmetry observed for stock indices vanishes if the temporal dependence structure is destroyed by scrambling the time series. We also show that an artificial index constructed by a simple average of a number of individual stocks display gain/loss asymmetry - this allows us to explicitly analyze the dependence between the index constituents. We consider mutual information and correlation based measures and show that the stock returns indeed have a higher degr...

  2. 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...

  3. 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.

  4. 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.

  5. 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.

  6. 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...

  7. 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.

  8. Temperature Measurement by a Nanoscale Electron Probe Using Energy Gain and Loss Spectroscopy

    Science.gov (United States)

    Idrobo, Juan Carlos; Lupini, Andrew R.; Feng, Tianli; Unocic, Raymond R.; Walden, Franklin S.; Gardiner, Daniel S.; Lovejoy, Tracy C.; Dellby, Niklas; Pantelides, Sokrates T.; Krivanek, Ondrej L.

    2018-03-01

    Heat dissipation in integrated nanoscale devices is a major issue that requires the development of nanoscale temperature probes. Here, we report the implementation of a method that combines electron energy gain and loss spectroscopy to provide a direct measurement of the local temperature in the nanoenvironment. Loss and gain peaks corresponding to an optical-phonon mode in boron nitride were measured from room temperature to ˜1600 K . Both loss and gain peaks exhibit a shift towards lower energies as the sample is heated up. First-principles calculations of the temperature-induced phonon frequency shifts provide insights into the origin of this effect and confirm the experimental data. The experiments and theory presented here open the doors to the study of anharmonic effects in materials by directly probing phonons in the electron microscope.

  9. Temporal structure and gain-loss asymmetry for real and artificial stock indices.

    Science.gov (United States)

    Siven, Johannes Vitalis; Lins, Jeffrey Todd

    2009-11-01

    Previous research has shown that for stock indices, the most likely time until a return of a particular size has been observed is longer for gains than for losses. We demonstrate that this so-called gain-loss asymmetry vanishes if the temporal dependence structure is destroyed by scrambling the time series. We also show that an artificial index constructed by a simple average of a number of individual stocks display gain-loss asymmetry-this allows us to explicitly analyze the dependence between the index constituents. We consider mutual information and correlation-based measures and show that the stock returns indeed have a higher degree of dependence in times of market downturns than upturns.

  10. 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...

  11. Kids, candy, brain and behavior: age differences in responses to candy gains and losses.

    Science.gov (United States)

    Luking, Katherine R; Luby, Joan L; Barch, Deanna M

    2014-07-01

    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. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. 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.

  13. Low-loss resonance modes in a gain-assisted plasmonic multimer

    Science.gov (United States)

    Pan, Gui-Ming; Yang, Da-Jie; Zhou, Li; Hao, Zhong-Hua

    2018-03-01

    We theoretically study the properties of optical losses in a plasmonic multimer and find modes with lower radiative losses due to the cancellation of the dipole moment. High order plasmonic resonances, including electric quadrupole and magnetic dipole resonances, can be achieved by the reduction of symmetry in a multimer. Meanwhile, the dipole moment can be significantly reduced in these high order modes, and consequently, the radiative losses decrease efficiently. The low-loss modes can lead to a lower gain threshold in the gain-assisted nanosystem. In particular, compared with the electric dipolar mode in a single nanoshell, the gain threshold of the electric quadrupolar and magnetic dipolar modes in a multimer can drop by 57.66% and 59.22%, respectively. On the other hand, the gain threshold can reflect the extent of the optical losses of the plasmonic mode in a nanosystem. These findings may have potential applications in the design of a nanolaser, plasmon waveguide and photo-thermal device.

  14. 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.

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

    Science.gov (United States)

    Sun, Peng; Zheng, Li; Li, Lin; Guo, Xiuyan; Zhang, Weidong; Zheng, Yijie

    2016-01-01

    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.

  16. 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

  17. Activation in the VTA and nucleus accumbens increases in anticipation of both gains and losses

    Directory of Open Access Journals (Sweden)

    R. McKell Carter

    2009-08-01

    Full Text Available To represent value for learning and decision making, the brain must encode information about both the motivational relevance and affective valence of anticipated outcomes. The nucleus accumbens (NAcc and ventral tegmental area (VTA are thought to play key roles in representing these and other aspects of valuation. Here, we manipulated the valence (i.e., monetary gain or loss and personal relevance (i.e., self-directed or charity-directed of anticipated outcomes within a variant of the monetary incentive delay task (MID. We scanned young-adult participants using functional magnetic resonance imaging (fMRI, utilizing imaging parameters targeted for the NAcc and VTA. For both self-directed and charity-directed trials, activation in the NAcc and VTA increased to anticipated gains, as predicted by prior work, but also increased to anticipated losses. Moreover, the magnitude of responses in both regions was positively correlated for gains and losses, across participants, while an independent reward-sensitivity covariate predicted the relative difference between and gain- and loss-related activation on self-directed trials. These results are inconsistent with the interpretation that these regions reflect anticipation of only positive-valence events. Instead, they indicate that anticipatory activation in reward-related regions largely reflects the motivational relevance of an upcoming event.

  18. 26 CFR 1.453-9 - Gain or loss on disposition of installment obligations.

    Science.gov (United States)

    2010-04-01

    ... partnership qualified as a life insurance company (as defined in section 801(a)). The N partnership held $30... gains and capital losses of individuals. (g) Disposition of installment obligations to life insurance... the disposition of an installment obligation by any person, other than a life insurance company (as...

  19. Primacy/Recency Effects in Student Ratings of Instruction: A Reinterpretation of Gain-Loss Effects.

    Science.gov (United States)

    Leventhal, Les; And Others

    1983-01-01

    This article describes how the effects of initial and final lecture quality on end-of-course student ratings can be predicted from seemingly unrelated gain-loss theory. The effects were investigated, along with the effect on ratings of student belief that the instructor will use midterm rating feedback to improve teaching. (Author)

  20. 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 ...

  1. 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...

  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. 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

  4. 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.

  5. 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.

  6. 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

  7. 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).

  8. 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

  9. 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.

  10. 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.

  11. 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)

  12. 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.

  13. 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.

  14. 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...... and lower optimum tilt settings. Furthermore, we show that a simple geometrically based tilt optimization algorithm can outperform other tilt profiles, including the setting applied by the cellular operator in the specific case. In general, the network performance is not highly sensitive to the tilt...

  15. Sodium channelopathies of skeletal muscle result from gain or loss of function

    OpenAIRE

    Jurkat-Rott, Karin; Holzherr, Boris; Fauler, Michael; Lehmann-Horn, Frank

    2010-01-01

    Five hereditary sodium channelopathies of skeletal muscle have been identified. Prominent symptoms are either myotonia or weakness caused by an increase or decrease of muscle fiber excitability. The voltage-gated sodium channel NaV1.4, initiator of the muscle action potential, is mutated in all five disorders. Pathogenetically, both loss and gain of function mutations have been described, the latter being the more frequent mechanism and involving not just the ion-conducting pore, but aberrant...

  16. Investigation of mode interaction on planar dielectric waveguides with loss and gain

    Science.gov (United States)

    Hanson, George W.; Yakovlev, Alexander B.

    1999-11-01

    On lossless isotropic planar waveguides the discrete proper modes of propagation form independent transverse electric and transverse magnetic sets such that there is no mode coupling or interaction between modes. In the event of material loss or gain, mode interactions are possible, leading to a complicated spectrum and apparent nonuniqueness of the modes. In this paper we analyze for the first time the cause of these modal interactions by studying the simplest canonical planar waveguide which exhibits these effects, the symmetric-slab waveguide. We show that mode interactions are due to the migration of complex-frequency-plane branch points associated with specific wave phenomena, with varying loss or gain. As these singularities move near the real-frequency axis they influence the modal behavior for time-harmonic (real-valued) frequencies, crossing the real axis at some critical value of loss or gain. It is shown that as time-harmonic frequency varies, passing above, below, or through these branch points results in different modal behavior. Passing above or below, and near to, the branch point yields mode coupling behavior, while passing through the branch point results in modal degeneracy. The result of this branch point migration is that the association of a particular mode with a certain branch of the dispersion function depends not only on the value of material loss or gain, but also on the order in which physical parameters of the problem are varied. Three different branch point types are identified and discussed, which leads to an understanding of the relevant wave phenomena and to a method for organizing the mode spectrum in a consistent and unique manner. While many of the observations described here are based on careful numerical analysis of the transverse magnetic modes existing on a certain symmetric-slab waveguide, the described phenomena are reasonably expected to be generally found in other open dielectric waveguiding structures.

  17. Nonlinear localized modes in PT-symmetric optical media with competing gain and loss

    Energy Technology Data Exchange (ETDEWEB)

    Midya, Bikashkali, E-mail: bikash.midya@gmail.com [Physics and Applied Mathematics Unit, Indian Statistical Institute, Kolkata 700108 (India); Roychoudhury, Rajkumar, E-mail: rroychoudhury123@gmail.com [Advanced Center for Nonlinear and Complex Phenomena, Kolkata 700075 (India)

    2014-02-15

    The existence and stability of the nonlinear spatial localized modes are investigated in parity-time symmetric optical media characterized by a generic complex hyperbolic refractive index distribution with competing gain and loss profile. The exact analytical expression of the localized modes are found for all values of the competing parameter and in the presence of both the self-focusing and self-defocusing Kerr nonlinearity. The effects of competing gain/loss profile on the stability structure of these localized modes are discussed with the help of linear stability analysis followed by the direct numerical simulation of the governing equation. The spatial localized modes in two-dimensional geometry as well as the transverse power-flow density associated with these localized modes are also examined. -- Highlights: • Existence of localized modes is investigated in PT-symmetric complex potentials. • Exact analytical expression of the localized modes is obtained. • Effect of gain/loss profile on the stability of these localized modes is discussed. • Localized modes in 2D and associated transverse power-flow density are also examined.

  18. 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

  19. 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

  20. Candy and the brain: neural response to candy gains and losses.

    Science.gov (United States)

    Luking, Katherine R; Barch, Deanna M

    2013-09-01

    Incentive processing is a critical component of a host of cognitive processes, including attention, motivation, and learning. Neuroimaging studies have clarified the neural systems underlying processing of primary and secondary rewards in adults. However, current reward paradigms have hindered comparisons across these reward types as well as between age groups. To address methodological issues regarding the timing of incentive delivery (during scan vs. postscan) and the age-appropriateness of the incentive type, we utilized fMRI and a modified version of a card-guessing game (CGG), in which candy pieces delivered postscan served as the reinforcer, to investigate neural responses to incentives. Healthy young adults 22-26 years of age won and lost large and small amounts of candy on the basis of their ability to guess the number on a mystery card. BOLD activity was compared following candy gain (large/small), loss (large/small), and neutral feedback. During candy gains, adults recruited regions typically involved in response to monetary and other rewards, such as the caudate, putamen, and orbitofrontal cortex. During losses, they displayed greater deactivation in the hippocampus than in response to neutral and gain feedback. Additionally, individual-difference analyses suggested a negative relationship between reward sensitivity (assessed by the Behavioral Inhibition/Behavioral Activation Scales) and the difference between high- and low-magnitude losses in the caudate and lateral orbitofrontal cortex. Also within the striatum, greater punishment sensitivity was positively related to the difference in activity following high as compared to low gains. Overall, these results show strong overlap with those from previous monetary versions of the CGG and provide a baseline for future work with developmental populations.

  1. Orthopoxvirus Genome Evolution: The Role of Gene Loss

    Directory of Open Access Journals (Sweden)

    Eneida L. Hatcher

    2010-09-01

    Full Text Available Poxviruses are highly successful pathogens, known to infect a variety of hosts. The family Poxviridae includes Variola virus, the causative agent of smallpox, which has been eradicated as a public health threat but could potentially reemerge as a bioterrorist threat. The risk scenario includes other animal poxviruses and genetically engineered manipulations of poxviruses. Studies of orthologous gene sets have established the evolutionary relationships of members within the Poxviridae family. It is not clear, however, how variations between family members arose in the past, an important issue in understanding how these viruses may vary and possibly produce future threats. Using a newly developed poxvirus-specific tool, we predicted accurate gene sets for viruses with completely sequenced genomes in the genus Orthopoxvirus. Employing sensitive sequence comparison techniques together with comparison of syntenic gene maps, we established the relationships between all viral gene sets. These techniques allowed us to unambiguously identify the gene loss/gain events that have occurred over the course of orthopoxvirus evolution. It is clear that for all existing Orthopoxvirus species, no individual species has acquired protein-coding genes unique to that species. All existing species contain genes that are all present in members of the species Cowpox virus and that cowpox virus strains contain every gene present in any other orthopoxvirus strain. These results support a theory of reductive evolution in which the reduction in size of the core gene set of a putative ancestral virus played a critical role in speciation and confining any newly emerging virus species to a particular environmental (host or tissue niche.

  2. 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…

  3. 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.

  4. Changes in weight bias and perceived employability following weight loss and gain.

    Science.gov (United States)

    Carels, Robert A; Rossi, James; Borushok, Jessica; Taylor, Maija B; Kiefner-Burmeister, Allison; Cross, Nicole; Hinman, Nova; Burmeister, Jacob M

    2015-03-01

    The present weight stigma study examined whether attitudes toward and employability of a normal weight person can change after learning that the person had been obese. Participants (N = 154) viewed an image of a normal weight woman and rated their impression of her. Next, participants rated their impression of her overweight image after learning how she had previously gained and subsequently lost weight. Participants rated the model far less favorably including perceived employability if they thought the once overweight model lost weight through surgery vs. diet and exercise. How the model initially gained the weight had little impact on participant ratings. Surgical weight loss had a significant impact on personality judgments. These negative views extended to hiring decisions.

  5. NALCN channelopathies: Distinguishing gain-of-function and loss-of-function mutations.

    Science.gov (United States)

    Bend, Eric G; Si, Yue; Stevenson, David A; Bayrak-Toydemir, Pinar; Newcomb, Tara M; Jorgensen, Erik M; Swoboda, Kathryn J

    2016-09-13

    To perform genotype-phenotype analysis in an infant with congenital arthrogryposis due to a de novo missense mutation in the NALCN ion channel and explore the mechanism of pathogenicity using a Caenorhabditis elegans model. We performed whole-exome sequencing in a preterm neonate with congenital arthrogryposis and a severe life-threatening clinical course. We examined the mechanism of pathogenicity of the associated NALCN mutation by engineering the orthologous mutation into the nematode C elegans using CRISPR-Cas9. We identified a de novo missense mutation in NALCN, c.1768C>T, in an infant with a severe neonatal lethal form of the recently characterized CLIFAHDD syndrome (congenital contractures of the limbs and face with hypotonia and developmental delay). We report novel phenotypic features including prolonged episodes of stimulus-sensitive sustained muscular contraction associated with life-threatening episodes of desaturation and autonomic instability, extending the severity of previously described phenotypes associated with mutations in NALCN. When engineered into the C elegans ortholog, this mutation results in a severe gain-of-function phenotype, with hypercontraction and uncoordinated movement. We engineered 6 additional CLIFAHDD syndrome mutations into C elegans and the mechanism of action could be divided into 2 categories: half phenocopied gain-of-function mutants and half phenocopied loss-of-function mutants. The clinical phenotype of our patient and electrophysiologic studies show sustained muscular contraction in response to transient sensory stimuli. In C elegans, this mutation causes neuronal hyperactivity via a gain-of-function NALCN ion channel. Testing human variants of NALCN in C elegans demonstrates that CLIFAHDD can be caused by dominant loss- or gain-of-function mutations in ion channel function. © 2016 American Academy of Neurology.

  6. 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.

  7. 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.

  8. Genome-Wide Phylogenetic Comparative Analysis of Plant Transcriptional Regulation: A Timeline of Loss, Gain, Expansion, and Correlation with Complexity

    Science.gov (United States)

    Lang, Daniel; Weiche, Benjamin; Timmerhaus, Gerrit; Richardt, Sandra; Riaño-Pachón, Diego M.; Corrêa, Luiz G. G.; Reski, Ralf; Mueller-Roeber, Bernd; Rensing, Stefan A.

    2010-01-01

    Evolutionary retention of duplicated genes encoding transcription-associated proteins (TAPs, comprising transcription factors and other transcriptional regulators) has been hypothesized to be positively correlated with increasing morphological complexity and paleopolyploidizations, especially within the plant kingdom. Here, we present the most comprehensive set of classification rules for TAPs and its application for genome-wide analyses of plants and algae. Using a dated species tree and phylogenetic comparative (PC) analyses, we define the timeline of TAP loss, gain, and expansion among Viridiplantae and find that two major bursts of gain/expansion occurred, coinciding with the water-to-land transition and the radiation of flowering plants. For the first time, we provide PC proof for the long-standing hypothesis that TAPs are major driving forces behind the evolution of morphological complexity, the latter in Plantae being shaped significantly by polyploidization and subsequent biased paleolog retention. Principal component analysis incorporating the number of TAPs per genome provides an alternate and significant proxy for complexity, ideally suited for PC genomics. Our work lays the ground for further interrogation of the shaping of gene regulatory networks underlying the evolution of organism complexity. PMID:20644220

  9. Radiant heat loss versus radiant heat gain in premature neonates under radiant warmers.

    Science.gov (United States)

    Baumgart, S

    1990-01-01

    Premature infants nursed on open radiant warmer beds are exposed to short-wavelength infrared power density distributed evenly over the bed surface. Additionally, infants' sides are exposed to relatively cooler nursery walls, and to the radiant warmer bed platform which may heat and reradiate to the baby. Therefore, infants may not only gain heat from the warmer (Q radiant warmer) but lose or gain radiant heat to the sides as well (+/- Q radiant loss). In order to quantitate these parameters, ten premature newborn infants nursed under radiant warmers servocontrolled to 36.5 degrees C skin temperature (weight 1.27 +/- 0.24 SD kg, gestation 31 +/- 3 weeks) were investigated, and partitional calorimetry previously reported. In the present study, calculation of net rate of radiant heat transfer (Q net radiant) was made from these data (-2.63 +/- -1.52 kcal/kg/h), and compared to direct measurements of Q radiant warmer (-2.49 +/- -0.90 kcal/kg/h). The present report further partitions net radiant heat transfer to evaluate Q radiant loss: -0.13 +/- 1.82 kcal/kg/h (range -3.16 to 1.93). From these calculations mean radiant temperature of this environment was estimated (45.3 +/- 4.3 degrees C) and compared to the radiant warmer temperature received (45.0 +/- 2.9 degrees C). This information suggests other strategies to reduce radiant heat loss as well as convective and evaporative losses in premature neonates nursed on open radiant warmer beds.

  10. Loss-of-Function and Gain-of-Function Mutations in KCNQ5 Cause Intellectual Disability or Epileptic Encephalopathy.

    Science.gov (United States)

    Lehman, Anna; Thouta, Samrat; Mancini, Grazia M S; Naidu, Sakkubai; van Slegtenhorst, Marjon; McWalter, Kirsty; Person, Richard; Mwenifumbo, Jill; Salvarinova, Ramona; Guella, Ilaria; McKenzie, Marna B; Datta, Anita; Connolly, Mary B; Kalkhoran, Somayeh Mojard; Poburko, Damon; Friedman, Jan M; Farrer, Matthew J; Demos, Michelle; Desai, Sonal; Claydon, Thomas

    2017-07-06

    KCNQ5 is a highly conserved gene encoding an important channel for neuronal function; it is widely expressed in the brain and generates M-type current. Exome sequencing identified de novo heterozygous missense mutations in four probands with intellectual disability, abnormal neurological findings, and treatment-resistant epilepsy (in two of four). Comprehensive analysis of this potassium channel for the four variants expressed in frog oocytes revealed shifts in the voltage dependence of activation, including altered activation and deactivation kinetics. Specifically, both loss-of-function and gain-of-function KCNQ5 mutations, associated with increased excitability and decreased repolarization reserve, lead to pathophysiology. Copyright © 2017 American Society of Human Genetics. All rights reserved.

  11. Impact of body-composition methodology on the composition of weight loss and weight gain.

    Science.gov (United States)

    Pourhassan, M; Schautz, B; Braun, W; Gluer, C-C; Bosy-Westphal, A; Müller, M J

    2013-05-01

    We intended to (i) to compare the composition of weight loss and weight gain using densitometry, deuterium dilution (D₂O), dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI) and the four-compartment (4C) model and (ii) to compare regional changes in fat mass (FM), fat-free mass (FFM) and skeletal muscle as assessed by DXA and MRI. Eighty-three study participants aged between 21 and 58 years with a body mass index range of 20.2-46.8 kg/m(2) had been assessed at two different occasions with a mean follow-up between 23.5 and 43.5 months. Body-weight changes within weight stable, a gain or a loss of >3% of initial weight was considered as a significant weight change. There was a considerable bias between the body-composition data obtained by the individual methods. When compared with the 4C model, mean bias of D₂O and densitometry was explained by the erroneous assumption of a constant hydration of FFM, thus, changes in FM were underestimated by D₂O but overestimated by densitometry. Because hydration does not normalize after weight loss, all two-component models have a systematic error in weight-reduced subjects. The bias between 4C model and DXA was mainly explained by FM% at baseline, whereas FFM hydration contributed to additional 5%. As to the regional changes in body composition, DXA data had a considerable bias and, thus, cannot replace MRI. To assess changes in body composition associated with weight changes, only the 4C model and MRI can be used with confidence.

  12. 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

  13. Gain of virulence by Soybean mosaic virus on Rsv4-genotype soybeans is associated with a relative fitness loss in a susceptible host.

    Science.gov (United States)

    Wang, Y; Hajimorad, M R

    2016-09-01

    'Gene-for-gene' theory predicts that gain of virulence by an avirulent pathogen on plants expressing resistance (R) genes is associated with fitness loss in susceptible hosts. However, the validity of this prediction has been studied in only a few plant viral pathosystems. In this study, the Soybean mosaic virus (SMV)-Rsv4 pathosystem was exploited to test this prediction. In Rsv4-genotype soybeans, P3 of avirulent SMV strains provokes an as yet uncharacterized resistance mechanism that restricts the invading virus to the inoculated leaves. A single amino acid substitution in P3 functionally converts an avirulent to a virulent strain, suggesting that the genetic composition of P3 plays a crucial role in virulence on Rsv4-genotype soybeans. In this study, we examined the impact of gain of virulence mutation(s) on the fitness of virulent variants derived from three avirulent SMV strains in a soybean genotype lacking the Rsv4 gene. Our data demonstrate that gain of virulence mutation(s) by all avirulent viruses on Rsv4-genotype soybean is associated with a relative fitness loss in a susceptible host. The implications of this finding on the durable deployment of the Rsv4 gene in soybean are discussed. © 2015 BSPP and John Wiley & Sons Ltd.

  14. Sodium channelopathies of skeletal muscle result from gain or loss of function

    Science.gov (United States)

    Jurkat-Rott, Karin; Holzherr, Boris; Fauler, Michael

    2010-01-01

    Five hereditary sodium channelopathies of skeletal muscle have been identified. Prominent symptoms are either myotonia or weakness caused by an increase or decrease of muscle fiber excitability. The voltage-gated sodium channel NaV1.4, initiator of the muscle action potential, is mutated in all five disorders. Pathogenetically, both loss and gain of function mutations have been described, the latter being the more frequent mechanism and involving not just the ion-conducting pore, but aberrant pores as well. The type of channel malfunction is decisive for therapy which consists either of exerting a direct effect on the sodium channel, i.e., by blocking the pore, or of restoring skeletal muscle membrane potential to reduce the fraction of inactivated channels. PMID:20237798

  15. 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.

  16. Sodium channelopathies of skeletal muscle result from gain or loss of function.

    Science.gov (United States)

    Jurkat-Rott, Karin; Holzherr, Boris; Fauler, Michael; Lehmann-Horn, Frank

    2010-07-01

    Five hereditary sodium channelopathies of skeletal muscle have been identified. Prominent symptoms are either myotonia or weakness caused by an increase or decrease of muscle fiber excitability. The voltage-gated sodium channel NaV1.4, initiator of the muscle action potential, is mutated in all five disorders. Pathogenetically, both loss and gain of function mutations have been described, the latter being the more frequent mechanism and involving not just the ion-conducting pore, but aberrant pores as well. The type of channel malfunction is decisive for therapy which consists either of exerting a direct effect on the sodium channel, i.e., by blocking the pore, or of restoring skeletal muscle membrane potential to reduce the fraction of inactivated channels.

  17. Probing Reward Function in Posttraumatic Stress Disorder: Expectancy and Satisfaction with Monetary Gains and Losses

    Science.gov (United States)

    Hopper, James W.; Pitman, Roger K.; Su, Zhaohui; Heyman, Gene M.; Lasko, Natasha B.; Macklin, Michael L.; Orr, Scott P.; Lukas, Scott E.; Elman, Igor

    2008-01-01

    Background Post-traumatic stress disorder (PTSD) may be associated with dysfunctional reward processing. The present study assessed for such dysfunction in both the expectancy and outcome phases of reward processing. Methods Male Vietnam veterans with (n=15) and without (n=11) combat-related PTSD were administered a wheel of fortune-type gambling task. Self-reported ratings of expectancy and satisfaction were collected respectively before and after each experience of monetary gain or loss. Results PTSD participants reported both lower expectancy of reward and lower satisfaction with reward when it was received. The latter result was manifest in a failure of PTSD participants to show the greater satisfaction that normally accompanies rewards received under conditions of low expectancy. Conclusion These results suggest reward function impairment in PTSD related to expectancy, satisfaction, and the expectancy-satisfaction relationship. PMID:18068725

  18. 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.

  19. 26 CFR 1.631-2 - Gain or loss upon the disposal of timber under cutting contract.

    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 timber under cutting contract. 1.631-2 Section 1.631-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Sales and Exchanges § 1.631-2 Gain or...

  20. 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

  1. 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.

  2. 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...

  3. 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.

  4. 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.

  5. Loss of photoreceptorness and gain of genomic alterations in retinoblastoma reveal tumor progression

    Science.gov (United States)

    Kooi, Irsan E.; Mol, Berber M.; Moll, Annette C.; van der Valk, Paul; de Jong, Marcus C.; de Graaf, Pim; van Mil, Saskia E.; Schouten-van Meeteren, Antoinette Y.N.; Meijers-Heijboer, Hanne; Kaspers, Gertjan L.; te Riele, Hein; Cloos, Jacqueline; Dorsman, Josephine C.

    2015-01-01

    Background Retinoblastoma is a pediatric eye cancer associated with RB1 loss or MYCN amplification (RB1+/+MYCNA). There are controversies concerning the existence of molecular subtypes within RB1−/− retinoblastoma. To test whether these molecular subtypes exist, we performed molecular profiling. Methods Genome-wide mRNA expression profiling was performed on 76 primary human retinoblastomas. Expression profiling was complemented by genome-wide DNA profiling and clinical, histopathological, and ex vivo drug sensitivity data. Findings RNA and DNA profiling identified major variability between retinoblastomas. While gene expression differences between RB1+/+MYCNA and RB1−/− tumors seemed more dichotomous, differences within the RB1−/− tumors were gradual. Tumors with high expression of a photoreceptor gene signature were highly differentiated, smaller in volume and diagnosed at younger age compared with tumors with low photoreceptor signature expression. Tumors with lower photoreceptor expression showed increased expression of genes involved in M-phase and mRNA and ribosome synthesis and increased frequencies of somatic copy number alterations. Interpretation Molecular, clinical and histopathological differences between RB1−/− tumors are best explained by tumor progression, reflected by a gradual loss of differentiation and photoreceptor expression signature. Since copy number alterations were more frequent in tumors with less photoreceptorness, genomic alterations might be drivers of tumor progression. Research in context Retinoblastoma is an ocular childhood cancer commonly caused by mutations in the RB1 gene. In order to determine optimal treatment, tumor subtyping is considered critically important. However, except for very rare retinoblastomas without an RB1 mutation, there are controversies as to whether subtypes of retinoblastoma do exist. Our study shows that retinoblastomas are highly diverse but rather than reflecting distinct tumor types with

  6. 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.

  7. Loss of presenilin function is associated with a selective gain of APP function

    Science.gov (United States)

    Deyts, Carole; Clutter, Mary; Herrera, Stacy; Jovanovic, Natalia; Goddi, Anna; Parent, Angèle T

    2016-01-01

    Presenilin 1 (PS1) is an essential γ-secretase component, the enzyme responsible for amyloid precursor protein (APP) intramembraneous cleavage. Mutations in PS1 lead to dominant-inheritance of early-onset familial Alzheimer’s disease (FAD). Although expression of FAD-linked PS1 mutations enhances toxic Aβ production, the importance of other APP metabolites and γ-secretase substrates in the etiology of the disease has not been confirmed. We report that neurons expressing FAD-linked PS1 variants or functionally deficient PS1 exhibit enhanced axodendritic outgrowth due to increased levels of APP intracellular C-terminal fragment (APP-CTF). APP expression is required for exuberant neurite outgrowth and hippocampal axonal sprouting observed in knock-in mice expressing FAD-linked PS1 mutation. APP-CTF accumulation initiates CREB signaling cascade through an association of APP-CTF with Gαs protein. We demonstrate that pathological PS1 loss-of-function impinges on neurite formation through a selective APP gain-of-function that could impact on axodendritic connectivity and contribute to aberrant axonal sprouting observed in AD patients. DOI: http://dx.doi.org/10.7554/eLife.15645.001 PMID:27196744

  8. The gain and loss of chromosomal integron systems in the Treponema species.

    Science.gov (United States)

    Wu, Yu-Wei; Doak, Thomas G; Ye, Yuzhen

    2013-01-22

    Integron systems are now recognized as important agents of bacterial evolution and are prevalent in most environments. One of the human pathogens known to harbor chromosomal integrons, the Treponema spirochetes are the only clade among spirochete species found to carry integrons. With the recent release of many new Treponema genomes, we were able to study the distribution of chromosomal integrons in this genus. We find that the Treponema spirochetes implicated in human periodontal diseases and those isolated from cow and swine intestines contain chromosomal integrons, but not the Treponema species isolated from termite guts. By examining the species tree of selected spirochetes (based on 31 phylogenetic marker genes) and the phylogenetic tree of predicted integron integrases, and assisted by our analysis of predicted integron recombination sites, we found that all integron systems identified in Treponema spirochetes are likely to have evolved from a common ancestor--a horizontal gain into the clade. Subsequent to this event, the integron system was lost in the branch leading to the speciation of T. pallidum and T. phagedenis (the Treponema sps. implicated in sexually transmitted diseases). We also find that the lengths of the integron attC sites shortened through Treponema speciation, and that the integron gene cassettes of T. denticola are highly strain specific. This is the first comprehensive study to characterize the chromosomal integron systems in Treponema species. By characterizing integron distribution and cassette contents in the Treponema sps., we link the integrons to the speciation of the various species, especially to the pathogens T. pallidum and T. phagedenis.

  9. 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.

  10. 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.

  11. 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.

  12. Polymorphism of the beta3-adrenergic receptor gene and weight gain in pregnant diabetic women.

    Science.gov (United States)

    Yanagisawa, K; Iwasaki, N; Sanaka, M; Minei, S; Kanamori, M; Omori, Y; Iwamoto, Y

    1999-04-01

    Inappropriate body weight gain during pregnancy has critical effects on the outcome for both mother and fetus. Therefore, body weight gain is an important issue in the management of pregnancy in women with diabetes. A Trp64Arg substitution in the beta3-AR gene has been reported to be associated with body weight gain and obesity in non-insulin-dependent diabetes mellitus (NIDDM) subjects. The aim of this study was to elucidate the contribution of the beta3-AR gene to body weight gain during pregnancy in subjects with diabetes. We analyzed 199 diabetic patients (NIDDM/IDDM; 131/68) and patient data was obtained from the first delivery of each individual. The mean age at diagnosis of diabetes was 22.9 +/- 7.5 years (mean +/- S.D.) and the mean age at delivery was 29.8 +/- 4.5 years. A polymorphism of the beta3-AR gene was detected by PCR-RFLP using Bst OI, which recognizes a Trp64Arg substitution. The frequency of the Trp64Arg allele was 0.15 in NIDDM and 0.17 in IDDM. Among the NIDDM subjects, excess weight gain during pregnancy, as defined by maximum BMI during pregnancy minus basal BMI before pregnancy exceeding five, was observed in 12.2% of the wild-type patients, 19.2% of heterozygotes and 28.6% of homozygotes. Homozygous subjects with NIDDM tended to show excess weight gain during pregnancy, however, this trend did not reach significance. None of the IDDM homozygotes showed excess weight gain. From our study, this beta3-AR gene polymorphism cannot be excluded as a contributing factor to excess weight gain during pregnancy in NIDDM subjects.

  13. 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

  14. Does stress influence sleep patterns, food intake, weight gain, abdominal obesity and weight loss interventions and vice versa?

    DEFF Research Database (Denmark)

    Geiker, Nina Rica Wium; Astrup, Arne; Hjorth, Mads Fiil

    2018-01-01

    subjects. This review summarizes the scientific evidence on the role mental stress (either in or not in association with impaired sleep) may play in poor sleep, enhanced appetite, cravings and decreased motivation for physical activity. All these factors contribute to weight gain and obesity, possibly via...... decreasing the efficacy of weight loss interventions. We also review evidence for the role that lifestyle and stress management may play in achieving weight loss in stress-vulnerable individuals with overweight....

  15. Immunological loss-of-function due to genetic gain-of-function in humans: autosomal dominance of the third kind.

    Science.gov (United States)

    Boisson, Bertrand; Quartier, Pierre; Casanova, Jean-Laurent

    2015-02-01

    All the human primary immunodeficiencies (PIDs) recognized as such in the 1950s were Mendelian traits and, whether autosomal or X-linked, displayed recessive inheritance. The first autosomal dominant (AD) PID, hereditary angioedema, was recognized in 1963. However, since the first identification of autosomal recessive (AR), X-linked recessive (XR) and AD PID-causing genes in 1985 (ADA; severe combined immunodeficiency), 1986 (CYBB, chronic granulomatous disease) and 1989 (SERPING1; hereditary angioedema), respectively, the number of genetically defined AD PIDs has increased more rapidly than that of any other type of PID. AD PIDs now account for 61 of the 260 known conditions (23%). All known AR PIDs are caused by alleles with some loss-of-function (LOF). A single XR PID is caused by gain-of-function (GOF) mutations (WASP-related neutropenia, 2001). In contrast, only 44 of 61 AD defects are caused by LOF alleles, which exert dominance by haploinsufficiency or negative dominance. Since 2003, up to 17 AD disorders of the third kind, due to GOF alleles, have been described. Remarkably, six of the 17 genes concerned also harbor monoallelic (STAT3), biallelic (C3, CFB, CARD11, PIK3R1) or both monoallelic and biallelic (STAT1) LOF alleles in patients with other clinical phenotypes. Most heterozygous GOF alleles result in auto-inflammation, auto-immunity, or both, with a wide range of immunological and clinical forms. Some also underlie infections and, fewer, allergies, by impairing or enhancing immunity to non-self. Malignancies are also rare. The enormous diversity of immunological and clinical phenotypes is thought provoking and mirrors the diversity and pleiotropy of the underlying genotypes. These experiments of nature provide a unique insight into the quantitative regulation of human immunity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. 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.

  17. Multiple gains of spliceosomal introns in a superfamily of vertebrate protease inhibitor genes

    Directory of Open Access Journals (Sweden)

    Frese Marc-André

    2009-08-01

    Full Text Available Abstract Background Intron gains reportedly are very rare during evolution of vertebrates, and the mechanisms underlying their creation are largely unknown. Previous investigations have shown that, during metazoan radiation, the exon-intron patterns of serpin superfamily genes were subject to massive changes, in contrast to many other genes. Results Here we investigated intron dynamics in the serpin superfamily in lineages pre- and postdating the split of vertebrates. Multiple intron gains were detected in a group of ray-finned fishes, once the canonical groups of vertebrate serpins had been established. In two genes, co-occurrence of non-standard introns was observed, implying that intron gains in vertebrates may even happen concomitantly or in a rapidly consecutive manner. DNA breakage/repair processes associated with genome compaction are introduced as a novel factor potentially favoring intron gain, since all non-canonical introns were found in a lineage of ray-finned fishes that experienced genomic downsizing. Conclusion Multiple intron acquisitions were identified in serpin genes of a lineage of ray-finned fishes, but not in any other vertebrates, suggesting that insertion rates for introns may be episodically increased. The co-occurrence of non-standard introns within the same gene discloses the possibility that introns may be gained simultaneously. The sequences flanking the intron insertion points correspond to the proto-splice site consensus sequence MAG↑N, previously proposed to serve as intron insertion site. The association of intron gains in the serpin superfamily with a group of fishes that underwent genome compaction may indicate that DNA breakage/repair processes might foster intron birth.

  18. Relative Persuasiveness of Gain- versus Loss-Framed Human Papillomavirus Vaccination Messages for the Present- and Future-Minded

    Science.gov (United States)

    Nan, Xiaoli

    2012-01-01

    This research examines how young adults' attitudes toward human papillomavirus (HPV) vaccination and their intentions to get the vaccine are influenced by the framing of health messages (gain vs. loss) and time orientation (i.e., the extent to which people value immediate vs. distant consequences of their decisions). Results of an experiment…

  19. 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...

  20. 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

  1. 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

  2. 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.

  3. Immediate gain is long-term loss: Are there foresighted decision makers in the Iowa Gambling Task?

    Directory of Open Access Journals (Sweden)

    Lin Shuyeu

    2008-03-01

    Full Text Available Abstract Background The Somatic Marker Hypothesis suggests that normal subjects are "foreseeable" and ventromedial prefrontal patients are "myopic" in making decisions, as the behavior shown in the Iowa Gambling Task. The present study questions previous findings because of the existing confounding between long-term outcome (expected value, EV and gain-loss frequency variables in the Iowa Gambling Task (IGT. A newly and symmetrically designed gamble, namely the Soochow Gambling Task (SGT, with a high-contrast EV between bad (A, B and good (C, D decks, is conducted to clarify the issue about IGT confounding. Based on the prediction of EV (a basic assumption of IGT, participants should prefer to choose good decks C and D rather than bad decks A and B in SGT. In contrast, according to the prediction of gain-loss frequency, subjects should prefer the decks A and B because they possessed relatively the high-frequency gain. Methods The present experiment was performed by 48 participants (24 males and 24 females. Most subjects are college students recruited from different schools. Each subject played the computer version SGT first and completed a questionnaire for identifying their final preference. The IGT experimental procedure was mostly followed to assure a similar condition of decision uncertainty. Results The SGT experiment demonstrated that the prediction of gain-loss frequency is confirmed. Most subjects preferred to choose the bad decks A and B than good decks C and D. The learning curve and questionnaire data indicate that subjects can not "hunch" the EV throughout the game. Further analysis of the effect of previous choice demonstrated that immediate gain increases the probability to stay at the same deck. Conclusion SGT provides a balanced structure to clarify the confounding inside IGT and demonstrates that gain-loss frequency rather than EV guides decision makers in these high-ambiguity gambles. Additionally, the choice behavior is mostly

  4. Immediate gain is long-term loss: Are there foresighted decision makers in the Iowa Gambling Task?

    Science.gov (United States)

    Chiu, Yao-Chu; Lin, Ching-Hung; Huang, Jong-Tsun; Lin, Shuyeu; Lee, Po-Lei; Hsieh, Jen-Chuen

    2008-03-19

    The Somatic Marker Hypothesis suggests that normal subjects are "foreseeable" and ventromedial prefrontal patients are "myopic" in making decisions, as the behavior shown in the Iowa Gambling Task. The present study questions previous findings because of the existing confounding between long-term outcome (expected value, EV) and gain-loss frequency variables in the Iowa Gambling Task (IGT). A newly and symmetrically designed gamble, namely the Soochow Gambling Task (SGT), with a high-contrast EV between bad (A, B) and good (C, D) decks, is conducted to clarify the issue about IGT confounding. Based on the prediction of EV (a basic assumption of IGT), participants should prefer to choose good decks C and D rather than bad decks A and B in SGT. In contrast, according to the prediction of gain-loss frequency, subjects should prefer the decks A and B because they possessed relatively the high-frequency gain. The present experiment was performed by 48 participants (24 males and 24 females). Most subjects are college students recruited from different schools. Each subject played the computer version SGT first and completed a questionnaire for identifying their final preference. The IGT experimental procedure was mostly followed to assure a similar condition of decision uncertainty. The SGT experiment demonstrated that the prediction of gain-loss frequency is confirmed. Most subjects preferred to choose the bad decks A and B than good decks C and D. The learning curve and questionnaire data indicate that subjects can not "hunch" the EV throughout the game. Further analysis of the effect of previous choice demonstrated that immediate gain increases the probability to stay at the same deck. SGT provides a balanced structure to clarify the confounding inside IGT and demonstrates that gain-loss frequency rather than EV guides decision makers in these high-ambiguity gambles. Additionally, the choice behavior is mostly following the "gain-stay, lose-randomize" strategy to cope

  5. Gain and Loss in an Optically Pumped Mid-Infrared Laser

    National Research Council Canada - National Science Library

    Ongstad, A. P; Kaspi, R; Moeller, C. M; Tilton, M. L; Chavez, J. R

    2003-01-01

    ...) spectrometer was used to measure the laser mode spectra below threshold. To obtain an accurate determination of the gain, a full curve fit to the spectral output of the Fabry-Perot cavity was utilized...

  6. 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

  7. Analyzing Operator Actions to Gain Time in Loss of AC Power with Subsequent Loss of Secondary Heat Sink Accident

    International Nuclear Information System (INIS)

    Krajnc, B; Parzer, I.

    2002-01-01

    The thermohydraulic analysis of plant response on total loss of AC power is very demanding and challenging job due to a number of phenomena included. Such an analysis became even more complicated and interesting if we include also the assumption of total loss of secondary heat sink. If we want to prevent escalation of this type of accident into severe accident, then the AC power should be restored before the core is uncovered or before the core is damaged. Core damage occurs if the core exit thermocouples indicate temperature above 923K for more than 30 minutes. In this situation the timing to perform mitigating actions is essential. Operators should restore AC power or at least secondary heat sink as soon as possible. There are some operator's actions that have very important influence on the available time. Available time is considered to be the time before the core is damaged - partially or completely melted or the time before the RCS fails due to core melting (creep failure of reactor vessel or primary piping). In this paper we are going to present the plant specific analysis of complete loss of AC power with subsequent total loss of secondary heat sink and influence of key operator actions on the available time to recover AC power before the core damage occurs. The analyses will be performed with three different state of the art codes used at NPP Krsko and IJS: RELAP5/mod2, MAAP4 and ANTHEM. The last two codes are used in the plant specific full scope simulator, one for the simulation of the design bases transients and accidents and second for simulation of the severe accidents. This type of analyses has been done also for the simulator validation, performed during acceptance testing. (author)

  8. Low Cognitive Impulsivity Is Associated with Better Gain and Loss Learning in a Probabilistic Decision-Making Task

    Science.gov (United States)

    Cáceres, Pablo; San Martín, René

    2017-01-01

    Many advances have been made over the last decades in describing, on the one hand, the link between reward-based learning and decision-making, and on the other hand, the link between impulsivity and decision-making. However, the association between reward-based learning and impulsivity remains poorly understood. In this study, we evaluated the association between individual differences in loss-minimizing and gain-maximizing behavior in a learning-based probabilistic decision-making task and individual differences in cognitive impulsivity. We found that low cognitive impulsivity was associated both with a better performance minimizing losses and maximizing gains during the task. These associations remained significant after controlling for mathematical skills and gender as potential confounders. We discuss potential mechanisms through which cognitive impulsivity might interact with reward-based learning and decision-making. PMID:28261137

  9. 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

  10. 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.

  11. Effect of weight gain and subsequent weight loss on glucose tolerance and insulin response in healthy cats.

    Science.gov (United States)

    Biourge, V; Nelson, R W; Feldman, E C; Willits, N H; Morris, J G; Rogers, Q R

    1997-01-01

    The effects of weight gain and subsequent weight loss on glucose tolerance and insulin response were evaluated in 12 healthy cats. Intravenous glucose tolerance tests (IVGTT) were performed at entry into the study, after a significant gain of body weight induced by feeding palatable commercial cat food ad libitum, after a significant loss of body weight induced by feeding a poorly palatable purified diet to discourage eating and promote fasting, and after recovery from fasting when body weight had returned to pre-study values and cats were eating commercial foods. A complete physical examination with measurement of body weight was performed weekly, a CBC and serum biochemistry panel were evaluated at the time of each IVGTT, and a liver biopsy specimen obtained 2 to 4 days after each IVGTT was evaluated histologically for each cat. Mean serum glucose and insulin concentrations after glucose infusion and total amount of insulin secreted during the second 60 minutes and entire 120 minutes after glucose infusion were significantly (P cats had hepatic lipidosis and serum biochemical abnormalities consistent with feline hepatic lipidosis. There was a significant (P glucose concentration and t1/2, and a significant (P glucose disappearance coefficient (K) after glucose infusion for measurements obtained after weight loss, compared with those obtained after weight gain and at baseline. Insulin peak response, insulinogenic index, and total amount of insulin secreted during the initial 10 minutes, 20 minutes, and 60 minutes after glucose infusion were decreased markedly (P measurements obtained after weight gain and at baseline. In addition, the total amount of insulin secreted for 120 minutes after glucose infusion was decreased markedly (P measurements obtained after weight loss, compared with those obtained after weight gain. At the end of recovery, all cats were voluntarily consuming food, serum biochemical abnormalities identified after weight loss had resolved, the

  12. Resonant interaction of ϕ4 kink with PT-symmetric perturbation with spatially periodic gain/loss coefficient

    Science.gov (United States)

    Saadatmand, Danial; Borisov, Denis I.; Kevrekidis, Panayotis G.; Zhou, Kun; Dmitriev, Sergey V.

