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Sample records for homeobox gene created

  1. Homeobox gene expression in Brachiopoda

    DEFF Research Database (Denmark)

    Altenburger, Andreas; Martinez, Pedro; Wanninger, Andreas

    2011-01-01

    The molecular control that underlies brachiopod ontogeny is largely unknown. In order to contribute to this issue we analyzed the expression pattern of two homeobox containing genes, Not and Cdx, during development of the rhynchonelliform (i.e., articulate) brachiopod Terebratalia transversa....... Not is a homeobox containing gene that regulates the formation of the notochord in chordates, while Cdx (caudal) is a ParaHox gene involved in the formation of posterior tissues of various animal phyla. The T. transversa homolog, TtrNot, is expressed in the ectoderm from the beginning of gastrulation until...... formation. TtrNot expression is absent in unfertilized eggs, in embryos prior to gastrulation, and in settled individuals during and after metamorphosis. Comparison with the expression patterns of Not genes in other metazoan phyla suggests an ancestral role for this gene in gastrulation and germ layer...

  2. Homeobox genes and melatonin synthesis

    DEFF Research Database (Denmark)

    Rohde, Kristian; Møller, Morten; Rath, Martin Fredensborg

    2014-01-01

    Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based indu......Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a c......AMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX......) transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating c...

  3. Homeobox Genes in the Rodent Pineal Gland

    DEFF Research Database (Denmark)

    Rath, Martin Fredensborg; Rohde, Kristian; Klein, David C

    2013-01-01

    The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential...... for normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene expression persists in the pineal gland of the adult brain. Accordingly, in addition to developmental...... functions, homeobox genes appear to be key regulators in postnatal phenotype maintenance in this tissue. In this paper, we review ontogenetic and phylogenetic aspects of pineal development and recent progress in understanding the involvement of homebox genes in rodent pineal development and adult function...

  4. Classification and nomenclature of all human homeobox genes

    Directory of Open Access Journals (Sweden)

    Bruford Elspeth A

    2007-10-01

    Full Text Available Abstract Background The homeobox genes are a large and diverse group of genes, many of which play important roles in the embryonic development of animals. Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development. Despite their importance, the full diversity of human homeobox genes has not previously been described. Results We have identified all homeobox genes and pseudogenes in the euchromatic regions of the human genome, finding many unannotated, incorrectly annotated, unnamed, misnamed or misclassified genes and pseudogenes. We describe 300 human homeobox loci, which we divide into 235 probable functional genes and 65 probable pseudogenes. These totals include 3 genes with partial homeoboxes and 13 pseudogenes that lack homeoboxes but are clearly derived from homeobox genes. These figures exclude the repetitive DUX1 to DUX5 homeobox sequences of which we identified 35 probable pseudogenes, with many more expected in heterochromatic regions. Nomenclature is established for approximately 40 formerly unnamed loci, reflecting their evolutionary relationships to other loci in human and other species, and nomenclature revisions are proposed for around 30 other loci. We use a classification that recognizes 11 homeobox gene 'classes' subdivided into 102 homeobox gene 'families'. Conclusion We have conducted a comprehensive survey of homeobox genes and pseudogenes in the human genome, described many new loci, and revised the classification and nomenclature of homeobox genes. The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass.

  5. Classification and expression analyses of homeobox genes

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 40; Issue 2 ... Articles Volume 40 Issue 2 June 2015 pp 241-255 ... When individual homeobox genes were compared with members of known class or family, we could further classify them into 3 groups, namely, TALE, OTHER and NOVEL classes, but no HOX family was ...

  6. The mammary gland and the homeobox gene Otx1.

    Science.gov (United States)

    Pagani, Ilaria S; Terrinoni, Alessandro; Marenghi, Laura; Zucchi, Ileana; Chiaravalli, Anna M; Serra, Valeria; Rovera, Francesca; Sirchia, Silvia; Dionigi, Gianlorenzo; Miozzo, Monica; Mozzo, Monica; Frattini, Annalisa; Ferrari, Alberta; Capella, Carlo; Pasquali, Francesco; Lo Curto, Francesco; Curto, Francesco L; Albertini, Alberto; Melino, Gerry; Porta, Giovanni

    2010-01-01

    The mammary gland, the unique organ that primarily form at puberty, is an ideal model to study the functions of homeobox (HB) genes in both development and tumorigenesis. HB genes comprise a large family of developmental regulators that have a critical role in cell growth and differentiation. In the normal mammary gland, homeobox genes are involved in ductal formation, epithelial branching, and lobulo-alveolar development by regulating epithelial proliferation and differentiation. The HB genes are controlled in a spatial and temporal manner in both stromal and epithelial cells. They are coordinately regulated by hormones and extracellular matrix, suggesting that many signaling pathways are involved in homeobox gene functions. When homeobox genes are misexpressed in animal models, different defects are displayed in mammary gland development. Aberrant expression of homeobox genes, overexpressed or downregulated, is found in primary carcinomas and in breast cancer. The Otx1 HB gene is a classic regulatory of nervous system development during embryogenesis. Postnatally Otx1 is transcribed in the anterior pituitary gland, where activates transcription of the pituitary hormones, and plays a role in hematopoiesis, enhancing pluripotent cells, and erythroid differentiation. Otx1 can still be detected in mature cells of the erythroid and megacaryocytic lineage. During cyclical development of mammary gland, the Otx1 gene is overexpressed in lactation, confirming a role of this transcription factor in cell differentiation. Recent studies report that Otx1 is overexpressed in breast cancer. Otx1 is expressed during embryogenesis, and it is expressed again during carcinogenesis, implying its possible function in differentiation of neoplastic cells. © 2010 Wiley Periodicals, Inc.

  7. Homeobox genes in the rodent pineal gland: roles in development and phenotype maintenance

    OpenAIRE

    Rath, Martin F.; Rohde, Kristian; Klein, David C.; Møller, Morten

    2012-01-01

    The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential for normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene e...

  8. The Aspergillus flavus homeobox gene, hbx1, is required for development and aflatoxin production

    Science.gov (United States)

    Homeobox proteins are a class of transcription factors that are well conserved in many eukaryotes including fungi. Homeobox proteins regulate the expression of target genes, especially those involved in development. Studies in several filamentous fungi have shown that homeobox genes are required for...

  9. Homeobox genes and melatonin synthesis: regulatory roles of the cone-rod homeobox transcription factor in the rodent pineal gland.

    Science.gov (United States)

    Rohde, Kristian; Møller, Morten; Rath, Martin Fredensborg

    2014-01-01

    Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX) transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating cAMP response element-based circadian melatonin production.

  10. Homeobox Genes and Melatonin Synthesis: Regulatory Roles of the Cone-Rod Homeobox Transcription Factor in the Rodent Pineal Gland

    Directory of Open Access Journals (Sweden)

    Kristian Rohde

    2014-01-01

    Full Text Available Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating cAMP response element-based circadian melatonin production.

  11. Homeobox Genes and Melatonin Synthesis: Regulatory Roles of the Cone-Rod Homeobox Transcription Factor in the Rodent Pineal Gland

    OpenAIRE

    Kristian Rohde; Morten Møller; Martin Fredensborg Rath

    2014-01-01

    Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT) enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processe...

  12. Homeobox genes: a molecular link between development and cancer Genes homeobox: uma relação molecular entre o desenvolvimento e o câncer

    Directory of Open Access Journals (Sweden)

    Fabio Daumas Nunes

    2003-03-01

    Full Text Available Homeobox genes are regulatory genes encoding nuclear proteins that act as transcription factors, regulating aspects of morphogenesis and cell differentiation during normal embryonic development of several animals. Vertebrate homeobox genes can be divided in two subfamilies: clustered, or HOX genes, and nonclustered, or divergent, homeobox genes. During the last decades, several homeobox genes, clustered and nonclustered ones, were identified in normal tissue, in malignant cells, and in different diseases and metabolic alterations. Homeobox genes are involved in the normal teeth development and in familial teeth agenesis. Normal development and cancer have a great deal in common, as both processes involve shifts between cell proliferation and differentiation. The literature is accumulating evidences that homeobox genes play an important role in oncogenesis. Many cancers exhibit expression of or alteration in homeobox genes. Those include leukemias, colon, skin, prostate, breast and ovarian cancers, among others. This review is aimed at introducing readers to some of the homeobox family functions in normal tissues and especially in cancer.Os genes homeobox são genes reguladores que codificam proteínas nucleares as quais atuam como fatores de transcrição, regulando vários aspectos da morfogênese e da diferenciação celular durante o desenvolvimento embrionário normal de diversos animais. Os genes homeobox de vertebrados podem ser subdivididos em duas famílias: os agrupados, ou HOX, e os não agrupados, ou divergentes. Durante as últimas décadas, vários genes homeobox, agrupados e não agrupados, foram identificados em tecidos normais, em células malignas e em diferentes doenças e condições metabólicas. Os genes homeobox estão envolvidos, por exemplo, no desenvolvimento normal do dente e em agenesias dentárias de ocorrência familiar. O desenvolvimento normal e o câncer têm muito em comum, já que ambos envolvem prolifera

  13. Early evolution of the LIM homeobox gene family

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Mansi; Larroux, Claire; Lu, Daniel R; Mohanty, Kareshma; Chapman, Jarrod; Degnan, Bernard M; Rokhsar, Daniel S

    2010-01-01

    LIM homeobox (Lhx) transcription factors are unique to the animal lineage and have patterning roles during embryonic development in flies, nematodes and vertebrates, with a conserved role in specifying neuronal identity. Though genes of this family have been reported in a sponge and a cnidarian, the expression patterns and functions of the Lhx family during development in non-bilaterian phyla are not known. We identified Lhx genes in two cnidarians and a placozoan and report the expression of Lhx genes during embryonic development in Nematostella and the demosponge Amphimedon. Members of the six major LIM homeobox subfamilies are represented in the genomes of the starlet sea anemone, Nematostella vectensis, and the placozoan Trichoplax adhaerens. The hydrozoan cnidarian, Hydra magnipapillata, has retained four of the six Lhx subfamilies, but apparently lost two others. Only three subfamilies are represented in the haplosclerid demosponge Amphimedon queenslandica. A tandem cluster of three Lhx genes of different subfamilies and a gene containing two LIM domains in the genome of T. adhaerens (an animal without any neurons) indicates that Lhx subfamilies were generated by tandem duplication. This tandem cluster in Trichoplax is likely a remnant of the original chromosomal context in which Lhx subfamilies first appeared. Three of the six Trichoplax Lhx genes are expressed in animals in laboratory culture, as are all Lhx genes in Hydra. Expression patterns of Nematostella Lhx genes correlate with neural territories in larval and juvenile polyp stages. In the aneural demosponge, A. queenslandica, the three Lhx genes are expressed widely during development, including in cells that are associated with the larval photosensory ring. The Lhx family expanded and diversified early in animal evolution, with all six subfamilies already diverged prior to the cnidarian-placozoan-bilaterian last common ancestor. In Nematostella, Lhx gene expression is correlated with neural

  14. Early evolution of the LIM homeobox gene family

    Directory of Open Access Journals (Sweden)

    Degnan Bernard M

    2010-01-01

    Full Text Available Abstract Background LIM homeobox (Lhx transcription factors are unique to the animal lineage and have patterning roles during embryonic development in flies, nematodes and vertebrates, with a conserved role in specifying neuronal identity. Though genes of this family have been reported in a sponge and a cnidarian, the expression patterns and functions of the Lhx family during development in non-bilaterian phyla are not known. Results We identified Lhx genes in two cnidarians and a placozoan and report the expression of Lhx genes during embryonic development in Nematostella and the demosponge Amphimedon. Members of the six major LIM homeobox subfamilies are represented in the genomes of the starlet sea anemone, Nematostella vectensis, and the placozoan Trichoplax adhaerens. The hydrozoan cnidarian, Hydra magnipapillata, has retained four of the six Lhx subfamilies, but apparently lost two others. Only three subfamilies are represented in the haplosclerid demosponge Amphimedon queenslandica. A tandem cluster of three Lhx genes of different subfamilies and a gene containing two LIM domains in the genome of T. adhaerens (an animal without any neurons indicates that Lhx subfamilies were generated by tandem duplication. This tandem cluster in Trichoplax is likely a remnant of the original chromosomal context in which Lhx subfamilies first appeared. Three of the six Trichoplax Lhx genes are expressed in animals in laboratory culture, as are all Lhx genes in Hydra. Expression patterns of Nematostella Lhx genes correlate with neural territories in larval and juvenile polyp stages. In the aneural demosponge, A. queenslandica, the three Lhx genes are expressed widely during development, including in cells that are associated with the larval photosensory ring. Conclusions The Lhx family expanded and diversified early in animal evolution, with all six subfamilies already diverged prior to the cnidarian-placozoan-bilaterian last common ancestor. In

  15. Homeobox genes in the rodent pineal gland: roles in development and phenotype maintenance.

    Science.gov (United States)

    Rath, Martin F; Rohde, Kristian; Klein, David C; Møller, Morten

    2013-06-01

    The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential for normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene expression persists in the pineal gland of the adult brain. Accordingly, in addition to developmental functions, homeobox genes appear to be key regulators in postnatal phenotype maintenance in this tissue. In this paper, we review ontogenetic and phylogenetic aspects of pineal development and recent progress in understanding the involvement of homebox genes in rodent pineal development and adult function. A working model is proposed for understanding the sequential action of homeobox genes in controlling development and mature circadian function of the mammalian pinealocyte based on knowledge from detailed developmental and daily gene expression analyses in rats, the pineal phenotypes of homebox gene-deficient mice and studies on development of the retinal photoreceptor; the pinealocyte and retinal photoreceptor share features not seen in other tissues and are likely to have evolved from the same ancestral photodetector cell.

  16. Extensive expression of craniofacial related homeobox genes in canine mammary sarcomas

    NARCIS (Netherlands)

    Wensman, H.; Goransson, H.; Leuchowius, K.J.; Stromberg, S.; Ponten, F.; Isaksson, A.; Rutteman, G.R.|info:eu-repo/dai/nl/074076663; Heldin, N.; Pejler, G.; Hellmen, E.

    2009-01-01

    Extensive expression of craniofacial related homeobox genes in canine mammary sarcomas Journal Breast Cancer Research and Treatment Publisher Springer Netherlands ISSN 0167-6806 (Print) 1573-7217 (Online) Issue Volume 118, Number 2 / November, 2009 Category Preclinical Study DOI

  17. The Homeobox Genes of Caenorhabditis elegans and Insights into Their Spatio-Temporal Expression Dynamics during Embryogenesis

    Science.gov (United States)

    Abou-Zied, Akram M.; Lüppert, Martin; Dethlefsen, Johan; Mukherjee, Krishanu; Tong, Yong Guang; Tang, Lois; Gangishetti, Umesh; Baillie, David L.; Bürglin, Thomas R.

    2015-01-01

    Homeobox genes play crucial roles for the development of multicellular eukaryotes. We have generated a revised list of all homeobox genes for Caenorhabditis elegans and provide a nomenclature for the previously unnamed ones. We show that, out of 103 homeobox genes, 70 are co-orthologous to human homeobox genes. 14 are highly divergent, lacking an obvious ortholog even in other Caenorhabditis species. One of these homeobox genes encodes 12 homeodomains, while three other highly divergent homeobox genes encode a novel type of double homeodomain, termed HOCHOB. To understand how transcription factors regulate cell fate during development, precise spatio-temporal expression data need to be obtained. Using a new imaging framework that we developed, Endrov, we have generated spatio-temporal expression profiles during embryogenesis of over 60 homeobox genes, as well as a number of other developmental control genes using GFP reporters. We used dynamic feedback during recording to automatically adjust the camera exposure time in order to increase the dynamic range beyond the limitations of the camera. We have applied the new framework to examine homeobox gene expression patterns and provide an analysis of these patterns. The methods we developed to analyze and quantify expression data are not only suitable for C. elegans, but can be applied to other model systems or even to tissue culture systems. PMID:26024448

  18. Expression of the organizer specific homeobox gene goosecoid (gsc) in porcine embryos

    NARCIS (Netherlands)

    Meijer, H.A.; Pavert, van de S.A.; Stroband, H.W.J.; Boerjan, M.L.

    2000-01-01

    The homeobox gene goosecoid is one of the first genes expressed in the organizer region of vertebrates and specifies future dorsal regions along the anterior/posterior axis of the embryo. Goosecoid (gsc) expression marks the posterior end of the anterior/posterior axis and might be a good marker to

  19. Homeobox gene expression in acute myeloid leukemia is linked to typical underlying molecular aberrations

    NARCIS (Netherlands)

    K.S. Kramarzova (Karolina Skvarova); K. Fiser (Karel); E. Mejstříková (Ester); K. Rejlova (Katerina); M. Zaliova (Marketa); M.W.J. Fornerod (Maarten); H.A. Drabkin (Harry); M.M. van den Heuvel-Eibrink (Marry); J. Stary (Jan); J. Trka (Jan); J. Starkova (Julia)

    2014-01-01

    markdownabstract__Background:__ Although distinct patterns of homeobox (HOX) gene expression have been described in defined cytogenetic and molecular subsets of patients with acute myeloid leukemia (AML), it is unknown whether these patterns are the direct result of transcriptional alterations or

  20. Ontogenetic expression of the Otx2 and Crx homeobox genes in the retina of the rat

    DEFF Research Database (Denmark)

    Rath, Martin F; Morin, Fabrice; Shi, Qiong

    2007-01-01

    Otx2 and Crx are vertebrate orthologs of the orthodenticle family of homeobox genes, which are involved in retinal development. In this study, the temporal expression patterns of Otx2 and Crx in the rat retina during embryonic and postnatal stages of development were analyzed in detail. This conf...

  1. Reinforcing the Egg-Timer: Recruitment of Novel Lophotrochozoa Homeobox Genes to Early and Late Development in the Pacific Oyster

    Science.gov (United States)

    Paps, Jordi; Xu, Fei; Zhang, Guofan; Holland, Peter W.H.

    2015-01-01

    The metazoan superclade Lophotrochozoa includes mollusks, annelids, and several other animal phyla. It is reasonable to assume that this organismal diversity may be traced, in part, to changes in developmentally important genes, such as the homeobox genes. Although most comparative studies have focussed on ancient homeobox gene families conserved across bilaterians, there are also “novel” homeobox genes that have arisen more recently in evolution, presumably by duplication followed by radical divergence and functional change. We classify 136 homeobox genes in the genome sequence of the Pacific oyster, Crassostrea gigas. The genome shows an unusually low degree of homeobox gene clustering, with disruption of the NK, Hox, and ParaHox gene clusters. Among the oyster genes, 31 do not fall into ancient metazoan or bilaterian homeobox gene families; we deduce that they originated in the lophotrochozoan clade. We compared eight lophotrochozoan genomes to trace the pattern of homeobox gene evolution across this clade, allowing us to define 19 new lophotrochozoan-specific clades within the ANTP, PRD, TALE, ZF, SIX, and CUT classes. Using transcriptome data, we compared temporal expression of each homeobox gene in oyster development, and discovered that the lophotrochozoan-specific homeobox genes have peak expression either in early development (egg to gastrula) or in late development (after the trochophore larval stage), but rarely in between. This finding is consistent with the egg-timer, hourglass or phylotypic stage model of developmental evolution, in which there is a conserved central phase of development, but more evolutionarily labile early and late phases. PMID:25631164

  2. Expression of the homeobox genes OTX2 and OTX1 in the early developing human brain

    DEFF Research Database (Denmark)

    Larsen, Karen B; Lutterodt, Melissa C; Møllgård, Kjeld

    2010-01-01

    protein was found in the subcommissural organ, pineal gland, and cerebellum. The early expression of OTX2 and OTX1 in proliferative cell layers of the human fetal brain supports the concept that these homeobox genes are important in neuronal cell development and differentiation: OTX1 primarily......In rodents, the Otx2 gene is expressed in the diencephalon, mesencephalon, and cerebellum and is crucial for the development of these brain regions. Together with Otx1, Otx2 is known to cooperate with other genes to develop the caudal forebrain and, further, Otx1 is also involved in differentiation...... of young neurons of the deeper cortical layers. We have studied the spatial and temporal expression of the two homeobox genes OTX2 and OTX1 in human fetal brains from 7 to 14 weeks postconception by in situ hybridization and immunohistochemistry. OTX2 was expressed in the diencephalon, mesencephalon...

  3. Regulation, overexpression, and target gene identification of Potato Homeobox 15 (POTH15) ? a class-I KNOX gene in potato

    OpenAIRE

    Mahajan, Ameya S.; Kondhare, Kirtikumar R.; Rajabhoj, Mohit P.; Kumar, Amit; Ghate, Tejashree; Ravindran, Nevedha; Habib, Farhat; Siddappa, Sundaresha; Banerjee, Anjan K.

    2016-01-01

    Potato Homeobox 15 (POTH15) is a KNOX-I (Knotted1-like homeobox) family gene in potato that is orthologous to Shoot Meristemless (STM) in Arabidopsis. Despite numerous reports on KNOX genes from different species, studies in potato are limited. Here, we describe photoperiodic regulation of POTH15, its overexpression phenotype, and identification of its potential targets in potato (Solanum tuberosum ssp. andigena). qRT-PCR analysis showed a higher abundance of POTH15 mRNA in shoot tips and sto...

  4. Growth pattern and body proportion in a female with short stature homeobox-containing gene overdosage and gonadal estrogen deficiency

    National Research Council Canada - National Science Library

    Ogata, T; Inokuchi, M; Ogawa, M

    2002-01-01

    Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan. t-ogata@po.iijnet.or.jp OBJECTIVE: To report on growth pattern and body proportion in the combination of short stature homeobox-containing gene...

  5. Hearing loss caused by progressive degeneration of cochlear hair cells in mice deficient for the Barhl1 homeobox gene

    National Research Council Canada - National Science Library

    Shengguo Li; Sandy M. Price; Hugh Cahill; David K. Ryugo; Michael M. Shen; Mengqing Xiang

    2002-01-01

    .... We report that targeted disruption of Barhl1 , a mouse homolog of the Drosophila BarH homeobox genes, results in severe to profound hearing loss, providing a unique model for the study of age-related...

  6. Identification and Characterization of TALE Homeobox Genes in the Endangered Fern Vandenboschia speciosa.

    Science.gov (United States)

    Ruiz-Estévez, Mercedes; Bakkali, Mohammed; Martín-Blázquez, Rubén; Garrido-Ramos, Manuel A

    2017-10-17

    We report and discuss the results of a quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of the expression patterns of seven three amino acid loop extension (TALE) homeobox genes (four KNOTTED-like homeobox (KNOX) and three BEL1-like homeobox (BELL) genes) identified after next generation sequencing (NGS) and assembly of the sporophyte and gametophyte transcriptomes of the endangered fern species Vandenboschia speciosa. Among the four KNOX genes, two belonged to the KNOX1 class and the other two belonged to the KNOX2 class. Analysis of the deduced amino acid sequences supported the typical domain structure of both types of TALE proteins, and the homology to TALE proteins of mosses, lycophytes, and seed plant species. The expression analyses demonstrate that these homeodomain proteins appear to have a key role in the establishment and development of the gametophyte and sporophyte phases of V. speciosa lifecycle, as well as in the control of the transition between both phases. Vandenboschia speciosa VsKNAT3 (a KNOX2 class protein) as well as VsBELL4 and VsBELL10 proteins have higher expression levels during the sporophyte program. On the contrary, one V. speciosa KNOX1 protein (VsKNAT6) and one KNOX2 protein (VsKNAT4) seem important during the development of the gametophyte phase. TALE homeobox genes might be among the key regulators in the gametophyte-to-sporophyte developmental transition in regular populations that show alternation of generations, since some of the genes analyzed here (VsKNAT3, VsKNAT6, VsBELL4, and VsBELL6) are upregulated in a non-alternating population in which only independent gametophytes are found (they grow by vegetative reproduction outside of the range of sporophyte distribution). Thus, these four genes might trigger the vegetative propagation of the gametophyte and the repression of the sexual development in populations composed of independent gametophytes. This study represents a comprehensive

  7. Aberrantly Expressed OTX Homeobox Genes Deregulate B-Cell Differentiation in Hodgkin Lymphoma.

    Directory of Open Access Journals (Sweden)

    Stefan Nagel

    Full Text Available In Hodgkin lymphoma (HL we recently reported that deregulated homeobox gene MSX1 mediates repression of the B-cell specific transcription factor ZHX2. In this study we investigated regulation of MSX1 in this B-cell malignancy. Accordingly, we analyzed expression and function of OTX homeobox genes which activate MSX1 transcription during embryonal development in the neural plate border region. Our data demonstrate that OTX1 and OTX2 are aberrantly expressed in both HL patients and cell lines. Moreover, both OTX loci are targeted by genomic gains in overexpressing cell lines. Comparative expression profiling and subsequent pathway modulations in HL cell lines indicated that aberrantly enhanced FGF2-signalling activates the expression of OTX2. Downstream analyses of OTX2 demonstrated transcriptional activation of genes encoding transcription factors MSX1, FOXC1 and ZHX1. Interestingly, examination of the physiological expression profile of ZHX1 in normal hematopoietic cells revealed elevated levels in T-cells and reduced expression in B-cells, indicating a discriminatory role in lymphopoiesis. Furthermore, two OTX-negative HL cell lines overexpressed ZHX1 in correlation with genomic amplification of its locus at chromosomal band 8q24, supporting the oncogenic potential of this gene in HL. Taken together, our data demonstrate that deregulated homeobox genes MSX1 and OTX2 respectively impact transcriptional inhibition of (B-cell specific ZHX2 and activation of (T-cell specific ZHX1. Thus, we show how reactivation of a specific embryonal gene regulatory network promotes disturbed B-cell differentiation in HL.

  8. Inhibition of Breast Cancer-Induced Angiogenesis by a Diverged Homeobox Gene

    Science.gov (United States)

    2006-05-01

    18.5 0.0302 NM_000963 Prostaglandin-endoperoxide synthase 2 Biosynthesis/metabolism -26.0 0.0303 NM_001993 Coagulation factor III ( thromboplastin ...more sensitive to TGF- . Second, we Figure 8. Effect of Gax expression on the level of E-selectin, VCAM-1, and ICAM-1. A. Quantitative real time PCR...Cillo et al. 1999). The 3 rostral genes are highly responsive to retinoic acid (RA), whereas the 5 cau- dal genes are less sensitive . Each homeobox

  9. The Homeobox BcHOX8 Gene in Botrytis Cinerea Regulates Vegetative Growth and Morphology

    Science.gov (United States)

    Antal, Zsuzsanna; Rascle, Christine; Cimerman, Agnès; Viaud, Muriel; Billon-Grand, Geneviève; Choquer, Mathias; Bruel, Christophe

    2012-01-01

    Filamentous growth and the capacity at producing conidia are two critical aspects of most fungal life cycles, including that of many plant or animal pathogens. Here, we report on the identification of a homeobox transcription factor encoding gene that plays a role in these two particular aspects of the development of the phytopathogenic fungus Botrytis cinerea. Deletion of the BcHOX8 gene in both the B. cinerea B05-10 and T4 strains causes similar phenotypes, among which a curved, arabesque-like, hyphal growth on hydrophobic surfaces; the mutants were hence named Arabesque. Expression of the BcHOX8 gene is higher in conidia and infection cushions than in developing appressorium or mycelium. In the Arabesque mutants, colony growth rate is reduced and abnormal infection cushions are produced. Asexual reproduction is also affected with abnormal conidiophore being formed, strongly reduced conidia production and dramatic changes in conidial morphology. Finally, the mutation affects the fungus ability to efficiently colonize different host plants. Analysis of the B. cinerea genome shows that BcHOX8 is one member of a nine putative homeobox genes family. Available gene expression data suggest that these genes are functional and sequence comparisons indicate that two of them would be specific to B. cinerea and its close relative Sclerotinia sclerotiorum. PMID:23133556

  10. The homeobox BcHOX8 gene in Botrytis cinerea regulates vegetative growth and morphology.

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Antal

    Full Text Available Filamentous growth and the capacity at producing conidia are two critical aspects of most fungal life cycles, including that of many plant or animal pathogens. Here, we report on the identification of a homeobox transcription factor encoding gene that plays a role in these two particular aspects of the development of the phytopathogenic fungus Botrytis cinerea. Deletion of the BcHOX8 gene in both the B. cinerea B05-10 and T4 strains causes similar phenotypes, among which a curved, arabesque-like, hyphal growth on hydrophobic surfaces; the mutants were hence named Arabesque. Expression of the BcHOX8 gene is higher in conidia and infection cushions than in developing appressorium or mycelium. In the Arabesque mutants, colony growth rate is reduced and abnormal infection cushions are produced. Asexual reproduction is also affected with abnormal conidiophore being formed, strongly reduced conidia production and dramatic changes in conidial morphology. Finally, the mutation affects the fungus ability to efficiently colonize different host plants. Analysis of the B. cinerea genome shows that BcHOX8 is one member of a nine putative homeobox genes family. Available gene expression data suggest that these genes are functional and sequence comparisons indicate that two of them would be specific to B. cinerea and its close relative Sclerotinia sclerotiorum.

  11. NKL homeobox gene activities in hematopoietic stem cells, T-cell development and T-cell leukemia.

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    Stefan Nagel

    Full Text Available T-cell acute lymphoblastic leukemia (T-ALL cells represent developmentally arrested T-cell progenitors, subsets of which aberrantly express homeobox genes of the NKL subclass, including TLX1, TLX3, NKX2-1, NKX2-5, NKX3-1 and MSX1. Here, we analyzed the transcriptional landscape of all 48 members of the NKL homeobox gene subclass in CD34+ hematopoietic stem and progenitor cells (HSPCs and during lymphopoiesis, identifying activities of nine particular genes. Four of these were expressed in HSPCs (HHEX, HLX1, NKX2-3 and NKX3-1 and three in common lymphoid progenitors (HHEX, HLX1 and MSX1. Interestingly, our data indicated downregulation of NKL homeobox gene transcripts in late progenitors and mature T-cells, a phenomenon which might explain the oncogenic impact of this group of genes in T-ALL. Using MSX1-expressing T-ALL cell lines as models, we showed that HHEX activates while HLX1, NKX2-3 and NKX3-1 repress MSX1 transcription, demonstrating the mutual regulation and differential activities of these homeobox genes. Analysis of a public T-ALL expression profiling data set comprising 117 patient samples identified 20 aberrantly activated members of the NKL subclass, extending the number of known NKL homeobox oncogene candidates. While 7/20 genes were also active during hematopoiesis, the remaining 13 showed ectopic expression. Finally, comparative analyses of T-ALL patient and cell line profiling data of NKL-positive and NKL-negative samples indicated absence of shared target genes but instead highlighted deregulation of apoptosis as common oncogenic effect. Taken together, we present a comprehensive survey of NKL homeobox genes in early hematopoiesis, T-cell development and T-ALL, showing that these genes generate an NKL-code for the diverse stages of lymphoid development which might be fundamental for regular differentiation.

  12. A novel homeobox gene overexpressed in thyroid carcinoma

    NARCIS (Netherlands)

    Pauws, Erwin; Sijmons, Gwendolyn G.; Yaka, Cigdem; Ris-Stalpers, Carrie

    2004-01-01

    Serial analysis of gene expression (SAGE) was applied to compare expression profiles of normal thyroid tissue and papillary thyroid carcinoma (PTC). A SAGE tag corresponding to the partial cDNA for the small protein 31 (SMAP31) is upregulated approximately 13-fold in papillary thyroid cancer (PTC)

  13. Analysis of four DLX homeobox genes in autistic probands

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    Carlson Elaine J

    2005-11-01

    Full Text Available Abstract Background Linkage studies in autism have identified susceptibility loci on chromosomes 2q and 7q, regions containing the DLX1/2 and DLX5/6 bigene clusters. The DLX genes encode homeodomain transcription factors that control craniofacial patterning and differentiation and survival of forebrain inhibitory neurons. We investigated the role that sequence variants in DLX genes play in autism by in-depth resequencing of these genes in 161 autism probands from the AGRE collection. Results Sequencing of exons, exon/intron boundaries and known enhancers of DLX1, 2, 5 and 6 identified several nonsynonymous variants in DLX2 and DLX5 and a variant in a DLX5/6intragenic enhancer. The nonsynonymous variants were detected in 4 of 95 families from which samples were sequenced. Two of these four SNPs were not observed in 378 undiagnosed samples from North American populations, while the remaining 2 were seen in one sample each. Conclusion Segregation of these variants in pedigrees did not generally support a contribution to autism susceptibility by these genes, although functional analyses may provide insight into the biological understanding of these important proteins.

  14. Regulation of endometrial receptivity by the highly expressed HOXA9, HOXA11 and HOXD10 HOX-class homeobox genes

    NARCIS (Netherlands)

    Xu, Bei; Geerts, Dirk; Bu, Zhiqin; Ai, Jihui; Jin, Lei; Li, Yufeng; Zhang, Hanwang; Zhu, Guijin

    2014-01-01

    Are other HOX genes, in addition to HOXA10, involved in endometrial receptivity? The highly expressed HOXA9, HOXA11 and HOXD10 genes also appear to be involved in endometrial receptivity. Within the HOX family of homeobox transcription factor genes are the leading candidates for the regulation of

  15. Loss and gain of domains during evolution of cut superclass homeobox genes.

    Science.gov (United States)

    Bürglin, Thomas R; Cassata, Giuseppe

    2002-01-01

    The cut superclass of homeobox genes has been divided into three classes: CUX, ONECUT and SATB. Given the various completed genomes, we have now made a comprehensive survey. We find that there are only two cut domain containing genes in Drosophila, one CUX and one ONECUT type. Caenorhabditis elegans has undergone an expansion of the ONECUT subclass genes and has a gene cluster with three ONECUT class genes, one of which has lost the cut domain. Two of these genes contain a conserved sequence motif, termed OCAM, which also occurs in another gene in C. elegans this motif seems to be nematode specific. A recently uncovered C. elegans CUX gene has sequence conservation in its amino-terminus with vertebrate CUX proteins. Further, the 5' end of this gene containing the conserved region can undergo alternative splicing to give rise to a protein with a different carboxy-terminus lacking the cut- and homeodomain. This protein is conserved in its entirety with vertebrate genes termed CASP--which are also alternative splice products of the CUX genes--and with plant and fungal genes. The highly divergent SATB genes share a conserved amino terminal domain, COMPASS, with the Drosophila defective proventriculus gene and a C. elegans ORF. These two "COMPASS" family genes encode two highly divergent homeodomains, may be homologues of the SATB genes and thus probably belong to the cut superclass, too.

  16. Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Marcinkiewicz, Katarzyna M.; Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu

    2014-01-01

    To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes. - Highlights: • RNAseq elucidates differences between non-tumorigenic and tumorigenic oral keratinocytes. • Changes in HOX mRNA in SCC-9 vs. OKF6-TERT1R cells are a result of altered epigenetic regulation. • RNAseq shows that retinoic acid (RA) influences gene expression in both OKF6-TERT1R and SCC-9 cells.

  17. Fine-tuning and autoregulation of the intestinal determinant and tumor suppressor homeobox gene CDX2 by alternative splicing

    NARCIS (Netherlands)

    Balbinot, Camille; Vanier, Marie; Armant, Olivier; Nair, Asmaa; Penichon, Julien; Soret, Christine; Martin, Elisabeth; Saandi, Thoueiba; Reimund, Jean-Marie; Deschamps, Jacqueline; Beck, Felix; Domon-Dell, Claire; Gross, Isabelle; Duluc, Isabelle; Freund, Jean-Noël

    2017-01-01

    On the basis of phylogenetic analyses, we uncovered a variant of the CDX2 homeobox gene, a major regulator of the development and homeostasis of the gut epithelium, also involved in cancer. This variant, miniCDX2, is generated by alternative splicing coupled to alternative translation initiation,

  18. A modulatory role of the Rax homeobox gene in mature pineal gland function

    DEFF Research Database (Denmark)

    Rohde, Kristian; Bering, Tenna; Furukawa, Takahisa

    2017-01-01

    The retinal and anterior neural fold homeobox gene (Rax) controls development of the eye and the forebrain. Postnatal expression of Rax in the brain is restricted to the pineal gland, a forebrain structure devoted to melatonin synthesis. The role of Rax in pineal function is unknown. In order...... to investigate the role of Rax in pineal function while circumventing forebrain abnormalities of the global Rax knockout, we generated an eye and pineal-specific Rax conditional knockout mouse. Deletion of Rax in the pineal gland did not affect morphology of the gland, suggesting that Rax is not essential...... for pineal gland development. In contrast, deletion of Rax in the eye generated an anophthalmic phenotype. In addition to the loss of central visual pathways, the suprachiasmatic nucleus of the hypothalamus housing the circadian clock was absent, indicating that the retinohypothalamic tract is required...

  19. The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus

    DEFF Research Database (Denmark)

    Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong

    2015-01-01

    Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx......9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain...... regions. Studies with C57BL/6J Lhx9 (-/-) mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal...

  20. Two human homeobox genes, c1 and c8: structure analysis and expression in embryonic development.

    Science.gov (United States)

    Simeone, A; Mavilio, F; Acampora, D; Giampaolo, A; Faiella, A; Zappavigna, V; D'Esposito, M; Pannese, M; Russo, G; Boncinelli, E

    1987-07-01

    Two human cDNA clones (HHO.c1.95 and HHO.c8.5111) containing a homeobox region have been characterized, and the respective genomic regions have been partially analyzed. Expression of the corresponding genes, termed c1 and c8, was evaluated in different organs and body parts during human embryonic/fetal development. HHO.c1.95 apparently encodes a 217-amino acid protein containing a class I homeodomain that shares 60 out of 61 amino acid residues with the Antennapedia homeodomain of Drosophila melanogaster. HHO.c8.5111 encodes a 153-amino acid protein containing a homeodomain identical to that of the frog AC1 gene. Clones HHO.c1 and HHO.c8 detect by blot-hydridization one and two specific polyadenylylated transcripts, respectively. These are differentially expressed in spinal cord, backbone rudiments, limb buds (or limbs), heart, and skin of human embryos and early fetuses in the 5- to 9-week postfertilization period, thus suggesting that the c1 and c8 genes play a key role in a variety of developmental processes. Together, the results of the embryonic/fetal expression of c1 and c8 and those of two previously analyzed genes (c10 and c13) indicate a coherent pattern of expression of these genes in early human ontogeny.

  1. Conserved, developmentally regulated mechanism couples chromosomal looping and heterochromatin barrier activity at the homeobox gene A locus

    Science.gov (United States)

    Kim, Yoon Jung; Cecchini, Katharine R.; Kim, Tae Hoon

    2011-01-01

    Establishment and segregation of distinct chromatin domains are essential for proper genome function. The insulator protein CCCTC-binding factor (CTCF) is involved in creating boundaries that segregate chromatin and functional domains and in organizing higher-order chromatin structures by promoting chromosomal loops across the vertebrate genome. Here, we investigate the insulation properties of CTCF at the human and mouse homeobox gene A (HOXA) loci. Although cohesin loading at the CTCF binding site is required for looping, we found that cohesin is dispensable for chromatin barrier activity at that site. Using mouse embryonic stem cells in both a pluripotent and differentiated neuronal progenitor state, we determined that embryonic stem cell pluripotency factor OCT4 antagonizes cohesin loading at the CTCF binding site. Loss of OCT4 in the committed and differentiated neuronal progenitor cells results in loading of cohesin and chromosome looping, which contributes to heterochromatin partitioning and selective gene activation across the HOXA locus. Our analysis reveals that chromatin barrier activity of CTCF is evolutionarily conserved and is responsible for the coordinated establishment of chromatin structure, higher-order architecture, and developmental expression of the HOXA locus. PMID:21502535

  2. DNA methylation analysis of Homeobox genes implicates HOXB7 hypomethylation as risk factor for neural tube defects

    OpenAIRE

    Rochtus, Anne; Izzi, Benedetta; Vangeel, Elise; Louwette, Sophie; Wittevrongel, Christine; Lambrechts, Diether; Moreau, Yves; Winand, Raf; Verpoorten, Carla; Jansen, Katrien; van Geet, Chris; Freson, Kathleen

    2015-01-01

    Abstract Neural tube defects (NTDs) are common birth defects of complex etiology. Though family- and population-based studies have confirmed a genetic component, the responsible genes for NTDs are still largely unknown. Based on the hypothesis that folic acid prevents NTDs by stimulating methylation reactions, epigenetic factors, such as DNA methylation, are predicted to be involved in NTDs. Homeobox (HOX) genes play a role in spinal cord development and are tightly regulated in a spatiotempo...

  3. Expression of the Otx2 homeobox gene in the developing mammalian brain: embryonic and adult expression in the pineal gland

    DEFF Research Database (Denmark)

    Rath, Martin F; Muñoz, Estela; Ganguly, Surajit

    2006-01-01

    that the level of Otx2 mRNA appears to be independent of the photoneural input to the gland. Our results are consistent with the view that pineal expression of Otx2 is required for development and we hypothesize that it plays a role in the adult in controlling the expression of the cluster of genes associated......Otx2 is a vertebrate homeobox gene, which has been found to be essential for the development of rostral brain regions and appears to play a role in the development of retinal photoreceptor cells and pinealocytes. In this study, the temporal expression pattern of Otx2 was revealed in the rat brain......, with special emphasis on the pineal gland throughout late embryonic and postnatal stages. Widespread high expression of Otx2 in the embryonic brain becomes progressively restricted in the adult to the pineal gland. Crx (cone-rod homeobox), a downstream target gene of Otx2, showed a pineal expression pattern...

  4. Mouse Obox and Crxos modulate preimplantation transcriptional profiles revealing similarity between paralogous mouse and human homeobox genes

    Directory of Open Access Journals (Sweden)

    Amy H. Royall

    2018-01-01

    Full Text Available Abstract Background ETCHbox genes are eutherian-specific homeobox genes expressed during preimplantation development at a time when the first cell lineage decisions are being made. The mouse has an unusual repertoire of ETCHbox genes with several gene families lost in evolution and the remaining two, Crxos and Obox, greatly divergent in sequence and number. Each has undergone duplication to give a double homeodomain Crxos locus and a large cluster of over 60 Obox loci. The gene content differences between species raise important questions about how evolution can tolerate loss of genes implicated in key developmental events. Results We find that Crxos internal duplication occurred in the mouse lineage, while Obox duplication was stepwise, generating subgroups with distinct sequence and expression. Ectopic expression of three Obox genes and a Crxos transcript in primary mouse embryonic cells followed by transcriptome sequencing allowed investigation into their functional roles. We find distinct transcriptomic influences for different Obox subgroups and Crxos, including modulation of genes related to zygotic genome activation and preparation for blastocyst formation. Comparison with similar experiments performed using human homeobox genes reveals striking overlap between genes downstream of mouse Crxos and genes downstream of human ARGFX. Conclusions Mouse Crxos and human ARGFX homeobox genes are paralogous rather than orthologous, yet they have evolved to regulate a common set of genes. This suggests there was compensation of function alongside gene loss through co-option of a different locus. Functional compensation by non-orthologous genes with dissimilar sequences is unusual but may indicate underlying distributed robustness. Compensation may be driven by the strong evolutionary pressure for successful early embryo development.

  5. A novel combination of homeobox genes is expressed in mesenchymal chorionic stem/stromal cells in first trimester and term pregnancies.

    Science.gov (United States)

    Liu, Haiying; Murthi, Padma; Qin, Sharon; Kusuma, Gina D; Borg, Anthony J; Knöfler, Martin; Haslinger, Peter; Manuelpillai, Ursula; Pertile, Mark D; Abumaree, Mohamed; Kalionis, Bill

    2014-11-01

    Human chorionic mesenchymal stem/stromal cells (CMSCs) derived from the placenta are similar to adult tissue-derived MSCs. The aim of this study was to investigate the role of these cells in normal placental development. Transcription factors, particularly members of the homeobox gene family, play crucial roles in maintaining stem cell proliferation and lineage specification in embryonic tissues. In adult tissues and organs, stem cells proliferate at low levels in their niche until they receive cues from the microenvironment to differentiate. The homeobox genes that are expressed in the CMSC niche in placental tissues have not been identified. We used the novel strategy of laser capture microdissection to isolate the stromal component of first trimester villi and excluded the cytotrophoblast and syncytiotrophoblast layers that comprise the outer layer of the chorionic villi. Microarray analysis was then used to screen for homeobox genes in the microdissected tissue. Candidate homeobox genes were selected for further RNA analysis. Immunohistochemistry of candidate genes in first trimester placental villous stromal tissue revealed homeobox genes Meis1, myeloid ectropic viral integration site 1 homolog 2 (MEIS2), H2.0-like Drosophila (HLX), transforming growth factor β-induced factor (TGIF), and distal-less homeobox 5 (DLX5) were expressed in the vascular niche where CMSCs have been shown to reside. Expression of MEIS2, HLX, TGIF, and DLX5 was also detected in scattered stromal cells. Real-time polymerase chain reaction and immunocytochemistry verified expression of MEIS2, HLX, TGIF, and DLX5 homeobox genes in first trimester and term CMSCs. These data suggest a combination of regulatory homeobox genes is expressed in CMSCs from early placental development to term, which may be required for stem cell proliferation and differentiation. © The Author(s) 2014.

  6. Regulation, overexpression, and target gene identification of Potato Homeobox 15 (POTH15) - a class-I KNOX gene in potato.

    Science.gov (United States)

    Mahajan, Ameya S; Kondhare, Kirtikumar R; Rajabhoj, Mohit P; Kumar, Amit; Ghate, Tejashree; Ravindran, Nevedha; Habib, Farhat; Siddappa, Sundaresha; Banerjee, Anjan K

    2016-07-01

    Potato Homeobox 15 (POTH15) is a KNOX-I (Knotted1-like homeobox) family gene in potato that is orthologous to Shoot Meristemless (STM) in Arabidopsis. Despite numerous reports on KNOX genes from different species, studies in potato are limited. Here, we describe photoperiodic regulation of POTH15, its overexpression phenotype, and identification of its potential targets in potato (Solanum tuberosum ssp. andigena). qRT-PCR analysis showed a higher abundance of POTH15 mRNA in shoot tips and stolons under tuber-inducing short-day conditions. POTH15 promoter activity was detected in apical and axillary meristems, stolon tips, tuber eyes, and meristems of tuber sprouts, indicating its role in meristem maintenance and leaf development. POTH15 overexpression altered multiple morphological traits including leaf and stem development, leaflet number, and number of nodes and branches. In particular, the rachis of the leaf was completely reduced and leaves appeared as a bouquet of leaflets. Comparative transcriptomic analysis of 35S::GUS and two POTH15 overexpression lines identified more than 6000 differentially expressed genes, including 2014 common genes between the two overexpression lines. Functional analysis of these genes revealed their involvement in responses to hormones, biotic/abiotic stresses, transcription regulation, and signal transduction. qRT-PCR of selected candidate target genes validated their differential expression in both overexpression lines. Out of 200 randomly chosen POTH15 targets, 173 were found to have at least one tandem TGAC core motif, characteristic of KNOX interaction, within 3.0kb in the upstream sequence of the transcription start site. Overall, this study provides insights to the role of POTH15 in controlling diverse developmental processes in potato. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  7. Over-expression of HOX-8, the human homologue of the mouse Hox-8 homeobox gene, in human tumors.

    Science.gov (United States)

    Suzuki, M; Tanaka, M; Iwase, T; Naito, Y; Sugimura, H; Kino, I

    1993-07-15

    A human ovarian yolk sac tumor cDNA library was screened for homeobox genes with an oligonucleotide probe under low stringent condition. Three homeobox genes were isolated, two of which were identified as HHO.c1 and HB24. The third was highly homologous with the mouse Hox-8 gene and was designated as HOX-8. Studies on RNAs from 25 human tumor tissues and cell lines showed that the profile of HOX-8 expression was different from those of HHO.c1 and HB24. The expression of HOX-8 was not detected in hematopoietic tumor cells, in which HHO.c1 and HB24 were highly expressed. HOX-8 was expressed at higher levels in a variety of tumors of epithelial origin than in their corresponding normal tissues more frequently than HHO.c1 and HB24. All three homeobox genes were highly expressed in a yolk sac tumor, an immature tumor of gonadal origin. These results suggest that HOX-8 plays a more important role in human tumors of epithelial origin than those of hematopoietic origin.

  8. Novel visual system homeobox 1 gene mutations in Turkish patients with keratoconus.

    Science.gov (United States)

    Bardak, H; Gunay, M; Yildiz, E; Bardak, Y; Gunay, B; Ozbas, H; Bagci, O

    2016-11-03

    The aim of this study was to screen the visual system homeobox 1 (VSX1) gene in Turkish patients with keratoconus (KC). The patient group consisted of 44 patients who had undergone corneal transplant surgery before the age of 30, for advanced and rapidly progressive KC. The control group comprised 250 healthy individuals. We detected two missense mutations, D144N and D295Y, in exon 2 and exon 5 of the VSX1 gene, respectively, using next-generation sequencing analysis. The pathologic effects of the D144N and D295Y missense mutations on protein function were determined with bioinformatic analysis tools, SIFT, PolyPhen, and MutationTaster. Aspartic acid at the 144th position was more preserved among species than aspartic acid at the 295th position of the VSX1 protein. In the control group, five different genetic variations were detected, two of which (rs8123716 and rs12480307) were synonymous with variations in the patient group. Our results suggested that the D144N and D295Y mutations might have a role in the pathogenesis of KC disease.

  9. Characterization of the Six1 homeobox gene in normal mammary gland morphogenesis

    Directory of Open Access Journals (Sweden)

    McManaman James L

    2010-01-01

    Full Text Available Abstract Background The Six1 homeobox gene is highly expressed in the embryonic mammary gland, continues to be expressed in early postnatal mammary development, but is lost when the mammary gland differentiates during pregnancy. However, Six1 is re-expressed in breast cancers, suggesting that its re-instatement in the adult mammary gland may contribute to breast tumorigenesis via initiating a developmental process out of context. Indeed, recent studies demonstrate that Six1 overexpression in the adult mouse mammary gland is sufficient for initiating invasive carcinomas, and that its overexpression in xenograft models of mammary cancer leads to metastasis. These data demonstrate that Six1 is causally involved in both breast tumorigenesis and metastasis, thus raising the possibility that it may be a viable therapeutic target. However, because Six1 is highly expressed in the developing mammary gland, and because it has been implicated in the expansion of mammary stem cells, targeting Six1 as an anti-cancer therapy may have unwanted side effects in the breast. Results We sought to determine the role of Six1 in mammary development using two independent mouse models. To study the effect of Six1 loss in early mammary development when Six1 is normally expressed, Six1-/- embryonic mammary glands were transplanted into Rag1-/- mice. In addition, to determine whether Six1 downregulation is required during later stages of development to allow for proper differentiation, we overexpressed Six1 during adulthood using an inducible, mammary-specific transgenic mouse model. Morphogenesis of the mammary gland occurred normally in animals transplanted with Six1-/- embryonic mammary glands, likely through the redundant functions of other Six family members such as Six2 and Six4, whose expression was increased in response to Six1 loss. Surprisingly, inappropriate expression of Six1 in the adult mammary gland, when levels are normally low to absent, did not inhibit

  10. Short stature homeobox-containing gene duplications in 3.7% of girls with tall stature and normal karyotypes

    DEFF Research Database (Denmark)

    Upners, Emmie N; Jensen, Rikke B; Rajpert-De Meyts, Ewa

    2017-01-01

    AIM: The short stature homeobox containing gene (SHOX) plays an important role in short stature, but has not been explored in detail in a tall stature population before. This study explored the prevalence of SHOX aberrations in girls diagnosed with idiopathic tall stature with a normal karyotype...... in three girls with tall stature and normal karyotypes. This article is protected by copyright. All rights reserved....

  11. De novo mutations in the cone-rod homeobox gene associated with leber congenital amaurosis in Chinese patients.

    Science.gov (United States)

    Zou, Xuan; Yao, Fengxia; Liang, Xiaofang; Xu, Fei; Li, Hui; Sui, Ruifang; Dong, Fangtian

    2015-03-01

    The cone-rod homeobox (CRX) gene plays an important role in photoreceptor development. Recently, mutant alleles of the CRX gene have been associated with autosomal dominant Leber congenital amaurosis (LCA) and cone-rod dystrophy. The purpose of this study was to analyze the CRX mutations in a cohort of Chinese patients with LCA or early-onset severe retinal dystrophy (EOSRD) and to provide the clinical features of these patients. Patients with LCA or EOSRD were enrolled from 2003 to 2012. Detailed ocular examinations including optical coherence tomography (OCT) and standardized electrophysiology were performed. Genomic DNA was isolated with standard methods of genetic diagnosis. All three exons of CRX were amplified with PCR and screened for mutations through direct DNA sequencing. A total of 200 unrelated healthy Chinese subjects were screened to exclude nonpathogenic polymorphisms. Offspring-parent relationship was tested to confirm de novo mutation. A total of 109 probands from 109 unrelated families were selected for mutation screening of the CRX gene. Two individuals with LCA were confirmed to carry de novo CRX mutations c.421delT (p.Ser141Pro fsX46) and c.571delT (p.Tyr191Met fsX3), respectively. The daughter of Case 1 also carried the same CRX mutation (c.421delT) and had LCA symptoms. Pigmentary retinopathy in the peripheral retina and macular atrophy were observed in the two probands. Macular atrophy without normal lamination structure was the retina phenotype under OCT. Two de novo mutations in CRX were found in Chinese patients with LCA. The CRX mutation might create a dominantly inherited trait.

  12. Role of the Barhl2 homeobox gene in the specification of glycinergic amacrine cells.

    Science.gov (United States)

    Mo, Zeqian; Li, Shengguo; Yang, Xuejie; Xiang, Mengqing

    2004-04-01

    The mammalian retina contains numerous morphological and physiological subtypes of amacrine cells necessary for integrating and modulating visual signals presented to the output neurons. Among subtypes of amacrine cells grouped by neurotransmitter phenotypes, the glycinergic and gamma-aminobutyric acid (GABA)ergic amacrine cells constitute two major subpopulations. To date, the molecular mechanisms governing the specification of subtype identity of amacrine cells remain elusive. We report here that during mouse development, the Barhl2 homeobox gene displays an expression pattern in the nervous system that is distinct from that of its homologue Barhl1. In the developing retina, Barhl2 expression is found in postmitotic amacrine, horizontal and ganglion cells, while Barhl1 expression is absent. Forced expression of Barhl2 in retinal progenitors promotes the differentiation of glycinergic amacrine cells, whereas a dominant-negative form of Barhl2 has the opposite effect. By contrast, they exert no effect on the formation of GABAergic neurons. Moreover, misexpressed Barhl2 inhibits the formation of bipolar and Müller glial cells, indicating that Barhl2 is able to function both as a positive and negative regulator, depending on different types of cells. Taken together, our data suggest that Barhl2 may function to specify the identity of glycinergic amacrine cells from competent progenitors during retinogenesis.

  13. Expression of the homeobox gene, Barx2, in wool follicle development.

    Science.gov (United States)

    Sander, G; Bawden, C S; Hynd, P I; Nesci, A; Rogers, G; Powell, B C

    2000-10-01

    We have cloned ovine Barx2, a member of the Bar class of homeobox genes, and present the first description of Barx2 expression in wool follicle development. Barx2 is uniformly expressed in the embryonic ectoderm but is transiently downregulated during the initiation of follicle morphogenesis. Subsequently, Barx2 is expressed throughout the epithelial component of the developing follicle except for a small group of cells at the leading edge of the follicle placode. These Barx2-negative cells are destined to form the follicle bulb and are the progenitors of the inner root sheath and hair shaft. In adult follicles, Barx2 is expressed throughout the outer root sheath but not in the inner root sheath or hair shaft, or in dermal cells associated with the follicle. The pattern of Barx2 expression in follicle morphogenesis is similar to that of the cell adhesion molecule E-cadherin, a similarity that echoes Barx2 coexpression with the L1 cell adhesion molecule in other tissues during mouse embryogenesis. Barx2 is also expressed in tongue and esophagus, two other keratinizing tissues, and we speculate that Barx2 may have a general function in controlling adhesive processes in keratinizing epithelia.

  14. The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus.

    Science.gov (United States)

    Yamazaki, Fumiyoshi; Møller, Morten; Fu, Cong; Clokie, Samuel J; Zykovich, Artem; Coon, Steven L; Klein, David C; Rath, Martin F

    2015-01-01

    Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9(-/-) mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9(-/-) mutant mice appear normal, severe hydrocephalus develops in about 70% of the Lhx9(-/-) mice at 5-8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9(-/-)mutant mice, the neonatal pineal gland in these animals is hypoplastic. Accordingly, it appears that Lhx9 is essential for early development of the mammalian pineal gland and that this effect is not secondary to hydrocephalus.

  15. Differential DNA methylation patterns of homeobox genes in proximal and distal colon epithelial cells

    Science.gov (United States)

    Barnicle, Alan; Seoighe, Cathal; Golden, Aaron; Greally, John M.

    2016-01-01

    Region and cell-type specific differences in the molecular make up of colon epithelial cells have been reported. Those differences may underlie the region-specific characteristics of common colon epithelial diseases such as colorectal cancer and inflammatory bowel disease. DNA methylation is a cell-type specific epigenetic mark, essential for transcriptional regulation, silencing of repetitive DNA and genomic imprinting. Little is known about any region-specific variations in methylation patterns in human colon epithelial cells. Using purified epithelial cells and whole biopsies (n = 19) from human subjects, we generated epigenome-wide DNA methylation data (using the HELP-tagging assay), comparing the methylation signatures of the proximal and distal colon. We identified a total of 125 differentially methylated sites (DMS) mapping to transcription start sites of protein-coding genes, most notably several members of the homeobox (HOX) family of genes. Patterns of differential methylation were validated with MassArray EpiTYPER. We also examined DNA methylation in whole biopsies, applying a computational technique to deconvolve variation in methylation within cell types and variation in cell-type composition across biopsies. Including inferred epithelial proportions as a covariate in differential methylation analysis applied to the whole biopsies resulted in greater overlap with the results obtained from purified epithelial cells compared with when the covariate was not included. Results obtained from both approaches highlight region-specific methylation patterns of HOX genes in colonic epithelium. Regional variation in methylation patterns has implications for the study of diseases that exhibit regional expression patterns in the human colon, such as inflammatory bowel disease and colorectal cancer. PMID:26812987

  16. The TALE class homeobox gene Smed-prep defines the anterior compartment for head regeneration.

    Directory of Open Access Journals (Sweden)

    Daniel A Felix

    2010-04-01

    Full Text Available Planaria continue to blossom as a model system for understanding all aspects of regeneration. They provide an opportunity to understand how the replacement of missing tissues from preexisting adult tissue is orchestrated at the molecular level. When amputated along any plane, planaria are capable of regenerating all missing tissue and rescaling all structures to the new size of the animal. Recently, rapid progress has been made in understanding the developmental pathways that control planarian regeneration. In particular Wnt/beta-catenin signaling is central in promoting posterior fates and inhibiting anterior identity. Currently the mechanisms that actively promote anterior identity remain unknown. Here, Smed-prep, encoding a TALE class homeodomain, is described as the first gene necessary for correct anterior fate and patterning during planarian regeneration. Smed-prep is expressed at high levels in the anterior portion of whole animals, and Smed-prep(RNAi leads to loss of the whole brain during anterior regeneration, but not during lateral regeneration or homeostasis in intact worms. Expression of markers of different anterior fated cells are greatly reduced or lost in Smed-prep(RNAi animals. We find that the ectopic anterior structures induced by abrogation of Wnt signaling also require Smed-prep to form. We use double knockdown experiments with the S. mediterranea ortholog of nou-darake (that when knocked down induces ectopic brain formation to show that Smed-prep defines an anterior fated compartment within which stem cells are permitted to assume brain fate, but is not required directly for this differentiation process. Smed-prep is the first gene clearly implicated as being necessary for promoting anterior fate and the first homeobox gene implicated in establishing positional identity during regeneration. Together our results suggest that Smed-prep is required in stem cell progeny as they form the anterior regenerative blastema and is

  17. Dysregulation of the homeobox transcription factor gene HOXB13: role in prostate cancer.

    Science.gov (United States)

    Decker, Brennan; Ostrander, Elaine A

    2014-01-01

    Prostate cancer (PC) is the most common noncutaneous cancer in men, and epidemiological studies suggest that about 40% of PC risk is heritable. Linkage analyses in hereditary PC families have identified multiple putative loci. However, until recently, identification of specific risk alleles has proven elusive. Cooney et al used linkage mapping and segregation analysis to identify a putative risk locus on chromosome 17q21-22. In search of causative variant(s) in genes from the candidate region, a novel, potentially deleterious G84E substitution in homeobox transcription factor gene HOXB13 was observed in multiple hereditary PC families. In follow-up testing, the G84E allele was enriched in cases, especially those with an early diagnosis or positive family history of disease. This finding was replicated by others, confirming HOXB13 as a PC risk gene. The HOXB13 protein plays diverse biological roles in embryonic development and terminally differentiated tissue. In tumor cell lines, HOXB13 participates in a number of biological functions, including coactivation and localization of the androgen receptor and FOXA1. However, no consensus role has emerged and many questions remain. All HOXB13 variants with a proposed role in PC risk are predicted to damage the protein and lie in domains that are highly conserved across species. The G84E variant has the strongest epidemiological support and lies in a highly conserved MEIS protein-binding domain, which binds cofactors required for activation. On the basis of epidemiological and biological data, the G84E variant likely modulates the interaction between the HOXB13 protein and the androgen receptor, as well as affecting FOXA1-mediated transcriptional programming. However, further studies of the mutated protein are required to clarify the mechanisms by which this translates into PC risk.

  18. A conserved cluster of three PRD-class homeobox genes (homeobrain, rx and orthopedia in the Cnidaria and Protostomia

    Directory of Open Access Journals (Sweden)

    Mazza Maureen E

    2010-07-01

    Full Text Available Abstract Background Homeobox genes are a superclass of transcription factors with diverse developmental regulatory functions, which are found in plants, fungi and animals. In animals, several Antennapedia (ANTP-class homeobox genes reside in extremely ancient gene clusters (for example, the Hox, ParaHox, and NKL clusters and the evolution of these clusters has been implicated in the morphological diversification of animal bodyplans. By contrast, similarly ancient gene clusters have not been reported among the other classes of homeobox genes (that is, the LIM, POU, PRD and SIX classes. Results Using a combination of in silico queries and phylogenetic analyses, we found that a cluster of three PRD-class homeobox genes (Homeobrain (hbn, Rax (rx and Orthopedia (otp is present in cnidarians, insects and mollusks (a partial cluster comprising hbn and rx is present in the placozoan Trichoplax adhaerens. We failed to identify this 'HRO' cluster in deuterostomes; in fact, the Homeobrain gene appears to be missing from the chordate genomes we examined, although it is present in hemichordates and echinoderms. To illuminate the ancestral organization and function of this ancient cluster, we mapped the constituent genes against the assembled genome of a model cnidarian, the sea anemone Nematostella vectensis, and characterized their spatiotemporal expression using in situ hybridization. In N. vectensis, these genes reside in a span of 33 kb with the same gene order as previously reported in insects. Comparisons of genomic sequences and expressed sequence tags revealed the presence of alternative transcripts of Nv-otp and two highly unusual protein-coding polymorphisms in the terminal helix of the Nv-rx homeodomain. A population genetic survey revealed the Rx polymorphisms to be widespread in natural populations. During larval development, all three genes are expressed in the ectoderm, in non-overlapping territories along the oral-aboral axis, with distinct

  19. Lim homeobox genes in the Ctenophore Mnemiopsis leidyi: the evolution of neural cell type specification

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    Simmons David K

    2012-01-01

    Full Text Available Abstract Background Nervous systems are thought to be important to the evolutionary success and diversification of metazoans, yet little is known about the origin of simple nervous systems at the base of the animal tree. Recent data suggest that ctenophores, a group of macroscopic pelagic marine invertebrates, are the most ancient group of animals that possess a definitive nervous system consisting of a distributed nerve net and an apical statocyst. This study reports on details of the evolution of the neural cell type specifying transcription factor family of LIM homeobox containing genes (Lhx, which have highly conserved functions in neural specification in bilaterian animals. Results Using next generation sequencing, the first draft of the genome of the ctenophore Mnemiopsis leidyi has been generated. The Lhx genes in all animals are represented by seven subfamilies (Lhx1/5, Lhx3/4, Lmx, Islet, Lhx2/9, Lhx6/8, and LMO of which four were found to be represented in the ctenophore lineage (Lhx1/5, Lhx3/4, Lmx, and Islet. Interestingly, the ctenophore Lhx gene complement is more similar to the sponge complement (sponges do not possess neurons than to either the cnidarian-bilaterian or placozoan Lhx complements. Using whole mount in situ hybridization, the Lhx gene expression patterns were examined and found to be expressed around the blastopore and in cells that give rise to the apical organ and putative neural sensory cells. Conclusion This research gives us a first look at neural cell type specification in the ctenophore M. leidyi. Within M. leidyi, Lhx genes are expressed in overlapping domains within proposed neural cellular and sensory cell territories. These data suggest that Lhx genes likely played a conserved role in the patterning of sensory cells in the ancestor of sponges and ctenophores, and may provide a link to the expression of Lhx orthologs in sponge larval photoreceptive cells. Lhx genes were later co-opted into patterning more

  20. Analysis of homeobox gene action may reveal novel angiogenic pathways in normal placental vasculature and in clinical pregnancy disorders associated with abnormal placental angiogenesis.

    Directory of Open Access Journals (Sweden)

    Padma eMurthi

    2014-06-01

    Full Text Available Homeobox genes are essential for both the development of the blood and lymphatic vascular systems, as well as for their maintenance in the adult. Homeobox genes comprise an important family of transcription factors, which are characterised by a well conserved DNA binding motif; the homeodomain. The specificity of the homeodomain allows the transcription factor to bind to the promoter regions of batteries of target genes and thereby regulates their expression. Target genes identified for homeodomain proteins have been shown to control fundamental cell processes such as proliferation, differentiation and apoptosis. We and others have reported that homeobox genes are expressed in the placental vasculature, but our knowledge of their downstream target genes is limited. This review highlights the importance of studying the cellular and molecular mechanisms by which homeobox genes and their downstream targets may regulate important vascular cellular processes such as proliferation, migration, and endothelial tube formation, which are essential for placental vasculogenesis and angiogenesis. A better understanding of the molecular targets of homeobox genes may lead to new therapies for aberrant angiogenesis associated with clinically important pregnancy pathologies, including fetal growth restriction and preeclampsia.

  1. Muscle segment homeobox genes direct embryonic diapause by limiting inflammation in the uterus

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Jeeyeon; Burnum-Johnson, Kristin E.; Bartos, Amanda; Li, Yingju; Baker, Erin Shammel; Tilton, Susan C.; Webb-Robertson, Bobbie-Jo M.; Piehowski, Paul D.; Monroe, Matthew E.; Jegga, Anil; Murata, Shigeo; Hirota, Yasushi; Dey, Sudhansu K.

    2015-06-11

    Embryonic diapause (delayed implantation) is a reproductive strategy widespread in the animal kingdom. Under this condition, embryos at the blastocyst stage become dormant simultaneously with uterine quiescence until environmental or physiological conditions are favorable for the survival of the mother and newborn. Under favorable conditions, activation of the blastocyst and uterus ensues with implantation and progression of pregnancy. Although endocrine factors are known to participate in this process, the underlying molecular mechanism coordinating this phenomenon is not clearly understood. We recently found that uterine muscle segment homeobox (Msx) transcription factors are critical for the initiation and maintenance of delayed implantation in mice. To better understand why Msx genes are critical for delayed implantation, we compared uterine proteomics profiles between littermate floxed (Msx1/Msx2f/f) mice and mice with uterine deletion of Msx genes (Msx1/Msx2d/d) under delayed conditions. In Msx1/Msx2d/d uteri, pathways including protein translation, ubiquitin-proteasome system, inflammation, chaperone-mediated protein folding, and endoplasmic reticulum (ER) stress were enriched, and computational modeling showed intersection of these pathways on inflammatory responses. Indeed, increases in the ubiquitin-proteasome system and inflammation conformed to proteotoxic and ER stress in Msx1/Msx2d/d uteri under delayed conditions. Interestingly, treatment with a proteasome inhibitor bortezomib further exacerbated ER stress in Msx1/Msx2d/d uteri with aggravated inflammatory response, deteriorating rate of blastocyst recovery and failure to sustain delayed implantation. This study highlights a previously unrecognized role for Msx in preventing proteotoxic stress and inflammatory responses to coordinate embryo dormancy and uterine quiescence during embryonic diapause.

  2. Mesoderm/mesenchyme homeobox gene l promotes vascular smooth muscle cell phenotypic modulation and vascular remodeling.

    Science.gov (United States)

    Wu, Bing; Zhang, Lei; Zhu, Yun-He; Zhang, You-En; Zheng, Fei; Yang, Jian-Ye; Guo, Ling-Yun; Li, Xing-Yuan; Wang, Lu; Tang, Jun-Ming; Chen, Shi-You; Wang, Jia-Ning

    2018-01-15

    To investigate the role of mesoderm/mesenchyme homeobox gene l (Meox1) in vascular smooth muscle cells (SMCs) phenotypic modulation during vascular remodeling. By using immunostaining, Western blot, and histological analyses, we found that Meox1 was up-regulated in PDGF-BB-treated SMCs in vitro and balloon injury-induced arterial SMCs in vivo. Meox1 knockdown by shRNA restored the expression of contractile SMCs phenotype markers including smooth muscle α-actin (α-SMA) and calponin. In contrast, overexpression of Moex1 inhibited α-SMA and calponin expressions while inducing the expressions of synthetic SMCs phenotype markers such as matrix gla protein, osteopontin, and proliferating cell nuclear antigen. Mechanistically, Meox1 mediated the SMCs phenotypic modulation through FAK-ERK1/2 signaling, which appears to induce autophagy in SMCs. In vivo, knockdown of Meox1 attenuated injury-induced neointima formation and promoted SMCs contractile proteins expressions. Meox1 knockdown also reduced the number of proliferating SMCs, suggesting that Meox1 was important for SMCs proliferation in vivo. Moreover, knockdown of Meox1 attenuated ERK1/2 signaling and autophagy markers expressions, suggesting that Meox1 may promote SMCs phenotypic modulation via ERK1/2 signaling-autophagy in vivo. Our data indicated that Meox1 promotes SMCs phenotypic modulation and injury-induced vascular remodeling by regulating the FAK-ERK1/2-autophagy signaling cascade. Thus, targeting Meox1 may be an attractive approach for treating proliferating vascular diseases. Copyright © 2017. Published by Elsevier B.V.

  3. Homeobox transcription factor Pitx2: The rise of an asymmetry gene in cardiogenesis and arrhythmogenesis

    NARCIS (Netherlands)

    Franco, Diego; Christoffels, Vincent M.; Campione, Marina

    2014-01-01

    The homeobox transcription factor Pitx2 displays a highly specific expression pattern during embryogenesis. Gain and loss of function experiments have unraveled its pivotal role in left-right signaling. Conditional deletion in mice has demonstrated a complex and intricate role for Pitx2 in distinct

  4. Dysregulation of the homeobox transcription factor gene HOXB13: role in prostate cancer

    Directory of Open Access Journals (Sweden)

    Decker B

    2014-08-01

    Full Text Available Brennan Decker1,2, Elaine A Ostrander1 1Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; 2Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK Abstract: Prostate cancer (PC is the most common noncutaneous cancer in men, and epidemiological studies suggest that about 40% of PC risk is heritable. Linkage analyses in hereditary PC families have identified multiple putative loci. However, until recently, identification of specific risk alleles has proven elusive. Cooney et al used linkage mapping and segregation analysis to identify a putative risk locus on chromosome 17q21-22. In search of causative variant(s in genes from the candidate region, a novel, potentially deleterious G84E substitution in homeobox transcription factor gene HOXB13 was observed in multiple hereditary PC families. In follow-up testing, the G84E allele was enriched in cases, especially those with an early diagnosis or positive family history of disease. This finding was replicated by others, confirming HOXB13 as a PC risk gene. The HOXB13 protein plays diverse biological roles in embryonic development and terminally differentiated tissue. In tumor cell lines, HOXB13 participates in a number of biological functions, including coactivation and localization of the androgen receptor and FOXA1. However, no consensus role has emerged and many questions remain. All HOXB13 variants with a proposed role in PC risk are predicted to damage the protein and lie in domains that are highly conserved across species. The G84E variant has the strongest epidemiological support and lies in a highly conserved MEIS protein-binding domain, which binds cofactors required for activation. On the basis of epidemiological and biological data, the G84E variant likely modulates the interaction between the HOXB13

  5. Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

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    Maruo Kouji

    2009-10-01

    Full Text Available Abstract Background Human hemangiosarcoma (HSA tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes. Methods Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF-A, basic fibroblast growth factors (bFGF, flt-1 and flk-1 (receptors of VEGF-A, FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR, using canine-specific primer sets. Results Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the

  6. Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

    Science.gov (United States)

    2009-01-01

    Background Human hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes. Methods Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factors (bFGF), flt-1 and flk-1 (receptors of VEGF-A), FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR), using canine-specific primer sets. Results Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF) was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the other tumors. Conclusion We

  7. A neuroanatomical and physiological study of the non-image forming visual system of the cone-rod homeobox gene (Crx) knock out mouse

    DEFF Research Database (Denmark)

    Rovsing, Louise; Rath, Martin F; Lund-Andersen, Casper

    2010-01-01

    The anatomy and physiology of the non-image forming visual system was investigated in a visually blind cone-rod homeobox gene (Crx) knock-out mouse (Crx(-)(/)(-)), which lacks the outer segments of the photoreceptors. We show that the suprachiasmatic nuclei (SCN) in the Crx(-/-) mouse exhibit...

  8. Homeobox gene expression in Brachiopoda: the role of Not and Cdx in bodyplan patterning, neurogenesis, and germ layer specification.

    Science.gov (United States)

    Altenburger, Andreas; Martinez, Pedro; Wanninger, Andreas

    2011-10-01

    The molecular control that underlies brachiopod ontogeny is largely unknown. In order to contribute to this issue we analyzed the expression pattern of two homeobox containing genes, Not and Cdx, during development of the rhynchonelliform (i.e., articulate) brachiopod Terebratalia transversa. Not is a homeobox containing gene that regulates the formation of the notochord in chordates, while Cdx (caudal) is a ParaHox gene involved in the formation of posterior tissues of various animal phyla. The T. transversa homolog, TtrNot, is expressed in the ectoderm from the beginning of gastrulation until completion of larval development, which is marked by a three-lobed body with larval setae. Expression starts at gastrulation in two areas lateral to the blastopore and subsequently extends over the animal pole of the gastrula. With elongation of the gastrula, expression at the animal pole narrows to a small band, whereas the areas lateral to the blastopore shift slightly towards the future anterior region of the larva. Upon formation of the three larval body lobes, TtrNot expressing cells are present only in the posterior part of the apical lobe. Expression ceases entirely at the onset of larval setae formation. TtrNot expression is absent in unfertilized eggs, in embryos prior to gastrulation, and in settled individuals during and after metamorphosis. Comparison with the expression patterns of Not genes in other metazoan phyla suggests an ancestral role for this gene in gastrulation and germ layer (ectoderm) specification with co-opted functions in notochord formation in chordates and left/right determination in ambulacrarians and vertebrates. The caudal ortholog, TtrCdx, is first expressed in the ectoderm of the gastrulating embryo in the posterior region of the blastopore. Its expression stays stable in that domain until the blastopore is closed. Thereafter, the expression is confined to the ventral portion of the mantle lobe in the fully developed larva. No Ttr

  9. Non-trisomic homeobox gene expression during craniofacial development in the Ts65Dn mouse model of Down syndrome.

    Science.gov (United States)

    Billingsley, Cherie N; Allen, Jared R; Baumann, Douglas D; Deitz, Samantha L; Blazek, Joshua D; Newbauer, Abby; Darrah, Andrew; Long, Brad C; Young, Brandon; Clement, Mark; Doerge, R W; Roper, Randall J

    2013-08-01

    Trisomy 21 in humans causes cognitive impairment, craniofacial dysmorphology, and heart defects collectively referred to as Down syndrome. Yet, the pathophysiology of these phenotypes is not well understood. Craniofacial alterations may lead to complications in breathing, eating, and communication. Ts65Dn mice exhibit craniofacial alterations that model Down syndrome including a small mandible. We show that Ts65Dn embryos at 13.5 days gestation (E13.5) have a smaller mandibular precursor but a normal sized tongue as compared to euploid embryos, suggesting a relative instead of actual macroglossia originates during development. Neurological tissues were also altered in E13.5 trisomic embryos. Our array analysis found 155 differentially expressed non-trisomic genes in the trisomic E13.5 mandible, including 20 genes containing a homeobox DNA binding domain. Additionally, Sox9, important in skeletal formation and cell proliferation, was upregulated in Ts65Dn mandible precursors. Our results suggest trisomy causes altered expression of non-trisomic genes in development leading to structural changes associated with DS. Identification of genetic pathways disrupted by trisomy is an important step in proposing rational therapies at relevant time points to ameliorate craniofacial abnormalities in DS and other congenital disorders. Copyright © 2013 Wiley Periodicals, Inc.

  10. Expression of the KNOTTED HOMEOBOX Genes in the Cactaceae Cambial Zone Suggests Their Involvement in Wood Development

    Science.gov (United States)

    Reyes-Rivera, Jorge; Rodríguez-Alonso, Gustavo; Petrone, Emilio; Vasco, Alejandra; Vergara-Silva, Francisco; Shishkova, Svetlana; Terrazas, Teresa

    2017-01-01

    The vascular cambium is a lateral meristem that produces secondary xylem (i.e., wood) and phloem. Different Cactaceae species develop different types of secondary xylem; however, little is known about the mechanisms underlying wood formation in the Cactaceae. The KNOTTED HOMEOBOX (KNOX) gene family encodes transcription factors that regulate plant development. The role of class I KNOX genes in the regulation of the shoot apical meristem, inflorescence architecture, and secondary growth is established in a few model species, while the functions of class II KNOX genes are less well understood, although the Arabidopsis thaliana class II KNOX protein KNAT7 is known to regulate secondary cell wall biosynthesis. To explore the involvement of the KNOX genes in the enormous variability of wood in Cactaceae, we identified orthologous genes expressed in species with fibrous (Pereskia lychnidiflora and Pilosocereus alensis), non-fibrous (Ariocarpus retusus), and dimorphic (Ferocactus pilosus) wood. Both class I and class II KNOX genes were expressed in the cactus cambial zone, including one or two class I paralogs of KNAT1, as well as one or two class II paralogs of KNAT3-KNAT4-KNAT5. While the KNOX gene SHOOTMERISTEMLESS (STM) and its ortholog ARK1 are expressed during secondary growth in the Arabidopsis and Populus stem, respectively, we did not find STM orthologs in the Cactaceae cambial zone, which suggests possible differences in the vascular cambium genetic regulatory network in these species. Importantly, while two class II KNOX paralogs from the KNAT7 clade were expressed in the cambial zone of A. retusus and F. pilosus, we did not detect KNAT7 ortholog expression in the cambial zone of P. lychnidiflora. Differences in the transcriptional repressor activity of secondary cell wall biosynthesis by the KNAT7 orthologs could therefore explain the differences in wood development in the cactus species. PMID:28316604

  11. Barhl1, a gene belonging to a new subfamily of mammalian homeobox genes, is expressed in migrating neurons of the CNS.

    Science.gov (United States)

    Bulfone, A; Menguzzato, E; Broccoli, V; Marchitiello, A; Gattuso, C; Mariani, M; Consalez, G G; Martinez, S; Ballabio, A; Banfi, S

    2000-05-22

    The BarH1 and BarH2 ( Bar ) Drosophila genes are homeobox-containing genes, which are required for the fate determination of external sensory organs in the fly. By means of a bioinformatic approach, we have identified in mouse and human two homeobox genes highly related to the Bar Drosophila genes, Barhl1 and Barhl2. While Barhl1 represents a novel gene, Barhl2 turned out to correspond to the mBH1 cDNA recently described in rat. We isolated and sequenced the full-length mouse Barhl1 and mapped both the human BARHL1 and BARHL2 genes to chromosomes 9q34 and 1p22, respectively. Detailed analysis of the murine Barhl1 expression pattern by in situ hybridization revealed that this transcript is exclusively expressed in restricted domains of the developing CNS, which suggests that this gene, similar to its Drosophila counterparts BarH1 and BarH2, may play a crucial role in cell fate determination of neural structures. In particular, Barhl1 showed specific domains of expression in the diencephalon and in the rhombencephalon where it was found to be expressed in migrating cells giving rise to the cerebellar external granular layer and to specific populations of dorsal sensory interneurons of the spinal cord. Thus, Barhl1 function may be required for the generation of these specific subtypes of neuronal progenitors. Furthermore, the mapping assignment and the expression pattern make BARHL1 an attractive positional candidate gene for a form of Joubert syndrome, a rare developmental anomaly of the cerebellum in humans.

  12. Zhx2 (zinc fingers and homeoboxes 2) regulates major urinary protein gene expression in the mouse liver.

    Science.gov (United States)

    Jiang, Jieyun; Creasy, Kate Townsend; Purnell, Justin; Peterson, Martha L; Spear, Brett T

    2017-04-21

    The mouse major urinary proteins (Mups) are encoded by a large family of highly related genes clustered on chromosome 4. Mups, synthesized primarily and abundantly in the liver and secreted through the kidneys, exhibit male-biased expression. Mups bind a variety of volatile ligands; these ligands, and Mup proteins themselves, influence numerous behavioral traits. Although urinary Mup protein levels vary between inbred mouse strains, this difference is most pronounced in BALB/cJ mice, which have dramatically low urinary Mup levels; this BALB/cJ trait had been mapped to a locus on chromosome 15. We previously identified Zhx2 (zinc fingers and homeoboxes 2) as a regulator of numerous liver-enriched genes. Zhx2 is located on chromosome 15, and a natural hypomorphic mutation in the BALB/cJ Zhx2 allele dramatically reduces Zhx2 expression. Based on these data, we hypothesized that reduced Zhx2 levels are responsible for lower Mup expression in BALB/cJ mice. Using both transgenic and knock-out mice along with in vitro assays, our data show that Zhx2 binds Mup promoters and is required for high levels of Mup expression in the adult liver. In contrast to previously identified Zhx2 targets that appear to be repressed by Zhx2, Mup genes are positively regulated by Zhx2. These data identify Zhx2 as a novel regulator of Mup expression and indicate that Zhx2 activates as well as represses expression of target genes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Hearing loss caused by progressive degeneration of cochlear hair cells in mice deficient for the Barhl1 homeobox gene.

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    Li, Shengguo; Price, Sandy M; Cahill, Hugh; Ryugo, David K; Shen, Michael M; Xiang, Mengqing

    2002-07-01

    The cochlea of the mammalian inner ear contains three rows of outer hair cells and a single row of inner hair cells. These hair cell receptors reside in the organ of Corti and function to transduce mechanical stimuli into electrical signals that mediate hearing. To date, the molecular mechanisms underlying the maintenance of these delicate sensory hair cells are unknown. We report that targeted disruption of Barhl1, a mouse homolog of the Drosophila BarH homeobox genes, results in severe to profound hearing loss, providing a unique model for the study of age-related human deafness disorders. Barhl1 is expressed in all sensory hair cells during inner ear development, 2 days after the onset of hair cell generation. Loss of Barhl1 function in mice results in age-related progressive degeneration of both outer and inner hair cells in the organ of Corti, following two reciprocal longitudinal gradients. Our data together indicate an essential role for Barhl1 in the long-term maintenance of cochlear hair cells, but not in the determination or differentiation of these cells.

  14. Clinicopathological features and pituitary homeobox 1 gene expression in the progression and prognosis of cutaneous malignant melanoma

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    Figen Barut

    2016-10-01

    Full Text Available The evidence that PITX1 (pituitary homeobox 1 is a significant tumor suppressor in human cancer remains largely circumstantial, but it clearly warrants further study as little is known about the tumor-inhibitory roles of PITX1 in cutaneous malignant melanoma. The aims of this study were to investigate PITX1 gene expression in patients with cutaneous malignant melanoma and to evaluate its potential relevance to clinicopathological characteristics and tumor cell proliferation. Clinicopathological findings of patients with cutaneous malignant melanoma were analyzed retrospectively. PITX1 and Ki-67 expression were detected by immunohistochemistry in malignant melanoma and healthy tissue samples from each patient. Labeling indices were calculated based on PITX1 gene and Ki-67 expression. The correlation between PITX1and Ki-67 expressions was analyzed in cutaneous malignant melanoma cases. The relationship between PITX1 expression intensity and clinicopathological characteristics was also analyzed. PITX1 expression was observed in all (100% normal healthy skin tissue samples. In addition, PITX1 expression was found in 56 (80% and was absent in 14 (20% of the 70 cutaneous malignant melanoma cases. Ki-67 positive expression was only detected in the 14 (20% PITX1-negative cases. PITX1-positive tumor cells were observed on the surface, but Ki-67 positive tumor cells were observed in deeper zones of the tumor nests. PITX1 expression was downregulated in human cutaneous malignant melanoma lesions compared with healthy skin tissue, but Ki-67 expression was upregulated in concordance with the progression of cutaneous malignant melanoma. PITX1 expression may be involved in tumor progression and is a potential tumor suppressor gene and prognostic marker for cutaneous malignant melanoma.

  15. GmSBH1, a homeobox transcription factor gene, relates to growth and development and involves in response to high temperature and humidity stress in soybean.

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    Shu, Yingjie; Tao, Yuan; Wang, Shuang; Huang, Liyan; Yu, Xingwang; Wang, Zhankui; Chen, Ming; Gu, Weihong; Ma, Hao

    2015-11-01

    GmSBH1 involves in response to high temperature and humidity stress. Homeobox transcription factors are key switches that control plant development processes. Glycine max H1 Sbh1 (GmSBH1) was the first homeobox gene isolated from soybean. In the present study, the full ORF of GmSBH1 was isolated, and the encoded protein was found to be a typical class I KNOX homeobox transcription factor. Subcellular localization and transcriptional activation assays showed that GmSBH1 is a nuclear protein and possesses transcriptional activation activity in the homeodomain. The KNOX1 domain was found to play a clear role in suppressing the transcriptional activation activity of GmSBH1. GmSBH1 showed different expression levels among different soybean tissues and was involved in response to high temperature and humidity (HTH) stress in developing soybean seeds. The overexpression of GmSBH1 in Arabidopsis altered leaf and stoma phenotypes and enhanced seed tolerance to HTH stress. Overall, our results indicated that GmSBH1 is involved in growth, development, and enhances tolerance to pre-harvest seed deterioration caused by HTH stress in soybean.

  16. Rapid evolution and copy number variation of primate RHOXF2, an X-linked homeobox gene involved in male reproduction and possibly brain function

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    Zhang Rui

    2011-10-01

    Full Text Available Abstract Background Homeobox genes are the key regulators during development, and they are in general highly conserved with only a few reported cases of rapid evolution. RHOXF2 is an X-linked homeobox gene in primates. It is highly expressed in the testicle and may play an important role in spermatogenesis. As male reproductive system is often the target of natural and/or sexual selection during evolution, in this study, we aim to dissect the pattern of molecular evolution of RHOXF2 in primates and its potential functional consequence. Results We studied sequences and copy number variation of RHOXF2 in humans and 16 nonhuman primate species as well as the expression patterns in human, chimpanzee, white-browed gibbon and rhesus macaque. The gene copy number analysis showed that there had been parallel gene duplications/losses in multiple primate lineages. Our evidence suggests that 11 nonhuman primate species have one RHOXF2 copy, and two copies are present in humans and four Old World monkey species, and at least 6 copies in chimpanzees. Further analysis indicated that the gene duplications in primates had likely been mediated by endogenous retrovirus (ERV sequences flanking the gene regions. In striking contrast to non-human primates, humans appear to have homogenized their two RHOXF2 copies by the ERV-mediated non-allelic recombination mechanism. Coding sequence and phylogenetic analysis suggested multi-lineage strong positive selection on RHOXF2 during primate evolution, especially during the origins of humans and chimpanzees. All the 8 coding region polymorphic sites in human populations are non-synonymous, implying on-going selection. Gene expression analysis demonstrated that besides the preferential expression in the reproductive system, RHOXF2 is also expressed in the brain. The quantitative data suggests expression pattern divergence among primate species. Conclusions RHOXF2 is a fast-evolving homeobox gene in primates. The rapid

  17. Rapid evolution and copy number variation of primate RHOXF2, an X-linked homeobox gene involved in male reproduction and possibly brain function.

    Science.gov (United States)

    Niu, Ao-lei; Wang, Yin-qiu; Zhang, Hui; Liao, Cheng-hong; Wang, Jin-kai; Zhang, Rui; Che, Jun; Su, Bing

    2011-10-12

    Homeobox genes are the key regulators during development, and they are in general highly conserved with only a few reported cases of rapid evolution. RHOXF2 is an X-linked homeobox gene in primates. It is highly expressed in the testicle and may play an important role in spermatogenesis. As male reproductive system is often the target of natural and/or sexual selection during evolution, in this study, we aim to dissect the pattern of molecular evolution of RHOXF2 in primates and its potential functional consequence. We studied sequences and copy number variation of RHOXF2 in humans and 16 nonhuman primate species as well as the expression patterns in human, chimpanzee, white-browed gibbon and rhesus macaque. The gene copy number analysis showed that there had been parallel gene duplications/losses in multiple primate lineages. Our evidence suggests that 11 nonhuman primate species have one RHOXF2 copy, and two copies are present in humans and four Old World monkey species, and at least 6 copies in chimpanzees. Further analysis indicated that the gene duplications in primates had likely been mediated by endogenous retrovirus (ERV) sequences flanking the gene regions. In striking contrast to non-human primates, humans appear to have homogenized their two RHOXF2 copies by the ERV-mediated non-allelic recombination mechanism. Coding sequence and phylogenetic analysis suggested multi-lineage strong positive selection on RHOXF2 during primate evolution, especially during the origins of humans and chimpanzees. All the 8 coding region polymorphic sites in human populations are non-synonymous, implying on-going selection. Gene expression analysis demonstrated that besides the preferential expression in the reproductive system, RHOXF2 is also expressed in the brain. The quantitative data suggests expression pattern divergence among primate species. RHOXF2 is a fast-evolving homeobox gene in primates. The rapid evolution and copy number changes of RHOXF2 had been driven by

  18. Screening the visual system homeobox 1 gene in keratoconus and posterior polymorphous dystrophy cohorts identifies a novel variant.

    Science.gov (United States)

    Vincent, Andrea L; Jordan, Charlotte; Sheck, Leo; Niederer, Rachel; Patel, Dipika V; McGhee, Charles N J

    2013-01-01

    Mutations in the visual system homeobox 1 (VSX1) gene have been described at a low frequency in keratoconus and posterior polymorphous corneal dystrophy (PPCD). The putative role is controversial for several reasons, including a lack of mutations detected in other population cohorts. This study aims to determine whether VSX1 contributes to the genetic pathogenesis of keratoconus and PPCD in a New Zealand population, and includes analysis of a Polynesian population. Recruitment of patients with keratoconus and PPCD, comprehensive clinical examination including corneal topography and pachymetry, and collection of biologic samples for DNA extraction were undertaken. Mutational analysis of VSX1 (exons 1-7) with PCR and sequencing with bioinformatic assessment of variants was performed. Probable pathogenic variants were screened for in a control population using high-resolution melting analysis. Forty-seven patients with keratoconus, including 15 familial cases, and ten unrelated patients with PPCD were recruited. Two pathogenic changes were detected; a novel change c.173C>T (p.Pro58Leu) was found in a patient with PPCD, predicted to be pathogenic, and not seen in 200 ethnically matched control alleles. The previously reported c.731A>G (p.His244Arg) was detected in a patient with sporadic keratoconus, and not present in the controls. No family members were available for segregation analysis. This study reports the presence of pathogenic mutations in VSX1 in PPCD and keratoconus, including a novel disease-causing variant. The affected numbers are small, but given the growing body of evidence of pathogenic segregating changes in VSX1 in disease cohorts, the expression in keratocytes as part of wound healing, and the documented association of PPCD and keratoconus, it seems likely that the role of VSX1 as a genetic factor contributing to disease is real.

  19. Molecular analysis and its expression of a pou homeobox protein gene during development and in response to salinity stress from brine shrimp, Artemia sinica.

    Science.gov (United States)

    Wang, Jia-Qing; Hou, Lin; Yi, Nan; Zhang, Riu-Feng; Zou, Xiang-Yang

    2012-01-01

    Brine shrimps of the genus Artemia are aquatic species of economic importance because of their important significance to aquaculture and are used as a model species in physiology and developmental biology. Research on Artemia POU homeobox gene function will enhance our understanding of the physiological and developmental processes of POU homeobox gene in animals. Herein, a full-length cDNA encoding an Artemia POU homeobox protein gene 1 (APH-1) from Artemia sinica (designated as As-APH-1) was cloned and characterized by a reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA end (RACE) method. The As-APH-1 gene encoded a protein of 388 amino acid polypeptide with a calculated molecular mass of 42.85kDa and an isoelectric point of 6.90 and the protein belongs to the POU III family. Multiple sequence alignments revealed that A. sinica As-APH-1 protein sequence shared a conserved POU homeobox domain with other species. The early and persistent expression of As-APH-1 in the naupliar stages by semi-quantitative RT-PCR and whole-mount embryonic immunohistochemistry suggest that As-APH-1 functions very early in the salt gland and may be required continuously in this organ. Later in development, expression of As-APH-1 begins to dramatically decrease and disappear in salt gland of the sub-adult Artemia. In addition, we also discovered that As-APH-1 increased obviously as the salinity increased, indicating that As-APH-1 might be used as a good indicator of salinity stress. In summary, we are the first to identify the As-APH-1 gene and to determine its gene expression patterns in early embryogenesis stages and in different salinity stress in brine shrimp, A. sinica. The result of expression of As-APH-1 affected by salinity changes will provide us further understanding of the underlying mechanisms of osmoregulation in Artemia early embryonic development. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Mutation in the human homeobox gene NKX5-3 causes an oculo-auricular syndrome.