    2018-03-01

    The resonant interaction of the ϕ4 kink with a PT-symmetric perturbation is observed in the numerical study performed in the frame of the continuum model and with the help of a two degree of freedom collective variable model derived in PRA 89, 010102(R). The perturbation is in the form of first partial derivative in time term with a spatially periodic gain/loss coefficient. When the kink interacts with the perturbation, the kink's internal mode is excited with the amplitude varying in time quasiperiodically. The maximal value of the amplitude was found to grow when the kink velocity is such that it travels one period of the gain/loss prefactor in nearly one period of the kink's internal mode. It is also found that the kink's translational and vibrational modes are coupled in a way that an increase in the kink's internal mode amplitude results in a decrease in kink velocity. The results obtained with the collective variable method are in a good qualitative agreement with the numerical simulations for the continuum model. The results of the present study suggest that kink dynamics in open systems with balanced gain and loss can have new features in comparison with the case of conservative systems.

  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. Methylenetetrahydrofolate reductase gene variants and antipsychotic-induced weight gain and metabolic disturbances.

    Science.gov (United States)

    Kao, A C C; Rojnic Kuzman, M; Tiwari, A K; Zivkovic, M V; Chowdhury, N I; Medved, V; Kekin, I; Zai, C C; Lieberman, J A; Meltzer, H Y; Bozina, T; Bozina, N; Kennedy, J L; Sertic, J; Müller, D J

    2014-07-01

    Weight gain and metabolic disturbances represent serious side-effects in antipsychotic (AP) treatment, particularly with clozapine and olanzapine. The methylenetetrahydrofolate reductase (MTHFR) gene is a key determinant in the folate metabolism and previous studies reported a significant effect on AP-induced weight gain and related metabolic abnormalities. Thus, we investigated MTHFR gene variants and changes in several important metabolic parameters in AP-treated patients. In this study, two functional MTHFR polymorphisms, rs1801133 (C677T) and rs1801131 (A1298C), were investigated for changes in weight and metabolic parameters. Genotypic associations were evaluated in a large population (n = 347 including 66 first episode psychosis, FEP patients) treated mostly with clozapine and olanzapine. We did not detect any genotypic association with weight changes (p > 0.05) in our total sample and in the sample refined for ancestry and medication. In our allelic analyses, we observed a trend for the 677-C allele to be associated with weight gain in the total sample (p = 0.03). This effect appeared to be driven by the FEP patients where those carrying the C-allele gained, on average, twice as much weight. Exploratory analyses revealed a significant association between the C677T and the A1298C polymorphism with HDL cholesterol serum levels in patients (p = 0.031). Overall we did not detect a major effect of two functional MTHFR gene variants and AP-induced weight gain. However, our findings suggest an effect of the C677T polymorphism in FEP patients and changes in weight and cholesterol levels. Further investigations in a larger sample are required. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  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. 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.

  2. 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... REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Sales and Exchanges § 1.631-3 Gain or loss upon the disposal of coal or domestic iron ore with a...

  3. A Matter of Taste: Lineage-Specific Loss of Function of Taste Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Marco Antinucci

    2017-11-01

    Full Text Available Vertebrates can perceive at least five different taste qualities, each of which is thought to have a specific role in the evolution of different species. The avoidance of potentially poisonous foods, which are generally bitter or sour tasting, and the search for more nutritious ones, those with high-fat and high-sugar content, are two of the most well-known examples. The study of taste genes encoding receptors that recognize ligands triggering taste sensations has helped to reconstruct several evolutionary adaptations to dietary changes. In addition, an increasing number of studies have focused on pseudogenes, genomic DNA sequences that have traditionally been considered defunct relatives of functional genes mostly because of the presence of deleterious mutations interrupting their open reading frames. The study of taste receptor pseudogenes has helped to shed light on how the evolutionary history of taste in vertebrates has been the result of a succession of gene gain and loss processes. This dynamic role in evolution has been explained by the “less-is-more” hypothesis, suggesting gene loss as a mechanism of evolutionary change in response to a dietary shift. This mini-review aims at depicting the major lineage-specific loss of function of taste receptor genes in vertebrates, stressing their evolutionary importance and recapitulating signatures of natural selection and their correlations with food habits.

  4. Some electron-gain and electron-loss reactions of molecules and ions in condensed phases

    International Nuclear Information System (INIS)

    Symons, M.C.R.

    1979-01-01

    In the presence of the compounds having the long-pair of electrons available for bonding, electron-loss radicals can stabilize themselves by forming 3-electron bonds. Primary loss-centers can be detected by ESR spectroscopy. When a compound is exposed to electrons, it may dissociate by a variety of routes (dissociative electron capture), and solvation may play a significant role. ESR evidence shows that unpaired electrons become more strongly localized on the 2 atoms directly in the sigma bond than they are in the parent radical. In some systems, there is competition between the electron capture into a localized sigma orbital and that into a delocalized π orbital. Important examples are halouracils. The electron capture into the C-halogen sigma level is extensive for bromide and iodide, but for chloride, only the capture into the π level was detected. Electron-loss from organic halides has not been widely studied, since R-halide + cations are orbitally degenerate and not detectable by ESR spectroscopy. Electron capture causes dissociation to give R and halogen - . The electron capture by metallo-enzymes (oxyhemoglobin and myoglobin, xanthine oxidase, hemocyanin) is discussed on the basis of the ESR studies on the effect of ionizing radiation on the organic derivatives of biological significance. (Yamashita, S.)

  5. Aberrations of MET are associated with copy number gain of EGFR and loss of PTEN and predict poor outcome in patients with salivary gland cancer.

    Science.gov (United States)

    Ach, Tobias; Zeitler, Katharina; Schwarz-Furlan, Stephan; Baader, Katharina; Agaimy, Abbas; Rohrmeier, Christian; Zenk, Johannes; Gosau, Martin; Reichert, Torsten E; Brockhoff, Gero; Ettl, Tobias

    2013-01-01

    Hepatocyte growth factor receptor (MET) is a key driver of oncogenic transformation. Copy number gain and amplification of MET positively enhance tumour growth, invasiveness and metastasis in different cancer types. In the present study, 266 carcinomas of the major and minor salivary glands were investigated for genomic MET status by fluorescence in situ hybridization and for protein expression by immunohistochemistry. Results were matched with clinicopathological parameters, long-term survival and the status of epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN). Low polysomy (n = 42), high polysomy (n = 27), amplification (n = 2) and deletion (n = 18) were found as aberrations of genomic MET in certain subtypes. MET aberrations were associated with increased patient age (>70 years, p = 0.003), male gender (p = 0.01), increased tumour size (p = 0.002), lymph node metastases (p < 0.001), high-grade malignancy (p < 0.001) and unfavourable overall survival (p < 0.001). Both copy number gain (p < 0.001) and deletion (p = 0.031) of MET correlated with copy number gain of EGFR. Tumours with genomic loss of PTEN (n = 48) concurrently presented aberration of genomic MET (p < 0.001). MET gene status significantly correlated with protein status (p = 0.038). In conclusion, gain but also loss of genomic MET activity correlates with aggressive tumour growth, nodal metastasis and worse overall survival in salivary gland cancer. Moreover, aberrations of MET are associated with EGFR and PTEN signalling and might possess relevance for targeted therapies of salivary gland carcinomas in the future.

  6. Phylogenomic Analysis Identifies Gene Gains That Define Salmonella enterica Subspecies I

    Science.gov (United States)

    Lienau, E. Kurt; Blazar, Jeffrey M.; Wang, Charles; Brown, Eric W.; Stones, Robert; Musser, Steven; Allard, Marc W.

    2013-01-01

    Comparative methods for analyzing whole genome sequence (WGS) data enable us to assess the genetic information available for reconstructing the evolutionary history of pathogens. We used the comparative approach to determine diagnostic genes for Salmonella enterica subspecies I. S. enterica subsp. I strains are known to infect warm-blooded organisms regularly while its close relatives tend to infect only cold-blooded organisms. We found 71 genes gained by the common ancestor of Salmonella enterica subspecies I and not subsequently lost by any member of this subspecies sequenced to date. These genes included many putative functional phenotypes. Twenty-seven of these genes are found only in Salmonella enterica subspecies I; we designed primers to test these genes for use as diagnostic sequence targets and data mined the NCBI Sequence Read Archive (SRA) database for draft genomes which carried these genes. We found that the sequence specificity and variability of these amplicons can be used to detect and discriminate among 317 different serovars and strains of Salmonella enterica subspecies I. PMID:24204679

  7. Genome Sizes in Hepatica Mill: (Ranunculaceae Show a Loss of DNA, Not a Gain, in Polyploids

    Directory of Open Access Journals (Sweden)

    B. J. M. Zonneveld

    2010-01-01

    , and a possible pentaploid. The somatic nuclear DNA contents (2C-value, as measured by flow cytometry with propidium iodide, were shown to range from 33 to 80 pg. The Asiatic and American species, often considered subspecies of H. nobilis, could be clearly distinguished from European H. nobilis. DNA content confirmed the close relationships in the Asiatic species, and these are here considered as subspecies of H. asiatica. Parents for the allotetraploid species could be suggested based on their nuclear DNA content. Contrary to the increase in genome size suggested earlier for Hepatica, a significant (6%–14% loss of nuclear DNA in the natural allopolyploids was found.

  8. Modeling the Population-Level Processes of Biodiversity Gain and Loss at Geological Timescales.

    Science.gov (United States)

    Fortelius, Mikael; Geritz, Stefan; Gyllenberg, Mats; Raia, Pasquale; Toivonen, Jaakko

    2015-12-01

    The path of species diversification is commonly observed by inspecting the fossil record. Yet, how species diversity changes at geological timescales relate to lower-level processes remains poorly understood. Here we use mathematical models of spatially structured populations to show that natural selection and gradual environmental change give rise to discontinuous phenotype changes that can be connected to speciation and extinction at the macroevolutionary level. In our model, new phenotypes arise in the middle of the environmental gradient, while newly appearing environments are filled by existing phenotypes shifting their adaptive optima. Slow environmental change leads to loss of phenotypes in the middle of the extant environmental range, whereas fast change causes extinction at one extreme of the environmental range. We compared our model predictions against a well-known yet partially unexplained pattern of intense hoofed mammal diversification associated with grassland expansion during the Late Miocene. We additionally used the model outcomes to cast new insight into Cope's law of the unspecialized. Our general finding is that the rate of environmental change determines where generation and loss of diversity occur in the phenotypic and physical spaces.

  9. 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.

  10. Loss of genes implicated in gastric function during platypus evolution.

    Science.gov (United States)

    Ordoñez, Gonzalo R; Hillier, Ladeana W; Warren, Wesley C; Grützner, Frank; López-Otín, Carlos; Puente, Xose S

    2008-01-01

    The duck-billed platypus (Ornithorhynchus anatinus) belongs to the mammalian subclass Prototheria, which diverged from the Theria line early in mammalian evolution. The platypus genome sequence provides a unique opportunity to illuminate some aspects of the biology and evolution of these animals. We show that several genes implicated in food digestion in the stomach have been deleted or inactivated in platypus. Comparison with other vertebrate genomes revealed that the main genes implicated in the formation and activity of gastric juice have been lost in platypus. These include the aspartyl proteases pepsinogen A and pepsinogens B/C, the hydrochloric acid secretion stimulatory hormone gastrin, and the alpha subunit of the gastric H+/K+-ATPase. Other genes implicated in gastric functions, such as the beta subunit of the H+/K+-ATPase and the aspartyl protease cathepsin E, have been inactivated because of the acquisition of loss-of-function mutations. All of these genes are highly conserved in vertebrates, reflecting a unique pattern of evolution in the platypus genome not previously seen in other mammalian genomes. The observed loss of genes involved in gastric functions might be responsible for the anatomical and physiological differences in gastrointestinal tract between monotremes and other vertebrates, including small size, lack of glands, and high pH of the monotreme stomach. This study contributes to a better understanding of the mechanisms that underlie the evolution of the platypus genome, might extend the less-is-more evolutionary model to monotremes, and provides novel insights into the importance of gene loss events during mammalian evolution.

  11. Resonant crossover of terahertz loss to the gain of a Bloch oscillating InAs/AlSb superlattice.

    Science.gov (United States)

    Savvidis, P G; Kolasa, B; Lee, G; Allen, S J

    2004-05-14

    Terahertz absorption in waveguides loaded with InAs/AlSb super-superlattice mesas reveals a frequency dependent crossover from loss to gain that is related to the Stark ladder produced by an applied dc electric field. Electric field domains appear to be suppressed in the super-superlattice composed of many very short segments of superlattice, interrupted by heavily doped InAs regions. Resonant crossover is indicated by an increase in terahertz transmission as the Stark splitting or Bloch frequency determined by the applied dc electric field exceeds the measurement frequency.

  12. 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

  13. The Trans-Pacific Partnership Agreement and health: few gains, some losses, many risks.

    Science.gov (United States)

    Labonté, Ronald; Schram, Ashley; Ruckert, Arne

    2016-06-06

    In early October 2015, 12 nations signed the Trans-Pacific Partnership Agreement (TPPA), promoted as a model '21(st) century' trade and investment agreement that other countries would eventually join. There are growing concerns amongst the public health community about the potential health implications of such WTO+ trade and investment agreements, but little existing knowledge on their potential health impacts. We conducted a health impact review which allows for a summary estimation of the most significant health impacts of a set of policies, in our case the TPPA. Our analysis shows that there are a number of potentially serious health risks, with the following key pathways linking trade to health: access to medicines, reduced regulatory space, investor-state dispute settlement (ISDS), and environmental protection and labor rights. We also note that economic gains that could translate into health benefits will likely be inequitably distributed. Our analysis demonstrates the need for the public health community to be knowledgeable about trade issues and more engaged in trade negotiations. In the context of the COP21 climate change Agreement, and the UN Sustainable Development Goals, this may be an opportune time for TPPA countries to reject it as drafted, and rethink what should be the purpose of such agreements in light of (still) escalating global wealth inequalities and fragile environmental resources-the two most foundational elements to global health equity.

  14. 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.

  15. Substantial Loss of Conserved and Gain of Novel MicroRNA Families in Flatworms

    Science.gov (United States)

    Fromm, Bastian; Worren, Merete Molton; Hahn, Christoph; Hovig, Eivind; Bachmann, Lutz

    2013-01-01

    Recent studies on microRNA (miRNA) evolution focused mainly on the comparison of miRNA complements between animal clades. However, evolution of miRNAs within such groups is poorly explored despite the availability of comparable data that in some cases lack only a few key taxa. For flatworms (Platyhelminthes), miRNA complements are available for some free-living flatworms and all major parasitic lineages, except for the Monogenea. We present the miRNA complement of the monogenean flatworm Gyrodactylus salaris that facilitates a comprehensive analysis of miRNA evolution in Platyhelminthes. Using the newly designed bioinformatics pipeline miRCandRef, the miRNA complement was disentangled from next-generation sequencing of small RNAs and genomic DNA without a priori genome assembly. It consists of 39 miRNA hairpin loci of conserved miRNA families, and 22 novel miRNAs. A comparison with the miRNA complements of Schmidtea mediterranea (Turbellaria), Schistosoma japonicum (Trematoda), and Echinococcus granulosus (Cestoda) reveals a substantial loss of conserved bilaterian, protostomian, and lophotrochozoan miRNAs. Eight of the 46 expected conserved miRNAs were lost in all flatworms, 16 in Neodermata and 24 conserved miRNAs could not be detected in the cestode and the trematode. Such a gradual loss of miRNAs has not been reported before for other animal phyla. Currently, little is known about miRNAs in Platyhelminthes, and for the majority of the lost miRNAs there is no prediction of function. As suggested earlier they might be related to morphological simplifications. The presence and absence of 153 conserved miRNAs was compared for platyhelminths and 32 other metazoan taxa. Phylogenetic analyses support the monophyly of Platyhelminthes (Turbellaria + Neodermata [Monogenea {Trematoda + Cestoda}]). PMID:24025793

  16. 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

  17. 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.

  18. Loss of magel2, a candidate gene for features of Prader-Willi syndrome, impairs reproductive function in mice.

    Directory of Open Access Journals (Sweden)

    Rebecca E Mercer

    Full Text Available BACKGROUND: MAGEL2 is one of several genes typically inactivated in the developmental obesity disorder Prader-Willi syndrome (PWS. The physiological consequences of loss of MAGEL2, but without the concurrent loss of other PWS genes, are not well understood. Gene-targeted mutation of Magel2 in mice disrupts circadian rhythm and metabolism causing reduced total activity, reduced weight gain before weaning, and increased adiposity after weaning. PRINCIPAL FINDINGS: We now show that loss of Magel2 in mice causes reduced fertility in both males and females through extended breeding intervals and early reproductive decline and termination. Female Magel2-null mice display extended and irregular estrous cycles, while males show decreased testosterone levels, and reduced olfactory preference for female odors. CONCLUSIONS: Our results suggest that loss of MAGEL2 contributes to the reproductive deficits seen in people with PWS, and further highlights the role of normal circadian rhythm in the maintenance of fertility.

  19. Multiplexing topologies and time scales: The gains and losses of synchrony

    Science.gov (United States)

    Makovkin, Sergey; Kumar, Anil; Zaikin, Alexey; Jalan, Sarika; Ivanchenko, Mikhail

    2017-11-01

    Inspired by the recent interest in collective dynamics of biological neural networks immersed in the glial cell medium, we investigate the frequency and phase order, i.e., Kuramoto type of synchronization in a multiplex two-layer network of phase oscillators of different time scales and topologies. One of them has a long-range connectivity, exemplified by the Erdős-Rényi random network, and supports both kinds of synchrony. The other is a locally coupled two-dimensional lattice that can reach frequency synchronization but lacks phase order. Drastically different layer frequencies disentangle intra- and interlayer synchronization. We find that an indirect but sufficiently strong coupling through the regular layer can induce both phase order in the originally nonsynchronized random layer and global order, even when an isolated regular layer does not manifest it in principle. At the same time, the route to global synchronization is complex: an initial onset of (partial) synchrony in the regular layer, when its intra- and interlayer coupling is increased, provokes the loss of synchrony even in the originally synchronized random layer. Ultimately, a developed asynchronous dynamics in both layers is abruptly taken over by the global synchrony of both kinds.

  20. Gain and loss of polyadenylation signals during evolution of green algae

    Directory of Open Access Journals (Sweden)

    Glöckner Gernot

    2007-04-01

    Full Text Available Abstract Background The Viridiplantae (green algae and land plants consist of two monophyletic lineages: the Chlorophyta and the Streptophyta. Most green algae belong to the Chlorophyta, while the Streptophyta include all land plants and a small group of freshwater algae known as Charophyceae. Eukaryotes attach a poly-A tail to the 3' ends of most nuclear-encoded mRNAs. In embryophytes, animals and fungi, the signal for polyadenylation contains an A-rich sequence (often AAUAAA or related sequence 13 to 30 nucleotides upstream from the cleavage site, which is commonly referred to as the near upstream element (NUE. However, it has been reported that the pentanucleotide UGUAA is used as polyadenylation signal for some genes in volvocalean algae. Results We set out to investigate polyadenylation signal differences between streptophytes and chlorophytes that may have emerged shortly after the evolutionary split between Streptophyta and Chlorophyta. We therefore analyzed expressed genes (ESTs from three streptophyte algae, Mesostigma viride, Klebsormidium subtile and Coleochaete scutata, and from two early-branching chlorophytes, Pyramimonas parkeae and Scherffelia dubia. In addition, to extend the database, our analyses included ESTs from six other chlorophytes (Acetabularia acetabulum, Chlamydomonas reinhardtii, Helicosporidium sp. ex Simulium jonesii, Prototheca wickerhamii, Scenedesmus obliquus and Ulva linza and one streptophyte (Closterium peracerosum. Our results indicate that polyadenylation signals in green algae vary widely. The UGUAA motif is confined to late-branching Chlorophyta. Most streptophyte algae do not have an A-rich sequence motif like that in embryophytes, animals and fungi. We observed polyadenylation signals similar to those of Arabidopsis and other land plants only in Mesostigma. Conclusion Polyadenylation signals in green algae show considerable variation. A new NUE (UGUAA was invented in derived chlorophytes and replaced

  1. Gain and loss of polyadenylation signals during evolution of green algae.

    Science.gov (United States)

    Wodniok, Sabina; Simon, Andreas; Glöckner, Gernot; Becker, Burkhard

    2007-04-18

    The Viridiplantae (green algae and land plants) consist of two monophyletic lineages: the Chlorophyta and the Streptophyta. Most green algae belong to the Chlorophyta, while the Streptophyta include all land plants and a small group of freshwater algae known as Charophyceae. Eukaryotes attach a poly-A tail to the 3' ends of most nuclear-encoded mRNAs. In embryophytes, animals and fungi, the signal for polyadenylation contains an A-rich sequence (often AAUAAA or related sequence) 13 to 30 nucleotides upstream from the cleavage site, which is commonly referred to as the near upstream element (NUE). However, it has been reported that the pentanucleotide UGUAA is used as polyadenylation signal for some genes in volvocalean algae. We set out to investigate polyadenylation signal differences between streptophytes and chlorophytes that may have emerged shortly after the evolutionary split between Streptophyta and Chlorophyta. We therefore analyzed expressed genes (ESTs) from three streptophyte algae, Mesostigma viride, Klebsormidium subtile and Coleochaete scutata, and from two early-branching chlorophytes, Pyramimonas parkeae and Scherffelia dubia. In addition, to extend the database, our analyses included ESTs from six other chlorophytes (Acetabularia acetabulum, Chlamydomonas reinhardtii, Helicosporidium sp. ex Simulium jonesii, Prototheca wickerhamii, Scenedesmus obliquus and Ulva linza) and one streptophyte (Closterium peracerosum). Our results indicate that polyadenylation signals in green algae vary widely. The UGUAA motif is confined to late-branching Chlorophyta. Most streptophyte algae do not have an A-rich sequence motif like that in embryophytes, animals and fungi. We observed polyadenylation signals similar to those of Arabidopsis and other land plants only in Mesostigma. Polyadenylation signals in green algae show considerable variation. A new NUE (UGUAA) was invented in derived chlorophytes and replaced not only the A-rich NUE but the complete poly

  2. Diversity, loss, and gain of malaria parasites in a globally invasive bird.

    Directory of Open Access Journals (Sweden)

    Alfonso Marzal

    Full Text Available Invasive species can displace natives, and thus identifying the traits that make aliens successful is crucial for predicting and preventing biodiversity loss. Pathogens may play an important role in the invasive process, facilitating colonization of their hosts in new continents and islands. According to the Novel Weapon Hypothesis, colonizers may out-compete local native species by bringing with them novel pathogens to which native species are not adapted. In contrast, the Enemy Release Hypothesis suggests that flourishing colonizers are successful because they have left their pathogens behind. To assess the role of avian malaria and related haemosporidian parasites in the global spread of a common invasive bird, we examined the prevalence and genetic diversity of haemosporidian parasites (order Haemosporida, genera Plasmodium and Haemoproteus infecting house sparrows (Passer domesticus. We sampled house sparrows (N = 1820 from 58 locations on 6 continents. All the samples were tested using PCR-based methods; blood films from the PCR-positive birds were examined microscopically to identify parasite species. The results show that haemosporidian parasites in the house sparrows' native range are replaced by species from local host-generalist parasite fauna in the alien environments of North and South America. Furthermore, sparrows in colonized regions displayed a lower diversity and prevalence of parasite infections. Because the house sparrow lost its native parasites when colonizing the American continents, the release from these natural enemies may have facilitated its invasion in the last two centuries. Our findings therefore reject the Novel Weapon Hypothesis and are concordant with the Enemy Release Hypothesis.

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

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    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.

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

    Science.gov (United States)

    Sanhueza, Mario; Zechini, Luigi; Gillespie, Trudy; Pennetta, Giuseppa

    2014-01-15

    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.

  5. 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)

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. Predictors and the role of attitude toward the message and perceived message quality in gain- and loss-frame antidrug persuasion of adolescents.

    Science.gov (United States)

    Cho, Hyunyi; Choi, Jounghwa

    2010-06-01

    This study examines predictors and the role of attitude toward the message and perceived message quality in the gain- and loss-framed antidrug persuasion of adolescents. Identification predicted the perceived effectiveness of gain- but not loss-frame ads, whereas perceived realism contributed to the perceived effectiveness of both frame ads. Positive affect predicted the attitude toward the gain-frame ads, whereas negative affect predicted the perceived quality of the loss-frame ads. Attitude toward the message was a stronger predictor of the effectiveness of gain-frame ads, while perceived message quality but not attitude toward the message was correlated with the effectiveness of loss-frame ads. Discussion focuses on implications for formative evaluation of health communication campaign messages.

  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. 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.

  13. 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.

  14. 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

  15. Gaining with loss

    Science.gov (United States)

    Pile, Interview by David F. P.

    2017-12-01

    Nature Photonics spoke to Demetrios Christodoulides, of CREOL, The College of Optics & Photonics, University of Central Florida, about the birth of the parity-time-symmetry concepts in optics and the challenges and prospects on the path ahead.

  16. Nature's loss, Immunologists gain?

    Science.gov (United States)

    Aluvihare

    2000-01-01

    Nature Reviews Molecular Cell Biology Nature Publishing Group (2000). ISSN 1471-0072. Monthly First there was Annual Reviews, then came the monthly Elsevier Trends Journals, both of which try to identify hot topics in their chosen fields. The Current Opinion journals followed several years later, and Current Opinion in Cell Biology is presently one of the highest 'impact factor' review journals, with a distinguished board of editors and advisors and a systematic approach to regular coverage of the major fields of cell biology. Important topics are visited once a year, whether or not something specially exciting happened in the last 12 months. Add to this list Seminars in Cell and Developmental Biology, the FASEB journal and the countless minireviews in 'real' journals, and you begin to wonder how anyone finds any time for doing experiments, or indeed reading the primary literature. So, into this already crowded field arrive three important newcomers: Nature Reviews in Molecular Cell Biology, Genetics, and Neurosciences, of which the first two will probably interest readers of Journal of Cell Science the most. Backed by the name and money of Nature and edited by experienced Nature staff, it is hard to see how these publications can possibly do other than succeed with writers and readers alike. What's inside the first issue? The cover of Nature Reviews in Molecular Cell Biology presents a 3-colour montage of a blue cell nucleus surrounded by splotches of green GPI-anchored GFP overlaid by orange actin stress fibres that seem to come from somewhere else. This image trails a comprehensive review from Kai Simons and Derek Toomre about Lipid Rafts. There are another five major review articles: calcium puffs and sparks, rings around DNA, HIV inhibitors, kinesin and the circadian clock provide a rich and varied mix of topics from authors who know what they're talking about. Surrounding this core is an entertaining mixture of 'highlights' at the front: news and views about a well-chosen selection of recent articles in the primary literature written by the three editors. These struck me as striking slightly too jokey a style. It is a terrible temptation and mistake in this kind of piece, I think, to equate lightheartedness with clarity. The sugar coating is more likely to irritate than enlighten. I would also question the wisdom, if it is indeed a policy, of only allowing editors to write in this section. I'm all for experienced writers writing, but I think I would prefer the variety of voice and authority evinced by the parental Nature News and Views. After the main reviews comes a section entitled 'perspectives', which include a 'Timeline' piece on Hayflick and his limit by Jerry Shay and Woodring Wright that I very much enjoyed, and a review (or Opinion) about cancer from Judah Folkman, Philip Hahnfeldt and Lynn Hlatky. In their own words, "the impetus for this Opinion article centres on the increasing awareness of the heterogeneity and instability of the cancer genome [. I]t is possible that suppressing this degenerative process may itself comprise an alternative constraint-based paradigm." The authors' fondness for portentous phrases of this kind rather spoiled their discussion for me. I also had trouble with an article on molecular computing. PCR reactions can solve the travelling salesman problem, it seems, but extremely slowly compared to a proper computer. The magazine has a nice heft to it, and is attractively designed and presented in glossy colour, although the main font is small enough to make reading difficult for your middle-aged reviewer in a particularly heavily overcast and rainy week in London. A first issue is supposed to be a kind of showcase, but if they can keep this up, the editors will surely have a success on their hands and you will probably be obliged to take out a personal subscription (£85), or persuade your library to part with £565. That's slightly cheaper than TiBS and a lot cheaper than Current Opinion in Cell Biology, both of which will have to run faster if they want to stay in the same place.

  17. Minimal alteration in muscle lipid genes following stabilized weight loss.

    Science.gov (United States)

    Coker, Robert H; Robinette, Leizleigh; Kern, Philip A

    2017-12-01

    Variations in skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), carntine palmitoyltransferase-1 (CPT-1), perilipin protein 2 (PLIN2), and adipose tissue triglyceride lipase (ATGL), and comparative gene identification-58 (CGI-58) have been described as playing important roles in the metabolic regulation of lipid oxidation, and may influence intramyocellular lipid (IMCL) and muscle lipid droplet size (LDS). While acute changes in caloric balance and/or aerobic capacity may affect lipid metabolism, the influence of sustained weight loss derived from caloric restriction with weight loss (CWL) compared with exercise training with weight loss (EWL) on the abovementioned parameters has not been fully elucidated. Using a combination of metabolic feeding and/or supervised exercise training, we evaluated the influence of stabilized weight loss elicited by CWL compared with EWL without the confounding influence of acute alterations in caloric balance on molecular markers of mitochondrial metabolism and lipid droplet size in middle-aged overweight individuals with impaired glucose tolerance. There were no significant changes in PGC-1α, CPT-1, PLIN2, ATGL and, CGI-58 messenger RNA (mRNA) in CWL and EWL. While there were no changes in ATGL mRNA in CWL, there was a strong trend (P = 0.05) for the ΔATGL mRNA in EWL with stabilized weight loss. There were no significant changes in IMCL or LDS within skeletal muscle in CWL or EWL, respectively. In conclusion, under the conditions of chronic caloric balance following dietary or exercise-based interventions, mediators of mitochondrial function, IMCL and LDS, were largely unaffected. Future studies should focus on intervention-based changes in protein expression and/or phosphorylation and the relationship to physiological endpoints.

  18. 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.

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

    Science.gov (United States)

    Tsuber, Viktoriia; Kadamov, Yunus; Brautigam, Lars; Berglund, Ulrika Warpman; Helleday, Thomas

    2017-07-03

    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.

  20. 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

  1. 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

  2. 26 CFR 1.1251-1 - General rule for treatment of gain from disposition of property used in farming where farm losses...

    Science.gov (United States)

    2010-04-01

    ... disposition of property used in farming where farm losses offset nonfarm income. 1.1251-1 Section 1.1251-1... of gain from disposition of property used in farming where farm losses offset nonfarm income. (a..., certain farming property (other than section 1250 property) described in paragraph (1), (3), or (4) of...

  3. Expanded insecticide catabolic activity gained by a single nucleotide substitution in a bacterial carbamate hydrolase gene.

    Science.gov (United States)

    Öztürk, Başak; Ghequire, Maarten; Nguyen, Thi Phi Oanh; De Mot, René; Wattiez, Ruddy; Springael, Dirk

    2016-12-01

    Carbofuran-mineralizing strain Novosphingobium sp. KN65.2 produces the CfdJ enzyme that converts the N-methylcarbamate insecticide to carbofuran phenol. Purified CfdJ shows a remarkably low K M towards carbofuran. Together with the carbaryl hydrolase CehA of Rhizobium sp. strain AC100, CfdJ represents a new protein family with several uncharacterized bacterial members outside the proteobacteria. Although both enzymes differ by only four amino acids, CehA does not recognize carbofuran as a substrate whereas CfdJ also hydrolyzes carbaryl. None of the CfdJ amino acids that differ from CehA were shown to be silent regarding carbofuran hydrolytic activity but one particular amino acid substitution, i.e., L152 to F152, proved crucial. CfdJ is more efficient in degrading methylcarbamate pesticides with an aromatic side chain whereas CehA is more efficient in degrading the oxime carbamate nematicide oxamyl. The presence of common flanking sequences suggest that the cfdJ gene is located on a remnant of the mobile genetic element Tnceh carrying cehA. Our results suggest that these enzymes can be acquired through horizontal gene transfer and can evolve to degrade new carbamate substrates by limited amino acid substitutions. We demonstrate that a carbaryl hydrolase can gain the additional capacity to degrade carbofuran by a single nucleotide transversion. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  4. 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.

  5. 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.

  6. 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.

  7. Skeletal muscle myopathy mutations at the actin tropomyosin interface that cause gain- or loss-of-function.

    Science.gov (United States)

    Memo, Massimiliano; Marston, Steven

    2013-08-01

    It is well known that the regulation of muscle contraction relies on the ability of tropomyosin to switch between different positions on the actin filament, but it is still not well understood which amino acids are directly involved in the different states of the interaction. Recently the structure of the actin-tropomyosin interface has been determined both in the absence and presence of myosin heads. Interestingly, a number of mutations in tropomyosin that are associated with skeletal muscle myopathy are located within this interface. We first give an overview of the functional effect of mutations on amino acids that are involved in the contact with actin asp25, which represent a pattern repeated seven times along tropomyosin. It is explained how some of these amino acids (R167 and R244) which are thought to be involved in a salt bridge contact with actin in the closed state can produce a loss-of-function when mutated, while other positively charged tropomyosin amino acids positioned on the downstream side of the contact (K7, K49, R91, K168) can produce a gain-of-function when mutated. We then consider mutations of amino acids involved in another salt bridge contact between the two proteins in the closed state, actin K326N (which binds on five different points of tropomyosin) and tropomyosin ∆E139 and E181K, and we report how all of these mutations produce a gain-of-function. These observations can be important to validate the proposed structures and to understand more deeply how mutations affect the function of these proteins and to enable prediction of their outcomes.

  8. Phosphodiesterase 4D gene polymorphisms in sudden sensorineural hearing loss.

    Science.gov (United States)

    Chien, Chen-Yu; Tai, Shu-Yu; Wang, Ling-Feng; Hsi, Edward; Chang, Ning-Chia; Wang, Hsun-Mo; Wu, Ming-Tsang; Ho, Kuen-Yao

    2016-09-01

    The phosphodiesterase 4D (PDE4D) gene has been reported as a risk gene for ischemic stroke. The vascular factors are between the hypothesized etiologies of sudden sensorineural hearing loss (SSNHL), and this genetic effect might be attributed for its role in SSNHL. We hypothesized that genetic variants of the PDE4D gene are associated with susceptibility to SSNHL. We conducted a case-control study with 362 SSNHL cases and 209 controls. Three single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. We carried out sex-specific analysis to analyze the overall data. All three SNPs were in HWE. When subjects were stratified by sex, the genetic effect was only evident in females but not in males. The TT genotype of rs702553 exhibited an adjusted odds ratio (OR) of 3.83 (95 % confidence interval = 1.46-11.18) (p = 0.006) in female SSNHL. The TT genotype of SNP rs702553 was associated with female SSNHL under the recessive model (p = 0.004, OR 3.70). In multivariate logistic regression analysis, TT genotype of rs702553 was significantly associated with female SSNHL (p = 0.0043, OR 3.70). These results suggest that PDE4D gene polymorphisms influence the susceptibility for the development of SSNHL in the southern Taiwanese female population.

  9. Changes in the secondary sexual adornments of male mandrills (Mandrillus sphinx) are associated with gain and loss of alpha status.

    Science.gov (United States)

    Setchell, J M; Dixson, A F

    2001-05-01

    Two semifree-ranging mandrill groups, inhabiting large, naturally rainforested enclosures in Gabon, were studied to measure morphological, endocrine, and behavioral changes that occurred when adult males rose, or fell, in dominance rank. Gaining alpha rank (N = 4 males) resulted in increased testicular size and circulating testosterone, reddening of the sexual skin on the face and genitalia, and heightened secretion from the sternal cutaneous gland. Blue sexual skin coloration was unaffected. New alpha males increased in rump "fattedness," but not in body mass, and spent more time associated with other group members, rather than ranging alone. Loss of alpha position (N = 4 males) resulted in less pronounced effects than those that occurred after males had risen to alpha positions. Deposed alpha males showed decreased testicular volume, decreased body mass, a reduction in the extent of red (but not blue) sexual skin coloration, and decreased sternal gland activity. Deposed males did not decrease in the brightness of sex skin coloration. These results demonstrate that male-male competition and rank reversals have remarkable effects upon testicular function, secondary sexual traits, and behavior in the adult male mandrill. Secondary sexual traits respond to changes in male social status and therefore may be important as intrasexual signals of dominance rank. Copyright 2001 Academic Press.

  10. 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.

  11. Titanium Mass-balance Analysis of Paso Robles Soils: Elemental Gains and Losses as Affected by Acid Alteration Fluids

    Science.gov (United States)

    Sutter, Brad; Ming, Douglas W.

    2010-01-01

    The Columbia Hills soils have been exposed to aqueous alteration in alkaline [1] as well as acid conditions [2,3]. The Paso Robles class soils are bright soils that possess the highest S concentration of any soil measured on Mars [2]. Ferric-sulfate detection by Moessbauer analysis indicated that acid solutions were involved in forming these soils [4]. These soils are proposed to have formed by alteration of nearby rock by volcanic hydrothermal or fumarolic activity. The Paso Robles soils consist of the original Paso Robles-disturbed-Pasadena (PR-dist), Paso Robles- PasoLight (PR-PL), Arad-Samra, Arad-Hula, Tyrone- Berker Island1 and Tyrone-MountDarwin [2 ,3. ]Chemical characteristics indicate that the PR-dist and PR-PL soils could be derived from acid weathering of local Wishstone rocks while the Samra and Hula soils are likely derived from local Algonquin-Iroquet rock [3]. The Paso Robles soils were exposed to acidic sulfur bearing fluids; however, little else is known about the chemistry of the alteration fluid and its effects on the alteration of the proposed parent materials. The objectives of this work are to conduct titanium normalized mass-balance analysis to1) assess elemental gains and losses from the parent materials in the formation of the Paso Robles soils and 2) utilize this information to indicate the chemical nature of the alteration fluids.

  12. 26 CFR 1.1502-22A - Consolidated net capital gain or loss generally applicable for consolidated return years...

    Science.gov (United States)

    2010-04-01

    ... consolidated net capital loss for any taxable year attributable to a foreign expropriation capital loss is the amount of the foreign expropriation capital losses of all the members for such year (but not in excess of... that any portion of a net capital loss attributable to a foreign expropriation capital loss to which...

  13. 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.

  14. 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

  15. Simultaneous Mutations in Multi-Viral Proteins Are Required for Soybean mosaic virus to Gain Virulence on Soybean Genotypes Carrying Different R Genes

    Science.gov (United States)

    Chowda-Reddy, R. V.; Sun, Haiyue; Hill, John H.; Poysa, Vaino; Wang, Aiming

    2011-01-01

    Background Genetic resistance is the most effective and sustainable approach to the control of plant pathogens that are a major constraint to agriculture worldwide. In soybean, three dominant R genes, i.e., Rsv1, Rsv3 and Rsv4, have been identified and deployed against Soybean mosaic virus (SMV) with strain-specificities. Molecular identification of virulent determinants of SMV on these resistance genes will provide essential information for the proper utilization of these resistance genes to protect soybean against SMV, and advance knowledge of virus-host interactions in general. Methodology/Principal Findings To study the gain and loss of SMV virulence on all the three resistance loci, SMV strains G7 and two G2 isolates L and LRB were used as parental viruses. SMV chimeras and mutants were created by partial genome swapping and point mutagenesis and then assessed for virulence on soybean cultivars PI96983 (Rsv1), L-29 (Rsv3), V94-5152 (Rsv4) and Williams 82 (rsv). It was found that P3 played an essential role in virulence determination on all three resistance loci and CI was required for virulence on Rsv1- and Rsv3-genotype soybeans. In addition, essential mutations in HC-Pro were also required for the gain of virulence on Rsv1-genotype soybean. To our best knowledge, this is the first report that CI and P3 are involved in virulence on Rsv1- and Rsv3-mediated resistance, respectively. Conclusions/Significance Multiple viral proteins, i.e., HC-Pro, P3 and CI, are involved in virulence on the three resistance loci and simultaneous mutations at essential positions of different viral proteins are required for an avirulent SMV strain to gain virulence on all three resistance loci. The likelihood of such mutations occurring naturally and concurrently on multiple viral proteins is low. Thus, incorporation of all three resistance genes in a soybean cultivar through gene pyramiding may provide durable resistance to SMV. PMID:22140577

  16. 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.

  17. Expression of cytokine genes and receptors in white blood cells associated with divergent body weight gain in beef steers

    Science.gov (United States)

    Previous work examining the transcriptome of steer tissue samples from animals with divergent gain have shown a relationship with the expression of genes with functions in immune and inflammatory pathways. The process of mounting an immune or inflammatory response is energetically expensive and vari...

  18. Extreme Rapid Weight Loss and Rapid Weight Gain Observed in UK Mixed Martial Arts Athletes Preparing for Competition.

    Science.gov (United States)

    Matthews, Joseph John; Nicholas, Ceri

    2017-04-01

    There is a lack of research documenting the weight-making practices of mixed-martial-arts (MMA) competitors. The purpose of the investigation was to quantify the magnitude and identify the methods of rapid weight loss (RWL) and rapid weight gain (RWG) in MMA athletes preparing for competition. Seven athletes (mean ± SD, age 24.6 ± 3.5 yrs, body mass 69.9 ± 5.7 kg, competitive experience 3.1 ± 2.2 yrs) participated in a repeated-measures design. Measures of dietary intake, urinary hydration status, and body mass were recorded in the week preceding competition. Body mass decreased significantly (p < .0005) from baseline by 5.6 ± 1.4 kg (8 ± 1.8%). During the RWG period (32 ± 1 hr) body mass increased significantly (p < .001) by 7.4 ± 2.8 kg (11.7 ± 4.7%), exceeding RWL. Mean energy and carbohydrate intake were 3176 ± 482 kcal・day -1 and 471 ± 124 g・day -1 , respectively. At the official weigh-in 57% of athletes were dehydrated (1033 ± 19 mOsmol・kg -1 ) and the remaining 43% were severely dehydrated (1267 ± 47 mOsmol・kg -1 ). Athletes reported using harmful dehydration-based RWL strategies, including sauna (43%) and training in plastic suits (43%). Results demonstrated RWG greater than RWL, this is a novel finding and may be attributable to the 32 hr duration from weigh-in till competition. The observed magnitude of RWL and strategies used are comparable to those which have previously resulted in fatalities. Rule changes which make RWL impractical should be implemented with immediate effect to ensure the health, safety and wellbeing of competitors.

  19. The use of LeptiCore® in reducing fat gain and managing weight loss in patients with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Ngondi Judith L

    2010-02-01

    Full Text Available Abstract Background LeptiCore® is a proprietary combination of various ingredients which have been shown to have properties which could be beneficial to weight loss in obese and overweight human subjects. This study evaluates the effect of Lepticore® on bodyweight as well as parameters associated with obesity and metabolic syndrome. Methods The study was an 8 week randomized, double-blind, placebo-controlled design involving 92 obese (mean BMI > 30 kg/m2 participants (37 males; 55 females; ages 19-52; mean age = 30.7. The participants were randomly divided into three groups: placebo (n = 30, LeptiCore® formula A (low dose (n = 31 and LeptiCore® formula B (high dose (n = 31. Capsules containing the placebo or active formulations were administered twice daily before meals with 300 ml of water. None of the participants followed any specific diet nor took any weight-reducing medications for the duration of the study. A total of 12 anthropomorphic and serological measurements were taken at the beginning of the study and after 2, 4, 6, and 8 weeks of treatment. Results Compared to the placebo group, the two active groups showed statistically significant differences on all 12 variables by week 8. These included four anthropomorphic variables (body weight, body fat, waist and hip size and eight measures of serological levels (plasma total cholesterol, LDL, HDL, triglycerides, blood glucose, serotonin, leptin, C-reactive protein. The two active groups also showed significant intra-group differences on all 12 variables between study onset and week 8. Conclusion The LeptiCore® formulation at both the low and high dosages appears to be helpful in the management of fat gain and its related complications. The higher dosage resulted in significantly greater reductions in body weight and triglyceride, blood glucose, and C-reactive protein levels, as well as increased serotonin levels.