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    Schorderet, Daniel F; Nichini, Olivia; Boisset, Gaëlle; Polok, Bozena; Tiab, Leila; Mayeur, Hélène; Raji, Bahija; de la Houssaye, Gauillaume; Abitbol, Marc M; Munier, Francis L

    2008-05-01

    Several dysmorphic syndromes affect the development of both the eye and the ear, but only a few are restricted to the eye and the external ear. We describe a developmental defect affecting the eye and the external ear in three members of a consanguineous family. This syndrome is characterized by ophthalmic anomalies (microcornea, microphthalmia, anterior-segment dysgenesis, cataract, coloboma of various parts of the eye, abnormalities of the retinal pigment epithelium, and rod-cone dystrophy) and a particular cleft ear lobule. Linkage analysis and mutation screening revealed in the first exon of the NKX5-3 gene a homozygous 26 nucleotide deletion, generating a truncating protein that lacked the complete homeodomain. Morpholino knockdown expression of the zebrafish nkx5-3 induced microphthalmia and disorganization of the developing retina, thus confirming that this gene represents an additional member implicated in axial patterning of the retina.

  1. The Arabidopsis thaliana homeobox gene ATHB12 is involved in symptom development caused by geminivirus infection.

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    Jungan Park

    Full Text Available BACKGROUND: Geminiviruses are single-stranded DNA viruses that infect a number of monocotyledonous and dicotyledonous plants. Arabidopsis is susceptible to infection with the Curtovirus, Beet severe curly top virus (BSCTV. Infection of Arabidopsis with BSCTV causes severe symptoms characterized by stunting, leaf curling, and the development of abnormal inflorescence and root structures. BSCTV-induced symptom development requires the virus-encoded C4 protein which is thought to interact with specific plant-host proteins and disrupt signaling pathways important for controlling cell division and development. Very little is known about the specific plant regulatory factors that participate in BSCTV-induced symptom development. This study was conducted to identify specific transcription factors that are induced by BSCTV infection. METHODOLOGY/PRINCIPAL FINDINGS: Arabidopsis plants were inoculated with BSCTV and the induction of specific transcription factors was monitored using quantitative real-time polymerase chain reaction assays. We found that the ATHB12 and ATHB7 genes, members of the homeodomain-leucine zipper family of transcription factors previously shown to be induced by abscisic acid and water stress, are induced in symptomatic tissues of Arabidopsis inoculated with BSCTV. ATHB12 expression is correlated with an array of morphological abnormalities including leaf curling, stunting, and callus-like structures in infected Arabidopsis. Inoculation of plants with a BSCTV mutant with a defective c4 gene failed to induce ATHB12. Transgenic plants expressing the BSCTV C4 gene exhibited increased ATHB12 expression whereas BSCTV-infected ATHB12 knock-down plants developed milder symptoms and had lower ATHB12 expression compared to the wild-type plants. Reporter gene studies demonstrated that the ATHB12 promoter was responsive to BSCTV infection and the highest expression levels were observed in symptomatic tissues where cell cycle genes also were

  2. Characterization of Leukemia-Inducing Genes Using a Proto-Oncogene/Homeobox Gene Retroviral Human cDNA Library in a Mouse In Vivo Model

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    Jang, Su Hwa; Lee, Sohyun; Chung, Hee Yong

    2015-01-01

    The purpose of this research is to develop a method to screen a large number of potential driver mutations of acute myeloid leukemia (AML) using a retroviral cDNA library and murine bone marrow transduction-transplantation system. As a proof-of-concept, murine bone marrow (BM) cells were transduced with a retroviral cDNA library encoding well-characterized oncogenes and homeobox genes, and the virus-transduced cells were transplanted into lethally irradiated mice. The proto-oncogenes responsible for leukemia initiation were identified by PCR amplification of cDNA inserts from genomic DNA isolated from leukemic cells. In an initial screen of ten leukemic mice, the MYC proto-oncogene was detected in all the leukemic mice. Of ten leukemic mice, 3 (30%) had MYC as the only transgene, and seven mice (70%) had additional proto-oncogene inserts. We repeated the same experiment after removing MYC-related genes from the library to characterize additional leukemia-inducing gene combinations. Our second screen using the MYC-deleted proto-oncogene library confirmed MEIS1and the HOX family as cooperating oncogenes in leukemia pathogenesis. The model system we introduced in this study will be valuable in functionally screening novel combinations of genes for leukemogenic potential in vivo, and the system will help in the discovery of new targets for leukemia therapy. PMID:26606454

  3. Regulation of retinal interneuron subtype identity by the Iroquois homeobox gene Irx6.

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    Star, Erin N; Zhu, Minyan; Shi, Zhiwei; Liu, Haiquan; Pashmforoush, Mohammad; Sauve, Yves; Bruneau, Benoit G; Chow, Robert L

    2012-12-01

    Interneuronal subtype diversity lies at the heart of the distinct molecular properties and synaptic connections that shape the formation of the neuronal circuits that are necessary for the complex spatial and temporal processing of sensory information. Here, we investigate the role of Irx6, a member of the Iroquois homeodomain transcription factor family, in regulating the development of retinal bipolar interneurons. Using a knock-in reporter approach, we show that, in the mouse retina, Irx6 is expressed in type 2 and 3a OFF bipolar interneurons and is required for the expression of cell type-specific markers in these cells, likely through direct transcriptional regulation. In Irx6 mutant mice, presumptive type 3a bipolar cells exhibit an expansion of their axonal projection domain to the entire OFF region of the inner plexiform layer, and adopt molecular features of both type 2 and 3a bipolar cells, highlighted by the ectopic upregulation of neurokinin 3 receptor (Nk3r) and Vsx1. These findings reveal Irx6 as a key regulator of type 3a bipolar cell identity that prevents these cells from adopting characteristic features of type 2 bipolar cells. Analysis of the Irx6;Vsx1 double null retina suggests that the terminal differentiation of type 2 bipolar cells is dependent on the combined expression of the transcription factors Irx6 and Vsx1, but also points to the existence of Irx6;Vsx1-independent mechanisms in regulating OFF bipolar subtype-specific gene expression. This work provides insight into the generation of neuronal subtypes by revealing a mechanism in which opposing, yet interdependent, transcription factors regulate subtype identity.

  4. Regulation and functions of the lms homeobox gene during development of embryonic lateral transverse muscles and direct flight muscles in Drosophila.

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    Dominik Müller

    Full Text Available BACKGROUND: Patterning and differentiation of developing musculatures require elaborate networks of transcriptional regulation. In Drosophila, significant progress has been made into identifying the regulators of muscle development and defining their interactive networks. One major family of transcription factors involved in these processes consists of homeodomain proteins. In flies, several members of this family serve as muscle identity genes to specify the fates of individual muscles, or groups thereof, during embryonic and/or adult muscle development. Herein, we report on the expression and function of a new Drosophila homeobox gene during both embryonic and adult muscle development. METHODOLOGY/PRINCIPAL FINDINGS: The newly described homeobox gene, termed lateral muscles scarcer (lms, which has yet uncharacterized orthologs in other invertebrates and primitive chordates but not in vertebrates, is expressed exclusively in subsets of developing muscle tissues. In embryos, lms is expressed specifically in the four lateral transverse (LT muscles and their founder cells in each hemisegment, whereas in larval wing imaginal discs, it is expressed in myoblasts that develop into direct flight muscles (DFMs, which are important for proper wing positioning. We have analyzed the regulatory inputs of various other muscle identity genes with overlapping or complementary expression patterns towards the cell type specific regulation of lms expression. Further we demonstrate that lms null mutants exhibit reduced numbers of embryonic LT muscles, and null mutant adults feature held-out-wing phenotypes. We provide a detailed description of the pattern and morphology of the direct flight muscles in the wild type and lms mutant flies by using the recently-developed ultramicroscopy and show that, in the mutants, all DFMs are present and present normal morphologies. CONCLUSIONS/SIGNIFICANCE: We have identified the homeobox gene lms as a new muscle identity gene

  5. A role for the homeobox protein Distal-less 3 in the activation of the glycoprotein hormone alpha subunit gene in choriocarcinoma cells.

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    Roberson, M S; Meermann, S; Morasso, M I; Mulvaney-Musa, J M; Zhang, T

    2001-03-30

    Synthesis and secretion of chorionic gonadotropin in trophoblast cells of the placenta is required for establishment of early pregnancy in primates. Chorionic gonadotropin is a heterodimeric glycoprotein hormone consisting of alpha and beta subunits. Regulation of the alpha subunit gene within the placenta requires an array of cis elements within the 5'-flanking region of the promoter. Within this array of elements, the junctional regulatory element (JRE) putatively binds a placental-specific transcription factor. The aim of our studies was to determine the identity and role of the transcriptional regulator that binds to the JRE in choriocarcinoma cells (JEG3 cells). Mutations within the JRE resulted in reduction in basal expression of an alpha subunit reporter gene, suggesting that the JRE binding factor was necessary for full basal activity. Using electrophoretic mobility shift assays, we determined that the JRE was capable of serving as a homeobox factor-binding site. The homeobox factor, Distal-less 3 (Dlx 3) was found to be expressed in JEG3 cells and in the trophoblast layer of human chorionic villus but not in a gonadotrope cell line that also expresses the alpha subunit gene. Electrophoretic mobility shift assays revealed that recombinant Dlx 3 could bind specifically to the JRE and endogenous Dlx 3 was present in JRE/JEG3 nuclear protein complexes. Overexpression of Dlx 3 resulted in activation of an alpha subunit reporter gene. A JRE mutation resulted in attenuated activation of the alpha subunit reporter via an adjacent cis element, suggesting that JRE/Dlx 3 interactions may facilitate regulation of the alpha subunit gene at sites immediately upstream of the JRE. Our studies support the conclusion that Dlx 3 is a placental-specific transcriptional regulator that binds to the JRE and contributes to expression of the alpha subunit gene in cells of trophoblast origin.

  6. A modulatory role of the Rax homeobox gene in mature pineal gland function: Investigating the photoneuroendocrine circadian system of a Rax conditional knockout mouse.

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    Rohde, Kristian; Bering, Tenna; Furukawa, Takahisa; Rath, Martin Fredensborg

    2017-10-01

    The retinal and anterior neural fold homeobox gene (Rax) controls development of the eye and the forebrain. Postnatal expression of Rax in the brain is restricted to the pineal gland, a forebrain structure devoted to melatonin synthesis. The role of Rax in pineal function is unknown. In order to investigate the role of Rax in pineal function while circumventing forebrain abnormalities of the global Rax knockout, we generated an eye and pineal-specific Rax conditional knockout mouse. Deletion of Rax in the pineal gland did not affect morphology of the gland, suggesting that Rax is not essential for pineal gland development. In contrast, deletion of Rax in the eye generated an anophthalmic phenotype. In addition to the loss of central visual pathways, the suprachiasmatic nucleus of the hypothalamus housing the circadian clock was absent, indicating that the retinohypothalamic tract is required for the nucleus to develop. Telemetric analyses confirmed the lack of a functional circadian clock. Arylalkylamine N-acetyltransferase (Aanat) transcripts, encoding the melatonin rhythm-generating enzyme, were undetectable in the pineal gland of the Rax conditional knockout under normal conditions, whereas the paired box 6 homeobox gene, known to regulate pineal development, was up-regulated. By injecting isoproterenol, which mimics a nocturnal situation in the pineal gland, we were able to induce pineal expression of Aanat in the Rax conditional knockout mouse, but Aanat transcript levels were significantly lower than those of Rax-proficient mice. Our data suggest that Rax controls pineal gene expression and via Aanat may modulate melatonin synthesis. © 2017 International Society for Neurochemistry.

  7. Analysis of the WUSCHEL-RELATED HOMEOBOX gene family in the conifer picea abies reveals extensive conservation as well as dynamic patterns

    Science.gov (United States)

    2013-01-01

    Background Members of the WUSCHEL-RELATED HOMEOBOX (WOX) gene family have important functions during all stages of plant development and have been implicated in the development of morphological novelties during evolution. Most studies have examined the function of these genes in angiosperms and very little is known from other plant species. Results In this study we examine the presence and expression of WOX genes in the conifer Picea abies. We have cloned 11 WOX genes from both mRNA and genomic DNA and examined their phylogenetic relationship to WOX genes from other species as well as their expression during somatic embryogenesis and in adult tissues. Conclusions Our study shows that all major radiations within the WOX gene family took place before the angiosperm-gymnosperm split and that there has been a recent expansion within the intermediate clade in the Pinaceae family. Furthermore, we show that the genes from the intermediate clade are preferentially expressed during embryo development in Picea abies. Our data also indicates that there are clear orthologs of both WUS and WOX5 present in the P. abies genome. PMID:23758772

  8. Genome-wide association mapping in dogs enables identification of the homeobox gene, NKX2-8, as a genetic component of neural tube defects in humans.

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    Noa Safra

    Full Text Available Neural tube defects (NTDs is a general term for central nervous system malformations secondary to a failure of closure or development of the neural tube. The resulting pathologies may involve the brain, spinal cord and/or vertebral column, in addition to associated structures such as soft tissue or skin. The condition is reported among the more common birth defects in humans, leading to significant infant morbidity and mortality. The etiology remains poorly understood but genetic, nutritional, environmental factors, or a combination of these, are known to play a role in the development of NTDs. The variable conditions associated with NTDs occur naturally in dogs, and have been previously reported in the Weimaraner breed. Taking advantage of the strong linkage-disequilibrium within dog breeds we performed genome-wide association analysis and mapped a genomic region for spinal dysraphism, a presumed NTD, using 4 affected and 96 unaffected Weimaraners. The associated region on canine chromosome 8 (pgenome  =3.0 × 10(-5, after 100,000 permutations, encodes 18 genes, including NKX2-8, a homeobox gene which is expressed in the developing neural tube. Sequencing NKX2-8 in affected Weimaraners revealed a G to AA frameshift mutation within exon 2 of the gene, resulting in a premature stop codon that is predicted to produce a truncated protein. The exons of NKX2-8 were sequenced in human patients with spina bifida and rare variants (rs61755040 and rs10135525 were found to be significantly over-represented (p=0.036. This is the first documentation of a potential role for NKX2-8 in the etiology of NTDs, made possible by investigating the molecular basis of naturally occurring mutations in dogs.

  9. Visual System Homeobox 1 (VSX1) Gene Analysis in Keratoconus: Design of Specific Primers and DNA Amplification Protocols for Accurate Molecular Characterization.

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    Ng, Jun B; Poh, Rozaida Y Y; Lee, Kenneth R; Subrayan, Visvaraja; Deva, Jenny P; Lau, Amy Y L; Tan, Jin A M A

    2016-09-01

    Keratoconus is an ocular degeneration characterized by the thinning of corneal stroma that may lead to varying degrees of myopia and visual impairment. Genetic factors have been reported in the pathology of keratoconus where Asians have a higher incidence, earlier onset, and undergo earlier corneal grafts compared to Caucasians. The visual system homeobox 1 (VSX1) gene forms part of a paired-like homeodomain transcription factor which is responsible for ocular development. The gene was marked as a candidate in genetic studies of keratoconus in various populations. Single nucleotide polymorphisms (SNPs) in the VSX1 gene have been reported to be associated with keratoconus. The detection of the SNPs involves DNA amplification of the VSX1 gene followed by genomic sequencing. Thus, the objective of this study aims to establish sensitive and accurate screening protocols for the molecular characterization of VSX1 polymorphisms. Keratoconic (n = 74) and control subjects (n = 96) were recruited based on clinical diagnostic tests and selection criteria. DNA extracted from the blood samples was used to genotype VSX1 polymorphisms. In-house designed primers and optimization of PCR conditions were carried out to amplify exons 1 and 3 of the VSX1 gene. PCR conditions including percentage GC content, melting temperatures, and differences in melting temperatures of primers were evaluated to produce sensitive and specific DNA amplifications. Genotyping was successfully carried out in 4 exons of the VSX1 gene. Primer annealing temperatures were observed to be crucial in enhancing PCR sensitivity and specificity. Annealing temperatures were carefully evaluated to produce increased specificity, yet not allowing sensitivity to be compromised. In addition, exon 1 of the VSX1 gene was amplified using 2 different sets of primers to produce 2 smaller amplified products with absence of non-specific bands. DNA amplification of exons 1 and 3 consistently showed single band products which

  10. Ectoderm from various regions of the developing chick limb bud differentially regulates the expression of the chicken homeobox-containing genes GHox-7 and GHox-8 by limb mesenchymal cells.

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    Coelho, C N; Upholt, W B; Kosher, R A

    1993-03-01

    The apical ectodermal ridge expresses high amounts of the homeobox gene GHox-8 when placed upon dissociated limb mesenchymal cells in culture and induces high expression of GHox-7, but only low expression of GHox-8, in the underlying mesenchymal cells. Ectoderm from the proximal anterior border of the limb induces high expression of both GHox-7 and GHox-8, while ectoderm from the proximal posterior border does not induce expression of either gene. Thus, ectoderm in various regions of the limb bud has distinct regulatory activities and may be involved in controlling the regionally specific expression of GHox-7 and GHox-8 in the mesoderm.

  11. Suppression of the homeobox gene HDTF1 enhances resistance to Verticillium dahliae and Botrytis cinerea in cotton.

    Science.gov (United States)

    Gao, Wei; Long, Lu; Xu, Li; Lindsey, Keith; Zhang, Xianlong; Zhu, Longfu

    2016-05-01

    Development of pathogen-resistant crops, such as fungus-resistant cotton, has significantly reduced chemical application and improved crop yield and quality. However, the mechanism of resistance to cotton pathogens such as Verticillium dahliae is still poorly understood. In this study, we characterized a cotton gene (HDTF1) that was isolated following transcriptome profiling during the resistance response of cotton to V. dahliae. HDTF1 putatively encodes a homeodomain transcription factor, and its expression was found to be down-regulated in cotton upon inoculation with V. dahliae and Botrytis cinerea. To characterise the involvement of HDTF1 in the response to these pathogens, we used virus-induced gene silencing (VIGS) to generate HDTF1-silenced cotton. VIGS reduction in HDTF1 expression significantly enhanced cotton plant resistance to both pathogens. HDTF1 silencing resulted in activation of jasmonic acid (JA)-mediated signaling and JA accumulation. However, the silenced plants were not altered in the accumulation of salicylic acid (SA) or the expression of marker genes associated with SA signaling. These results suggest that HDTF1 is a negative regulator of the JA pathway, and resistance to V. dahliae and B. cinerea can be engineered by activation of JA signaling. © 2015 Institute of Botany, Chinese Academy of Sciences.

  12. miR-224 promotion of cell migration and invasion by targeting Homeobox D 10 gene in human hepatocellular carcinoma.

    Science.gov (United States)

    Li, Qiong; Ding, Chenchen; Chen, Chuan; Zhang, Zhimin; Xiao, He; Xie, Fei; Lei, Lin; Chen, Yuanyuan; Mao, Bijing; Jiang, Mei; Li, Jian; Wang, Dong; Wang, Ge

    2014-04-01

    MicroRNAs (miRNAs) are small noncoding RNA molecules that control target gene expression and are implicated in the regulation of diverse cellular pathways. In our previous research, we have demonstrated that miR-224 was overexpressed in liver cancer cells and tissues, which was an important factor in the regulation of cell migration and invasion. This study aimed to further explore the regulatory mechanism of miR-224 in the migration and invasion in liver cancer cells. A luciferase reporter assay was used to confirm that the HOXD10 gene was a direct target of miR-224. Quantitative reverse transcriptase-polymerase chain reaction, Western blotting, Transwell migration, and Matrigel invasion assays were performed to clarify the molecular mechanism of miR-224 in the regulation of cell migration and invasion in human hepatocellular carcinoma (HCC). (i) The expression of miR-224 was strongly upregulated in MHHC97H and MHCC97L cells, and its expression level was significantly associated with cell invasive potential. (ii) The HOXD10 gene was confirmed to be a direct target of miR-224. Compared with normal liver tissues and cells, HOXD10 had lower expression in HCC tissues and cells and inversely regulated HCC cell invasion. (iii) miR-224 promoted expression of the tumor invasion-associated proteins p-PAK4 and MMP-9 by directly targeting HOXD10. Our findings suggest a previously undescribed regulatory pathway in which the miR-224/HOXD10/p-PAK4/MMP-9 signaling pathway contributes to the regulation of cell migration and invasion and provides a new biotarget for HCC treatment. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  13. An amphioxus LIM-homeobox gene, AmphiLim1/5, expressed early in the invaginating organizer region and later in differentiating cells of the kidney and central nervous system

    OpenAIRE

    James A. Langeland, Linda Z. Holland, Roger A. Chastain, Nicholas D. Holland

    2006-01-01

    A LIM-homeobox gene, AmphiLim1/5, from the Florida amphioxus (Branchiostoma floridae) encodes a protein that phylogenetic analysis positions at the base of a clade comprising vertebrate Lim1 and Lim5. Amphioxus AmphiLim1/5 is expressed in domains that are a composite of those of vertebrate Lim1 and Lim5, which evidently underwent subfunctionalization after duplication of an ancestral protochordate Lim1/5. During amphioxus development, transcription is first detected in the ectoderm of the bla...

  14. Timing the generation of distinct retinal cells by homeobox proteins.

    Directory of Open Access Journals (Sweden)

    Sarah Decembrini

    2006-09-01

    Full Text Available The reason why different types of vertebrate nerve cells are generated in a particular sequence is still poorly understood. In the vertebrate retina, homeobox genes play a crucial role in establishing different cell identities. Here we provide evidence of a cellular clock that sequentially activates distinct homeobox genes in embryonic retinal cells, linking the identity of a retinal cell to its time of generation. By in situ expression analysis, we found that the three Xenopus homeobox genes Xotx5b, Xvsx1, and Xotx2 are initially transcribed but not translated in early retinal progenitors. Their translation requires cell cycle progression and is sequentially activated in photoreceptors (Xotx5b and bipolar cells (Xvsx1 and Xotx2. Furthermore, by in vivo lipofection of "sensors" in which green fluorescent protein translation is under control of the 3' untranslated region (UTR, we found that the 3' UTRs of Xotx5b, Xvsx1, and Xotx2 are sufficient to drive a spatiotemporal pattern of translation matching that of the corresponding proteins and consistent with the time of generation of photoreceptors (Xotx5b and bipolar cells (Xvsx1 and Xotx2. The block of cell cycle progression of single early retinal progenitors impairs their differentiation as photoreceptors and bipolar cells, but is rescued by the lipofection of Xotx5b and Xvsx1 coding sequences, respectively. This is the first evidence to our knowledge that vertebrate homeobox proteins can work as effectors of a cellular clock to establish distinct cell identities.

  15. Expression of interferon regulatory factor 6, muscle segment homeobox 1, paired box gene 9, homeo box B3, and related to tyrosine kinases in human cleft-affected tissue

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    Benita Krivicka-Uzkurele

    2016-01-01

    Full Text Available Background and Aim: Recent studies demonstrate direct roles of different genes during formation of secondary palate, but there are no still data about local expression and distribution of gene products in cleft palate affected human tissue. Thus, the aim of our study was to investigate cleft disordered cartilage and bone for detection of local expression of key regulators of palatogenesis and its correlations. Materials and Methods: The study involved 16 patients with unilateral cleft lip and palate. Tissue samples were proceeded for detection of interferon regulatory factor 6 (IRF6, muscle segment homeobox 1 (MSX1, paired box gene 9 (PAX9, homeo box B3 (HOXB3, and related to tyrosine kinases with biotin-streptavidin immunohistochemistry. Distribution of immunoreactive structures was detected semiquantitatively. Statistical analysis included the Mann-Whitney test and Pearson′s correlation test. Results: Statistically significant differences were found between expression of IGFR6, MSX1, and HOXB3 in the cartilage and bone. We also detected statistically significant correlation between the expressions of PAX9 and MSX1 in the bone tissue. Conclusions: Cleft lip and palate disordered cartilage is characterized by more pronounced expression of IRF6, MSX1, and PAX9. Expression of HOXB3 is more characteristic for cleft lip and palate affected bone. Considered as a whole, our results suggest that the cleft lip and palate affected cartilage seems more plastic in tissue remodeling what can probably result in qualitative postoperative tissue reconstruction.

  16. A 20 bp Duplication in Exon 2 of the Aristaless-Like Homeobox 4 Gene (ALX4 Is the Candidate Causative Mutation for Tibial Hemimelia Syndrome in Galloway Cattle.

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    Bertram Brenig

    Full Text Available Aristaless-like homeobox 4 (ALX4 gene is an important transcription regulator in skull and limb development. In humans and mice ALX4 mutations or loss of function result in a number of skeletal and organ malformations, including polydactyly, tibial hemimelia, omphalocele, biparietal foramina, impaired mammary epithelial morphogenesis, alopecia, coronal craniosynostosis, hypertelorism, depressed nasal bridge and ridge, bifid nasal tip, hypogonadism, and body agenesis. Here we show that a complex skeletal malformation of the hind limb in Galloway cattle together with other developmental anomalies is a recessive autosomal disorder most likely caused by a duplication of 20 bp in exon 2 of the bovine ALX4 gene. A second duplication of 34 bp in exon 4 of the same gene has no known effect, although both duplications result in a frameshift and premature stop codon leading to a truncated protein. Genotyping of 1,688 Black/Red/Belted/Riggit Galloway (GA and 289 White Galloway (WGA cattle showed that the duplication in exon 2 has allele frequencies of 1% in GA and 6% in WGA and the duplication in exon 4 has frequencies of 23% in GA and 38% in WGA. Both duplications were not detected in 876 randomly selected German Holstein Friesian and 86 cattle of 21 other breeds. Hence, we have identified a candidate causative mutation for tibial hemimelia syndrome in Galloway cattle and selection against this mutation can be used to eliminate the mutant allele from the breed.

  17. Deoxyribonucleic-binding homeobox proteins are augmented in human cancer

    DEFF Research Database (Denmark)

    Wewer, U M; Mercurio, A M; Chung, S Y

    1990-01-01

    the highly conserved 60 amino acid homeodomain. This peptide antiserum recognized a protein species of molecular weight 63,000 in immunoblots of nuclear extracts obtained from several tumor cell lines. The predominant molecular weight 63,000 nuclear protein recognized by the peptide antiserum...... the same patients exhibited little immunoreactivity. Both the peptide antiserum and the polyclonal antiserum against the native protein immunoblotted a molecular weight 63,000 protein in nuclear extracts of tumor tissue, but not significantly in extracts of normal tissue. At the molecular level......Homeobox genes encode sequence-specific DNA-binding proteins that are involved in the regulation of gene expression during embryonic development. In this study, we examined the expression of homeobox proteins in human cancer. Antiserum was obtained against a synthetic peptide derived from...

  18. The homeobox gene Gsx2 regulates the self-renewal and differentiation of neural stem cells and the cell fate of postnatal progenitors.

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    Héctor R Méndez-Gómez

    Full Text Available The Genetic screened homeobox 2 (Gsx2 transcription factor is required for the development of olfactory bulb (OB and striatal neurons, and for the regional specification of the embryonic telencephalon. Although Gsx2 is expressed abundantly by progenitor cells in the ventral telencephalon, its precise function in the generation of neurons from neural stem cells (NSCs is not clear. Similarly, the role of Gsx2 in regulating the self-renewal and multipotentiality of NSCs has been little explored. Using retroviral vectors to express Gsx2, we have studied the effect of Gsx2 on the growth of NSCs isolated from the OB and ganglionic eminences (GE, as well as its influence on the proliferation and cell fate of progenitors in the postnatal mouse OB. Expression of Gsx2 reduces proliferation and the self-renewal capacity of NSCs, without significantly affecting cell death. Furthermore, Gsx2 overexpression decreases the differentiation of NSCs into neurons and glia, and it maintains the cells that do not differentiate as cycling progenitors. These effects were stronger in GESCs than in OBSCs, indicating that the actions of Gsx2 are cell-dependent. In vivo, Gsx2 produces a decrease in the number of Pax6+ cells and doublecortin+ neuroblasts, and an increase in Olig2+ cells. In summary, our findings show that Gsx2 inhibits the ability of NSCs to proliferate and self-renew, as well as the capacity of NSC-derived progenitors to differentiate, suggesting that this transcription factor regulates the quiescent and undifferentiated state of NSCs and progenitors. Furthermore, our data indicate that Gsx2 negatively regulates neurogenesis from postnatal progenitor cells.

  19. A knotted1-like homeobox protein regulates abscission in tomato by modulating the auxin pathway

    Science.gov (United States)

    KD1, a gene encoding a KNOTTED1-LIKE HOMEOBOX transcription factor is known to be involved, in tomato, in ontogeny of the compound leaf. KD1 is also highly expressed in both leaf and flower abscission zones. Reducing abundance of transcripts of this gene in tomato, using both virus induced gene sile...

  20. Multiple Versions of the a Mating Type Locus of Coprinus Cinereus Are Generated by Three Paralogous Pairs of Multiallelic Homeobox Genes

    Science.gov (United States)

    Pardo, E. H.; O'Shea, S. F.; Casselton, L. A.

    1996-01-01

    The A mating type locus of Coprinus cinereus determines mating compatibility by regulating essential steps in sexual development. Each A locus contains several genes separated into two functionally independent complexes termed Aα and Aβ, and the multiple alleles of these genes generate an estimated 160 A mating specificities. The genes encode two classes of homeodomain-containing proteins designated HD1 and HD2. In this report we describe two newly cloned loci, A2 and A5, and compare them with A42, A43 and A6 that we have described previously. An Aβ-null locus, retaining just a single active HD1 gene from the α-complex, was generated by mutation. Using this as a transformation host, gene combinations that promote A-regulated development were identified. We demonstrate that each A locus contains members of three paralogous pairs of HD1 and HD2 genes. Different allelic versions of gene pairs are compatible but paralogous genes are incompatible. The genes present in four uncloned A loci were deduced using Southern analyses and transformations with available cloned genes. The combined analysis of nine A factors identifies sufficient A gene alleles to generate at least 72 A mating specificities. PMID:8878675

  1. An amphioxus LIM-homeobox gene, AmphiLim1/5, expressed early in the invaginating organizer region and later in differentiating cells of the kidney and central nervous system

    Science.gov (United States)

    Langeland, James A.; Holland, Linda Z.; Chastain, Roger A.; Holland, Nicholas D.

    2006-01-01

    A LIM-homeobox gene, AmphiLim1/5, from the Florida amphioxus (Branchiostoma floridae) encodes a protein that phylogenetic analysis positions at the base of a clade comprising vertebrate Lim1 and Lim5. Amphioxus AmphiLim1/5 is expressed in domains that are a composite of those of vertebrate Lim1 and Lim5, which evidently underwent subfunctionalization after duplication of an ancestral protochordate Lim1/5. During amphioxus development, transcription is first detected in the ectoderm of the blastula. Then, in the gastrula, a second expression domain appears in the mesendoderm just within the dorsal lip of the blastopore, a region known to have organizer properties in amphioxus. This mesendodermal expression corresponds to Lim1 expression in the Spemann organizer of vertebrates. At least one of the functions of vertebrate Lim1 in the organizer is to control the transcription of genes involved in cell and tissue movements during gastrulation, and a comparable early function seems likely for AmphiLim1/5 during gastrular invagination of amphioxus. Later embryos and larvae of amphioxus express AmphiLim1/5 in clusters of cells, probably motoneurons, in the anterior part of the central nervous system, in the hindgut, in Hatschek's right diverticulum (a rudiment of the rostral coelom), and in the wall of the first somite on the left side (a precursor of Hatschek's nephridium). In the early larva, expression continues in neural cells, in Hatschek's nephridium, in the wall of the rostral coelom, in the epidermis of the upper lip, and in mesoderm cells near the opening of the second gill slit. The developmental expression in Hatschek's nephridium is especially interesting because it helps support the homology between this amphioxus organ and the vertebrate pronephros. PMID:16763670

  2. An amphioxus LIM-homeobox gene, AmphiLim1/5, expressed early in the invaginating organizer region and later in differentiating cells of the kidney and central nervous system.

    Science.gov (United States)

    Langeland, James A; Holland, Linda Z; Chastain, Roger A; Holland, Nicholas D

    2006-01-01

    A LIM-homeobox gene, AmphiLim1/5, from the Florida amphioxus (Branchiostoma floridae) encodes a protein that phylogenetic analysis positions at the base of a clade comprising vertebrate Lim1 and Lim5. Amphioxus AmphiLim1/5 is expressed in domains that are a composite of those of vertebrate Lim1 and Lim5, which evidently underwent subfunctionalization after duplication of an ancestral protochordate Lim1/5. During amphioxus development, transcription is first detected in the ectoderm of the blastula. Then, in the gastrula, a second expression domain appears in the mesendoderm just within the dorsal lip of the blastopore, a region known to have organizer properties in amphioxus. This mesendodermal expression corresponds to Lim1 expression in the Spemann organizer of vertebrates. At least one of the functions of vertebrate Lim1 in the organizer is to control the transcription of genes involved in cell and tissue movements during gastrulation, and a comparable early function seems likely for AmphiLim1/5 during gastrular invagination of amphioxus. Later embryos and larvae of amphioxus express AmphiLim1/5 in clusters of cells, probably motoneurons, in the anterior part of the central nervous system, in the hindgut, in Hatschek's right diverticulum (a rudiment of the rostral coelom), and in the wall of the first somite on the left side (a precursor of Hatschek's nephridium). In the early larva, expression continues in neural cells, in Hatschek's nephridium, in the wall of the rostral coelom, in the epidermis of the upper lip, and in mesoderm cells near the opening of the second gill slit. The developmental expression in Hatschek's nephridium is especially interesting because it helps support the homology between this amphioxus organ and the vertebrate pronephros.

  3. Short stature homeobox-containing gene duplication on the der(X) chromosome in a female with 45,X/46,X, der(X), gonadal dysgenesis, and tall stature.

    Science.gov (United States)

    Ogata, T; Kosho, T; Wakui, K; Fukushima, Y; Yoshimoto, M; Miharu, N

    2000-08-01

    We report on a Japanese female with 45,X[40]/46,X, der(X)[60], primary amenorrhea, and tall stature. She was confirmed to have complete gonadal dysgenesis at 19 yr of age and was placed on hormone replacement therapy. Growth assessment revealed that she had a low normal height until her early teens, but continued to grow with a nearly constant height velocity in her late teens, attaining a final height of 172 cm (+ 2.9 SD), which surpassed her target height range. Fluorescence in situ hybridization analysis for 10 loci/regions on the X-chromosome together with the whole X-chromosome and the Xp-specific and Xq-specific paintings showed that the der(X) chromosome was associated with duplication of roughly distal half of Xp, including SHOX (short stature homeobox-containing gene), and deletion of most of Xq. Microsatellite analysis for eight loci at Xp22 and nine loci at Xq26-28 indicated that the normal X-chromosome was of maternal origin, and the der(X) chromosome was of paternal origin. The results, in conjunction with the adult height data in 47,XXX, 46,XX gonadal dysgenesis, 47,XXY, 46,XY gonadal dysgenesis, and 46,X, idic(Xq-), suggest that the tall stature of this female is caused by the combined effects of SHOX duplication on the der(X) chromosome and gonadal estrogen deficiency. Furthermore, the similarity in the growth pattern between this female and patients with estrogen resistance or aromatase deficiency implies that the association of an extra copy of SHOX with gonadal estrogen deficiency may represent the further clinical entity for tall stature resulting from continued growth in late teens or into adulthood.

  4. XLMR in MRX families 29, 32, 33 and 38 results from the dup24 mutation in the ARX (Aristaless related homeobox gene

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    MacMillan Andrée

    2005-04-01

    Full Text Available Abstract Background X-linked mental retardation (XLMR is the leading cause of mental retardation in males. Mutations in the ARX gene in Xp22.1 have been found in numerous families with both nonsyndromic and syndromic XLMR. The most frequent mutation in this gene is a 24 bp duplication in exon 2. Based on this fact, a panel of XLMR families linked to Xp22 was tested for this particular ARX mutation. Methods Genomic DNA from XLMR families linked to Xp22.1 was amplified for exon 2 in ARX using a Cy5 labeled primer pair. The resulting amplicons were sized using the ALFexpress automated sequencer. Results A panel of 11 families with X-linked mental retardation was screened for the ARX 24dup mutation. Four nonsyndromic XLMR families – MRX29, MRX32, MRX33 and MRX38 – were found to have this particular gene mutation. Conclusion We have identified 4 additional XLMR families with the ARX dup24 mutation from a panel of 11 XLMR families linked to Xp22.1. This finding makes the ARX dup24 mutation the most common mutation in nonsyndromic XLMR families linked to Xp22.1. As this mutation can be readily tested for using an automated sequencer, screening should be considered for any male with nonsyndromic MR of unknown etiology.

  5. XLMR in MRX families 29, 32, 33 and 38 results from the dup24 mutation in the ARX (Aristaless related homeobox) gene

    Science.gov (United States)

    Stepp, Monica L; Cason, A Lauren; Finnis, Merran; Mangelsdorf, Marie; Holinski-Feder, Elke; Macgregor, David; MacMillan, Andrée; Holden, Jeanette JA; Gecz, Jozef; Stevenson, Roger E; Schwartz, Charles E

    2005-01-01

    Background X-linked mental retardation (XLMR) is the leading cause of mental retardation in males. Mutations in the ARX gene in Xp22.1 have been found in numerous families with both nonsyndromic and syndromic XLMR. The most frequent mutation in this gene is a 24 bp duplication in exon 2. Based on this fact, a panel of XLMR families linked to Xp22 was tested for this particular ARX mutation. Methods Genomic DNA from XLMR families linked to Xp22.1 was amplified for exon 2 in ARX using a Cy5 labeled primer pair. The resulting amplicons were sized using the ALFexpress automated sequencer. Results A panel of 11 families with X-linked mental retardation was screened for the ARX 24dup mutation. Four nonsyndromic XLMR families – MRX29, MRX32, MRX33 and MRX38 – were found to have this particular gene mutation. Conclusion We have identified 4 additional XLMR families with the ARX dup24 mutation from a panel of 11 XLMR families linked to Xp22.1. This finding makes the ARX dup24 mutation the most common mutation in nonsyndromic XLMR families linked to Xp22.1. As this mutation can be readily tested for using an automated sequencer, screening should be considered for any male with nonsyndromic MR of unknown etiology. PMID:15850492

  6. Differential transcription of Barhl1 homeobox gene in restricted functional domains of the central nervous system suggests a role in brain patterning.

    Science.gov (United States)

    Rachidi, Mohammed; Lopes, Carmela

    2006-02-01

    The mouse Barhl1 homeogene, member of the BarH subfamily, play a crucial role in the cerebellum development and its human ortholog BARHL1 has been proposed as a positional and functional candidate gene for the Joubert syndrome, a form of cerebellar ataxia. The Barhl1 expression has been demonstrated to be induced by the transcription factor Math1 involved in BMP responses. We isolated the mouse Barhl1 by screening of a cDNA library with the Xenopus Xvent-2, member of the BarH subfamily, which acts in the BMP4 pathway during embryonic patterning and neural plate differentiation. We studied the detailed Barhl1 expression pattern and showed its transcription in spatio-temporally and functionally restricted domains of the developing central nervous system (CNS). Using our new optical microscopy technology, we compare the transcript steady state level and cell density in the Barhl1-expressing regions. We found that Barhl1 was transcribed in superior and inferior colliculi in the dorsal mesencephalon at a relatively low transcriptional level. In the diencephalon, Barhl1 was found higher expressed first within the basal plate and later in the mammillary region. In the cerebellum, Barhl1 showed the highest transcriptional level restricted to the anterior and posterior rhombic lips giving rise to the external and internal cerebellar granular cells and to the deep nuclei. In the spinal cord, Barhl1 showed similar expression level than in the cerebellum and is delimited to a subset of dorsal interneurons. Therefore, our results indicated that Barhl1 homeodomain gene is exclusively transcribed in restricted CNS domain at differential transcription levels which suggest a highly regulated transcriptional mechanism. In addition, these regional and cellular specificities indicated that Barhl1 may be involved in the differentiation of the specific subsets of neuronal progenitors.

  7. DNA methylation of the homeobox genes PITX2 and SHOX2 predicts outcome in non-small-cell lung cancer patients.

    Science.gov (United States)

    Dietrich, Dimo; Hasinger, Oliver; Liebenberg, Volker; Field, John K; Kristiansen, Glen; Soltermann, Alex

    2012-06-01

    Biomarkers that facilitate prediction of disease progression in lung cancer patients might be clinically valuable in optimizing individualized therapy. In this study, the ability of the DNA methylation biomarkers PITX2 and SHOX2 to predict disease outcome in lung cancer patients has been evaluated. Quantitative, methylation-specific (HeavyMethyl), real-time polymerase chain reaction assays were used to measure DNA methylation of PITX2 and SHOX2 in bisulfite-converted DNA from formalin-fixed, paraffin-embedded tissues from 474 non-small-cell lung cancer patients. In univariate Cox Proportional Hazard analysis, high methylation of SHOX2 and PITX2 was a significant predictor of progression-free survival [SHOX2: n=465, hazard ratio (HR)=1.395 (1.130 to 1.721), P=0.002; PITX2: n=445, HR=1.312 (1.059 to 1.625), P=0.013]. Patients with low methylation of either PITX2 and/or SHOX2 (n=319) showed a significantly higher risk of disease progression as compared with patients with higher methylation of both genes [n=126; HR=1.555 (1.210 to 1.999), P=0.001]. This was particularly true for the subgroup of patients receiving no adjuvant radiotherapy or chemotherapy [n=258, HR=1.838 (1.252 to 2.698), P=0.002]. In multivariate analysis, both biomarkers added significant independent prognostic information to pT, pN, pM, and grade. Another interesting finding of this study was that SHOX2 and PITX2 DNA methylation was shown to be inversely correlated with TTF1 (also known as NKX2-1) expression (PITX2: P=0.018, SHOX2: PPITX2 and SHOX2 is an independent prognostic biomarker for disease progression in non-small-cell lung cancer patients.

  8. Characterization of chicken octamer-binding proteins demonstrates that POU domain-containing homeobox transcription factors have been highly conserved during vertebrate evolution

    Energy Technology Data Exchange (ETDEWEB)

    Petryniak, B.; Postema, C.E.; McCormack, W.T.; Thompson, C.B. (Univ. of Michigan Medical Center, Ann Arbor (USA)); Staudt, L.M. (National Cancer Institute, Bethesda, MD (USA))

    1990-02-01

    The DNA sequence motif ATTTGCAT (octamer) or its inverse complement has been identified as an evolutionarily conserved element in the promoter region of immunoglobulin genes. Two major DNA-binding proteins that bind in a sequence-specific manner to the octamer DNA sequence have been identified in mammalian species--a ubiquitously expressed protein (Oct-1) and a lymphoid-specific protein (Oct-2). During characterization of the promoter region of the chicken immunoglobulin light chain gene, the authors identified two homologous octamer-binding proteins in chicken B cells. when the cloning of the human gene for Oct-2 revealed it to be a member of a distinct family of homeobox genes, they sought to determine if the human Oct-2 cDNA could be used to identify homologous chicken homeobox genes. Using a human Oct-2 homeobox-specific DNA probe, they were able to identify 6-10 homeobox-containing genes in the chicken genome, demonstrating that the Oct-2-related subfamily of homeobox genes exists in avian species. DNA sequence analysis revealed it to be the chicken homologue of the human Oct-1 gene. Together, the data show that the POU-containing subfamily of homeobox genes have been highly conserved during vertebrate evolution, apparently as a result of selection for their DNA-binding and transcriptional regulatory properties.

  9. Gorgeous mosaic of mitochondrial genes created by horizontal transfer and gene conversion.

    Science.gov (United States)

    Hao, Weilong; Richardson, Aaron O; Zheng, Yihong; Palmer, Jeffrey D

    2010-12-14

    The best known outcome of horizontal gene transfer (HGT) is the introduction of novel genes, but other outcomes have been described. When a transferred gene has a homolog in the recipient genome, the native gene may be functionally replaced (and subsequently lost) or partially overwritten by gene conversion with transiently present foreign DNA. Here we report the discovery, in two lineages of plant mitochondrial genes, of novel gene combinations that arose by conversion between coresident native and foreign homologs. These lineages have undergone intricate conversion between native and foreign copies, with conversion occurring repeatedly and differentially over the course of speciation, leading to radiations of mosaic genes involved in respiration and intron splicing. Based on these findings, we develop a model--the duplicative HGT and differential gene conversion model--that integrates HGT and ongoing gene conversion in the context of speciation. Finally, we show that one of these HGT-driven gene-conversional radiations followed two additional types of conversional chimerism, namely, intramitochondrial retroprocessing and interorganellar gene conversion across the 2 billion year divide between mitochondria and chloroplasts. These findings expand our appreciation of HGT and gene conversion as creative evolutionary forces, establish plant mitochondria as a premiere system for studying the evolutionary dynamics of HGT and its genetic reverberations, and recommend careful examination of bacterial and other genomes for similar, likely overlooked phenomena.

  10. When a mid-intronic variation of DMD gene creates an ESE site.

    Science.gov (United States)

    Trabelsi, Madiha; Beugnet, Caroline; Deburgrave, Nathalie; Commere, Virgine; Orhant, Lucie; Leturcq, France; Chelly, Jamel

    2014-12-01

    Duchenne and Becker muscular dystrophy are X-linked allelic disorders caused by mutations in the DMD gene. The majority (65%) of these mutations are intragenic deletions/duplications that often lead to frameshift errors. Among the remaining ones, we find the mid-intronic mutations that usually create cryptic exons by activating potential splice sites. In this report, we identified, in a Becker muscular dystrophy patient, a mid-intronic variation that creates two ESE sites in intron 26 of DMD gene resulting in the insertion of a new cryptic exon in mRNA. Despite the out of frame character of this mutation, we observed the production of a reduced amount of full-size dystrophin which could be explained by the alternation between normal and altered splicing of dystrophin mRNA in this patient. To our knowledge, this is the first case report describing this novel pathogenic mechanism of mid-intronic variations of DMD gene. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. The Hlx homeobox transcription factor is required early in enteric nervous system development

    Directory of Open Access Journals (Sweden)

    Kaul Ajay

    2006-07-01

    Full Text Available Abstract Background Development of the enteric nervous system (ENS requires interactions between migrating neural crest cells and the nascent gastrointestinal tract that are dependent upon genes expressed by both cell compartments. Hlx, a homeobox transcription factor gene that is expressed in mouse intestinal and hepatic mesenchyme, is required for normal embryonic growth of intestine and liver, and the Hlx-/- genotype is embryonic lethal. We hypothesized that Hlx is required for ENS development. Results Enteric neurons were identified in Hlx+/+ and Hlx-/- mouse embryos by immunostaining of embryo sections for the neural markers PGP9.5 and Phox2b, or by staining for β-galactosidase in whole-mount embryos containing the dopamine β-hydroxylase-nLacZ transgene. In Hlx+/+ embryos, neural crest cells/enteric neurons have moved from the stomach into the intestine by E10.5. By contrast, neural crest cells/enteric neurons remain largely restricted to the lateral stomach mesenchyme of Hlx-/- embryos, with only a few scattered neural crest cells/enteric neurons in the intestine between E10.5–16.5. Conclusion The Hlx homeobox transcription factor is required for early aspects of ENS development.

  12. The peach (Prunus persica [L.] Batsch) homeobox gene KNOPE3, which encodes a class 2 knotted-like transcription factor, is regulated during leaf development and triggered by sugars.

    Science.gov (United States)

    Testone, Giulio; Condello, Emiliano; Verde, Ignazio; Caboni, Emilia; Iannelli, Maria Adelaide; Bruno, Leonardo; Mariotti, Domenico; Bitonti, Maria Beatrice; Giannino, Donato

    2009-07-01

    Class 1 KNOTTED1-like transcription factors (KNOX) are known to regulate plant development, whereas information on class 2 KNOX has been limited. The peach KNOPE3 gene was cloned, belonged to a family of few class 2 members and was located at 66 cM in the Prunus spp. G1 linkage-group. The mRNA localization was diversified in leaf, stem, flower and drupe, but recurred in all organ sieves, suggesting a role in sap nutrient transport. During leaf development, the mRNA earliest localized to primordia sieves and subsequently to mesophyll cells of growing leaves. Consistently, its abundance augmented with leaf expansion. The transcription was monitored in leaves responding to darkening, supply and transport block of sugars. It peaked at 4 h after darkness and dropped under prolonged obscurity, showing a similar kinetic to that of sucrose content variation. Feeding leaflets via the transpiration stream caused KNOPE3 up-regulation at 3 h after fructose, glucose and sucrose absorption and at 12 h after sorbitol. In girdling experiments, leaf KNOPE3 was triggered from 6 h onwards along with sucrose and sorbitol raise. Both the phloem-associated expression and sugar-specific gene modulation suggest that KNOPE3 may play a role in sugar translocation during the development of agro-relevant organs such as drupe.

  13. Msh homeobox 1 (Msx1)- andMsx2-overexpressing bone marrow-derived mesenchymal stem cells resemble blastema cells and enhance regeneration in mice.

    Science.gov (United States)

    Taghiyar, Leila; Hesaraki, Mahdi; Sayahpour, Forough Azam; Satarian, Leila; Hosseini, Samaneh; Aghdami, Naser; Baghaban Eslaminejad, Mohamadreza

    2017-06-23

    Amputation of the proximal region in mammals is not followed by regeneration because blastema cells (BCs) and expression of regenerative genes, such as Msh homeobox ( Msx ) genes, are absent in this animal group. The lack of BCs and positional information in other cells is therefore the main obstacle to therapeutic approaches for limb regeneration. Hence, this study aimed to create blastema-like cells (BlCs) by overexpressing Msx1 and Msx2 genes in mouse bone marrow-derived mesenchymal stem cells (mBMSCs) to regenerate a proximally amputated digit tip. We transduced mBMSCs with Msx1 and Msx2 genes and compared osteogenic activity and expression levels of several Msx -regulated genes ( Bmp4 , Fgf8 , and keratin 14 ( K14 )) in BlC groups, including MSX1, MSX2, and MSX1/2 (in a 1:1 ratio) with those in mBMSCs and BCs in vitro and in vivo following injection into the amputation site. We found that Msx gene overexpression increased expression of specific blastemal markers and enhanced the proliferation rate and osteogenesis of BlCs compared with mBMSCs and BCs via activation of Fgf8 and Bmp4 Histological analyses indicated full regrowth of digit tips in the Msx -overexpressing groups, particularly in MSX1/2, through endochondral ossification 6 weeks post-injection. In contrast, mBMSCs and BCs formed abnormal bone and nail. Full digit tip was regenerated only in the MSX1/2 group and was related to boosted Bmp4, Fgf8 , and K14 gene expression and to limb-patterning properties resulting from Msx1 and Msx2 overexpression. We propose that Msx -transduced cells that can regenerate epithelial and mesenchymal tissues may potentially be utilized in limb regeneration. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Homeobox transcription factor muscle segment homeobox 2 (Msx2) correlates with good prognosis in breast cancer patients and induces apoptosis in vitro.

    LENUS (Irish Health Repository)

    Lanigan, Fiona

    2010-01-01

    The homeobox-containing transcription factor muscle segment homeobox 2 (Msx2) plays an important role in mammary gland development. However, the clinical implications of Msx2 expression in breast cancer are unclear. The aims of this study were to investigate the potential clinical value of Msx2 as a breast cancer biomarker and to clarify its functional role in vitro.

  15. Classification and expression analyses of homeobox genes from ...

    Indian Academy of Sciences (India)

    Supplementary figure 2. Domain architecture analyses of the 14 homeodomain containing proteins from D. discoideum. These were derived using the online software SMART with Pfam database. The domains present in each protein are shown with their respective genomic positions. The figure is not drawn up to the scale.

  16. Control of plant architecture by distinctive TALE homeobox gene interactions

    NARCIS (Netherlands)

    Bao, D.

    2009-01-01

    In eukaryotes, transcription factor (TF)-based network is a widely used mechanism to regulate fundamental developmental processes. Both animals and plants utilize three-amino-acid-loop-extension (TALE) homeodomain (HD) transcription factors to subdivide their body plan. In animals, MEIS/PBC TF

  17. Classification and expression analyses of homeobox genes from ...

    Indian Academy of Sciences (India)

    2015-04-27

    Apr 27, 2015 ... Mus musculus; Xl: Xenopus laevis; Sc: Saccharomyces cerevisiae;; Cf: Camponotus floridanus; Tc: Tribolium castaneum; Dp: Danaus plexippus; Hsa: Harpegnathos .... sequences on the aligned homeodomains is marked. Box marks the characteristic three amino acids in the loop region of TALE class.

  18. Timing and Scope of Genomic Expansion within Annelida: Evidence from Homeoboxes in the Genome of the Earthworm Eisenia fetida.

    Science.gov (United States)

    Zwarycz, Allison S; Nossa, Carlos W; Putnam, Nicholas H; Ryan, Joseph F

    2015-12-10

    Annelida represents a large and morphologically diverse group of bilaterian organisms. The recently published polychaete and leech genome sequences revealed an equally dynamic range of diversity at the genomic level. The availability of more annelid genomes will allow for the identification of evolutionary genomic events that helped shape the annelid lineage and better understand the diversity within the group. We sequenced and assembled the genome of the common earthworm, Eisenia fetida. As a first pass at understanding the diversity within the group, we classified 363 earthworm homeoboxes and compared them with those of the leech Helobdella robusta and the polychaete Capitella teleta. We inferred many gene expansions occurring in the lineage connecting the most recent common ancestor (MRCA) of Capitella and Eisenia to the Eisenia/Helobdella MRCA. Likewise, the lineage leading from the Eisenia/Helobdella MRCA to the leech H. robusta has experienced substantial gains and losses. However, the lineage leading from Eisenia/Helobdella MRCA to E. fetida is characterized by extraordinary levels of homeobox gain. The evolutionary dynamics observed in the homeoboxes of these lineages are very likely to be generalizable to all genes. These genome expansions and losses have likely contributed to the remarkable biology exhibited in this group. These results provide a new perspective from which to understand the diversity within these lineages, show the utility of sub-draft genome assemblies for understanding genomic evolution, and provide a critical resource from which the biology of these animals can be studied. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. Smad4-dependent suppressor pituitary homeobox 2 promotes PPP2R2A-mediated inhibition of Akt pathway in pancreatic cancer

    OpenAIRE

    Wang, Qi; Li, Juanjuan; Wu, Wei; Shen, Ruizhe; Jiang, He; Qian, Yuting; Tang, Yanping; Bai, Tingting; Wu, Sheng; Wei, Lumin; Zang, Yi; Zhang, Ji; Wang, Lifu

    2016-01-01

    The importance of Pituitary homeobox 2 (Pitx2) in malignancy remains enigmatic, and Pitx2 has not been previously implicated in pancreatic ductal adenocarcinoma (PDAC). In this study, we performed gene expression profiling of human PDAC tissues and identified Pitx2 as a promising candidate. Pitx2 expression was decreased from 2.6- to 19-fold in human PDAC tissues from microarray units. Immunochemistry staining showed that Pitx2 expression was moderate to intense in normal pancreatic and pancr...

  20. Short Stature Homeobox-Containing Haploinsufficiency in Seven Siblings with Short Stature

    Directory of Open Access Journals (Sweden)

    Elizabeth S. Sandberg

    2017-01-01

    Full Text Available Deficiency of the short stature homeobox-containing (SHOX gene is a frequent cause of short stature in children (2–15%. Here, we report 7 siblings with SHOX deficiency due to a point mutation in the SHOX gene. Index case was a 3-year-old male who presented for evaluation of short stature. His past medical history and birth history were unremarkable. Family history was notable for multiple individuals with short stature. Physical exam revealed short stature, with height standard deviation score (SDS of −2.98, as well as arm span 3 cm less than his height. His laboratory workup was noncontributory for common etiologies of short stature. Due to significant familial short stature and shortened arm span, SHOX gene analysis was performed and revealed patient is heterozygous for a novel SHOX gene mutation at nucleotide position c.582. This mutation is predicted to cause termination of the SHOX protein at codon 194, effectively causing haploinsufficiency. Six out of nine other siblings were later found to also be heterozygous for the same mutation. Growth hormone was initiated in all seven siblings upon diagnosis and they have demonstrated improved height SDS.

  1. Recurrent Rearrangements of Human Amylase Genes Create Multiple Independent CNV Series.

    Science.gov (United States)

    Shwan, Nzar A A; Louzada, Sandra; Yang, Fengtang; Armour, John A L

    2017-05-01

    The human amylase gene cluster includes the human salivary (AMY1) and pancreatic amylase genes (AMY2A and AMY2B), and is a highly variable and dynamic region of the genome. Copy number variation (CNV) of AMY1 has been implicated in human dietary adaptation, and in population association with obesity, but neither of these findings has been independently replicated. Despite these functional implications, the structural genomic basis of CNV has only been defined in detail very recently. In this work, we use high-resolution analysis of copy number, and analysis of segregation in trios, to define new, independent allelic series of amylase CNVs in sub-Saharan Africans, including a series of higher-order expansions of a unit consisting of one copy each of AMY1, AMY2A, and AMY2B. We use fiber-FISH (fluorescence in situ hybridization) to define unexpected complexity in the accompanying rearrangements. These findings demonstrate recurrent involvement of the amylase gene region in genomic instability, involving at least five independent rearrangements of the pancreatic amylase genes (AMY2A and AMY2B). Structural features shared by fundamentally distinct lineages strongly suggest that the common ancestral state for the human amylase cluster contained more than one, and probably three, copies of AMY1. © 2017 WILEY PERIODICALS, INC.

  2. The fusion partner specifies the oncogenic potential of NUP98 fusion proteins

    OpenAIRE

    Saw, Jesslyn; Curtis, David J.; Hussey, Damian J.; Dobrovic, Alexander; Aplan, Peter D.; Slape, Christopher I.

    2013-01-01

    NUP98 is among the most promiscuously translocated genes in hematological diseases. Among the 28 known fusion partners, there are two categories: homeobox genes and non-homeobox genes. The homeobox fusion partners are well-studied in animal models, resulting in HoxA cluster overexpression and hematological disease. The non- homeobox fusion partners are less well studied. We created transgenic animal models for three NUP98 fusion genes (one homeobox, two non- homeobox), and show that in this s...

  3. A cancer-predisposing "hot spot" mutation of the fumarase gene creates a dominant negative protein.

    Science.gov (United States)

    Lorenzato, Annalisa; Olivero, Martina; Perro, Mario; Brière, Jean Jacques; Rustin, Pierre; Di Renzo, Maria Flavia

    2008-02-15

    The Fumarase (Fumarate Hydratase, FH) is a tumor suppressor gene whose germline heterozygous mutations predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC). The FH gene encodes an enzyme of the Krebs cycle, functioning as a homotetramer and catalyzing the hydration of fumarate to malate. Among the numerous FH mutations reported so far, the R190H missense mutation is the most frequent in HLRCC patients. Here we show the functional analyses of the R190H, in comparison to the better characterized E319Q mutation. We first expressed wild-type and mutated proteins in FH deficient human skin fibroblasts, using lentiviral vectors. The wild-type transgene was able to restore the FH enzymatic activity in cells, while the R190H- and E319Q-FH were not. More interestingly, when the same transgenes were expressed in normal, FH-proficient cells, only the R190H-FH reduced the endogenous FH enzymatic activity. By enforcing the expression of equal amount of wild-type and R190H-FH in the same cell, we showed that the mutated FH protein directly inhibited enzymatic activity by nearly abrogating the FH homotetramer formation. These data demonstrate the dominant negative effect of the R190H missense mutation in the FH gene and suggest that the FH tumor-suppressing activity might be impaired in cells carrying a heterozygous mutation. (c) 2007 Wiley-Liss, Inc.

  4. Homeobox transcription factors are required for conidiation and appressorium development in the rice blast fungus Magnaporthe oryzae.

    Directory of Open Access Journals (Sweden)

    Seryun Kim

    2009-12-01

    Full Text Available The appropriate development of conidia and appressoria is critical in the disease cycle of many fungal pathogens, including Magnaporthe oryzae. A total of eight genes (MoHOX1 to MoHOX8 encoding putative homeobox transcription factors (TFs were identified from the M. oryzae genome. Knockout mutants for each MoHOX gene were obtained via homology-dependent gene replacement. Two mutants, DeltaMohox3 and DeltaMohox5, exhibited no difference to wild-type in growth, conidiation, conidium size, conidial germination, appressorium formation, and pathogenicity. However, the DeltaMohox1 showed a dramatic reduction in hyphal growth and increase in melanin pigmentation, compared to those in wild-type. DeltaMohox4 and DeltaMohox6 showed significantly reduced conidium size and hyphal growth, respectively. DeltaMohox8 formed normal appressoria, but failed in pathogenicity, probably due to defects in the development of penetration peg and invasive growth. It is most notable that asexual reproduction was completely abolished in DeltaMohox2, in which no conidia formed. DeltaMohox2 was still pathogenic through hypha-driven appressoria in a manner similar to that of the wild-type. However, DeltaMohox7 was unable to form appressoria either on conidial germ tubes, or at hyphal tips, being non-pathogenic. These factors indicate that M. oryzae is able to cause foliar disease via hyphal appressorium-mediated penetration, and MoHOX7 is mutually required to drive appressorium formation from hyphae and germ tubes. Transcriptional analyses suggest that the functioning of M. oryzae homeobox TFs is mediated through the regulation of gene expression and is affected by cAMP and Ca(2+ signaling and/or MAPK pathways. The divergent roles of this gene set may help reveal how the genome and regulatory pathways evolved within the rice blast pathogen and close relatives.

  5. Origins and Evolution of WUSCHEL-Related Homeobox Protein Family in Plant Kingdom

    Directory of Open Access Journals (Sweden)

    Gaibin Lian

    2014-01-01

    Full Text Available WUSCHEL-related homeobox (WOX is a large group of transcription factors specifically found in plants. WOX members contain the conserved homeodomain essential for plant development by regulating cell division and differentiation. However, the evolutionary relationship of WOX members in plant kingdom remains to be elucidated. In this study, we searched 350 WOX members from 50 species in plant kingdom. Linkage analysis of WOX protein sequences demonstrated that amino acid residues 141–145 and 153–160 located in the homeodomain are possibly associated with the function of WOXs during the evolution. These 350 members were grouped into 3 clades: the first clade represents the conservative WOXs from the lower plant algae to higher plants; the second clade has the members from vascular plant species; the third clade has the members only from spermatophyte species. Furthermore, among the members of Arabidopsis thaliana and Oryza sativa, we observed ubiquitous expression of genes in the first clade and the diversified expression pattern of WOX genes in distinct organs in the second clade and the third clade. This work provides insight into the origin and evolutionary process of WOXs, facilitating their functional investigations in the future.

  6. Airway epithelial transcription factor NK2 homeobox 1 inhibits mucous cell metaplasia and Th2 inflammation.

    Science.gov (United States)

    Maeda, Yutaka; Chen, Gang; Xu, Yan; Haitchi, Hans Michael; Du, Lingling; Keiser, Angela R; Howarth, Peter H; Davies, Donna E; Holgate, Stephen T; Whitsett, Jeffrey A

    2011-08-15

    Airway mucous cell metaplasia and chronic inflammation are pathophysiological features that influence morbidity and mortality associated with asthma and other chronic pulmonary disorders. Elucidation of the molecular mechanisms regulating mucous metaplasia and hypersecretion provides the scientific basis for diagnostic and therapeutic opportunities to improve the care of chronic pulmonary diseases. To determine the role of the airway epithelial–specific transcription factor NK2 homeobox 1 (NKX2-1, also known as thyroid transcription factor-1 [TTF-1]) in mucous cell metaplasia and lung inflammation. Expression of NKX2-1 in airway epithelial cells from patients with asthma was analyzed. NKX2-1 +/-gene targeted or transgenic mice expressing NKX2-1 in conducting airway epithelial cells were sensitized to the aeroallergen ovalbumin. In vitro studies were used to identify mechanisms by which NKX2-1 regulates mucous cell metaplasia and inflammation. NKX2-1 was suppressed in airway epithelial cells from patients with asthma. Reduced expression of NKX2-1 in heterozygous NKX2-1 +/- gene targeted mice increased mucous metaplasia in the small airways after pulmonary sensitization to ovalbumin. Conversely, mucous cell metaplasia induced by aeroallergen was inhibited by expression of NKX2-1 in the respiratory epithelium in vivo. Genome-wide mRNA analysis of lung tissue from ovalbumin-treated mice demonstrated that NKX2-1 inhibited mRNAs associated with mucous metaplasia and Th2-regulated inflammation,including Spdef, Ccl17, and Il13. In vitro, NKX2-1 inhibited SPDEF, a critical regulator of airway mucous cell metaplasia,and the Th2 chemokine CCL26. The present data demonstrate a novel function for NKX2-1 in a gene network regulating mucous cell metaplasia and allergic inflammation in the respiratory epithelium.

  7. Creating standards: Creating illusions?

    DEFF Research Database (Denmark)

    Linneberg, Mai Skjøtt

    written standards may open up for the creation of illusions. These are created when written standards' content is not in accordance with the perception standard adopters and standard users have of the specific practice phenomenon's content. This general theoretical argument is exemplified by the specific...

  8. Hypothalamic neurosecretory and circadian vasopressinergic neuronal systems in the blind cone-rod homeobox knock out mouse (Crx(-/-) ) and the 129sv wild type mouse

    DEFF Research Database (Denmark)

    Rovsing, Louise; Rath, Martin Fredensborg; Møller, Morten

    2013-01-01

    Vasopressin (AVP) is both a neuroendocrine hormone located in magnocellular neurosecretory neurons of the hypothalamus of mammals but also a neurotransmitter/neuromodulator in the parvocellular suprachiasmatic nucleus (SCN). The SCN is the endogenous clock of the brain and exhibits a prominent...... circadian AVP-rhythm. We have in this study of the brown 129sv mouse and the visual blind cone-rod homeobox gene knock out mouse (Crx(-/-) ) with degeneration of the retinal rods and cones, but a preserved non-image forming optic system, studied the temporal Avp-expression in both the neurosecretory...

  9. Pancreas duodenal homeobox-1 expression and significance in pancreatic cancer

    Science.gov (United States)

    Liu, Tao; Gou, Shan-Miao; Wang, Chun-You; Wu, He-Shui; Xiong, Jiong-Xin; Zhou, Feng

    2007-01-01

    AIM: To study the correlations of Pancreas duodenal homeobox-1 with pancreatic cancer characteristics, including pathological grading, TNM grading, tumor metastasis and tumor cell proliferation. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect PDX-1 mRNA expression in pancreatic cancer tissue and normal pancreatic tissue. The expression of PDX-1 protein was measured by Western blot and immunohistochemistry. Immunohistochemistry was also used to detect proliferative cell nuclear antigen (PCNA). Correlations of PDX-1 with pancreatic cancer characteristics, including pathological grading, TNM grading, tumor metastasis and tumor cell proliferation, were analyzed by using χ2 test. RESULTS: Immunohistochemistry showed that 41.1% of pancreatic cancers were positive for PDX-1 expression, but normal pancreatic tissue except islets showed no staining for PDX-1. In consistent with the result of imunohistochemistry, Western blot showed that 37.5% of pancreatic cancers were positive for PDX-1. RT-PCR showed that PDX-1 expression was significantly higher in pancreatic cancer tissues than normal pancreatic tissues (2-3.56 ± 0.35 vs 2-8.76 ± 0.14, P < 0.01). Lymph node metastasis (P < 0.01), TNM grading (P < 0.05), pathological grading (P < 0.05) and tumor cell proliferation (P < 0.01) were significantly correlated with PDX-1 expression levels. CONCLUSION: PDX-1 is re-expressed in pancreatic cancer, and PDX-1-positive pancreatic cancer cells show more malignant potential compared to PDX-1-negative cells. Therefore, PDX-1-positive cells may be tumor stem cells and PDX-1 may act as alternate surface marker of pancreatic cancer stem cells. PMID:17552012

  10. Ambiguity of human gene symbols in LocusLink and MEDLINE: creating an inventory and a disambiguation test collection

    NARCIS (Netherlands)

    M. Weeber (Marc); R.J.A. Schijvenaars (Bob); E.M. van Mulligen (Erik); B. Mons (Barend); R. Jelier (Rob); C.C. van der Eijk (Christiaan); J.A. Kors (Jan)

    2003-01-01

    textabstractGenes are discovered almost on a daily basis and new names have to be found. Although there are guidelines for gene nomenclature, the naming process is highly creative. Human genes are often named with a gene symbol and a longer, more descriptive term; the short form is

  11. Reduced homeobox protein MSX1 in human endometrial tissue is linked to infertility.

    Science.gov (United States)

    Bolnick, Alan D; Bolnick, Jay M; Kilburn, Brian A; Stewart, Tamika; Oakes, Jonathan; Rodriguez-Kovacs, Javier; Kohan-Ghadr, Hamid-Reza; Dai, Jing; Diamond, Michael P; Hirota, Yasushi; Drewlo, Sascha; Dey, Sudhansu K; Armant, D Randall

    2016-09-01

    Is protein expression of the muscle segment homeobox gene family member MSX1 altered in the human secretory endometrium by cell type, developmental stage or fertility? MSX1 protein levels, normally elevated in the secretory phase endometrium, were significantly reduced in endometrial biopsies obtained from women of infertile couples. Molecular changes in the endometrium are important for fertility in both animals and humans. Msx1 is expressed in the preimplantation mouse uterus and regulates uterine receptivity for implantation. The MSX protein persists a short time, after its message has been down-regulated. Microarray analysis of the human endometrium reveals a similar pattern of MSX1 mRNA expression that peaks before the receptive period, with depressed expression at implantation. Targeted deletion of uterine Msx1 and Msx2 in mice prevents the loss of epithelial cell polarity during implantation and causes infertility. MSX1 mRNA and cell type-specific levels of MSX1 protein were quantified from two retrospective cohorts during the human endometrial cycle. MSX1 protein expression patterns were compared between fertile and infertile couples. Selected samples were dual-labeled by immunofluorescence microscopy to localize E-cadherin and β-catenin in epithelial cells. MSX1 mRNA was quantified by PCR in endometrium from hysterectomies (n = 14) determined by endometrial dating to be in the late-proliferative (cycle days 10-13), early-secretory (cycle days 14-19) or mid-secretory (cycle days 20-24) phase. MSX1 protein was localized using high-throughput, semi-quantitative immunohistochemistry with sectioned endometrial biopsy tissues from fertile (n = 89) and infertile (n = 89) couples. Image analysis measured stain intensity specifically within the luminal epithelium, glands and stroma during the early-, mid- and late- (cycle days 25-28) secretory phases. MSX1 transcript increased 5-fold (P endometrial cellular compartments. MSX1 protein decreased (P human MSX2 is not

  12. Proliferation and osteo/odontogenic differentiation of stem cells from apical papilla regulated by Zinc fingers and homeoboxes 2: An in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Fang [Department of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China); VIP Center, Shandong Provincial Key Laboratory of Oral Biomedicine, School and Hospital of Stomatology, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China); Gao, Lifen [Department of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China); Lu, Yating [VIP Center, Shandong Provincial Key Laboratory of Oral Biomedicine, School and Hospital of Stomatology, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China); Ma, Hongxin; Wang, Hongxing; Liang, Xiaohong [Department of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China); Wang, Yan, E-mail: wangyan1965@sdu.edu.cn [VIP Center, Shandong Provincial Key Laboratory of Oral Biomedicine, School and Hospital of Stomatology, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China); Ma, Chunhong, E-mail: machunhong@sdu.edu.cn [Department of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China)

    2016-01-15

    In the process of tooth root development, stem cells from the apical papilla (SCAPs) can differentiate into odontoblasts and form root dentin, however, molecules regulating SCAPs differentiation have not been elucidated. Zinc fingers and homeoboxes 2 (ZHX2) is a novel transcriptional inhibitor. It is reported to modulate the development of nerve cells, liver cells, B cells, red blood cells, and so on. However, the role of ZHX2 in tooth root development remains unclear. In this study, we explored the potential role of ZHX2 in the process of SCAPs differentiation. The results showed that overexpression of ZHX2 upregulated the expression of osteo/odontogenic related genes and ALP activity, inhibited the proliferation of SCAPs. Consistently, ZHX2 knockdown reduced SCAPs mineralization and promoted SCAPs proliferation. These results indicated that ZHX2 plays a critical role in the proliferation and osteo/odontogenic differentiation of SCAPs. - Highlights: • Zinc fingers and homeoboxes 2 (ZHX2) is a novel transcriptional inhibitor. • we found another new biological function of ZHX2 for the first time. • ZHX2 inhibit SCAPs proliferation. • ZHX2 promote the osteo/odontogenic differentiation of SCAPs.

  13. Circadian Dynamics of the Cone-Rod Homeobox (CRX) Transcription Factor in the Rat Pineal Gland and Its Role in Regulation of Arylalkylamine N-Acetyltransferase (AANAT)

    DEFF Research Database (Denmark)

    Rohde, Kristian; Rovsing, Louise; Ho, Anthony K

    2014-01-01

    The cone-rod homeobox (Crx) gene encodes a transcription factor in the retina and pineal gland. Crx deficiency influences the pineal transcriptome, including a reduced expression of arylalkylamine N-acetyltransferase (Aanat), a key enzyme in nocturnal pineal melatonin production. However, previous...... functional studies on pineal Crx have been performed in melatonin-deficient mice. In this study, we have investigated the role of Crx in the melatonin-proficient rat pineal gland. The current study shows that pineal Crx transcript levels exhibit a circadian rhythm with a peak in the middle of the night......, which is transferred into daily changes in CRX protein. The study further shows that the sympathetic innervation of the pineal gland controls the Crx rhythm. By use of adenovirus-mediated short hairpin RNA gene knockdown targeting Crx mRNA in primary rat pinealocyte cell culture, we here show...

  14. Heterozygous Deletion in Exons 4-5 of SHOX Gene in a Patient Diagnosed as Idiopathic Short Stature

    Directory of Open Access Journals (Sweden)

    David Anna

    2017-09-01

    Full Text Available Introduction: Isolated Short Stature Homeobox (SHOX gene haploinsufficiency can be found in 2-15% of individuals diagnosed with idiopathic short stature determining different skeletal phenotypes.

  15. Exchange of Lipooligosaccharide Synthesis Genes Creates Potential Guillain-Barré Syndrome-Inducible Strains of Campylobacter jejuni

    OpenAIRE

    Phongsisay, Vongsavanh; Perera, Viraj N.; Fry, Benjamin N.

    2006-01-01

    Human ganglioside-like structures, such as GM1, found on some Campylobacter jejuni strains have been linked to inducing the Guillain-Barré Syndrome (GBS). This study shows that a C. jejuni strain without GM1-like molecules acquired large DNA fragments, including lipooligosaccharide synthesis genes, from a strain expressing GM1-like molecules and consequently transformed into a number of potential GBS-inducible transformants, which exhibited a high degree of genetic and phenotypic diversity.

  16. Exchange of lipooligosaccharide synthesis genes creates potential Guillain-Barre syndrome-inducible strains of Campylobacter jejuni.

    Science.gov (United States)

    Phongsisay, Vongsavanh; Perera, Viraj N; Fry, Benjamin N

    2006-02-01

    Human ganglioside-like structures, such as GM1, found on some Campylobacter jejuni strains have been linked to inducing the Guillain-Barré Syndrome (GBS). This study shows that a C. jejuni strain without GM1-like molecules acquired large DNA fragments, including lipooligosaccharide synthesis genes, from a strain expressing GM1-like molecules and consequently transformed into a number of potential GBS-inducible transformants, which exhibited a high degree of genetic and phenotypic diversity.

  17. The WUSCHEL Related Homeobox Protein WOX7 Regulates the Sugar Response of Lateral Root Development in Arabidopsis thaliana.

    Science.gov (United States)

    Kong, Danyu; Hao, Yueling; Cui, Hongchang

    2016-02-01

    Sugars promote lateral root formation at low levels but become inhibitory at high C/N or C/P ratios. How sugars suppress lateral root formation is unclear, however. Here we report that WOX7, a member of the WUSCHEL related homeobox (WOX) family transcription factors, inhibits lateral root development in a sugar-dependent manner. The number of lateral root primordia increased in wox7 mutants but decreased in plants over-expressing WOX7. Plants expressing the WOX7-VP16 fusion protein produced even more lateral roots than wox7, suggesting that WOX7 acts as a transcriptional repressor in lateral root development. WOX7 is expressed at all stages of lateral root development, but it is primarily involved in lateral root initiation. Consistent with this, the wox7 mutant had a higher mitotic activity only at early stages of lateral root development. Further studies suggest that WOX7 regulates lateral root development through direct repression of cell cycle genes, particularly CYCD6;1. WOX7 expression was enhanced by sugar, reduced by auxin, but did not respond to salt and mannitol. In the wox7 mutant, the effect of sugar on lateral root formation was mitigated. These results together suggest that WOX7 plays an important role in coupling the lateral root development program and sugar status in plants. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

  18. Estrogen-dependent expression of sine oculis homeobox 1 in the mouse uterus during the estrous cycle

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Sijeong [Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do 13488 (Korea, Republic of); Kwon, Hwang [Fertility Center of CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do 13496 (Korea, Republic of); Yoon, Hyemin [Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do 13488 (Korea, Republic of); Park, Miseon [Fertility Center of CHA Gangnam Medical Center, Seoul 06135 (Korea, Republic of); Kim, Hye-Ryun; Song, Haengseok [Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do 13488 (Korea, Republic of); Hong, Kwonho, E-mail: kwonho.hong@dankook.ac.kr [Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan-si, Chungcheongnam-do 31116 (Korea, Republic of); Choi, Youngsok, E-mail: youngsokchoi@cha.ac.kr [Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do 13488 (Korea, Republic of); Fertility Center of CHA Gangnam Medical Center, Seoul 06135 (Korea, Republic of)

    2016-04-08

    The sine oculis homeobox 1 (SIX1) is a member of the Six gene family. SIX1 is involved in tissue development by regulating proliferation, apoptosis, and differentiation. However, function of SIX1 in the uterus remains unknown. Here, we found that Six1 expression is regulated along the estrous cycle in mouse uterus. Six1 expression was significantly increased at estrus stage and decreased at the rest of stages. SIX1 is detected in the luminal and glandular epithelium of uterine endometrium at the estrus stage. Estrogen injection increased Six1 expression in the ovariectomized mouse uterus, whereas progesterone had no effect on its expression. Estrogen receptor antagonist inhibited estrogen-induced Six1 expression. Our findings imply that SIX1 may play a role as an important regulator to orchestrate the dynamic of uterine endometrium in response to estrogen level during the estrous cycle. These results will give us a better understanding of uterine biology. - Highlights: • Six1 expression is regulated during the estrous cycle in mouse uterus. • Six1 is highly expressed at the estrus stage of estrous cycle. • SIX1 is detected in luminal/glandular epithelium of the uterus at the estrus stage. • Estrogen stimulates Six1 expression in an estrogen receptor-dependent manner.

  19. The Evolution of Mobile DNAs: When Will Transposons Create Phylogenies That Look As If There Is a Master Gene?

    Science.gov (United States)

    Brookfield, John F. Y.; Johnson, Louise J.

    2006-01-01

    Some families of mammalian interspersed repetitive DNA, such as the Alu SINE sequence, appear to have evolved by the serial replacement of one active sequence with another, consistent with there being a single source of transposition: the “master gene.” Alternative models, in which multiple source sequences are simultaneously active, have been called “transposon models.” Transposon models differ in the proportion of elements that are active and in whether inactivation occurs at the moment of transposition or later. Here we examine the predictions of various types of transposon model regarding the patterns of sequence variation expected at an equilibrium between transposition, inactivation, and deletion. Under the master gene model, all bifurcations in the true tree of elements occur in a single lineage. We show that this property will also hold approximately for transposon models in which most elements are inactive and where at least some of the inactivation events occur after transposition. Such tree shapes are therefore not conclusive evidence for a single source of transposition. PMID:16790583

  20. A role for the transcription factor NK2 homeobox 1 in schizophrenia: Convergent evidence from animal and human studies

    Directory of Open Access Journals (Sweden)

    Eva Albertsen Malt

    2016-03-01

    Full Text Available Schizophrenia is a highly heritable disorder with diverse mental and somatic symptoms. The molecular mechanisms leading from genes to disease pathology in schizophrenia remain largely unknown. Genome-wide association studies have shown that common single-nucleotide polymorphisms associated with specific diseases are enriched in the recognition sequences of transcription factors that regulate physiological processes relevant to the disease. We have used a bottom-up approach and tracked a developmental trajectory from embryology to physiological processes and behavior and recognized that the transcription factor NK2 homeobox 1 (NKX2-1 possesses properties of particular interest for schizophrenia. NKX2-1 is selectively expressed from prenatal development to adulthood in the brain, thyroid gland, parathyroid gland, lungs, skin, and enteric ganglia, and has key functions at the interface of the brain, the endocrine-, and the immune system. In the developing brain, NKX2-1-expressing progenitor cells differentiate into distinct subclasses of forebrain GABAergic and cholinergic neurons, astrocytes, and oligodendrocytes. The transcription factor is highly expressed in mature limbic circuits related to context-dependent goal-directed patterns of behavior, social interaction and reproduction, fear responses, responses to light, and other homeostatic processes. It is essential for development and mature function of the thyroid gland and the respiratory system, and is involved in calcium metabolism and immune responses. NKX2-1 interacts with a number of genes identified as susceptibility genes for schizophrenia. We suggest that NKX2-1 may lie at the core of several dose dependent pathways that are dysregulated in schizophrenia. We correlate the symptoms seen in schizophrenia with the temporal and spatial activities of NKX2-1 in order to highlight promising future research areas.

  1. Homeobox A7 increases cell proliferation by up-regulation of epidermal growth factor receptor expression in human granulosa cells

    Directory of Open Access Journals (Sweden)

    Yanase Toshihiko

    2010-06-01

    Full Text Available Abstract Background Homeobox (HOX genes encode transcription factors, which regulate cell proliferation, differentiation, adhesion, and migration. The deregulation of HOX genes is frequently associated with human reproductive system disorders. However, knowledge regarding the role of HOX genes in human granulosa cells is limited. Methods To determine the role of HOXA7 in the regulation and associated mechanisms of cell proliferation in human granulosa cells, HOXA7 and epidermal growth factor receptor (EGFR expressions were examined in primary granulosa cells (hGCs, an immortalized human granulosa cell line, SVOG, and a granulosa tumor cell line, KGN, by real-time PCR and Western blotting. To manipulate the expression of HOXA7, the HOXA7 specific siRNA was used to knockdown HOXA7 in KGN. Conversely, HOXA7 was overexpressed in SVOG by transfection with the pcDNA3.1-HOAX7 vector. Cell proliferation was measured by the MTT assay. Results Our results show that HOXA7 and EGFR were overexpressed in KGN cells compared to hGCs and SVOG cells. Knockdown of HOXA7 in KGN cells significantly decreased cell proliferation and EGFR expression. Overexpression of HOXA7 in SVOG cells significantly promoted cell growth and EGFR expression. Moreover, the EGF-induced KGN proliferation was abrogated, and the activation of downstream signaling was diminished when HOXA7 was knocked down. Overexpression of HOXA7 in SVOG cells had an opposite effect. Conclusions Our present study reveals a novel mechanistic role for HOXA7 in modulating granulosa cell proliferation via the regulation of EGFR. This finding contributes to the knowledge of the pro-proliferation effect of HOXA7 in granulosa cell growth and differentiation.

  2. Creating a family health history

    Science.gov (United States)

    Family health history; Create a family health history; Family medical history ... include your: Genes Diet and exercise habits Environment Family members tend to share certain behaviors, genetic traits, ...

  3. WUSCHEL-RELATED HOMEOBOX 2 is important for protoderm and suspensor development in the gymnosperm Norway spruce.

    Science.gov (United States)

    Zhu, Tianqing; Moschou, Panagiotis N; Alvarez, José M; Sohlberg, Joel J; von Arnold, Sara

    2016-01-19

    Distinct expression domains of WUSCHEL-RELATED HOMEOBOX (WOX) gene family members are involved in patterning and morphogenesis of the early embryo in Arabidopsis. However, the role of WOX genes in other taxa, including gymnosperms, remains elusive. Here, we use somatic embryos and reverse genetics for studying expression and function of PaWOX2, the corresponding homolog of AtWOX2 in the gymnosperm Picea abies (Pa; Norway spruce). The mRNA level of PaWOX2 was transiently up-regulated during early and late embryogeny. PaWOX2 mRNA in early and early late embryos was detected both in the embryonal mass and in the upper part of the suspensor. Down-regulation of PaWOX2 during development of early embryos resulted in aberrant early embryos, which failed to form a proper protoderm. Cells on the surface layer of the embryonal mass became vacuolated, and new embryogenic tissue differentiated from the embryonal mass. In addition, the aberrant early embryos lacked a distinct border between the embryonal mass, and the suspensor and the length of the suspensor cells was reduced. Down-regulation of PaWOX2 in the beginning of embryo development, before late embryos were formed, caused a significant decrease in the yield of mature embryos. On the contrary, down-regulation of PaWOX2 after late embryos were formed had no effect on further embryo development and maturation. Our data suggest an evolutionarily conserved function of WOX2 in protoderm formation early during embryo development among seed plants. In addition, PaWOX2 might exert a unique function in suspensor expansion in gymnosperms.

  4. Wuschel-related homeobox 8/9 is important for proper embryo patterning in the gymnosperm Norway spruce.

    Science.gov (United States)

    Zhu, Tianqing; Moschou, Panagiotis N; Alvarez, José M; Sohlberg, Joel J; von Arnold, Sara

    2014-12-01

    Proper embryo development is crucial as that is when the primary body axes are established. In Arabidopsis, AtWOX8 and AtWOX9, members of the Wuschel-related homeobox (WOX) gene family, are critical for embryo development. In Norway spruce, PaWOX8/9, which is expressed in embryos, is the homologue of AtWOX8 and AtWOX9. In this work, it is shown that the transcript abundance of PaWOX8/9 is high during early and late embryogeny and that it decreases when the maturation phase starts. To address the function of PaWOX8/9 during embryo development, RNAi lines were established to down-regulate the transcript level of PaWOX8/9, using both constitutive and inducible promoters. Embryos in the PaWOX8/9 RNAi lines show an aberrant morphology caused by disturbed orientation of the cell division plane at the basal part of the embryonal mass during early and late embryogeny. In addition, the transcript level of several key cell-cycle-regulating genes, for example, PaE2FAB-like and PaCYCLIN B-like, are affected in the PaWOX8/9 RNAi lines. Taken together, our results suggest that PaWOX8/9 may perform an evolutionarily conserved function as a regulator of the establishment of the apical-basal embryo pattern. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  5. Generation of a multipurpose Prdm16 mouse allele by targeted gene trapping

    Directory of Open Access Journals (Sweden)

    Alexander Strassman

    2017-07-01

    Full Text Available Gene trap mutagenesis is a powerful tool to create loss-of-function mutations in mice and other model organisms. Modifications of traditional gene trap cassettes, including addition of conditional features in the form of Flip-excision (FlEx arrays to enable directional gene trap cassette inversions by Cre and Flpe site-specific recombinases, greatly enhanced their experimental potential. By taking advantage of these conditional gene trap cassettes, we developed a generic strategy for generating conditional mutations and validated this strategy in mice carrying a multipurpose allele of the Prdm16 transcription factor gene. We demonstrate that the gene trap insertion creates a null mutation replicating the Pierre Robin sequence-type cleft palate phenotype of other Prdm16 mutant mice. Consecutive breeding to Flpe and Emx1IREScre deleter mice spatially restricted Prdm16 loss to regions of the forebrain expressing the homeobox gene Emx1, demonstrating the utility of the technology for the analysis of tissue-specific gene functions.

  6. Creating Poetry.

    Science.gov (United States)

    Drury, John

    Encouraging exploration and practice, this book offers hundreds of exercises and numerous tips covering every step involved in creating poetry. Each chapter is a self-contained unit offering an overview of material in the chapter, a definition of terms, and poetry examples from well-known authors designed to supplement the numerous exercises.…

  7. LHC Create

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    LHC Create is an upcoming 2-day workshop held at IdeaSquare in November. Participants from CERN and IPAC school of design will compete to design an exhibit that explains why CERN does what it does. The winner will have their exhibit fully realised and made available to experiments, institutes, and tourism agencies around the world.

  8. Protein Inhibitors of Activated STAT (Pias1 and Piasy) Differentially Regulate Pituitary Homeobox 2 (PITX2) Transcriptional Activity*

    Science.gov (United States)

    Wang, Jianbo; Sun, Zhao; Zhang, Zichao; Saadi, Irfan; Wang, Jun; Li, Xiao; Gao, Shan; Engle, Jamison J.; Kuburas, Adisa; Fu, Xueyao; Yu, Wenjie; Klein, William H.; Russo, Andrew F.; Amendt, Brad A.

    2013-01-01

    Protein inhibitors of activated STAT (Pias) proteins can act independent of sumoylation to modulate the activity of transcription factors and Pias proteins interacting with transcription factors can either activate or repress their activity. Pias proteins are expressed in many tissues and cells during development and we asked if Pias proteins regulated the pituitary homeobox 2 (PITX2) homeodomain protein, which modulates developmental gene expression. Piasy and Pias1 proteins are expressed during craniofacial/tooth development and directly interact and differentially regulate PITX2 transcriptional activity. Piasy and Pias1 are co-expressed in craniofacial tissues with PITX2. Yeast two-hybrid, co-immunoprecipitation and pulldown experiments demonstrate Piasy and Pias1 interactions with the PITX2 protein. Piasy interacts with the PITX2 C-terminal tail to attenuate its transcriptional activity. In contrast, Pias1 interacts with the PITX2 C-terminal tail to increase PITX2 transcriptional activity. The E3 ligase activity associated with the RING domain in Piasy is not required for the attenuation of PITX2 activity, however, the RING domain of Pias1 is required for enhanced PITX2 transcriptional activity. Bimolecular fluorescence complementation assays reveal PITX2 interactions with Piasy and Pias1 in the nucleus. Piasy represses the synergistic activation of PITX2 with interacting co-factors and Piasy represses Pias1 activation of PITX2 transcriptional activity. In contrast, Pias1 did not affect the synergistic interaction of PITX2 with transcriptional co-factors. Last, we demonstrate that Pias proteins form a complex with PITX2 and Lef-1, and PITX2 and β-catenin. Lef-1, β-catenin, and Pias interactions with PITX2 provide new molecular mechanisms for the regulation of PITX2 transcriptional activity and the activity of Pias proteins. PMID:23515314

  9. Protein inhibitors of activated STAT (Pias1 and Piasy) differentially regulate pituitary homeobox 2 (PITX2) transcriptional activity.

    Science.gov (United States)

    Wang, Jianbo; Sun, Zhao; Zhang, Zichao; Saadi, Irfan; Wang, Jun; Li, Xiao; Gao, Shan; Engle, Jamison J; Kuburas, Adisa; Fu, Xueyao; Yu, Wenjie; Klein, William H; Russo, Andrew F; Amendt, Brad A

    2013-05-03

    Protein inhibitors of activated STAT (Pias) proteins can act independent of sumoylation to modulate the activity of transcription factors and Pias proteins interacting with transcription factors can either activate or repress their activity. Pias proteins are expressed in many tissues and cells during development and we asked if Pias proteins regulated the pituitary homeobox 2 (PITX2) homeodomain protein, which modulates developmental gene expression. Piasy and Pias1 proteins are expressed during craniofacial/tooth development and directly interact and differentially regulate PITX2 transcriptional activity. Piasy and Pias1 are co-expressed in craniofacial tissues with PITX2. Yeast two-hybrid, co-immunoprecipitation and pulldown experiments demonstrate Piasy and Pias1 interactions with the PITX2 protein. Piasy interacts with the PITX2 C-terminal tail to attenuate its transcriptional activity. In contrast, Pias1 interacts with the PITX2 C-terminal tail to increase PITX2 transcriptional activity. The E3 ligase activity associated with the RING domain in Piasy is not required for the attenuation of PITX2 activity, however, the RING domain of Pias1 is required for enhanced PITX2 transcriptional activity. Bimolecular fluorescence complementation assays reveal PITX2 interactions with Piasy and Pias1 in the nucleus. Piasy represses the synergistic activation of PITX2 with interacting co-factors and Piasy represses Pias1 activation of PITX2 transcriptional activity. In contrast, Pias1 did not affect the synergistic interaction of PITX2 with transcriptional co-factors. Last, we demonstrate that Pias proteins form a complex with PITX2 and Lef-1, and PITX2 and β-catenin. Lef-1, β-catenin, and Pias interactions with PITX2 provide new molecular mechanisms for the regulation of PITX2 transcriptional activity and the activity of Pias proteins.

  10. Zinc fingers and homeoboxes 2 inhibits hepatocellular carcinoma cell proliferation and represses expression of Cyclins A and E.