  20. Activation of the prefrontal cortex by unilateral transcranial direct current stimulation leads to an asymmetrical effect on risk preference in frames of gain and loss.

    Science.gov (United States)

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

    2016-10-01

    Previous brain imaging and brain stimulation studies have suggested that the dorsolateral prefrontal cortex may be critical in regulating risk-taking behavior, although its specific causal effect on people's risk preference remains controversial. This paper studied the independent modulation of the activity of the right and left dorsolateral prefrontal cortex using various configurations of transcranial direct current stimulation. We designed a risk-measurement table and adopted a within-subject design to compare the same participant's risk preference before and after unilateral stimulation when presented with different frames of gain and loss. The results confirmed a hemispheric asymmetry and indicated that the right dorsolateral prefrontal cortex has an asymmetric effect on risk preference regarding frames of gain and loss. Enhancing the activity of the right dorsolateral prefrontal cortex significantly decreased the participants' degree of risk aversion in the gain frame, whereas it increased the participants' degree of risk aversion in the loss frame. Our findings provide important information regarding the impact of transcranial direct current stimulation on the risk preference of healthy participants. The effects observed in our experiment compared with those of previous studies provide further evidence of the effects of hemispheric and frame-dependent asymmetry. These findings may be helpful in understanding the neural basis of risk preference in humans, especially when faced with decisions involving possible gain or loss relative to the status quo. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Exploring weight gain in year before treatment for binge eating disorder: a different context for interpreting limited weight losses in treatment studies.

    Science.gov (United States)

    Blomquist, Kerstin K; Barnes, Rachel D; White, Marney A; Masheb, Robin M; Morgan, Peter T; Grilo, Carlos M

    2011-07-01

    To examine weight changes in obese patients with binge-eating disorder (BED) during the year before seeking treatment and to explore correlates of weight changes. Seventy-eight consecutive, treatment-seeking, obese BED patients were assessed with structured interviews and self-report questionnaires. Overall, participants reported a mean weight gain of 15.1 pounds during the 12 months before treatment. This overall weight gain comprised remarkable heterogeneity, ranging from a 30-pound loss to a 53-pound gain. The subgroup of participants who reported gaining weight (76% of sample) reported gaining an average of 22.2 pounds during the 12 months before treatment. Weight change was associated with significantly more frequent binge eating and overeating during breakfasts. Treatment-seeking obese patients with BED reported having gained substantial amounts of weight during the previous year. These findings provide an important context for interpreting the modest weight losses typically reported by treatment studies of BED. Copyright © 2010 Wiley Periodicals, Inc.

  2. 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.

  3. 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.

  4. Calorie-restricted weight loss reverses high-fat diet-induced ghrelin resistance, which contributes to rebound weight gain in a ghrelin-dependent manner.

    Science.gov (United States)

    Briggs, Dana I; Lockie, Sarah H; Wu, Qunli; Lemus, Moyra B; Stark, Romana; Andrews, Zane B

    2013-02-01

    Twelve weeks of high-fat diet feeding causes ghrelin resistance in arcuate neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons. In the current study, we investigated whether diet-induced weight loss could restore NPY/AgRP neuronal responsiveness to ghrelin and whether ghrelin mediates rebound weight gain after calorie-restricted (CR) weight loss. Diet-induced obese (DIO) mice were allocated to one of two dietary interventions until they reached the weight of age-matched lean controls. DIO mice received chow diet ad libitum or chow diet with 40% CR. Chow-fed and high-fat-fed mice served as controls. Both dietary interventions normalized body weight, glucose tolerance, and plasma insulin. We show that diet-induced weight loss with CR increases total plasma ghrelin, restores ghrelin sensitivity, and increases hypothalamic NPY and AgRP mRNA expression. We propose that long-term DIO creates a higher body weight set-point and that weight loss induced by CR, as seen in the high-fat CR group, provokes the brain to protect the new higher set-point. This adaptation to weight loss likely contributes to rebound weight gain by increasing peripheral ghrelin concentrations and restoring the function of ghrelin-responsive neuronal populations in the hypothalamic arcuate nucleus. Indeed, we also show that DIO ghrelin-knockout mice exhibit reduced body weight regain after CR weight loss compared with ghrelin wild-type mice, suggesting ghrelin mediates rebound weight gain after CR weight loss.

  5. Intron gain by tandem genomic duplication: a novel case in a potato gene encoding RNA-dependent RNA polymerase

    Directory of Open Access Journals (Sweden)

    Ming-Yue Ma

    2016-07-01

    Full Text Available The origin and subsequent accumulation of spliceosomal introns are prominent events in the evolution of eukaryotic gene structure. However, the mechanisms underlying intron gain remain unclear because there are few proven cases of recently gained introns. In an RNA-dependent RNA polymerase (RdRp gene, we found that a tandem duplication occurred after the divergence of potato and its wild relatives among other Solanum plants. The duplicated sequence crosses the intron-exon boundary of the first intron and the second exon. A new intron was detected at this duplicated region, and it includes a small previously exonic segment of the upstream copy of the duplicated sequence and the intronic segment of the downstream copy of the duplicated sequence. The donor site of this new intron was directly obtained from the small previously exonic segment. Most of the splicing signals were inherited directly from the parental intron/exon structure, including a putative branch site, the polypyrimidine tract, the 3′ splicing site, two putative exonic splicing enhancers, and the GC contents differed between the intron and exon. In the widely cited model of intron gain by tandem genomic duplication, the duplication of an AGGT-containing exonic segment provides the GT and AG splicing sites for the new intron. Our results illustrate that the tandem duplication model of intron gain should be diverse in terms of obtaining the proper splicing signals.

  6. 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

  7. Sub-megabase resolution tiling (SMRT array-based comparative genomic hybridization profiling reveals novel gains and losses of chromosomal regions in Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma cell lines

    Directory of Open Access Journals (Sweden)

    Lam Wan L

    2008-01-01

    Full Text Available Abstract Background Hodgkin lymphoma (HL and Anaplastic Large Cell Lymphoma (ALCL, are forms of malignant lymphoma defined by unique morphologic, immunophenotypic, genotypic, and clinical characteristics, but both overexpress CD30. We used sub-megabase resolution tiling (SMRT array-based comparative genomic hybridization to screen HL-derived cell lines (KMH2 and L428 and ALCL cell lines (DEL and SR-786 in order to identify disease-associated gene copy number gains and losses. Results Significant copy number gains and losses were observed on several chromosomes in all four cell lines. Assessment of copy number alterations with 26,819 DNA segments identified an average of 20 genetic alterations. Of the recurrent minimally altered regions identified, 11 (55% were within previously published regions of chromosomal alterations in HL and ALCL cell lines while 9 (45% were novel alterations not previously reported. HL cell lines L428 and KMH2 shared gains in chromosome cytobands 2q23.1-q24.2, 7q32.2-q36.3, 9p21.3-p13.3, 12q13.13-q14.1, and losses in 13q12.13-q12.3, and 18q21.32-q23. ALCL cell lines SR-786 and DEL, showed gains in cytobands 5p15.32-p14.3, 20p12.3-q13.11, and 20q13.2-q13.32. Both pairs of HL and ALCL cell lines showed losses in 18q21.32-18q23. Conclusion This study is considered to be the first one describing HL and ALCL cell line genomes at sub-megabase resolution. This high-resolution analysis allowed us to propose novel candidate target genes that could potentially contribute to the pathogenesis of HL and ALCL. FISH was used to confirm the amplification of all three isoforms of the trypsin gene (PRSS1/PRSS2/PRSS3 in KMH2 and L428 (HL and DEL (ALCL cell lines. These are novel findings that have not been previously reported in the lymphoma literature, and opens up an entirely new area of research that has not been previously associated with lymphoma biology. The findings raise interesting possibilities about the role of signaling

  8. 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.

  9. 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.

  10. 26 CFR 1.741-1 - Recognition and character of gain or loss on sale or exchange.

    Science.gov (United States)

    2010-04-01

    ... partnership that holds appreciated collectibles or section 1250 property with section 1250 capital gain, see... TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Transfers of Interests in A Partnership § 1.741-1... partnership shall, except to the extent section 751(a) applies, be treated as the sale or exchange of a...

  11. 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 ...

  12. Gaining insights into the codon usage patterns of TP53 gene across eight mammalian species.

    Directory of Open Access Journals (Sweden)

    Tarikul Huda Mazumder

    Full Text Available TP53 gene is known as the "guardian of the genome" as it plays a vital role in regulating cell cycle, cell proliferation, DNA damage repair, initiation of programmed cell death and suppressing tumor growth. Non uniform usage of synonymous codons for a specific amino acid during translation of protein known as codon usage bias (CUB is a unique property of the genome and shows species specific deviation. Analysis of codon usage bias with compositional dynamics of coding sequences has contributed to the better understanding of the molecular mechanism and the evolution of a particular gene. In this study, the complete nucleotide coding sequences of TP53 gene from eight different mammalian species were used for CUB analysis. Our results showed that the codon usage patterns in TP53 gene across different mammalian species has been influenced by GC bias particularly GC3 and a moderate bias exists in the codon usage of TP53 gene. Moreover, we observed that nature has highly favored the most over represented codon CTG for leucine amino acid but selected against the ATA codon for isoleucine in TP53 gene across all mammalian species during the course of evolution.

  13. Quantifying the Source and in-Stream Gain/Loss of Nitrate Using Continuously-Collected Water Quality Data

    Science.gov (United States)

    Miller, M. P.; Tesoriero, A. J.; Capel, P.

    2014-12-01

    High frequency in situ nitrate data from three streams spanning gradients in hydrologic conditions, land use, and watershed size were used to quantify the mass loading of nitrate to streams from two sources - groundwater discharged and event flow nitrate - at a daily time step for one year. Temporal variability in net in-stream loss or production of nitrate and environmental controls on nitrate processing were also quantified. Nitrate in groundwater discharge was identified as contributing approximately 70% of the total nitrate load to a large river and small agricultural stream, compared with 45% to a small urban stream. The greatest in-stream losses of nitrate occurred during the summer and fall months, with net in-stream losses of up to 70% of total nitrate load in the large river, 60% in the agricultural stream, and 50% in the urban stream. Photosynthetically active radiation was identified as the most likely mechanism of in-stream nitrate loss in the large river, whereas baseflow discharge and temperature were the most likely mechanisms of nitrate loss in the small agricultural and urban streams, respectively. As more high frequency nitrate data become available, the approach described here can be applied to further understand nitrate sources to streams and controls on in-stream nitrate production and retention.

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

    Science.gov (United States)

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

    2014-01-13

    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.

  15. 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

  16. 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.

  17. Complete Chloroplast Genome of Medicinal Plant Lonicera japonica: Genome Rearrangement, Intron Gain and Loss, and Implications for Phylogenetic Studies

    Directory of Open Access Journals (Sweden)

    Liu He

    2017-02-01

    Full Text Available The complete chloroplast (cp genome of Lonicera japonica, a common ornamental and medicinal plant in North America and East Asia, was sequenced and analyzed. The length of the L. japonica cp genome is 155,078 bp, contains a pair of inverted repeat regions (IRa and IRb, of 23,774 bp each, as well as large (LSC, 88,858 bp and small (SSC, 18,672 bp single-copy regions. A total of 129 genes were identified in the cp genome, 16 of which were duplicated within the IR regions. Relative to other plant cp genomes, the L. japonica cp genome had a unique rearrangement between trnI-CAU and trnN-GUU. In L. japonica cpDNA, rps19, rpl2, and rpl23 move to the LSC region, from the IR region. The ycf1 pesudogene in the IR region is lost, and only one copy locates in the SSC region. Comparative cp DNA sequence analyses of L. japonica with other cp genomes reveal that the gene order, and the gene and intron contents, are slightly different. The introns in ycf2 and rps18 genes are found for the first time. Four genes (clpP, petB, petD, and rpl16 lost introns. However, its genome structure, GC content, and codon usage were similar to those of typical angiosperm cp genomes. All preferred synonymous codons were found to use codons ending with A/T. The AT-rich sequences were less abundant in the coding regions than in the non-coding ones. A phylogenetic analysis based on 71 protein-coding genes supported the idea that L. japonica is a sister of the Araliaceae species. This study identified unique characteristics of the L. japonica cp genome that contribute to our understanding of the cpDNA evolution. It offers valuable information for the phylogenetic and specific barcoding of this medicinal plant.

  18. 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.

  19. 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.

  20. On the study of threshold intensity dependence on the gain and loss processes in laser induced spark ignition of molecular hydrogen

    Science.gov (United States)

    Omar, M. M.; Aboulfotouh, A. M.; Gamal, Y. E. E.

    2015-03-01

    In the present work, a numerical analysis is performed to investigate the comparative contribution of the mechanisms responsible for electron gain and losses in laser spark ignition and plasma formation of H2. The analysis considered H2 over pressure range 150 -3000 torr irradiated by a Nd:YAG laser radiation at wavelengths 1064 and 532 nm with pulse length 5.5 ns. The study based on a modified electron cascade model by one of the authors which solves numerically the time dependent Boltzmann equation as well as a set of rate equations that describe the rate of change of the excited states population. The model includes most of the physical processes that might take place during the interaction. Computations of The threshold intensity are performed for the combined and separate contribution of each of the gain and loss processes. Reasonable agreement with the measured values over the tested pressure range is obtained only for the case of the combined contribution. Basing on the calculation of the electron energy distribution function, the determined relations of the time evolution of the electrons density for selected values of the tested gas pressure region revealed that photo-ionization of the excited states could determine the time of electron generation and hence spark ignition. Collisional ionization contributes to this phenomenon only at the high pressure regime. Loss processes due to electron diffusion, vibrational excitation are found to have significant effect over examined pressure values for the two applied laser wavelengths.

  1. Eating in the absence of hunger is related to loss-of-control eating, hedonic hunger, and short-term weight gain in normal-weight women.

    Science.gov (United States)

    Feig, Emily H; Piers, Amani D; Kral, Tanja V E; Lowe, Michael R

    2018-04-01

    Eating beyond physiological need contributes to obesity onset. Measuring this behavior could help identify those at risk for weight gain. This study measured eating in the absence of hunger (EAH) and its relationship with weight change and self-report measures related to appetite and eating behavior. EAH was assessed in 46 lean young women (69% pre-selected for weight gain proneness) after lunch and defined as the number of calories subsequently consumed from snacks. Participants also completed questionnaires, and their body weights were measured regularly over the next year. Participants consumed a mean 188 calories (±140) during the EAH test. Caloric intake during the EAH test was associated with hedonic hunger (p emotional eating, disinhibition, and longer-term weight change. Amount of the test meal eaten in a hungry state was unrelated to these variables. While EAH has mainly been examined in children, these results expand its utility to adults. EAH seems to reflect naturalistic eating behavior, as shown by its relationship with short-term weight gain, drive to overconsume foods, and loss of control over eating. EAH may be a useful test to identify young adults at risk for weight gain and/or disordered eating, and may be a target for intervention. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Uni- and multi-variable modelling of flood losses: experiences gained from the Secchia river inundation event.

    Science.gov (United States)

    Carisi, Francesca; Domeneghetti, Alessio; Kreibich, Heidi; Schröter, Kai; Castellarin, Attilio

    2017-04-01

    Flood risk is function of flood hazard and vulnerability, therefore its accurate assessment depends on a reliable quantification of both factors. The scientific literature proposes a number of objective and reliable methods for assessing flood hazard, yet it highlights a limited understanding of the fundamental damage processes. Loss modelling is associated with large uncertainty which is, among other factors, due to a lack of standard procedures; for instance, flood losses are often estimated based on damage models derived in completely different contexts (i.e. different countries or geographical regions) without checking its applicability, or by considering only one explanatory variable (i.e. typically water depth). We consider the Secchia river flood event of January 2014, when a sudden levee-breach caused the inundation of nearly 200 km2 in Northern Italy. In the aftermath of this event, local authorities collected flood loss data, together with additional information on affected private households and industrial activities (e.g. buildings surface and economic value, number of company's employees and others). Based on these data we implemented and compared a quadratic-regression damage function, with water depth as the only explanatory variable, and a multi-variable model that combines multiple regression trees and considers several explanatory variables (i.e. bagging decision trees). Our results show the importance of data collection revealing that (1) a simple quadratic regression damage function based on empirical data from the study area can be significantly more accurate than literature damage-models derived for a different context and (2) multi-variable modelling may outperform the uni-variable approach, yet it is more difficult to develop and apply due to a much higher demand of detailed data.

  3. 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...

  4. Further psychometric validation of the BODY-Q: ability to detect change following bariatric surgery weight gain and loss.

    Science.gov (United States)

    Klassen, Anne F; Cano, Stefan J; Kaur, Manraj; Breitkopf, Trisia; Pusic, Andrea L

    2017-11-25

    Recent systematic reviews have identified that current patient-reported outcome instruments have content limitations when used to measure change following bariatric surgery. The aim of this study was to measure change after bariatric surgery using the BODY-Q, a PRO instrument designed for weight loss and body contouring. The BODY-Q is composed of 18 independently functioning scales and an obesity-specific symptom checklist that measure appearance, health-related quality of life (HR-QOL) and experience of health-care. The sample for this study included patients who were exploring or seeking bariatric surgery in Hamilton (Canada) at the time of the BODY-Q field-test study and who agreed to further contact from the research team. These patients were invited to complete 12 BODY-Q scales and the symptom checklist between 7 June 2016 and 29 November 2016. Data were collected online (REDCap) and via postal surveys. Clinical change was measured using paired t-tests with effect sizes and standardized response means. The survey was completed by 58 of 89 (65%) pre-bariatric participants from the original BODY-Q field-test sample. The non-participants did not differ from participants in terms of age, gender, ethnicity, BMI or initial BODY-Q scale scores. Participants who had undergone bariatric surgery had a mean BMI of 49 (SD = 7) at time 1 and 35 (SD = 7) at time 2. Time since bariatric surgery was on average 2 years (SD = 0.5) (range 0.4 to 3 years). Percentage total weight loss ranged from 12 to 51 (mean 31, SD = 9). The difference in the proportion of patients to report an obesity-specific symptom on the BODY-Q checklist was significantly lower at follow-up for 5 of 10 symptoms. Participants improved on BODY-Q scales measuring appearance (of abdomen, back, body, buttocks, hips/outer thighs, inner thigh), body image and physical function (p weight loss. BODY-Q scales were responsive to measuring clinical change associated with weight loss 2 years after

  5. The Moderating Role of Mood and Personal Relevance on Persuasive Effects of Gain- and Loss-Framed Health Messages.

    Science.gov (United States)

    Wirtz, John G; Sar, Sela; Ghuge, Shreyas

    2015-01-01

    We predicted that mood would moderate the relation between message framing and two outcome variables, message evaluation and behavioral intention, when the message was personally relevant to the target audience. Participants (N = 242) were randomly assigned to an experimental condition in which a positive or negative mood was induced. Participants then read and evaluated a health message that emphasized potential benefits or risks associated with a vaccine. As predicted, participants who received a loss-framed message reported higher message evaluation and intention scores but only when the message was personally relevant and they were in a positive mood.

  6. Recurrent gene loss correlates with the evolution of stomach phenotypes in gnathostome history.

    Science.gov (United States)

    Castro, L Filipe C; Gonçalves, Odete; Mazan, Sylvie; Tay, Boon-Hui; Venkatesh, Byrappa; Wilson, Jonathan M

    2014-01-22

    The stomach, a hallmark of gnathostome evolution, represents a unique anatomical innovation characterized by the presence of acid- and pepsin-secreting glands. However, the occurrence of these glands in gnathostome species is not universal; in the nineteenth century the French zoologist Cuvier first noted that some teleosts lacked a stomach. Strikingly, Holocephali (chimaeras), dipnoids (lungfish) and monotremes (egg-laying mammals) also lack acid secretion and a gastric cellular phenotype. Here, we test the hypothesis that loss of the gastric phenotype is correlated with the loss of key gastric genes. We investigated species from all the main gnathostome lineages and show the specific contribution of gene loss to the widespread distribution of the agastric condition. We establish that the stomach loss correlates with the persistent and complete absence of the gastric function gene kit--H(+)/K(+)-ATPase (Atp4A and Atp4B) and pepsinogens (Pga, Pgc, Cym)--in the analysed species. We also find that in gastric species the pepsinogen gene complement varies significantly (e.g. two to four in teleosts and tens in some mammals) with multiple events of pseudogenization identified in various lineages. We propose that relaxation of purifying selection in pepsinogen genes and possibly proton pump genes in response to dietary changes led to the numerous independent events of stomach loss in gnathostome history. Significantly, the absence of the gastric genes predicts that reinvention of the stomach in agastric lineages would be highly improbable, in line with Dollo's principle.

  7. Loss of genes implicated in gastric function during platypus evolution

    OpenAIRE

    Ordoñez, Gonzalo R; Hillier, LaDeana W; Warren, Wesley C; Grützner, Frank; López-Otín, Carlos; Puente, Xose S

    2008-01-01

    Background The duck-billed platypus (Ornithorhynchus anatinus) belongs to the mammalian subclass Prototheria, which diverged from the Theria line early in mammalian evolution. The platypus genome sequence provides a unique opportunity to illuminate some aspects of the biology and evolution of these animals. Results We show that several genes implicated in food digestion in the stomach have been deleted or inactivated in platypus. Comparison with other vertebrate genomes revealed that the main...

  8. 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.

  9. Fermented Barley Supplementation Modulates the Expression of Hypothalamic Genes and Reduces Energy Intake and Weight Gain in Rats.

    Science.gov (United States)

    Pichiah, P B Tirupathi; Cho, Suk-Ho; Han, Seong-Kyu; Cha, Youn-Soo

    2016-04-01

    Dietary fiber and proteins are individually known to decrease feeding, but could result greater weight management benefit when both are combined. We hypothesized that supplementing the diet with fermented barley, being rich in both dietary fiber and proteins, could lower energy intake by modulating the mRNA expression level of hypothalamic genes associated with the regulation of feeding behavior and satiety; thereby decreasing body weight gain. To test our hypothesis, four groups of Sprague Dawley rats were arranged in a 2 × 2 factorial design (n = 6), low-fat diet with either guar gum (LFD-G) or fermented barley (LFD-FB) and high-fat diet with either guar gum (HFD-G) or fermented barley (HFD-FB). Using oral gavage, fermented barley was given at a dosage of 1500 mg/kg body weight and guar gum was supplemented in an equivalent quantity to that of the fiber in the fermented barley. After 19 weeks, the fermented barley-supplemented groups showed a significant reduction in energy intake, triglyceride, body weight gain, and serum leptin, compared to the guar gum-supplemented groups in both the low- and high-fat diet groups. Likewise, the anorexigenic gene proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) mRNA level were significantly higher in the fermented barley-supplemented groups compared to the guar gum-supplemented groups in rats fed on both high- and low-fat diets. In conclusion, fermented barley supplementation upregulated hypothalamic POMC/CART, decreased energy intake in both low- and high-fat diet groups, and prevented excessive weight gain in rats.

  10. Reciprocal mouse and human limb phenotypes caused by gain- and loss-of-function mutations affecting Lmbr1.

    OpenAIRE

    Clark, R M; Marker, P C; Roessler, E; Dutra, A; Schimenti, J C; Muenke, M; Kingsley, D M

    2001-01-01

    The major locus for dominant preaxial polydactyly in humans has been mapped to 7q36. In mice the dominant Hemimelic extra toes (Hx) and Hammertoe (Hm) mutations map to a homologous chromosomal region and cause similar limb defects. The Lmbr1 gene is entirely within the small critical intervals recently defined for both the mouse and human mutations and is misexpressed at the exact time that the mouse Hx phenotype becomes apparent during limb development. This result suggests that Lmbr1 may un...

  11. High CpG island methylation of p16 gene and loss of p16 protein ...

    Indian Academy of Sciences (India)

    ... in p16 promoters in ToF patients was negatively correlated with p16 protein and gene expression (both P < 0.05). Our study reports that high CpG island methylation of p16 gene and loss of p16 protein expression associate with the development and progression of ToF, which may have significant therapeutic applications ...

  12. Impact of gene patents and licensing practices on access to genetic testing for hearing loss.

    Science.gov (United States)

    Chandrasekharan, Subhashini; Fiffer, Melissa

    2010-04-01

    Genetic testing for heritable hearing loss involves a mix of patented and unpatented genes, mutations and testing methods. More than half of all hearing loss is linked to inherited mutations, and five genes are most commonly tested for in the United States. There are no patents on three of these genes, but Athena Diagnostics holds exclusive licenses to test for a common mutation in the GJB2 gene associated with about 50% of all cases as well as mutations in the MTRNR1 gene. This fragmented intellectual property landscape made hearing loss a useful case study to assess whether patent rights in genetic testing can proliferate or overlap, and whether it is possible to gather the rights necessary to perform testing. Testing for hearing loss is widely available, primarily from academic medical centers. Based on literature reviews and interviews with researchers, research on the genetics of hearing loss has generally not been impeded by patents. There is no consistent evidence of a premium in testing prices attributable to patent status. Athena Diagnostics has, however, used its intellectual property to discourage other providers from offering some tests. There is no definitive answer about the suitability of current patenting and licensing of commonly tested genes because of continuing legal uncertainty about the extent of enforcement of patent rights. Clinicians have also expressed concerns that multiplex tests will be difficult to develop because of overlapping intellectual property and conflict with Athena's sole provider business model.

  13. 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.

  14. Effect of feeding a weight loss food beyond a caloric restriction period on body composition and resistance to weight gain in dogs.

    Science.gov (United States)

    Floerchinger, Amanda M; Jackson, Matthew I; Jewell, Dennis E; MacLeay, Jennifer M; Paetau-Robinson, Inke; Hahn, Kevin A

    2015-08-15

    To determine the effect of feeding a food with coconut oil and supplemental L-carnitine, lipoic acid, lysine, leucine, and fiber on weight loss and maintenance in dogs. Prospective clinical study. 50 overweight dogs. The study consisted of 2 trials. During trial 1, 30 dogs were allocated to 3 groups (10 dogs/group) to be fed a dry maintenance dog food to maintain body weight (group 1) or a dry test food at the same amount on a mass (group 2) or energy (group 3) basis as group 1. During trial 2, each of 20 dogs was fed the test food and caloric intake was adjusted to maintain a weight loss rate of 1% to 2%/wk (weight loss phase). Next, each dog was fed the test food in an amount calculated to maintain the body weight achieved at the end of the weight loss phase (weight maintenance phase). Dogs were weighed and underwent dual-energy x-ray absorptiometry monthly. Metabolomic data were determined before (baseline) and after each phase. During trial 1, dogs in groups 2 and 3 lost significantly more weight than did those in group 1. During trial 2, dogs lost a significant amount of body weight and fat mass but retained lean body mass (LBM) during the weight loss phase and continued to lose body fat but gained LBM during the weight maintenance phase. Evaluation of metabolomic data suggested that fat metabolism and LBM retention were improved from baseline for dogs fed the test food. Results suggested that feeding overweight dogs the test food caused weight loss and improvements in body condition during the weight-maintenance phase, possibly because the food composition improved energy metabolism.

  15. Comparative genomics of the bacterial genus Listeria: Genome evolution is characterized by limited gene acquisition and limited gene loss

    Directory of Open Access Journals (Sweden)

    Barker Melissa

    2010-12-01

    Full Text Available Abstract Background The bacterial genus Listeria contains pathogenic and non-pathogenic species, including the pathogens L. monocytogenes and L. ivanovii, both of which carry homologous virulence gene clusters such as the prfA cluster and clusters of internalin genes. Initial evidence for multiple deletions of the prfA cluster during the evolution of Listeria indicates that this genus provides an interesting model for studying the evolution of virulence and also presents practical challenges with regard to definition of pathogenic strains. Results To better understand genome evolution and evolution of virulence characteristics in Listeria, we used a next generation sequencing approach to generate draft genomes for seven strains representing Listeria species or clades for which genome sequences were not available. Comparative analyses of these draft genomes and six publicly available genomes, which together represent the main Listeria species, showed evidence for (i a pangenome with 2,032 core and 2,918 accessory genes identified to date, (ii a critical role of gene loss events in transition of Listeria species from facultative pathogen to saprotroph, even though a consistent pattern of gene loss seemed to be absent, and a number of isolates representing non-pathogenic species still carried some virulence associated genes, and (iii divergence of modern pathogenic and non-pathogenic Listeria species and strains, most likely circa 47 million years ago, from a pathogenic common ancestor that contained key virulence genes. Conclusions Genome evolution in Listeria involved limited gene loss and acquisition as supported by (i a relatively high coverage of the predicted pan-genome by the observed pan-genome, (ii conserved genome size (between 2.8 and 3.2 Mb, and (iii a highly syntenic genome. Limited gene loss in Listeria did include loss of virulence associated genes, likely associated with multiple transitions to a saprotrophic lifestyle. The genus

  16. 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

    2017-04-01

    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 Victoria Study). Parent-completed communication tools were used. As a group, children with autism spectrum disorder demonstrated slower median skill gain, with an increasing gap between trajectories compared to children with typical development and language impairment. A proportion from all groups lost skills in at least one domain (autism spectrum disorder (41%), language impairment (30%), typical development (26%)), with more children with autism spectrum disorder losing skills in more than one domain (autism spectrum disorder (47%), language impairment (15%, p = 0.0003), typical development (16%, p disorder (27%; language impairment (12%, p = 0.03), typical development (14%, p = 0.03)). A higher proportion of children with autism spectrum disorder also lost skills in gesture (p = 0.01), sounds (p = 0.009) and understanding (p = 0.004) compared to children with typical development but not with language impairment. These findings add to our understanding of early communication development and highlight that loss is not unique to autism spectrum disorder.

  17. 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.

  18. Thrombophilic gene polymorphisms and recurrent pregnancy loss in Greek women.

    Science.gov (United States)

    Chatzidimitriou, M; Chatzidimitriou, D; Mavridou, M; Anetakis, C; Chatzopoulou, F; Lialiaris, T; Mitka, S

    2017-12-01

    Recurrent pregnancy loss (RPL) is a multifactorial disorder. The aim of this study was the detection of various genetic polymorphisms and their correlation to RPL, in Greek women. The impact of 12 thrombophilic polymorphisms was evaluated, among 48 Greek women with a history of RPL, vs 27 healthy parous women. Multiplex PCR and in situ hybridization on nitrocellulose films were performed, to investigate 12 genetic polymorphisms previously reported as risk factors for RPL. Heterozygous FV Leiden, homozygous PAI-1 4G/4G, heterozygous MTHFR C677T, homozygous MTHFR A1298C, as much as the combined thrombophilic genotypes MTHFR 677T + ACE Ι/D, MTHFR 677T/1298C + ACE D/D, ACE I/D + b-fibrinogen -455 G/A, FV HR2 + b-fibrinogen -455 G/A showed a correlation as risk factors for RPL, whereas the rest of the investigated polymorphisms and their combinations did not render statistically significant differences between the two groups in study. The results of this study, as well as those of similar studies, concerning the detection of genetic, environmental, and physiological factors underlying RPL, will prove of critical significance in the investigation and treatment of thrombophilic predisposition, in cases of RPL. © 2017 John Wiley & Sons Ltd.

  19. Gene expression profiles resulting from stable loss of p53 mirrors its role in tissue differentiation.

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    Oliver Couture

    Full Text Available The tumor suppressor gene p53 is involved in a variety of cellular activities such as cellular stress responses, cell cycle regulation and differentiation. In our previous studies we have shown p53's transcription activating role to be important in osteoblast differentiation. There is still a debate in the literature as to whether p53 inhibits or promotes differentiation. We have found p53 heterozygous mice to show a p53 dependency on some bone marker gene expression that is absent in knockout mice. Mice heterozygous for p53 also show a higher incidence of osteosarcomas than p53 knockout mice. This suggests that p53 is able to modify the environment within osteoblasts. In this study we compare changes in gene expression resulting after either a transient or stable reduction in p53. Accordingly we reduced p53 levels transiently and stably in C2C12 cells, which are capable of both myoblast and osteoblast differentiation, and compared the changes in gene expression of candidate genes regulated by the p53 pathway. Using a PCR array to assay for p53 target genes, we have found different expression profiles when comparing stable versus transient knockdown of p53. As expected, several genes with profound changes after transient p53 loss were related to apoptosis and cell cycle regulation. In contrast, stable p53 loss produced a greater change in MyoD and other transcription factors with tissue specific roles, suggesting that long term loss of p53 affects tissue homeostasis to a greater degree than changes resulting from acute loss of p53. These differences in gene expression were validated by measuring promoter activity of different pathway specific genes involved in differentiation. These studies suggest that an important role for p53 is context dependent, with a stable reduction in p53 expression affecting normal tissue physiology more than acute loss of p53.

  20. A single origin for nymphalid butterfly eyespots followed by widespread loss of associated gene expression.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Oliver

    Full Text Available Understanding how novel complex traits originate involves investigating the time of origin of the trait, as well as the origin of its underlying gene regulatory network in a broad comparative phylogenetic framework. The eyespot of nymphalid butterflies has served as an example of a novel complex trait, as multiple genes are expressed during eyespot development. Yet the origins of eyespots remain unknown. Using a dataset of more than 400 images of butterflies with a known phylogeny and gene expression data for five eyespot-associated genes from over twenty species, we tested origin hypotheses for both eyespots and eyespot-associated genes. We show that eyespots evolved once within the family Nymphalidae, approximately 90 million years ago, concurrent with expression of at least three genes associated with early eyespot development. We also show multiple losses of expression of most genes from this early three-gene cluster, without corresponding losses of eyespots. We propose that complex traits, such as eyespots, may have originated via co-option of a large pre-existing complex gene regulatory network that was subsequently streamlined of genes not required to fulfill its novel developmental function.

  1. Trabecular bone loss after administration of the second-generation antipsychotic risperidone is independent of weight gain

    Science.gov (United States)

    Motyl, Katherine J.; Dick-de-Paula, Ingrid; Maloney, Ann E.; Lotinun, Sutada; Bornstein, Sheila; de Paula, Francisco J. A.; Baron, Roland; Houseknecht, Karen L.; Rosen, Clifford J.

    2011-01-01

    Second generation antipsychotics (SGAs) have been linked to metabolic and bone disorders in clinical studies, but the mechanisms of these side effects remain unclear. Additionally, no studies have examined whether SGAs cause bone loss in mice. Using in vivo and in vitro modeling we examined the effects of risperidone, the most commonly prescribed SGA, on bone in C57BL6/J (B6) mice. Mice were treated with risperidone orally by food supplementation at a dose of 1.25 mg/kg daily for 5 and 8 weeks, starting at 3.5 weeks of age. Risperidone reduced trabecular BV/TV, trabecular number and percent cortical area. Trabecular histomorphometry demonstrated increased resorption parameters, with no change in osteoblast number or function. Risperidone also altered adipose tissue distribution such that white adipose tissue mass was reduced and liver had significantly higher lipid infiltration. Next, in order to tightly control risperidone exposure, we administered risperidone by chronic subcutaneous infusion with osmotic minipumps (0.5 mg/kg daily for 4 weeks) in 7 week old female B6 mice. Similar trabecular and cortical bone differences were observed compared to the orally treated groups (reduced trabecular BV/TV, and connectivity density, and reduced percent cortical area) with no change in body mass, percent body fat, glucose tolerance or insulin sensitivity. Unlike in orally treated mice, risperidone infusion reduced bone formation parameters (serum P1NP, MAR and BFR/BV). Resorption parameters were elevated, but this increase did not reach statistical significance. To determine if risperidone could directly affect bone cells, primary bone marrow cells were cultured with osteoclast or osteoblast differentiation media. Risperidone was added to culture medium in clinically relevant doses of 0, 2.5 or 25 ng/ml. The number of osteoclasts was significantly increased by addition in vitro of risperidone while osteoblast differentiation was not altered. These studies indicate that

  2. Adipose and muscle tissue gene expression of two genes (NCAPG and LCORL) located in a chromosomal region associated with cattle feed intake and gain.

    Science.gov (United States)

    Lindholm-Perry, Amanda K; Kuehn, Larry A; Oliver, William T; Sexten, Andrea K; Miles, Jeremy R; Rempel, Lea A; Cushman, Robert A; Freetly, Harvey C

    2013-01-01

    A region on bovine chromosome 6 has been implicated in cattle birth weight, growth, and length. Non-SMC conodensin I complex subunit G (NCAPG) and ligand dependent nuclear receptor corepressor-like protein (LCORL) are positional candidate genes within this region. Previously identified genetic markers in both genes were associated with average daily gain (ADG) and average daily feed intake (ADFI) in a crossbred population of beef steers. These markers were also associated with hot carcass weight, ribeye area and adjusted fat thickness suggesting that they may have a role in lean muscle growth and/or fat deposition. The purpose of this study was to determine whether the transcript abundance of either of these genes in cattle adipose and muscle tissue was associated with variation in feed intake and average daily gain phenotypes. Transcript abundance for NCAPG and LCORL in adipose and muscle tissue was measured in heifers (adipose only), cows and steers using real-time polymerase chain reaction. In the adipose tissue from cows and heifers, a negative correlation between LCORL transcript abundance and ADFI were detected (P = 0.05). In the muscle tissue from cows, transcript abundance of NCAPG was associated with ADG (r = 0.26; P = 0.009). A positive correlation between LCORL transcript abundance from muscle tissue of steers and ADFI was detected (P = 0.04). LCORL protein levels in the muscle of steers were investigated and were associated with ADFI (P = 0.01). These data support our earlier genetic associations with ADFI and ADG within this region and represent the potential for biological activity of these genes in the muscle and adipose tissues of beef cattle; however, they also suggest that sex, age and/or nutrition-specific interactions may affect the expression of NCAPG and LCORL in these tissues.

  3. Adipose and Muscle Tissue Gene Expression of Two Genes (NCAPG and LCORL) Located in a Chromosomal Region Associated with Cattle Feed Intake and Gain

    Science.gov (United States)

    Lindholm-Perry, Amanda K.; Kuehn, Larry A.; Oliver, William T.; Sexten, Andrea K.; Miles, Jeremy R.; Rempel, Lea A.; Cushman, Robert A.; Freetly, Harvey C.

    2013-01-01

    A region on bovine chromosome 6 has been implicated in cattle birth weight, growth, and length. Non-SMC conodensin I complex subunit G (NCAPG) and ligand dependent nuclear receptor corepressor-like protein (LCORL) are positional candidate genes within this region. Previously identified genetic markers in both genes were associated with average daily gain (ADG) and average daily feed intake (ADFI) in a crossbred population of beef steers. These markers were also associated with hot carcass weight, ribeye area and adjusted fat thickness suggesting that they may have a role in lean muscle growth and/or fat deposition. The purpose of this study was to determine whether the transcript abundance of either of these genes in cattle adipose and muscle tissue was associated with variation in feed intake and average daily gain phenotypes. Transcript abundance for NCAPG and LCORL in adipose and muscle tissue was measured in heifers (adipose only), cows and steers using real-time polymerase chain reaction. In the adipose tissue from cows and heifers, a negative correlation between LCORL transcript abundance and ADFI were detected (P = 0.05). In the muscle tissue from cows, transcript abundance of NCAPG was associated with ADG (r = 0.26; P = 0.009). A positive correlation between LCORL transcript abundance from muscle tissue of steers and ADFI was detected (P = 0.04). LCORL protein levels in the muscle of steers were investigated and were associated with ADFI (P = 0.01). These data support our earlier genetic associations with ADFI and ADG within this region and represent the potential for biological activity of these genes in the muscle and adipose tissues of beef cattle; however, they also suggest that sex, age and/or nutrition-specific interactions may affect the expression of NCAPG and LCORL in these tissues. PMID:24278337

  4. Adipose and muscle tissue gene expression of two genes (NCAPG and LCORL located in a chromosomal region associated with cattle feed intake and gain.

    Directory of Open Access Journals (Sweden)

    Amanda K Lindholm-Perry

    Full Text Available A region on bovine chromosome 6 has been implicated in cattle birth weight, growth, and length. Non-SMC conodensin I complex subunit G (NCAPG and ligand dependent nuclear receptor corepressor-like protein (LCORL are positional candidate genes within this region. Previously identified genetic markers in both genes were associated with average daily gain (ADG and average daily feed intake (ADFI in a crossbred population of beef steers. These markers were also associated with hot carcass weight, ribeye area and adjusted fat thickness suggesting that they may have a role in lean muscle growth and/or fat deposition. The purpose of this study was to determine whether the transcript abundance of either of these genes in cattle adipose and muscle tissue was associated with variation in feed intake and average daily gain phenotypes. Transcript abundance for NCAPG and LCORL in adipose and muscle tissue was measured in heifers (adipose only, cows and steers using real-time polymerase chain reaction. In the adipose tissue from cows and heifers, a negative correlation between LCORL transcript abundance and ADFI were detected (P = 0.05. In the muscle tissue from cows, transcript abundance of NCAPG was associated with ADG (r = 0.26; P = 0.009. A positive correlation between LCORL transcript abundance from muscle tissue of steers and ADFI was detected (P = 0.04. LCORL protein levels in the muscle of steers were investigated and were associated with ADFI (P = 0.01. These data support our earlier genetic associations with ADFI and ADG within this region and represent the potential for biological activity of these genes in the muscle and adipose tissues of beef cattle; however, they also suggest that sex, age and/or nutrition-specific interactions may affect the expression of NCAPG and LCORL in these tissues.

  5. On the study of threshold intensity dependence on the gain and loss processes in laser induced spark ignition of molecular hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Omar, M. M., E-mail: magdymomar@gmail.com; Aboulfotouh, A. M. [Department of physics, Faculty of Science, Cairo University, Giza (Egypt); Gamal, Y. E. E. [National Institute of Laser Enhanced Sciences, Cairo University, Giza (Egypt)

    2015-03-30

    In the present work, a numerical analysis is performed to investigate the comparative contribution of the mechanisms responsible for electron gain and losses in laser spark ignition and plasma formation of H{sub 2}. The analysis considered H{sub 2} over pressure range 150 -3000 torr irradiated by a Nd:YAG laser radiation at wavelengths 1064 and 532 nm with pulse length 5.5 ns. The study based on a modified electron cascade model by one of the authors which solves numerically the time dependent Boltzmann equation as well as a set of rate equations that describe the rate of change of the excited states population. The model includes most of the physical processes that might take place during the interaction. Computations of The threshold intensity are performed for the combined and separate contribution of each of the gain and loss processes. Reasonable agreement with the measured values over the tested pressure range is obtained only for the case of the combined contribution. Basing on the calculation of the electron energy distribution function, the determined relations of the time evolution of the electrons density for selected values of the tested gas pressure region revealed that photo-ionization of the excited states could determine the time of electron generation and hence spark ignition. Collisional ionization contributes to this phenomenon only at the high pressure regime. Loss processes due to electron diffusion, vibrational excitation are found to have significant effect over examined pressure values for the two applied laser wavelengths.

  6. Massive losses of taste receptor genes in toothed and baleen whales.

    Science.gov (United States)

    Feng, Ping; Zheng, Jinsong; Rossiter, Stephen J; Wang, Ding; Zhao, Huabin

    2014-05-06

    Taste receptor genes are functionally important in animals, with a surprising exception in the bottlenose dolphin, which shows extensive losses of sweet, umami, and bitter taste receptor genes. To examine the generality of taste gene loss, we examined seven toothed whales and five baleen whales and sequenced the complete repertoire of three sweet/umami (T1Rs) and ten bitter (T2Rs) taste receptor genes. We found all amplified T1Rs and T2Rs to be pseudogenes in all 12 whales, with a shared premature stop codon in 10 of the 13 genes, which demonstrated massive losses of taste receptor genes in the common ancestor of whales. Furthermore, we analyzed three genome sequences from two toothed whales and one baleen whale and found that the sour taste marker gene Pkd2l1 is a pseudogene, whereas the candidate salty taste receptor genes are intact and putatively functional. Additionally, we examined three genes that are responsible for taste signal transduction and found the relaxation of functional constraints on taste signaling pathways along the ancestral branch leading to whales. Together, our results strongly suggest extensive losses of sweet, umami, bitter, and sour tastes in whales, and the relaxation of taste function most likely arose in the common ancestor of whales between 36 and 53 Ma. Therefore, whales represent the first animal group to lack four of five primary tastes, probably driven by the marine environment with high concentration of sodium, the feeding behavior of swallowing prey whole, and the dietary switch from plants to meat in the whale ancestor. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  7. Gain-loss study of lower San Pedro Creek and the San Antonio River, San Antonio, Texas, May-October 1999

    Science.gov (United States)

    Ockerman, Darwin J.