    Science.gov (United States)

    Yue, Xuetian; Zhang, Zhenyu; Liang, Xiaohong; Gao, Lifen; Zhang, Xiaoning; Zhao, Di; Liu, Xiao; Ma, Hongxin; Guo, Min; Spear, Brett T; Gong, Yaoqin; Ma, Chunhong

    2012-06-01

    Zinc-fingers and homeoboxes 2 (ZHX2) represses transcription of several genes associated with liver cancer. However, little is known about the role of ZHX2 in the development of hepatocellular carcinoma (HCC). We investigated the mechanisms by which ZHX2 might affect proliferation of HCC cells. We overexpressed and knocked down ZHX2 in HCC cells and analyzed the effects on proliferation, colony formation, and the cell cycle. We also analyzed the effects of ZHX2 overexpression in growth of HepG2.2.15 tumor xenografts in nude mice. Chromatin immunoprecipitation and luciferase reporter assays were used to measure binding of ZHX2 target promoters. Levels of ZHX2 in HCC samples were evaluated by immunohistochemistry. ZHX2 overexpression significantly reduced proliferation of HCC cells and growth of tumor xenografts in mice; it led to G1 arrest and reduced levels of Cyclins A and E in HCC cell lines. ZHX2 bound to promoter regions of CCNA2 (which encodes Cyclin A) and CCNE1 (which encodes Cyclin E) and inhibited their transcription. Knockdown of Cyclin A or Cyclin E reduced the increased proliferation mediated by ZHX2 knockdown. Nuclear localization of ZHX2 was required for it to inhibit proliferation of HCC cells in culture and in mice. Nuclear localization of ZHX2 was reduced in human HCC samples, even in small tumors (diameter, <5 cm), compared with adjacent nontumor tissues. Moreover, reduced nuclear levels of ZHX2 correlated with reduced survival times of patients, high levels of tumor microvascularization, and hepatocyte proliferation. ZHX2 inhibits HCC cell proliferation by preventing expression of Cyclins A and E, and reduces growth of xenograft tumors in mice. Loss of nuclear ZHX2 might be an early step in the development of HCC. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Modeling human retinal development with patient-specific induced pluripotent stem cells reveals multiple roles for visual system homeobox 2.

    Science.gov (United States)

    Phillips, M Joseph; Perez, Enio T; Martin, Jessica M; Reshel, Samantha T; Wallace, Kyle A; Capowski, Elizabeth E; Singh, Ruchira; Wright, Lynda S; Clark, Eric M; Barney, Patrick M; Stewart, Ron; Dickerson, Sarah J; Miller, Michael J; Percin, E Ferda; Thomson, James A; Gamm, David M

    2014-06-01

    Human induced pluripotent stem cells (hiPSCs) have been shown to differentiate along the retinal lineage in a manner that mimics normal mammalian development. Under certain culture conditions, hiPSCs form optic vesicle-like structures (OVs), which contain proliferating progenitors capable of yielding all neural retina (NR) cell types over time. Such observations imply conserved roles for regulators of retinogenesis in hiPSC-derived cultures and the developing embryo. However, whether and to what extent this assumption holds true has remained largely uninvestigated. We examined the role of a key NR transcription factor, visual system homeobox 2 (VSX2), using hiPSCs derived from a patient with microphthalmia caused by an R200Q mutation in the VSX2 homeodomain region. No differences were noted between (R200Q)VSX2 and sibling control hiPSCs prior to OV generation. Thereafter, (R200Q)VSX2 hiPSC-OVs displayed a significant growth deficit compared to control hiPSC-OVs, as well as increased production of retinal pigmented epithelium at the expense of NR cell derivatives. Furthermore, (R200Q)VSX2 hiPSC-OVs failed to produce bipolar cells, a distinctive feature previously observed in Vsx2 mutant mice. (R200Q)VSX2 hiPSC-OVs also demonstrated delayed photoreceptor maturation, which could be overcome via exogenous expression of wild-type VSX2 at early stages of retinal differentiation. Finally, RNAseq analysis on isolated hiPSC-OVs implicated key transcription factors and extracellular signaling pathways as potential downstream effectors of VSX2-mediated gene regulation. Our results establish hiPSC-OVs as versatile model systems to study retinal development at stages not previously accessible in humans and support the bona fide nature of hiPSC-OV-derived retinal progeny. © 2014 AlphaMed Press.

  12. The human mucin MUC4 is transcriptionally regulated by caudal-related homeobox, hepatocyte nuclear factors, forkhead box A, and GATA endodermal transcription factors in epithelial cancer cells.

    Science.gov (United States)

    Jonckheere, Nicolas; Vincent, Audrey; Perrais, Michaël; Ducourouble, Marie-Paule; Male, Anita Korteland-van; Aubert, Jean-Pierre; Pigny, Pascal; Carraway, Kermit L; Freund, Jean-Noël; Renes, Ingrid B; Van Seuningen, Isabelle

    2007-08-03

    The human gene MUC4 encodes a large transmembrane mucin that is developmentally regulated and expressed along the undifferentiated pseudostratified epithelium, as early as 6.5 weeks during fetal development. Immunohistochemical analysis of Muc4 expression in developing mouse lung and gastrointestinal tract showed a different spatio-temporal pattern of expression before and after cytodifferentiation. The molecular mechanisms governing MUC4 expression during development are, however, unknown. Hepatocyte nuclear factors (HNF), forkhead box A (FOXA), GATA, and caudal-related homeobox transcription factors (TFs) are known to control cell differentiation of gut endoderm derived-tissues during embryonic development. They also control the expression of cell- and tissue-specific genes and may thus control MUC4 expression. To test this hypothesis, we studied and deciphered the molecular mechanisms responsible for MUC4 transcriptional regulation by these TFs. Experiments using small interfering RNA, cell co-transfection, and site-directed mutagenesis indicated that MUC4 is regulated at the transcriptional level by CDX-1 and -2, HNF-1 alpha and -1 beta, FOXA1/A2, HNF-4 alpha and -4 gamma, and GATA-4, -5, and -6 factors in a cell-specific manner. Binding of TFs was assessed by chromatin immunoprecipitation, and gel-shift assays. Altogether, these results demonstrate that MUC4 is a target gene of endodermal TFs and thus point out an important role for these TFs in regulating MUC4 expression during epithelial differentiation during development, cancer, and repair.

  13. Expression of the Drosophila homeobox gene, Distal-less, supports an ancestral role in neural development

    National Research Council Canada - National Science Library

    Plavicki, Jessica S; Squirrell, Jayne M; Eliceiri, Kevin W; Boekhoff-Falk, Grace

    2016-01-01

    .... Based on earlier observations in the limbless nematode Caenorhabditis elegans and the primitive chordate amphioxus, it was proposed that Dll had an ancestral function in nervous system development...

  14. The Populus homeobox gene ARBORKNOX2 regulates cell differentiation during secondary growth

    Science.gov (United States)

    Juan Du; Shawn D. Mansfield; Andrew T. Groover

    2009-01-01

    The stem cells of the vascular cambium divide to produce daughter cells, which in turn divide before undergoing differentiation during the radial growth of woody stems. The genetic regulation of these developmental events is poorly understood, however. We report here the cloning and functional characterization of a Populus class-I KNOX...

  15. Control of plant architecture by the TALE homeobox genes ATH1 and PENNYWISE

    NARCIS (Netherlands)

    Rutjens, B.P.W.

    2007-01-01

    In plants, pattern formation is an ongoing process that starts during embryogenesis and lasts the entire life span. Most of the plant adult body is formed post-embryonically by continuous organogenic potential of the root and shoot meristems. Proper shoot apical meristem (SAM) function requires

  16. Dysregulation of the homeobox transcription factor gene HOXB13: role in prostate cancer

    OpenAIRE

    Decker B; Ostrander EA

    2014-01-01

    Brennan Decker1,2, Elaine A Ostrander1 1Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; 2Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK Abstract: Prostate cancer (PC) is the most common noncutaneous cancer in men, and epidemiological studies suggest that about 40% of PC risk is heritable. Linkag...

  17. HOXB4 Gene Expression Is Regulated by CDX2 in Intestinal Epithelial Cells

    DEFF Research Database (Denmark)

    Jørgensen, Steffen; Coshun, Mehmet; Mikkelsen Homburg, Keld

    2016-01-01

    The mammalian Caudal-related homeobox transcription factor 2 (CDX2) plays a key role in the homeobox regulatory network and is essential in regulating the expression of several homeobox (HOX) genes during embryonic development, particularly in the gut. Genome-wide CDX2 chromatin immunoprecipitation...... analysis and expression data from Caco2 cells also suggests a role for CDX2 in the regulation of HOXB4 gene expression in the intestinal epithelium. Thus, the aim of this study was to investigate whether HOXB4 gene expression is regulated by CDX2 in the intestinal epithelium. We demonstrated binding of CDX...... demonstrating the CDX2 regulation of HOXB4 gene expression in the developed intestinal epithelium, indicating a possible role for HOXB4 in intestinal homeostasis....

  18. Recombination between the dfrA12-orfF-aadA2 Cassette Array and an aadA1 Gene Cassette Creates a Hybrid Cassette, aadA8b

    Science.gov (United States)

    Gestal, Alicia M.; Stokes, H. W.; Partridge, Sally R.; Hall, Ruth M.

    2005-01-01

    Homologous recombination between closely related gene cassettes, such as aadA1 and aadA2, which are 89% identical, can create hybrid cassettes and hybrids of existing cassette arrays. A new cassette array, dfrA12-orfF-aadA8b, which was created by such a recombination event occurring within the aadA2 cassette in the dfrA12-orfF-aadA2 array, has been identified. PMID:16251327

  19. Epigenomic study identifies a novel mesenchyme homeobox2-GLI1 transcription axis involved in cancer drug resistance, overall survival and therapy prognosis in lung cancer patients

    Science.gov (United States)

    Armas-López, Leonel; Piña-Sánchez, Patricia; Arrieta, Oscar; de Alba, Enrique Guzman; Ortiz-Quintero, Blanca; Santillán-Doherty, Patricio; Christiani, David C.; Zúñiga, Joaquín; Ávila-Moreno, Federico

    2017-01-01

    Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis. Chromatin immunoprecipitation (ChIP) assays derived from non-small cell lung carcinomas (NSCLC) hybridized on gene promoter tiling arrays and bioinformatics analyses were performed, and quantitative, functional and clinical validation were also carried out. We statistically identified a common profile consisting of 78 gene promoter targets, including Hedgehog-GLI1 gene promoter sequences (FDR≤0.1 and FDR≤0.2). The GLI-1 gene promoter region from −2,192 to −109 was occupied by MEOX2, accompanied by transcriptionally active RNA Pol II and was epigenetically linked to the active histones H3K27Ac and H3K4me3; these associations were quantitatively validated. Moreover, siRNA genetic silencing assays identified a MEOX2-GLI1 axis involved in cellular cytotoxic resistance to cisplatinum in a dose-dependent manner, as well as cellular migration and proliferation. Finally, Kaplan-Maier survival analyses identified significant MEOX2-dependent GLI-1 protein expression associated with clinical progression and poorer overall survival using an independent cohort of NSCLC patients undergoing platinum-based oncological therapy with both epidermal growth factor receptor (EGFR)-non-mutated and EGFR-mutated status. In conclusion, this is the first study to investigate epigenome-wide MEOX2-transcription factor occupation identifying a novel overexpressed MEOX2-GLI1 axis and its clinical association with platinum-based cancer drug resistance and EGFR

  20. New insights into somatic embryogenesis: leafy cotyledon1, baby boom1 and WUSCHEL-related homeobox4 are epigenetically regulated in Coffea canephora.

    Science.gov (United States)

    Nic-Can, Geovanny I; López-Torres, Adolfo; Barredo-Pool, Felipe; Wrobel, Kazimierz; Loyola-Vargas, Víctor M; Rojas-Herrera, Rafael; De-la-Peña, Clelia

    2013-01-01

    Plant cells have the capacity to generate a new plant without egg fertilization by a process known as somatic embryogenesis (SE), in which differentiated somatic cells can form somatic embryos able to generate a functional plant. Although there have been advances in understanding the genetic basis of SE, the epigenetic mechanism that regulates this process is still unknown. Here, we show that the embryogenic development of Coffea canephora proceeds through a crosstalk between DNA methylation and histone modifications during the earliest embryogenic stages of SE. We found that low levels of DNA methylation, histone H3 lysine 9 dimethylation (H3K9me2) and H3K27me3 change according to embryo development. Moreover, the expression of LEAFY cotyledon1 (LEC1) and BABY BOOM1 (BBM1) are only observed after SE induction, whereas WUSCHEL-related homeobox4 (WOX4) decreases its expression during embryo maturation. Using a pharmacological approach, it was found that 5-Azacytidine strongly inhibits the embryogenic response by decreasing both DNA methylation and gene expression of LEC1 and BBM1. Therefore, in order to know whether these genes were epigenetically regulated, we used Chromatin Immunoprecipitation (ChIP) assays. It was found that WOX4 is regulated by the repressive mark H3K9me2, while LEC1 and BBM1 are epigenetically regulated by H3K27me3. We conclude that epigenetic regulation plays an important role during somatic embryogenic development, and a molecular mechanism for SE is proposed.

  1. Circadian dynamics of the cone-rod homeobox (CRX) transcription factor in the rat pineal gland and its role in regulation of arylalkylamine N-acetyltransferase (AANAT).

    Science.gov (United States)

    Rohde, Kristian; Rovsing, Louise; Ho, Anthony K; Møller, Morten; Rath, Martin F

    2014-08-01

    The cone-rod homeobox (Crx) gene encodes a transcription factor in the retina and pineal gland. Crx deficiency influences the pineal transcriptome, including a reduced expression of arylalkylamine N-acetyltransferase (Aanat), a key enzyme in nocturnal pineal melatonin production. However, previous functional studies on pineal Crx have been performed in melatonin-deficient mice. In this study, we have investigated the role of Crx in the melatonin-proficient rat pineal gland. The current study shows that pineal Crx transcript levels exhibit a circadian rhythm with a peak in the middle of the night, which is transferred into daily changes in CRX protein. The study further shows that the sympathetic innervation of the pineal gland controls the Crx rhythm. By use of adenovirus-mediated short hairpin RNA gene knockdown targeting Crx mRNA in primary rat pinealocyte cell culture, we here show that intact levels of Crx mRNA are required to obtain high levels of Aanat expression, whereas overexpression of Crx induces Aanat transcription in vitro. This regulatory function of Crx is further supported by circadian analysis of Aanat in the pineal gland of the Crx-knockout mouse. Our data indicate that the rhythmic nature of pineal CRX protein may directly modulate the daily profile of Aanat expression by inducing nighttime expression of this enzyme, thus facilitating nocturnal melatonin synthesis in addition to its role in ensuring a correct tissue distribution of Aanat expression.

  2. The pancreatic and duodenal homeobox protein PDX-1 regulates the ductal specific keratin 19 through the degradation of MEIS1 and DNA binding.

    Directory of Open Access Journals (Sweden)

    Johannes von Burstin

    Full Text Available BACKGROUND: Pancreas organogenesis is the result of well-orchestrated and balanced activities of transcription factors. The homeobox transcription factor PDX-1 plays a crucial role in the development and function of the pancreas, both in the maintenance of progenitor cells and in determination and maintenance of differentiated endocrine cells. However, the activity of homeobox transcription factors requires coordination with co-factors, such as PBX and MEIS proteins. PBX and MEIS proteins belong to the family of three amino acid loop extension (TALE homeodomain proteins. In a previous study we found that PDX-1 negatively regulates the transcriptional activity of the ductal specific keratin 19 (Krt19. In this study, we investigate the role of different domains of PDX-1 and elucidate the functional interplay of PDX-1 and MEIS1 necessary for Krt19 regulation. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate that PDX-1 exerts a dual manner of regulation of Krt19 transcriptional activity. Deletion studies highlight that the NH(2-terminus of PDX-1 is functionally relevant for the down-regulation of Krt19, as it is required for DNA binding of PDX-1 to the Krt19 promoter. Moreover, this effect occurs independently of PBX. Second, we provide insight on how PDX-1 regulates the Hox co-factor MEIS1 post-transcriptionally. We find specific binding of MEIS1 and MEIS2 to the Krt19 promoter using IP-EMSA, and siRNA mediated silencing of Meis1, but not Meis2, reduces transcriptional activation of Krt19 in primary pancreatic ductal cells. Over-expression of PDX-1 leads to a decreased level of MEIS1 protein, and this decrease is prevented by inhibition of the proteasome. CONCLUSIONS/SIGNIFICANCE: Taken together, our data provide evidence for a dual mechanism of how PDX-1 negatively regulates Krt19 ductal specific gene expression. These findings imply that transcription factors may efficiently regulate target gene expression through diverse, non

  3. A genome-wide survey of HD-Zip genes in rice and analysis of drought-responsive family members

    NARCIS (Netherlands)

    Agalou, A.; Purwantomo, S.; Övernäs, E.; Johannesson, H.; Zhu, X.; Estiati, A.; Kam, R.J.de; Engström, P.; Slamet-Loedin, I.H.; Zhu, Z.; Wang, M.; Xiong, L.; Meijer, A.H.; Ouwerkerk, P.B.F.

    2008-01-01

    The homeodomain leucine zipper (HD-Zip) genes encode transcription factors that have diverse functions in plant development and have often been implicated in stress adaptation. The HD-Zip genes are the most abundant group of homeobox (HB) genes in plants and do not occur in other eukaryotes. This

  4. DUX4 binding to retroelements creates promoters that are active in FSHD muscle and testis.

    Directory of Open Access Journals (Sweden)

    Janet M Young

    2013-11-01

    Full Text Available The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues. Facioscapulohumeral muscular dystrophy (FSHD is caused by mutations that decrease the epigenetic repression of DUX4 in somatic tissues and result in mis-expression of this transcription factor in skeletal muscle. DUX4 binds sites in the human genome that contain a double-homeobox sequence motif, including sites in unique regions of the genome as well as many sites in repetitive elements. Using ChIP-seq and RNA-seq on myoblasts transduced with DUX4 we show that DUX4 binds and activates transcription of mammalian apparent LTR-retrotransposons (MaLRs, endogenous retrovirus (ERVL and ERVK elements, and pericentromeric satellite HSATII sequences. Some DUX4-activated MaLR and ERV elements create novel promoters for genes, long non-coding RNAs, and antisense transcripts. Many of these novel transcripts are expressed in FSHD muscle cells but not control cells, and thus might contribute to FSHD pathology. For example, HEY1, a repressor of myogenesis, is activated by DUX4 through a MaLR promoter. DUX4-bound motifs, including those in repetitive elements, show evolutionary conservation and some repeat-initiated transcripts are expressed in healthy testis, the normal expression site of DUX4, but more rarely in other somatic tissues. Testis expression patterns are known to have evolved rapidly in mammals, but the mechanisms behind this rapid change have not yet been identified: our results suggest that mobilization of MaLR and ERV elements during mammalian evolution altered germline gene expression patterns through transcriptional activation by DUX4. Our findings demonstrate a role for DUX4 and repetitive elements in mammalian germline evolution and in FSHD muscular dystrophy.

  5. Down-regulation of the zinc-finger homeobox protein TSHZ2 releases GLI1 from the nuclear repressor complex to restore its transcriptional activity during mammary tumorigenesis

    Science.gov (United States)

    Riku, Miho; Inaguma, Shingo; Ito, Hideaki; Tsunoda, Takumi; Ikeda, Hiroshi; Kasai, Kenji

    2016-01-01

    Although breast cancer is one of the most common malignancies, the molecular mechanisms underlying its development and progression are not fully understood. To identify key molecules involved, we screened publicly available microarray datasets for genes differentially expressed between breast cancers and normal mammary glands. We found that three of the genes predicted in this analysis were differentially expressed among human mammary tissues and cell lines. Of these genes, we focused on the role of the zinc-finger homeobox protein TSHZ2, which is down-regulated in breast cancer cells. We found that TSHZ2 is a nuclear protein harboring a bipartite nuclear localization signal, and we confirmed its function as a C-terminal binding protein (CtBP)-dependent transcriptional repressor. Through comprehensive screening, we identified TSHZ2-suppressing genes such as AEBP1 and CXCR4, which are conversely up-regulated by GLI1, the downstream transcription factor of Hedgehog signaling. We found that GLI1 forms a ternary complex with CtBP2 in the presence of TSHZ2 and that the transcriptional activity of GLI1 is suppressed by TSHZ2 in a CtBP-dependent manner. Indeed, knockdown of TSHZ2 increases the expression of AEBP1 and CXCR4 in TSHZ2-expressing immortalized mammary duct epithelium. Concordantly, immunohistochemical staining of mammary glands revealed that normal duct cells expresses GLI1 in the nucleus along with TSHZ2 and CtBP2, whereas invasive ductal carcinoma cells, which does not express TSHZ2, show the increase in the expression of AEBP1 and CXCR4 and in the cytoplasmic localization of GLI1. Thus, we propose that down-regulation of TSHZ2 is crucial for mammary tumorigenesis via the activation of GLI1. PMID:26744317

  6. Smad4-dependent suppressor pituitary homeobox 2 promotes PPP2R2A-mediated inhibition of Akt pathway in pancreatic cancer

    Science.gov (United States)

    Wang, Qi; Li, Juanjuan; Wu, Wei; Shen, Ruizhe; Jiang, He; Qian, Yuting; Tang, Yanping; Bai, Tingting; Wu, Sheng; Wei, Lumin; Zang, Yi; Zhang, Ji; Wang, Lifu

    2016-01-01

    The importance of Pituitary homeobox 2 (Pitx2) in malignancy remains enigmatic, and Pitx2 has not been previously implicated in pancreatic ductal adenocarcinoma (PDAC). In this study, we performed gene expression profiling of human PDAC tissues and identified Pitx2 as a promising candidate. Pitx2 expression was decreased from 2.6- to 19-fold in human PDAC tissues from microarray units. Immunochemistry staining showed that Pitx2 expression was moderate to intense in normal pancreatic and pancreatic intraepithelial neoplastic lesions, whereas low in human PDAC tissues. The Pitx2 levels correlated with overall patient survival post-operatively in PDAC. Induction of Pitx2 expression partly inhibited the malignant phenotype of PDAC cells. Interestingly, low Pitx2 expression was correlated with Smad4 mutant inactivation, but not with Pitx2 DNA-methylation. Furthermore, Smad4 protein bound to Pitx2 promoter and stimulated Pitx2 expression in PDAC. In addition, Pitx2 protein bound to the promoter of the protein phosphatase 2A regulatory subunit B55α (PPP2R2A) and upregulated PPP2R2A expression, which may activate dephosphorylation of Akt in PDAC. These findings provide new mechanistic insights into Pitx2 as a tumor suppressor in the downstream of Smad4. And Pitx2 protein promotes PPP2R2A expression which may inhibit Akt pathway. Therefore, we propose that the Smad4-Pitx2-PPP2R2A axis, a new signaling pathway, suppresses the pancreatic carcinogenesis. PMID:26848620

  7. Silibinin modulates caudal-type homeobox transcription factor (CDX2), an intestine specific tumor suppressor to abrogate colon cancer in experimental rats.

    Science.gov (United States)

    Sangeetha, N; Nalini, N

    2015-01-01

    To authenticate the colon cancer preventive potential of silibinin, the efficacy of silibinin needs to be tested by evaluating an organ-specific biomarker. The aim of this study was to evaluate the impact of silibinin on the colonic expression of the caudal-type homeobox transcription factor (CDX2) an intestine specific tumor suppressor gene and its downstream targets in the colon of rats challenged with 1,2 dimethyl hydrazine (DMH). Rats of groups 1 and 2 were treated as control and silibinin control. Rats under groups 3 and 4 were given DMH (20 mg/kg body weight (b.w.) subcutaneously) once a week for 15 consecutive weeks from the 4th week of the experimental period. In addition, group 4 rats alone were treated with silibinin (50 mg/kg b.w. per os) everyday throughout the study period of 32 weeks. Histological investigation and messenger RNA and protein expression studies were performed in the colonic tissues of experimental rats. Findings of the study revealed that DMH administration significantly decreased the expression of CDX2 and Guanylyl cyclase C (GCC) in the colon of experimental rats. Further the decreased levels of CDX2 protein, colonic mucin content, and increased number of mast cells in the colon of DMH alone-administered rats reflects the onset of carcinogenesis. The pathological changes caused due to CDX2 suppression were attenuated by silibinin supplementation. © The Author(s) 2014.

  8. Arabidopsis class I KNOTTED-like homeobox proteins act downstream in the IDA-HAE/HSL2 floral abscission signaling pathway.

    Science.gov (United States)

    Shi, Chun-Lin; Stenvik, Grethe-Elisabeth; Vie, Ane Kjersti; Bones, Atle M; Pautot, Véronique; Proveniers, Marcel; Aalen, Reidunn B; Butenko, Melinka A

    2011-07-01

    Floral organ abscission in Arabidopsis thaliana is regulated by the putative ligand-receptor system comprising the signaling peptide INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) and the two receptor-like kinases HAESA and HAESA-LIKE2. The IDA signaling pathway presumably activates a MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) cascade to induce separation between abscission zone (AZ) cells. Misexpression of IDA effectuates precocious floral abscission and ectopic cell separation in latent AZ cell regions, which suggests that negative regulators are in place to prevent unrestricted and untimely AZ cell separation. Through a screen for mutations that restore floral organ abscission in ida mutants, we identified three new mutant alleles of the KNOTTED-LIKE HOMEOBOX gene BREVIPEDICELLUS (BP)/KNOTTED-LIKE FROM ARABIDOPSIS THALIANA1 (KNAT1). Here, we show that bp mutants, in addition to shedding their floral organs prematurely, have phenotypic commonalities with plants misexpressing IDA, such as enlarged AZ cells. We propose that BP/KNAT1 inhibits floral organ cell separation by restricting AZ cell size and number and put forward a model whereby IDA signaling suppresses BP/KNAT1, which in turn allows KNAT2 and KNAT6 to induce floral organ abscission.

  9. Comparative expression pattern analysis of WUSCHEL-related homeobox 2 (WOX2) and WOX8/9 in developing seeds and somatic embryos of the gymnosperm Picea abies.

    Science.gov (United States)

    Palovaara, Joakim; Hallberg, Henrik; Stasolla, Claudio; Hakman, Inger

    2010-10-01

    • In seed plants, current knowledge concerning embryonic pattern formation by polar auxin transport (PAT) and WUSCHEL-related homeobox (WOX) gene activity is primarily derived from studies on angiosperms, while less is known about these processes in gymnosperms. In view of the differences in their embryogeny, and the fact that somatic embryogenesis is used for mass propagation of conifers, a better understanding of embryo development is vital. • The expression patterns of PaWOX2 and PaWOX8/9 were followed with quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) during seed and somatic embryo development in Norway spruce (Picea abies), and in somatic embryos treated with the PAT inhibitor N-1-naphthylphthalamic acid (NPA). • Both PaWOX2 and PaWOX8/9 were highly expressed at the early growth stages of zygotic and somatic embryos, and shared a similar expression pattern over the entire embryo. At later embryo stages, high expression of PaWOX8/9 became restricted to cotyledon primordia, epidermis, procambium and root apical meristem (RAM), which became most evident in NPA-treated somatic embryos, while expression of PaWOX2 was much lower. • Our results suggest an ancestral role of WOX in seed plant embryo development, and strengthen the proposed connection between PAT, PIN-FORMED (PIN) and WOX in the regulation of embryo patterning in seed plants.

  10. Enrichment of HP1a on Drosophila chromosome 4 genes creates an alternate chromatin structure critical for regulation in this heterochromatic domain.

    Directory of Open Access Journals (Sweden)

    Nicole C Riddle

    2012-09-01

    Full Text Available Chromatin environments differ greatly within a eukaryotic genome, depending on expression state, chromosomal location, and nuclear position. In genomic regions characterized by high repeat content and high gene density, chromatin structure must silence transposable elements but permit expression of embedded genes. We have investigated one such region, chromosome 4 of Drosophila melanogaster. Using chromatin-immunoprecipitation followed by microarray (ChIP-chip analysis, we examined enrichment patterns of 20 histone modifications and 25 chromosomal proteins in S2 and BG3 cells, as well as the changes in several marks resulting from mutations in key proteins. Active genes on chromosome 4 are distinct from those in euchromatin or pericentric heterochromatin: while there is a depletion of silencing marks at the transcription start sites (TSSs, HP1a and H3K9me3, but not H3K9me2, are enriched strongly over gene bodies. Intriguingly, genes on chromosome 4 are less frequently associated with paused polymerase. However, when the chromatin is altered by depleting HP1a or POF, the RNA pol II enrichment patterns of many chromosome 4 genes shift, showing a significant decrease over gene bodies but not at TSSs, accompanied by lower expression of those genes. Chromosome 4 genes have a low incidence of TRL/GAGA factor binding sites and a low T(m downstream of the TSS, characteristics that could contribute to a low incidence of RNA polymerase pausing. Our data also indicate that EGG and POF jointly regulate H3K9 methylation and promote HP1a binding over gene bodies, while HP1a targeting and H3K9 methylation are maintained at the repeats by an independent mechanism. The HP1a-enriched, POF-associated chromatin structure over the gene bodies may represent one type of adaptation for genes embedded in repetitive DNA.

  11. Pituitary homeobox 2 (PITX2) protects renal cancer cell lines against doxorubicin toxicity by transcriptional activation of the multidrug transporter ABCB1.

    Science.gov (United States)

    Lee, Wing-Kee; Chakraborty, Prabir K; Thévenod, Frank

    2013-08-01

    The multidrug resistance (MDR) P-glycoprotein ABCB1 plays a major role in MDR of malignant cells and is regulated by various transcription factors, including Wnt/β-catenin/TCF4. The transcription factor PITX2 (Pituitary homeobox-2) is essential for embryonic development. PITX2 operates by recruiting and interacting with β-catenin to increase the expression of growth-regulating genes, such as cyclin D1/2 and c-Myc. The importance of PITX2 in malignancy is not yet known. Here we demonstrate that in the renal cancer cell lines ACHN and A498, the level of ABCB1 expression and function correlate with nuclear PITX2 localization and PITX2-luciferase reporter gene activity (A498 > ACHN). In A498 cells, doxorubicin toxicity is augmented by the ABCB1 inhibitor, PSC833. PITX2 overexpression increases ABCB1 expression and cell survival in ACHN cells. Silencing of PITX2 by siRNA downregulates ABCB1 and induces a greater chemotherapeutic response to doxorubicin in A498 cells, as determined by MTT cell viability and clonogenic survival assays. Two PITX2 binding sequences were identified in the ABCB1 promoter sequence. PITX2 binding was confirmed by chromatin immunoprecipitation. β-Catenin is not required for PITX2 upregulation of ABCB1 because ABCB1 mRNA increased and doxorubicin toxicity decreased upon PITX2 overexpression in β-catenin(-/-) cells. The data show for the first time that ABCB1 is a target gene of PITX2 transcriptional activity, promoting MDR and cell survival of cancer cells. Copyright © 2013 UICC.

  12. D-subgenome bias of Xcm resistance genes in tetraploid Gossypium (cotton) suggests that polyploid formation has created novel avenues for evolution.

    Science.gov (United States)

    Wright, R J; Thaxton, P M; El-Zik, K M; Paterson, A H

    1998-08-01

    A detailed RFLP map was used to determine the chromosomal locations and subgenomic distributions of cotton (Gossypium) genes/QTLs that confer resistance to the bacterial blight pathogen, Xanthomonas campestris pv. malvacearum (Xcm). Genetic mapping generally corroborated classic predictions regarding the number and dosage effects of genes conferring Xcm resistance. One recessive allele (b6) was a noteworthy exception to the genetic dominance of most plant resistance alleles. This recessive allele appeared to uncover additional QTLs from both resistant and ostensibly susceptible genotypes, some of which corresponded in location to resistance (R)-genes effective against other Xcm races. One putatively "defeated" resistance allele (B3) reduced severity of Xcm damage by "virulent" races. Among the six resistance genes derived from tetraploid cottons, five (83%) mapped to D-subgenome chromosomes-if each subgenome were equally likely to evolve new R-gene alleles, this level of bias would occur in only about 1.6% of cases. Possible explanations of this bias include biogeographic factors, differences in evolutionary rates between subgenomes, gene conversion or other intergenomic exchanges that escaped detection by genetic mapping, or other factors. A significant D-subgenome bias of Xcm resistance genes may suggest that polyploid formation has offered novel avenues for phenotypic response to selection.

  13. Highly expressed captured genes and cross-kingdom domains present in Helitrons create novel diversity in Pleurotus ostreatus and other fungi.

    Science.gov (United States)

    Castanera, Raúl; Pérez, Gúmer; López, Leticia; Sancho, Rubén; Santoyo, Francisco; Alfaro, Manuel; Gabaldón, Toni; Pisabarro, Antonio G; Oguiza, José A; Ramírez, Lucía

    2014-12-05

    Helitrons are class-II eukaryotic transposons that transpose via a rolling circle mechanism. Due to their ability to capture and mobilize gene fragments, they play an important role in the evolution of their host genomes. We have used a bioinformatics approach for the identification of helitrons in two Pleurotus ostreatus genomes using de novo detection and homology-based searching. We have analyzed the presence of helitron-captured genes as well as the expansion of helitron-specific helicases in fungi and performed a phylogenetic analysis of their conserved domains with other representative eukaryotic species. Our results show the presence of two helitron families in P. ostreatus that disrupt gene colinearity and cause a lack of synteny between their genomes. Both putative autonomous and non-autonomous helitrons were transcriptionally active, and some of them carried highly expressed captured genes of unknown origin and function. In addition, both families contained eukaryotic, bacterial and viral domains within the helitron's boundaries. A phylogenetic reconstruction of RepHel helicases using the Helitron-like and PIF1-like helicase conserved domains revealed a polyphyletic origin for eukaryotic helitrons. P. ostreatus helitrons display features similar to other eukaryotic helitrons and do not tend to capture host genes or gene fragments. The occurrence of genes probably captured from other hosts inside the helitrons boundaries pose the hypothesis that an ancient horizontal transfer mechanism could have taken place. The viral domains found in some of these genes and the polyphyletic origin of RepHel helicases in the eukaryotic kingdom suggests that virus could have played a role in a putative lateral transfer of helitrons within the eukaryotic kingdom. The high similarity of some helitrons, along with the transcriptional activity of its RepHel helicases indicates that these elements are still active in the genome of P. ostreatus.

  14. A Large Number of Nuclear Genes in the Human Parasite Blastocystis Require mRNA Polyadenylation to Create Functional Termination Codons

    OpenAIRE

    Klimeš, Vladimír; Gentekaki, Eleni; Roger, Andrew J.; Eliáš, Marek

    2014-01-01

    Termination codons in mRNA molecules are typically specified directly by the sequence of the corresponding gene. However, in mitochondria of a few eukaryotic groups, some mRNAs contain the termination codon UAA deriving one or both adenosines from transcript polyadenylation. Here, we show that a similar phenomenon occurs for a substantial number of nuclear genes in Blastocystis spp., divergent unicellular eukaryote gut parasites. Our analyses of published genomic data from Blastocystis sp. su...

  15. Creating Genetic Resistance to HIV

    Science.gov (United States)

    Burnett, John C.; Zaia, John A.; Rossi, John J.

    2012-01-01

    HIV/AIDS remains a chronic and incurable disease, in spite of the notable successes of highly active antiretroviral therapy. Gene therapy offers the prospect of creating genetic resistance to HIV that supplants the need for antiviral drugs. In sight of this goal, a variety of anti-HIV genes have reached clinical testing, including gene-editing enzymes, protein-based inhibitors, and RNA-based therapeutics. Combinations of therapeutic genes against viral and host targets are designed to improve the overall antiviral potency and reduce the likelihood of viral resistance. In cell-based therapies, therapeutic genes are expressed in gene modified T lymphocytes or in hematopoietic stem cells that generate an HIV-resistant immune system. Such strategies must promote the selective proliferation of the transplanted cells and the prolonged expression of therapeutic genes. This review focuses on the current advances and limitations in genetic therapies against HIV, including the status of several recent and ongoing clinical studies. PMID:22985479

  16. Identification of a putative nuclear export signal motif in human NANOG homeobox domain

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung-Won; Do, Hyun-Jin; Huh, Sun-Hyung; Sung, Boreum [Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-Do (Korea, Republic of); Uhm, Sang-Jun [Department of Animal Science and Biotechnology, Sangji Youngseo College, Wonju, Gwangwon-Do (Korea, Republic of); Song, Hyuk [Department of Animal and Food Bioscience, College of Natural Science, Konkuk University, ChungJu, Chungbuk (Korea, Republic of); Kim, Nam-Hyung [Department of Animal Sciences, Chungbuk National University, Cheongju, Chungbuk (Korea, Republic of); Kim, Jae-Hwan, E-mail: jaehwan_k@cha.ac.kr [Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-Do (Korea, Republic of)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer We found the putative nuclear export signal motif within human NANOG homeodomain. Black-Right-Pointing-Pointer Leucine-rich residues are important for human NANOG homeodomain nuclear export. Black-Right-Pointing-Pointer CRM1-specific inhibitor LMB blocked the potent human NANOG NES-mediated nuclear export. -- Abstract: NANOG is a homeobox-containing transcription factor that plays an important role in pluripotent stem cells and tumorigenic cells. To understand how nuclear localization of human NANOG is regulated, the NANOG sequence was examined and a leucine-rich nuclear export signal (NES) motif ({sup 125}MQELSNILNL{sup 134}) was found in the homeodomain (HD). To functionally validate the putative NES motif, deletion and site-directed mutants were fused to an EGFP expression vector and transfected into COS-7 cells, and the localization of the proteins was examined. While hNANOG HD exclusively localized to the nucleus, a mutant with both NLSs deleted and only the putative NES motif contained (hNANOG HD-{Delta}NLSs) was predominantly cytoplasmic, as observed by nucleo/cytoplasmic fractionation and Western blot analysis as well as confocal microscopy. Furthermore, site-directed mutagenesis of the putative NES motif in a partial hNANOG HD only containing either one of the two NLS motifs led to localization in the nucleus, suggesting that the NES motif may play a functional role in nuclear export. Furthermore, CRM1-specific nuclear export inhibitor LMB blocked the hNANOG potent NES-mediated export, suggesting that the leucine-rich motif may function in CRM1-mediated nuclear export of hNANOG. Collectively, a NES motif is present in the hNANOG HD and may be functionally involved in CRM1-mediated nuclear export pathway.

  17. Intestine-specific homeobox (ISX) induces intestinal metaplasia and cell proliferation to contribute to gastric carcinogenesis.

    Science.gov (United States)

    Sue, Soichiro; Shibata, Wataru; Kameta, Eri; Sato, Takeshi; Ishii, Yasuaki; Kaneko, Hiroaki; Miwa, Haruo; Sasaki, Tomohiko; Tamura, Toshihide; Kondo, Masaaki; Maeda, Shin

    2016-10-01

    Helicobacter pylori induces chronic inflammation and intestinal metaplasia (IM) through genetic and epigenetic changes and activation of intracellular signaling pathways that contribute to gastric carcinogenesis. However, the precise mechanism of IM in gastric carcinogenesis has not been fully elucidated. We previously found that intestine-specific homeobox (ISX) mRNA expression increased in organoids cultured from Helicobacter-infected mouse mucosa. In this study, we elucidate the role of ISX in the development of IM and gastric carcinogenesis. ISX expression was assessed in Helicobacter-infected mouse and human gastric mucosa. MKN45 gastric cancer cells were co-cultured with H. pylori to determine whether Helicobacter infection induced ISX expression. We established stable MKN45 transfected cells expressing ISX (Stable-ISX MKN45) and performed a spheroid colony formation assay and a xenograft model. We performed ISX immunohistochemistry in cancer and adjacent gastric tissues. ISX expression was increased in mouse and human gastric mucosa infected with Helicobacter. The presence of IM and H. pylori infection in human stomach was correlated with ISX expression. H. pylori induced ISX mRNA and protein expression. CDX1/2, cyclinD1, and MUC2 were upregulated in Stable-ISX MKN45, whereas MUC5AC was downregulated. Stable-ISX MKN45 cells formed more spheroid colonies, and had high tumorigenic ability. ISX expression in gastric cancer and adjacent mucosa were correlated. ISX expression induced by H. pylori infection may lead to IM and hyperproliferation of gastric mucosa through CDX1/2 and cyclinD1 expression, contributing to gastric carcinogenesis.

  18. A large number of nuclear genes in the human parasite blastocystis require mRNA polyadenylation to create functional termination codons.

    Science.gov (United States)

    Klimeš, Vladimír; Gentekaki, Eleni; Roger, Andrew J; Eliáš, Marek

    2014-07-10

    Termination codons in mRNA molecules are typically specified directly by the sequence of the corresponding gene. However, in mitochondria of a few eukaryotic groups, some mRNAs contain the termination codon UAA deriving one or both adenosines from transcript polyadenylation. Here, we show that a similar phenomenon occurs for a substantial number of nuclear genes in Blastocystis spp., divergent unicellular eukaryote gut parasites. Our analyses of published genomic data from Blastocystis sp. subtype 7 revealed that polyadenylation-mediated creation of termination codons occurs in approximately 15% of all nuclear genes. As this phenomenon has not been noticed before, the procedure previously employed to annotate the Blastocystis nuclear genome sequence failed to correctly define the structure of the 3'-ends of hundreds of genes. From sequence data we have obtained from the distantly related Blastocystis sp. subtype 1 strain, we show that this phenomenon is widespread within the Blastocystis genus. Polyadenylation in Blastocystis appears to be directed by a conserved GU-rich element located four nucleotides downstream of the polyadenylation site. Thus, the highly precise positioning of the polyadenylation in Blastocystis has allowed reduction of the 3'-untranslated regions to the point that, in many genes, only one or two nucleotides of the termination codon are left. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. Targeted gene expression without a tissue-specific promoter: creating mosaic embryos using laser-induced single-cell heat shock

    Science.gov (United States)

    Halfon, M. S.; Kose, H.; Chiba, A.; Keshishian, H.

    1997-01-01

    We have developed a method to target gene expression in the Drosophila embryo to a specific cell without having a promoter that directs expression in that particular cell. Using a digitally enhanced imaging system to identify single cells within the living embryo, we apply a heat shock to each cell individually by using a laser microbeam. A 1- to 2-min laser treatment is sufficient to induce a heat-shock response but is not lethal to the heat-shocked cells. Induction of heat shock was measured in a variety of cell types, including neurons and somatic muscles, by the expression of beta-galactosidase from an hsp26-lacZ reporter construct or by expression of a UAS target gene after induction of hsGAL4. We discuss the applicability of this technique to ectopic gene expression studies, lineage tracing, gene inactivation studies, and studies of cells in vitro. Laser heat shock is a versatile technique that can be adapted for use in a variety of research organisms and is useful for any studies in which it is desirable to express a given gene in only a distinct cell or clone of cells, either transiently or constitutively, at a time point of choice.

  20. Illegitimate translation causes unexpected gene expression from on-target out-of-frame alleles created by CRISPR-Cas9.

    Science.gov (United States)

    Makino, Shigeru; Fukumura, Ryutaro; Gondo, Yoichi

    2016-12-21

    CRISPR-Cas9 is efficient enough to knock out both alleles directly by introducing out-of-frame mutations. We succeeded in making biallelic on-target frameshift mutations of the endogenous Gli3 gene; however, the GLI3 protein was expressed in all six of the established cell lines carrying homozygous out-of-frame mutations. We developed a dual-tagged expression vector and proved that illegitimate translation (ITL) was the cause of the unexpected Gli3 expression. Thus, gene expression must be examined even if designed on-target out-of-frame sequences are introduced by genome editing. In addition, it is highly recommended to pre-examine the occurrence of ITL in vitro prior to the design and construction of any genome-editing vectors. In vitro assay systems such as the dual-tagged ITL assay system developed in this study should aid the identification and elucidation of ITL-based human diseases and gene expression.

  1. A muscle-specific promoter directs Pitx3 gene expression in skeletal muscle cells

    NARCIS (Netherlands)

    Coulon, Vincent; L'Honoré, Aurore; Ouimette, Jean-François; Dumontier, Emilie; van den Munckhof, Pepijn; Drouin, Jacques

    2007-01-01

    The Pitx homeobox transcription factor genes have been implicated in different developmental processes, including determination of hind limb identity for Pitx1, left-right asymmetry for Pitx2, and eye development and survival of midbrain dopaminergic neurons for Pitx3. Pitx1 and Pitx2 have partly

  2. Iroquois genes influence proximo-distal morphogenesis during rat lung development

    NARCIS (Netherlands)

    W.G. van Tuyl (Minke); J. Liu (Jason); F. Groenman (Frederick); R. Ridsdale (Ross); R.N.N. Han (Robin N.); V. Venkatesh (Vikram); D. Tibboel (Dick); M.R. Post (Martin)

    2006-01-01

    textabstractLung development is a highly regulated process directed by mesenchymal-epithelial interactions, which coordinate the temporal and spatial expression of multiple regulatory factors required for proper lung formation. The Iroquois homeobox (Irx) genes have been implicated in the patterning

  3. Identification of novel SHOX target genes in the developing limb using a transgenic mouse model

    NARCIS (Netherlands)

    Beiser, Katja U.; Glaser, Anne; Kleinschmidt, Kerstin; Scholl, Isabell; Röth, Ralph; Li, Li; Gretz, Norbert; Mechtersheimer, Gunhild; Karperien, Hermanus Bernardus Johannes; Marchini, Antonio; Richter, Wiltrud; Rappold, Gudrun A.

    2014-01-01

    Deficiency of the human short stature homeobox-containing gene (SHOX) has been identified in several disorders characterized by reduced height and skeletal anomalies such as Turner syndrome, Léri-Weill dyschondrosteosis and Langer mesomelic dysplasia as well as isolated short stature. SHOX acts as a

  4. The LIM homeodomain transcription factor LHX6: a transcriptional repressor that interacts with pituitary homeobox 2 (PITX2) to regulate odontogenesis.

    Science.gov (United States)

    Zhang, Zichao; Gutierrez, Diana; Li, Xiao; Bidlack, Felicitas; Cao, Huojun; Wang, Jianbo; Andrade, Kelsey; Margolis, Henry C; Amendt, Brad A

    2013-01-25

    LHX6 is a LIM-homeobox transcription factor expressed during embryogenesis; however, the molecular mechanisms regulating LHX6 transcriptional activities are unknown. LHX6 and the PITX2 homeodomain transcription factor have overlapping expression patterns during tooth and craniofacial development, and in this report, we demonstrate new transcriptional mechanisms for these factors. PITX2 and LHX6 are co-expressed in the oral and dental epithelium and epithelial cell lines. Lhx6 expression is increased in Pitx2c transgenic mice and decreased in Pitx2 null mice. PITX2 activates endogenous Lhx6 expression and the Lhx6 promoter, whereas LHX6 represses its promoter activity. Chromatin immunoprecipitation experiments reveal endogenous PITX2 binding to the Lhx6 promoter. LHX6 directly interacts with PITX2 to inhibit PITX2 transcriptional activities and activation of multiple promoters. Bimolecular fluorescence complementation assays reveal an LHX6·PITX2 nuclear interaction in living cells. LHX6 has a dominant repressive effect on the PITX2 synergistic activation with LEF-1 and β-catenin co-factors. Thus, LHX6 acts as a transcriptional repressor and represses the expression of several genes involved in odontogenesis. We have identified specific defects in incisor, molar, mandible, bone, and root development and late stage enamel formation in Lhx6 null mice. Amelogenin and ameloblastin expression is reduced and/or delayed in the Lhx6 null mice, potentially resulting from defects in dentin deposition and ameloblast differentiation. Our results demonstrate that LHX6 regulates cell proliferation in the cervical loop and promotes cell differentiation in the anterior region of the incisor. We demonstrate new molecular mechanisms for LHX6 and an interaction with PITX2 for normal craniofacial and tooth development.