    2002-01-01

    Five streamflow gain-loss measurement surveys were made along lower San Pedro Creek and the San Antonio River from Mitchell Street to South Loop 410 east of Kelly Air Force Base in San Antonio, Texas, during May–October 1999. All of the measurements were made during dry periods, when stormwater runoff was not occurring and effects of possible bank storage were minimized. San Pedro Creek and the San Antonio River were divided into six subreaches, and streamflow measurements were made simultaneously at the boundaries of these subreaches so that streamflow gains or losses and estimates of inflow from or outflow to shallow ground water could be quantified for each subreach. There are two possible sources of ground-water inflow to lower San Pedro Creek and the San Antonio River east of Kelly Air Force Base. One source is direct inflow of shallow ground water into the streams. The other source is ground water that enters tributaries that flow into the San Antonio River. The estimated mean direct inflow of ground water to the combined San Pedro Creek and San Antonio River study reach was 3.0 cubic feet per second or 1.9 million gallons per day. The mean tributary inflow of ground water was estimated to be 1.9 cubic feet per second or 1.2 million gallons per day. The total estimated inflow of shallow ground water was 4.9 cubic feet per second or 3.2 million gallons per day. The amount of inflow from springs and seeps (estimated by observation) is much less than the amount of direct ground-water inflow estimated from the gain-loss measurements. Therefore, the presence of springs and seeps might not be a reliable indicator of the source of shallow ground water entering the river. Most of the shallow ground water that enters the San Antonio River from tributary inflow enters from the west side, through Concepcion Creek, inflows near Riverside Golf Course, and Six-Mile Creek. 

  8. Prolactin receptor gene polymorphism and the risk of recurrent pregnancy loss: a case-control study.

    Science.gov (United States)

    Kim, Jin Ju; Choi, Young Min; Lee, Sung Ki; Yang, Kwang Moon; Paik, Eun Chan; Jeong, Hyeon Jeong; Jun, Jong Kwan; Han, Ae Ra; Hwang, Kyu Ri; Hong, Min A

    2018-02-01

    Since the first study was published reporting the candidate association between the prolactin receptor gene intron C/T polymorphism (rs37389) and recurrent miscarriage, no replication study has been performed. In this study, we investigated the role of the prolactin receptor gene C/T polymorphism in 311 Korean women with recurrent pregnancy loss and 314 controls. Genotyping for prolactin receptor gene intron C/T polymorphism was performed using a TaqMan assay. The significance of difference in the genotype distribution was assessed using a chi-square test, and continuous variables were compared using a Student's t-test. The genotype distribution of the prolactin receptor gene C/T polymorphism in the recurrent pregnancy loss group did not differ from that in the control group (CC/CT/TT rates were 49.8%/41.5%/8.7% and 52.5%/37.6%/9.9% for the recurrent pregnancy loss patient and control groups, respectively, p = .587). When the analysis was restricted to patients with three or more consecutive spontaneous miscarriages or patients without prior live birth, there were also no differences in the genotype distribution between these subgroups and controls. In conclusion, the findings of the current study suggest that the prolactin receptor gene intron C/T polymorphism is not a major determinant of the development of recurrent pregnancy loss. Impact statement What is already known: Many studies have investigated whether there is a genetic component for the risk of recurrent pregnancy loss. Recently, one study investigated whether genetic polymorphisms involved in the regulation of the hypothalamic-pituitary-ovarian axis would be associated with recurrent miscarriage. Among 35 polymorphisms in 20 candidate genes, genotype distribution with regard to the prolactin receptor gene intron C/T polymorphism (rs37389) differed between the recurrent miscarriage and the control groups. Since this study reporting the candidate association between the prolactin receptor gene and

  9. The Evolution of Occupational Segregation in the United States, 1940-2010: Gains and Losses of Gender-Race/Ethnicity Groups.

    Science.gov (United States)

    del Río, Coral; Alonso-Villar, Olga

    2015-06-01

    The aim of this article is twofold: (1) to descriptively explore the evolution of occupational segregation of women and men of different racial/ethnic groups in the United States during 1940-2010, and (2) to assess the consequences of segregation for each group. For that purpose, in this article, we propose a simple index that measures the monetary loss or gain of a group derived from its overrepresentation in some occupations and underrepresentation in others. This index has a clear economic interpretation. It represents the per capita advantage (if the index is positive) or disadvantage (if the index is negative) of the group, derived from its segregation, as a proportion of the average wage of the economy. Our index is a helpful tool not only for academics but also for institutions concerned with inequalities among demographic groups because it makes it possible to rank them according to their segregational nature.

  10. Multi-dimensional stable fundamental solitons and excitations in PT-symmetric harmonic-Gaussian potentials with unbounded gain-and-loss distributions

    Science.gov (United States)

    Chen, Yong; Yan, Zhenya

    2018-04-01

    We demonstrate the parity-time- (PT-) symmetric harmonic-Gaussian potential with unbounded gain-and-loss distribution can support entirely-real linear spectra, stable spatial and spatio-temporal solitons in an inhomogeneous nonlinear medium (e.g., cubic nonlinear Schrödinger equation with the self-focusing and defocusing cases). Exact analytical solitons are derived in both one-dimensional (1D) and higher-dimensional (e.g., 2D, 3D) geometries such that they are verified to be stable in the given parameters regions. Particularly, several families of numerical fundamental solitons (especially the 1D double-peaked solitons, 2D vortex solitons, and 3D double bullets) can be found to be stable around the propagation parameters for exact solitons. Other significant properties of solitons are also explored including the interactions of solitons, stable soliton excitations, and transverse power flows. The results may excite the corresponding theoretical analysis and experiment designs.

  11. A preliminary assessment of streamflow gains and losses for selected stream reaches in the lower Guadalupe River Basin, Texas, 2010-12

    Science.gov (United States)

    Wehmeyer, Loren L.; Winters, Karl E.; Ockerman, Darwin J.

    2013-01-01

    The U.S. Geological Survey, in cooperation with the U.S. Army Corps of Engineers–Fort Worth District, the Texas Water Development Board, the Guadalupe-Blanco River Authority, and the Edwards Aquifer Authority, investigated streamflow gains and losses in the lower Guadalupe River Basin during four selected base-flow periods in March 2010, April 2011, August 2011, and, for a stream reach between Seguin, Tex., and Gonzales, Tex., in September 2012. Major sources of streamflow in this basin include releases from Canyon Lake, inflow from major springs (Comal Springs, San Marcos Springs, and Hueco Springs), and base flow (groundwater seeping to streams). Streamflow and spring-flow data were collected at 35 streamflow-gaging stations (including 6 deployed for this study) during the base-flow periods. This report describes streamflow in the lower Guadalupe River Basin, which consists of the Guadalupe River drainage basin downstream from Canyon Lake to the Guadalupe River near Tivoli, Tex.

  12. De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.

    Science.gov (United States)

    Blanchard, Maxime G; Willemsen, Marjolein H; Walker, Jaclyn B; Dib-Hajj, Sulayman D; Waxman, Stephen G; Jongmans, Marjolijn C J; Kleefstra, Tjitske; van de Warrenburg, Bart P; Praamstra, Peter; Nicolai, Joost; Yntema, Helger G; Bindels, René J M; Meisler, Miriam H; Kamsteeg, Erik-Jan

    2015-05-01

    Mutations of SCN8A encoding the neuronal voltage-gated sodium channel NaV1.6 are associated with early-infantile epileptic encephalopathy type 13 (EIEE13) and intellectual disability. Using clinical exome sequencing, we have detected three novel de novo SCN8A mutations in patients with intellectual disabilities, and variable clinical features including seizures in two patients. To determine the causality of these SCN8A mutations in the disease of those three patients, we aimed to study the (dys)function of the mutant sodium channels. The functional consequences of the three SCN8A mutations were assessed using electrophysiological analyses in transfected cells. Genotype-phenotype correlations of these and other cases were related to the functional analyses. The first mutant displayed a 10 mV hyperpolarising shift in voltage dependence of activation (gain of function), the second did not form functional channels (loss of function), while the third mutation was functionally indistinguishable from the wildtype channel. Comparison of the clinical features of these patients with those in the literature suggests that gain-of-function mutations are associated with severe EIEE, while heterozygous loss-of-function mutations cause intellectual disability with or without seizures. These data demonstrate that functional analysis of missense mutations detected by clinical exome sequencing, both inherited and de novo, is valuable for clinical interpretation in the age of massive parallel sequencing. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. FCGR3B copy number loss rather than gain is a risk factor for systemic lupus erythematous and lupus nephritis: a meta-analysis.

    Science.gov (United States)

    Yuan, Jin; Zhao, Dongbao; Wu, Lijun; Xu, Xia; Pang, Yafei; Zhang, Jun; Ma, Yanyun; Liu, Jie; Wang, Jiucun

    2015-05-01

    Some studies have been performed to elucidate the association between Fc gamma receptor 3B (FCGR3B) copy number (CN) and the risk of systemic lupus erythematosus (SLE) and/or lupus nephritis (LN), yet the results remain conflicting. Therefore, we have undertaken a systematic review of all the studies published and carried out a meta-analysis to obtain a better understanding of the role of FCGR3B CN in the susceptibility of SLE and LN. A computerized literature search was conducted in databases of PubMed, ISI Web of Knowledge for all studies investigating the association between FCGR3B CN and SLE and/or LN, published up to May 2013. A total of six articles meeting all of the criteria were included in this study. There were five comparisons of SLE between 2490 patients and 4286 controls, and four comparisons of LN between 689 patients and 1924 controls. Our results showed that individuals with FCGR3B CN gain did not suffer an increased risk of SLE or LN as compared to the normal genotype in the total analysis (SLE: OR = 1.07, 95% CI = 0.79-1.45, P = 0.65; LN: OR = 0.83, 95% CI = 0.47-1.46, P = 0.52). However, individuals with FCGR3B CN loss exhibited an increased risk of SLE or LN (SLE: OR = 1.77, 95% CI = 1.51-2.06, P < 0.00001; LN: OR = 2.02, 95% CI = 1.59-2.57, P < 0.00001). Our meta-analysis indicated that FCGR3B CN loss rather than CN gain was associated with susceptibility to SLE and LN. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  14. 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.

  15. Molecular characterization of five porcine candidate genes for drip loss in pork.

    Science.gov (United States)

    Karol, Agnieszka; Drögemuller, Cord; Wimmers, Klaus; Schellander, Karl; Leeb, Tosso

    2010-04-01

    Drip loss is the loss of fluid from a piece of meat without mechanical force and represents an important meat quality trait. Previous work revealed a quantitative trait locus (QTL) for drip loss in pork in an experimental Duroc x Pietrain (DUPI) F2 family on SSC 5. Based on functional data indicating their possible involvement in water holding capacity and their expression in skeletal muscle, we selected five positional candidates (ACO2, ADSL, CBY1, KCNJ4, PLA2AG6) out of 130 predicted genes in the QTL interval for further analysis. We performed a mutation analysis of all coding exons and discovered 204 polymorphisms. We genotyped 39 single nucleotide polymorphisms (SNPs) in 192 Pietrain pigs with extreme drip loss phenotypes and detected a possible association with drip loss for one non-coding SNP in the ADSL gene (ss107793818, p(raw) = 0.021). Correspondingly, ADSL diplotypes were associated with drip loss and pH1 of M. longissimus dorsi. However, after correction for multiple testing, none of the tested SNPs were significantly associated with drip loss. One possible explanation for these results is that one of the QTL-alleles from the experimental DUPI family may be fixed or nearly fixed in the tested Pietrain population.

  16. Loss of Major DNase I Hypersensitive Sites in Duplicatedglobin Gene Cluster Incompletely Silences HBB Gene Expression

    Czech Academy of Sciences Publication Activity Database

    Reading, N. S.; Shooter, C.; Song, J.; Miller, R.; Agarwal, A.; Láníková, Lucie; Clark, B.; Thein, S.L.; Divoký, V.; Prchal, J.T.

    2016-01-01

    Roč. 37, č. 11 (2016), s. 1153-1156 ISSN 1059-7794 R&D Projects: GA MŠk(CZ) LH15223 Institutional support: RVO:68378050 Keywords : globin gene s * regulation * sickle cell disease * HBB duplication Subject RIV: EB - Gene tics ; Molecular Biology Impact factor: 4.601, year: 2016

  17. Clinical and prognostic value of MET gene copy number gain and chromosome 7 polysomy in primary colorectal cancer patients.

    Science.gov (United States)

    Seo, An Na; Park, Kyoung Un; Choe, Gheeyoung; Kim, Woo Ho; Kim, Duck-Woo; Kang, Sung-Bum; Lee, Hye Seung

    2015-12-01

    We aimed to explore the clinical and prognostic influence of numeric alterations of MET gene copy number (GCN) and chromosome 7 (CEP7) CN in colorectal cancer (CRC) patients. MET GCN and CEP7 CN were investigated in tissue arrayed tumors from 170 CRC patients using silver in situ hybridization (SISH). MET GCN gain was defined as ≥4 copies of MET, and CEP7 polysomy was prespecified as ≥3 copies of CEP7. Additionally, MET messenger RNA (mRNA) transcription was evaluated using mRNA ISH and compared with MET GCN. MET GCN gain was observed in 14.7 % (25/170), which correlated with advanced stage (P = 0.037), presence of distant metastasis (P = 0.006), and short overall survival (OS) (P = 0.009). In contrast, CEP7 polysomy was found in 6.5 % (11/170), which was related to tumor location in the left colon (P = 0.027) and poor OS (P = 0.029). MET GCN positively correlated with CEP7 CN (R = 0.659, P patients (n = 123). In multivariate analysis, CEP7 polysomy was an independent prognostic factor for poor OS in all patients (P = 0.009; hazard ratio [HR], 2.220; 95 % confidence interval [CI], 1.233-3.997) and in stage II/III CRC patients (P patients, especially CEP7 polysomy has the most powerful prognostic impact in stage II/III CRC patients.

  18. Extensive loss of translational genes in the structurally dynamic mitochondrial genome of the angiosperm Silene latifolia

    Directory of Open Access Journals (Sweden)

    Sloan Daniel B

    2010-09-01

    Full Text Available Abstract Background Mitochondrial gene loss and functional transfer to the nucleus is an ongoing process in many lineages of plants, resulting in substantial variation across species in mitochondrial gene content. The Caryophyllaceae represents one lineage that has experienced a particularly high rate of mitochondrial gene loss relative to other angiosperms. Results In this study, we report the first complete mitochondrial genome sequence from a member of this family, Silene latifolia. The genome can be mapped as a 253,413 bp circle, but its structure is complicated by a large repeated region that is present in 6 copies. Active recombination among these copies produces a suite of alternative genome configurations that appear to be at or near "recombinational equilibrium". The genome contains the fewest genes of any angiosperm mitochondrial genome sequenced to date, with intact copies of only 25 of the 41 protein genes inferred to be present in the common ancestor of angiosperms. As observed more broadly in angiosperms, ribosomal proteins have been especially prone to gene loss in the S. latifolia lineage. The genome has also experienced a major reduction in tRNA gene content, including loss of functional tRNAs of both native and chloroplast origin. Even assuming expanded wobble-pairing rules, the mitochondrial genome can support translation of only 17 of the 61 sense codons, which code for only 9 of the 20 amino acids. In addition, genes encoding 18S and, especially, 5S rRNA exhibit exceptional sequence divergence relative to other plants. Divergence in one region of 18S rRNA appears to be the result of a gene conversion event, in which recombination with a homologous gene of chloroplast origin led to the complete replacement of a helix in this ribosomal RNA. Conclusions These findings suggest a markedly expanded role for nuclear gene products in the translation of mitochondrial genes in S. latifolia and raise the possibility of altered

  19. A systematic survey of loss-of-function variants in human protein-coding genes

    NARCIS (Netherlands)

    MacArthur, D.G.; Balasubramanian, S.; Frankish, A.; Huang, N.; Morris, J.; Walter, K.; Jostins, L.; Habegger, L.; Pickrell, J.K.; Montgomery, S.B.; Albers, C.A.; Zhang, Z.D.; Conrad, D.F.; Lunter, G.; Zheng, H.; Ayub, Q.; DePristo, M.A.; Banks, E.; Hu, M.; Handsaker, R.E.; Rosenfeld, J.A.; Fromer, M.; Jin, M.; Mu, X.J.; Khurana, E.; Ye, K.; Kay, M.; Saunders, G.I.; Suner, M.M.; Hunt, T.; Barnes, I.H.; Amid, C.; Carvalho-Silva, D.R.; Bignell, A.H.; Snow, C.; Yngvadottir, B.; Bumpstead, S.; Cooper, D.N.; Xue, Y.; Romero, I.G.; Genomes Project, C.; Wang, J; Li, Y.; Gibbs, R.A.; McCarroll, S.A.; Dermitzakis, E.T.; Pritchard, J.K.; Barrett, J.C.; Harrow, J.; Hurles, M.E.; Gerstein, M.B.; Tyler-Smith, C.

    2012-01-01

    Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to

  20. An enigmatic fourth runt domain gene in the fugu genome: ancestral gene loss versus accelerated evolution

    Directory of Open Access Journals (Sweden)

    Hood Leroy

    2004-11-01

    Full Text Available Abstract Background The runt domain transcription factors are key regulators of developmental processes in bilaterians, involved both in cell proliferation and differentiation, and their disruption usually leads to disease. Three runt domain genes have been described in each vertebrate genome (the RUNX gene family, but only one in other chordates. Therefore, the common ancestor of vertebrates has been thought to have had a single runt domain gene. Results Analysis of the genome draft of the fugu pufferfish (Takifugu rubripes reveals the existence of a fourth runt domain gene, FrRUNT, in addition to the orthologs of human RUNX1, RUNX2 and RUNX3. The tiny FrRUNT packs six exons and two putative promoters in just 3 kb of genomic sequence. The first exon is located within an intron of FrSUPT3H, the ortholog of human SUPT3H, and the first exon of FrSUPT3H resides within the first intron of FrRUNT. The two gene structures are therefore "interlocked". In the human genome, SUPT3H is instead interlocked with RUNX2. FrRUNT has no detectable ortholog in the genomes of mammals, birds or amphibians. We consider alternative explanations for an apparent contradiction between the phylogenetic data and the comparison of the genomic neighborhoods of human and fugu runt domain genes. We hypothesize that an ancient RUNT locus was lost in the tetrapod lineage, together with FrFSTL6, a member of a novel family of follistatin-like genes. Conclusions Our results suggest that the runt domain family may have started expanding in chordates much earlier than previously thought, and exemplify the importance of detailed analysis of whole-genome draft sequence to provide new insights into gene evolution.

  1. 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.

  2. Gene-Gene Interplay and Gene-Diet Interactions Involving the MTNR1B rs10830963 Variant with Body Weight Loss.

    Science.gov (United States)

    Goni, Leticia; Cuervo, Marta; Milagro, Fermin I; Martínez, J Alfredo

    2014-01-01

    Investigation of the genetic makeup may facilitate the implementation of more personalized nutritional interventions. The aims were to examine whether the rs10830963 MTNR1B polymorphism affects weight loss in response to a hypocaloric diet and to find potential gene-gene interplays and gene-diet interactions. 167 subjects enrolled in a personalized nutritional intervention for weight loss (3-6 weeks) were examined for anthropometric measurements, dietary habits and physical activity at baseline and at the first follow-up visit. Three polymorphisms, which have previously been associated with body weight regulation, rs10830963 (MTNR1B), rs9939609 (FTO) and rs17782313 (MC4R), were analyzed using the Luminex® 100/200™ System. After adjusting for covariates, females with the rs10830963 CG/GG genotype showed lower weight loss than those with the CC genotype. In the total population, carriers of variant alleles of both FTO and MC4R showed a significant association with MTNR1B and weight loss outcome. Moreover, among women, higher total protein and animal protein intakes were associated with a lower weight loss in G allele carriers of the MTNR1B variant. Our data evidenced that rs10830963 MTNR1B polymorphism could be associated with individual differences in weight loss induced by a hypocaloric diet. This association was influenced by FTO and MC4R loci and modified by baseline protein intake. © 2015 S. Karger AG, Basel.

  3. 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.

  4. Alpha-1 Antitrypsin Gene Therapy Ameliorates Bone Loss in Ovariectomy-Induced Osteoporosis Mouse Model.

    Science.gov (United States)

    Akbar, Mohammad Ahsanul; Cao, Jay J; Lu, Yuanqing; Nardo, David; Chen, Mong-Jen; Elshikha, Ahmed S; Ahamed, Rubina; Brantly, Mark; Holliday, L Shannon; Song, Sihong

    2016-09-01

    Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at menopause. Therefore, anti-inflammatory strategies hold a great potential for the prevention of postmenopausal osteoporosis. In this study, we investigated the effect of gene therapy of recombinant adeno-associated virus (rAAV)-mediated human alpha-1 antitrypsin (hAAT), a multifunctional protein that has anti-inflammatory property, on bone loss in an ovariectomy-induced osteoporosis mouse model. Adult ovariectomized (OVX) mice were intraperitoneally (i.p.) injected with hAAT (protein therapy), rAAV8-CB-hAAT (gene therapy), or phosphate buffer saline (PBS). Age-matched and sham-operated animals were used as controls. Eight weeks after the treatment, animals were sacrificed and bone-related biomarkers and vertebral bone structure were evaluated. Results showed that hAAT gene therapy significantly decreased serum IL-6 level and receptor activator of NF-κB (RANK) gene expression in bone. Importantly, hAAT gene therapy increased bone volume/total volume and decreased structure model index (SMI) compared to PBS injection in OVX mice. These results demonstrate that hAAT gene therapy by rAAV vector efficiently mitigates bone loss possibly through inhibition of proinflammatory cytokine IL-6 and RANK gene expression. Considering the safety profile of hAAT and rAAV vector in humans, our results provide a new alternative for the treatment of osteoporosis.

  5. 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.

  6. 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.

  7. Prothrombotic gene mutations in patients with sudden sensorineural hearing loss and cardiovascular thrombotic disease.

    Science.gov (United States)

    Capaccio, Pasquale; Cuccarini, Valeria; Ottaviani, Francesco; Fracchiolla, Nicola Stefano; Bossi, Anna; Pignataro, Lorenzo

    2009-03-01

    Impaired cochlear perfusion seems to be an important event in sudden sensorineural hearing loss. Prothrombotic gene mutations have been related to vascular disorders and sudden hearing loss. We assessed the prothrombotic risk in 10 patients with sudden sensorineural hearing loss who had previously experienced cardiovascular events to support its vascular pathogenesis. Ten patients underwent hematologic tests (MTHFR C677T/A1298C, prothrombin G20210A, platelet GlyIIIaA1/A2, and V Leiden G1691A genotyping; fibrinogenemia; cholesterolemia: homocysteinemia; folatemia). The results were compared with those of 100 previously investigated patients with sudden hearing loss alone and those of 200 healthy controls. DNA was isolated from peripheral blood leukocytes, and the gene mutations were investigated by polymerase chain reaction and a LightCycler DNA analyzer. Two patients had 2 mutant alleles, 6 had 3, and 2 had 4. The mean homocysteine, cholesterol, and fibrinogen levels were above the upper limit of normal; the mean folate levels were slightly above the lower limit of normal. Multiple mutations were more frequent in the patient group than in the previously analyzed patients and healthy controls. The association between inherited and acquired prothrombotic factors in patients with sudden sensorineural hearing loss and thrombotic diseases in other sites suggests that a multifactorial mechanism may underlie microvascular cochlear impairment. Hematologic investigation, including MTHFR, prothrombin, platelet, and V Leiden genotyping, may help to detect patients at potential risk of recurrent hearing loss and multiple microvascular diseases, and could be usefully performed in otherwise idiopathic sudden sensorineural hearing loss.

  8. Non-syndromic hearing loss gene identification: A brief history and glimpse into the future.

    Science.gov (United States)

    Vona, Barbara; Nanda, Indrajit; Hofrichter, Michaela A H; Shehata-Dieler, Wafaa; Haaf, Thomas

    2015-10-01

    From the first identified non-syndromic hearing loss gene in 1995, to those discovered in present day, the field of human genetics has witnessed an unparalleled revolution that includes the completion of the Human Genome Project in 2003 to the $1000 genome in 2014. This review highlights the classical and cutting-edge strategies for non-syndromic hearing loss gene identification that have been used throughout the twenty year history with a special emphasis on how the innovative breakthroughs in next generation sequencing technology have forever changed candidate gene approaches. The simplified approach afforded by next generation sequencing technology provides a second chance for the many linked loci in large and well characterized families that have been identified by linkage analysis but have presently failed to identify a causative gene. It also discusses some complexities that may restrict eventual candidate gene discovery and calls for novel approaches to answer some of the questions that make this simple Mendelian disorder so intriguing. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. 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...

  10. A BOSE-EINSTEIN CONDENSATE WITH PT-SYMMETRIC DOUBLE-DELTA FUNCTION LOSS AND GAIN IN A HARMONIC TRAP: A TEST OF RIGOROUS ESTIMATES

    Directory of Open Access Journals (Sweden)

    Daniel Haag

    2014-04-01

    Full Text Available We consider the linear and nonlinear Schrödinger equation for a Bose-Einstein condensate in a harmonic trap with PT-symmetric double-delta function loss and gain terms. We verify that the conditions for the applicability of a recent proposition by Mityagin and Siegl on singular perturbations of harmonic oscillator type self-adjoint operators are fulfilled. In both the linear and nonlinear case we calculate numerically the shifts of the unperturbed levels with quantum numbers n of up to 89 in dependence on the strength of the non-Hermiticity and compare with rigorous estimates derived by those authors. We confirm that the predicted 1/n1/2 estimate provides a valid upper bound on the shrink rate of the numerical eigenvalues. Moreover, we find that a more recent estimate of log(n/n3/2 is in excellent agreement with the numerical results. With nonlinearity the shrink rates are found to be smaller than without nonlinearity, and the rigorous estimates, derived only for the linear case, are no longer applicable.

  11. Somatic segregation errors predominantly contribute to the gain or loss of a paternal chromosome leading to uniparental disomy for chromosome 15.

    Science.gov (United States)

    Robinson, W P; Christian, S L; Kuchinka, B D; Peñaherrera, M S; Das, S; Schuffenhauer, S; Malcolm, S; Schinzel, A A; Hassold, T J; Ledbetter, D H

    2000-05-01

    Paternal uniparental disomy (UPD) for chromosome 15 (UPD15), which is found in approximately 2% of Angelman syndrome (AS) patients, is much less frequent than maternal UPD15, which is found in 25% of Prader-Willi syndrome patients. Such a difference cannot be easily accounted for if 'gamete complementation' is the main mechanism leading to UPD. If we assume that non-disjunction of chromosome 15 in male meiosis is relatively rare, then the gain or loss of the paternal chromosome involved in paternal and maternal UPD15, respectively, may be more likely to result from a post-zygotic rather than a meiotic event. To test this hypothesis, the origin of the extra chromosome 15 was determined in 21 AS patients with paternal UPD15 with a paternal origin of the trisomy. Only 4 of 21 paternal UPD15 cases could be clearly attributed to a meiotic error. Furthermore, significant non-random X-chromosome inactivation (XCI) observed in maternal UPD15 patients (p UPD15 cases are increased as compared with normal controls. This may be simply the consequence of an age association with maternal non-disjunction leading to nullisomy for chromosome 15 in the oocyte, although the higher paternal age in paternal UPD15 as compared with maternal UPD15 cases is suggestive that paternal age may also play a role in the origin of paternal UPD15.

  12. Prognostic impact of gene polymorphisms in patients with idiopathic sudden sensorineural hearing loss.

    Science.gov (United States)

    Kitoh, Ryosuke; Nishio, Shin-Ya; Usami, Shin-Ichi

    2017-01-01

    To investigate whether genetic polymorphisms (single-nucleotide polymorphism [SNPs]) have a prognostic influence on hearing recovery after standardized corticosteroid therapy. A total of 192 gene samples from idiopathic sudden sensorineural hearing loss (SSNHL) patients registered in the Intractable Inner Ear Disease Gene Bank were enrolled and, as the candidate genes, 16 SNPs from 13 genes were selected for this study. Fischer's exact test was used to compare allele frequencies in each SNP between the patients with good hearing recovery and patients with poor hearing recovery. The SNPs of the GSR gene (rs2251780 and rs3779647) and NOS3 gene (rs1799983) were associated with treatment outcome (p < .05). Furthermore, there was a marginal correlation between the SNP of the NR3C1 gene (rs4912910) and treatment outcome (p = .05). The results of this study indicate that the analysis of genetic factors might make it possible to predict the treatment outcome, at least in part, in patients with idiopathic SSNHL.

  13. Contribution of chromosomal abnormalities and genes of the major histocompatibility complex to early pregnancy losses

    Directory of Open Access Journals (Sweden)

    Tkach I. R.

    2015-02-01

    Full Text Available Aim. The determination of chromosomal abnormalities in samples from early pregnancy losses and allelic polymorphism of HLA–DRB1 and DQA1 genes in couples with recurrent miscarriage. Methods. Banding cytogenetic and interphase mFISH analysis, DNA extraction by salting method, PCR, agarose gel electrophoresis. Results. Cytogenetic and molecular-cytogenetic investigations of SA material identified karyotype anomalies in 32.4 % of cases with prevalence of autosomal trisomy – 42.65 %, triploidy – 30.38 % and monosomy X – 19.11 %. Complex analysis of frequency and distribution of allelic variants of genes HLA-DRB1 and HLA-DQA1 allowed establishing the alleles DRB1*0301, DRB1*1101-1104 and DQA1*0501 to be aggressor alleles in women with recurrent pregnancy loss (RPL. The cumulative homology of allelic polymorphism of more than 50 % of HLA-DRB1 and HLA-DQA1 loci between partners increases the risk of RPL by almost four times. Conclusion. The detected chromosome aneuploidies in the samples from products of conception and the changes in the major histocompatibility complex genes can cause the failure of a couples reproductive function and can lead to an early fetal loss.

  14. 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

  15. Expression of toll-like receptor genes in leukocytes of patients with sudden sensorineural hearing loss.

    Science.gov (United States)

    Yang, Chao-Hui; Hwang, Chung-Feng; Yang, Ming-Yu; Lin, Pai-Mei; Chuang, Jiin-Haur

    2015-12-01

    Sudden sensorineural hearing loss (SNNHL) is a disease entity that could be caused by multiple etiologies in which the innate immunity status of the patients might be involved. The aim of this study is to investigate the expression of Toll-like receptor (TLR) genes in peripheral blood leukocytes of SNNHL patients. Basic research. We examined the expression of six TLR genes in the peripheral blood leukocytes of SNNHL patients and normal controls using real-time quantitative reverse transcriptase-polymerase chain reaction. We found significantly higher expression of TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 genes in SNNHL patients as compared with normal controls (P hearing loss compared with those with less severe hearing loss (P hearing thresholds of the affected ear (P < 0.05). Our study implies a role for TLRs in SNNHL. The expression of TLR2 in particular correlates with the severity of the disease. N/A. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  16. Methylenetetrahydrofolate reductase gene polymorphisms in Egyptian women with unexplained recurrent pregnancy loss.

    Science.gov (United States)

    Settin, Ahmad; Elshazli, Rami; Salama, Afrah; ElBaz, Rizk

    2011-12-01

    This work aims at testing for the association of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with unexplained recurrent pregnancy loss (RPL) among Egyptian women. Participants were 70 cases having a history of two or more events of unexplained RPL and 136 controls with a good obstetric history. Detection of MTHFR C677T and A1298C mutations was done by polymerase chain reaction with restriction fragment length polymorphisms assay using restriction enzymes HinfI and MboII respectively. Compared with controls, cases with unexplained pregnancy loss showed higher frequency of the homozygous mutant MTHFR 677 TT, 1298 CC genotypes, and the mutant haplotype 677T/1298C, although not reaching statistical significance. The frequency of 677 mutant genotypes (TT or TC) combined with either the mutant 1298 (CC or AC) or normal 1298 (AA) genotypes was significantly increased among cases with late-stage pregnancy loss versus those with early-stage pregnancy loss (p=0.001). There was also increased frequency of the 677 mutant genotypes among cases with secondary infertility compared with those with primary infertility and among cases with pregnancy loss >4 times compared with those with ≤4 times but with no statistical significance. Regarding other risk factors, it was noted that the frequency of mutations among cases with no or just one risk factor did not differ significantly from those having two or more risk factors (p=0.98). Mutations related to the MTHFR gene are increased but not statistically significant in Egyptian women with unexplained pregnancy loss. Interaction with other genetic variants might be speculated and need to be investigated.

  17. The evolution of pepsinogen C genes in vertebrates: duplication, loss and functional diversification.

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    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

  18. Assessment and Reconstruction of Novel HSP90 Genes: Duplications, Gains and Losses in Fungal and Animal Lineages

    Czech Academy of Sciences Publication Activity Database

    Pantzartzi, Chrysoula; Drosopoulou, E.; Scouras, Z.

    2013-01-01

    Roč. 8, č. 9 (2013), s. 1-11 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : Hsp90s * Fungi * duplication events Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.534, year: 2013

  19. [Common deafness gene mutations of non-syndromic hearing loss in Liaoning].

    Science.gov (United States)

    Tian, Ying; Wang, Zheng; Yang, Ning; Hui, Lian; Jiang, Xuejun

    2014-08-01

    Investigate common deafness gene mutations in patients with severe and profound non-syndromic hearing loss in Liaoning in order to understand their hereditary etiologies and characteristics at the molecular level. Peripheral blood samples were obtained and the DNA templates were extracted from 128 non-syndromic hearing loss patients who are sporadic in clinics. The deafness gene chip was applied to detect hot-spot deafness gene mutations including GJB2, GJB3, SLC26A4 and mitochondrial 12S rRNA. Deafness etiology questionnaires, pure tone audiometry, auditory brainstem response, tympanometry and temporal bone CT were also applied. Various types of gene locus mutations were seen in 52 of the 128 patients (40.6%); (1) GJB2 gene mutations (n=22) included c. 235 del C homozygous mutation (n=10), c. 235 del C heterozygous mutation (n=5); c. 176_191 del 16 heterozygous mutation (n=l); c 35 del G heterozygous mutation (n=l); c. 235 del C/c. 299_300 del AT mutation (n=l), c. 235 del C/c. 176_191 del 16 mutation (n=l), c. 35 del G/c. 176_191 del 16 mutation (n=l); c. 299_300 del AT/c. 919-2 A>G mutation (n=l), c. 235 del C/c. 919-2 A>G mutation (n=l). (2) SLC26A4 gene mutations (n=30) included c. 919-2 A>G homozygous mutation (n=6), c. 919-2 A>G heterozygous mutation (n=17), c. 2168 A>G homozygous mutation (n=l), c. 2168 A>G heterozygous mutation (n=2), c. 2168 A>G/c. 919-2 A>G mutation (n=2), c. 919-2 A>G/GJB2 c. 235 del C mutation (n=2); (3) No GJB3 and mitochondrial 12S rRNA mutation. Genetic deafness was confirmed at the gene level in 24 cases (18.8%) and 28 patients (21.9%) were diagnosed as carriers of genetic deafness gene mutations. Genetic deafness occupies a large population in deaf community in Liaoning. Molecular genetic screening for these mutations and genetic counseling are effective methods to prevent the occurrence of hereditary hearing loss and provide theoretical guidance.

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

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    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

  1. Association of allelic variation in genes mediating aspects of energy homeostasis with weight gain during administration of antipsychotic drugs (CATIE Study

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    Hemant K Tiwari

    2011-09-01

    Full Text Available Antipsychotic drugs are widely used in treating schizophrenia, bipolar disorder, and other psychiatric disorders. Many of these drugs, despite their therapeutic advantages, substantially increase body weight. We assessed the association of alleles of 31 genes implicated in body weight regulation with weight gain among patients being treated with specific antipsychotic medications in the CATIE trial, we found that rs2237988 in ATP-binding cassette subfamily C member 8 (ABCC8 , and rs11643744 and rs9922047 in Fat Mass and Obesity Associated (FTO were associated with such weight gain.

  2. Polar zoobenthos blue carbon storage increases with sea ice losses, because across-shelf growth gains from longer algal blooms outweigh ice scour mortality in the shallows.

    Science.gov (United States)

    Barnes, David K A

    2017-12-01

    One of the major climate-forced global changes has been white to blue to green; losses of sea ice extent in time and space around Arctic and West Antarctic seas has increased open water and the duration (though not magnitude) of phytoplankton blooms. Blueing of the poles has increases potential for heat absorption for positive feedback but conversely the longer phytoplankton blooms have increased carbon export to storage and sequestration by shelf benthos. However, ice shelf collapses and glacier retreat can calve more icebergs, and the increased open water allows icebergs more opportunities to scour the seabed, reducing zoobenthic blue carbon capture and storage. Here the size and variability in benthic blue carbon in mega and macrobenthos was assessed in time and space at Ryder and Marguerite bays of the West Antarctic Peninsula (WAP). In particular the influence of the duration of primary productivity and ice scour are investigated from the shallows to typical shelf depths of 500 m. Ice scour frequency dominated influence on benthic blue carbon at 5 m, to comparable with phytoplankton duration by 25 m depth. At 500 m only phytoplankton duration was significant and influential. WAP zoobenthos was calculated to generate ~10 7 , 4.5 × 10 6 and 1.6 × 10 6 tonnes per year (between 2002 and 2015) in terms of production, immobilization and sequestration of carbon respectively. Thus about 1% of annual primary productivity has sequestration potential at the end of the trophic cascade. Polar zoobenthic blue carbon capture and storage responses to sea ice losses, the largest negative feedback on climate change, has been underestimated despite some offsetting of gain by increased ice scouring with more open water. Equivalent survey of Arctic and sub-Antarctic shelves, for which new projects have started, should reveal the true extent of this feedback and how much its variability contributes to uncertainty in climate models. © 2017 John Wiley & Sons Ltd.

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

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    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.

  4. Black patients sustain vision loss while White and South Asian patients gain vision following delamination or segmentation surgery for tractional complications associated with proliferative diabetic retinopathy.

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    Mastropasqua, R; Luo, Y H-L; Cheah, Y S; Egan, C; Lewis, J J; da Cruz, L

    2017-10-01

    PurposeThis retrospective comparative case series aims to determine whether patient ethnicity (White versus South Asian versus Black) is related to the outcome of surgical treatment for traction complications of severe proliferative diabetic retinopathy (PDR).SettingMoorfields Eye Hospital London, UK.MethodsAll patients who underwent vitrectomy with, delamination and/or segmentation for PDR over a 5-year period (2009-2014) were reviewed retrospectively. Patients were divided into White, South Asian or Black groups, and their age, gender, HbA1C and type of diabetes were recorded. A total of 484 patients (253 White, 117 South Asian, 114 Black) were included. Twenty-one patients were excluded due to inadequate documentation.OutcomesLogMAR Visual acuity (converted from Snellen) (VA), was recorded pre-operatively and ~6 months post surgery (range 5-8 months). Surgical outcome was classified according to the type and duration of tamponade required post-operatively.ResultsPre-operative VA and HbA1C values were similar across all three ethnic groups (P=0.64 and 0.569, respectively). Change in VA (mean±SD) was 0.41±0.78, 0.14±0.76 and -0.26±0.57 in White, South Asian and Black patient groups respectively (PAsian patient groups.ConclusionsThis study demonstrates that Black patients on average lose vision following delamination surgery for traction complications of PDR while White and South Asian patients gain vision. The same group is also at higher risk of retaining silicone more than 6 months after surgery. This difference remains even when corrected for glycaemic control. The higher risk of visual loss and long-term retention of silicone oil in black patients requires further investigation. If these results are confirmed, surgeons should consider their patients' ethnicity before proceeding with surgical treatment of diabetic tractional detachment.

  5. Alanine-scanning mutagenesis of human signal transducer and activator of transcription 1 to estimate loss- or gain-of-function variants.

    Science.gov (United States)

    Kagawa, Reiko; Fujiki, Ryoji; Tsumura, Miyuki; Sakata, Sonoko; Nishimura, Shiho; Itan, Yuval; Kong, Xiao-Fei; Kato, Zenichiro; Ohnishi, Hidenori; Hirata, Osamu; Saito, Satoshi; Ikeda, Maiko; El Baghdadi, Jamila; Bousfiha, Aziz; Fujiwara, Kaori; Oleastro, Matias; Yancoski, Judith; Perez, Laura; Danielian, Silvia; Ailal, Fatima; Takada, Hidetoshi; Hara, Toshiro; Puel, Anne; Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; Casanova, Jean-Laurent; Ohara, Osamu; Okada, Satoshi; Kobayashi, Masao

    2017-07-01

    Germline heterozygous mutations in human signal transducer and activator of transcription 1 (STAT1) can cause loss of function (LOF), as in patients with Mendelian susceptibility to mycobacterial diseases, or gain of function (GOF), as in patients with chronic mucocutaneous candidiasis. LOF and GOF mutations are equally rare and can affect the same domains of STAT1, especially the coiled-coil domain (CCD) and DNA-binding domain (DBD). Moreover, 6% of patients with chronic mucocutaneous candidiasis with a GOF STAT1 mutation have mycobacterial disease, obscuring the functional significance of the identified STAT1 mutations. Current computational approaches, such as combined annotation-dependent depletion, do not distinguish LOF and GOF variants. We estimated variations in the CCD/DBD of STAT1. We mutagenized 342 individual wild-type amino acids in the CCD/DBD (45.6% of full-length STAT1) to alanine and tested the mutants for STAT1 transcriptional activity. Of these 342 mutants, 201 were neutral, 30 were LOF, and 111 were GOF mutations in a luciferase assay. This assay system correctly estimated all previously reported LOF mutations (100%) and slightly fewer GOF mutations (78.1%) in the CCD/DBD of STAT1. We found that GOF alanine mutants occurred at the interface of the antiparallel STAT1 dimer, suggesting that they destabilize this dimer. This assay also precisely predicted the effect of 2 hypomorphic and dominant negative mutations, E157K and G250E, in the CCD of STAT1 that we found in 2 unrelated patients with Mendelian susceptibility to mycobacterial diseases. The systematic alanine-scanning assay is a useful tool to estimate the GOF or LOF status and the effect of heterozygous missense mutations in STAT1 identified in patients with severe infectious diseases, including mycobacterial and fungal diseases. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Concomitant loss of NDH complex-related genes within chloroplast and nuclear genomes in some orchids.

    Science.gov (United States)

    Lin, Choun-Sea; Chen, Jeremy J W; Chiu, Chi-Chou; Hsiao, Han C W; Yang, Chen-Jui; Jin, Xiao-Hua; Leebens-Mack, James; de Pamphilis, Claude W; Huang, Yao-Ting; Yang, Ling-Hung; Chang, Wan-Jung; Kui, Ling; Wong, Gane Ka-Shu; Hu, Jer-Ming; Wang, Wen; Shih, Ming-Che

    2017-06-01

    The chloroplast NAD(P)H dehydrogenase-like (NDH) complex consists of about 30 subunits from both the nuclear and chloroplast genomes and is ubiquitous across most land plants. In some orchids, such as Phalaenopsis equestris, Dendrobium officinale and Dendrobium catenatum, most of the 11 chloroplast genome-encoded ndh genes (cp-ndh) have been lost. Here we investigated whether functional cp-ndh genes have been completely lost in these orchids or whether they have been transferred and retained in the nuclear genome. Further, we assessed whether both cp-ndh genes and nucleus-encoded NDH-related genes can be lost, resulting in the absence of the NDH complex. Comparative analyses of the genome of Apostasia odorata, an orchid species with a complete complement of cp-ndh genes which represents the sister lineage to all other orchids, and three published orchid genome sequences for P. equestris, D. officinale and D. catenatum, which are all missing cp-ndh genes, indicated that copies of cp-ndh genes are not present in any of these four nuclear genomes. This observation suggests that the NDH complex is not necessary for some plants. Comparative genomic/transcriptomic analyses of currently available plastid genome sequences and nuclear transcriptome data showed that 47 out of 660 photoautotrophic plants and all the heterotrophic plants are missing plastid-encoded cp-ndh genes and exhibit no evidence for maintenance of a functional NDH complex. Our data indicate that the NDH complex can be lost in photoautotrophic plant species. Further, the loss of the NDH complex may increase the probability of transition from a photoautotrophic to a heterotrophic life history. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

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

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    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

  8. Human SOD1 ALS Mutations in a Drosophila Knock-In Model Cause Severe Phenotypes and Reveal Dosage-Sensitive Gain- and Loss-of-Function Components.

    Science.gov (United States)

    Şahin, Aslı; Held, Aaron; Bredvik, Kirsten; Major, Paxton; Achilli, Toni-Marie; Kerson, Abigail G; Wharton, Kristi; Stilwell, Geoff; Reenan, Robert

    2017-02-01

    Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset motor neuron disease and familial forms can be caused by numerous dominant mutations of the copper-zinc superoxide dismutase 1 (SOD1) gene. Substantial efforts have been invested in studying SOD1-ALS transgenic animal models; yet, the molecular mechanisms by which ALS-mutant SOD1 protein acquires toxicity are not well understood. ALS-like phenotypes in animal models are highly dependent on transgene dosage. Thus, issues of whether the ALS-like phenotypes of these models stem from overexpression of mutant alleles or from aspects of the SOD1 mutation itself are not easily deconvolved. To address concerns about levels of mutant SOD1 in disease pathogenesis, we have genetically engineered four human ALS-causing SOD1 point mutations (G37R, H48R, H71Y, and G85R) into the endogenous locus of Drosophila SOD1 (dsod) via ends-out homologous recombination and analyzed the resulting molecular, biochemical, and behavioral phenotypes. Contrary to previous transgenic models, we have recapitulated ALS-like phenotypes without overexpression of the mutant protein. Drosophila carrying homozygous mutations rendering SOD1 protein enzymatically inactive (G85R, H48R, and H71Y) exhibited neurodegeneration, locomotor deficits, and shortened life span. The mutation retaining enzymatic activity (G37R) was phenotypically indistinguishable from controls. While the observed mutant dsod phenotypes were recessive, a gain-of-function component was uncovered through dosage studies and comparisons with age-matched dsod null animals, which failed to show severe locomotor defects or nerve degeneration. We conclude that the Drosophila knock-in model captures important aspects of human SOD1-based ALS and provides a powerful and useful tool for further genetic studies. Copyright © 2017 by the Genetics Society of America.

  9. Independent losses of visual perception genes Gja10 and Rbp3 in echolocating bats (Order: Chiroptera.

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    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.

  10. 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.

  11. Investigation on estrogen receptor alpha gene polymorphisms in Iranian women with recurrent pregnancy loss

    Science.gov (United States)

    Mahdavipour, Marzieh; Idali, Farah; Zarei, Saeed; Talebi, Saeed; Fatemi, Ramina; Jeddi-Tehrani, Mahmood; Pahlavan, Somayeh; Rajaei, Farzad

    2014-01-01

    Background: Recurrent pregnancy loss (RPL) is a multifactorial disorder. Environmental factors and genetics can affect pregnancy outcomes. Objective: Conflicting data suggest an association between estrogen receptor alpha (ESR1) gene polymorphisms and RPL. In this study, such association was investigated in Iranian women with RPL. Materials and Methods: In this case control study, blood samples were collected from 244 women with a history of three or more consecutive pregnancy losses and 104 healthy women with at least two live births. Using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), we studied -397C/T and -351A/G polymorphisms on ESR1 gene in case and control subjects. Results: The genotypic frequencies of -397C/T and -351A/G polymorphisms on ESR1were not significantly different between RPL and control groups (p=0.20 and p=0.09, respectively). A significantly negative correlation was observed between -397C/T and -351A/G (r=-0.852, p<0.001) in RPL women and complete linkage disequilibrium between the investigated polymorphisms was found (D’: 0.959; r-square= 0.758, p<0.001). Conclusion: This investigation suggests that the analyzed polymorphisms on ESR1gene are not associated with an increased risk of RPL in the studied population. PMID:25071847

  12. 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.

  13. Effect of rate of weight gain of steers during the stocker phase. III. Gene expression of adipose tissues and skeletal muscle in growing-finishing beef cattle.

    Science.gov (United States)

    Lancaster, P A; Sharman, E D; Horn, G W; Krehbiel, C R; Starkey, J D

    2014-04-01

    The objective of this study was to determine the impact of stocker production systems differing in growth rate on differential adipogenic and lipogenic gene expression of intramuscular (IM), subcutaneous (SC), and perirenal (PR) adipose tissues. Angus steers were assigned to 4 stocker cattle production systems in 2 consecutive years: 1) cottonseed meal-based supplement while grazing dormant native range (CON), 2) ground corn/soybean meal-based supplement while grazing dormant native range (CORN), 3) grazing wheat pasture at a high stocking rate for a low rate of BW gain (LGWP), and 4) grazing wheat pasture at a low stocking rate for a high rate of BW gain (HGWP). Steers were harvested during the stocker phase at similar age (different carcass weight) in Exp. 1 (3 steers/treatment) or at similar carcass weight in Exp. 2 (4 steers/treatment). Adipose tissues were analyzed for mRNA expression of adipogenic (peroxisome proliferator activated receptor γ [PPARγ], sterol regulatory element binding factor 1 [SREBF1], CAATT/enhancer binding protein β, and delta-like homolog 1) and lipogenic (glycerol-3-phosphate dehydrogenase [GPDH], fatty acid synthase [FASN], and diacylglycerol acyltransferase 2 [DGAT2]) genes. Multivariate analysis was used to evaluate the expression of adipogenic or lipogenic genes collectively. There was not a treatment × adipose tissue interaction (F-test, P > 0.15) when steers were harvested at similar age, but a treatment × adipose tissue interaction (F-test, P 0.10) on the canonical variate of adipogenic or lipogenic mRNA expression in IM adipose tissue, but faster rates of gain of LGWP and HGWP steers increased (P gain has little influence on differentiation and lipid synthesis of IM adipose tissue at similar carcass weight but faster rates of gain increase differentiation and lipid synthesis of SC and PR adipose tissue even at similar carcass weight.

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

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    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

  15. Do Generous Welfare States Generate Efficiency Gains Which Counterbalance Short Run Losses? Testing Downside Risk Theory with Economic Panel Data for the U.S., Germany and the Netherlands

    Science.gov (United States)

    Headey, Bruce; Muffels, Ruud

    2008-01-01

    The purpose of the paper is to assess the theory that the downside risk insurance provided by more generous welfare states generates long run efficiency gains, which counterbalance the short run efficiency losses caused by work disincentives in these states (Feldstein 1974, 1976; Sinn 1995, 1996). Testing downside risk theory requires long term…

  16. 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.

  17. Gene copy number gain of EGFR is a poor prognostic biomarker in gastric cancer: evaluation of 855 patients with bright-field dual in situ hybridization (DISH) method.

    Science.gov (United States)

    Higaki, Eiji; Kuwata, Takeshi; Nagatsuma, Akiko Kawano; Nishida, Yasunori; Kinoshita, Takahiro; Aizawa, Masaki; Nitta, Hiroaki; Nagino, Masato; Ochiai, Atsushi

    2016-01-01

    EGFR overexpression is a prognostic biomarker and is expected to be a predictive biomarker for anti-EGFR therapies in gastric cancer. However, few studies have reported the clinical impact of EGFR gene copy number (GCN) and its correlation with EGFR overexpression. We used dual in situ hybridization (DISH) to detect EGFR GCN and chromosome 7 centromere (CEN7) in a set of tissue microarrays representing 855 patients with gastric cancer. These data were compared with those of immunohistochemical (IHC) analysis of EGFR expression to evaluate prognostic value. EGFR GCN gain (≥ 2.5 EGFR signals per cell) was detected in 194 patients (22.7%) and indicated poor prognosis. Among 194 patients, EGFR amplification (EGFR/CEN7 ≥ 2.0) was observed in 29 patients (14.9%), which was almost identical to the IHC 3+ subgroup and worst prognostic subgroup. Patients with EGFR GCN gain but not amplification, including those exhibiting polysomy, also exhibited poorer prognosis than GCN non-gain patients and were distributed between IHC 0/1+ and 2+ subgroups. GCN gain was frequently observed in patients with more advanced disease, but served as an independent prognostic factor regardless of the pathological stage. EGFR GCN gain is a more accurate prognostic biomarker than EGFR overexpression in patients with gastric cancer.

  18. A gain-loss framework based on ensemble flow forecasts to switch the urban drainage-wastewater system management towards energy optimization during dry periods

    Science.gov (United States)

    Courdent, Vianney; Grum, Morten; Munk-Nielsen, Thomas; Mikkelsen, Peter S.

    2017-05-01

    Precipitation is the cause of major perturbation to the flow in urban drainage and wastewater systems. Flow forecasts, generated by coupling rainfall predictions with a hydrologic runoff model, can potentially be used to optimize the operation of integrated urban drainage-wastewater systems (IUDWSs) during both wet and dry weather periods. Numerical weather prediction (NWP) models have significantly improved in recent years, having increased their spatial and temporal resolution. Finer resolution NWP are suitable for urban-catchment-scale applications, providing longer lead time than radar extrapolation. However, forecasts are inevitably uncertain, and fine resolution is especially challenging for NWP. This uncertainty is commonly addressed in meteorology with ensemble prediction systems (EPSs). Handling uncertainty is challenging for decision makers and hence tools are necessary to provide insight on ensemble forecast usage and to support the rationality of decisions (i.e. forecasts are uncertain and therefore errors will be made; decision makers need tools to justify their choices, demonstrating that these choices are beneficial in the long run). This study presents an economic framework to support the decision-making process by providing information on when acting on the forecast is beneficial and how to handle the EPS. The relative economic value (REV) approach associates economic values with the potential outcomes and determines the preferential use of the EPS forecast. The envelope curve of the REV diagram combines the results from each probability forecast to provide the highest relative economic value for a given gain-loss ratio. This approach is traditionally used at larger scales to assess mitigation measures for adverse events (i.e. the actions are taken when events are forecast). The specificity of this study is to optimize the energy consumption in IUDWS during low-flow periods by exploiting the electrical smart grid market (i.e. the actions are taken

  19. 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.

  20. Patterns of CDKN2A gene loss in sequential oral epithelial dysplasias and carcinomas.

    Science.gov (United States)

    Shahnavaz, S A; Bradley, G; Regezi, J A; Thakker, N; Gao, L; Hogg, D; Jordan, R C

    2001-03-15

    The CDKN2A gene locus encodes two different proteins derived from alternative splicing. p16 (exons 1alpha, 2, and 3) acts as a G1 cell cycle regulator, and p14ARF (exons 1beta, 2, and 3) acts to modulate MDM2-mediated degradation of p53. Inactivation of p16 is a common finding in many cancers; however, there is little data on CDKN2A gene abnormalities in oral precancer. In this longitudinal study, we examined changes in the CDKN2A gene locus in sequential epithelial dysplasias and oral carcinomas from 11 patients. Genomic DNA was extracted from laser-microdissected lesional tissue, and exons 1alpha, 1beta, and 2 were analyzed by duplex PCR. Immunohistochemistry was done to identify p16 and p14ARF protein expression. Two adjacent polymorphic microsatellite markers were used for allelotyping. Homozygous deletion of exon 1alpha was identified in 2 of 17 (12%) precancerous lesions. Loss of either exon 1alpha, exon 2, or both was seen in seven of nine (78%) carcinomas. In five of these carcinomas, there was loss of only exon 1alpha. No case showed deletion of exon 1beta. In 5 of 11 patients, microsatellite markers showed differing patterns of allelic imbalance in the precancerous lesions and the subsequent carcinoma, suggesting a complex genetic pattern of progression from dysplasia to carcinoma. We conclude that during oral carcinogenesis homozygous deletion of exon 1alpha of the CDKN2A gene is common but that deletion of exon 2 and 1beta is less frequent. Moreover, our results suggest that the progression from oral precancer to cancer, in some cases, is more complex genetically than predicted by linear models of carcinogenesis.

  1. 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....

  2. Filaggrin gene loss-of-function mutations explain discordance of atopic dermatitis within dizygotic twin pairs

    DEFF Research Database (Denmark)

    Thomsen, Simon Francis; Elmose, Camilla; Szecsi, Pal Bela

    2016-01-01

    OBJECTIVES: This study was designed to examine the association between loss-of-function mutations in the filaggrin gene (FLG) and atopic dermatitis (AD) and asthma in adult twins. METHODS: A previously well-characterized cohort of 575 adult twins were genotyped for the loss-of-function mutations...... no significant differences in risk for asthma by FLG mutation status in individuals with and without AD, respectively (P-value for interaction, 0.595). In 11 dizygotic twin pairs discordant for FLG mutation status, risk for AD was higher in the twin carrying the FLG mutation (five of 11 [45.5%] twins had...... developed AD) than in the non-carrier co-twin (two of 11 [18.2%] twins had developed AD) (OR 2.50, 95% CI 0.45-13.85; P = 0.293). FLG status did not explain a significant proportion of the variation in AD (P = 0.328) or asthma (P = 0.321). CONCLUSIONS: Filaggrin gene mutations are risk factors...

  3. 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

  4. Human telomerase RNA gene (TERC) gain and polysomy of chromosome 3 in cervicovaginal liquid-based pap preparations: a fluorescence in situ hybridization study.

    Science.gov (United States)

    Sui, W; Ou, M; Chen, J; Yu, J; Zhang, Y; Lan, H; Huang, H; Dai, Y

    2010-01-01

    PURPOSE. This study investigated human telomerase RNA gene (TERC) gain and polysomy of chromosome 3 in cervicovaginal liquid-based pap preparations in Guilin, China, and assessed the relationship between FISH findings and clinical diagnoses. METHODS. Slides prepared from 63 liquid-based preparations with cytologic diagnoses of negative for squamous intraepithelial lesion or malignancy (NILM n = 9), atypical squamous cells of undetermined significance (ASCUS, n = 18), low-grade squamous intraepithelial lesion (LSIL, n = 14), high-grade squamous intraepithelial lesion (HSIL, n = 9), and cervical squamous cell carcinoma (SCCA, n = 13) were analyzed for TERC gain and polysomy of chromosome 3 using a commercially available two-color FISH probe. The results of the cytologic analysis and those of concurrent or subsequent biopsies, when available, were compared with the FISH findings. The Mann-Whitney test was used to assess associations between FISH findings and diagnoses. RESULTS. TERC gain and polysomy of chromosome 3 were significantly associated with the cytologic diagnosis (p? 0.001). Patients with HSIL or SCCA cytology diagnoses had a significantly higher percentage of cells with TERC gain and polysomy of chromosome 3 than did patients with NILM, ASCUS or LSIL cytologic diagnoses. Those abnormal cases with CIN1 histological diagnosis had a significantly lower percentage of cells with TERC gain and polysomy of chromosome 3 than did patients with a CIN2, CIN3 and SCCA histological diagnosis. CONCLUSIONS. TERC gain and polysomy of chromosome 3 may be important associated genetic events in cervical intraepithelial neoplasia and carcinoma. FISH is a potential tool for the diagnoses of uterine cervix disease.

  5. Iowa Gambling Task: There is more to consider than long-term outcome.Using a linear equation model to disentangle the impact of outcome and frequency of gains and losses.

    Directory of Open Access Journals (Sweden)

    Annette eHorstmann

    2012-05-01

    Full Text Available The Iowa Gambling Task (IGT has been widely used to assess differences in decision-making under uncertainty. Recently, several studies have shown that healthy subjects do not meet the basic predictions of the task (i.e. prefer options with positive long-term outcome, hence questioning its basic assumptions. Since choice options are characterized by gain and net loss frequency in addition to long-term outcome, we hypothesized that a combination of features rather than a single feature would influence participants’ choices. Offering an alternative way of modeling IGT data, we propose to use a system of linear equations to estimate weights that quantify the influence of each individual feature on decision-making in the IGT. With our proposed model it is possible to disentangle and quantify the impact of each of these features.Results from 119 healthy young subjects suggest that choice behavior is predominantly influenced by gain and loss frequency. Subjects preferred choices associated with high frequency gains to those with low frequency gains, regardless of long-term outcome. However, among options with low frequency gains, subjects learned to distinguish between choices that led to advantageous and disadvantageous long-term consequences. This is reflected in the relationship between the weights for gain frequency (highest, loss frequency (intermediate and long-term outcome (lowest. Further, cluster analysis of estimated feature weights revealed subgroups of participants with distinct weight patterns and associated advantageous decision behavior. However, subjects in general do not learn to solely base their preference for particular decks on expected long-term outcome. Consequently, long-term outcome alone is not able to drive choice behavior on the IGT. In sum, our model facilitates a more focused conclusion about the factors guiding decision-making in the IGT. In addition, differences between clinical groups can be assessed for each factor

  6. Weight gain induced by an isocaloric pair-fed high fat diet: a nutriepigenetic study on FASN and NDUFB6 gene promoters.

    Science.gov (United States)

    Lomba, Almudena; Martínez, J Alfredo; García-Díaz, Diego F; Paternain, Laura; Marti, Amelia; Campión, Javier; Milagro, Fermín I

    2010-01-01

    Experimental studies have demonstrated that dietary macronutrient distribution plays an important role in insulin regulation, a risk factor associated to obesity, diabetes and other metabolic disorders. To assess whether the macronutrient composition of the diet could be related to obesity onset by affecting the epigenetic regulation of gene expression, we investigated in rats the metabolic effects of two pair-fed isocaloric diets: control (rich in carbohydrates) and high fat diet (rich in fat; HFD). Compared to controls, HFD induced higher weight gain and adiposity and impaired glucose tolerance, which was accompanied by a slight increase in adiponectin levels and liver steatosis. Epididymal adipose tissue expression of the fatty acid synthase (FASN) gene and NADH dehydrogenase (ubiquinone) 1β-subcomplex 6 (NDUFB6) were significantly reduced in HFD group. These variations in mRNA levels were accompanied by changes in the methylation patterns of several CpG islands located in the promoter region of these genes. However, no correlations were found between gene expression and the methylation status. These results suggest that high fat intake produces overweighted rats independently of total energy intake. These diets could also induce some epigenetic changes in the promoters of key genes that could influence gene expression and may be behind metabolic alterations. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Gain-of-function analysis of poplar CLE genes in Arabidopsis by exogenous application and over-expression assays.

    Science.gov (United States)

    Liu, Yisen; Yang, Shaohui; Song, Yingjin; Men, Shuzhen; Wang, Jiehua

    2016-04-01

    Among 50 CLE gene family members in the Populus trichocarpa genome, three and six PtCLE genes encode a CLE motif sequence highly homologous to Arabidopsis CLV3 and TDIF peptides, respectively, which potentially make them functional equivalents. To test and compare their biological activity, we first chemically synthesized each dodecapeptide and analysed itsi n vitro bioactivity on Arabidopsis seedlings. Similarly, but to a different extent, three types of poplar CLV3-related peptides caused root meristem consumption, phyllotaxis disorder, anthocyanin accumulation and failure to enter the bolting stage. In comparison, application of two poplar TDIF-related peptides led to root length promotion in a dose-dependent manner with an even stronger effect observed for poplar TDIF-like peptide than TDIF. Next, we constructed CaMV35S:PtCLE transgenic plants for each of the nine PtCLE genes. Phenotypic abnormalities exemplified by arrested shoot apical meristem and abnormal flower structure were found to be more dominant and severe in 35S:PtCLV3 and 35S:PtCLV3-like2 lines than in the 35S:PtCLV3-like line. Disordered vasculature was detected in both stem and hypocotyl cross-sections in Arabidopsis plants over-expressing poplar TDIF-related genes with the most defective vascular patterning observed for TDIF2 and two TDIF-like genes. Phenotypic difference consistently observed in peptide application assay and transgenic analysis indicated the functional diversity of nine poplar PtCLE genes under investigation. This work represents the first report on the functional analysis of CLE genes in a tree species and constitutes a basis for further study of the CLE peptide signalling pathway in tree development. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  8. The late flowering phenotype of fwa mutants is caused by gain-of-function epigenetic alleles of a homeodomain gene

    NARCIS (Netherlands)

    Soppe, W.J.J.; Jacobsen, S.E.; Alonso-Blanco, C.; Jackson, J.P.; Kakutani, T.; Koornneef, M.; Peeters, A.J.M.

    2000-01-01

    The transition to flowering in Arabidopsis thaliana is delayed in fwa mutant plants. FWA was identified by loss-of-function mutations in normally flowering revertants of the fwa mutant, and it encodes a homeodomain-containing transcription factor. The DNA sequence of wild-type and fwa mutant alleles

  9. Base flow (1966-2009) and streamflow gain and loss (2010) of the Brazos River from the New Mexico-Texas State line to Waco, Texas

    Science.gov (United States)

    Baldys, Stanley; Schalla, Frank E.

    2012-01-01

    During 2010–11, the U.S. Geological Survey (USGS), in cooperation with the Texas Water Development Board, used hydrograph separation to quantify historical base flow at 11 USGS streamflow-gaging stations between water years 1966–2009 and streamflow gains and losses from two sets of synoptic measurements of streamflow and specific conductance (the first in June 2010, followed by another set in October 2010) in the upper Brazos River Basin from the New Mexico–Texas State line to Waco, Texas. The following subbasins compose the study area: Salt Fork Brazos River Basin, Double Mountain Fork Brazos River Basin, Clear Fork Brazos River Basin, North Bosque River Basin, and the Brazos River Basin (main stem) (including its tributaries). Base-flow analysis was done using historical streamflow data from 11 USGS streamflow-gaging stations in the upper Brazos River Basin to compute yearly base-flow indexes (base flow divided by total streamflow) for each station. The base-flow index was used to indicate the fraction of flow consisting of base flow on an annual basis for the period of record evaluated at each streamflow-gaging station. At nine stations there were long-term streamflow data from water years 1966–2009 (October 1965 through September 2009); at two stations slightly shorter periods of record (water years 1967–2009 and 1969–2009) were available. The median base-flow indexes were 0.16 and 0.15 at USGS streamflow-gaging stations 08082000 Salt Fork Brazos River near Aspermont, Tex., and 08080500 Double Mountain Fork Brazos River near Aspermont, Tex., respectively. The amount of the total streamflow consisting of base flow was larger at sites in the Clear Fork Brazos River Basin compared to sites in the Salt Fork Brazos River Basin or Double Mountain Fork Brazos River Basin; at USGS streamflow-gaging stations 08084000 Clear Fork Brazos River at Nugent, Tex., and at 08085500 Clear Fork Brazos River at Fort Griffin, Tex., the median base-flow indexes were 0

  10. A mathematical model of weight loss under total starvation: evidence against the thrifty-gene hypothesis

    Directory of Open Access Journals (Sweden)

    John R. Speakman

    2013-01-01

    The thrifty-gene hypothesis (TGH posits that the modern genetic predisposition to obesity stems from a historical past where famine selected for genes that promote efficient fat deposition. It has been previously argued that such a scenario is unfeasible because under such strong selection any gene favouring fat deposition would rapidly move to fixation. Hence, we should all be predisposed to obesity: which we are not. The genetic architecture of obesity that has been revealed by genome-wide association studies (GWAS, however, calls into question such an argument. Obesity is caused by mutations in many hundreds (maybe thousands of genes, each with a very minor, independent and additive impact. Selection on such genes would probably be very weak because the individual advantages they would confer would be very small. Hence, the genetic architecture of the epidemic may indeed be compatible with, and hence support, the TGH. To evaluate whether this is correct, it is necessary to know the likely effects of the identified GWAS alleles on survival during starvation. This would allow definition of their advantage in famine conditions, and hence the likely selection pressure for such alleles to have spread over the time course of human evolution. We constructed a mathematical model of weight loss under total starvation using the established principles of energy balance. Using the model, we found that fatter individuals would indeed survive longer and, at a given body weight, females would survive longer than males, when totally starved. An allele causing deposition of an extra 80 g of fat would result in an extension of life under total starvation by about 1.1–1.6% in an individual with 10 kg of fat and by 0.25–0.27% in an individual carrying 32 kg of fat. A mutation causing a per allele effect of 0.25% would become completely fixed in a population with an effective size of 5 million individuals in 6000 selection events. Because there have probably been about 24

  11. Brain Regions Showing White Matter Loss in Huntington's Disease Are Enriched for Synaptic and Metabolic Genes.

    Science.gov (United States)

    McColgan, Peter; Gregory, Sarah; Seunarine, Kiran K; Razi, Adeel; Papoutsi, Marina; Johnson, Eileanoir; Durr, Alexandra; Roos, Raymund A C; Leavitt, Blair R; Holmans, Peter; Scahill, Rachael I; Clark, Chris A; Rees, Geraint; Tabrizi, Sarah J

    2018-03-01

    The earliest white matter changes in Huntington's disease are seen before disease onset in the premanifest stage around the striatum, within the corpus callosum, and in posterior white matter tracts. While experimental evidence suggests that these changes may be related to abnormal gene transcription, we lack an understanding of the biological processes driving this regional vulnerability. Here, we investigate the relationship between regional transcription in the healthy brain, using the Allen Institute for Brain Science transcriptome atlas, and regional white matter connectivity loss at three time points over 24 months in subjects with premanifest Huntington's disease relative to control participants. The baseline cohort included 72 premanifest Huntington's disease participants and 85 healthy control participants. We show that loss of corticostriatal, interhemispheric, and intrahemispheric white matter connections at baseline and over 24 months in premanifest Huntington's disease is associated with gene expression profiles enriched for synaptic genes and metabolic genes. Corticostriatal gene expression profiles are predominately associated with motor, parietal, and occipital regions, while interhemispheric expression profiles are associated with frontotemporal regions. We also show that genes with known abnormal transcription in human Huntington's disease and animal models are overrepresented in synaptic gene expression profiles, but not in metabolic gene expression profiles. These findings suggest a dual mechanism of white matter vulnerability in Huntington's disease, in which abnormal transcription of synaptic genes and metabolic disturbance not related to transcription may drive white matter loss. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Dt2 is a gain-of-function MADS-Domain factor gene that controls semi-determinacy in soybean

    Science.gov (United States)

    Similar to Arabidopsis, the wild soybean (Glycine soja) and many soybean (Glycine max) cultivars exhibit indeterminate stem growth controlled by a gene Dt1 – the functional counterpart of the Arabidopsis TFL1. Mutations in TFL1 and Dt1 both result in the shoot apical meristem (SAM) switching from ve...

  13. Pseudomonas community structure and antagonistic potential in the rhizosphere : insights gained by combining phylogenetic and functional gene-based analyses

    NARCIS (Netherlands)

    Costa, Rodrigo; Gomes, Newton C. M.; Kroegerrecklenfort, Ellen; Opelt, Katja; Berg, Gabriele; Smalla, Kornelia

    The Pseudomonas community structure and antagonistic potential in the rhizospheres of strawberry and oilseed rape (host plants of the fungal phytopathogen Verticillium dahliae) were assessed. The use of a new PCR-DGGE system, designed to target Pseudomonas-specific gacA gene fragments in

  14. 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.

  15. Dt2 Is a Gain-of-Function MADS-Domain Factor Gene That Specifies Semideterminacy in Soybean[C][W

    Science.gov (United States)

    Ping, Jieqing; Liu, Yunfeng; Sun, Lianjun; Zhao, Meixia; Li, Yinghui; She, Maoyun; Sui, Yi; Lin, Feng; Liu, Xiaodong; Tang, Zongxiang; Nguyen, Hanh; Tian, Zhixi; Qiu, Lijuan; Nelson, Randall L.; Clemente, Thomas E.; Specht, James E.; Ma, Jianxin

    2014-01-01

    Similar to Arabidopsis thaliana, the wild soybeans (Glycine soja) and many cultivars exhibit indeterminate stem growth specified by the shoot identity gene Dt1, the functional counterpart of Arabidopsis TERMINAL FLOWER1 (TFL1). Mutations in TFL1 and Dt1 both result in the shoot apical meristem (SAM) switching from vegetative to reproductive state to initiate terminal flowering and thus produce determinate stems. A second soybean gene (Dt2) regulating stem growth was identified, which, in the presence of Dt1, produces semideterminate plants with terminal racemes similar to those observed in determinate plants. Here, we report positional cloning and characterization of Dt2, a dominant MADS domain factor gene classified into the APETALA1/SQUAMOSA (AP1/SQUA) subfamily that includes floral meristem (FM) identity genes AP1, FUL, and CAL in Arabidopsis. Unlike AP1, whose expression is limited to FMs in which the expression of TFL1 is repressed, Dt2 appears to repress the expression of Dt1 in the SAMs to promote early conversion of the SAMs into reproductive inflorescences. Given that Dt2 is not the gene most closely related to AP1 and that semideterminacy is rarely seen in wild soybeans, Dt2 appears to be a recent gain-of-function mutation, which has modified the genetic pathways determining the stem growth habit in soybean. PMID:25005919

  16. 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

  17. Biophysical characterization of the short QT mutation hERG-N588K reveals a mixed gain-and loss-of-function

    DEFF Research Database (Denmark)

    Grunnet, M.; Diness, T.G.; Hansen, R.S.

    2008-01-01

    The short QT syndrome is a newly discovered pro-arrhythmic condition, which may cause ventricular fibrillation and sudden death. Short QT can originate from the apparent gain-of-function mutation N588K in the hERG potassium channel that conducts repolarising I(Kr) current. The present study...

  18. Flowering Without Vernalization in Winter Canola (Brassica napus: use of Virus-Induced Gene Silencing (VIGS to accelerate genetic gain

    Directory of Open Access Journals (Sweden)

    Raúl Álvarez-Venegas

    2010-01-01

    Full Text Available Ciclos de reproducción cortos y la oportunidad de incrementar la ganancia genética, junto con el estudio de las bases moleculares de la vernalización, son áreas esenciales de investigación dentro de la biología de plantas. Varios métodos se han empleado para lograr el silenciamiento génico en plantas, pero ninguno reportado a la fecha para canola (Brassica napus, y en particular para inducir la floración sin vernalización en líneas de invierno a través del uso de secuencias sentido de DNA en vectores diseñados para el silenciamiento génico inducido por virus (VIGS. La presente investigación provee los métodos para transitoriamente regular a la baja, por medio de VIGS, genes de la vernalización en plantas anuales de invierno, específicamente la familia de genes de Flowering Locus C (FLC en canola de invierno (BnFLC1 a BnFLC5. La regulación a la baja de estos genes permite a las plantas anuales de invierno florecer sin vernalización y, consecuentemente, provee los medios para acelerar la ganancia genética. El sistema de silenciamiento propuesto puede ser utilizado para regular a la baja familias de genes, para determinar la función génica, y para inducir la floración sin la vernalización en líneas de invierno tanto del género Brassica como de muchos cultivos importantes de invierno.

  19. Expression Analyses of ABCDE Model Genes and Changes in Levels of Endogenous Hormones in Chinese Cabbage Exhibiting Petal-Loss

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    Chuan MENG

    2017-07-01

    Full Text Available Abnormal formation of floral organs affects plant reproduction and can directly interfere with the progress of breeding programs. Using PCR amplification, ABCDE model genes BraAP2, BraAP3, BraPI, BraAG, BraSHP, and BraSEP were isolated from Chinese cabbage (Brassica rapa L. ssp. pekinensis. We examined six development stages of floral buds collected from Chinese cabbage and compared between a line demonstrating normal flowering (A-8 and two mutated lines that exhibited plants having petal-loss (A-16 and A-17. The expression of ABCDE model genes has been analyzed by qRT-PCR. Compared with flower buds of petal-loss plants and normal plants, the expression of A-class gene BraAP2 was significantly decreased during the first to fourth stages, C-class gene BraAG expression was significantly decreased during the first to fifth stages, and D-class gene BraSHP expression was significantly decreased during the first to third stages. Furthermore, B-class gene BraAP3 and BraPI and E-class gene BraSEP expressions were significantly decreased during all six stages of petal-loss plants compared with normal plants. Enzyme-linked immunosorbent assays detected nine endogenous phytohormones during all stages examined here. Except for the second-stage and third-stage buds, levels of the auxin IAA and cytokinin dhZR were always higher in the petal-loss plants than the normal plants at corresponding time points. Meanwhile, concentrations of GA1+3 at the first, fourth, and fifth stages were higher in the petal-loss plants than in the normal plants. Our results provide a theoretical basis for future exploration of the molecular mechanism that determines petal loss and the effects that hormones have on such development in Chinese cabbage plants.

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

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    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.

  1. Higher Flexibility and Better Immediate Spontaneous Correction May Not Gain Better Results for Nonstructural Thoracic Curve in Lenke 5C AIS Patients: Risk Factors for Its Correction Loss.

    Science.gov (United States)

    Zhang, Yanbin; Lin, Guanfeng; Wang, Shengru; Zhang, Jianguo; Shen, Jianxiong; Wang, Yipeng; Guo, Jianwei; Yang, Xinyu; Zhao, Lijuan

    2016-11-15

    Retrospective study. To study the behavior of the unfused thoracic curve in Lenke type 5C during the follow-up and to identify risk factors for its correction loss. Few studies have focused on the spontaneous behaviors of the unfused thoracic curve after selective thoracolumbar or lumbar fusion during the follow-up and the risk factors for spontaneous correction loss. We retrospectively reviewed 45 patients (41 females and 4 males) with AIS who underwent selective TL/L fusion from 2006 to 2012 in a single institution. The follow-up averaged 36 months (range, 24-105 months). Patients were divided into two groups. Thoracic curves in group A improved or maintained their curve magnitude after spontaneous correction, with a negative or no correction loss during the follow-up. Thoracic curves in group B deteriorated after spontaneous correction with a positive correction loss. Univariate analysis and multivariate analysis were built to identify the risk factors for correction loss of the unfused thoracic curves. The minor thoracic curve was 26° preoperatively. It was corrected to 13° immediately with a spontaneous correction of 48.5%. At final follow-up it was 14° with a correction loss of 1°. Thoracic curves did not deteriorate after spontaneous correction in 23 cases in group A, while 22 cases were identified with thoracic curve progressing in group B. In multivariate analysis, two risk factors were independently associated with thoracic correction loss: higher flexibility and better immediate spontaneous correction rate of thoracic curve. Posterior selective TL/L fusion with pedicle screw constructs is an effective treatment for Lenke 5C AIS patients. Nonstructural thoracic curves with higher flexibility or better immediate correction are more likely to progress during the follow-up and close attentions must be paid to these patients in case of decompensation. 4.

  2. Analysis of loss of heterozygosity of the tumor suppressor genes p53 and BRCA1 in ovarial carcinomas

    OpenAIRE

    Luković Ljiljana; Popović Branka; Atanacković Jasmina; Novaković Ivana; Perović Milica; Petrović Bojana; Petković Spasoje

    2006-01-01

    Background/aim: Among the genes involved in ovarian carcinogenesis, there has been increased interest in tumor-suppressor genes p53 and BRCA1. Both of the genes make control of cell cycle, DNA repair and apoptosis. The p53 is a "genome guardian" inactivated in more than 50% of human cancers, while BRCA1 mutations are found mostly in breast and ovarian cancer. The aim of this investigation was to establish the frequency of loss of heterozygosity (LOH) in the regions of the genes p53 and BRCA1 ...

  3. BPK AND BPKP IN DETERMINING STATE FINANCE LOSS IN ORDER TO GAIN ANTI-CORRUPTION LAW EFFICIENCY OF ANTI-CORRUPTION LAW

    Directory of Open Access Journals (Sweden)

    Gabrielia Febrianty Shofiana

    2016-05-01

    Full Text Available Corruption case in Indonesia has been growing rapidly, therefore it needs big efforts to eradicate and prevent corruption, such as establishment of Corruption Eradication Commission (KPK and the enactment of Law No. 31 Year 1999 as amended by Law No. 20 Year 2001 (Anti-Corruption Law. Corruption itself, as regulated in Article 2 and 3 Anti-Corruption Law, consists of some main elementswhose subject is anyone.The illegal act must exist which aims to enrich themselves and should create loss of state finance or economy. The efficiency of Anti-Corruption Law can be seen by how every article can be fully and properly fulfilled. Only authorized legal entities can determine state finance loss as one of corruption elements. Then, the problems emerge from the legal entity which actually has authority to determine state finance loss, yet if the fulfillment element of state finance loss is not discovered, it means that the corruption suspected cannot be charged. Supreme Audit Board (BPK/SAB and Finance & Development Supervisory Board (BPKP/FDSB are legal entities which have authority to conduct audit investigation. This study, by using normative-empirical research method, will discuss whether both or only one of those state agencies have authority to determine state finance loss.

  4. [Association between eye absent homolog 4 gene polymorphisms and occupational noise-induced hearing loss].

    Science.gov (United States)

    Yang, Q Y; Xu, X R; Jiao, J; Zheng, Y X; He, L H; Yu, S F; Gu, G Z; Chen, G S; Zhou, W H; Wu, H; Li, Y H; Zhang, H L; Zhang, Z R

    2017-01-06

    Objective: To identify the association between genetic polymorphisms in the eye absent homolog 4 (EYA4) gene and noise-induced hearing loss (NIHL). Method: A nested case control study was conducted based on a cohort of noise-exposed subjects. In total, 292 cases were selected from a steel factory from 6 297 subjects during Jan 1, 2006 to Dec 12, 2015,who had an average hearing threshold of more than 40 dB(A); 584 matched control subjects for each case were designated on the basis of matched criteria including same gender, age (±5 years) and duration of exposure to noise (±2 years). What's more, the control group had an average hearing threshold of less than 35 dB(A) in high frequency and less than 25 dB(A) in speech frequency. Four single nucleotide polymorphisms (SNPs) of the EYA4 gene were genotyped using a SNPscan TM multiplex SNP genotyping kit. Hardy-Weinberg equilibrium tests were performed using a χ 2 test for goodness-of-fit for each SNP among the control group, and the effects of genotypes of the EYA4 gene on NIHL were analyzed by logistic regression. The haplotypes were established and their frequencies in the two groups were assessed using Haploview 4.2 and Phase 2.1 software, and interactive effects between haplotypes and cumulative noise exposure were analyzed. Results: The average age of the subjects was (40.1±8.4) years and the average number of noise-exposed working years was 20.3 (8.4, 27.3) years. The range of noise exposure levels and the cumulative noise exposure were 80.2- 98.8 dB (A) and 86.6- 111.2 dB(A) · year, respectively. After adjustment for covariates including height, blood pressure, drinking status and smoking status, in the noise intensity>85 dB (A) group, subjects carrying the rs3813346 TT genotype had a higher NIHL risk than those carrying the GG genotype, and the adjusted OR (95% CI ) value was 2.12 (1.21- 3.69). In the cumulative noise exposure>98 dB (A) · year group, compared with haplotype TGC, haplotype CGT showed a

  5. Evolutionary acquisition and loss of saxitoxin biosynthesis in dinoflagellates: the second "core" gene, sxtG.

    Science.gov (United States)

    Orr, Russell J S; Stüken, Anke; Murray, Shauna A; Jakobsen, Kjetill S

    2013-04-01

    Saxitoxin and its derivatives are potent neurotoxins produced by several cyanobacteria and dinoflagellate species. SxtA is the initial enzyme in the biosynthesis of saxitoxin. The dinoflagellate full mRNA and partial genomic sequences have previously been characterized, and it appears that sxtA originated in dinoflagellates through a horizontal gene transfer from a bacterium. So far, little is known about the remaining genes involved in this pathway in dinoflagellates. Here we characterize sxtG, an amidinotransferase enzyme gene that putatively encodes the second step in saxitoxin biosynthesis. In this study, the entire sxtG transcripts from Alexandrium fundyense CCMP1719 and Alexandrium minutum CCMP113 were amplified and sequenced. The transcripts contained typical dinoflagellate spliced leader sequences and eukaryotic poly(A) tails. In addition, partial sxtG transcript fragments were amplified from four additional Alexandrium species and Gymnodinium catenatum. The phylogenetic inference of dinoflagellate sxtG, congruent with sxtA, revealed a bacterial origin. However, it is not known if sxtG was acquired independently of sxtA. Amplification and sequencing of the corresponding genomic sxtG region revealed noncanonical introns. These introns show a high interspecies and low intraspecies variance, suggesting multiple independent acquisitions and losses. Unlike sxtA, sxtG was also amplified from Alexandrium species not known to synthesize saxitoxin. However, amplification was not observed for 22 non-saxitoxin-producing dinoflagellate species other than those of the genus Alexandrium or G. catenatum. This result strengthens our hypothesis that saxitoxin synthesis has been secondarily lost in conjunction with sxtA for some descendant species.

  6. 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

  7. Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice

    OpenAIRE

    Panchenko, Polina E.; Voisin, Sarah; Jouin, M?lanie; Jouneau, Luc; Pr?zelin, Audrey; Lecoutre, Simon; Breton, Christophe; Jammes, H?l?ne; Junien, Claudine; Gabory, Anne

    2016-01-01

    Background Maternal obesity impacts fetal growth and pregnancy outcomes. To counteract the deleterious effects of obesity on fertility and pregnancy issue, preconceptional weight loss is recommended to obese women. Whether this weight loss is beneficial/detrimental for offspring remains poorly explored. Epigenetic mechanisms could be affected by maternal weight changes, perturbing expression of key developmental genes in the placenta or fetus. Our aim was to investigate the effects of chronic...

  8. 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.

  9. Stepping Back to Gain Perspective: Pregnancy Loss History, Depression, and Parenting Capacity in the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B)

    Science.gov (United States)

    Price, Sarah Kye

    2008-01-01

    Previous empirical studies of pregnancy loss have predominantly focused on complex grief response and emergent problems associated with future parenting in self-selected samples of bereaved women. This article presents findings from a retrospective secondary data analysis conducted with a racially and ethnically diverse sample of currently…

  10. Evolutionary redesign of the Atlantic cod (Gadus morhua L.) Toll-like receptor repertoire by gene losses and expansions

    OpenAIRE

    Solbakken, Monica H.; T?rresen, Ole K.; Nederbragt, Alexander J.; Seppola, Marit; Gregers, Tone F.; Jakobsen, Kjetill S.; Jentoft, Sissel

    2016-01-01

    Published version. Source at http://doi.org/10.1038/srep25211. License CC BY 4.0. Genome sequencing of the teleost Atlantic cod demonstrated loss of the Major Histocompatibility Complex (MHC) class II, an extreme gene expansion of MHC class I and gene expansions and losses in the innate pattern recognition receptor (PRR) family of Toll-like receptors (TLR). In a comparative genomic setting, using an improved version of the genome, we characterize PRRs in Atlantic cod with emphasis on TL...

  11. MYC and Human Telomerase Gene (TERC) Copy Number Gain in Early-stage Non–small Cell Lung Cancer

    Science.gov (United States)

    Flacco, Antonella; Ludovini, Vienna; Bianconi, Fortunato; Ragusa, Mark; Bellezza, Guido; Tofanetti, Francesca R.; Pistola, Lorenza; Siggillino, Annamaria; Vannucci, Jacopo; Cagini, Lucio; Sidoni, Angelo; Puma, Francesco; Varella-Garcia, Marileila; Crinò, Lucio

    2015-01-01

    Objectives We investigated the frequency of MYC and TERC increased gene copy number (GCN) in early-stage non–small cell lung cancer (NSCLC) and evaluated the correlation of these genomic imbalances with clinicopathologic parameters and outcome. Materials and Methods Tumor tissues were obtained from 113 resected NSCLCs. MYC and TERC GCNs were tested by fluorescence in situ hybridization (FISH) according to the University of Colorado Cancer Center (UCCC) criteria and based on the receiver operating characteristic (ROC) classification. Results When UCCC criteria were applied, 41 (36%) cases for MYC and 41 (36%) cases for TERC were considered FISH-positive. MYC and TERC concurrent FISH-positive was observed in 12 cases (11%): 2 (17%) cases with gene amplification and 10 (83%) with high polysomy. By using the ROC analysis, high MYC (mean ≥2.83 copies/cell) and TERC (mean ≥2.65 copies/cell) GCNs were observed in 60 (53.1%) cases and 58 (51.3%) cases, respectively. High TERC GCN was associated with squamous cell carcinoma (SCC) histology (P = 0.001). In univariate analysis, increased MYC GCN was associated with shorter overall survival (P = 0.032 [UCCC criteria] or P = 0.02 [ROC classification]), whereas high TERC GCN showed no association. In multivariate analysis including stage and age, high MYC GCN remained significantly associated with worse overall survival using both the UCCC criteria (P = 0.02) and the ROC classification (P = 0.008). Conclusions Our results confirm MYC as frequently amplified in early-stage NSCLC and increased MYC GCN as a strong predictor of worse survival. Increased TERC GCN does not have prognostic impact but has strong association with squamous histology. PMID:25806711

  12. [The study on 235delC mutation of GJB2 gene in patients with idiopathic sudden hearing loss].

    Science.gov (United States)

    Zhan, Yue; Hu, Yujuan; Huang, Xiang; Chen, Huamao; Guo, Changkai; Xiao, Hongjun; Shi, Hong; Kong, Weijia

    2014-05-01

    To analyze the rate of 235delC mutation in GJB2 gene in patients with idiopathic sudden hearing loss, and to explore its possible correlation with pathogenesis of idiopathic sudden hearing loss. Two hundred and thirty-four patients with diagnosis of idiopathic sudden hearing loss in otolaryngology department were recruited as experimental group. Eighty people with normal hearing level were enrolled as control group. Their peripheral blood samples were obtained and genomic DNA was extracted. Using polymerase chain reaction, the coding region of GJB2 gene was amplified, and 235delC mutation is screened for in GJB2 gene by restriction endonuclease. At same time the clinical data of 234 patients was collected to analyze. In 234 cases of idiopathic sudden hearing loss, 5 cases were found to have heterozygous 235delC mutation, none of them harbored homozygous 235delC mutation, the 235delC mutation rate was 2.1% (5/234). No 235delC mutation was found in control group. The rate of 235delC mutation in two group showed no statistically significant difference (P > 0.05). This research shows that the rate of 235delC mutation in GJB2 is low in patients with idiopathic sudden hearing loss, and suggest that 235delC mutation possible has no correlation with idiopathic sudden hearing loss.