  5. Establishment of a congenital tooth agenesis related gene MSX1 knockout human embryonic stem cell lines by CRISPR-Cas9 technology

    Directory of Open Access Journals (Sweden)

    Yanting Xue

    2017-10-01

    Full Text Available Human MSX1 gene is mapped to chromosome 4 and encodes a 303aa homeobox protein MSX1. MSX1 expression appears during early tooth development of vertebrate embryogenesis. Mutations in this protein are related to human tooth anomalie, cleft lip and palate and congenital ectodermal dysplasia syndrome. Most of the confirmed pathogenic mutations are located in exon2 encoded homeobox domain. Here, we report the establishment of MSX1 gene knockout human embryonic stem (hES cell lines by CRISPR-Cas9 technology. These cell lines provide good materials for further studies of the roles MSX1 plays in human tooth development and congenital tooth agenesis.

  6. Create Your Plate

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    Full Text Available ... A A A Listen En Español Create Your Plate Create Your Plate is a simple and effective ... and that your options are endless. Create Your Plate! Click on the plate sections below to add ...

  7. Create Your Plate

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    Full Text Available ... Plate Create Your Plate is a simple and effective way to manage your blood glucose levels and ... Steps to Create Your Plate It's simple and effective for both managing diabetes and losing weight. Creating ...

  8. CRISPR/Cas9-mediated gene manipulation to create single-amino-acid-substituted and floxed mice with a cloning-free method.

    Science.gov (United States)

    Ma, Xiaolong; Chen, Chao; Veevers, Jennifer; Zhou, XinMin; Ross, Robert S; Feng, Wei; Chen, Ju

    2017-02-08

    Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology is a powerful tool to manipulate the genome with extraordinary simplicity and speed. To generate genetically modified animals, CRISPR/Cas9-mediated genome editing is typically accomplished by microinjection of a mixture of Cas9 DNA/mRNA and single-guide RNA (sgRNA) into zygotes. However, sgRNAs used for this approach require manipulation via molecular cloning as well as in vitro transcription. Beyond these complexities, most mutants obtained with this traditional approach are genetically mosaic, yielding several types of cells with different genetic mutations. Recently, a growing body of studies has utilized commercially available Cas9 protein together with sgRNA and a targeting construct to introduce desired mutations. Here, we report a cloning-free method to target the mouse genome by pronuclear injection of a commercial Cas9 protein:crRNA:tracrRNA:single-strand oligodeoxynucleotide (ssODN) complex into mouse zygotes. As illustration of this method, we report the successful generation of global gene-knockout, single-amino-acid-substituted, as well as floxed mice that can be used for conditional gene-targeting. These models were produced with high efficiency to generate non-mosaic mutant mice with a high germline transmission rate.

  9. Create Your Plate

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    Full Text Available ... Planning Meals Diabetes Meal Plans Create Your Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook ... Create Your Plate Meal Planning for Vegetarian Diets Gluten Free Diets Holiday Meal Planning Cook with Heart- ...

  10. Create Your Plate

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    Full Text Available ... treatments for those living with diabetes. Other Ways to Give Become a Member Vehicle Donation Planned Giving ... Share Create Your Plate ! Share: Seven Simple Steps to Create Your Plate It's simple and effective for ...

  11. Homeobox gene expression in adult dorsal root ganglia during sciatic nerve regeneration: is regeneration a recapitulation of development?

    NARCIS (Netherlands)

    Gispen, W.H.; Vogelaar, C.F.; Hoekman, M.F.; Burbach, J.P.H.

    2003-01-01

    After damage of the sciatic nerve, a regeneration process is initiated. Neurons in the dorsal root ganglion regrow their axons and functional connections. The molecular mechanisms of this neuronal regenerative process have remained elusive, but a relationship with developmental processes has been

  12. MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells

    Directory of Open Access Journals (Sweden)

    Yamashita Shunichi

    2011-03-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is often diagnosed at later stages until they are incurable. MicroRNA (miR is a small, non-coding RNA that negatively regulates gene expression mainly via translational repression. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. The aim of this study was to identify miR that could be specifically expressed and exert distinct biological actions in ESCC. Methods Total RNA was extracted from ESCC cell lines, OE21 and TE10, and a non-malignant human esophageal squamous cell line, Het-1A, and subjected to microarray analysis. Expression levels of miR that showed significant differences between the 2 ESCC and Het-1A cells based on the comprehensive analysis were analyzed by the quantitative reverse transcriptase (RT-PCR method. Then, functional analyses, including cellular proliferation, apoptosis and Matrigel invasion and the wound healing assay, for the specific miR were conducted. Using ESCC tumor samples and paired surrounding non-cancerous tissue obtained endoscopically, the association with histopathological differentiation was examined with quantitative RT-PCR. Results Based on the miR microarray analysis, there were 14 miRs that showed significant differences (more than 2-fold in expression between the 2 ESCC cells and non-malignant Het-1A. Among the significantly altered miRs, miR-205 expression levels were exclusively higher in 5 ESCC cell lines examined than any other types of malignant cell lines and Het-1A. Thus, miR-205 could be a specific miR in ESCC. Modulation of miR-205 expression by transfection with its precursor or anti-miR-205 inhibitor did not affect ESCC cell proliferation and apoptosis, but miR-205 was found to be involved in cell invasion and migration. Western blot revealed that knockdown of miR-205 expression in ESCC cells substantially enhanced expression of zinc finger E-box binding homeobox 2

  13. Create Your Plate

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    Full Text Available ... Diabetes Meal Plans Create Your Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook with Heart-Healthy Foods Holiday Meal Planning ... Planning Meals Diabetes Meal Plans and a Healthy Diet Create Your Plate Meal Planning for Vegetarian Diets ...

  15. Create Your Plate

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    Full Text Available ... Share: Print Page Text Size: A A A Listen En Español Create Your Plate Create Your Plate is a simple and effective way to manage your blood glucose levels and lose weight. With this method, you fill your plate with more non-starchy veggies ...

  16. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  17. All the three ParaHox genes are present in Nuttallochiton mirandus (Mollusca: polyplacophora): evolutionary considerations.

    Science.gov (United States)

    Barucca, Marco; Biscotti, Maria A; Olmo, Ettore; Canapa, Adriana

    2006-03-15

    The ParaHox gene cluster contains three homeobox genes, Gsx, Xlox and Cdx and has been demonstrated to be an evolutionary sister of the Hox gene cluster. Among deuterostomes the three genes are found in the majority of taxa, whereas among protostomes they have so far been isolated only in the phylum Sipuncula. We report the partial sequences of all three ParaHox genes in the polyplacophoran Nuttallochiton mirandus, the first species of the phylum Mollusca where all ParaHox genes have been isolated. This finding has phylogenetic implications for the phylum Mollusca and for its relationships with the other lophotrochozoan taxa. Copyright 2005 Wiley-Liss, Inc.

  18. Aberrant endometrial DNA methylome of homeobox A10 and catechol-O-methyltransferase in endometriosis.

    Science.gov (United States)

    Ji, Fei; Yang, Xinhua; He, Yan; Wang, Hui; Aili, Aixingzi; Ding, Yan

    2017-03-01

    Differential methylation of both HOXA10 and catechol-O-methyltransferase (COMT) has been reported in different endometrium disorders, and the two genes are linked through the estrogen pathway. The current study investigates the DNA methylation of HOXA10 and COMT in ectopic and eutopic endometrial tissues and its correlation with and the occurrence of endometriosis in women from Xinjiang province in China. In the current study, 120 patients with endometriosis were recruited from our hospital between January 2011 and June 2014. The DNA methylation sites of HOXA10 and COMT were detected using a DNA methylation array. The methylation levels of specific sites were compared between ectopic and eutopic endometrial tissues via pyrosequencing. Five differentially expressed CpGs were localized in the promoter region of the COMT gene and expressed significantly higher in the ectopic endometrium than the eutopic endometrium (P < 0.001). Two out of the five differentially expressed CpGs in the HOXA10 gene located in the promoter region were both significantly lower (nearly half) in the ectopic endometrium than the eutopic endometrium (P < 0.001). To summarize, significant differential methylation of HOXA10 and COMT promoter regions was found between the ectopic and eutopic endometrial tissues. This is the first study investigating the methylation of HOXA10 and COMT genes and their linkage to endometriosis in Chinese patients.

  19. Prospero-related homeobox 1 (Prox1 at the crossroads of diverse pathways during adult neural fate specification

    Directory of Open Access Journals (Sweden)

    Athanasios eStergiopoulos

    2015-01-01

    Full Text Available Over the last decades, adult neurogenesis in the central nervous system (CNS has emerged as a fundamental process underlying physiology and disease. Recent evidence indicates that the homeobox transcription factor Prox1 is a critical intrinsic regulator of neurogenesis in the embryonic CNS and adult dentate gyrus (DG of the hippocampus, acting in multiple ways and instructed by extrinsic cues and intrinsic factors. In the embryonic CNS, Prox1 is mechanistically involved in the regulation of proliferation versus differentiation decisions of NSCs, promoting cell cycle exit and neuronal differentiation, while inhibits astrogliogenesis. During the complex differentiation events in adult hippocampal neurogenesis, Prox1 is required for maintenance of intermediate progenitors (IPs, differentiation and maturation of glutamatergic interneurons, as well as specification of DG cell identity over CA3 pyramidal fate. The mechanism by which Prox1 exerts multiple functions involves distinct signaling pathways currently not fully highlighted. In this mini-review, we thoroughly discuss the Prox1-dependent phenotypes and molecular pathways in adult neurogenesis in relation to different upstream signaling cues and cell fate determinants. In addition, we discuss the possibility that Prox1 may act as a cross-talk point between diverse signaling cascades to achieve specific outcomes during adult neurogenesis.

  20. The homeobox protein CEH-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in C. elegans.

    Directory of Open Access Journals (Sweden)

    Ludivine Walter

    2011-06-01

    Full Text Available Recent findings indicate that perturbations of the mitochondrial electron transport chain (METC can cause extended longevity in evolutionarily diverse organisms. To uncover the molecular basis of how altered METC increases lifespan in C. elegans, we performed an RNAi screen and revealed that three predicted transcription factors are specifically required for the extended longevity of mitochondrial mutants. In particular, we demonstrated that the nuclear homeobox protein CEH-23 uniquely mediates the longevity but not the slow development, reduced brood size, or resistance to oxidative stress associated with mitochondrial mutations. Furthermore, we showed that ceh-23 expression levels are responsive to altered METC, and enforced overexpression of ceh-23 is sufficient to extend lifespan in wild-type background. Our data point to mitochondria-to-nucleus communications to be key for longevity determination and highlight CEH-23 as a novel longevity factor capable of responding to mitochondrial perturbations. These findings provide a new paradigm for how mitochondria impact aging and age-dependent diseases.

  1. Over-Expression of POU Class 1 Homeobox 1 Transcription Factor (Pit-1) Predicts Poor Prognosis for Breast Cancer Patients.

    Science.gov (United States)

    Gao, Zhongcheng; Xue, Kecheng; Zhang, Lianfang; Wei, Meng

    2016-10-31

    The POU class 1 homeobox 1 transcription factor (POU1F1, also known as Pit-1) was reported to be associated with tumor progression and metastasis. The purpose of this study was to evaluate the prognostic value of Pit-1 in breast cancer patients. The relative expression levels of Pit-1 in breast cancer patients were detected by quantitative real-time PCR (qRT-PCR). Chi-square analysis was used to analyze the association between Pit-1 expression and clinical features. The Kaplan-Meier method was used to estimate the overall survival of the patients and Cox regression analysis was used to analyze the prognostic value of Pit-1. Increased expression of Pit-1 was detected in the tumor tissues compared with the normal tissues (1.086 vs. 0.541) and the abnormal expression was associated with tumor size, clinical stage, tumor grade, and lymph node metastasis (PPit-1 was significantly associated with poor overall survival of the patients (P=0.001) and Cox regression analysis indicated that Pit-1 might be a prognostic factor for breast cancer prognosis (HR=1.955, 95% CI=1.295-3.035, P=0.003). Pit-1 may be a potential prognostic biomarker for breast cancer patients and it is associated with tumor progression.

  2. Prospero-related homeobox 1 (Prox1) at the crossroads of diverse pathways during adult neural fate specification.

    Science.gov (United States)

    Stergiopoulos, Athanasios; Elkouris, Maximilianos; Politis, Panagiotis K

    2014-01-01

    Over the last decades, adult neurogenesis in the central nervous system (CNS) has emerged as a fundamental process underlying physiology and disease. Recent evidence indicates that the homeobox transcription factor Prox1 is a critical intrinsic regulator of neurogenesis in the embryonic CNS and adult dentate gyrus (DG) of the hippocampus, acting in multiple ways and instructed by extrinsic cues and intrinsic factors. In the embryonic CNS, Prox1 is mechanistically involved in the regulation of proliferation vs. differentiation decisions of neural stem cells (NSCs), promoting cell cycle exit and neuronal differentiation, while inhibiting astrogliogenesis. During the complex differentiation events in adult hippocampal neurogenesis, Prox1 is required for maintenance of intermediate progenitors (IPs), differentiation and maturation of glutamatergic interneurons, as well as specification of DG cell identity over CA3 pyramidal fate. The mechanism by which Prox1 exerts multiple functions involves distinct signaling pathways currently not fully highlighted. In this mini-review, we thoroughly discuss the Prox1-dependent phenotypes and molecular pathways in adult neurogenesis in relation to different upstream signaling cues and cell fate determinants. In addition, we discuss the possibility that Prox1 may act as a cross-talk point between diverse signaling cascades to achieve specific outcomes during adult neurogenesis.

  3. Creating more effective graphs

    CERN Document Server

    Robbins, Naomi B

    2012-01-01

    A succinct and highly readable guide to creating effective graphs The right graph can be a powerful tool for communicating information, improving a presentation, or conveying your point in print. If your professional endeavors call for you to present data graphically, here's a book that can help you do it more effectively. Creating More Effective Graphs gives you the basic knowledge and techniques required to choose and create appropriate graphs for a broad range of applications. Using real-world examples everyone can relate to, the author draws on her years of experience in gr

  4. Fibroblast growth factor 9 (FGF9)-pituitary homeobox 2 (PITX2) pathway mediates transforming growth factor β (TGFβ) signaling to regulate cell proliferation in palatal mesenchyme during mouse palatogenesis.

    Science.gov (United States)

    Iwata, Jun-ichi; Tung, Lily; Urata, Mark; Hacia, Joseph G; Pelikan, Richard; Suzuki, Akiko; Ramenzoni, Liza; Chaudhry, Obaid; Parada, Carolina; Sanchez-Lara, Pedro A; Chai, Yang

    2012-01-20

    Cleft palate represents one of the most common congenital birth defects. Transforming growth factor β (TGFβ) signaling plays crucial functions in regulating craniofacial development, and loss of TGFβ receptor type II in cranial neural crest cells leads to craniofacial malformations, including cleft palate in mice (Tgfbr2(fl/fl);Wnt1-Cre mice). Here we have identified candidate target genes of TGFβ signaling during palatal formation. These target genes were selected based on combining results from gene expression profiles of embryonic day 14.5 palates from Tgfbr2(fl/fl);Wnt1-Cre mice and previously identified cleft palate phenotypes in genetically engineered mouse models. We found that fibroblast growth factor 9 (Fgf9) and transcription factor pituitary homeobox 2 (Pitx2) expressions are significantly down-regulated in the palate of Tgfbr2(fl/fl);Wnt1-Cre mice, and Fgf9 and Pitx2 loss of function mutations result in cleft palate in mice. Pitx2 expression is down-regulated by siRNA knockdown of Fgf9, suggesting that Fgf9 is upstream of Pitx2. We detected decreased expression of both cyclins D1 and D3 in the palates of Tgfbr2(fl/fl);Wnt1-Cre mice, consistent with the defect in cell proliferation. Significantly, exogenous FGF9 restores expression of cyclins D1 and D3 in a Pitx2-dependent manner and rescues the cell proliferation defect in the palatal mesenchyme of Tgfbr2(fl/fl);Wnt1-Cre mice. Our study indicates that a TGFβ-FGF9-PITX2 signaling cascade regulates cranial neural crest cell proliferation during palate formation.

  5. Create Your Plate

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    Full Text Available ... Health Care Professionals Law Enforcement Driver's License For Lawyers Food & Fitness Home Food MyFoodAdvisor Recipes Association Cookbook Recipes Planning Meals Diabetes Meal Plans Create Your Plate Gluten ...

  6. Create Your Plate

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    Full Text Available ... Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for ... Diabetes Meal Plans Create Your Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook with Heart- ...

  7. Create Your Plate

    Science.gov (United States)

    ... Your Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook with Heart-Healthy Foods Holiday Meal ... Healthy Diet Create Your Plate Meal Planning for Vegetarian Diets Gluten Free Diets Holiday Meal Planning Cook ...

  8. Create Your Plate

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    Full Text Available ... Your Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook with Heart-Healthy Foods Holiday Meal ... Healthy Diet Create Your Plate Meal Planning for Vegetarian Diets Gluten Free Diets Holiday Meal Planning Cook ...

  9. Create Your Plate

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    Full Text Available ... Pacific Islanders American Indian/Alaska Native Programs Older Adults Family Link Diabetes EXPO Upcoming Diabetes EXPOs EXPO ... Plate! Click on the plate sections below to add your food choices. Reset Plate Share Create Your ...

  10. Create Your Plate

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    Full Text Available ... of Diabetes Research & Practice Home We Are Research Leaders World's Largest Diabetes Meeting Recent Advances Type 1 ... Your Plate It's simple and effective for both managing diabetes and losing weight. Creating your plate lets ...

  11. Create Your Plate

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    Full Text Available ... Now - match-donate-now.html Match – Donate Now Make your year-end donation today and ... Tour Registration Is Open It starts with you. Sign up to ride in Tour de Cure and create ...

  12. Create Your Plate

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    Full Text Available ... Your Plate It's simple and effective for both managing diabetes and losing weight. Creating your plate lets you still choose the foods you want, but changes the portion sizes so you are getting larger ...

  13. Create Your Plate

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    Full Text Available ... this interactive tool. The healthy meal combinations are endless! Ready to try it at home? Just follow ... non-starchy vegetables and that your options are endless. Create Your Plate! Click on the plate sections ...

  14. Create Your Plate

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    Full Text Available ... and Pacific Islanders American Indian/Alaska Native Programs Older Adults Family Link Diabetes EXPO Upcoming Diabetes EXPOs ... Planning Meals Diabetes Meal Plans and a Healthy Diet Create Your Plate Meal Planning for Vegetarian Diets ...

  15. Create Your Plate

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    Full Text Available ... Plate! Click on the plate sections below to add your food choices. Reset Plate Share Create Your ... your protein. See this list of protein foods . Add a serving of fruit , a serving of dairy ...

  16. Create Your Plate

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    Full Text Available ... losing weight. Creating your plate lets you still choose the foods you want, but changes the portion ... dairy or both as your meal plan allows. Choose healthy fats in small amounts. For cooking, use ...

  17. Create Your Plate

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    Full Text Available ... Please Join Us in the Fight for a Cure Your tax-deductible gift today can fund critical ... you. Sign up to ride in Tour de Cure and create your team today! More from diabetes. ...

  18. Create Your Plate

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    Full Text Available ... that your options are endless. Create Your Plate! Click on the plate sections below to add your ... down the middle of the plate. Then on one side, cut it again so you will have ...

  19. Creating unreal audio

    OpenAIRE

    Rudsengen, Mathias Flaten

    2014-01-01

    Creating unreal audio” refers to the act of designing a sound effect that is intended to sound like a completely fictional object. This thesis is a practical venture into digital audio design. During the process of creating a sound effect anchored in a specific thematic framework, I will describe my work process and the challenges and problems faced, showing my personal work process and how modern digital sound effect creation can be undertaken. To provide context, I will also describe and re...

  20. Creating a learning culture.

    Science.gov (United States)

    Mathewson, Karyn

    2014-03-01

    This column describes the efforts of an agency to build a learning culture as part of changing their approach to service delivery, when adopting a focus on psychiatric rehabilitation and recovery. This example of one organization's challenges and successes in workforce development provides an alternative approach to the common single-session staff training that typically fails to change practice. This description draws from published material on communities of practice, technical consultation, and agency experience. Training alone is not enough to create change. An organizational commitment to ongoing quality improvement, along with available and accessible technical assistance for staff, creates an environment where change is anticipated, managed, and celebrated.

  1. Creating Web Pages Simplified

    CERN Document Server

    Wooldridge, Mike

    2011-01-01

    The easiest way to learn how to create a Web page for your family or organization Do you want to share photos and family lore with relatives far away? Have you been put in charge of communication for your neighborhood group or nonprofit organization? A Web page is the way to get the word out, and Creating Web Pages Simplified offers an easy, visual way to learn how to build one. Full-color illustrations and concise instructions take you through all phases of Web publishing, from laying out and formatting text to enlivening pages with graphics and animation. This easy-to-follow visual guide sho

  2. LIM homeobox protein 5 (Lhx5 is essential for mamillary body development

    Directory of Open Access Journals (Sweden)

    Amaya eMiquelajauregui

    2015-10-01

    Full Text Available The mamillary body (MM is a group of hypothalamic nuclei related to memory and spatial navigation that interconnects hippocampal, thalamic, and tegmental regions. Here we demonstrate that Lhx5, a LIM-HD domain transcription factor expressed early in the developing posterior hypothalamus, is required for the generation of the MM and its derived tracts. The MM markers Foxb1, Sim2 and Lhx1 are absent in Lhx5 knock-out mice from early embryonic stages, suggesting abnormal specification of this region. This was supported by the absence of Nkx2.1 and expansion of Shh in the prospective mamillary area. Interestingly, we also found an ectopic domain expressing Lhx2 and Lhx9 along the anterio-posterior hypothalamic axis. Our results suggest that Lhx5 controls early aspects of hypothalamic development by regulating gene expression and cellular specification in the prospective MM.

  3. Metformin Restrains Pancreatic Duodenal Homeobox-1 (PDX-1) Function by Inhibiting ERK Signaling in Pancreatic Ductal Adenocarcinoma.

    Science.gov (United States)

    Zhou, G; Yu, J; Wang, A; Liu, S-H; Sinnett-Smith, J; Wu, J; Sanchez, R; Nemunaitis, J; Ricordi, C; Rozengurt, E; Brunicardi, F C

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most potent and perilous diseases known, with a median survival rate of 3-5 months due to the combination of only advanced stage diagnosis and ineffective therapeutic options. Metformin (1,1-Dimethylbiguanide hydrochloride), the leading drug used for type 2 diabetes mellitus, emerges as a potential therapy for PDAC and other human cancers. Metformin exerts its anticancer action via a variety of adenosine monophosphate (AMP)-activated protein kinase (AMPK)- dependent and/or AMPK-independent mechanisms. We present data here showing that metformin downregulated pancreatic transcription factor pancreatic duodenal homeobox-1 (PDX-1), suggesting a potential novel mechanism by which metformin exerts its anticancer action. Metformin inhibited PDX-1 expression at both protein and mRNA levels and PDX-1 transactivity as well in PDAC cells. Extracellular signal-regulated kinase (ERK) was identified as a PDX-1-interacting protein by antibody array screening in GFP-PDX-1 stable HEK293 cells. Co-transfection of ERK1 with PDX-1 resulted in an enhanced PDX-1 expression in HEK293 cells in a dose-dependent manner. Immunoprecipitation/Western blotting analysis confirmed the ERK-PDX-1 interaction in PANC-1 cells stimulated by epidermal growth factor (EGF). EGF induced an enhanced PDX-1 expression in PANC-1 cells and this stimulation was inhibited by MEK inhibitor PD0325901. Metformin inhibited EGF-stimulated PDX-1 expression with an accompanied inhibition of ERK kinase activation in PANC- 1 cells. Taken together, our studies show that PDX-1 is a potential novel target for metformin in PDAC cells and that metformin may exert its anticancer action in PDAC by down-regulating PDX-1 via a mechanism involving inhibition of ERK signaling.

  4. In vitro pancreas duodenal homeobox-1 enhances the differentiation of pancreatic ductal epithelial cells into insulin-producing cells

    Science.gov (United States)

    Liu, Tao; Wang, Chun-You; Yu, Feng; Gou, Shan-Miao; Wu, He-Shui; Xiong, Jiong-Xin; Zhou, Feng

    2007-01-01

    AIM: To observe whether pancreatic and duodenal homeobox factor-1 enhances the differentiation of pancreatic ductal epithelial cells into insulin-producing cells in vitro. METHODS: Rat pancreatic tissue was submitted to digestion by collagenase, ductal epithelial cells were separated by density gradient centrifugation and then cultured in RPMI1640 medium with 10% fetal bovine serum. After 3-5 passages, the cells were incubated in a six-well plate for 24 h before transfection of recombination plasmid XlHbox8VP16. Lightcycler quantitative real-time RT-PCR was used to detect the expression of PDX-1 and insulin mRNA in pancreatic epithelial cells. The expression of PDX-1 and insulin protein was analyzed by Western blotting. Insulin secretion was detected by radioimmunoassay. Insulin-producing cells were detected by dithizone-staining. RESULTS: XlHbox8 mRNA was expressed in pancreatic ductal epithelial cells. PDX-1 and insulin mRNA as well as PDX-1 and insulin protein were significantly increased in the transfected group. The production and insulin secretion of insulin-producing cells differentiated from pancreatic ductal epithelial cells were higher than those of the untransfected cells in vitro with a significant difference (1.32 ± 0.43 vs 3.48 ± 0.81, P < 0.01 at 5.6 mmol/L; 4.86 ± 1.15 vs 10.25 ± 1.32, P < 0.01 at 16.7 mmol/L). CONCLUSION: PDX-1 can differentiate rat pancreatic ductal epithelial cells into insulin-producing cells in vitro. In vitro PDX-1 transfection is a valuable strategy for increasing the source of insulin-producing cells. PMID:17876894

  5. Metformin Restrains Pancreatic Duodenal Homeobox-1 (PDX-1) Function by Inhibiting ERK Signaling in Pancreatic Ductal Adenocarcinoma

    Science.gov (United States)

    Zhou, G.; Yu, J.; Wang, A.; Liu, S.-H.; Sinnett-Smith, J.; Wu, J.; Sanchez, R.; Nemunaitis, J.; Ricordi, C.; Rozengurt, E.; Brunicardi, F.C.

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most potent and perilous diseases known, with a median survival rate of 3-5 months due to the combination of only advanced stage diagnosis and ineffective therapeutic options. Metformin (1,1-Dimethylbiguanide hydrochloride), the leading drug used for type 2 diabetes mellitus, emerges as a potential therapy for PDAC and other human cancers. Metformin exerts its anticancer action via a variety of adenosine monophosphate (AMP)-activated protein kinase (AMPK)- dependent and/or AMPK-independent mechanisms. We present data here showing that metformin down- regulated pancreatic transcription factor pancreatic duodenal homeobox-1 (PDX-1), suggesting a potential novel mechanism by which metformin exerts its anticancer action. Metformin inhibited PDX-1 expression at both protein and mRNA levels and PDX-1 transactivity as well in PDAC cells. Extracellular signal-regulated kinase (ERK) was identified as a PDX-1-interacting protein by antibody array screening in GFP-PDX-1 stable HEK293 cells. Co-transfection of ERK1 with PDX-1 resulted in an enhanced PDX-1 expression in HEK293 cells in a dose-dependent manner. Immunoprecipitation/Western blotting analysis confirmed the ERK-PDX-1 interaction in PANC-1 cells stimulated by epidermal growth factor (EGF). EGF induced an enhanced PDX-1 expression in PANC-1 cells and this stimulation was inhibited by MEK inhibitor PD0325901. Metformin inhibited EGF-stimulated PDX-1 expression with an accompanied inhibition of ERK kinase activation in PANC- 1 cells. Taken together, our studies show that PDX-1 is a potential novel target for metformin in PDAC cells and that metformin may exert its anticancer action in PDAC by down-regulating PDX-1 via a mechanism involving inhibition of ERK signaling. PMID:26695692

  6. Create Your Plate

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    Full Text Available ... Plate It's simple and effective for both managing diabetes and losing weight. Creating your plate lets you still choose the ... Help Enroll in the Living WIth Type 2 Diabetes Program Food & Fitness Food Recipes Planning Meals What Can I Eat Weight Loss Fitness In My Community Calendar of Events ...

  7. Create Your Plate

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    Full Text Available ... For Lawyers Food & Fitness Home Food MyFoodAdvisor Recipes Association Cookbook Recipes Planning Meals Diabetes Meal Plans Create ... Become a Volunteer American Diabetes Month® American Diabetes Association Alert Day® Become a Member Advocacy Home Take ...

  8. Creating an Interactive PDF

    Science.gov (United States)

    Branzburg, Jeffrey

    2008-01-01

    There are many ways to begin a PDF document using Adobe Acrobat. The easiest and most popular way is to create the document in another application (such as Microsoft Word) and then use the Adobe Acrobat software to convert it to a PDF. In this article, the author describes how he used Acrobat's many tools in his project--an interactive…

  9. Creating resilient SMEs

    DEFF Research Database (Denmark)

    Dahlberg, Rasmus; Guay, Fanny

    2015-01-01

    According to the EU, during the past five years, small and medium enterprises (SMEs) have created 85% of new jobs and two-thirds of private sector employment in the region. SMEs are considered the backbone of the economy in Europe and represent more than 95% of enterprises in USA and Australia...

  10. Create Your Plate

    Medline Plus

    Full Text Available ... meal-planning, In this section Food Planning Meals Diabetes Meal Plans and a Healthy Diet Create Your Plate Meal Planning for Vegetarian Diets Gluten Free Diets Holiday Meal Planning Cook with Heart-Healthy Foods ... your year-end donation today and help fight diabetes. Donate Today We Can Help - we-can-help. ...

  11. Create Your Plate

    Medline Plus

    Full Text Available ... 1 Type 2 About Us Online Community Meal Planning Sign In Search: Search More Sites Search ≡ Are ... Fitness Home Food MyFoodAdvisor Recipes Association Cookbook Recipes Planning Meals Diabetes Meal Plans Create Your Plate Gluten ...

  12. Creating snags with explosives.

    Science.gov (United States)

    Evelyn L. Bull; Arthur D. Partridge; Wayne G. Williams

    1981-01-01

    The tops of ponderosa pine (Pinus ponderosa) trees were blown off with dynamite to create nest sites for cavity-nesting wildlife. The procedure included drilling a hole almost through the trunk, inserting the dynamite, and setting the charge with primacord and fuse. Trees were simultaneously innoculated with a decay organism. The average cost was $...

  13. Creating Special Events

    Science.gov (United States)

    deLisle, Lee

    2009-01-01

    "Creating Special Events" is organized as a systematic approach to festivals and events for students who seek a career in event management. This book looks at the evolution and history of festivals and events and proceeds to the nuts and bolts of event management. The book presents event management as the means of planning, organizing, directing,…

  14. Creating White Australia

    DEFF Research Database (Denmark)

    McLisky, Claire Louise; Carey, Jane

    Vedtagelsen af White Australien som regeringens politik i 1901 viser, at hvidheden var afgørende for den måde, hvorpå den nye nation i Australien blev konstitueret. Og alligevel har historikere i vid udstrækning overset hvidhed i deres studier af Australiens race fortid. 'Creating White Australia...

  15. Create Your Plate

    Medline Plus

    Full Text Available ... Your Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook with Heart-Healthy Foods Holiday Meal Planning What Can I Eat? ... Healthy Diet Create Your Plate Meal Planning for Vegetarian Diets Gluten Free Diets Holiday ... Foods donate en -- Limited Time MATCH Offer - limited- ...

  16. Creating a Virtual Gymnasium

    Science.gov (United States)

    Fiorentino, Leah H.; Castelli, Darla

    2005-01-01

    Physical educators struggle with the challenges of assessing student performance, providing feedback about motor skills, and creating opportunities for all students to engage in game-play on a daily basis. The integration of technology in the gymnasium can address some of these challenges by improving teacher efficiency and increasing student…

  17. Creating Pupils' Internet Magazine

    Science.gov (United States)

    Bognar, Branko; Šimic, Vesna

    2014-01-01

    This article presents an action research, which aimed to improve pupils' literary creativity and enable them to use computers connected to the internet. The study was conducted in a small district village school in Croatia. Creating a pupils' internet magazine appeared to be an excellent way for achieving the educational aims of almost all…

  18. The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons

    Directory of Open Access Journals (Sweden)

    Brand Andrea H

    2006-11-01

    Full Text Available Abstract Background While developmental processes such as axon pathfinding and synapse formation have been characterized in detail, comparatively less is known of the intrinsic developmental mechanisms that regulate transcription of ion channel genes in embryonic neurons. Early decisions, including motoneuron axon targeting, are orchestrated by a cohort of transcription factors that act together in a combinatorial manner. These transcription factors include Even-skipped (Eve, islet and Lim3. The perdurance of these factors in late embryonic neurons is, however, indicative that they might also regulate additional aspects of neuron development, including the acquisition of electrical properties. Results To test the hypothesis that a combinatorial code transcription factor is also able to influence the acquisition of electrical properties in embryonic neurons we utilized the molecular genetics of Drosophila to manipulate the expression of Eve in identified motoneurons. We show that increasing expression of this transcription factor, in two Eve-positive motoneurons (aCC and RP2, is indeed sufficient to affect the electrical properties of these neurons in early first instar larvae. Specifically, we observed a decrease in both the fast K+ conductance (IKfast and amplitude of quantal cholinergic synaptic input. We used charybdotoxin to pharmacologically separate the individual components of IKfast to show that increased Eve specifically down regulates the Slowpoke (a BK Ca2+-gated potassium channel, but not Shal, component of this current. Identification of target genes for Eve, using DNA adenine methyltransferase identification, revealed strong binding sites in slowpoke and nAcRα-96Aa (a nicotinic acetylcholine receptor subunit. Verification using real-time PCR shows that pan-neuronal expression of eve is sufficient to repress transcripts for both slo and nAcRα-96Aa. Conclusion Taken together, our findings demonstrate, for the first time, that Eve

  19. Creating bulk nanocrystalline metal.

    Energy Technology Data Exchange (ETDEWEB)

    Fredenburg, D. Anthony (Georgia Institute of Technology, Atlanta, GA); Saldana, Christopher J. (Purdue University, West Lafayette, IN); Gill, David D.; Hall, Aaron Christopher; Roemer, Timothy John (Ktech Corporation, Albuquerque, NM); Vogler, Tracy John; Yang, Pin

    2008-10-01

    Nanocrystalline and nanostructured materials offer unique microstructure-dependent properties that are superior to coarse-grained materials. These materials have been shown to have very high hardness, strength, and wear resistance. However, most current methods of producing nanostructured materials in weapons-relevant materials create powdered metal that must be consolidated into bulk form to be useful. Conventional consolidation methods are not appropriate due to the need to maintain the nanocrystalline structure. This research investigated new ways of creating nanocrystalline material, new methods of consolidating nanocrystalline material, and an analysis of these different methods of creation and consolidation to evaluate their applicability to mesoscale weapons applications where part features are often under 100 {micro}m wide and the material's microstructure must be very small to give homogeneous properties across the feature.

  20. Creating organizational cultures

    DEFF Research Database (Denmark)

    Mouton, Nicolaas T.O.; Just, Sine Nørholm; Gabrielsen, Jonas

    2012-01-01

    Purpose – The purpose of this paper is to re-conceptualize the relations between rhetorical strategies and material practices in the processes whereby leaders create or change organizational cultures. Design/methodology/approach – The authors compare and contrast two broad perspectives on cultural...... insights. The authors propose an integrated perspective in which material practices and rhetorical strategies are seen as two analytical sides of the same ontological coin. This enables a fuller and more detailed explanation of how organizational cultures are created or changed. A brief illustration...... is provided of the merits of this approach by revisiting the case of Enron. Originality/value – The paper constitutes an initial exploration of how social scientific and rhetorical perspectives on organizational change may be brought closer together. It may provide the first step towards the development...

  1. Can Computers Create Art?

    OpenAIRE

    Hertzmann, Aaron

    2018-01-01

    This paper discusses whether computers, using Artifical Intelligence (AI), could create art. The first part concerns AI-based tools for assisting with art making. The history of technologies that automated aspects of art is covered, including photography and animation. In each case, we see initial fears and denial of the technology, followed by a blossoming of new creative and professional opportunities for artists. The hype and reality of Artificial Intelligence (AI) tools for art making is ...

  2. Creating product line architectures

    OpenAIRE

    Bayer, J.; Flege, O.; Gacek, C.

    2000-01-01

    The creation and validation of product line software architectures are inherently more complex than those of software architectures for single systems. This paper compares a process for creating and evaluating a traditional, one-of-a- kind software architecture with one for a reference software architecture. The comparison is done in the context of PuLSE-DSSA, a customizable process that integrates both product line architecture creation and evaluation.

  3. Creating flat design websites

    CERN Document Server

    Pratas, Antonio

    2014-01-01

    This book contains practical, step-by-step tutorials along with plenty of explanation about designing your flat website. Each section is introduced sequentially, building up your web design skills and completing your website.Creating Flat Design Websites is ideal for you if you are starting on your web development journey, but this book will also benefit seasoned developers wanting to start developing in flat.

  4. Creating Geoscience Leaders

    Science.gov (United States)

    Buskop, J.; Buskop, W.

    2013-12-01

    The United Nations Educational, Scientific, and Cultural Organization recognizes 21 World Heritage in the United States, ten of which have astounding geological features: Wrangell St. Elias National Park, Olympic National Park, Mesa Verde National Park, Chaco Canyon, Glacier National Park, Carlsbad National Park, Mammoth Cave, Great Smokey Mountains National Park, Hawaii Volcanoes National Park, and Everglades National Park. Created by a student frustrated with fellow students addicted to smart phones with an extreme lack of interest in the geosciences, one student visited each World Heritage site in the United States and created one e-book chapter per park. Each chapter was created with original photographs, and a geological discovery hunt to encourage teen involvement in preserving remarkable geological sites. Each chapter describes at least one way young adults can get involved with the geosciences, such a cave geology, glaciology, hydrology, and volcanology. The e-book describes one park per chapter, each chapter providing a geological discovery hunt, information on how to get involved with conservation of the parks, geological maps of the parks, parallels between archaeological and geological sites, and how to talk to a ranger. The young author is approaching UNESCO to publish the work as a free e-book to encourage involvement in UNESCO sites and to prove that the geosciences are fun.

  5. PHOX2B-mediated regulation of ALK expression: in vitro identification of a functional relationship between two genes involved in neuroblastoma

    OpenAIRE

    Tiziana Bachetti; Daniela Di Paolo; Simona Di Lascio; Valentina Mirisola; Chiara Brignole; Marta Bellotti; Irene Caffa; Chiara Ferraris; Michele Fiore; Diego Fornasari; Roberto Chiarle; Silvia Borghini; Ulrich Pfeffer; Mirco Ponzoni; Isabella Ceccherini

    2010-01-01

    BACKGROUND: Neuroblastoma (NB) is a severe pediatric tumor originating from neural crest derivatives and accounting for 15% of childhood cancer mortality. The heterogeneous and complex genetic etiology has been confirmed with the identification of mutations in two genes, encoding for the receptor tyrosine kinase Anaplastic Lymphoma Kinase (ALK) and the transcription factor Paired-like Homeobox 2B (PHOX2B), in a limited proportion of NB patients. Interestingly, these two genes are overexpresse...

  6. Antagonistic Roles for KNOX1 and KNOX2 Genes in Patterning the Land Plant Body Plan Following an Ancient Gene Duplication

    Science.gov (United States)

    Furumizu, Chihiro; Alvarez, John Paul; Sakakibara, Keiko; Bowman, John L.

    2015-01-01

    Neofunctionalization following gene duplication is thought to be one of the key drivers in generating evolutionary novelty. A gene duplication in a common ancestor of land plants produced two classes of KNOTTED-like TALE homeobox genes, class I (KNOX1) and class II (KNOX2). KNOX1 genes are linked to tissue proliferation and maintenance of meristematic potentials of flowering plant and moss sporophytes, and modulation of KNOX1 activity is implicated in contributing to leaf shape diversity of flowering plants. While KNOX2 function has been shown to repress the gametophytic (haploid) developmental program during moss sporophyte (diploid) development, little is known about KNOX2 function in flowering plants, hindering syntheses regarding the relationship between two classes of KNOX genes in the context of land plant evolution. Arabidopsis plants harboring loss-of-function KNOX2 alleles exhibit impaired differentiation of all aerial organs and have highly complex leaves, phenocopying gain-of-function KNOX1 alleles. Conversely, gain-of-function KNOX2 alleles in conjunction with a presumptive heterodimeric BELL TALE homeobox partner suppressed SAM activity in Arabidopsis and reduced leaf complexity in the Arabidopsis relative Cardamine hirsuta, reminiscent of loss-of-function KNOX1 alleles. Little evidence was found indicative of epistasis or mutual repression between KNOX1 and KNOX2 genes. KNOX proteins heterodimerize with BELL TALE homeobox proteins to form functional complexes, and contrary to earlier reports based on in vitro and heterologous expression, we find high selectivity between KNOX and BELL partners in vivo. Thus, KNOX2 genes confer opposing activities rather than redundant roles with KNOX1 genes, and together they act to direct the development of all above-ground organs of the Arabidopsis sporophyte. We infer that following the KNOX1/KNOX2 gene duplication in an ancestor of land plants, neofunctionalization led to evolution of antagonistic biochemical

  7. Creating sustainable performance.

    Science.gov (United States)

    Spreitzer, Gretchen; Porath, Christine

    2012-01-01

    What makes for sustainable individual and organizational performance? Employees who are thriving-not just satisfied and productive but also engaged in creating the future. The authors found that people who fit this description demonstrated 16% better overall performance, 125% less burnout, 32% more commitment to the organization, and 46% more job satisfaction than their peers. Thriving has two components: vitality, or the sense of being alive and excited, and learning, or the growth that comes from gaining knowledge and skills. Some people naturally build vitality and learning into their jobs, but most employees are influenced by their environment. Four mechanisms, none of which requires heroic effort or major resources, create the conditions for thriving: providing decision-making discretion, sharing information about the organization and its strategy, minimizing incivility, and offering performance feedback. Organizations such as Alaska Airlines, Zingerman's, Quicken Loans, and Caiman Consulting have found that helping people grow and remain energized at work is valiant on its own merits-but it can also boost performance in a sustainable way.

  8. Tourist-created Content

    DEFF Research Database (Denmark)

    Munar, Ana Maria

    2011-01-01

    study of social media sites and destination brands, relying on qualitative research methods, content analysis and field research. Findings – Tourists are largely contributing to destination image formation, while avoiding the use of the formal elements of the brands. The most popular strategies used...... by destination management organizations exhibit some crucial weaknesses. However, a strategy based on analytics brings new opportunities for destination branding. Originality/value – The study provides an innovative analysis of tourist-created content and its impact on destination branding and presents......Purpose – The purpose of this paper is to analyze the relationship between tourists' user-generated content on the web and destination branding, as well as to discuss the online strategies used by destination management organizations. Design/methodology/approach – The research adopts an exploratory...

  9. Creating nanostars with buckyballs

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Young K., E-mail: ykbae@ykbcorp.com

    2013-12-17

    We report creating superradiant quantum nanoplasmas (nanostars) by impacting buckyballs at hypervelocities (v>100 km/s) in an innovative tabletop apparatus. The nanostars are estimated to have ∼10 TPa transient pressures and convert ∼35% of impact energy into soft-X-ray energy. The ultrahigh-efficiency conversion is proposed to result from Dicke Superradiance of Metastable Innershell Molecular State, originally discovered by the author and his colleagues in 1994. The usage of buckyballs and successful orders-of-magnitude scaling down of the apparatus size and complexity establish an innovative tabletop method for generating, studying, and utilizing matter in planetary or stellar interiors and open doors to numerous unprecedented applications.

  10. Creating Griffith Observatory

    Science.gov (United States)

    Cook, Anthony

    2013-01-01

    Griffith Observatory has been the iconic symbol of the sky for southern California since it began its public mission on May 15, 1935. While the Observatory is widely known as being the gift of Col. Griffith J. Griffith (1850-1919), the story of how Griffith’s gift became reality involves many of the people better known for other contributions that made Los Angeles area an important center of astrophysics in the 20th century. Griffith began drawing up his plans for an observatory and science museum for the people of Los Angeles after looking at Saturn through the newly completed 60-inch reflector on Mt. Wilson. He realized the social impact that viewing the heavens could have if made freely available, and discussing the idea of a public observatory with Mt. Wilson Observatory’s founder, George Ellery Hale, and Director, Walter Adams. This resulted, in 1916, in a will specifying many of the features of Griffith Observatory, and establishing a committee managed trust fund to build it. Astronomy popularizer Mars Baumgardt convinced the committee at the Zeiss Planetarium projector would be appropriate for Griffith’s project after the planetarium was introduced in Germany in 1923. In 1930, the trust committee judged funds to be sufficient to start work on creating Griffith Observatory, and letters from the Committee requesting help in realizing the project were sent to Hale, Adams, Robert Millikan, and other area experts then engaged in creating the 200-inch telescope eventually destined for Palomar Mountain. A Scientific Advisory Committee, headed by Millikan, recommended that Caltech Physicist Edward Kurth be put in charge of building and exhibit design. Kurth, in turn, sought help from artist Russell Porter. The architecture firm of John C. Austin and Fredrick Ashley was selected to design the project, and they adopted the designs of Porter and Kurth. Philip Fox of the Adler Planetarium was enlisted to manage the completion of the Observatory and become its

  11. Creating the living brand.

    Science.gov (United States)

    Bendapudi, Neeli; Bendapudi, Venkat

    2005-05-01

    It's easy to conclude from the literature and the lore that top-notch customer service is the province of a few luxury companies and that any retailer outside that rarefied atmosphere is condemned to offer mediocre service at best. But even companies that position themselves for the mass market can provide outstanding customer-employee interactions and profit from them, if they train employees to reflect the brand's core values. The authors studied the convenience store industry in depth and focused on two that have developed a devoted following: QuikTrip (QT) and Wawa. Turnover rates at QT and Wawa are 14% and 22% respectively, much lower than the typical rate in retail. The authors found six principles that both firms embrace to create a strong culture of customer service. Know what you're looking for: A focus on candidates' intrinsic traits allows the companies to hire people who will naturally bring the right qualities to the job. Make the most of talent: In mass-market retail, talent is generally viewed as a commodity, but that outlook becomes a self-fulfilling prophesy. Create pride in the brand: Service quality depends directly on employees' attachment to the brand. Build community: Wawa and QT have made concerted efforts to build customer loyalty through a sense of community. Share the business context: Employees need a clear understanding of how their company operates and how it defines success. Satisfy the soul: To win an employee's passionate engagement, a company must meet his or her needs for security, esteem, and justice.

  12. Oryza sativa Homeobox 6

    African Journals Online (AJOL)

    Jane

    2011-03-07

    Mar 7, 2011 ... 1Genomics Division, National Academy of Agricultural Science (NAAS), Rural Development Administration (RDA), ... 2Policy Development Office, Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and .... transcription-PCR (RT-PCR), 2 g of total RNA was treated with.

  13. MSX1 gene in the etiology orofacial deformities

    Directory of Open Access Journals (Sweden)

    Anna Paradowska-Stolarz

    2015-12-01

    Full Text Available The muscle segment homeobox (MSX1 gene plays a crucial role in epithelial-mesenchymal tissue interactions in craniofacial development. It plays a regulative role in cellular proliferation, differentiation and cell death. The human MSX1 domain was also found in cow (Bt 302906, mouse (Mm 123311, rat (Rn13592001, chicken (Gg 170873 and clawed toad (XI 547690. Cleft lip and palate is the most common anomaly of the facial part of the skull. The etiology is not fully understood, but it is believed that the key role is played by the genetic factor activated by environmental factors. Among the candidate genes whose mutations could lead to formation of the cleft, the MSX1 homeobox gene is mentioned. Mutations in the gene MSX1 can lead to isolated cleft deformities, but also cause other dismorphic changes. Among the most frequently mentioned is loss of permanent tooth buds (mostly of less than 4 teeth – hypodontia, including second premolars. Mutations of MSX1 are observed in the Pierre- Robin sequence, which may be one of the features of congenital defects or is observed as an isolated defect. Mutation of the gene can lead to the occurrence of a rare congenital defect Wiktop (dental-nail syndrome. Deletion of a fragment MSX1 (4p16.3 located in the WHS critical region, may be a cause of some symptoms of Wolf-Hirschhorn syndrome.

  14. Creating alternatives in science

    Science.gov (United States)

    2009-01-01

    Traditional scientist training at the PhD level does not prepare students to be competitive in biotechnology or other non-academic science careers. Some universities have developed biotechnology-relevant doctoral programmes, but most have not. Forming a life science career club makes a statement to university administrators that it is time to rework the curriculum to include biotechnology-relevant training. A career club can supplement traditional PhD training by introducing students to available career choices, help them develop a personal network and teach the business skills that they will need to be competitive in science outside of academia. This paper is an instructional guide designed to help students create a science career club at their own university. These suggestions are based on the experience gained in establishing such a club for the Graduate School at the University of Colorado Denver. We describe the activities that can be offered, the job descriptions for the offices required and potential challenges. With determination, a creative spirit, and the guidance of this paper, students should be able to greatly increase awareness of science career options, and begin building the skills necessary to become competitive in non-academic science. PMID:20161069

  15. Creating an open mind.

    Science.gov (United States)

    Monaghan, Duncan

    2011-07-01

    Duncan Monaghan is 33 years old and in his second year of an Arts degree in Creative Writing. He is a published poet and is currently producing a music CD. Duncan has a history of bipolar disorder which was diagnosed when he was nineteen: "It worried me at first a lot. It played on my mind constantly. I felt different from everybody else--I did not understand what was happening to me." Drawing on his life experiences, Duncan has been enhancing his recovery through creativity--in poetry, lyrics, music and story. "Life for me was a constant battle of relying on medication and appointments with my case manager...until I realized I could combine my recovery with my passions as a tool to use as an outlet to many of the "mind traps" I so often found hindering my own recovery." Duncan is Aboriginal and has experience of the mental health systems in most states and territories and now lives in Brisbane. This is a shortened version of his presentation at Creating Futures 2010.

  16. The SUMOylation of zinc-fingers and homeoboxes 1 (ZHX1) by Ubc9 regulates its stability and transcriptional repression activity.

    Science.gov (United States)

    Chen, Shuliang; Yu, Xiao; Lei, Quan; Ma, Lixin; Guo, Deyin

    2013-10-01

    Zinc-fingers and homeoboxes protein 1 (ZHX1) belongs to the ZF (zinc-fingers) class of homeodomain transcription factors, and its function remains largely unknown. ZHX1 has been previously found to interact with the activation domain of the nuclear factor Y subunit A (NFYA) and to have a transcriptional repression activity. Here, we report that the SUMO-E2 conjugating enzyme Ubc9 was identified to interact with ZHX1 by an interaction screen using a yeast two-hybrid system. This interaction was confirmed by co-immunoprecipitation and co-localization assays. Further study showed that ZHX1 is SUMOylated by Ubc9 with SUMO1 at the sites K159, K454, and K626. Furthermore, we demonstrated that the SUMOylation of ZHX1 regulated the stability, ubiquitination and transcriptional activity of ZHX1. Copyright © 2013 Wiley Periodicals, Inc.

  17. Analysis of RNA splicing defects in PITX2 mutants supports a gene dosage model of Axenfeld-Rieger syndrome

    Directory of Open Access Journals (Sweden)

    Semina Elena V

    2006-07-01

    Full Text Available Abstract Background Axenfeld-Rieger syndrome (ARS is associated with mutations in the PITX2 gene that encodes a homeobox transcription factor. Several intronic PITX2 mutations have been reported in Axenfeld-Rieger patients but their effects on gene expression have not been tested. Methods We present two new families with recurrent PITX2 intronic mutations and use PITX2c minigenes and transfected cells to address the hypothesis that intronic mutations effect RNA splicing. Three PITX2 mutations have been analyzed: a G>T mutation within the AG 3' splice site (ss junction associated with exon 4 (IVS4-1G>T, a G>C mutation at position +5 of the 5' (ss of exon 4 (IVS4+5G>C, and a previously reported A>G substitution at position -11 of 3'ss of exon 5 (IVS5-11A>G. Results Mutation IVS4+5G>C showed 71% retention of the intron between exons 4 and 5, and poorly expressed protein. Wild-type protein levels were proportionally expressed from correctly spliced mRNA. The G>T mutation within the exon 4 AG 3'ss junction shifted splicing exclusively to a new AG and resulted in a severely truncated, poorly expressed protein. Finally, the A>G substitution at position -11 of the 3'ss of exon 5 shifted splicing exclusively to a newly created upstream AG and resulted in generation of a protein with a truncated homeodomain. Conclusion This is the first direct evidence to support aberrant RNA splicing as the mechanism underlying the disorder in some patients and suggests that the magnitude of the splicing defect may contribute to the variability of ARS phenotypes, in support of a gene dosage model of Axenfeld-Rieger syndrome.

  18. The C terminus of the synovial sarcoma-associated SSX proteins interacts with the LIM homeobox protein LHX4.

    NARCIS (Netherlands)

    Bruijn, D.R.H. de; Dijk, A.H.A.; Willemse, M.P.; Geurts van Kessel, A.H.M.

    2008-01-01

    As a result of the synovial sarcoma-associated t(X;18) translocation, the SS18 gene on chromosome 18 is fused to either one of the three closely related SSX genes on the X chromosome. The SS18 protein is thought to act as a transcriptional co-activator, whereas the SSX proteins are thought to act as

  19. Evidence for intron length conservation in a set of mammalian genes associated with embryonic development

    LENUS (Irish Health Repository)

    2011-10-05

    Abstract Background We carried out an analysis of intron length conservation across a diverse group of nineteen mammalian species. Motivated by recent research suggesting a role for time delays associated with intron transcription in gene expression oscillations required for early embryonic patterning, we searched for examples of genes that showed the most extreme conservation of total intron content in mammals. Results Gene sets annotated as being involved in pattern specification in the early embryo or containing the homeobox DNA-binding domain, were significantly enriched among genes with highly conserved intron content. We used ancestral sequences reconstructed with probabilistic models that account for insertion and deletion mutations to distinguish insertion and deletion events on lineages leading to human and mouse from their last common ancestor. Using a randomization procedure, we show that genes containing the homeobox domain show less change in intron content than expected, given the number of insertion and deletion events within their introns. Conclusions Our results suggest selection for gene expression precision or the existence of additional development-associated genes for which transcriptional delay is functionally significant.

  20. SHAREPOINT SITE CREATING AND SETTING

    Directory of Open Access Journals (Sweden)

    Oleksandr V. Tebenko

    2011-02-01

    Full Text Available Tools for sites building that offer users the ability to work together, an actual theme in information society and modern Web technologies. This article considers the SharePoint system, which enables to create sites of any complexity, including large portals with a complex structure of documents. Purpose of this article is to consider the main points of site creating and its setting with tools of SharePoint system, namely: a site template creating and configuring, web application environment to create and configure Web applications, change of existing and creation of new theme site, a web part setting.

  1. Creating

    DEFF Research Database (Denmark)

    Andersen, Kristina Vaarst; Lorenzen, Mark; Laursen, Stine

    2012-01-01

    This unique book reveals the procedural aspects of knowledge-based urban planning, development and assessment. Concentrating on major knowledge city building processes, and providing state-of-the-art experiences and perspectives, this important compendium explores innovative models, approaches an...

  2. Creating Our Own Online Community

    Directory of Open Access Journals (Sweden)

    Mihaela TUTUNEA

    2006-01-01

    Full Text Available Creating our own online community is easy to do, by welcoming those who have an active presence online; first of all, we must have a well developed strategy of our own "empire", starting from the idea of creating the final benefit for our cyber-consumers.

  3. Creating Student-Friendly Tests

    Science.gov (United States)

    Salend, Spencer J.

    2011-01-01

    Creating a fair, reliable, teacher-made test is a challenge. Every year poorly designed tests fail to accurately measure many students' learning--and negatively affect their academic futures. Salend, a well-known writer on assessment for at-risk students who consults with schools on assessment procedures, offers guidelines for creating tests that…

  4. Synergizing genomic analysis with biological knowledge to identify and validate novel genes in pancreatic development.

    Science.gov (United States)

    Sarkar, Suparna A; Lee, Catherine E; Tipney, Hannah; Karimpour-Fard, Anis; Dinella, Jason D; Juhl, Kirstine; Walters, Jay A; Hutton, John C; Hunter, Lawrence E

    2012-08-01

    This study investigated the utility of advanced computational techniques to large-scale genome-based data to identify novel genes that govern murine pancreatic development. An expression data set for mouse pancreatic development was complemented with high-throughput data analyzer to identify and prioritize novel genes. Quantitative real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry were used to validate selected genes. Four new genes whose roles in the development of murine pancreas have not previously been established were identified: cystathionine β-synthase (Cbs), Meis homeobox 1, growth factor independent 1, and aldehyde dehydrogenase 18 family, member A1. Their temporal expression during development was documented. Cbs was localized in the cytoplasm of the tip cells of the epithelial chords of the undifferentiated progenitor cells at E12.5 and was coexpressed with the pancreatic and duodenal homeobox 1 and pancreas-specific transcription factor, 1a-positive cells. In the adult pancreas, Cbs was localized primarily within the acinar compartment. In silico analysis of high-throughput microarray data in combination with background knowledge about genes provides an additional reliable method of identifying novel genes. To our knowledge, the expression and localization of Cbs have not been previously documented during mouse pancreatic development.

  5. GenBank blastx search result: AK287639 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287639 J065078H11 AF287967.1 AF287967 Homo sapiens homeobox B7 (HOXB7) gene, partial cds; and home...obox B6 (HOXB6), homeobox B5 (HOXB5), homeobox B4 (HOXB4), and homeobox B3 (HOXB3) genes, complete cds. PRI 0.0 0 ...

  6. The deep intronic c.903+469T>C mutation in the MTRR gene creates an SF2/ASF binding exonic splicing enhancer, which leads to pseudoexon activation and causes the cblE type of homocystinuria.

    Science.gov (United States)

    Homolova, Katerina; Zavadakova, Petra; Doktor, Thomas Koed; Schroeder, Lisbeth Dahl; Kozich, Viktor; Andresen, Brage S

    2010-04-01

    Deep intronic mutations are often ignored as possible causes of human diseases. A deep intronic mutation in the MTRR gene, c.903+469T>C, is the most frequent mutation causing the cblE type of homocystinuria. It is well known to be associated with pre-mRNA mis-splicing, resulting in pseudoexon inclusion; however, the pathological mechanism remains unknown. We used minigenes to demonstrate that this mutation is the direct cause of MTRR pseudoexon inclusion, and that the pseudoexon is normally not recognized due to a suboptimal 5' splice site. Within the pseudoexon we identified an exonic splicing enhancer (ESE), which is activated by the mutation. Cotransfection and siRNA experiments showed that pseudoexon inclusion depends on the cellular amounts of SF2/ASF and in vitro RNA-binding assays showed dramatically increased SF2/ASF binding to the mutant MTRR ESE. The mutant MTRR ESE sequence is identical to an ESE of the alternatively spliced MST1R proto-oncogene, which suggests that this ESE could be frequently involved in splicing regulation. Our study conclusively demonstrates that an intronic single nucleotide change is sufficient to cause pseudoexon activation via creation of a functional ESE, which binds a specific splicing factor. We suggest that this mechanism may cause genetic disease much more frequently than previously reported. (c) 2010 Wiley-Liss, Inc.

  7. Industrial Engineering: creating a network!

    OpenAIRE

    Prado-Prado, José Carlos

    2016-01-01

    [EN] This paper presents a brief history of the Industrial Engineering Conference (CIO), and specially reinforces the role of the CIOs as a forum for building a network and creating log-term relationships Prado-Prado, JC. (2016). Industrial Engineering: creating a network!. International Journal of Production Management and Engineering. 4(2):41-42. doi:10.4995/ijpme.2016.5964. 41 42 4 2

  8. Creating visual explanations improves learning.

    Science.gov (United States)

    Bobek, Eliza; Tversky, Barbara

    2016-01-01

    Many topics in science are notoriously difficult for students to learn. Mechanisms and processes outside student experience present particular challenges. While instruction typically involves visualizations, students usually explain in words. Because visual explanations can show parts and processes of complex systems directly, creating them should have benefits beyond creating verbal explanations. We compared learning from creating visual or verbal explanations for two STEM domains, a mechanical system (bicycle pump) and a chemical system (bonding). Both kinds of explanations were analyzed for content and learning assess by a post-test. For the mechanical system, creating a visual explanation increased understanding particularly for participants of low spatial ability. For the chemical system, creating both visual and verbal explanations improved learning without new teaching. Creating a visual explanation was superior and benefitted participants of both high and low spatial ability. Visual explanations often included crucial yet invisible features. The greater effectiveness of visual explanations appears attributable to the checks they provide for completeness and coherence as well as to their roles as platforms for inference. The benefits should generalize to other domains like the social sciences, history, and archeology where important information can be visualized. Together, the findings provide support for the use of learner-generated visual explanations as a powerful learning tool.

  9. Evidence for independent Hox gene duplications in the hagfish lineage: a PCR-based gene inventory of Eptatretus stoutii.

    Science.gov (United States)

    Stadler, Peter F; Fried, Claudia; Prohaska, Sonja J; Bailey, Wendy J; Misof, Bernhard Y; Ruddle, Frank H; Wagner, Günter P

    2004-09-01

    Hox genes code for transcription factors that play a major role in the development of all animal phyla. In invertebrates these genes usually occur as tightly linked cluster, with a few exceptions where the clusters have been dissolved. Only in vertebrates multiple clusters have been demonstrated which arose by duplication from a single ancestral cluster. This history of Hox cluster duplications, in particular during the early elaboration of the vertebrate body plan, is still poorly understood. In this paper we report the results of a PCR survey on genomic DNA of the pacific hagfish Eptatretus stoutii. Hagfishes are one of two clades of recent jawless fishes that are an offshoot of the early radiation of jawless vertebrates. Our data provide evidence for at least 33 distinct Hox genes in the hagfish genome, which is most compatible with the hypothesis of multiple Hox clusters. The largest number, seven, of distinct homeobox fragments could be assigned to paralog group 9, which could imply that the hagfish has more than four clusters. Quartet mapping reveals that within each paralog group the hagfish sequences are statistically more closely related to gnathostome Hox genes than with either amphioxus or lamprey genes. These results support two assumptions about the history of Hox genes: (1) The association of hagfish homeobox sequences with gnathostome sequences suggests that at least one Hox cluster duplication event happened in the stem of vertebrates, i.e., prior to the most recent common ancestor of jawed and jawless vertebrates. (2) The high number of paralog group 9 sequences in hagfish and the phylogenetic position of hagfish suggests that the hagfish lineage underwent additional independent Hox cluster/-gene duplication events.

  10. Developmental and daily expression of the Pax4 and Pax6 homeobox genes in the rat retina: localization of Pax4 in photoreceptor cells

    DEFF Research Database (Denmark)

    Rath, Martin F; Bailey, Michael J; Kim, Jong-So

    2009-01-01

    in the foetal eye. Histological analysis revealed that Pax4 mRNA is exclusively expressed in the retinal photoreceptors, whereas Pax6 mRNA and protein are present in the inner nuclear layer and in the ganglion cell layer of the mature retina. In the adult retina, Pax4 transcripts exhibit a diurnal rhythm...

  11. TARGET Researchers Identify Mutations in SIX1/2 and microRNA Processing Genes in Favorable Histology Wilms Tumor | Office of Cancer Genomics

    Science.gov (United States)

    TARGET researchers molecularly characterized favorable histology Wilms tumor (FHWT), a pediatric renal cancer. Comprehensive genome and transcript analyses revealed single-nucleotide substitution/deletion mutations in microRNA processing genes (15% of FHWT patients) and Sine Oculis Homeobox Homolog 1/2 (SIX1/2) genes (7% of FHWT patients). SIX1/2 genes play a critical role in renal development and were not previously associated with FHWT, thus presenting a novel role for SIX1/2 pathway aberrations in this disease.

  12. Creating Porcine Biomedical Models Through Recombineering

    Directory of Open Access Journals (Sweden)

    Lawrence B. Schook

    2006-03-01

    Full Text Available Recent advances in genomics provide genetic information from humans and other mammals (mouse, rat, dog and primates traditionally used as models as well as new candidates (pigs and cattle. In addition, linked enabling technologies, such as transgenesis and animal cloning, provide innovative ways to design and perform experiments to dissect complex biological systems. Exploitation of genomic information overcomes the traditional need to choose naturally occurring models. Thus, investigators can utilize emerging genomic knowledge and tools to create relevant animal models. This approach is referred to as reverse genetics. In contrast to ‘forward genetics’, in which gene(s responsible for a particular phenotype are identified by positional cloning (phenotype to genotype, the ‘reverse genetics’ approach determines the function of a gene and predicts the phenotype of a cell, tissue, or organism (genotype to phenotype. The convergence of classical and reverse genetics, along with genomics, provides a working definition of a ‘genetic model’ organism (3. The recent construction of phenotypic maps defining quantitative trait loci (QTL in various domesticated species provides insights into how allelic variations contribute to phenotypic diversity. Targeted chromosomal regions are characterized by the construction of bacterial artificial chromosome (BAC contigs to isolate and characterize genes contributing towards phenotypic variation. Recombineering provides a powerful methodology to harvest genetic information responsible for phenotype. Linking recombineering with gene-targeted homologous recombination, coupled with nuclear transfer (NT technology can provide ‘clones’ of genetically modified animals.

  13. Creating an Innovative Learning Organization

    Science.gov (United States)

    Salisbury, Mark

    2010-01-01

    This article describes how to create an innovative learning (iLearning) organization. It begins by discussing the life cycle of knowledge in an organization, followed by a description of the theoretical foundation for iLearning. Next, the article presents an example of iLearning, followed by a description of the distributed nature of work, the…

  14. On Creating and Sustaining Alternatives

    DEFF Research Database (Denmark)

    Kyng, Morten

    2015-01-01

    (PD) as well as from innovation theory and software ecosystems. Last, but not least, the ongoing debate on public finances/economy versus tax evasion by major private companies has been an important element in shaping the vision and creating support for the initiative. This vision is about democratic...

  15. SPECIAL REPORT: Creating Conference Video

    Directory of Open Access Journals (Sweden)

    Noel F. Peden

    2008-12-01

    Full Text Available Capturing video at a conference is easy. Doing it so the product is useful is another matter. Many subtle problems come into play so that video and audio obtained can be used to create a final product. This article discusses what the author learned in the two years of shooting and editing video for Code4Lib conference.

  16. Creating Space for Children's Literature

    Science.gov (United States)

    Serafini, Frank

    2011-01-01

    As teachers struggle to balance the needs of their students with the requirements of commercial reading materials, educators need to consider how teachers will create space for children's literature in today's classrooms. In this article, 10 practical recommendations for incorporating children's literature in the reading instructional framework…

  17. We create our own reality

    CERN Multimedia

    2003-01-01

    " Yes, we create our own reality. This is one of the most fundamental tenets of the ancient oriental religions, such as Buddhism. And during the last century, modern particle physics or quantum mechanics has discovered exactly the same thing" (1 page).

  18. Creating legitimacy across international contexts

    DEFF Research Database (Denmark)

    Andersen, Poul Houman; Rask, Morten

    2014-01-01

    in Denmark, Israel, Canada, and Australia using expert interviews as well as content analysis of newspaper articles and other secondary sources. Storytelling, which is found to be central to the legitimacy-creating efforts of international business ventures, interacts with existing discourses in the diverse...

  19. Creating Presentations on ICT Classes

    Science.gov (United States)

    Marchis, Iuliana

    2010-01-01

    The article focuses on the creation of presentations on ICT classes. The first part highlights the most important steps when creating a presentation. The main idea is, that the computer presentation shouldn't consist only from the technological part, i.e. the editing of the presentation in a computer program. There are many steps before and after…

  20. Creating speech-synchronized animation.

    Science.gov (United States)

    King, Scott A; Parent, Richard E

    2005-01-01

    We present a facial model designed primarily to support animated speech. Our facial model takes facial geometry as input and transforms it into a parametric deformable model. The facial model uses a muscle-based parameterization, allowing for easier integration between speech synchrony and facial expressions. Our facial model has a highly deformable lip model that is grafted onto the input facial geometry to provide the necessary geometric complexity needed for creating lip shapes and high-quality renderings. Our facial model also includes a highly deformable tongue model that can represent the shapes the tongue undergoes during speech. We add teeth, gums, and upper palate geometry to complete the inner mouth. To decrease the processing time, we hierarchically deform the facial surface. We also present a method to animate the facial model over time to create animated speech using a model of coarticulation that blends visemes together using dominance functions. We treat visemes as a dynamic shaping of the vocal tract by describing visemes as curves instead of keyframes. We show the utility of the techniques described in this paper by implementing them in a text-to-audiovisual-speech system that creates animation of speech from unrestricted text. The facial and coarticulation models must first be interactively initialized. The system then automatically creates accurate real-time animated speech from the input text. It is capable of cheaply producing tremendous amounts of animated speech with very low resource requirements.

  1. Fine-tuning the onset of myogenesis by homeobox proteins that interact with the Myf5 limb enhancer

    Directory of Open Access Journals (Sweden)

    Philippe Daubas

    2015-12-01

    Full Text Available Skeletal myogenesis in vertebrates is initiated at different sites of skeletal muscle formation during development, by activation of specific control elements of the myogenic regulatory genes. In the mouse embryo, Myf5 is the first myogenic determination gene to be expressed and its spatiotemporal regulation requires multiple enhancer sequences, extending over 120 kb upstream of the Mrf4-Myf5 locus. An enhancer, located at −57/−58 kb from Myf5, is responsible for its activation in myogenic cells derived from the hypaxial domain of the somite, that will form limb muscles. Pax3 and Six1/4 transcription factors are essential activators of this enhancer, acting on a 145-bp core element. Myogenic progenitor cells that will form the future muscle masses of the limbs express the factors necessary for Myf5 activation when they delaminate from the hypaxial dermomyotome and migrate into the forelimb bud, however they do not activate Myf5 and the myogenic programme until they have populated the prospective muscle masses. We show that Msx1 and Meox2 homeodomain-containing transcription factors bind in vitro and in vivo to specific sites in the 145-bp element, and are implicated in fine-tuning activation of Myf5 in the forelimb. Msx1, when bound between Pax and Six sites, prevents the binding of these key activators, thus inhibiting transcription of Myf5 and consequent premature myogenic differentiation. Meox2 is required for Myf5 activation at the onset of myogenesis via direct binding to other homeodomain sites in this sequence. Thus, these homeodomain factors, acting in addition to Pax3 and Six1/4, fine-tune the entry of progenitor cells into myogenesis at early stages of forelimb development.

  2. Evaluation of zinc finger E-box binding homeobox 1 and transforming growth factor-beta2 expression in bladder cancer tissue in comparison with healthy adjacent tissue

    Directory of Open Access Journals (Sweden)

    Ali Mahdavinezhad

    2017-03-01

    Full Text Available Purpose: The fifth most common cancer is allocated to bladder cancer (BC worldwide. Understanding the molecular mechanisms of BC invasion and metastasis to identify target therapeutic strategies will improve disease survival. So the aim of this study was to measure expression rate of zinc finger E-box binding homeobox 1 (ZEB1 and transforming growth factor-beta2 (TGF-β2 mRNA in tissue samples of patients with BC and its healthy adjacent tissue samples and their association with muscle invasion, size and grade of the tumor. Materials and Methods: Tissue samples were collected from 35 newly diagnosed untreated patients with BC from 2013 to 2014. Total RNA was extracted from about 50-mg tissue samples using TRIzol reagent. TAKARA SYBR Premix EX Tag II was applied to determine the rate of mRNA expression by real-time polymerase chain reaction (PCR. To obtain final validation, PCR product of ZEB1 and TGF-β2 were sequenced. STATA 11 software was used to analyze the data. Results: The expression level of ZEB1 in tumor samples was significantly more than of in healthy adjacent tissue samples. Up-regulation of TGF-β2 showed a strong association with muscle invasion (p=0.017. There was also demonstrated a relationship between over expression of ZEB1 with the tumor size (p=0.050. Conclusions: It looks ZEB1 and TGF-β2 had a role in BC patients. In this study ZEB1 expression was higher in BC tissues than that of in healthy control tissues. There was demonstrated a markedly association between overexpression of TGF-β2 and muscle invasion. Therefore, they are supposed to be candidate as potential biomarkers for early detection and progression of BC.

  3. Diurnal expression of proteins in the retina of the blind cone-rod homeobox (Crx-/- ) mouse and the 129/Sv mouse: a proteomic study.

    Science.gov (United States)

    Møller, Morten; Rath, Martin Fredensborg; Ludvigsen, Maja; Honoré, Bent; Vorum, Henrik

    2017-11-01

    The vertebrate retina contains a circadian clock participating in adaptations to day and night vision. This peripheral clock is independent of the master clock in the suprachiasmatic nucleus (SCN). The retinal clock is located in several cell types, including the photoreceptors. To investigate the role of the circadian clock of the photoreceptor cells in regulation of retinal protein rhythms, we analysed diurnal protein expression in the photoreceptor-deficient cone-rod homeobox knockout mouse (Crx-/- ) and the 129/Sv mouse. 2D gels were made from retinal homogenates of 129/Sv and Crx-/- mice killed at midday and midnight. Stained gels were analysed by use of PDQuest 2D gel analysis software. After trypsin digestion of differential expressed spots, the proteins were identified by LC-MS/MS using a nano-liquid chromatograph connected to a Q-TOF Premier mass spectrometer. These data were used to search the SWISS-PROT database. Both the retinae of the control and the Crx-/- mice exhibited diurnal proteins rhythms. As expected, proteins involved in phototransduction were not detected in the Crx-/- mouse; in this phenotype, however, proteins from spots showing diurnal rhythms were specifically identified as enzymes involved in glucose metabolism, Krebs cycle, and mitochondrial enzymes. Data are available via ProteomeXchange with identifier PXD005556. We show diurnal protein rhythms in the retina of a mouse lacking the rods and cones. The diurnal protein rhythms in this genotype, lacking the circadian clock of the photoreceptors, might be caused by a circadian clock in other retinal cell types or a direct light input to the retina. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  4. Antagonistic roles for KNOX1 and KNOX2 genes in patterning the land plant body plan following an ancient gene duplication.

    Directory of Open Access Journals (Sweden)

    Chihiro Furumizu

    2015-02-01

    Full Text Available Neofunctionalization following gene duplication is thought to be one of the key drivers in generating evolutionary novelty. A gene duplication in a common ancestor of land plants produced two classes of KNOTTED-like TALE homeobox genes, class I (KNOX1 and class II (KNOX2. KNOX1 genes are linked to tissue proliferation and maintenance of meristematic potentials of flowering plant and moss sporophytes, and modulation of KNOX1 activity is implicated in contributing to leaf shape diversity of flowering plants. While KNOX2 function has been shown to repress the gametophytic (haploid developmental program during moss sporophyte (diploid development, little is known about KNOX2 function in flowering plants, hindering syntheses regarding the relationship between two classes of KNOX genes in the context of land plant evolution. Arabidopsis plants harboring loss-of-function KNOX2 alleles exhibit impaired differentiation of all aerial organs and have highly complex leaves, phenocopying gain-of-function KNOX1 alleles. Conversely, gain-of-function KNOX2 alleles in conjunction with a presumptive heterodimeric BELL TALE homeobox partner suppressed SAM activity in Arabidopsis and reduced leaf complexity in the Arabidopsis relative Cardamine hirsuta, reminiscent of loss-of-function KNOX1 alleles. Little evidence was found indicative of epistasis or mutual repression between KNOX1 and KNOX2 genes. KNOX proteins heterodimerize with BELL TALE homeobox proteins to form functional complexes, and contrary to earlier reports based on in vitro and heterologous expression, we find high selectivity between KNOX and BELL partners in vivo. Thus, KNOX2 genes confer opposing activities rather than redundant roles with KNOX1 genes, and together they act to direct the development of all above-ground organs of the Arabidopsis sporophyte. We infer that following the KNOX1/KNOX2 gene duplication in an ancestor of land plants, neofunctionalization led to evolution of antagonistic

  5. Creating a climate for excellence.

    Science.gov (United States)

    Lancaster, J

    1985-01-01

    Some people are motivated to achieve in a manner consistent with the goals of their organization while others pursue individual goals. The attitudes people hold determine their behavior. Therefore, the manager is charged with creating an environment that fosters employee commitment to organizational goals. To create a climate for achievement, managers must recognize that all employees want recognition. Employees perform more effectively when they understand the goals of the organization, know what is expected of them, and are part of a system that includes feedback and reinforcement. Generally, people perform more effectively in an environment with minimal threat and punishment; individual responsibility should be encouraged, rewards based on results, and a climate of trust and open communication should prevail.

  6. Creating advanced health informatics certification.

    Science.gov (United States)

    Gadd, Cynthia S; Williamson, Jeffrey J; Steen, Elaine B; Fridsma, Douglas B

    2016-07-01

    In 2005, AMIA leaders and members concluded that certification of advanced health informatics professionals would offer value to individual practitioners, organizations that hire them, and society at large. AMIA's work to create advanced informatics certification began by leading a successful effort to create the clinical informatics subspecialty for American Board of Medical Specialties board-certified physicians. Since 2012, AMIA has been working to establish advanced health informatics certification (AHIC) for all health informatics practitioners regardless of their primary discipline. In November 2015, AMIA completed the first of 3 key tasks required to establish AHIC, with the AMIA Board of Directors' endorsement of proposed eligibility requirements. This AMIA Board white paper describes efforts to establish AHIC, reports on the current status of AHIC components, and provides a context for the proposed AHIC eligibility requirements. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Leadership Networking Connect, Collaborate, Create

    CERN Document Server

    (CCL), Center for Creative Leadership; Baldwin, David

    2011-01-01

    Networking is essential to effective leadership in today's organizations. Leaders who are skilled networkers have access to people, information, and resources to help solve problems and create opportunities. Leaders who neglect their networks are missing out on a critical component of their role as leaders. This book will help leaders take a new view of networking and provide insight into how to enhance their networks and become effective at leadership networking.

  8. Creating a Mobile Library Website

    Science.gov (United States)

    Cutshall, Tom C.; Blake, Lindsay; Bandy, Sandra L.

    2011-01-01

    The overwhelming results were iPhones and Android devices. Since the library wasn't equipped technologically to develop an in-house application platform and because we wanted the content to work across all mobile platforms, we decided to focus on creating a mobile web-based platform. From the NLM page of mobile sites we chose the basic PubMed/…

  9. Creating and Sustaining Competitive Advantage

    OpenAIRE

    Lage Hansen, Jakob

    2010-01-01

    The paper provides a general framework for examining how governance choice affects competitive advantage. I argue that firms rely on assets for competing, and that these assets can be accessed by different governance structures (i.e., they can be in- or outsourced). The transaction cost economics framework is used to expose strengths and weaknesses of governance structures with respect to creating and sustaining competitive advantage. The result is a tradeoff to consider when choosing how to ...

  10. An atypical canonical bone morphogenetic protein (BMP) signaling pathway regulates Msh homeobox 1 (Msx1) expression during odontogenesis.

    Science.gov (United States)

    Yang, Guobin; Yuan, Guohua; Ye, Wenduo; Cho, Ken W Y; Chen, YiPing

    2014-11-07

    Bone morphogenetic protein (BMP) signaling plays an essential role in early tooth development, evidenced by disruption of BMP signaling leading to an early arrested tooth development. Despite being a central mediator of BMP canonical signaling pathway, inactivation of Smad4 in dental mesenchyme does not result in early developmental defects. In the current study, we investigated the mechanism of receptor-activated Smads (R-Smads) and Smad4 in the regulation of the odontogenic gene Msx1 expression in the dental mesenchyme. We showed that the canonical BMP signaling is not operating in the early developing tooth, as assessed by failed activation of the BRE-Gal transgenic allele and the absence of phospho-(p)Smad1/5/8-Smad4 complexes. The absence of pSmad1/5/8-Smad4 complex appeared to be the consequence of saturation of Smad4 by pSmad2/3 in the dental mesenchyme as knockdown of Smad2/3 or overexpression of Smad4 led to the formation of pSmad1/5/8-Smad4 complexes and activation of canonical BMP signaling in dental mesenchymal cells. We showed that Smad1/5 but not Smad4 are required for BMP-induced expression of Msx1 in dental mesenchymal cells. We further presented evidence that in the absence of Smad4, BMPs are still able to induce pSmad1/5/8 nuclear translocation and their binding to the Msx1 promoter directly in dental mesenchymal cells. Our results demonstrate the functional operation of an atypical canonical BMP signaling (Smad4-independent and Smad1/5/8-dependent) pathway in the dental mesenchyme during early odontogenesis, which may have general implication in the development of other organs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. An Atypical Canonical Bone Morphogenetic Protein (BMP) Signaling Pathway Regulates Msh Homeobox 1 (Msx1) Expression during Odontogenesis*

    Science.gov (United States)

    Yang, Guobin; Yuan, Guohua; Ye, Wenduo; Cho, Ken W. Y.; Chen, YiPing

    2014-01-01

    Bone morphogenetic protein (BMP) signaling plays an essential role in early tooth development, evidenced by disruption of BMP signaling leading to an early arrested tooth development. Despite being a central mediator of BMP canonical signaling pathway, inactivation of Smad4 in dental mesenchyme does not result in early developmental defects. In the current study, we investigated the mechanism of receptor-activated Smads (R-Smads) and Smad4 in the regulation of the odontogenic gene Msx1 expression in the dental mesenchyme. We showed that the canonical BMP signaling is not operating in the early developing tooth, as assessed by failed activation of the BRE-Gal transgenic allele and the absence of phospho-(p)Smad1/5/8-Smad4 complexes. The absence of pSmad1/5/8-Smad4 complex appeared to be the consequence of saturation of Smad4 by pSmad2/3 in the dental mesenchyme as knockdown of Smad2/3 or overexpression of Smad4 led to the formation of pSmad1/5/8-Smad4 complexes and activation of canonical BMP signaling in dental mesenchymal cells. We showed that Smad1/5 but not Smad4 are required for BMP-induced expression of Msx1 in dental mesenchymal cells. We further presented evidence that in the absence of Smad4, BMPs are still able to induce pSmad1/5/8 nuclear translocation and their binding to the Msx1 promoter directly in dental mesenchymal cells. Our results demonstrate the functional operation of an atypical canonical BMP signaling (Smad4-independent and Smad1/5/8-dependent) pathway in the dental mesenchyme during early odontogenesis, which may have general implication in the development of other organs. PMID:25274628

  12. Repression of Lateral Organ Boundary Genes by PENNYWISE and POUND-FOOLISH Is Essential for Meristem Maintenance and Flowering in Arabidopsis1[OPEN

    Science.gov (United States)

    Khan, Madiha; Ragni, Laura; Tabb, Paul; Salasini, Brenda C.; Chatfield, Steven; Datla, Raju; Lock, John; Kuai, Xiahezi; Després, Charles; Proveniers, Marcel; Yongguo, Cao; Xiang, Daoquan; Morin, Halima; Rullière, Jean-Pierre; Citerne, Sylvie; Hepworth, Shelley R.; Pautot, Véronique

    2015-01-01

    In the model plant Arabidopsis (Arabidopsis thaliana), endogenous and environmental signals acting on the shoot apical meristem cause acquisition of inflorescence meristem fate. This results in changed patterns of aerial development seen as the transition from making leaves to the production of flowers separated by elongated internodes. Two related BEL1-like homeobox genes, PENNYWISE (PNY) and POUND-FOOLISH (PNF), fulfill this transition. Loss of function of these genes impairs stem cell maintenance and blocks internode elongation and flowering. We show here that pny pnf apices misexpress lateral organ boundary genes BLADE-ON-PETIOLE1/2 (BOP1/2) and KNOTTED-LIKE FROM ARABIDOPSIS THALIANA6 (KNAT6) together with ARABIDOPSIS THALIANA HOMEOBOX GENE1 (ATH1). Inactivation of genes in this module fully rescues pny pnf defects. We further show that BOP1 directly activates ATH1, whereas activation of KNAT6 is indirect. The pny pnf restoration correlates with renewed accumulation of transcripts conferring floral meristem identity, including FD, SQUAMOSA PROMOTER-BINDING PROTEIN LIKE genes, LEAFY, and APETALA1. To gain insight into how this module blocks flowering, we analyzed the transcriptome of BOP1-overexpressing plants. Our data suggest a central role for the microRNA156-SQUAMOSA PROMOTER BINDING PROTEIN-LIKE-microRNA172 module in integrating stress signals conferred in part by promotion of jasmonic acid biosynthesis. These data reveal a potential mechanism by which repression of lateral organ boundary genes by PNY-PNF is essential for flowering. PMID:26417006

  13. Preventive Indicators for Creating Brownfields

    Directory of Open Access Journals (Sweden)

    Marija Burinskienė

    2015-05-01

    Full Text Available Although the problem of brownfields in urban territories is successfully limited, it is a negative phenomenon of a sustainable city. Moreover, the number of recently created brownfield territories has become higher than that of the regenerated ones. Such territories reduce the quality of the social and economic setting of a city as well as visually and physically affect the life quality of city residents. Unfortunately, methods for the revitalization of brownfield land have been applied to deal with the consequences of the problem rather than to limit the problem itself. The authors of the article have investigated the aspects to be avoided to not create brownfields. The indicators that enable predicting the probability of a territory becoming a brownfield have been analyzed in this paper. Countries develop and exist under different social and economic conditions. Therefore, there is no uniform and universally accepted system of indicators for brownfield prevention that can be applied in any country or city. The authors have attempted to implement a recently developed idea of indicators for prevention under Lithuanian conditions and have selected those facilitating the identification of brownfields with an aim of identifying the most significant ones warning about the potential harm from the creation of brownfields in Lithuania. The selected indicators have been grouped, taking into account social, economic, natural, building and infrastructure settings of the city and ranked by a group of experts in urban planning. The established hierarchy of indicators in the groups of urban setting has allowed the authors to select the most significant preventive indicators for brownfields. The created system of indicators could be applied in practice as a basis for monitoring pertinent data and tracking their change.

  14. Creating a digital medical illustration.

    Science.gov (United States)

    Culley, Joanna

    2016-01-01

    This paper covers the steps required to complete a medical illustration in a digital format using Adobe Illustrator and Photoshop. The project example is the surgical procedure for the release of the glenohumeral joint for the condition known as 'frozen shoulder'. The purpose is to demonstrate one method which an artist can use within digital media to create a colour illustration such as the release of the glenohumeral joint. Included is a general overview as how to deal with the administration of a medical illustration commission through the experience of a professional freelance artist.

  15. Pitx2, an atrial fibrillation predisposition gene, directly regulates ion transport and intercalated disc genes.

    Science.gov (United States)

    Tao, Ye; Zhang, Min; Li, Lele; Bai, Yan; Zhou, Yuefang; Moon, Anne M; Kaminski, Henry J; Martin, James F

    2014-02-01

    Pitx2 is the homeobox gene located in proximity to the human 4q25 familial atrial fibrillation (AF) locus. When deleted in the mouse germline, Pitx2 haploinsufficiency predisposes to pacing-induced AF, indicating that reduced Pitx2 promotes an arrhythmogenic substrate. Previous work focused on Pitx2 developmental functions that predispose to AF. Although Pitx2 is expressed in postnatal left atrium, it is unknown whether Pitx2 has distinct postnatal and developmental functions. To investigate Pitx2 postnatal function, we conditionally inactivated Pitx2 in the postnatal atrium while leaving its developmental function intact. Unstressed adult Pitx2 homozygous mutant mice display variable R-R interval with diminished P-wave amplitude characteristic of sinus node dysfunction, an AF risk factor in human patients. An integrated genomics approach in the adult heart revealed Pitx2 target genes encoding cell junction proteins, ion channels, and critical transcriptional regulators. Importantly, many Pitx2 target genes have been implicated in human AF by genome-wide association studies. Immunofluorescence and transmission electron microscopy studies in adult Pitx2 mutant mice revealed structural remodeling of the intercalated disc characteristic of human patients with AF. Our findings, revealing that Pitx2 has genetically separable postnatal and developmental functions, unveil direct Pitx2 target genes that include channel and calcium handling genes, as well as genes that stabilize the intercalated disc in postnatal atrium.

  16. Roles of lignin biosynthesis and regulatory genes in plant development

    Science.gov (United States)

    Yoon, Jinmi; Choi, Heebak

    2015-01-01

    Abstract Lignin is an important factor affecting agricultural traits, biofuel production, and the pulping industry. Most lignin biosynthesis genes and their regulatory genes are expressed mainly in the vascular bundles of stems and leaves, preferentially in tissues undergoing lignification. Other genes are poorly expressed during normal stages of development, but are strongly induced by abiotic or biotic stresses. Some are expressed in non‐lignifying tissues such as the shoot apical meristem. Alterations in lignin levels affect plant development. Suppression of lignin biosynthesis genes causes abnormal phenotypes such as collapsed xylem, bending stems, and growth retardation. The loss of expression by genes that function early in the lignin biosynthesis pathway results in more severe developmental phenotypes when compared with plants that have mutations in later genes. Defective lignin deposition is also associated with phenotypes of seed shattering or brittle culm. MYB and NAC transcriptional factors function as switches, and some homeobox proteins negatively control lignin biosynthesis genes. Ectopic deposition caused by overexpression of lignin biosynthesis genes or master switch genes induces curly leaf formation and dwarfism. PMID:26297385

  17. Creating your own leadership brand.

    Science.gov (United States)

    Kerfoot, Karlene

    2002-01-01

    Building equity in a brand happens through many encounters. The initial attraction must be followed by the meeting of expectations. This creates a loyalty that is part of an emotional connection to that brand. This is the same process people go through when they first meet a leader and decide if this is a person they want to buy into. People will examine your style, your competence, and your standards. If you fail on any of these fronts, your ability to lead will be severely compromised. People expect more of leaders now, because they know and recognize good leaders. And, predictably, people are now more cynical of leaders because of the well-publicized excess of a few leaders who advanced their own causes at the expense of their people and their financial future. This will turn out to be a good thing, because it will create a higher standard of leadership that all must aspire to achieve. When the bar is raised for us, our standards of performance are also raised.

  18. OPPOSITIONS CREATING HOMOUR IN JOKES

    Directory of Open Access Journals (Sweden)

    Umral Deveci

    2016-12-01

    Full Text Available Human beings, who perceive the reality of death however who do not know when it will happen, begin their life with this deficiency. Therefore, throughout their lives, they struggle to consummate and make up for the things that they perceive as deficiency or shortcomings through different ways. Humor is one of these means. The fact that deficiencies are eliminated results in superiority and relaxation. The sense of humor and relaxation simultaneously provide laughter. When theories of humor such as superiority, incongruous and relief are taken into consideration, it seems that these theories are related and support each other. Each text is whole with its form and content, which should be evaluated as a whole as much as possible. Hence this study dwells on shortcomings in jokes and in the lights of these shortcomings and theories of humor, it is intended tomake humor in stories, in terms of structural and semantic context, more concrete. Five stories/jokes randomly selected through samples are analyzed in this article. There are two basic types of opposition. The firstone is opposition that creates situation, the second one is thatcreates laughter. The first opposition depicts the shortcomings of knowledge, skill, patience arrogance and jealousyand prepares the second opposition. The opposition that creates laughter make up for shortcomings through cause and effect relationship and laughter comes out.

  19. Can the Universe create itself?

    Science.gov (United States)

    Gott, J. Richard, III; Li, Li-Xin

    1998-07-01

    The question of first-cause has troubled philosophers and cosmologists alike. Now that it is apparent that our universe began in a big bang explosion, the question of what happened before the big bang arises. Inflation seems like a very promising answer, but as Borde and Vilenkin have shown, the inflationary state preceding the big bang could not have been infinite in duration-it must have had a beginning also. Where did it come from? Ultimately, the difficult question seems to be how to make something out of nothing. This paper explores the idea that this is the wrong question-that that is not how the Universe got here. Instead, we explore the idea of whether there is anything in the laws of physics that would prevent the Universe from creating itself. Because spacetimes can be curved and multiply connected, general relativity allows for the possibility of closed timelike curves (CTCs). Thus, tracing backwards in time through the original inflationary state we may eventually encounter a region of CTCs-giving no first-cause. This region of CTCs may well be over by now (being bounded toward the future by a Cauchy horizon). We illustrate that such models-with CTCs-are not necessarily inconsistent by demonstrating self-consistent vacuums for Misner space and a multiply connected de Sitter space in which the renormalized energy-momentum tensor does not diverge as one approaches the Cauchy horizon and solves Einstein's equations. Some specific scenarios (out of many possible ones) for this type of model are described. For example, a metastable vacuum inflates producing an infinite number of (big-bang-type) bubble universes. In many of these, either by natural causes or by action of advanced civilizations, a number of bubbles of metastable vacuum are created at late times by high energy events. These bubbles will usually collapse and form black holes, but occasionally one will tunnel to create an expanding metastable vacuum (a baby universe) on the other side of the

  20. Creating Interdisciplinarity within Monodisciplinary Structures

    DEFF Research Database (Denmark)

    Lindvig, Katrine

    The objectives of the PhD project were to explore the linkages between interdisciplinary research and education, and to follow the concrete development and execution of interdisciplinary educational activities. In order to meet these objectives, an extensive literature study and a two......-year ethnographic fieldwork were conducted. The PhD project was part of the development project ‘Interdisciplinary education at UCPH’, with the aim of improving and supporting interdisciplinary teaching and learning at the University of Copenhagen (UCPH). The findings of the PhD study point towards wide...... discrepancies in the use of the term interdisciplinarity, which have repercussions for the practices and incentives of creating interdisciplinary education, research and collaboration. Overall, the thesis shows that interdisciplinary teaching and learning practices have to engage in a continuous balancing...