  13. 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

  14. Conservation of the abscission signaling peptide IDA during Angiosperm evolution: withstanding genome duplications and gain and loss of the receptors HAE/HSL2

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    Ida M. Stø

    2015-10-01

    Full Text Available The peptide INFLORESCENCE DEFICIENT IN ABSCISSION (IDA, which signals through the leucine-rich repeat receptor-like kinases HAESA (HAE and HAESA-LIKE2 (HSL2, controls different cell separation events in Arabidopsis thaliana. We hypothesize the involvement of this signaling module in abscission processes in other plant species even though they may shed other organs than A. thaliana. As the first step towards testing this hypothesis from an evolutionarily perspective we have identified genes encoding putative orthologues of IDA and its receptors by BLAST searches of publically available protein, nucleotide and genome databases for angiosperms. Genes encoding IDA or IDA-LIKE (IDL peptides and HSL proteins were found in all investigated species, which were selected as to represent each angiosperm order with available genomic sequences. The 12 amino acids representing the bioactive peptide in A. thaliana have virtually been unchanged throughout the evolution of the angiosperms; however, the number of IDL and HSL genes varies between different orders and species. The phylogenetic analyses suggest that IDA, HSL2 and the related HSL1 gene, were present in the species that gave rise to the angiosperms. HAE has arisen from HSL1 after a genome duplication that took place after the monocot - eudicots split. HSL1 has also independently been duplicated in the monocots, while HSL2 has been lost in gingers (Zingiberales and grasses (Poales. IDA has been duplicated in eudicots to give rise to functionally divergent IDL peptides. We postulate that the high number of IDL homologs present in the core eudicots is a result of multiple whole genome duplications. We substantiate the involvement of IDA and HAE/HSL2 homologs in abscission by providing gene expression data of different organ separation events from various species.

  15. 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.

  16. 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.

  17. Estimation of the temperature, heat gain and heat loss by solar parabolic trough collector under Algerian climate using different thermal oils

    International Nuclear Information System (INIS)

    Ouagued, Malika; Khellaf, Abdallah; Loukarfi, Larbi

    2013-01-01

    Highlights: • Estimation of direct solar radiations for different tracking systems at six typical locations in Algeria. • PTC thermal model uses energy balances from the HTF to the atmosphere. • The model depends on the collector type, nature of HTF, optical properties, and ambient conditions. • Estimation of temperature, heat gain and energy cost of thermal oils used in the model. • Comparison between monthly mean heat gain of the various thermal oils for six Algerian locations. - Abstract: Algeria is blessed with a very important renewable, and more particularly solar, energy potential. This potential opens for Algeria reel opportunities to cope with the increasing energy demand and the growing environmental problems link to the use of fossil fuel. In order to develop and to promote concrete actions in the areas of renewable energy and energy efficiency, Algeria has introduced a national daring program for the period 2011–2030. In this program, solar energy, and more particularly solar thermal energy plays an important role. In this paper, the potential of direct solar irradiance in Algeria and the performance of solar parabolic trough collector (PTC) are estimated under the climate conditions of the country. These two factors are treated as they play an important role in the design of solar thermal plant. In order to determine the most promising solar sites in Algeria, monthly mean daily direct solar radiation have been estimated and compared for different locations corresponding to different climatic region. Different tilted and tracking collectors are considered so as to determine the most efficient system for the PTC. In order to evaluate the performance of a tracking solar parabolic trough collector, a heat transfer model is developed. The receiver, heat collector element (HCE), is divided into several segments and heat balance is applied in each segment over a section of the solar receiver. Different oils are considered to determine the thermal

  18. Discovery of MYH14 as an important and unique deafness gene causing prelingually severe autosomal dominant nonsyndromic hearing loss.

    Science.gov (United States)

    Kim, Bong Jik; Kim, Ah Reum; Han, Jin Hee; Lee, Chung; Oh, Doo Yi; Choi, Byung Yoon

    2017-04-01

    Pathogenic variants of MYH14 are known to be associated (in either a syndromic or nonsyndromic manner) with hearing loss. Interestingly, all reported cases to date of MYH14-related nonsyndromic hearing loss with detailed phenotypes have demonstrated mild-to-moderate progressive hearing loss with postlingual onset. In the present study, targeted resequencing (TRS) of known deafness genes was performed to identify the causative variant in two multiplex families segregating autosomal dominant (AD) inherited hearing loss. TRS uncovered two novel variants of MYH14 (c.A572G: p.Asp191Gly in the myosin head domain and c.C73T:p.Gln25* in exon 2) from two multiplex deafness Korean families. Notably, both probands showed phenotypes of congenital or prelingual severe hearing loss. It is remarkably uncommon to encounter such a severe-to-profound, prelingual, AD hearing loss. Given that the first variant, p. Asp191Gly, was the first documented missense allele discovered in the myosin head domain of this gene related to either congenital or prelingual severe nonsyndromic hearing loss, and also that the second variant, p. Gln25*, lead to a null allele, more severe phenotypes from our probands may have been the result of either genotype-phenotype correlation or genetic backgrounds, or both. In the present study, we report that MYH14 can manifest as nonsyndromic prelingual severe sensorineural hearing loss in an AD fashion in Koreans. The results of the present study suggest that further genetic studies of similar patients should consider MYH14 as a causative gene, and cochlear implantation during infant or early childhood should be indicated for those patients with certain MYH14 pathogenic variants. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Cancer-associated loss of TARSH gene expression in human primary lung cancer.

    Science.gov (United States)

    Terauchi, Kunihiko; Shimada, Junichi; Uekawa, Natsuko; Yaoi, Takeshi; Maruyama, Mitsuo; Fushiki, Shinji

    2006-01-01

    We have previously identified mouse Tarsh as one of the cellular senescence-related genes and showed the loss of expression of TARSH mRNA in four human lung cancer cell lines. TARSH is a presumptive signal transduction molecule interacting with NESH, which is implicated to have some roles in lung cancer metastasis. The amplification of complete ORF-encoding TARSH cDNA was done with reverse transcription-PCR. Northern blotting was carried out using TARSH cDNA probes. To clarify the relationship between TARSH and lung cancer, we quantified TARSH mRNA expression in 15 human lung cancer cell lines and 32 primary non-small cell lung cancers. We first determined the complete ORF-encoding cDNA sequence which is expressed in the human lung. On the Northern hybridization analysis, TARSH was strongly expressed in the human lung. The expression of TARSH mRNA is remarkably downregulated in all the lung cancer cell lines examined. Furthermore, TARSH expression was significantly low in all of the tumor specimens when compared to the expression in corresponding non-neoplastic lung tissue specimens. The cancer-associated transcriptional inactivation of TARSH suggests that TARSH could be used as a biomarker for lung cancer development as well as a molecular adjunct for lung carcinogenesis in human.

  20. Male pattern hair loss: Taking one for the team: The selfless gene.

    Science.gov (United States)

    Uzoigwe, Chika Edward; Sanchez Franco, Luis Carlos; Gascon Conde, Ignacio; Sanchez Campoy, Adrian

    2018-05-01

    Male pattern hair loss (MPHL) is exceedingly common. It is characterised by onset in early adulthood and progression with age. It has a strong heritable component. The reason for its existence remains unexplained. Given that MPHL is progressive and has its earliest manifestations in young adults it may be a barometer of age. Here we suggest that MPHL may have atavistically allowed women in our species and ancestor species to select younger (but not necessarily the youngest) adult mates. Evidence suggests that conceptions by younger fathers are more likely to lead to live births and less likely to result in miscarriage. Further children fathered by younger men may have improved health and be less likely to suffer from a number of co-morbidities. This is collectively known as the "paternal age affect". Hence the selection of younger males mediated by the MPHL may improve the fitness of the population and of the species at the expense of the individual. Indeed MPHL may have been an evolutionary "nudge" directing women to favour younger partners. It is conceivable that for a species whose success is predicated upon co-operation, collaboration and altruism the gene cannot be exclusively selfish and must have a selfless allele. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. 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...

  2. BPK AND BPKP IN DETERMINING STATE FINANCE LOSS IN ORDER TO GAIN ANTI-CORRUPTION LAW EFFICIENCY OF ANTI-CORRUPTION LAW

    OpenAIRE

    Gabrielia Febrianty Shofiana

    2016-01-01

    Corruption case in Indonesia has been growing rapidly, therefore it needs big efforts to eradicate and prevent corruption, such as establishment of Corruption Eradication Commission (KPK) and the enactment of Law No. 31 Year 1999 as amended by Law No. 20 Year 2001 (Anti-Corruption Law). Corruption itself, as regulated in Article 2 and 3 Anti-Corruption Law, consists of some main elementswhose subject is anyone.The illegal act must exist which aims to enrich themselves and should create loss o...

  3. 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.

  4. Analysis of losses of heterozygosity of the candidate tumour suppressor gene DMBT1 in melanoma resection specimens

    DEFF Research Database (Denmark)

    Deichmann, M; Mollenhauer, J; Helmke, B

    2002-01-01

    Deleted in malignant brain tumours 1 (DMBT1), a candidate tumour suppressor gene located on chromosome 10q25.3-q26.1, has recently been identified and found to be deleted in several different types of human tumours. In melanomas, the chromosomal region 10q22-qter is commonly affected by losses......, hence we screened primary melanoma samples for losses of heterozygosity (LOH), and acquired melanocytic naevi and melanomas for transcription of DMBT1 and protein expression. Of 38 informative melanomas, 1 nodular melanoma and 2 subcutaneous metastases showed LOH of both microsatellites flanking...... the gene, suggesting loss of 1 DMBT1 allele. Three further melanomas showed LOH at 1 informative locus but were heterozygous for the second marker. Applying reverse-transcription polymerase chain reaction (RT-PCR), DMBT1 transcription was not found in melanomas. However, DMBT1 transcription was also absent...

  5. Analysis of losses of heterozygosity of the candidate tumour suppressor gene DMBT1 in melanoma resection specimens

    DEFF Research Database (Denmark)

    Deichmann, M; Mollenhauer, J; Helmke, B

    2002-01-01

    , hence we screened primary melanoma samples for losses of heterozygosity (LOH), and acquired melanocytic naevi and melanomas for transcription of DMBT1 and protein expression. Of 38 informative melanomas, 1 nodular melanoma and 2 subcutaneous metastases showed LOH of both microsatellites flanking......Deleted in malignant brain tumours 1 (DMBT1), a candidate tumour suppressor gene located on chromosome 10q25.3-q26.1, has recently been identified and found to be deleted in several different types of human tumours. In melanomas, the chromosomal region 10q22-qter is commonly affected by losses...... the gene, suggesting loss of 1 DMBT1 allele. Three further melanomas showed LOH at 1 informative locus but were heterozygous for the second marker. Applying reverse-transcription polymerase chain reaction (RT-PCR), DMBT1 transcription was not found in melanomas. However, DMBT1 transcription was also absent...

  6. Expression and copy number gains of the RET gene in 631 early and mid stage non-small cell lung cancer cases.

    Science.gov (United States)

    Tan, Ling; Hu, Yerong; Tao, Yongguang; Wang, Bin; Xiao, Jun; Tang, Zhenjie; Lu, Ting; Tang, Hao

    2018-02-23

    To identify whether RET is a potential target for NSCLC treatment, we examined the status of the RET gene in 631 early and mid stage NSCLC cases from south central China. RET expression was identified by Western blot. RET-positive expression samples were verified by immunohistochemistry. RET gene mutation, copy number variation, and rearrangement were analyzed by DNA Sanger sequencing, TaqMan copy number assays, and reverse transcription-PCR. ALK and ROS1 expression levels were tested by Western blot and EGFR mutation using Sanger sequencing. The RET-positive rate was 2.5% (16/631). RET-positive expression was related to poorer tumor differentiation (P < 0.05). In the 16 RET-positive samples, only two samples of moderately and poorly differentiated lung adenocarcinomas displayed RET rearrangement, both in RET-KIF5B fusion partners. Neither ALK nor ROS1 translocation was found. The EGFR mutation rate in RET-positive samples was significantly lower than in RET-negative samples (P < 0.05). RET-positive expression in early and mid stage NSCLC cases from south central China is relatively low and is related to poorer tumor differentiation. RET gene alterations (copy number gain and rearrangement) exist in all RET-positive samples. RET-positive expression is a relatively independent factor in NSCLC patients, which indicates that the RET gene may be a novel target site for personalized treatment of NSCLC. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  7. Serial gene losses and foreign DNA underlie size and sequence variation in the plastid genomes of diatoms.

    Science.gov (United States)

    Ruck, Elizabeth C; Nakov, Teofil; Jansen, Robert K; Theriot, Edward C; Alverson, Andrew J

    2014-03-01

    Photosynthesis by diatoms accounts for roughly one-fifth of global primary production, but despite this, relatively little is known about their plastid genomes. We report the completely sequenced plastid genomes for eight phylogenetically diverse diatoms and show them to be variable in size, gene and foreign sequence content, and gene order. The genomes contain a core set of 122 protein-coding genes, with 15 additional genes exhibiting complex patterns of 1) gene losses at varying phylogenetic scales, 2) functional transfers to the nucleus, 3) gene duplication, divergence, and differential retention of paralogs, and 4) acquisitions of putatively functional recombinase genes from resident plasmids. The newly sequenced genomes also contain several previously unreported genes, highlighting how poorly characterized diatom plastid genomes are overall. Genome size variation reflects major expansions of the inverted repeat region in some cases but, more commonly, large-scale expansions of intergenic regions, many of which contain unique open reading frames of likely foreign origin. Although many gene clusters are conserved across species, rearrangements appear to be frequent in most lineages.

  8. Aging induced loss of stemness with concomitant gain of myogenic properties of a pure population of CD34(+)/CD45(-) muscle derived stem cells.

    Science.gov (United States)

    Bose, Bipasha; Shenoy, P Sudheer

    2016-01-01

    Aging is accompanied by the functional decline of cells, tissues, and organs, as well as, a striking increase in susceptibility to a wide range of diseases. Within a tissue, both differentiated cells and adult stem cells are susceptible to intrinsic and extrinsic changes while aging. Muscle derived stem cells (MDSCs) are tissue specific stem cells which have been studied well for their multipotential nature. Although there are reports relating to diminished function and regenerative capacity of aged MDSCs as compared to their young counterparts, not much has been reported relating to the concomitant gain in unipotent nature of aged MDSCs. In this study, we report an inverse correlation between aging and expression of adult/mesenchymal stem cell markers and a direct correlation between aging and myogenecity in MDSCs. Aged MDSCs were able to generate a greater number of dystrophin positive myofibres, as compared to, the young MDSCs when transplanted in muscle of dystrophic mice. Our data, therefore, suggests that aging stress adds to the decline in stem cell characteristics with a concomitant increase in unipotency, in terms of, myogenecity of MDSCs. This study, hence, also opens the possibilities of using unipotent aged MDSCs as potential candidates for transplantation in patients with muscular dystrophies. Copyright © 2015. Published by Elsevier Ltd.

  9. Identifying the mechanisms of intron gain: progress and trends

    Directory of Open Access Journals (Sweden)

    Yenerall Paul

    2012-09-01

    Full Text Available Abstract Continued improvements in Next-Generation DNA/RNA sequencing coupled with advances in gene annotation have provided researchers access to a plethora of annotated genomes. Subsequent analyses of orthologous gene structures have identified numerous intron gain and loss events that have occurred both recently and in the very distant past. This research has afforded exceptional insight into the temporal and lineage-specific rates of intron gain and loss among various species throughout evolution. Numerous studies have also attempted to identify the molecular mechanisms of intron gain and loss. However, even after considerable effort, very little is known about these processes. In particular, the mechanism(s of intron gain have proven exceptionally enigmatic and remain topics of considerable debate. Currently, there exists no definitive consensus as to what mechanism(s may generate introns. Because many introns are known to affect gene expression, it is necessary to understand the molecular process(es by which introns may be gained. Here we review the seven most commonly purported mechanisms of intron gain and, when possible, summarize molecular evidence for or against the occurrence of each of these mechanisms. Furthermore, we catalogue indirect evidence that supports the occurrence of each mechanism. Finally, because these proposed mechanisms fail to explain the mechanistic origin of many recently gained introns, we also look at trends that may aid researchers in identifying other potential mechanism(s of intron gain. Reviewers This article was reviewed by Eugene Koonin, Scott Roy (nominated by W. Ford Doolittle, and John Logsdon.

  10. Expression of epigenetic machinery genes is sensitive to maternal obesity and weight loss in relation to fetal growth in mice.

    Science.gov (United States)

    Panchenko, Polina E; Voisin, Sarah; Jouin, Mélanie; Jouneau, Luc; Prézelin, Audrey; Lecoutre, Simon; Breton, Christophe; Jammes, Hélène; Junien, Claudine; Gabory, Anne

    2016-01-01

    Maternal obesity impacts fetal growth and pregnancy outcomes. To counteract the deleterious effects of obesity on fertility and pregnancy issue, preconceptional weight loss is recommended to obese women. Whether this weight loss is beneficial/detrimental for offspring remains poorly explored. Epigenetic mechanisms could be affected by maternal weight changes, perturbing expression of key developmental genes in the placenta or fetus. Our aim was to investigate the effects of chronic maternal obesity on feto-placental growth along with the underlying epigenetic mechanisms. We also tested whether preconceptional weight loss could alleviate these effects. Female mice were fed either a control diet (CTRL group), a high-fat diet (obese (OB) group), or a high-fat diet switched to a control diet 2 months before conception (weight loss (WL) group). At mating, OB females presented an obese phenotype while WL females normalized metabolic parameters. At embryonic day 18.5 (E18.5), fetuses from OB females presented fetal growth restriction (FGR; -13 %) and 28 % of the fetuses were small for gestational age (SGA). Fetuses from WL females normalized this phenotype. The expression of 60 epigenetic machinery genes and 32 metabolic genes was measured in the fetal liver, placental labyrinth, and junctional zone. We revealed 23 genes altered by maternal weight trajectories in at least one of three tissues. The fetal liver and placental labyrinth were more responsive to maternal obesity than junctional zone. One third (18/60) of the epigenetic machinery genes were differentially expressed between at least two maternal groups. Interestingly, genes involved in the histone acetylation pathway were particularly altered (13/18). In OB group, lysine acetyltransferases and Bromodomain-containing protein 2 were upregulated, while most histone deacetylases were downregulated. In WL group, the expression of only a subset of these genes was normalized. This study highlights the high

  11. Balanced conditions or slight mass gain of glaciers in the Lahaul and Spiti region (northern India, Himalaya during the nineties preceded recent mass loss

    Directory of Open Access Journals (Sweden)

    C. Vincent

    2013-04-01

    Full Text Available The volume change of the Chhota Shigri Glacier (India, 32° 20 N, 77° 30' E between 1988 and 2010 has been determined using in situ geodetic measurements. This glacier has experienced only a slight mass loss between 1988 and 2010 (−3.8 ± 2.0 m w.e. (water equivalent corresponding to −0.17 ± 0.09 m w.e. yr−1. Using satellite digital elevation models (DEM differencing and field measurements, we measure a negative mass balance (MB between 1999 and 2010 (−4.8 ± 1.8 m w.e. corresponding to −0.44 ± 0.16 m w.e. yr−1. Thus, we deduce a slightly positive or near-zero MB between 1988 and 1999 (+1.0 ± 2.7 m w.e. corresponding to +0.09 ± 0.24 m w.e. yr−1. Furthermore, satellite DEM differencing reveals that the MB of the Chhota Shigri Glacier (−0.39 ± 0.15 m w.e. yr−1 has been only slightly less negative than the MB of a 2110 km2 glaciarized area in the Lahaul and Spiti region (−0.44 ± 0.09 m w.e. yr−1 during 1999−2011. Hence, we conclude that the ice wastage is probably moderate in this region over the last 22 yr, with near equilibrium conditions during the nineties, and an ice mass loss after. The turning point from balanced to negative mass budget is not known but lies probably in the late nineties and at the latest in 1999. This positive or near-zero MB for Chhota Shigri Glacier (and probably for the surrounding glaciers of the Lahaul and Spiti region during at least part of the 1990s contrasts with a recent compilation of MB data in the Himalayan range that indicated ice wastage since 1975. However, in agreement with this compilation, we confirm more negative balances since the beginning of the 21st century.

  12. Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair.

    Science.gov (United States)

    Reumann, Marie K; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Stephen B; Lukashova, Lyudmila; Boskey, Adele L; Mayer-Kuckuk, Philipp

    2011-10-01

    Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. [Association between variations in protocadherin 15 gene and occupational noise-induced hearing loss].

    Science.gov (United States)

    Xu, X R; Yang, Q Y; Jiao, J; Zheng, Y X; He, L H; Yu, S F; Gu, G Z; Chen, G S; Zhou, W H; Wu, H; Li, Y H; Zhang, H L; Zhang, Z R

    2017-01-06

    Objective: The aim of this study was to investigate whether genetic variability in the protocadherin 15 (PCDH15) gene may correspond with increased susceptibility to noise-induced hearing loss (NIHL) in a Chinese population. Methods: A nested case-control study was performed that followed a cohort of 7 445 noise-exposed workers in a steel factory of Henan province in China from January 1, 2006 to December 31, 2015. In this study, 394 cases who had an average hearing threshold of more than 40 dB (A) in high frequency were defined as the case group, and 721 controls who had an average hearing threshold of less than 35 dB (A) in high frequency and less than 25 dB (A) in speech frequency were defined as the control group. A questionnaire was completed by participants and a physical test was also conducted. SNP genotyping was performed using the SNPscan TM Kit. Multivariate unconditional logistic regression additive models were used to analyze the genotypes in different groups, and the association with NIHL. Unconditional logistic regression models were used to assess the associations between the genotypes and NIHL. Results: The average age of study participants was (40.5±8.3) years and the median number of noise-exposed working years M ( P 25 , P 75 ) was 21.1 (9.1, 27.3). The range of noise exposed levels and the levels of cumulative noise exposure (CNE) were 80.1- 98.8 dB(A) and 86.6- 111.2 dB(A), respectively. Only the distribution of the genotypes (TT/CC/CT) of rs11004085 in the PCDH15 gene showed a significant difference between the case and control groups ( P= 0.049). In the case group, the distribution was 370 (93.9%), 24 (6.1%) and 0; in the control group, the distribution was 694 (96.3%), 23 (3.2%) and 1 (0.1% ). After smoking, drinking, hypertension, height and CNE adjustment, compared with the TT genotype individuals with the CC/CT genotype had a 1.90-fold increased risk of NIHL (95% CI: 1.06- 3.40). After stratified these data by the noise exposure level

  14. Molecular characterization of the porcine JHDM1A gene associated with average daily gain: evaluation its role in skeletal muscle development and growth.

    Science.gov (United States)

    Peng, Yong-Bo; Fan, Bin; Han, Xue-Lei; Xu, Xue-Wen; Rothschild, Max F; Yerle, Martine; Liu, Bang

    2011-10-01

    JHDM1A, a member of the JHDM (JmjC-domain-containing histone demethylase) family, plays an central role in gene silencing, cell cycle, cell growth and cancer development through histone H3K36 demethylation modification. Here reported the cloning, expression, chromosomal location and association analysis with growth traits of porcine JHDM1A gene. Sequence analysis showed that the porcine JHDM1A gene encodes 1,162 amino acids and contains JmjC, F-box, and CXXC zinc-finger domains, which coding sequence and deduced protein shares 91 and 99% similarity with human JHDM1A, respectively. Spatio-Temporal expression analysis indicated that the mRNA expression of porcine JHDM1A had significantly higher levels in the middle (65 days) and later (90 days) period's embryo skeletal muscle than that of 33 days, and showed a ubiquitously expression but with the highest abundance in kidney, lung and liver of an adult pig. Radiation hybrid mapping and the following linkage mapping data indicate that JHDM1A maps to 2p17 region of pig chromosome 2 (SSC2). Allele frequency differences were detected in different pig breeds and an association study was performed with a SNP within 3'UTR. The results showed that there is a tendency for allele frequencies to differ between the fast growth breeds (Yorkshire) and slow growth pig breeds (Qingping pigs, Yushan Black pigs, Erhualian pigs and Dahuabai pigs). The association analysis using a Berkshire × Yorkshire F(2) population indicated that the C224G polymorphism had a highly significant association with average daily gain on test (P muscle shear force and average lactate content in μmol/g. This study provides the first evidence that JHDM1A is differentially expressed in porcine embryonic skeletal muscle and associated with meat growth and quality traits.

  15. Balance between carbon gain and loss under long-term drought: impacts on foliar respiration and photosynthesis in Quercus ilex L

    Science.gov (United States)

    Sperlich, D.; Barbeta, A.; Ogaya, R.; Sabaté, S.; Peñuelas, J.

    2016-01-01

    Terrestrial carbon exchange is a key process of the global carbon cycle consisting of a delicate balance between photosynthetic carbon uptake and respiratory release. We have, however, a limited understanding how long-term decreases in precipitation induced by climate change affect the boundaries and mechanisms of photosynthesis and respiration. We examined the seasonality of photosynthetic and respiratory traits and evaluated the adaptive mechanism of the foliar carbon balance of Quercus ilex L. experiencing a long-term rainfall-exclusion experiment. Day respiration (R d) but not night respiration (R n) was generally higher in the drought treatment leading to an increased R d/R n ratio. The limitation of mesophyll conductance (g m) on photosynthesis was generally stronger than stomatal limitation (g s) in the drought treatment, reflected in a lower g m/g s ratio. The peak photosynthetic activity in the drought treatment occurred in an atypical favourable summer in parallel with lower R d/R n and higher g m/g s ratios. The plant carbon balance was thus strongly improved through: (i) higher photosynthetic rates induced by g m; and (ii) decreased carbon losses mediated by R d. Interestingly, photosynthetic potentials (V c,max, J max, and TPU) were not affected by the drought treatment, suggesting a dampening effect on the biochemical level in the long term. In summary, the trees experiencing a 14-year-long drought treatment adapted through higher plasticity in photosynthetic and respiratory traits, so that eventually the atypical favourable growth period was exploited more efficiently. PMID:26552882

  16. Sediment losses and gains across a gradient of livestock grazing and plant invasion in a cool, semi-arid grassland, Colorado Plateau, USA

    Science.gov (United States)

    Belnap, J.; Reynolds, R.L.; Reheis, M.C.; Phillips, S.L.; Urban, F.E.; Goldstein, H.L.

    2009-01-01

    Large sediment fluxes can have significant impacts on ecosystems. We measured incoming and outgoing sediment across a gradient of soil disturbance (livestock grazing, plowing) and annual plant invasion for 9 years. Our sites included two currently ungrazed sites: one never grazed by livestock and dominated by perennial grasses/well-developed biocrusts and one not grazed since 1974 and dominated by annual weeds with little biocrusts. We used two currently grazed sites: one dominated by annual weeds and the other dominated by perennial plants, both with little biocrusts. Precipitation was highly variable, with years of average, above-average, and extremely low precipitation. During years with average and above-average precipitation, the disturbed sites consistently produced 2.8 times more sediment than the currently undisturbed sites. The never grazed site always produced the least sediment of all the sites. During the drought years, we observed a 5600-fold increase in sediment production from the most disturbed site (dominated by annual grasses, plowed about 50 years previously and currently grazed by livestock) relative to the never grazed site dominated by perennial grasses and well-developed biocrusts, indicating a non-linear, synergistic response to increasing disturbance types and levels. Comparing sediment losses among the sites, biocrusts were most important in predicting site stability, followed by perennial plant cover. Incoming sediment was similar among the sites, and while inputs were up to 9-fold higher at the most heavily disturbed site during drought years compared to average years, the change during the drought conditions was small relative to the large change seen in the sediment outputs. ?? 2009 Elsevier B.V. All rights reserved.

  17. Potential health gains and health losses in eleven EU countries attainable through feasible prevalences of the life-style related risk factors alcohol, BMI, and smoking: a quantitative health impact assessment.

    Science.gov (United States)

    Lhachimi, Stefan K; Nusselder, Wilma J; Smit, Henriette A; Baili, Paolo; Bennett, Kathleen; Fernández, Esteve; Kulik, Margarete C; Lobstein, Tim; Pomerleau, Joceline; Boshuizen, Hendriek C; Mackenbach, Johan P

    2016-08-05

    Influencing the life-style risk-factors alcohol, body mass index (BMI), and smoking is an European Union (EU) wide objective of public health policy. The population-level health effects of these risk-factors depend on population specific characteristics and are difficult to quantify without dynamic population health models. For eleven countries-approx. 80 % of the EU-27 population-we used evidence from the publicly available DYNAMO-HIA data-set. For each country the age- and sex-specific risk-factor prevalence and the incidence, prevalence, and excess mortality of nine chronic diseases are utilized; including the corresponding relative risks linking risk-factor exposure causally to disease incidence and all-cause mortality. Applying the DYNAMO-HIA tool, we dynamically project the country-wise potential health gains and losses using feasible, i.e. observed elsewhere, risk-factor prevalence rates as benchmarks. The effects of the "worst practice", "best practice", and the currently observed risk-factor prevalence on population health are quantified and expected changes in life expectancy, morbidity-free life years, disease cases, and cumulative mortality are reported. Applying the best practice smoking prevalence yields the largest gains in life expectancy with 0.4 years for males and 0.3 year for females (approx. 332,950 and 274,200 deaths postponed, respectively) while the worst practice smoking prevalence also leads to the largest losses with 0.7 years for males and 0.9 year for females (approx. 609,400 and 710,550 lives lost, respectively). Comparing morbidity-free life years, the best practice smoking prevalence shows the highest gains for males with 0.4 years (342,800 less disease cases), whereas for females the best practice BMI prevalence yields the largest gains with 0.7 years (1,075,200 less disease cases). Smoking is still the risk-factor with the largest potential health gains. BMI, however, has comparatively large effects on morbidity. Future

  18. Simultaneous expression of growth hormone releasing hormone (GHRH) and hepatitis B surface antigen/somatostatin (HBsAg/SS) fusion genes in a construct in the skeletal muscle enhances rabbit weight gain.

    Science.gov (United States)

    Dai, Jian-wei; Liu, Song-cai; Hao, Lin-lin; Zhang, Yong-liang; Zhang, Qianqian; Ren, Xiao-hui; Jiang, Qing-yan

    2008-01-01

    Somatostatin (SS) and growth hormone-releasing hormone (GHRH) are synthesized and secreted by the hypothalamus, which can control the synthesis and secretion of the growth hormone (GH) from the hypophysis as well as regulate the GH concentrations in animals and humans. In this article, we describe the regulation of animal growth using plasmid DNA encoding both the GHRH gene and the SS gene fused with the hepatitis B surface antigen (HBsAg) gene. We constructed a series of expression plasmids to express the GHRH and HBsAg-SS fusion genes individually as well as collectively. The fusion gene and GHRH were successfully expressed in Chinese hamster ovary (CHO) cells, as proven by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting tests. Poly D, L-lactide-co-glycolic acid (PLGA) plasmid-encapsulating microspheres were prepared and injected intramuscularly into the leg skeletal muscles of rabbits. Weight gain/day and the levels of insulinlike growth factor-I (IGF-I), SS, and hepatitis B surface antibody (HBsAb) were monitored. During days 30 postinjection, increase in weight gain/day and IGF- I concentration and decrease in SS were observed in treatment groups. From days 15 to 30 postinjection, the weight gain/day significantly increased (P gain/day (P gain/day in rabbits.

  19. Investigating Seven Recently Identified Genes in 100 Iranian Families with Autosomal Recessive Non-syndromic Hearing Loss

    Directory of Open Access Journals (Sweden)

    Reihaneh Alikhani

    2015-09-01

    Full Text Available Objectives: Hearing loss (HL is the most common sensory disorder, and affects 1 in 1000 newborns. About 50% of HL is due to genetics and 70% of them are non-syndromic with a recessive pattern of inheritance. Up to now, more than 50 genes have been detected which are responsible for autosomal recessive non-syndromic hearing loss, (ARNSHL. In  Iran, HL is one of the most common disabilities due to consanguineous marriages. The aim was to investigate the prevalence of three new ARHL genes (GJB4, GJC3, and SLITRK6 reported in neighboring countries among Iranian families with ARNSHL. Methods: One hundred unrelated families with at least two affected siblings in consanguineous marriage, who were negative for GJB2 gene mutations, were selected. By using three STR markers for each gene, homozygosity mapping was performed. Results: Two families showed linkage to GJB4, six families were linked to GJC3 and only one family linked to SLITRK6. The samples of these families who showed linkage were sent for Sanger sequencing to detect the causative mutations. However, after analyzing the sequencing results, no mutation could be detected in either of the families. Molecular analysis for these nine families is underway in order to determine the pathogenic mutations using whole exome sequencing. Discussion: These data demonstrate a very low prevalence of mutation in these three genes (GJB4, GJC3, and SLITRK6 in the Iranian population, since no mutation was detected in our study group of 100 families.

  20. Evolution of C2H2-zinc finger genes and subfamilies in mammals: Species-specific duplication and loss of clusters, genes and effector domains

    Directory of Open Access Journals (Sweden)

    Aubry Muriel

    2008-06-01

    Full Text Available Abstract Background C2H2 zinc finger genes (C2H2-ZNF constitute the largest class of transcription factors in humans and one of the largest gene families in mammals. Often arranged in clusters in the genome, these genes are thought to have undergone a massive expansion in vertebrates, primarily by tandem duplication. However, this view is based on limited datasets restricted to a single chromosome or a specific subset of genes belonging to the large KRAB domain-containing C2H2-ZNF subfamily. Results Here, we present the first comprehensive study of the evolution of the C2H2-ZNF family in mammals. We assembled the complete repertoire of human C2H2-ZNF genes (718 in total, about 70% of which are organized into 81 clusters across all chromosomes. Based on an analysis of their N-terminal effector domains, we identified two new C2H2-ZNF subfamilies encoding genes with a SET or a HOMEO domain. We searched for the syntenic counterparts of the human clusters in other mammals for which complete gene data are available: chimpanzee, mouse, rat and dog. Cross-species comparisons show a large variation in the numbers of C2H2-ZNF genes within homologous mammalian clusters, suggesting differential patterns of evolution. Phylogenetic analysis of selected clusters reveals that the disparity in C2H2-ZNF gene repertoires across mammals not only originates from differential gene duplication but also from gene loss. Further, we discovered variations among orthologs in the number of zinc finger motifs and association of the effector domains, the latter often undergoing sequence degeneration. Combined with phylogenetic studies, physical maps and an analysis of the exon-intron organization of genes from the SCAN and KRAB domains-containing subfamilies, this result suggests that the SCAN subfamily emerged first, followed by the SCAN-KRAB and finally by the KRAB subfamily. Conclusion Our results are in agreement with the "birth and death hypothesis" for the evolution of

  1. Estimates of gains and losses from unmeasured sources and sinks for streamflow and dissolved-solids load in selected reaches of the Arkansas River, southeastern Colorado, 2009-2010

    Science.gov (United States)

    Ortiz, Roderick F.

    2013-01-01

    The Arkansas River is an important municipal water supply and is the primary supply for about 400,000 acres of irrigated land in southeastern Colorado. The suitability of this water for domestic, agricultural, and industrial use is affected by high salinity in parts of the Arkansas River. There is a need to quantify mass loading of dissolved solids (DS) in the Arkansas River. In 2009, the U.S. Geological Survey, in cooperation with the Arkansas River Basin Regional Resource Planning Group and the Colorado Water Conservation Board, began a study to estimate gains and losses from unmeasured sources and sinks for streamflow and DS load in selected reaches of the Arkansas River in southeastern Colorado. Two study reaches were selected for investigation—Canon City to just upstream from Pueblo Reservoir (UARB) and Avondale to Las Animas (LARB). The results from the water-budget analyses indicated that potential areas of unmeasured sources and sinks of streamflow were identifiable in the two study reaches. In the UARB, a substantial volume of water in the subreach from Ark at Canon City to the seasonal gaging station 5 miles downstream (Ark nr Canon City) was unaccounted for by the methodology used in this analysis. The daily gain from unmeasured sources in this subreach was estimated to be about 100 cubic feet per second (ft3/s) or about 20 ft3/s per river mile. Water-budget estimates for the remaining 18 miles of the UARB study reach indicated that gains or losses from unmeasured sources or sinks were within the measurement error as defined for this report. In the LARB, gains and losses from unmeasured sources and sinks were identified in some of the subreaches but the magnitude of the flux generally was small. Unmeasured sources ranging from less than 2 to 3 ft3/s per mile were identified in the river subreaches from Ark at Catlin Dam downstream to Ark at Swink. A streamflow loss was indicated along the subreach from Ark at Nepesta to Ark at Catlin Dam, particularly

  2. Origin and loss of nested LRRTM/α-catenin genes during vertebrate evolution.

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    Pavel Uvarov

    Full Text Available Leucine-rich repeat transmembrane neuronal proteins (LRRTMs form in mammals a family of four postsynaptic adhesion proteins, which have been shown to bind neurexins and heparan sulphate proteoglycan (HSPG glypican on the presynaptic side. Mutations in the genes encoding LRRTMs and neurexins are implicated in human cognitive disorders such as schizophrenia and autism. Our analysis shows that in most jawed vertebrates, lrrtm1, lrrtm2, and lrrtm3 genes are nested on opposite strands of large conserved intron of α-catenin genes ctnna2, ctnna1, and ctnna3, respectively. No lrrtm genes could be found in tunicates or lancelets, while two lrrtm genes are found in the lamprey genome, one of which is adjacent to a single ctnna homolog. Based on similar highly positive net charge of lamprey LRRTMs and the HSPG-binding LRRTM3 and LRRTM4 proteins, we speculate that the ancestral LRRTM might have bound HSPG before acquiring neurexins as binding partners. Our model suggests that lrrtm gene translocated into the large ctnna intron in early vertebrates, and that subsequent duplications resulted in three lrrtm/ctnna gene pairs present in most jawed vertebrates. However, we detected three prominent exceptions: (1 the lrrtm3/ctnna3 gene structure is absent in the ray-finned fish genomes, (2 the genomes of clawed frogs contain ctnna1 but lack the corresponding nested (lrrtm2 gene, and (3 contain lrrtm3 gene in the syntenic position but lack the corresponding host (ctnna3 gene. We identified several other protein-coding nested gene structures of which either the host or the nested gene has presumably been lost in the frog or chicken lineages. Interestingly, majority of these nested genes comprise LRR domains.

  3. Relative frequency of GJB2 gene mutations in autosomal recessive non-syndromic hearing loss (ARNSHL patients in Lorestan population

    Directory of Open Access Journals (Sweden)

    mitra Sapahvand

    2007-01-01

    Conclusion: Unexpectedly, in this research just 17 percent of cases are covered. In this study 510 insCGAA mutation was seen. This is a new mutation which is not reported in other studied populations in the world. Hence, this research shows that – at least in our studied population- the effect of other genes that could cause non-syndromic hearing loss is possible and should be studied

  4. From retroviral vector production to gene transfer: spontaneous inactivation is caused by loss of reverse transcription capacity.

    Science.gov (United States)

    Carmo, M; Panet, A; Carrondo, M J T; Alves, P M; Cruz, P E

    2008-04-01

    The loss of gene transfer capacity in retroviral vectors constitutes a major disadvantage in the development of retroviral vectors for gene therapy applications. In the present work the loss of a vector's capacity to perform reverse transcription was studied as a possible explanation for the low stability of retroviral vectors from the production stage to the target cell gene transfer event. Inactivation studies were performed with murine leukemia virus vectors at 37 degrees C and several residual activities were tested, including viral infectivity, reverse transcription capacity, reverse transcriptase (RT) activities and viral RNA stability. The results indicate a high correlation between loss of infectivity and the capacity of the virus to perform the initial steps of reverse transcription. To further understand the thermosensitivity of the reverse transcription process, the two enzyme activities of RT were investigated. The results indicate that, although the inactivation rate of the DNA polymerase is faster than that of RNase H, the decline of these two enzyme activities is significantly slower than that of reverse transcription. Also, viral RNA stability is not implicated in the loss of the virus capacity to perform reverse transcription as the rate of viral RNA degradation was very slow. Furthermore, it was observed that the amount of viral RNA that entered the cells decreased slowly due to viral inactivation at 37 degrees C. The reverse transcription process is thermolabile and this sensitivity determines the rate of retroviral inactivation. Strategies targeting stabilization of the reverse transcription complex should be pursued to improve the applicability of retroviral vectors in gene therapy studies. (c) 2008 John Wiley & Sons, Ltd.

  5. Associations of Filaggrin Gene Loss-of-Function Variants with Urinary Phthalate Metabolites and Testicular Function in Young Danish Men

    DEFF Research Database (Denmark)

    Joensen, Ulla Nordström; Jørgensen, Niels; Meldgaard, Michael

    2014-01-01

    variants in a cross-sectional study of 861 young men from the general Danish population. METHODS: All men were genotyped for FLG R501X, 2282del4, and R2447X loss-of-function variants. We measured urinary concentrations of 14 phthalate metabolites and serum levels of reproductive hormones. We also evaluated...... not significantly associated with reproductive hormones or semen quality parameters. CONCLUSION: This study provides evidence that carriers of FLG loss-of-function alleles may have higher internal exposure to phthalates, possibly due to increased transepidermal absorption. FLG loss-of-function variants may indicate......BACKGROUND: Filaggrin is an epidermal protein that is crucial for skin barrier function. Up to 10% of Europeans and 5% of Asians carry at least one null allele in the filaggrin gene (FLG). Reduced expression of filaggrin in carriers of the null allele is associated with facilitated transfer...

  6. A birth-season/DRD4 gene interaction predicts weight gain and obesity in women with seasonal affective disorder: A seasonal thrifty phenotype hypothesis.

    Science.gov (United States)

    Levitan, Robert D; Masellis, Mario; Lam, Raymond W; Kaplan, Allan S; Davis, Caroline; Tharmalingam, Subi; Mackenzie, Bronwyn; Basile, Vincenzo S; Kennedy, James L

    2006-11-01

    We have recently described an association between the hypofunctional 7-repeat allele (7R) of the dopamine-4 receptor gene (DRD4), weight gain, and obesity in women with seasonal affective disorder (SAD). In the current study, we examined whether season-of-birth might interact with the 7R allele to influence body weight regulation in SAD. In 182 female probands with SAD, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) with both the exon-3 variable number of tandem repeat polymorphism of DRD4 and season-of-birth as independent variables, and age as the covariate. The overall model was highly significant (F = 4.42, df = 8, 173, p obesity (maximal BMI > 30 kg/m2) was also significantly higher in the 7R/spring birth group (9/17=52.9% vs 32/165=19.4%; chi2 = 9.94, df = 1, p = 0.002; odds ratio = 4.68, 95% CI = 1.67-13.07). These data may reflect a novel gene-environment interaction, during early brain development, which establishes an increased risk for obesity in women with SAD. Although the mechanism for season-of-birth effects in psychiatric disorders is unknown, a characteristic pattern of melatonin exposure during the second and third trimesters may be of particular relevance in this study population. We speculate that these data may reflect the vestigial expression of a seasonal thrifty phenotype that contributed to the positive selection of the 7R allele over the past 40,000 years.

  7. Effect of constitutive inactivation of the myostatin gene on the gain in muscle strength during postnatal growth in two murine models.

    Science.gov (United States)

    Stantzou, Amalia; Ueberschlag-Pitiot, Vanessa; Thomasson, Remi; Furling, Denis; Bonnieu, Anne; Amthor, Helge; Ferry, Arnaud

    2017-02-01

    The effect of constitutive inactivation of the gene encoding myostatin on the gain in muscle performance during postnatal growth has not been well characterized. We analyzed 2 murine myostatin knockout (KO) models, (i) the Lee model (KO Lee ) and (ii) the Grobet model (KO Grobet ), and measured the contraction of tibialis anterior muscle in situ. Absolute maximal isometric force was increased in 6-month-old KO Lee and KO Grobet mice, as compared to wild-type mice. Similarly, absolute maximal power was increased in 6-month-old KO Lee mice. In contrast, specific maximal force (relative maximal force per unit of muscle mass was decreased in all 6-month-old male and female KO mice, except in 6-month-old female KO Grobet mice, whereas specific maximal power was reduced only in male KO Lee mice. Genetic inactivation of myostatin increases maximal force and power, but in return it reduces muscle quality, particularly in male mice. Muscle Nerve 55: 254-261, 2017. © 2016 Wiley Periodicals, Inc.

  8. Alpha-1 antitrypsin gene therapy prevented bone loss in ovariectomy induced osteoporosis mouse model

    Science.gov (United States)

    Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at meno...

  9. Lineage-Specific Loss of Function of Bitter Taste Receptor Genes in Humans and Nonhuman Primates

    OpenAIRE

    Go, Yasuhiro; Satta, Yoko; Takenaka, Osamu; Takahata, Naoyuki

    2005-01-01

    Since the process of becoming dead genes or pseudogenes (pseudogenization) is irreversible and can occur rather rapidly under certain environmental circumstances, it is one plausible determinant for characterizing species specificity. To test this evolutionary hypothesis, we analyzed the tempo and mode of duplication and pseudogenization of bitter taste receptor (T2R) genes in humans as well as in 12 nonhuman primates. The results show that primates have accumulated more pseudogenes than mice...

  10. 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.

  11. Loss of neurogenesis in Hydra leads to compensatory regulation of neurogenic and neurotransmission genes in epithelial cells.

    Science.gov (United States)

    Wenger, Y; Buzgariu, W; Galliot, B

    2016-01-05

    Hydra continuously differentiates a sophisticated nervous system made of mechanosensory cells (nematocytes) and sensory-motor and ganglionic neurons from interstitial stem cells. However, this dynamic adult neurogenesis is dispensable for morphogenesis. Indeed animals depleted of their interstitial stem cells and interstitial progenitors lose their active behaviours but maintain their developmental fitness, and regenerate and bud when force-fed. To characterize the impact of the loss of neurogenesis in Hydra, we first performed transcriptomic profiling at five positions along the body axis. We found neurogenic genes predominantly expressed along the central body column, which contains stem cells and progenitors, and neurotransmission genes predominantly expressed at the extremities, where the nervous system is dense. Next, we performed transcriptomics on animals depleted of their interstitial cells by hydroxyurea, colchicine or heat-shock treatment. By crossing these results with cell-type-specific transcriptomics, we identified epithelial genes up-regulated upon loss of neurogenesis: transcription factors (Dlx, Dlx1, DMBX1/Manacle, Ets1, Gli3, KLF11, LMX1A, ZNF436, Shox1), epitheliopeptides (Arminins, PW peptide), neurosignalling components (CAMK1D, DDCl2, Inx1), ligand-ion channel receptors (CHRNA1, NaC7), G-Protein Coupled Receptors and FMRFRL. Hence epitheliomuscular cells seemingly enhance their sensing ability when neurogenesis is compromised. This unsuspected plasticity might reflect the extended multifunctionality of epithelial-like cells in early eumetazoan evolution. © 2015 The Authors.

  12. 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

  13. Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter DNA hypermethylation.

    Directory of Open Access Journals (Sweden)

    Kevin Pruitt

    2006-03-01

    Full Text Available The class III histone deactylase (HDAC, SIRT1, has cancer relevance because it regulates lifespan in multiple organisms, down-regulates p53 function through deacetylation, and is linked to polycomb gene silencing in Drosophila. However, it has not been reported to mediate heterochromatin formation or heritable silencing for endogenous mammalian genes. Herein, we show that SIRT1 localizes to promoters of several aberrantly silenced tumor suppressor genes (TSGs in which 5' CpG islands are densely hypermethylated, but not to these same promoters in cell lines in which the promoters are not hypermethylated and the genes are expressed. Heretofore, only type I and II HDACs, through deactylation of lysines 9 and 14 of histone H3 (H3-K9 and H3-K14, respectively, had been tied to the above TSG silencing. However, inhibition of these enzymes alone fails to re-activate the genes unless DNA methylation is first inhibited. In contrast, inhibition of SIRT1 by pharmacologic, dominant negative, and siRNA (small interfering RNA-mediated inhibition in breast and colon cancer cells causes increased H4-K16 and H3-K9 acetylation at endogenous promoters and gene re-expression despite full retention of promoter DNA hypermethylation. Furthermore, SIRT1 inhibition affects key phenotypic aspects of cancer cells. We thus have identified a new component of epigenetic TSG silencing that may potentially link some epigenetic changes associated with aging with those found in cancer, and provide new directions for therapeutically targeting these important genes for re-expression.

  14. Dopamine signaling leads to loss of Polycomb repression and aberrant gene activation in experimental parkinsonism.

    Directory of Open Access Journals (Sweden)

    Erik Södersten

    2014-09-01

    Full Text Available Polycomb group (PcG proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state. PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3, catalyzed by the Polycomb repressive complex 2. Here, we present in vivo evidence for a previously unrecognized plasticity of PcG-repressed genes in terminally differentiated brain neurons of parkisonian mice. We show that acute administration of the dopamine precursor, L-DOPA, induces a remarkable increase in H3K27me3S28 phosphorylation. The induction of the H3K27me3S28p histone mark specifically occurs in medium spiny neurons expressing dopamine D1 receptors and is dependent on Msk1 kinase activity and DARPP-32-mediated inhibition of protein phosphatase-1. Chromatin immunoprecipitation (ChIP experiments showed that increased H3K27me3S28p was accompanied by reduced PcG binding to regulatory regions of genes. An analysis of the genome wide distribution of L-DOPA-induced H3K27me3S28 phosphorylation by ChIP sequencing (ChIP-seq in combination with expression analysis by RNA-sequencing (RNA-seq showed that the induction of H3K27me3S28p correlated with increased expression of a subset of PcG repressed genes. We found that induction of H3K27me3S28p persisted during chronic L-DOPA administration to parkisonian mice and correlated with aberrant gene expression. We propose that dopaminergic transmission can activate PcG repressed genes in the adult brain and thereby contribute to long-term maladaptive responses including the motor complications, or dyskinesia, caused by prolonged administration of L-DOPA in Parkinson's disease.

  15. Meclozine promotes longitudinal skeletal growth in transgenic mice with achondroplasia carrying a gain-of-function mutation in the FGFR3 gene.

    Science.gov (United States)

    Matsushita, Masaki; Hasegawa, Satoru; Kitoh, Hiroshi; Mori, Kensaku; Ohkawara, Bisei; Yasoda, Akihiro; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2015-02-01

    Achondroplasia (ACH) is one of the most common skeletal dysplasias causing short stature owing to a gain-of-function mutation in the FGFR3 gene, which encodes the fibroblast growth factor receptor 3. We found that meclozine, an over-the-counter drug for motion sickness, inhibited elevated FGFR3 signaling in chondrocytic cells. To examine the feasibility of meclozine administration in clinical settings, we investigated the effects of meclozine on ACH model mice carrying the heterozygous Fgfr3(ach) transgene. We quantified the effect of meclozine in bone explant cultures employing limb rudiments isolated from developing embryonic tibiae from Fgfr3(ach) mice. We found that meclozine significantly increased the full-length and cartilaginous primordia of embryonic tibiae isolated from Fgfr3(ach) mice. We next analyzed the skeletal phenotypes of growing Fgfr3(ach) mice and wild-type mice with or without meclozine treatment. In Fgfr3(ach) mice, meclozine significantly increased the body length after 2 weeks of administration. At skeletal maturity, the bone lengths including the cranium, radius, ulna, femur, tibia, and vertebrae were significantly longer in meclozine-treated Fgfr3(ach) mice than in untreated Fgfr3(ach) mice. Interestingly, meclozine also increased bone growth in wild-type mice. The plasma concentration of meclozine during treatment was within the range that has been used in clinical settings for motion sickness. Increased longitudinal bone growth in Fgfr3(ach) mice by oral administration of meclozine in a growth period suggests potential clinical feasibility of meclozine for the improvement of short stature in ACH.

  16. Clinical Significance of Umami Taste and Umami-Related Gene Expression Analysis for the Objective Assessment of Umami Taste Loss.

    Science.gov (United States)

    Shoji, Noriaki; Satoh-Ku Riwada, Shizuko; Sasano, Takashi

    2016-01-01

    Loss of umami taste sensation affects quality of life and causes weight loss and health problems, particularly in the elderly. We recently expanded the use of the filter paper disc method to include assessment of umami taste sensitivity, using monosodium glutamate as the test solution. This test showed high diagnostic performance for discriminating between normal taste function and disorders in sensation of the umami taste, according to established cut-off values. The test also revealed: (1) some elderly patients suffered from specific loss of umami taste sensation with preservation of the other four taste sensations (sweet, salty, sour, and bitter); (2) umami taste disorder caused a loss of appetite and decline in weight, resulting in poor health; (3) appetite, weight and overall health improved after appropriate treatment for umami taste disorder. Because of the subjective nature of the test, however, it may not be useful for patients who cannot express which taste sensation is induced by a tastant, such as those with dementia. Most recently, using tissue samples collected from the tongue by scraping the foliate papillae, we showed that evaluation of umami taste receptor gene expression may be clinically useful for the objective genetic diagnosis of umami taste disorders.

  17. A novel missense mutation in the SLC26A4 gene causes nonsyndromic hearing loss and enlarged vestibular aqueduct.

    Science.gov (United States)

    He, Xiaoguang; Peng, Qi; Li, Siping; Zhu, Pengyuan; Wu, Chunqiu; Rao, Chunbao; Chang, Jiang; Xie, Mingyu; Zhong, Baimao; Lu, Xiaomei

    2017-04-01

    We aimed to investigate the genetic causes of hearing loss in a Chinese proband with nonsyndromic hearing loss and enlarged vestibular aqueduct syndrome. We conducted clinical and genetic evaluations in a deaf proband and his normal-hearing parents. Multiplex PCR technology combined with Ion Torrent™ next-generation sequencing technology was used to detect the pathogenic mutations. As a control, a group of 1500 previously studied healthy newborns from the same ethnic background were subjected to deafness gene screening using the same method as in our previous study. The proband harbored two mutations in the SLC26A4 gene in the form of compound heterozygosity. He was found to be heterozygous for a novel mutation named c.1742 G > T (p.Arg581Met) in exon 13 and for the known mutation c.589 G > A (p.Gly197Arg). These variants were carried in the heterozygous state by the parents and therefore co-segregated with the genetic disease. The c.1742 G > T (p.Arg581Met) mutation was absent in 1500 healthy newborns. Protein alignment indicated high evolutionary conservation of the p.R581 residue, and this mutation was predicted by PolyPhen-2 and other online tools to be damaging. This study demonstrates that the novel mutation c.1742 G > T (p.Arg581Met) in compound heterozygosity with c.589 G > A in the SLC26A4 gene is the main cause of deafness in a family clinically diagnosed with enlarged vestibular aqueduct (EVA). Our study will provide a basic foundation for further investigations to elucidate the SLC26A4-related mechanisms of hearing loss. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Partial loss of heterozygosity events at the mutated gene in tumors from MLH1/MSH2 large genomic rearrangement carriers

    International Nuclear Information System (INIS)

    Zavodna, Katarina; Krivulcik, Tomas; Bujalkova, Maria Gerykova; Slamka, Tomas; Martinicky, David; Ilencikova, Denisa; Bartosova, Zdena

    2009-01-01

    Depending on the population studied, large genomic rearrangements (LGRs) of the mismatch repair (MMR) genes constitute various proportions of the germline mutations that predispose to hereditary non-polyposis colorectal cancer (HNPCC). It has been reported that loss of heterozygosity (LOH) at the LGR region occurs through a gene conversion mechanism in tumors from MLH1/MSH2 deletion carriers; however, the converted tracts were delineated only by extragenic microsatellite markers. We sought to determine the frequency of LGRs in Slovak HNPCC patients and to study LOH in tumors from LGR carriers at the LGR region, as well as at other heterozygous markers within the gene to more precisely define conversion tracts. The main MMR genes responsible for HNPCC, MLH1, MSH2, MSH6, and PMS2, were analyzed by MLPA (multiplex ligation-dependent probe amplification) in a total of 37 unrelated HNPCC-suspected patients whose MLH1/MSH2 genes gave negative results in previous sequencing experiments. An LOH study was performed on six tumors from LGR carriers by combining MLPA to assess LOH at LGR regions and sequencing to examine LOH at 28 SNP markers from the MLH1 and MSH2 genes. We found six rearrangements in the MSH2 gene (five deletions and dup5-6), and one aberration in the MLH1 gene (del5-6). The MSH2 deletions were of three types (del1, del1-3, del1-7). We detected LOH at the LGR region in the single MLH1 case, which was determined in a previous study to be LOH-negative in the intragenic D3S1611 marker. Three tumors displayed LOH of at least one SNP marker, including two cases that were LOH-negative at the LGR region. LGRs accounted for 25% of germline MMR mutations identified in 28 Slovakian HNPCC families. A high frequency of LGRs among the MSH2 mutations provides a rationale for a MLPA screening of the Slovakian HNPCC families prior scanning by DNA sequencing. LOH at part of the informative loci confined to the MLH1 or MSH2 gene (heterozygous LGR region, SNP, or

  19. [Association between single nucleotide polymorphismsin human heat shock protein 70 gene and susceptibility to noise-induced hearing loss].

    Science.gov (United States)

    Li, Y H; Chen, G S; Jiao, J; Zhou, W H; Wu, H; Gu, G Z; Zhang, H L; Zheng, Y X; Yu, S F

    2016-12-20

    Objective: To investigate the association between the single nucleotide polymorphisms (SNPs) at rs1043618, rs2075800, and rs2763979 in human heat shock protein 70 (HSP70) gene and susceptibility to noise - induced hearing loss (NIHL) . Methods: A case-control study was performed, and 5 934 workers exposed to noise in an iron and steel plant in Henan, China, who underwent physical examination from 2006 to 2015, were enrolled as study subjects. According to the criteria of binaural average high - frequency (3000, 4000, and 6000 Hz) hearing threshold≥40 dB (HL) and monauralaverage speech - frequency (500, 1000, 2000 Hz) hearing threshold≥26 dB (HL) on the basis of binauralhigh frequency loss measured by pure tone audiometry, as well as the exclusion of NIHL, a total of 286 workers were enrolled as hearing loss group; after the adjustment for sex, type of work, age (difference≤5 years) , and working years of noise exposure (difference ≤2 years) , 286 workers were enrolled as control group. A 2 ml blood genomic DNA extraction kit was used to perform DNA extraction for the peripheral blood samples, and a multiple SNP typing kit was used to determine the genotypes at the three loci in 572 samples. The association between the SNPs at the three loci and susceptibility to NIHL was analyzed. Results: In all workers, the equivalent sound level ( L (Aeq)) of noise was 75.0 ~ 96.8 dB (A) . The hearing loss group had a significantly higher binauralhigh - frequencyhearing threshold than the control group ( t =56.908, P 0.05) . After the adjustment for confounding factors including smoking and drinking, haplotype CCT was associated with the susceptibility to NIHL ( OR =1.425, 95% CI 1.035 - 1.961) . Conclusion: TT genotype at rs2763979 of HSP70 gene and haplotype CCT are risk factors for NIHL.

  20. TEC family kinases in health and disease--loss-of-function of BTK and ITK and the gain-of-function fusions ITK-SYK and BTK-SYK.

    Science.gov (United States)

    Hussain, Alamdar; Yu, Liang; Faryal, Rani; Mohammad, Dara K; Mohamed, Abdalla J; Smith, C I Edvard

    2011-06-01

    The TEC family is ancient and constitutes the second largest family of cytoplasmic tyrosine kinases. In 1993, loss-of-function mutations in the BTK gene were reported as the cause of X-linked agammaglobulinemia. Of all the existing 90 tyrosine kinases in humans, Bruton's tyrosine kinase (BTK) is the kinase for which most mutations have been identified. These experiments of nature collectively provide a form of mutation scanning with direct implications for the several hundred endogenous signaling proteins carrying domains also found in BTK. In 2009, an inactivating mutation in the ITK gene was shown to cause susceptibility to lethal Epstein-Barr virus infection. Both kinases represent interesting targets for inhibition: in the case of BTK, as an immunosuppressant, whereas there is evidence that the inhibition of inducible T-cell kinase (ITK) could influence the infectivity of HIV and also have anti-inflammatory activity. Since 2006, several patients carrying a fusion protein, originating from a translocation joining genes encoding the kinases ITK and spleen tyrosine kinase (SYK), have been shown to develop T-cell lymphoma. We review these disease processes and also describe the role of the N-terminal pleckstrin homology-Tec homology (PH-TH) domain doublet of BTK and ITK in the downstream intracellular signaling of such fusion proteins. © 2011 The Authors Journal compilation © 2011 FEBS.

  1. 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 (pbirth 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.

  2. Loss of Cardioprotective Effects at theADAMTS7Locus as a Result of Gene-Smoking Interactions.

    Science.gov (United States)

    Saleheen, Danish; Zhao, Wei; Young, Robin; Nelson, Christopher P; Ho, WeangKee; Ferguson, Jane F; Rasheed, Asif; Ou, Kristy; Nurnberg, Sylvia T; Bauer, Robert C; Goel, Anuj; Do, Ron; Stewart, Alexandre F R; Hartiala, Jaana; Zhang, Weihua; Thorleifsson, Gudmar; Strawbridge, Rona J; Sinisalo, Juha; Kanoni, Stavroula; Sedaghat, Sanaz; Marouli, Eirini; Kristiansson, Kati; Hua Zhao, Jing; Scott, Robert; Gauguier, Dominique; Shah, Svati H; Smith, Albert Vernon; van Zuydam, Natalie; Cox, Amanda J; Willenborg, Christina; Kessler, Thorsten; Zeng, Lingyao; Province, Michael A; Ganna, Andrea; Lind, Lars; Pedersen, Nancy L; White, Charles C; Joensuu, Anni; Edi Kleber, Marcus; Hall, Alistair S; März, Winfried; Salomaa, Veikko; O'Donnell, Christopher; Ingelsson, Erik; Feitosa, Mary F; Erdmann, Jeanette; Bowden, Donald W; Palmer, Colin N A; Gudnason, Vilmundur; Faire, Ulf De; Zalloua, Pierre; Wareham, Nicholas; Thompson, John R; Kuulasmaa, Kari; Dedoussis, George; Perola, Markus; Dehghan, Abbas; Chambers, John C; Kooner, Jaspal; Allayee, Hooman; Deloukas, Panos; McPherson, Ruth; Stefansson, Kari; Schunkert, Heribert; Kathiresan, Sekar; Farrall, Martin; Marcel Frossard, Philippe; Rader, Daniel J; Samani, Nilesh J; Reilly, Muredach P

    2017-06-13

    Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with genotypes that have been shown to associate with CHD risk. We analyzed data on 60 919 CHD cases and 80 243 controls from 29 studies for gene-smoking interactions for genetic variants at 45 loci previously reported to be associated with CHD risk. We also studied 5 loci associated with smoking behavior. Study-specific gene-smoking interaction effects were calculated and pooled using fixed-effects meta-analyses. Interaction analyses were declared to be significant at a P value of smoking interaction for a variant upstream of the ADAMTS7 gene. Every T allele of rs7178051 was associated with lower CHD risk by 12% in never-smokers ( P =1.3×10 -16 ) in comparison with 5% in ever-smokers ( P =2.5×10 -4 ), translating to a 60% loss of CHD protection conferred by this allelic variation in people who smoked tobacco (interaction P value=8.7×10 -5 ). The protective T allele at rs7178051 was also associated with reduced ADAMTS7 expression in human aortic endothelial cells and lymphoblastoid cell lines. Exposure of human coronary artery smooth muscle cells to cigarette smoke extract led to induction of ADAMTS7. CONCLUSIONS: Allelic variation at rs7178051 that associates with reduced ADAMTS7 expression confers stronger CHD protection in never-smokers than in ever-smokers. Increased vascular ADAMTS7 expression may contribute to the loss of CHD protection in smokers. © 2017 American Heart Association, Inc.

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

    Science.gov (United States)

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

    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...

  4. Loss of hMSH2 gene expression correlates with improved survival in ...

    Indian Academy of Sciences (India)

    Introduction. A mismatch repair gene hMSH2 (human mutS homolog 2) is involved in the correction of mispairing during replication, and its mutation is associated with both microsatellite insta- bility and hereditary colorectal cancer. We have also evalu- ated its involvement in sporadic colorectal cancer tumorige- nesis.

  5. High CpG island methylation ofp16 gene and loss of p16 protein ...

    Indian Academy of Sciences (India)

    Navya

    Curr Opin Immunol 21, 431-439.Majid,. S., Kikuno, N., Nelles, J., Noonan, E., Tanaka, Y., Kawamoto, K., et al. 2008 Genistein induces the. p21WAF1/CIP1 and p16INK4a tumor suppressor genes in prostate cancer cells by epigenetic mechanisms.

  6. High CpG island methylation of p16 gene and loss of p16 protein ...

    Indian Academy of Sciences (India)

    SI-JU GAO

    proposed for cell therapy based on interventions in heart fail- ure, and HFC senescence is associated with upregulation of p16 expression (Golubnitschaja et al. 2003; Ball and Levine. 2005). Although, the involvement of CpG island methylation in suppression of p16 gene expression has been discussed in cancer settings ...

  7. Capsule loss or death: the position of mutations among capsule genes sways the destiny of Streptococcus suis.

    Science.gov (United States)

    Lakkitjaroen, Nattakan; Takamatsu, Daisuke; Okura, Masatoshi; Sato, Masumi; Osaki, Makoto; Sekizaki, Tsutomu

    2014-05-01

    Streptococcus suis, an emerging zoonotic pathogen, is responsible for various diseases in swine and humans. Most S. suis strains from clinical cases possess a group of capsular polysaccharide synthesis (cps) genes and phenotypically express capsular polysaccharides (CPs). Although CPs are considered to be an important virulence factor, our previous study showed that many S. suis isolates from porcine endocarditis lost their CPs, and some of these unencapsulated isolates had large insertions or deletions in the cps gene clusters. We further investigated 25 endocarditis isolates with no obvious genetic alterations to elucidate the unencapsulation mechanisms and found that a single-nucleotide substitution and frameshift mutation in two glycosyltransferase genes (cps2E and cps2F) were the main causes of the capsule loss. Moreover, mutations in the genes involved in side-chain formation (cps2J and cps2N), polymerase (cps2I), and flippase (cps2O) appeared to be lethal; however, these lethal effects were relieved by mutations in the cps2EF region. As unencapsulation and even the death of individual cells have recently been suggested to be beneficial to the pathogenesis of infections, the results of the present study provide a further insight into understanding the biological significance of cps mutations during the course of S. suis infections. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  8. Loss-of-function mutations in chitin responsive genes show increased susceptibility to the powdery mildew pathogen Erysiphe cichoracearum.

    Science.gov (United States)

    Ramonell, Katrina; Berrocal-Lobo, Marta; Koh, Serry; Wan, Jinrong; Edwards, Herb; Stacey, Gary; Somerville, Shauna

    2005-06-01

    Chitin is a major component of fungal walls and insect exoskeletons. Plants produce chitinases upon pathogen attack and chito-oligomers induce defense responses in plants, though the exact mechanism behind this response is unknown. Using the ATH1 Affymetrix microarrays consisting of about 23,000 genes, we examined the response of Arabidopsis (Arabidopsis thaliana) seedlings to chito-octamers and hydrolyzed chitin after 30 min of treatment. The expression patterns elicited by the chito-octamer and hydrolyzed chitin were similar. Microarray expression profiles for several genes were verified via northern analysis or quantitative reverse transcription-PCR. We characterized T-DNA insertion mutants for nine chito-oligomer responsive genes. Three of the mutants were more susceptible to the fungal pathogen, powdery mildew, than wild type as measured by conidiophore production. These three mutants included mutants of genes for two disease resistance-like proteins and a putative E3 ligase. The isolation of loss-of-function mutants with enhanced disease susceptibility provides direct evidence that the chito-octamer is an important oligosaccharide elicitor of plant defenses. Also, this study demonstrates the value of microarray data for identifying new components of uncharacterized signaling pathways.

  9. Gene duplication, loss and selection in the evolution of saxitoxin biosynthesis in alveolates.

    Science.gov (United States)

    Murray, Shauna A; Diwan, Rutuja; Orr, Russell J S; Kohli, Gurjeet S; John, Uwe

    2015-11-01

    A group of marine dinoflagellates (Alveolata, Eukaryota), consisting of ∼10 species of the genus Alexandrium, Gymnodinium catenatum and Pyrodinium bahamense, produce the toxin saxitoxin and its analogues (STX), which can accumulate in shellfish, leading to ecosystem and human health impacts. The genes, sxt, putatively involved in STX biosynthesis, have recently been identified, however, the evolution of these genes within dinoflagellates is not clear. There are two reasons for this: uncertainty over the phylogeny of dinoflagellates; and that the sxt genes of many species of Alexandrium and other dinoflagellate genera are not known. Here, we determined the phylogeny of STX-producing and other dinoflagellates based on a concatenated eight-gene alignment. We determined the presence, diversity and phylogeny of sxtA, domains A1 and A4 and sxtG in 52 strains of Alexandrium, and a further 43 species of dinoflagellates and thirteen other alveolates. We confirmed the presence and high sequence conservation of sxtA, domain A4, in 40 strains (35 Alexandrium, 1 Pyrodinium, 4 Gymnodinium) of 8 species of STX-producing dinoflagellates, and absence from non-producing species. We found three paralogs of sxtA, domain A1, and a widespread distribution of sxtA1 in non-STX producing dinoflagellates, indicating duplication events in the evolution of this gene. One paralog, clade 2, of sxtA1 may be particularly related to STX biosynthesis. Similarly, sxtG appears to be generally restricted to STX-producing species, while three amidinotransferase gene paralogs were found in dinoflagellates. We investigated the role of positive (diversifying) selection following duplication in sxtA1 and sxtG, and found negative selection in clades of sxtG and sxtA1, clade 2, suggesting they were functionally constrained. Significant episodic diversifying selection was found in some strains in clade 3 of sxtA1, a clade that may not be involved in STX biosynthesis, indicating pressure for diversification

  10. Gene Loss and Error-Prone RNA Editing in the Mitochondrion of Perkinsela, an Endosymbiotic Kinetoplastid

    Czech Academy of Sciences Publication Activity Database

    David, Vojtěch; Flegontov, P.; Gerasimov, E.; Tanifuji, G.; Hashimi, Hassan; Logacheva, M.D.; Maruyama, S.; Onodera, N. T.; Gray, M.W.; Archibald, J.M.; Lukeš, Julius

    2015-01-01

    Roč. 6, č. 6 (2015), e01498-15 ISSN 2150-7511 R&D Projects: GA MŠk LH12104; GA ČR GAP305/12/2261 EU Projects: European Commission(XE) 316304; European Commission(XE) 289007 Institutional support: RVO:60077344 Keywords : kinetoplastid * protist * RNA-seq Subject RIV: EB - Gene tics ; Molecular Biology Impact factor: 6.975, year: 2015

  11. High CpG island methylation of p16 gene and loss of p16 protein ...

    Indian Academy of Sciences (India)

    FQ-PCR results derived from RVOT revealed that p16 protein expression was significantly lower in ToF group compared to the control group (0.76 ± 0.21 versus 2.31 ± 0.35; P < 0.001), and p16 gene expression was also markedly decreased in ToF ..... Piepkorn M. 2000 Melanoma genetics: an update with focus on the.

  12. A Randomized, Comparative Pilot Trial of Family-Based Interpersonal Psychotherapy for Reducing Psychosocial Symptoms, Disordered-eating, and Excess Weight Gain in At-Risk Preadolescents with Loss-of-control-eating

    Science.gov (United States)

    Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Matherne, Camden E.; Mehari, Rim D.; Olsen, Cara H.; Marwitz, Shannon E.; Bakalar, Jennifer L.; Ranzenhofer, Lisa M.; Kelly, Nichole R.; Schvey, Natasha A.; Burke, Natasha L.; Cassidy, Omni; Brady, Sheila M.; Dietz, Laura J.; Wilfley, Denise E.; Yanovski, Susan Z.; Yanovski, Jack A.

    2018-01-01

    Objective Preadolescent loss-of-control-eating (LOC-eating) is a risk factor for excess weight gain and binge-eating-disorder. We evaluated feasibility and acceptability of a preventive family-based interpersonal psychotherapy (FB-IPT) program. FB-IPT was compared to family-based health education (FB-HE) to evaluate changes in children’s psychosocial functioning, LOC-eating, and body mass. Method A randomized, controlled pilot trial was conducted with 29 children, 8 to 13 years who had overweight/obesity and LOC-eating. Youth-parent dyads were randomized to 12-week FB-IPT (n=15) or FB-HE (n=14) and evaluated at post-treatment, six-months, and one-year. Changes in child psychosocial functioning, LOC-eating, BMI, and adiposity by dual-energy-X-ray-absorptiometry were assessed. Missing follow-up data were multiply imputed. Results FB-IPT feasibility and acceptability were indicated by good attendance (83%) and perceived benefits to social interactions and eating. Follow-up assessments were completed by 73% FB-IPT and 86% FB-HE at post-treatment, 60% and 64% at six-months, and 47% and 57% at one-year. At post-treatment, children in FB-IPT reported greater decreases in depression (95% CI −7.23, −2.01, Cohen’s d=1.23) and anxiety (95% CI −6.08, −0.70, Cohen’s d=.79) and less odds of LOC-eating (95% CI −3.93, −0.03, Cohen’s d=.38) than FB-HE. At six-months, children in FB-IPT had greater reductions in disordered-eating attitudes (95% CI −0.72, −0.05, Cohen’s d=.66) and at one-year, tended to have greater decreases in depressive symptoms (95% CI −8.82, 0.44, Cohen’s d=.69) than FB-HE. There was no difference in BMI gain between the groups. Discussion Family-based approaches that address interpersonal and emotional underpinnings of LOC-eating in preadolescents with overweight/obesity show preliminary promise, particularly for reducing internalizing symptoms. Whether observed psychological benefits translate into sustained prevention of

  13. A randomized, comparative pilot trial of family-based interpersonal psychotherapy for reducing psychosocial symptoms, disordered-eating, and excess weight gain in at-risk preadolescents with loss-of-control-eating.

    Science.gov (United States)

    Shomaker, Lauren B; Tanofsky-Kraff, Marian; Matherne, Camden E; Mehari, Rim D; Olsen, Cara H; Marwitz, Shannon E; Bakalar, Jennifer L; Ranzenhofer, Lisa M; Kelly, Nichole R; Schvey, Natasha A; Burke, Natasha L; Cassidy, Omni; Brady, Sheila M; Dietz, Laura J; Wilfley, Denise E; Yanovski, Susan Z; Yanovski, Jack A

    2017-09-01

    Preadolescent loss-of-control-eating (LOC-eating) is a risk factor for excess weight gain and binge-eating-disorder. We evaluated feasibility and acceptability of a preventive family-based interpersonal psychotherapy (FB-IPT) program. FB-IPT was compared to family-based health education (FB-HE) to evaluate changes in children's psychosocial functioning, LOC-eating, and body mass. A randomized, controlled pilot trial was conducted with 29 children, 8 to 13 years who had overweight/obesity and LOC-eating. Youth-parent dyads were randomized to 12-week FB-IPT (n = 15) or FB-HE (n = 14) and evaluated at post-treatment, six-months, and one-year. Changes in child psychosocial functioning, LOC-eating, BMI, and adiposity by dual-energy-X-ray-absorptiometry were assessed. Missing follow-up data were multiply imputed. FB-IPT feasibility and acceptability were indicated by good attendance (83%) and perceived benefits to social interactions and eating. Follow-up assessments were completed by 73% FB-IPT and 86% FB-HE at post-treatment, 60% and 64% at six-months, and 47% and 57% at one-year. At post-treatment, children in FB-IPT reported greater decreases in depression (95% CI -7.23, -2.01, Cohen's d = 1.23) and anxiety (95% CI -6.08, -0.70, Cohen's d = .79) and less odds of LOC-eating (95% CI -3.93, -0.03, Cohen's d = .38) than FB-HE. At six-months, children in FB-IPT had greater reductions in disordered-eating attitudes (95% CI -0.72, -0.05, Cohen's d = .66) and at one-year, tended to have greater decreases in depressive symptoms (95% CI -8.82, 0.44, Cohen's d = .69) than FB-HE. There was no difference in BMI gain between the groups. Family-based approaches that address interpersonal and emotional underpinnings of LOC-eating in preadolescents with overweight/obesity show preliminary promise, particularly for reducing internalizing symptoms. Whether observed psychological benefits translate into sustained prevention of disordered-eating or excess

  14. 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...

  15. Duplication and Loss of Function of Genes Encoding RNA Polymerase III Subunit C4 Causes Hybrid Incompatibility in Rice

    Directory of Open Access Journals (Sweden)

    Giao Ngoc Nguyen

    2017-08-01

    Full Text Available Reproductive barriers are commonly observed in both animals and plants, in which they maintain species integrity and contribute to speciation. This report shows that a combination of loss-of-function alleles at two duplicated loci, DUPLICATED GAMETOPHYTIC STERILITY 1 (DGS1 on chromosome 4 and DGS2 on chromosome 7, causes pollen sterility in hybrid progeny derived from an interspecific cross between cultivated rice, Oryza sativa, and an Asian annual wild rice, O. nivara. Male gametes carrying the DGS1 allele from O. nivara (DGS1-nivaras and the DGS2 allele from O. sativa (DGS2-T65s were sterile, but female gametes carrying the same genotype were fertile. We isolated the causal gene, which encodes a protein homologous to DNA-dependent RNA polymerase (RNAP III subunit C4 (RPC4. RPC4 facilitates the transcription of 5S rRNAs and tRNAs. The loss-of-function alleles at DGS1-nivaras and DGS2-T65s were caused by weak or nonexpression of RPC4 and an absence of RPC4, respectively. Phylogenetic analysis demonstrated that gene duplication of RPC4 at DGS1 and DGS2 was a recent event that occurred after divergence of the ancestral population of Oryza from other Poaceae or during diversification of AA-genome species.

  16. Balanced gene losses, duplications and intensive rearrangements led to an unusual regularly sized genome in Arbutus unedo chloroplasts.

    Directory of Open Access Journals (Sweden)

    Fernando Martínez-Alberola

    Full Text Available Completely sequenced plastomes provide a valuable source of information about the duplication, loss, and transfer events of chloroplast genes and phylogenetic data for resolving relationships among major groups of plants. Moreover, they can also be useful for exploiting chloroplast genetic engineering technology. Ericales account for approximately six per cent of eudicot diversity with 11,545 species from which only three complete plastome sequences are currently available. With the aim of increasing the number of ericalean complete plastome sequences, and to open new perspectives in understanding Mediterranean plant adaptations, a genomic study on the basis of the complete chloroplast genome sequencing of Arbutus unedo and an updated phylogenomic analysis of Asteridae was implemented. The chloroplast genome of A. unedo shows extensive rearrangements but a medium size (150,897 nt in comparison to most of angiosperms. A number of remarkable distinct features characterize the plastome of A. unedo: five-fold dismissing of the SSC region in relation to most angiosperms; complete loss or pseudogenization of a number of essential genes; duplication of the ndhH-D operon and its location within the two IRs; presence of large tandem repeats located near highly re-arranged regions and pseudogenes. All these features outline the primary evolutionary split between Ericaceae and other ericalean families. The newly sequenced plastome of A. unedo with the available asterid sequences allowed the resolution of some uncertainties in previous phylogenies of Asteridae.

  17. Polymorphisms in the leptin (rs7799039) gene are associated with an increased risk of excessive gestational weight gain but not with leptin concentration during pregnancy.

    Science.gov (United States)

    Martins, Maisa Cruz; Trujillo, Janet; Farias, Dayana Rodrigues; Kac, Gilberto

    2017-11-01

    Single nucleotide polymorphisms (SNPs) in leptin (LEP) and leptin receptor (LEPR) have been shown to be linked to obesity-related metabolic markers and phenotype. Therefore, we hypothesized that the LEP-rs7799039 and LEPR-rs1137101 SNPs are related to the risk of pre-pregnancy overweight/obesity (body mass index ≥25 kg/m 2 ) as well as to excessive gestational weight gain (GWG) and high concentrations of leptin throughout pregnancy. We investigated a prospective cohort of 147 Brazilian pregnant women through weeks 5-13, 20-26, and 30-36 of gestation. Genetic variants of LEP and LEPR were analyzed by real-time polymerase chain reaction and leptin by enzyme-linked immunosorbent assay. Statistical analyses included multiple linear regression, linear mixed effects, and Poisson regression models. Genotype AA carriers for the LEP-rs7799039 gene maintained a lower body weight throughout pregnancy compared with those with genotypes GG or GA + GG (β AAvsGG = -7.91 kg; 95% confidence interval [CI], -14.21 to -1.61; P = .01; and β AAvsGA + GG = -7.66 kg; 95% CI, -14.07 to -1.25; P = .02). The A allele was significantly associated with an increased risk for excessive GWG (relative risk LEP-GAvsGG , 2.16; 95% CI, 1.23-3.80; and relative risk LEP-AAvsGG , 2.37; 95% CI, 1.04-5.39). Neither the LEP-rs7799039 nor LEPR-rs1137101 SNP was significantly associated with pre-pregnancy overweight/obesity risk and leptin concentrations during pregnancy. In conclusion, our results indicate that women who had the AA genotype for LEP-rs7799039 displayed a lower body weight throughout pregnancy compared with GG or GA + GG carriers. LEP-rs7799039 was significantly associated with an increased risk for excessive GWG, but the results do not support significant associations of the LEP-rs7799039 and LEPR-rs1137101 polymorphisms with pre-pregnancy overweight/obesity risk and leptin concentrations throughout pregnancy. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Analysis of loss of heterozygosity of the tumor suppressor genes p53 and BRCA1 in ovarial carcinomas

    Directory of Open Access Journals (Sweden)

    Luković Ljiljana

    2006-01-01

    Full Text Available Background/aim: Among the genes involved in ovarian carcinogenesis, there has been increased interest in tumor-suppressor genes p53 and BRCA1. Both of the genes make control of cell cycle, DNA repair and apoptosis. The p53 is a "genome guardian" inactivated in more than 50% of human cancers, while BRCA1 mutations are found mostly in breast and ovarian cancer. The aim of this investigation was to establish the frequency of loss of heterozygosity (LOH in the regions of the genes p53 and BRCA1 in ovarian carcinomas, and to analyze the association of LOH with the disease stage and prognosis. Methods. We analyzed 20 patients with a confirmed diagnosis of epithelilal ovarian carcinoma. DNA for molecular-genetic analysis was extracted from the tumor tissue and blood as normal tissue of each person. Microsatellite markers of the regions of genes p53 and BRCA1 were amplified by PCR method. The determination of allelic status of microsatellites and detection of LOH was performed after PAA gel electroforesis. Results. Both of the analyzed microsatellite markers were informative in 13/20 (65% cases. In the region of gene p53, LOH was established in 4/13 (30.7% tumors. One of them had histological gradus G1, one had gradus G2, and two of them had gradus G3, while all were with the International Federation of Gynecology and Obstetrics (FIGO IIIc stage. In the region of gene BRCA1, LOH was detected in 5/13 (38.5% tumors. Four of them had histological gradus G2, and one had gradus G3, while by the (FIGO classification one was with stage Ib, one was with stage IIIb, while the three were with stage IIIc. LOH in both of the analyzed regions was detected in one tumor (7.7%, with histological gradus G3 and the FIGO IIIc stage. Conclusion. The frequency of LOH in epthelial ovarian carcinomas was 30.7% and 38.5% for p53 and BRCA1 gene regions, respectively. Most of tumors with LOH had histological gradus G2 or G3, and the clinical FIGO stage IIIc, suggesting the

  19. [Analysis of loss of heterozygosity of the tumor suppressor genes p53 and BRCA1 in ovarial carcinomas].

    Science.gov (United States)

    Petrović, Bojana; Perović, Milica; Novaković, Ivana; Atanacković, Jasmina; Popović, Branka; Luković, Ljiljana; Petković, Spasoje

    2006-09-01

    Among the genes involved in ovarian carcinogenesis, there has been increased interest in tumor-suppressor genes p53 and BRCA1. Both of the genes make control of cell cycle, DNA repair and apoptosis. The p53 is a "genome guardian" inactivated in more than 50% of human cancers, while BRCA1 mutations are found mostly in breast and ovarian cancer. The aim of this investigation was to establish the frequency of loss of heterozygosity (LOH) in the regions of the genes p53 and BRCA1 in ovarian carcinomas, and to analyze the association of LOH with the disease stage and prognosis. We analyzed 20 patients with a confirmed diagnosis of epithelilal ovarian carcinoma. DNA for molecular-genetic analysis was extracted from the tumor tissue and blood as normal tissue of each person. Microsatellite markers of the regions of genes p53 and BRCA1 were amplified by PCR method. The determination of allelic status of microsatellites and detection of LOH was performed after PAA gel electroforesis. Both of the analyzed microsatellite markers were informative in 13/20 (65%) cases. In the region of gene p53, LOH was established in 4/13 (30.7%) tumors. One of them had histological gradus G1, one had gradus G2, and two of them had gradus G3, while all were with the International Federation of Gynecology and Obstetrics (FIGO) IIIc stage. In the region of gene BRCA1, LOH was detected in 5/13 (38.5%) tumors. Four of them had histological gradus G2, and one had gradus G3, while by the (FIGO) classification one was with stage Ib, one was with stage IIIb, while the three were with stage IlIc. LOH in both of the analyzed regions was detected in one tumor (7.70), with histological gradus G3 and the FIGO IIIc stage. The frequency of LOH in epthelial ovarian carcinomas was 30.7% and 38.5% for p53 and BRCA1 gene regions, respectively. Most of tumors with LOH had histological gradus G2 or G3, and the clinical FIGO stage IIIc, suggesting the association of this occurrence with a later phase of the disease.

  20. Direct Reprogramming of Spiral Ganglion Non-neuronal Cells into Neurons: Toward Ameliorating Sensorineural Hearing Loss by Gene Therapy

    Directory of Open Access Journals (Sweden)

    Teppei Noda

    2018-02-01

    Full Text Available Primary auditory neurons (PANs play a critical role in hearing by transmitting sound information from the inner ear to the brain. Their progressive degeneration is associated with excessive noise, disease and aging. The loss of PANs leads to permanent hearing impairment since they are incapable of regenerating. Spiral ganglion non-neuronal cells (SGNNCs, comprised mainly of glia, are resident within the modiolus and continue to survive after PAN loss. These attributes make SGNNCs an excellent target for replacing damaged PANs through cellular reprogramming. We used the neurogenic pioneer transcription factor Ascl1 and the auditory neuron differentiation factor NeuroD1 to reprogram SGNNCs into induced neurons (iNs. The overexpression of both Ascl1 and NeuroD1 in vitro generated iNs at high efficiency. Transcriptome analyses revealed that iNs displayed a transcriptome profile resembling that of endogenous PANs, including expression of several key markers of neuronal identity: Tubb3, Map2, Prph, Snap25, and Prox1. Pathway analyses indicated that essential pathways in neuronal growth and maturation were activated in cells upon neuronal induction. Furthermore, iNs extended projections toward cochlear hair cells and cochlear nucleus neurons when cultured with each respective tissue. Taken together, our study demonstrates that PAN-like neurons can be generated from endogenous SGNNCs. This work suggests that gene therapy can be a viable strategy to treat sensorineural hearing loss caused by degeneration of PANs.

  1. Direct Reprogramming of Spiral Ganglion Non-neuronal Cells into Neurons: Toward Ameliorating Sensorineural Hearing Loss by Gene Therapy.

    Science.gov (United States)

    Noda, Teppei; Meas, Steven J; Nogami, Jumpei; Amemiya, Yutaka; Uchi, Ryutaro; Ohkawa, Yasuyuki; Nishimura, Koji; Dabdoub, Alain

    2018-01-01

    Primary auditory neurons (PANs) play a critical role in hearing by transmitting sound information from the inner ear to the brain. Their progressive degeneration is associated with excessive noise, disease and aging. The loss of PANs leads to permanent hearing impairment since they are incapable of regenerating. Spiral ganglion non-neuronal cells (SGNNCs), comprised mainly of glia, are resident within the modiolus and continue to survive after PAN loss. These attributes make SGNNCs an excellent target for replacing damaged PANs through cellular reprogramming. We used the neurogenic pioneer transcription factor Ascl1 and the auditory neuron differentiation factor NeuroD1 to reprogram SGNNCs into induced neurons (iNs). The overexpression of both Ascl1 and NeuroD1 in vitro generated iNs at high efficiency. Transcriptome analyses revealed that iNs displayed a transcriptome profile resembling that of endogenous PANs, including expression of several key markers of neuronal identity: Tubb3, Map2, Prph, Snap25, and Prox1. Pathway analyses indicated that essential pathways in neuronal growth and maturation were activated in cells upon neuronal induction. Furthermore, iNs extended projections toward cochlear hair cells and cochlear nucleus neurons when cultured with each respective tissue. Taken together, our study demonstrates that PAN-like neurons can be generated from endogenous SGNNCs. This work suggests that gene therapy can be a viable strategy to treat sensorineural hearing loss caused by degeneration of PANs.

  2. Identification of Pathogenic Genes of Nonsyndromic Hearing Loss in Uyghur Families Using Massively Parallel DNA Sequencing Technique

    Directory of Open Access Journals (Sweden)

    Yu Chen

    2018-01-01

    Full Text Available We aim to identify the mutations of deafness genes using massively parallel DNA sequencing in the 12 Uyghur families. SNPscan method was used to screen against the 124 sites in the common deafness genes in probands. Subjects with SNPscan negativity were subject to massively parallel DNA sequencing for the sequencing of 97 genes known to be responsible for hearing loss. Eight families (66.7% showed biallelic mutations in probands, including MYO15A mutation (6892C>T in J02 family, 9514C>T/7894G>T in J07 family, and 9514C>T in J16 family, MYO7A mutation (1258A>T in J03 family, TMC1 mutation (773G>A in J09 family and 1247T>G/1312G>A in J11 family, and PCDH15 mutation (4658delT in J08 and J13 families. Six novel types of mutation were identified including 6892C>T, 9514C>T/7894G>T, and 9514C>T in MYO15A gene, 1258A>T in MYO7A, 773G>A in TMC1, and 4658delT in PCDH15. The ratio of nonsense mutation and frameshift mutation was comparatively high. All these indicated that the mutation types reported in this study were rare. In conclusion, rare deafness genes were identified in the Uyghur families using massively parallel DNA sequencing, part of which were suggested to be related to the pathogenesis of the disease.

  3. Gene Network Polymorphism Illuminates Loss and Retention of Novel RNAi Silencing Components in the Cryptococcus Pathogenic Species Complex.

    Directory of Open Access Journals (Sweden)

    Marianna Feretzaki

    2016-03-01

    Full Text Available RNAi is a ubiquitous pathway that serves central functions throughout eukaryotes, including maintenance of genome stability and repression of transposon expression and movement. However, a number of organisms have lost their RNAi pathways, including the model yeast Saccharomyces cerevisiae, the maize pathogen Ustilago maydis, the human pathogen Cryptococcus deuterogattii, and some human parasite pathogens, suggesting there may be adaptive benefits associated with both retention and loss of RNAi. By comparing the RNAi-deficient genome of the Pacific Northwest Outbreak C. deuterogattii strain R265 with the RNAi-proficient genomes of the Cryptococcus pathogenic species complex, we identified a set of conserved genes that were lost in R265 and all other C. deuterogattii isolates examined. Genetic and molecular analyses reveal several of these lost genes play roles in RNAi pathways. Four novel components were examined further. Znf3 (a zinc finger protein and Qip1 (a homolog of N. crassa Qip were found to be essential for RNAi, while Cpr2 (a constitutive pheromone receptor and Fzc28 (a transcription factor are involved in sex-induced but not mitosis-induced silencing. Our results demonstrate that the mitotic and sex-induced RNAi pathways rely on the same core components, but sex-induced silencing may be a more specific, highly induced variant that involves additional specialized or regulatory components. Our studies further illustrate how gene network polymorphisms involving known components of key cellular pathways can inform identification of novel elements and suggest that RNAi loss may have been a core event in the speciation of C. deuterogattii and possibly contributed to its pathogenic trajectory.

  4. MRPS18CP2 alleles and DEFA3 absence as putative chromosome 8p23.1 modifiers of hearing loss due to mtDNA mutation A1555G in the 12S rRNA gene

    Directory of Open Access Journals (Sweden)

    Fischel-Ghodsian Nathan

    2007-12-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA mutations account for at least 5% of cases of postlingual, nonsyndromic hearing impairment. Among them, mutation A1555G is frequently found associated with aminoglycoside-induced and/or nonsyndromic hearing loss in families presenting with extremely variable clinical phenotypes. Biochemical and genetic data have suggested that nuclear background is the main factor involved in modulating the phenotypic expression of mutation A1555G. However, although a major nuclear modifying locus was located on chromosome 8p23.1 and regardless intensive screening of the region, the gene involved has not been identified. Methods With the aim to gain insights into the factors that determine the phenotypic expression of A1555G mutation, we have analysed in detail different genetic and genomic elements on 8p23.1 region (DEFA3 gene absence, CLDN23 gene and MRPS18CP2 pseudogene in a group of 213 A1555G carriers. Results Family based association studies identified a positive association for a polymorphism on MRPS18CP2 and an overrepresentation of DEFA3 gene absence in the deaf group of A1555G carriers. Conclusion Although none of the factors analysed seem to have a major contribution to the phenotype, our findings provide further evidences of the involvement of 8p23.1 region as a modifying locus for A1555G 12S rRNA gene mutation.

  5. Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene.

    Science.gov (United States)

    Oshima, M; Oshima, H; Kitagawa, K; Kobayashi, M; Itakura, C; Taketo, M

    1995-05-09

    Mutations in the APC (adenomatous polyposis coli) gene appear to be responsible for not only familial adenomatous polyposis but also many sporadic cases of gastrointestinal cancers. Using homologous recombination in mouse embryonic stem cells, we constructed mice that contained a mutant gene encoding a product truncated at a 716 (Apc delta 716). Mendelian transmission of the gene caused most homozygous mice to die in utero before day 8 of gestation. The heterozygotes developed multiple polyps throughout the intestinal tract, mostly in the small intestine. The earliest polyps arose multifocally during the third week after birth, and new polyps continued to appear thereafter. Surprisingly, every nascent polyp consisted of a microadenoma covered with a layer of the normal villous epithelium. These microadenomas originated from single crypts by forming abnormal outpockets into the inner (lacteal) side of the neighboring villi. We carefully dissected such microadenomas from nascent polyps by peeling off the normal epithelium and determined their genotype by PCR: all microadenomas had already lost the wild-type Apc allele, whereas the mutant allele remained unchanged. These results indicate that loss of heterozygosity followed by formation of intravillous microadenomas is responsible for polyposis in Apc delta 716 intestinal mucosa. It is therefore unlikely that the truncated product interacts directly with the wild-type protein and causes the microadenomas by a dominant negative mechanism.

  6. Transition to an Aquatic Habitat Permitted the Repeated Loss of the Pleiotropic KLK8 Gene in Mammals.

    Science.gov (United States)

    Hecker, Nikolai; Sharma, Virag; Hiller, Michael

    2017-11-01

    Kallikrein related peptidase 8 (KLK8; also called neuropsin) is a serine protease that plays distinct roles in the skin and hippocampus. In the skin, KLK8 influences keratinocyte proliferation and desquamation, and activates antimicrobial peptides in sweat. In the hippocampus, KLK8 affects memory acquisition. Here, we examined the evolution of KLK8 in mammals and discovered that, out of 70 placental mammals, KLK8 is exclusively lost in three independent fully-aquatic lineages, comprising dolphin, killer whale, minke whale, and manatee. In addition, while the sperm whale has an intact KLK8 reading frame, the gene evolves neutrally in this species. We suggest that the distinct functions of KLK8 likely became obsolete in the aquatic environment, leading to the subsequent loss of KLK8 in several fully-aquatic mammalian lineages. First, the cetacean and manatee skin lacks sweat glands as an adaptation to the aquatic environment, which likely made the epidermal function of KLK8 obsolete. Second, cetaceans and manatees exhibit a proportionally small hippocampus, which may have rendered the hippocampal functions of KLK8 obsolete. Together, our results shed light on the genomic changes that correlate with skin and neuroanatomical differences of aquatic mammals, and show that even pleiotropic genes can be lost during evolution if an environmental change nullifies the need for the different functions of such genes. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  7. Dopamine signaling leads to loss of Polycomb repression and aberrant gene activation in experimental parkinsonism

    DEFF Research Database (Denmark)

    Södersten, Erik; Feyder, Michael; Lerdrup, Mads

    2014-01-01

    was accompanied by reduced PcG binding to regulatory regions of genes. An analysis of the genome wide distribution of L-DOPA-induced H3K27me3S28 phosphorylation by ChIP sequencing (ChIP-seq) in combination with expression analysis by RNA-sequencing (RNA-seq) showed that the induction of H3K27me3S28p correlated....... The induction of the H3K27me3S28p histone mark specifically occurs in medium spiny neurons expressing dopamine D1 receptors and is dependent on Msk1 kinase activity and DARPP-32-mediated inhibition of protein phosphatase-1. Chromatin immunoprecipitation (ChIP) experiments showed that increased H3K27me3S28p...

  8. Age-related hearing loss: Aquaporin 4 gene expression changes in the mouse cochlea and auditory midbrain

    Science.gov (United States)

    Christensen, Nathan; D'Souza, Mary; Zhu, Xiaoxia; Frisina, Robert D.

    2009-01-01

    Presbycusis – age-related hearing loss, is the number one communication disorder, and one of the top three chronic medical conditions of our aged population. Aquaporins, particularly aquaporin 4 (Aqp4), are membrane proteins with important roles in water and ion flux across cell membranes, including cells of the inner ear and pathways of the brain used for hearing. To more fully understand the biological bases of presbycusis, 39 CBA mice, a well-studied animal model of presbycusis, underwent non-invasive hearing testing as a function of sound frequency (auditory brainstem response – ABR thresholds, and distortion-product otoacoustic emission – DPOAE magnitudes), and were clustered into four groups based on age and hearing ability. Aqp4 gene expression, as determined by genechip microarray analysis and quantitative real-time PCR, was compared to the young adult control group in the three older groups: middle aged with good hearing, old age with mild presbycusis, and old age with severe presbycusis. Linear regression and ANOVA showed statistically significant changes in Aqp4 gene expression and ABR and DPOAE hearing status in the cochlea and auditory midbrain – inferior colliculus. Down-regulation in the cochlea was seen, and an initial down-, then up-regulation was discovered for the inferior colliculus Aqp4 expression. It is theorized that these changes in Aqp4 gene expression represent an age-related disruption of ion flux in the fluids of the cochlea that are responsible for ionic gradients underlying sound transduction in cochlear hair cells necessary for hearing. In regard to central auditory processing at the level of the auditory midbrain, aquaporin gene expression changes may affect neurotransmitter cycling involving supporting cells, thus impairing complex sound neural processing with age. PMID:19070604

  9. Tetrapod V1R-like ora genes in an early-diverging ray-finned fish species: the canonical six ora gene repertoire of teleost fish resulted from gene loss in a larger ancestral repertoire.

    Science.gov (United States)

    Zapilko, Veronika; Korsching, Sigrun I

    2016-01-27

    present in the most recent common ancestor of lobe- and ray-finned fish. Thus, the presence of just six canonical ora genes in many teleost species is not the ancestral feature of the ray-finned lineage, but caused by loss of two ancestral genes in teleosts.

  10. Gene structure, phylogeny and expression profile of the sucrose ...

    Indian Academy of Sciences (India)

    2015-09-16

    Bruni et al. 2000). Sucrose is the pri- marymolecule of fat biosynthesis and seed development; and sucrose concentration is limiting ...... 1998 Intron loss and gain during evolution of the catalase gene family in angiosperms.

  11. Deletion of the Developmentally Essential Gene ATR in Adult Mice Leads to Age-Related Phenotypes and Stem Cell Loss

    Science.gov (United States)

    Ruzankina, Yaroslava; Pinzon-Guzman, Carolina; Asare, Amma; Ong, Tony; Pontano, Laura; Cotsarelis, George; Zediak, Valerie P.; Velez, Marielena; Bhandoola, Avinash; Brown, Eric J.

    2010-01-01

    Summary Developmental abnormalities, cancer and premature aging each have been linked to defects in the DNA damage response (DDR). Mutations in the ATR checkpoint regulator cause developmental defects in mice (pre-gastrulation lethality) and humans (Seckel syndrome). Herein we show that eliminating ATR in adult mice leads to defects in tissue homeostasis and the rapid appearance of age-related phenotypes, such as hair graying, alopecia, kyphosis, osteoporosis, thymic involution, fibrosis and other abnormalities. Histological and genetic analyses indicate that ATR deletion causes acute cellular loss in tissues where continuous cell proliferation is required for maintenance. Importantly, thymic involution and alopecia and hair graying in ATR knockout mice were associated with dramatic reductions in tissue-specific stem and progenitor cells and exhaustion of tissue renewal and homeostatic capacity. In aggregate, these studies suggest that reduced regenerative capacity in adults via deletion of a developmentally essential DDR gene is sufficient to cause characteristics of premature aging. PMID:18371340

  12. Shallow gene pools in the high intertidal: extreme loss of genetic diversity in viviparous sea stars (Parvulastra)

    Science.gov (United States)

    Keever, Carson C.; Puritz, Jonathan B.; Addison, Jason A.; Byrne, Maria; Grosberg, Richard K.; Toonen, Robert J.; Hart, Michael W.

    2013-01-01

    We document an extreme example of reproductive trait evolution that affects population genetic structure in sister species of Parvulastra cushion stars from Australia. Self-fertilization by hermaphroditic adults and brood protection of benthic larvae causes strong inbreeding and range-wide genetic poverty. Most samples were fixed for a single allele at nearly all nuclear loci; heterozygotes were extremely rare (0.18%); mitochondrial DNA sequences were more variable, but few populations shared haplotypes in common. Isolation-with-migration models suggest that these patterns are caused by population bottlenecks (relative to ancestral population size) and low gene flow. Loss of genetic diversity and low potential for dispersal between high-intertidal habitats may have dire consequences for extinction risk and potential for future adaptive evolution in response to climate and other selective agents. PMID:23925835

  13. EZH2 expression in gliomas: Correlation with CDKN2A gene deletion/ p16 loss and MIB-1 proliferation index.

    Science.gov (United States)

    Purkait, Suvendu; Sharma, Vikas; Jha, Prerana; Sharma, Mehar Chand; Suri, Vaishali; Suri, Ashish; Sharma, B S; Sarkar, Chitra

    2015-10-01

    Enhancer of zeste homolog 2 (EZH2) mediated down-regulation of CDKN2A/p16 has been observed in cell lines as well as in a few carcinomas. However, there is no study correlating EZH2 expression with CDKN2A/p16 status in gliomas. Hence, the present study was conducted to evaluate EZH2 expression in astrocytic and oligodendroglial tumors and correlate with CDKN2A/p16 status as well as MIB-1 labeling index (LI). Gliomas of all grades (n = 118) were studied using immunohistochemistry to assess EZH2, p16 and MIB-1 LI and fluorescence in situ hybrization to evaluate CDKN2A gene status. EZH2 expression and CDKN2A homozygous deletion (HD) were both significantly more frequent in high-grade gliomas (HGG). Further, strong EZH2 expression (LI ≥ 25%) was significantly more common in HGGs without CDKN2A HD (48.7%; 19/39) as compared to cases with deletion (15.8%; 3/19). Loss of p16 expression was noted in 100% and 51.3% of CDKN2A deleted and non-deleted tumors, respectively. Notably, 80% (16/20) of the CDKN2A non-deleted HGGs with p16 loss had strong EZH2 expression, in contrast to only 15.8% (3/19) in the deleted group. Loss of p16 expression significantly correlated with MIB-1 LI, irrespective of EZH2 status. Thus, this study shows that EZH2 expression correlates with tumor grade in both astrocytic and oligodendroglial tumors and hence can be used as a diagnostic marker to differentiate between low and HGGs. Further, this is the first report demonstrating an inverse correlation of strong EZH2 expression with CDKN2A HD in HGGs. Loss of p16 protein expression is mostly attributable to CDKN2A HD and correlates significantly with MIB-1 LI. Notably, our study for the first time suggests a possible epigenetic mechanism of p16 loss in CDKN2A non-deleted HGGs mediated by strong EZH2 expression. A hypothetical model for control of proliferative activity in low versus HGGs is therefore proposed. © 2015 Japanese Society of Neuropathology.

  14. Honey bee thermal/chemical sensor, AmHsTRPA, reveals neofunctionalization and loss of transient receptor potential channel genes.

    Science.gov (United States)

    Kohno, Keigo; Sokabe, Takaaki; Tominaga, Makoto; Kadowaki, Tatsuhiko

    2010-09-15

    Insects are relatively small heterothermic animals, thus they are highly susceptible to changes in ambient temperature. However, a group of honey bees is able to maintain the brood nest temperature between 32°C and 36°C by either cooling or heating the nest. Nevertheless, how honey bees sense the ambient temperature is not known. We identified a honey bee Hymenoptera-specific transient receptor potential A (HsTRPA) channel (AmHsTRPA), which is activated by heat with an apparent threshold temperature of 34°C and insect antifeedants such as camphor in vitro. AmHsTRPA is expressed in the antennal flagellum, and ablation of the antennal flagella and injection of AmHsTRPA inhibitors impair warmth avoidance of honey bees. Gustatory responses of honey bees to sucrose are suppressed by noxious heat and insect antifeedants, but are relieved in the presence of AmHsTRPA inhibitors. These results suggest that AmHsTRPA may function as a thermal/chemical sensor in vivo. As shown previously, Hymenoptera has lost the ancient chemical sensor TRPA1; however, AmHsTRPA is able to complement the function of Drosophila melanogaster TRPA1. These results demonstrate that HsTRPA, originally arisen by the duplication of Water witch, has acquired thermal- and chemical-responsive properties, which has resulted in the loss of ancient TRPA1. Thus, this is an example of neofunctionalization of the duplicated ion channel gene followed by the loss of the functionally equivalent ancient gene.

  15. Loss or gain of function in NIH3T3 and PC12 cells produced by different mutations in the RET tyrosine kinase domain may explain phenotypic diversity between Hirchsprung disease and MEN 2B

    Energy Technology Data Exchange (ETDEWEB)

    Pasini, B.; Seri, M.; Yin, L. [Laboratorio di Genetica Molecolare, Genova (Italy)] [and others

    1994-09-01

    The RET protooncogene encodes a receptor tyrosine kinase involved in the control differentiation of neural crest derived cells. Point mutations of the RET tyrosine kinase domain were identified among others in 2 distinct genetic disorders, Hirchsprung disease (HSCR) and Multiple Endocrine Neoplasia 2B (MEN 2B). In order to test the biological effect of HSCR and MEN 2B mutations we used a system based on RET-PTC2, a chimeric activated form of the RET protoocogene isolated from a papillary thyroid carcinoma, which shows a detectable transforming activity in NIH3T3 cells and induction of differentiation in PC12 cells. By site-direct mutagenesis we introduced into RET-PTC2 cDNA the mutations at codon 918 (Met{yields}thr, typical of MEN 2B), at codon 765 (Ser{yields}Pro, observed in HSCR) and at codon 897 (Arg{yields}Gln, also observed in HSCR). The former mutation appears to increase the transforming activity of RET-PTC2 in NIH3T3 cells. The latter two mutations abolish the oncogenic activity in NIH3T3 cells as well as its differentiating effect in PC12 cells. These results suggest that RET mutations may cause MEN 2B and HSCR phenotypes through a mechanism of gain or loss of function respectively. Finally, co-transfection experiments of wild-type RET-PTC2 with either HSCR mutation are in progress in order to test the hypothesis of a dominant negative effect in heterozygous state.

  16. 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)

  17. Evolutionary Acquisition and Loss of Saxitoxin Biosynthesis in Dinoflagellates: the Second “Core” Gene, sxtG

    Science.gov (United States)

    Orr, Russell J. S.; Stüken, Anke; Murray, Shauna A.

    2013-01-01

    Saxitoxin and its derivatives are potent neurotoxins produced by several cyanobacteria and dinoflagellate species. SxtA is the initial enzyme in the biosynthesis of saxitoxin. The dinoflagellate full mRNA and partial genomic sequences have previously been characterized, and it appears that sxtA originated in dinoflagellates through a horizontal gene transfer from a bacterium. So far, little is known about the remaining genes involved in this pathway in dinoflagellates. Here we characterize sxtG, an amidinotransferase enzyme gene that putatively encodes the second step in saxitoxin biosynthesis. In this study, the entire sxtG transcripts from Alexandrium fundyense CCMP1719 and Alexandrium minutum CCMP113 were amplified and sequenced. The transcripts contained typical dinoflagellate spliced leader sequences and eukaryotic poly(A) tails. In addition, partial sxtG transcript fragments were amplified from four additional Alexandrium species and Gymnodinium catenatum. The phylogenetic inference of dinoflagellate sxtG, congruent with sxtA, revealed a bacterial origin. However, it is not known if sxtG was acquired independently of sxtA. Amplification and sequencing of the corresponding genomic sxtG region revealed noncanonical introns. These introns show a high interspecies and low intraspecies variance, suggesting multiple independent acquisitions and losses. Unlike sxtA, sxtG was also amplified from Alexandrium species not known to synthesize saxitoxin. However, amplification was not observed for 22 non-saxitoxin-producing dinoflagellate species other than those of the genus Alexandrium or G. catenatum. This result strengthens our hypothesis that saxitoxin synthesis has been secondarily lost in conjunction with sxtA for some descendant species. PMID:23335767

  18. Conditional Loss of Hoxa5 Function Early after Birth Impacts on Expression of Genes with Synaptic Function

    Directory of Open Access Journals (Sweden)

    Benoit Lizen

    2017-11-01

    Full Text Available Hoxa5 is a member of the Hox gene family that plays critical roles in successive steps of the central nervous system formation during embryonic and fetal development. In the mouse, Hoxa5 was recently shown to be expressed in the medulla oblongata and the pons from fetal stages to adulthood. In these territories, Hoxa5 transcripts are enriched in many precerebellar neurons and several nuclei involved in autonomic functions, while the HOXA5 protein is detected mainly in glutamatergic and GABAergic neurons. However, whether HOXA5 is functionally required in these neurons after birth remains unknown. As a first approach to tackle this question, we aimed at determining the molecular programs downstream of the HOXA5 transcription factor in the context of the postnatal brainstem. A comparative transcriptomic analysis was performed in combination with gene expression localization, using a conditional postnatal Hoxa5 loss-of-function mouse model. After inactivation of Hoxa5 at postnatal days (P1–P4, we established the transcriptome of the brainstem from P21 Hoxa5 conditional mutants using RNA-Seq analysis. One major finding was the downregulation of several genes associated with synaptic function in Hoxa5 mutant specimens including different actors involved in glutamatergic synapse, calcium signaling pathway, and GABAergic synapse. Data were confirmed and extended by reverse transcription quantitative polymerase chain reaction analysis, and the expression of several HOXA5 candidate targets was shown to co-localize with Hoxa5 transcripts in precerebellar nuclei. Together, these new results revealed that HOXA5, through the regulation of key actors of the glutamatergic/GABAergic synapses and calcium signaling, might be involved in synaptogenesis, synaptic transmission, and synaptic plasticity of the cortico-ponto-cerebellar circuitry in the postnatal brainstem.

  19. Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem cells carrying allelic fluorescent protein genes

    Directory of Open Access Journals (Sweden)

    Stringer Saundra L

    2006-10-01

    Full Text Available Abstract Background Loss of heterozygosity (LOH contributes to many cancers, but the rate at which these events occur in normal cells of the body is not clear. LOH would be detectable in diverse cell types in the body if this event were to confer an obvious cellular phenotype. Mice that carry two different fluorescent protein genes as alleles of a locus would seem to be a useful tool for addressing this issue because LOH would change a cell's phenotype from dichromatic to monochromatic. In addition, LOH caused by mitotic crossing over might be discernable in tissues because this event produces a pair of neighboring monochromatic cells that are different colors. Results As a step in assessing the utility of this approach, we derived primary embryonic fibroblast populations and embryonic stem cell lines from mice that carried two different fluorescent protein genes as alleles at the chromosome 6 locus, ROSA26. Fluorescence activated cell sorting (FACS showed that the vast majority of cells in each line expressed the two marker proteins at similar levels, and that populations exhibited expression noise similar to that seen in bacteria and yeast. Cells with a monochromatic phenotype were present at frequencies on the order of 10-4 and appeared to be produced at a rate of approximately 10-5 variant cells per mitosis. 45 of 45 stably monochromatic ES cell clones exhibited loss of the expected allele at the ROSA26 locus. More than half of these clones retained heterozygosity at a locus between ROSA26 and the centromere. Other clones exhibited LOH near the centromere, but were disomic for chromosome 6. Conclusion Allelic fluorescent markers allowed LOH at the ROSA26 locus to be detected by FACS. LOH at this locus was usually not accompanied by LOH near the centromere, suggesting that mitotic recombination was the major cause of ROSA26 LOH. Dichromatic mouse embryonic cells provide a novel system for studying genetic/karyotypic stability and factors

  20. 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

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    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.

  1. Common variants in genes related to lipid and energy metabolism are associated with weight loss after an intervention in overweight/obese adolescents

    OpenAIRE

    Moleres, A. (Adriana); Milagro-Yoldi, F.I. (Fermín Ignacio); Marcos, A. (Ascensión); Gonzalez-Zorzano, E. (Eduardo); Campoy, C. (Cristina); Garagorri, J.M. (Jesús Maria); Azcona-San-Julian, M.C. (María Cristina); Martinez, J.A. (José Alfredo); Marti, A. (Amelia); EVASYON

    2014-01-01

    Background: Some SNPs related to lipid and energy metabolism may be implicated not only in the development of obesity and associated comorbidities, but also in the weight loss response after a nutritional intervention. Objective: In this context, the present study analyzed four SNPs located within four genes known to be associated with obesity and other obesity-related complications, and their putative role in a weight-loss intervention in overweight/obese adolescents....

  2. Complete mtDNA sequences of two millipedes suggest a new model for mitochondrial gene rearrangements: Duplication and non-random loss

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    Lavrov, Dennis V.; Boore, Jeffrey L.; Brown, Wesley M.

    2001-11-08

    We determined the complete mtDNA sequences of the millipedes Narceus annularus and Thyropygus sp. (Arthropoda: Diplopoda) and identified in both genomes all 37 genes typical for metazoan mtDNA. The arrangement of these genes is identical in the two millipedes, but differs from that inferred to be ancestral for arthropods by the location of four genes/gene clusters. This novel gene arrangement is unusual for animal mtDNA, in that genes with opposite transcriptional polarities are clustered in the genome and the two clusters are separated by two non-coding regions. The only exception to this pattern is the gene for cysteine tRNA, which is located in the part of the genome that otherwise contains all genes with the opposite transcriptional polarity. We suggest that a mechanism involving complete mtDNA duplication followed by the loss of genes, predetermined by their transcriptional polarity and location in the genome, could generate this gene arrangement from the one ancestral for arthropods. The proposed mechanism has important implications for phylogenetic inferences that are drawn on the basis of gene arrangement comparisons.

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

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    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

  4. DFNB59 Gene Mutation Screening Using PCR-SSCP/HA Technique in Non-syndromic Genetic Hearing Loss in Bushehr Province

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    Fatemeh Azadegan Dehkordi

    2010-09-01

    Full Text Available Background: Hearing impairment (HI is the most prevalent Neurosensory disorder which is heterogenous and can also occur due to environmental causes. The majority of hearing deficiencies are of genetic origin affecting about 60% of the HI cases. A novel gene DFNB59 encodes pejvakin has been recently shown to cause deafness. This study aims to determine the frequency of DFNB59 gene mutations in coding region the gene in Bushehr province. Methods: In this descriptive experimental study, we investigated the presence of DFNB59 gene mutations in Exons (2-7 of the gene in 80 deaf subjects. DNA was extracted using standard phenol –chloroform method. The screening of gene mutations was performed by PCR-SSCP/HA procedure. Finally, the possible mutations were confirmed by direct sequencing. Results: In all, 9 polymorphisms 793C>G were found in 80 non-syndromic, genetic hearing loss subjects studied. However no DFNB59 gene mutation was identified. Conclusion: We conclude that the association of DFNB59 gene mutations with hearing loss is very low in samples studies

  5. Methylenetetrahydrofolate reductase gene A1298C polymorphism and susceptibility to recurrent pregnancy loss: a meta-analysis.

    Science.gov (United States)

    Rai, V

    2014-06-27

    Environmental and genetic factors are thought to be involved in the pathogenesis of recurrent pregnancy loss (RPL)/spontaneous abortions (SA), which include endocrine, anatomical abnormalities within the genital organs, autoimmune diseases and some gene variants. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of the folate/methionine metabolic pathway and it is well established fact that folate deficiency causes pregnancy complications like recurrent pregnancy loss, preeclempsia and birth defects affected pregnancies. MTHFR A1298C polymorphism reduces the enzymatic activity and mimics as folate deficiency. To date, many studies have investigated the association between MTHFR A1298C polymorphism and RPL risk; however, the result is still controversial and inconclusive. The aim of the present study was to address the association of MTHFR A1298C polymorphism with RPL risk by meta—analysis. By searching electronic databases, total seventeen studies were identified for present meta—analysis. Crude odds ratios (OR) with 95 % confidence intervals (CIs) was used to assess the strength of association between A1298C polymorphism and RPL. The results indicate that the A1298C polymorphism is not associated with RPL (ORCvs A = 1.13 ,95 % CI= 0.87—1.46, P = 0.36 ; ORACvs AA = 1.22 ,95 % CI= 0.94— 1.6, P = 0.13; ORCCvsAA =1.35, 95 % CI= 76—2.36, P = 0.30; ORCC+AC vs AA = 1.15, 95 % CI= 88 —1.49, P = 0.29; ORCCvs AC+AA = 1.29, 95 % CI= 76 —2.12, P = 0.34). Further prospective studies were needed to confirm the precise relationship between the MTHFR A1298C polymorphism and RPL.

  6. Streamflow conditions in the Guadalupe River Basin, south-central Texas, water years 1987-2006 - An assessment of streamflow gains and losses and relative contribution of major springs to streamflow

    Science.gov (United States)

    Ockerman, Darwin J.; Slattery, Richard N.

    2008-01-01

    The U.S. Geological Survey, in cooperation with the Edwards Aquifer Authority, assessed available streamflow data in the Guadalupe River Basin to determine streamflow gains and losses and the relative contribution of flow from major springs - Comal Springs, San Marcos Springs, and Hueco Springs - to streamflow in reaches of the Guadalupe River and its tributaries. The assessment is based primarily on long-term (1987-2006) and short-term (January 1999, August 1999, August 2000, and August 2006) streamflow conditions. For each analysis period, the ratio of flow from the major springs (measured at the spring source) to the sum of inflows (measured at the source of inflow to the river system) is computed for reaches of the Comal River and San Marcos River that include springflows from major springs, and for Guadalupe River reaches downstream from Canyon Dam. The ratio of springflow to the sum of inflows to the reach is an estimate of the contribution of flows from major springs to streamflow. For 1987-2006, the ratio of springflow from the major springs to the sum of inflows for the most upstream reach that includes inflow from all three major springs, Guadalupe River - above Comal River to Gonzales, is 27 percent. At the lowermost downstream reach, Guadalupe River - Bloomington to the San Antonio River, the percentage of the sum of inflows attributed to springflow is 18 percent. At that lowermost reach, the ratio of Canyon Lake releases to the sum of inflows was 20 percent. For the short-term periods August 2000 and August 2006 (periods of relatively low flow), springflow in the reach Guadalupe River - above Comal River to Gonzales accounted for 77 and 78 percent, respectively, of the sum of inflows in that reach. At the lowermost reach Guadalupe River - Bloomington to San Antonio River, springflow was 52 and 53 percent of the sum of inflows, respectively, during August 2000 and August 2006 (compared with 18 percent during 1987-2006); and during August 2000 and August

  7. Mutation at intronic repeats of the ataxia-telangiectasia mutated (ATM gene and ATM protein loss in primary gastric cancer with microsatellite instability.

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    Hee Sung Kim

    Full Text Available Ataxia-telangiectasia mutated (ATM is a Ser/Thr protein kinase that plays a critical role in DNA damage-induced signaling and initiation of cell cycle checkpoint signaling in response to DNA-damaging agents such as ionizing radiation. We have previously reported the ATM protein loss by immunohistochemistry (IHC in 16% of human gastric cancer (GC tissue. We hypothesized that ATM gene intron mutations targeted by microsatellite instability (MSI cause ATM protein loss in a subset of GC. We studied mononucleotide mutations at the intron of ATM gene, ATM IHC and MSI in GC. Ten human gastric cancer cell lines were studied for the ATM gene mutation at introns, RT-PCR, direct sequencing, and immunohistochemistry. GC tissues of 839 patients were analyzed for MSI and ATM IHC. Among them, 604 cases were analyzed for the ATM mutations at introns preceding exon 6, exon 10 and exon 20. Two human GC cell lines (SNU-1 and -638 showed ATM intron mutations, deletion in RT-PCR and direct sequencing, and ATM protein loss by IHC. The frequencies of ATM mutation, MSI, and ATM protein loss were 12.9% (78/604, 9.2% (81/882 and 15.2% (134/839, respectively. Analysis of associations among MSI, ATM gene mutation, and ATM protein loss revealed highly co-existing ATM gene alterations and MSI. ATM intron mutation and ATM protein loss were detected in 69.3% (52/75 and 53.3% (40/75 of MSI positive GC. MSI positivity and ATM protein loss were present in 68.4% (52/76 and 48.7% (37/76 of GC with ATM intron mutation. ATM mutation and ATM protein loss had characteristics of old age, distal location of tumor, large tumor size, and histologic intestinal type. Our study might be interpreted as that ATM gene mutation at intron might be targeted by MSI and lead to ATM protein loss in a selected group of GC.

  8. Association of genetic variations in FOXO3 gene with susceptibility to noise induced hearing loss in a Chinese population.

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    Haoran Guo

    Full Text Available Noise induced hearing loss (NIHL, a multifactorial disease involving both genetic and environmental factors, is one of the most important occupational health hazards. Nonetheless, the influence of FOXO3 variants on NIHL risk have not been illuminated. This research was conducted to explore the effects of FOXO3 polymorphisms on individual susceptibility to NIHL. A total of 2689 industrial workers from one textile factory of east China were recruited to participate in the current research. Venous blood was collected, questionnaire and pure-tone audiometry (PTA was conducted by specialist physicians. Then, we performed genotyping of three selected SNPs (rs2802292, rs10457180, and rs12206094 in FOXO3 gene in 566 NIHL patients and 566 controls. Subsequently, the main effects of genotype and its interactions were evaluated. Our results revealed that individuals with the G allele of rs2802292, G allele of rs10457180, T allele of rs12206094 (OR = 1.43, 1.43, and 1.31 respectively and the haplotype GAC and others (TGT/GGT/GGC/GAT (rs2802292-rs10457180-rs12206094 (OR = 1.49 and 2.09 respectively are associated with an increased risk of NIHL in a Chinese population. Stratified analysis showed that an increased NIHL risk was found in the subjects who exposed to noise >16 years with rs2802292 GG/GT and rs10457180 AG/GG genotype with an OR of 1.62 and 1.66 respectively. Multifactor dimensionality reduction analysis indicated that rs10457180, rs2802292, and rs12206094 have interactions and are related to increased NIHL risk (OR = 1.53. The genetic polymorphism rs2802292, rs10457180, and rs12206094 within FOXO3 gene are associated with an increased risk of NIHL in a Chinese population and have potential to be biomarkers for noise exposed workers.

  9. Independent evolution of the core and accessory gene sets in the genus Neisseria: insights gained from the genome of Neisseria lactamica isolate 020-06

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    White Brian

    2010-11-01

    Full Text Available Abstract Background The genus Neisseria contains two important yet very different pathogens, N. meningitidis and N. gonorrhoeae, in addition to non-pathogenic species, of which N. lactamica is the best characterized. Genomic comparisons of these three bacteria will provide insights into the mechanisms and evolution of pathogenesis in this group of organisms, which are applicable to understanding these processes more generally. Results Non-pathogenic N. lactamica exhibits very similar population structure and levels of diversity to the meningococcus, whilst gonococci are essentially recent descendents of a single clone. All three species share a common core gene set estimated to comprise around 1190 CDSs, corresponding to about 60% of the genome. However, some of the nucleotide sequence diversity within this core genome is particular to each group, indicating that cross-species recombination is rare in this shared core gene set. Other than the meningococcal cps region, which encodes the polysaccharide capsule, relatively few members of the large accessory gene pool are exclusive to one species group, and cross-species recombination within this accessory genome is frequent. Conclusion The three Neisseria species groups represent coherent biological and genetic groupings which appear to be maintained by low rates of inter-species horizontal genetic exchange within the core genome. There is extensive evidence for exchange among positively selected genes and the accessory genome and some evidence of hitch-hiking of housekeeping genes with other loci. It is not possible to define a 'pathogenome' for this group of organisms and the disease causing phenotypes are therefore likely to be complex, polygenic, and different among the various disease-associated phenotypes observed.

  10. Molecular decay of the tooth gene Enamelin (ENAM mirrors the loss of enamel in the fossil record of placental mammals.

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    Robert W Meredith

    2009-09-01

    Full Text Available Vestigial structures occur at both the anatomical and molecular levels, but studies documenting the co-occurrence of morphological degeneration in the fossil record and molecular decay in the genome are rare. Here, we use morphology, the fossil record, and phylogenetics to predict the occurrence of "molecular fossils" of the enamelin (ENAM gene in four different orders of placental mammals (Tubulidentata, Pholidota, Cetacea, Xenarthra with toothless and/or enamelless taxa. Our results support the "molecular fossil" hypothesis and demonstrate the occurrence of frameshift mutations and/or stop codons in all toothless and enamelless taxa. We then use a novel method based on selection intensity estimates for codons (omega to calculate the timing of iterated enamel loss in the fossil record of aardvarks and pangolins, and further show that the molecular evolutionary history of ENAM predicts the occurrence of enamel in basal representatives of Xenarthra (sloths, anteaters, armadillos even though frameshift mutations are ubiquitous in ENAM sequences of living xenarthrans. The molecular decay of ENAM parallels the morphological degeneration of enamel in the fossil record of placental mammals and provides manifest evidence for the predictive power of Darwin's theory.

  11. The Ter Mutation In The Dead End Gene Causes Germ Cell Loss And Testicular Germ Cell Tumours

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    Youngren, Kirsten K.; Coveney, Douglas; Peng, Xiaoning; Bhattacharya, Chitralekha; Schmidt, Laura S.; Nickerson, Michael L.; Lamb, Bruce T.; Deng Jian Min; Behringer, Richard R.; Capel, Blanche; Rubin, Edward M.; Nadeau, Joseph H.; Matin, Angabin

    2005-01-01

    In mice, the Ter mutation causes primordial germ cell (PGC) loss in all genetic backgrounds1. Ter is also a potent modifier of spontaneous testicular germ cell tumour (TGCT) susceptibility in the 129 family of inbred strains, and markedly increases TGCT incidence in 129-Ter/Ter males2 4. In 129-Ter/Ter mice, some of the remaining PGCs transform into undifferentiated pluripotent embryonal carcinoma cells2 6, and after birth differentiate into various cells and tissues that compose TGCTs. Here, we report the positional cloning of Ter, revealing a point mutation that introduces a termination codon in the mouse orthologue (Dnd1) of the zebrafish dead end (dnd) gene. PGC deficiency is corrected both with bacterial artificial chromosomes that contain Dnd1 and with a Dnd1-encoding transgene. Dnd1 is expressed in fetal gonads during the critical period when TGCTs originate. DND1 has an RNA recognition motif and is most similar to the apobec complementation factor, a component of the cytidine t o uridine RNA-editing complex. These results suggest that Ter may adversely affect essential aspects of RNA biology during PGC development. DND1 is the first protein known to have an RNA recognition motif directly implicated as a heritable cause of spontaneous tumorigenesis. TGCT development in the 129-Ter mouse strain models paediatric TGCT in humans. This work will have important implications for our understanding of the genetic control of TGCT pathogenesis and PGC biology.

  12. A loss of aggressive behaviour and its reinstatement by oestrogen in mice lacking the aromatase gene (Cyp19).

    Science.gov (United States)

    Toda, K; Saibara, T; Okada, T; Onishi, S; Shizuta, Y

    2001-02-01

    Aromatase P450 (CYP19) is an enzyme responsible for conversion of androgens to oestrogens. We generated CYP19 knockout (ArKO) mice by targeting disruption of the CYP19 gene and observed that the ArKO males exhibited a complete loss of aggressive behaviour against intruder mice when examined using a resident-intruder paradigm. The defect in the behaviour of ArKO males was reinstated when the mice received supplements of 17beta-oestradiol soon after birth. Nevertheless, the cumulative duration of the behaviour displayed by the treated mice during the test period of 15 min was 19+/-10 s, which was much shorter than that displayed by wild-type males, 90+/-17 s. When the supplementation was started at 7 days after birth, the defect was not restored. These findings illustrate an absolute requirement for oestrogen during the neonatal stage of a male's life for the development of the potential for aggression observed in adulthood. Furthermore, the present study demonstrates that ArKO males are a useful model in which to investigate the neural mechanisms by which aggressive behaviour is controlled.

  13. Frequency of Thrombophilic Gene Mutations in Patients with Deep Vein Thrombosis and in Women with Recurrent Pregnancy Loss

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    Elgari Mahmoud Mohamed

    2017-05-01

    Full Text Available Thrombophilia may be anticipated by single or combined hereditary defects in encoding genes factor V, Prothrombin, and MTHFR. The aim of this study was to determine the prevalence and associated risks of V Leiden (G1691A, Prothrombin (G20210A, and MTHFR (C677T mutations in Saudi women with Deep Vein Thrombosis (DVT and women with recurrent pregnancy loss (RPL. Protein C and protein S activity were measured to determine combined effects, if any. We examined 60 women with a history of DVT and 60 with RPL, extracted DNA from EDTA blood and determined three mutations by using multiplex PCR reactions followed by Strip Assay KIT. Pro C Global assay was used to determine the cutoff value [PCATNR = 0.80]. Protein C/S chromogenic assay was used to estimate protein C and S percentages. Frequency of Factor V Leiden G/A genotype in patients with DVT 7 (11.6% had a significant association for DVT χ2 (OR = 5.1, P = 0.03. In women with RPL the three mutations did not show any significant association, levels of Protein C, protein S and PCAT-NR in patient groups not different from controls (P > 0.05. In conclusion, we recommend expanding on these data to provide larger-scale studies.

  14. Targeted disruption of the PME-1 gene causes loss of demethylated PP2A and perinatal lethality in mice.

    Science.gov (United States)

    Ortega-Gutiérrez, Silvia; Leung, Donmienne; Ficarro, Scott; Peters, Eric C; Cravatt, Benjamin F

    2008-07-02

    Phosphoprotein phosphatase 2A (PP2A), a major serine-threonine protein phosphatase in eukaryotes, is an oligomeric protein comprised of structural (A) and catalytic (C) subunits to which a variable regulatory subunit (B) can associate. The C subunit contains a methyl ester post-translational modification on its C-terminal leucine residue, which is removed by a specific methylesterase (PME-1). Methylesterification is thought to control the binding of different B subunits to AC dimers, but little is known about its physiological significance in vivo. Here, we show that targeted disruption of the PME-1 gene causes perinatal lethality in mice, a phenotype that correlates with a virtually complete loss of the demethylated form of PP2A in the nervous system and peripheral tissues. Interestingly, PP2A catalytic activity over a peptide substrate was dramatically reduced in PME-1(-/-) tissues, which also displayed alterations in phosphoproteome content. These findings suggest a role for the demethylated form of PP2A in maintenance of enzyme function and phosphorylation networks in vivo.

  15. Targeted disruption of the PME-1 gene causes loss of demethylated PP2A and perinatal lethality in mice.

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    Silvia Ortega-Gutiérrez

    2008-07-01

    Full Text Available Phosphoprotein phosphatase 2A (PP2A, a major serine-threonine protein phosphatase in eukaryotes, is an oligomeric protein comprised of structural (A and catalytic (C subunits to which a variable regulatory subunit (B can associate. The C subunit contains a methyl ester post-translational modification on its C-terminal leucine residue, which is removed by a specific methylesterase (PME-1. Methylesterification is thought to control the binding of different B subunits to AC dimers, but little is known about its physiological significance in vivo.Here, we show that targeted disruption of the PME-1 gene causes perinatal lethality in mice, a phenotype that correlates with a virtually complete loss of the demethylated form of PP2A in the nervous system and peripheral tissues. Interestingly, PP2A catalytic activity over a peptide substrate was dramatically reduced in PME-1(-/- tissues, which also displayed alterations in phosphoproteome content.These findings suggest a role for the demethylated form of PP2A in maintenance of enzyme function and phosphorylation networks in vivo.

  16. A predictive model of the association between gene polymorphism and the risk of noise-induced hearing loss caused by gunfire noise

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    Ben-Chih Yuan

    2012-01-01

    Conclusion: In this study, we found that although loud noise could usually result in hearing damage, the clinical characteristics of hearing loss were irrelevant to gunfire noise. The gene polymorphisms provide predictors for us to evaluate the risk of NIHL prior to gunshot training.

  17. 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.

  18. Controlling noise in plasmonic structures with gai