  1. Creating and Recreating. Microcomputing Working Paper Series.

    Science.gov (United States)

    Arms, Valarie

    This document describes a software program, CREATE, which was developed at Drexel University to guide students in creating English compositions. A second program, ReCREATE, guides students in reading their finished papers and making global revisions. CREATE asks 20 questions that a teacher might ask a student in a pre-writing conference. Unlike…

  2. Using the Developmental Gene Bicoid to Identify Species of Forensically Important Blowflies (Diptera: Calliphoridae

    Directory of Open Access Journals (Sweden)

    Seong Hwan Park

    2013-01-01

    Full Text Available Identifying species of insects used to estimate postmortem interval (PMI is a major subject in forensic entomology. Because forensic insect specimens are morphologically uniform and are obtained at various developmental stages, DNA markers are greatly needed. To develop new autosomal DNA markers to identify species, partial genomic sequences of the bicoid (bcd genes, containing the homeobox and its flanking sequences, from 12 blowfly species (Aldrichina grahami, Calliphora vicina, Calliphora lata, Triceratopyga calliphoroides, Chrysomya megacephala, Chrysomya pinguis, Phormia regina, Lucilia ampullacea, Lucilia caesar, Lucilia illustris, Hemipyrellia ligurriens and Lucilia sericata; Calliphoridae: Diptera were determined and analyzed. This study first sequenced the ten blowfly species other than C. vicina and L. sericata. Based on the bcd sequences of these 12 blowfly species, a phylogenetic tree was constructed that discriminates the subfamilies of Calliphoridae (Luciliinae, Chrysomyinae, and Calliphorinae and most blowfly species. Even partial genomic sequences of about 500 bp can distinguish most blowfly species. The short intron 2 and coding sequences downstream of the bcd homeobox in exon 3 could be utilized to develop DNA markers for forensic applications. These gene sequences are important in the evolution of insect developmental biology and are potentially useful for identifying insect species in forensic science.

  3. Creating responsible partnerships in tourism

    Directory of Open Access Journals (Sweden)

    Ana Spitzer

    2012-06-01

    Full Text Available RQ: Organisations do not provide sufficient time and effort to seek out companies for partners that would, with the assistance of responsible cooperation, contribute to better quality offers and consequently to increased income and the good reputation of both companies. Responsibilities and ethics is where organizations on bothsides would take on and accept their own norms, tasks, obligations and be aware that in a relationship there is a need to give explanations and justify one’s actions, such partnerships will be long and prosperous. This requires a great deal of knowledge and maturity together with a very important personal characteristic that is care. This study examines whether the creation of long term partnerships through responsible and more personal (friendlyrelations brings the organization to greater success.Purpose: The purpose of this research is to determine how important it is for organizations in the tourism industry to build long term relationships, what it should be based on and whether companies are willing to change the current methods of operations.Method: The method of research was an interview with individuals that had a certain position within a tourism company and had contacts with partners and were obligated to see out new ones. A paradigm model was built and the responses analysed.Results: The survey results are encouraging. The interviews showed that respondents were aware that it is necessary to have long term and responsible partnerships. They recognized that in today’s world there is a lack of collaboration that is based on understanding andthat there should be more relations on a personal level. It isrequired that this changes in the future. The participants specifically highlight financial irresponsibility in many companies that destroys collaboration.Organization: With the help of this study, the author attempts to contribute ideas to organizations on how to create solid collaboration with partners, as

  4. Adolescents and HIV: creating partnerships.

    Science.gov (United States)

    Tierney, S

    1998-05-01

    Despite the President's directive on youth and HIV in 1997 to focus the nation's attention on adolescents and the battle against AIDS, prevention programs continue to be ineffective. The number of seropositive youth, ages 13 to 24 years old, is unclear due to inconsistent definitions of age ranges and inadequate access to testing. Youth have not sought testing for many reasons, including failing to perceive their vulnerability to HIV, confidentiality concerns, and not realizing the effectiveness of early treatment. Adolescents are creating independence, establishing relationships, and learning about drugs and alcohol. Young gay and bisexual men, drug-using youth, and youth of color are at high risk of HIV transmission. Identifying the population involved in risk-taking behavior and eliminating the behavior is an ineffective strategy for adolescent HIV prevention programs. Complicating the issue further, the goals and expectations of adolescents differ from the adults who design and deliver prevention programs. HIV education and prevention efforts need to address solutions to hopelessness, isolation, and violence, rather than focusing on the negative effects risky behaviors will have in the future. Effective programs combine a youth/adult partnership to take advantage of the strengths of each individual. Strategies for implementing prevention programs that address the specific needs of adolescents are suggested.

  5. Creating healthy and just bioregions.

    Science.gov (United States)

    Pezzoli, Keith; Leiter, Robert Allen

    2016-03-01

    Dramatic changes taking place locally, regionally, globally, demand that we rethink strategies to improve public health, especially in disadvantaged communities where the cumulative impacts of toxicant exposure and other environmental and social stressors are most damaging. The emergent field of Sustainability Science, including a new bioregionalism for the 21st Century, is giving rise to promising place-based (territorially rooted) approaches. Embedded in this bioregional approach is an integrated planning framework (IPF) that enables people to map and develop plans and strategies that cut across various scales (e.g. from regional to citywide to neighborhood scale) and various topical areas (e.g. urban land use planning, water resource planning, food systems planning and "green infrastructure" planning) with the specific intent of reducing the impacts of toxicants to public health and the natural environment. This paper describes a case of bioregionally inspired integrated planning in San Diego, California (USA). The paper highlights food-water-energy linkages and the importance of "rooted" community-university partnerships and knowledge-action collaboratives in creating healthy and just bioregions.

  6. Laser Created Relativistic Positron Jets

    Energy Technology Data Exchange (ETDEWEB)

    Chen, H; Wilks, S C; Meyerhofer, D D; Bonlie, J; Chen, C D; Chen, S N; Courtois, C; Elberson, L; Gregori, G; Kruer, W; Landoas, O; Mithen, J; Murphy, C; Nilson, P; Price, D; Scheider, M; Shepherd, R; Stoeckl, C; Tabak, M; Tommasini, R; Beiersdorder, P

    2009-10-08

    Electron-positron jets with MeV temperature are thought to be present in a wide variety of astrophysical phenomena such as active galaxies, quasars, gamma ray bursts and black holes. They have now been created in the laboratory in a controlled fashion by irradiating a gold target with an intense picosecond duration laser pulse. About 10{sup 11} MeV positrons are emitted from the rear surface of the target in a 15 to 22-degree cone for a duration comparable to the laser pulse. These positron jets are quasi-monoenergetic (E/{delta}E {approx} 5) with peak energies controllable from 3-19 MeV. They have temperatures from 1-4 MeV in the beam frame in both the longitudinal and transverse directions. Positron production has been studied extensively in recent decades at low energies (sub-MeV) in areas related to surface science, positron emission tomography, basic antimatter science such as antihydrogen experiments, Bose-Einstein condensed positronium, and basic plasma physics. However, the experimental tools to produce very high temperature positrons and high-flux positron jets needed to simulate astrophysical positron conditions have so far been absent. The MeV temperature jets of positrons and electrons produced in our experiments offer a first step to evaluate the physics models used to explain some of the most energetic phenomena in the universe.

  7. Creating experimental color harmony map

    Science.gov (United States)

    Chamaret, Christel; Urban, Fabrice; Lepinel, Josselin

    2014-02-01

    Starting in the 17th century with Newton, color harmony is a topic that did not reach a consensus on definition, representation or modeling so far. Previous work highlighted specific characteristics for color harmony on com- bination of color doublets or triplets by means of a human rating on a harmony scale. However, there were no investigation involving complex stimuli or pointing out how harmony is spatially located within a picture. The modeling of such concept as well as a reliable ground-truth would be of high value for the community, since the applications are wide and concern several communities: from psychology to computer graphics. We propose a protocol for creating color harmony maps from a controlled experiment. Through an eye-tracking protocol, we focus on the identification of disharmonious colors in pictures. The experiment was composed of a free viewing pass in order to let the observer be familiar with the content before a second pass where we asked "to search for the most disharmonious areas in the picture". Twenty-seven observers participated to the experiments that was composed of a total of 30 different stimuli. The high inter-observer agreement as well as a cross-validation confirm the validity of the proposed ground-truth.

  8. India creates social marketing organization.

    Science.gov (United States)

    1984-01-01

    India, in a major policy shift toward reversible birth controls methods, will form a new organization to promote private sector contraceptive sales. The government, through a recently signed agreement with the Agency for International Development (AID), plans to establish a private nonprofit Contraceptive Marketing Organization (CMO) in fiscal year 1984. This momentous move marks a full circle return to a 1969 proposal by AID and Ford Foundation consultants. Funded at about $500 million over a 7 year period, the CMO will function as a semi-autonomous entity run by a board of governors representing government and such public and public sectors as health, communications, management, manufacturing, marketing, advertising, and market research. According to the agreement called the India Family Planning Communications and Marketing Plan, the CMO's activities will cover procurement and distribution of condoms, oral contraceptives (OCs), and other yet to be determined contraceptive methods. Of the $500 million in funds, the government of India has pledged 2/3, AID roughly $50 million in grants and loans, with the balance expected from such sources as the UN Fund for Population Activities. The CMO's goal is a marked increase in contraceptive use by married couples of reproductive age from the current 6% rate to 20% by 1990. As of 1982, India has 122 million such couples, with 1% purchasing commercial products, 2% buying Nirodh Marketing Program condoms and 3% relying on free government contraceptives. Besides creating the CMO, the India/AID pact outlines intensified public sector family planning promotions and activities. Some Indian health experts believe the government's decision to expand social marketing's role rests with a significant decade long decline in the popularity of such permanent birth control measures as vasectomy and tubal ligation.

  9. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  10. [shRNAs targeting high mobility group box-1 lead to inhibition of E-selectin expression via homeobox A9 in human umbilical vein endothelial cells].

    Science.gov (United States)

    Zhang, Xiaojuan; Jiao, Lili; Luan, Zhenggang; Ma, Xiaochun

    2015-08-01

    To approach the regulatory mechanism of high mobility group box-1 ( HMGB1 ) on the expression of E-selectin in human umbilical vein endothelial cell ( HUVEC ). Homeobox A9 ( HOXA9 ) siRNA was transfected to HUVEC at logarithmic phase, real-time fluorescence quantitative polymerase chain reaction ( real-time qPCR ) and Western Blot were used to determine the HOXA9 mRNA expression and protein expressions; a blank control group and a nonsilence negative control group were set. HUVEC stable transfected with pRNA-u6.1/Neo-HMGB1 shRNA plasmids ( HUVEC with low-expression HMGB1 ) was obtained, and HOXA9 and E-selectin mRNA expressions were determined with real-time qPCR; a nonsilence transfection group served as the negative control. The HOXA9 siRNA was transfected to HUVEC with low-expression HMGB1 as co-transfection group, and the E-selectin expressions was determined with real-time qPCR; a HMGB1 shRNA group and a HOXA9 nonsilence group served as control. (1) HOXA9 mRNA ( 2(-Δ ΔCT) ) and protein expression ( integral A value ) in blank control group were 1.094±0.115 and 1.031±0.060. Compared with nonsilence transfection group, HOXA9 siRNA transfection group could significantly reduced mRNA and protein expression of HOXA9 [ HOXA9 mRNA ( 2(-Δ ΔCT) ): 0.257±0.030 vs. 1.035±0.091, t = 14.010, P = 0.002; HOXA9 protein ( integral A value ): 0.278±0.042 vs. 0.975±0.014, t = 27.310, P = 0.002 ]. (2) Compared with nonsilence transfection group, HMGB1 shRNA transfection could up-regulate HOXA9 mRNA expression in HUVEC ( 2(-Δ ΔCT) : 2.519±0.278 vs. 0.856±0.063, t = 10.100, P = 0.001 ), also could down-regulate E-selectin mRNA expression ( 0.311±0.046 vs. 1.080±0.201, t = 7.415, P = 0.000 ). (3) Compared with HOXA9 nonsilence group and HMGB1 shRNA group, HMGB1 shRNA and HOXA9 siRNA co-transfected HUVEC cells could significantly elevate E-selectin mRNA expression ( 2(-Δ ΔCT) : 3.445±0.428 vs. 1.085±0.212, 1.004±0.104, t(1) = 8.507, t(2) = 9.603, both P < 0

  11. Creating Shared Value by Combatting Corruption

    National Research Council Canada - National Science Library

    Philip M Nichols

    2016-01-01

      Creating Shared Value The creating shared value strategy is similar to corporate social responsibility and to social impact in that it focusses on the intersection between business and the rest of society...

  12. Genes regulating hypothalamic and pituitary development.

    Science.gov (United States)

    Parks, J S; Adess, M E; Brown, M R

    1997-11-01

    Several pituitary transcription factors have been identified in the last 3 years. They offer new insights into the processes that direct organogenesis, cell commitment, proliferation and differentiated function. All are DNA-binding proteins, but they have ties to different families of homeodomain proteins. They differ in their distribution and in the timing of their appearance and extinction. The Rathke's pouch homeobox protein (Rpx) has a paired-like homeodomain. In mice, it appears on embryonic day 8.5 (day e8.5) and is gone by day e14.5. Its targets for activation are unknown. Pituitary OTX has a tryptophan--phenylalanine--lysine motif in its homeodomain. It appears early and persists. It shows independent activation of the alpha-glycoprotein subunit (alpha-GSU) and pro-opiomelanocortin genes and co-operates with Pit-1 in activation of the growth hormone and prolactin genes. Pituitary Lim (P-Lim) protein also acts independently on the alpha-GSU gene, and acts in concert with Pit-1 to activate other genes. A fourth protein, termed the 'Prophet of Pit-1', or Prop-1, is the recently discovered cause of Ames dwarfism in mice. This paired-like protein is necessary for the subsequent expression of Pit-1 in somatotrophs, lactotrophs and thyrotrophs. Any or all of the newly discovered pituitary genes are candidates for mutations causing hypopituitarism in humans. As several are expressed transiently in tissues other than the pituitary during organogenesis, the phenotypes produced by mutations in these genes may prove to be complex.

  13. Creating the Environment for Continuous Competition

    Science.gov (United States)

    2012-09-01

    The Limits of Competition in Defense Acquisition Defense Acquisition University Research Symposium, September 2012 CREATING THE ENVIRONMENT FOR...3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Creating the Environment for Continuous Competition 5a. CONTRACT NUMBER 5b...Information Technology (IT) Box A Primer. Retrieved from http: www.dau.mil/IT_Box_Primer_RDT_02142012.pptx. Creating the Environment for Continuous

  14. VSX1 gene and keratoconus: genetic analysis in Korean patients.

    Science.gov (United States)

    Jeoung, Jin Wook; Kim, Mee Kum; Park, Sung Sup; Kim, Sung Yeun; Ko, Hyun Soo; Wee, Won Ryang; Lee, Jin Hak

    2012-07-01

    The visual system homeobox 1 (VSX1) gene variants have recently been shown to be associated with keratoconus. To replicate this finding, we performed a genetic analysis of the VSX1 gene in a Korean case-control sample. Patients with keratoconus and healthy control subjects were recruited from Seoul National University Hospital. A diagnosis of keratoconus was made based on clinical examinations and the presence of characteristic topographic features. For all patients and controls, the whole coding region and the exon-intron junctions of the VSX1 gene were analyzed by direct sequencing. Fifty-three patients with keratoconus and 100 healthy volunteers were included. We observed 2 novel missense substitutions (Leu17Val and Val199Leu) and 1 previously reported substitution (Gly160Val) in 6 of the 53 affected probands. Because these substitutions have been identified in unaffected individuals, they were not considered to be pathogenic. No intragenic polymorphism was associated with a significantly increased risk of keratoconus. We cannot confirm the previously reported association of the VSX1 gene variants with keratoconus. Our results suggest that the VSX1 gene and its mutations with amino acid changes do not play a major role in the pathogenesis of keratoconus.

  15. Positional cloning of the gene for pre-axial polydactyly

    Energy Technology Data Exchange (ETDEWEB)

    Heutink, P.; Breedveld, G.J.; Zguricas, J. [Erasmus Univ., Rotterdam (Netherlands)] [and others

    1994-09-01

    Pre-axial polydactyly can occur as an isolated anomaly, in association with other abnormalities of the hand or as a component of complex developmental disorders. We recently localized the gene for pre-axial polydactyly to the most distal part of chromosome 7q. Identification and characterization of the gene defect and studies of the expression pattern during embryonic development may help clarify questions about the role of this gene in other developmental processes than those in hands. A key element involved in the formation of the separate digits of the developing limb is the apical ectodermal ridge (AER). In the AER and in the adjacent mesoderm, homeobox genes as well as genes regulating programmed cell death, growth factors or receptors are expressed. Disruption of any of these genes might potentially interfere with normal differentiation. How these genes interact and which genes are involved in the formation of the five digits is still largely unknown. We have ascertained additional families and performed haplotype analysis to define the critical region. Currently, we are developing new STS polymorphic markers to narrow down this critical region. YAC and cosmid contigs are being developed. On the syntenic region of human 7q36, the mouse chromosome 5p, a mutation has been localized that resembles the human polydactyly phenotype. Hx is a candidate gene for the disease gene in the families studied. YACs from the critical regions of the human and mouse phenotypes are being used to identify conserved sequences. These sequences are used to isolate cDNAs which will be used for mutation analysis in human family material in order to isolate the responsible gene for pre-axial polydactyly. Our most recent results will be presented.

  16. Independent Gene Discovery and Testing

    Science.gov (United States)

    Palsule, Vrushalee; Coric, Dijana; Delancy, Russell; Dunham, Heather; Melancon, Caleb; Thompson, Dennis; Toms, Jamie; White, Ashley; Shultz, Jeffry

    2010-01-01

    A clear understanding of basic gene structure is critical when teaching molecular genetics, the central dogma and the biological sciences. We sought to create a gene-based teaching project to improve students' understanding of gene structure and to integrate this into a research project that can be implemented by instructors at the secondary level…

  17. Knock-in strategy at 3'-end of Crx gene by CRISPR/Cas9 system shows the gene expression profiles during human photoreceptor differentiation.

    Science.gov (United States)

    Homma, Kohei; Usui, Sumiko; Kaneda, Makoto

    2017-03-01

    Fluorescent reporter gene knock-in induced pluripotent stem cell (iPSC) lines have been used to evaluate the efficiency of differentiation into specific cell lineages. Here, we report a knock-in strategy for the generation of human iPSC reporter lines in which a 2A peptide sequence and a red fluorescent protein (E2-Crimson) gene were inserted at the termination codon of the cone-rod homeobox (Crx) gene, a photoreceptor-specific transcriptional factor gene. The knock-in iPSC lines were differentiated into fluorescence-expressing cells in 3D retinal differentiation culture, and the fluorescent cells also expressed Crx specifically in the nucleus. We found that the fluorescence intensity was positively correlated with the expression levels of Crx mRNA and that fluorescent cells expressed rod photoreceptor-specific genes in the later stage of differentiation. Finally, we treated the fluorescent cells with DAPT, a Notch inhibitor, and found that DAPT-enhanced retinal differentiation was associated with up-regulation of Crx, Otx2 and NeuroD1, and down-regulation of Hes5 and Ngn2. These suggest that this knock-in strategy at the 3'-end of the target gene, combined with the 2A peptide linked to fluorescent proteins, offers a useful tool for labeling specific cell lineages or monitoring expression of any marker genes without affecting the function of the target gene. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  18. Process to create simulated lunar agglutinate particles

    Science.gov (United States)

    Gustafson, Robert J. (Inventor); Gustafson, Marty A. (Inventor); White, Brant C. (Inventor)

    2011-01-01

    A method of creating simulated agglutinate particles by applying a heat source sufficient to partially melt a raw material is provided. The raw material is preferably any lunar soil simulant, crushed mineral, mixture of crushed minerals, or similar material, and the heat source creates localized heating of the raw material.

  19. ICT and Pragmatism: Creating sustainable Employment for ...

    African Journals Online (AJOL)

    Thus, unless there is effort to create self employment, this can galvanize unexpected revolution whose consequences will be very grave. The reading public will have to apply the advice provided in this article to create self employment. Key Words: e-commerce, online transaction, broadband stimulus, unemployment.

  20. Creating Safe Spaces for Music Learning

    Science.gov (United States)

    Hendricks, Karin S.; Smith, Tawnya D.; Stanuch, Jennifer

    2014-01-01

    This article offers a practical model for fostering emotionally safe learning environments that instill in music students a positive sense of self-belief, freedom, and purpose. The authors examine the implications for music educators of creating effective learning environments and present recommendations for creating a safe space for learning,…

  1. Exclusion of Lhx9 as a candidate gene for Sry-negative XX sex reversal in the American cocker spaniel model.

    Science.gov (United States)

    Pujar, S; Kothapalli, K S; Kirkness, E; Van Wormer, R H; Meyers-Wallen, V N

    2005-01-01

    XX sex reversal is known in 17 breeds of dogs. In the American cocker spaniel, it segregates as an autosomal recessive trait, and the affected animals lack the testis determining Sry gene. In the search for an autosomal gene that causes this trait, we considered the possibility of Lhx9, a gene encoding LIM homeobox containing transcription factor 9, as a candidate gene. An American cocker spaniel pedigree showing Sry-negative XX sex reversal phenotype was genotyped with an intronic Lhx9 microsatellite marker. Segregation of the Lhx9 marker in the pedigree indicated that a mutation in canine Lhx9 is not likely to be the cause of Sry-negative XX sex reversal. In addition, using the recently available 7.6X canine genomic sequence, we report the location and genomic organization of canine Lhx9.

  2. [The methylation of ZHX2 gene promoter enhances AFP gene expression in hepatocellular carcinoma].

    Science.gov (United States)

    Lv, Zili; DU, Yangjun; Wen, Jianming

    2013-07-01

    To investigate the relationship between Zinc-fingers and homeoboxes 2 (ZHX2) promoter methylation and alpha-fetoprotein (AFP) gene expression, and analyze the mechanism of AFP gene expression. HepG2 cell line was cultured with 0.5, 1.0 or 5.0 μmol/L of 5-aza-deoxycytidine (5-Aza-Dc). RT-PCR and Western blotting were used to detect the expressions of ZHX2 and AFP in HepG2 cell line. Methylation-specific PCR was used to detect ZHX2 promoter methylation in 38 hepatocellular carcinoma tissues. The HepG2 cell line showed a low level of ZHX2 mRNA, negative expression of ZHX2 protein, but high expression of AFP at both mRNA and protein levels. After the HepG2 cells were treated with 1.0 or 5.0 μmol/L 5-Aza-Dc for 6 d, the expression of ZHX2 mRNA and protein increased and the expression of AFP mRNA and protein decreased. Among 38 hepatocellular carcinoma tissues, ZHX2 promoter methylation was found in 16 hepatocellular carcinoma tissues with AFP>25 ng/mL in serum. No methylation of ZHX2 promoter was found in 8 hepatocellular carcinoma tissues with AFPexpression.

  3. Creating mobile apps with Appcelerator Titanium

    CERN Document Server

    Brousseau, Christian

    2013-01-01

    Creating Mobile Apps with Appcelerator Titanium provides a hands-on approach and working examples on creating apps and games as well as embedding them onto a social networking website. Developers can then move on from there to develop their own applications based on the ones they have developed throughout the course of this book.""Creating Mobile Apps with Appcelerator Titanium"" is for developers who have experience with modern languages and development environments. Also, if you are familiar with the concepts of Object-oriented Programming (OOP), reusable components, AJAX closures, and so on

  4. Creating Web Sites The Missing Manual

    CERN Document Server

    MacDonald, Matthew

    2006-01-01

    Think you have to be a technical wizard to build a great web site? Think again. For anyone who wants to create an engaging web site--for either personal or business purposes--Creating Web Sites: The Missing Manual demystifies the process and provides tools, techniques, and expert guidance for developing a professional and reliable web presence. Like every Missing Manual, you can count on Creating Web Sites: The Missing Manual to be entertaining and insightful and complete with all the vital information, clear-headed advice, and detailed instructions you need to master the task at hand. Autho

  5. Kinship structures create persistent channels for language transmission.

    Science.gov (United States)

    Lansing, J Stephen; Abundo, Cheryl; Jacobs, Guy S; Guillot, Elsa G; Thurner, Stefan; Downey, Sean S; Chew, Lock Yue; Bhattacharya, Tanmoy; Chung, Ning Ning; Sudoyo, Herawati; Cox, Murray P

    2017-11-20

    Languages are transmitted through channels created by kinship systems. Given sufficient time, these kinship channels can change the genetic and linguistic structure of populations. In traditional societies of eastern Indonesia, finely resolved cophylogenies of languages and genes reveal persistent movements between stable speech communities facilitated by kinship rules. When multiple languages are present in a region and postmarital residence rules encourage sustained directional movement between speech communities, then languages should be channeled along uniparental lines. We find strong evidence for this pattern in 982 individuals from 25 villages on two adjacent islands, where different kinship rules have been followed. Core groups of close relatives have stayed together for generations, while remaining in contact with, and marrying into, surrounding groups. Over time, these kinship systems shaped their gene and language phylogenies: Consistently following a postmarital residence rule turned social communities into speech communities. Copyright © 2017 the Author(s). Published by PNAS.

  6. The anterior determinant bicoid of Drosophila is a derived Hox class 3 gene

    Science.gov (United States)

    Stauber, Michael; Jäckle, Herbert; Schmidt-Ott, Urs

    1999-01-01

    The Drosophila gene bicoid functions as the anterior body pattern organizer of Drosophila. Embryos lacking maternally expressed bicoid fail to develop anterior segments including head and thorax. In wild-type eggs, bicoid mRNA is localized in the anterior pole region and the bicoid protein forms an anterior-to-posterior concentration gradient. bicoid activity is required for transcriptional activation of zygotic segmentation genes and the translational suppression of uniformly distributed maternal caudal mRNA in the anterior region of the embryo. caudal genes as well as other homeobox genes or members of the Drosophila segmentation gene cascade have been found to be conserved in animal evolution. In contrast, bicoid homologs have been identified only in close relatives of the schizophoran fly Drosophila. This poses the question of how the bicoid gene evolved and adopted its unique function in organizing anterior–posterior polarity. We have cloned bicoid from a basal cyclorrhaphan fly, Megaselia abdita (Phoridae, Aschiza), and show that the gene originated from a recent duplication of the direct homolog of the vertebrate gene Hox3, termed zerknüllt, which specifies extraembryonic tissues in insects. PMID:10097115

  7. Creating Healthy Environments For Youth Athletes

    Science.gov (United States)

    EPA has created a presentation and companion checklist to help coaches and athletic administrators better understand the environmental health risks associated with youth sports and the steps they can follow to protect young athletes.

  8. More Sci- than Fi, Physicists Create Antimatter

    CERN Document Server

    Overbye, Dennis

    2002-01-01

    Physicists working in Europe announced yesterday that they had passed through nature's looking glass and had created atoms made of antimatter, or antiatoms, opening up the possibility of experiments in a realm once reserved for science fiction writers (5 pages)

  9. How to Create a Personal Health Record

    Science.gov (United States)

    ... currently available to help you create your own personal health record ( PHR ). PHR s are an inevitable and critical step in the evolution of health information management ( HIM ). The book, “The ...

  10. A summary of the CMS Create event

    CERN Multimedia

    CERN. Geneva; GASTAL, Martin

    2016-01-01

    The maiden CMS Create event took place in November 2015 and was a huge success. The output from all the participants was fantastic. As organisers we learnt a lot and hope to build on our experience for the 2016 event!

  11. Taking medicine at home - create a routine

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000613.htm Taking medicine at home - create a routine To use the ... teeth. Find Ways to Help You Remember Your Medicines You can: Set the alarm on your clock, ...

  12. How to Create a Reference from XML

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This module walks through the process of manually creating a ‘Geospatial Data’ record from an eXtensible Markup Language (XML) metadata file. It assumes that you...

  13. Creating competence: perspectives and practices in organizations

    NARCIS (Netherlands)

    Mulder, Martin

    2000-01-01

    Creating competence has become a major issue in organizations. Various authors contend that competency management has the potential of integrating organizational strategy, human-resource instruments, and human-resource development; that competency development can lead to performance improvement; and

  14. Creating Math Videos: Comparing Platforms and Software

    Science.gov (United States)

    Abbasian, Reza O.; Sieben, John T.

    2016-01-01

    In this paper we present a short tutorial on creating mini-videos using two platforms--PCs and tablets such as iPads--and software packages that work with these devices. Specifically, we describe the step-by-step process of creating and editing videos using a Wacom Intuos pen-tablet plus Camtasia software on a PC platform and using the software…

  15. Co-creating meaning through Artful Inquiry

    DEFF Research Database (Denmark)

    Darsø, Lotte

    2017-01-01

    contribution of this chapter is the introduction of a model for Artful Inquiry, which involves constructing powerful questions and finding appropriate artistic methods for reflecting and for co-creating with people or with artistic material. It is argued that Artful Inquiry can access deeper layers of knowing...... of leadership icons as well as co-creating with tangible materials can give rise to new meaning and transformational learning....

  16. ISO 55000: Creating an asset management system.

    Science.gov (United States)

    Bradley, Chris; Main, Kevin

    2015-02-01

    In the October 2014 issue of HEJ, Keith Hamer, group vice-president, Asset Management & Engineering at Sodexo, and marketing director at Asset Wisdom, Kevin Main, argued that the new ISO 55000 standards present facilities managers with an opportunity to create 'a joined-up, whole lifecycle approach' to managing and delivering value from assets. In this article, Kevin Main and Chris Bradley, who runs various asset management projects, examine the process of creating an asset management system.

  17. VSX1 gene analysis in keratoconus.

    Science.gov (United States)

    Tanwar, Mukesh; Kumar, Manoj; Nayak, Bhagabat; Pathak, Dhananjay; Sharma, Namrata; Titiyal, Jeewan S; Dada, Rima

    2010-11-16

    To screen the visual system homeobox 1 (VSX1) gene in keratoconus patients. The enntire coding region of VSX1, including intron-exon boundaries were amplified in keratoconus cases (n=50) and controls (n=50). All sequences were analyzed against the ensemble sequence (ENSG00000100987) for VXS1. Sequencing analysis showed four alterations (p.A182A, p.R217H, p.P237P, and g.25059612C>T) in VSX1 of which g.25059612C>T (in intron 2) was found to be novel. Of these four, p.A182A and p.P237P were present in both cases as well as controls while p.R217H and g.25059612C>T were limited to cases only. All these changes were non-pathogenic. In our study no pathogenic VSX1 mutation was identified. The role of VSX1 in the pathogenesis of keratoconus is still controversial. VSX1 mutations are responsible for a very small fraction of all observed keratoconus cases. The absence of pathogenic mutations in VSX1 in our patients indicates that other genetic loci like 13q32 as suggested by a recent study may be involved in the pathogenesis of this disorder.

  18. Creating genetically modified pigs by using nuclear transfer

    Directory of Open Access Journals (Sweden)

    Prather Randall S

    2003-11-01

    Full Text Available Abstract Nuclear transfer (NT is a procedure by which genetically identical individuals can be created. The technology of pig somatic NT, including in vitro maturation of oocytes, isolation and treatment of donor cells, artificial activation of reconstructed oocytes, embryo culture and embryo transfer, has been intensively studied in recent years, resulting in birth of cloned pigs in many labs. While it provides an efficient method for producing transgenic pigs, more importantly, it is the only way to produce gene-targeted pigs. So far pig cloning has been successfully used to produce transgenic pigs expressing the green fluorescence protein, expand transgenic pig groups and create gene targeted pigs which are deficient of alpha-1,3-galactosyltransferase. The production of pigs with genetic modification by NT is now in the transition from investigation to practical use. Although the efficiency of somatic cell NT in pig, when measured as development to term as a proportion of oocytes used, is not high, it is anticipated that the ability of making specific modifications to the swine genome will result in this technology having a large impact not only on medicine but also on agriculture.

  19. Cloning and characterization of two members of the vertebrate Dlx gene family.

    Science.gov (United States)

    Simeone, A; Acampora, D; Pannese, M; D'Esposito, M; Stornaiuolo, A; Gulisano, M; Mallamaci, A; Kastury, K; Druck, T; Huebner, K

    1994-01-01

    A number of vertebrate genes of the Dlx gene family have been cloned in mouse, frog, and zebrafish. These genes contain a homeobox related to that of Distalless, a gene expressed in the developing head and limbs of Drosophila embryos. We cloned and studied the expression of two members of this family, which we named Dlx5 and Dlx6, in human and mouse. The two human genes, DLX5 and DLX6, are closely linked in an inverted convergent configuration in a region of chromosome 7, at 7q22. Similarly, the two human genes DLX1 and DLX2 are closely linked in a convergent configuration at 2q32, near the HOXD (previously HOX4) locus. In situ hybridization experiments in mouse embryos revealed expression of Dlx5 and Dlx6 mRNA in restricted regions of ventral diencephalon and basal telencephalon, with a distribution very similar to that reported for Dlx1 and Dlx2 mRNA. A surprising feature of Dlx5 and Dlx6 is that they are also expressed in all skeletal structures of midgestation embryos after the first cartilage formation. The expression pattern of these genes, together with their chromosome localization, may provide useful cues for the study of congenital disorders in which there is a combination of craniofacial and limb defects. Images PMID:7907794

  20. Epigenetic silencing of downstream genes mediated by tandem orientation in lung cancer.

    Science.gov (United States)

    Kiehl, Steffen; Zimmermann, Tobias; Savai, Rajkumar; Pullamsetti, Soni S; Seeger, Werner; Bartkuhn, Marek; Dammann, Reinhard H

    2017-06-20

    Epigenetic deregulation is of importance in tumorigenesis. In particular CpG islands (CGI), are frequently hypermethylated. Here, genome-wide DNA-methylation profiles of 480,000 CpGs in lung cancer cells were generated. It was observed that intra- and intergenic CGI exhibited higher methylation compared to normal cells. The functional annotation of hypermethylated CGI revealed that the hypermethylation was associated with homeobox domain genes and targets marked by repressive histone modifications. The strongest methylation variation was observed in transitional areas of CGI, termed shores. 5'-shores of promoter-associated CGI in lung cancer cell lines were higher methylated than 3'-shores. Within two tandem-oriented genes, a significant hypermethylation of the downstream-located CGI promoters was revealed. Hypermethylation correlates with the length of the intergenic region between such tandem genes. As the RASSF1A tumor suppressor gene represents such a downstream tandem gene, its silencing was analyzed using an inducible system. It was determined that the induction of an upstream gene led to a repression of RASSF1A through a process involving histone deacetylases and CPSF1. A tumor-specific increase in expression of histone deacetylases and CPSF1 was detected in lung cancer. Our results suggest that the downstream gene could be susceptible to epigenetic silencing when organized in a tandem orientation.

  1. Molecular analysis of the VSX1 gene in familial keratoconus

    Science.gov (United States)

    Liskova, Petra; Ebenezer, Neil D.; Hysi, Pirro G.; Gwilliam, Rhian; El-Ashry, Mohamed F.; Moodaley, Lalitha C.; Hau, Scott; Twa, Michael; Tuft, Stephen J.; Bhatacharya, Shomi S.

    2017-01-01

    Purpose To evaluate the role of the visual system homeobox gene 1 (VSX1) in the pathogenesis of familial keratoconus. Methods Families with two or more individuals with keratoconus were recruited and their members examined. The coding region and intron-exon junctions of the VSX1 gene were sequenced in affected individuals. In cases where there were possible pathogenic changes, segregation within the pedigree was analyzed. Meta analysis of reports on an association of p.D144E change with keratoconus phenotype was performed. Results Probands from a panel of 85 apparently unrelated keratoconus families were included. Eleven sequence variants were observed, including the previously reported c.432C>G (p.D144E) change and two novel intronic single nucleotide polymorphisms. However, these three changes did not cosegregate with the disease phenotype. Conclusions We excluded the c.432C>G sequence alteration as the direct cause of the disease. Lack of possibly pathogenic VSX1 sequence variants in the familial panel suggests that involvement of this gene in the pathogenesis of keratoconus is likely to be confined to a small number of pedigrees, at least in the population studied. PMID:17960127

  2. Glaucoma and Cytochrome P4501B1 Gene Mutations

    Directory of Open Access Journals (Sweden)

    Mukesh Tanwar

    2010-01-01

    Full Text Available Developmental anomalies of the ocular anterior chamber angle may lead to an incomplete development of the structures that form the conventional aqueous outflow pathway. Thus, disorders that present with such dysfunction tend to be associated with glaucoma. Among them, Axenfeld-Rieger (ARS malformation is a rare clinical entity with an estimated prevalence of one in every 200,000 individuals. The changes in eye morphogenesis in ARS are highly penetrant and are associated with 50% risk of development of glaucoma. Mutations in the cytochrome P4501B1 (CYP1B1 gene have been reported to be associated with primary congenital glaucoma and other forms of glaucoma and mutations in pituitary homeobox 2 (PITX2 gene have been identified in ARS in various studies. This case was negative for PITX2 mutations and compound heterozygote for CYP1B1 mutations. Clinical manifestations of this patient include bilateral elevated intraocular pressure (>40 mmHg with increased corneal diameter (>14 mm and corneal opacity. Patient also had iridocorneal adhesions, anteriorly displaced Schwalbe line, anterior insertion of iris, broad nasal bridge and protruding umbilicus. This is the first study from north India reporting CYP1B1 mutations in Axenfeld-Rieger syndrome with bilateral buphthalmos and early onset glaucoma. Result of this study supports the role of CYP1B1 as a causative gene in ASD disorders and its role in oculogenesis.

  3. [Create or copy... Which is the difference?].

    Science.gov (United States)

    López P, Ricardo

    2009-01-01

    Creating and copying are two different processes; we must not confuse creativity with plagiarism. However, this distinction is problematic, because there is no possibility of creating from scratch, this implies that any creative act necessarily arises from accumulative experience, inevitably producing a continuity between old and new. Even so it is necessary to establish clearly the difference between creating and copying. It is not desirable that a matter of such importance remains in the nebula or that the relationship between creativity and ethics is kept unaware. There are many cases of plagiarism, but this cannot be a consolation. There is no gain when the existence of a plagiarism is ignored or concealed and less when it is unjustified.

  4. Gene therapy: An overview

    Directory of Open Access Journals (Sweden)

    Sudip Indu

    2013-01-01

    Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.

  5. Comparative analysis of weighted gene co-expression networks in human and mouse.

    Science.gov (United States)

    Eidsaa, Marius; Stubbs, Lisa; Almaas, Eivind

    2017-01-01

    The application of complex network modeling to analyze large co-expression data sets has gained traction during the last decade. In particular, the use of the weighted gene co-expression network analysis framework has allowed an unbiased and systems-level investigation of genotype-phenotype relationships in a wide range of systems. Since mouse is an important model organism for biomedical research on human disease, it is of great interest to identify similarities and differences in the functional roles of human and mouse orthologous genes. Here, we develop a novel network comparison approach which we demonstrate by comparing two gene-expression data sets from a large number of human and mouse tissues. The method uses weighted topological overlap alongside the recently developed network-decomposition method of s-core analysis, which is suitable for making gene-centrality rankings for weighted networks. The aim is to identify globally central genes separately in the human and mouse networks. By comparing the ranked gene lists, we identify genes that display conserved or diverged centrality-characteristics across the networks. This framework only assumes a single threshold value that is chosen from a statistical analysis, and it may be applied to arbitrary network structures and edge-weight distributions, also outside the context of biology. When conducting the comparative network analysis, both within and across the two species, we find a clear pattern of enrichment of transcription factors, for the homeobox domain in particular, among the globally central genes. We also perform gene-ontology term enrichment analysis and look at disease-related genes for the separate networks as well as the network comparisons. We find that gene ontology terms related to regulation and development are generally enriched across the networks. In particular, the genes FOXE3, RHO, RUNX2, ALX3 and RARA, which are disease genes in either human or mouse, are on the top-10 list of globally

  6. Can Physical Examination Create a Stener Lesion?

    Science.gov (United States)

    Lankachandra, Manesha; Eggers, John P; Bogener, James W; Hutchison, Richard L

    2017-09-01

    The purpose of this study is to determine whether a Stener lesion can be created while testing stability of the ulnar collateral ligament (UCL) of the thumb. Testing was performed in a manner that reproduced clinical examination. Six fresh frozen hand and forearm specimens underwent sequential sectioning of the accessory UCL, the proper UCL, and the ulnar sagittal band. Measurements of radial deviation of the metacarpophalangeal (MCP) joint were taken with the thumb in neutral rotation, pronation and supination, both with 0 degrees and with 30 degrees of flexion of the MCP joint. Visual examination was performed to assess the presence of a Stener lesion. No Stener lesion was created in any position as long as the fascial origin of the ulnar sagittal band at the adductor pollicis longus remained intact. After creating a defect in the ulnar sagittal band, a Stener lesion was created in two specimens, but only when the thumb was flexed and supinated. Pronation provided more stability, and supination provided less stability, with one or both components cut, especially when testing at 30° of flexion. Compared to both components cut without flexion or rotation, there was a statistically significant difference in angulation with the 30 degrees of MCP joint flexion in both neutral rotation in supination. Performing a physical examination to assess the amount of instability of an ulnar collateral ligament injury did not create a Stener lesion if the exam was performed in a controlled, gentle manner with the thumb held without rotation. If the thumb is held in neutral rotation during the exam, an iatrogenic Stener lesion should not be created.

  7. How to create a serious game?

    Directory of Open Access Journals (Sweden)

    O. Heidmann

    2015-11-01

    Full Text Available Serious games are video games designed to achieve an educational effect and achieve some degree of training in a certain area. They are nowadays used in industries such as defense, education, scientific exploration, health care, emergency management, city planning, engineering, and many others. As it still a nascent subject who doesn’t follow exactly the same rules and practices than the commercial video games industry, questions remain about how to create and use serious games. This article presents some know-how on the subject of creating serious games.

  8. Creating e-learning games with Unity

    CERN Document Server

    Horachek, David

    2014-01-01

    Unity is a fully integrated development engine providing the required functionality to create games and interactive 3D content, while reducing the time, effort, and cost of developing the content. Nowadays, many people have started to use Unity in an eLearning setting as it allows them to create real-world scenarios, or models, for training purposes. With Unity, one can develop video games that are not only fun, but are also effective teaching and learning tools. When properly designed, an engaging game is an ideal platform for the presentation, testing, and application of learning objectives.

  9. Creating dynamic UI with Android fragments

    CERN Document Server

    Wilson, Jim

    2013-01-01

    A fast-paced tutorial that guides you through everything you need to know about dynamic UI design for Android devices.This book is for developers with a basic understanding of Android programming who would like to improve the appearance and usability of their applications. Whether you're looking to create a more interactive user experience, create more dynamically adaptive UIs, provide better support for tablets and smartphones in a single app, reduce the complexity of managing your app UIs, or you are just trying to expand your UI design philosophy, then this book is for you.

  10. Creating a Website The Missing Manual

    CERN Document Server

    MacDonald, Matthew

    2011-01-01

    Think you need an army of skilled programmers to build a website? Think again. With nothing more than an ordinary PC, some raw ambition, and this book, you'll learn how to create and maintain a professional-looking, visitor-friendly site. This Missing Manual gives you all the tools, techniques, and expert advice you need. Plan your site. Create web pages by learning the basics of HTML and HTML5.Control page design with CSS. Format text, images, links, tables, and other elements.Attract visitors. Ensure that people can find your site through popular search engines.Build a community. Add forums

  11. Creating a web site the missing manual

    CERN Document Server

    MacDonald, Matthew

    2008-01-01

    Think you have to be a technical wizard to build a great web site? Think again. If you want to create an engaging web site, this thoroughly revised, completely updated edition of Creating a Web Site: The Missing Manual demystifies the process and provides tools, techniques, and expert guidance for developing a professional and reliable web presence. Whether you want to build a personal web site, an e-commerce site, a blog, or a web site for a specific occasion or promotion, this book gives you detailed instructions and clear-headed advice for: Everything from planning to launching. From pi

  12. Creating Gaze Annotations in Head Mounted Displays

    DEFF Research Database (Denmark)

    Mardanbeigi, Diako; Qvarfordt, Pernilla

    2015-01-01

    , the user simply captures an image using the HMD’s camera, looks at an object of interest in the image, and speaks out the information to be associated with the object. The gaze location is recorded and visualized with a marker. The voice is transcribed using speech recognition. Gaze annotations can......To facilitate distributed communication in mobile settings, we developed GazeNote for creating and sharing gaze annotations in head mounted displays (HMDs). With gaze annotations it possible to point out objects of interest within an image and add a verbal description. To create an annota- tion...

  13. Creating an Economically Enabling and Competitive Business ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Creating an Economically Enabling and Competitive Business Environment in the West Bank and Gaza Strip. The prospect of indefinite Israeli occupation of the ... Impact of implementing the Palestinian banking law on the performance of the private sector [Arabic language]. Documents. Impact of the commercial agents law ...

  14. Creating sustainable environmental management in Senegal's cities ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2016-04-28

    Apr 28, 2016 ... IAGU specializes in action research, technical support, and information on the urban environment including urban agriculture, solid waste management, strategic environmental planning, and urban risk management. It works with African city administrations to create sustainable, participatory systems for ...

  15. Mental Mapping: A Lesson that Creates Itself

    Science.gov (United States)

    Comenetz, Joshua

    2005-01-01

    Mental image and place-preference maps of college students in Florida were created through a two-part lesson. The patterns revealed by these maps were linked to students' life experiences, census data on migration and income, and similar studies conducted in other states. Students prefer states with established migration links to Florida and…

  16. Creating a Positive Classroom Environment for Children.

    Science.gov (United States)

    Prutzman, Priscilla

    1983-01-01

    Describes cooperation and affirmation activities designed to create a classroom environment in which children interact peacefully and resolve conflicts creatively. Exercises include cooperation drawing, group hand prints and shadow murals, a circle game entitled "Rainstorm," student interviews, affirmation shows using video, affirmation clapping,…

  17. Creating Career Awareness Among Secondary School Students ...

    African Journals Online (AJOL)

    This paper discussed the need for creating career awareness among Secondary School Students through career fair Career selection is a critical issue for secondary school students who may not be aware of the existing occupations in the labour market. It is important that career information be made available to students ...

  18. Understanding Critical Thinking to Create Better Doctors

    Science.gov (United States)

    Zayapragassarazan, Zayabalaradjane; Menon, Vikas; Kar, Sitanshu Sekhar; Batmanabane, Gitanjali

    2016-01-01

    Medical students master an enormous body of knowledge, but lack systematic problem solving ability and effective clinical decision making. High profile reports have called for reforms in medical education to create a better generation of doctors who can cope with the system based problems they would encounter in an interdisciplinary and…

  19. Creating a Character as a Writing Exercise.

    Science.gov (United States)

    Latta, Alan D.

    2001-01-01

    Suggests an approach to teaching German as a second language in which students jointly create a character and her family and then write a series of stories during he year about the character in various everyday situations. Benefits include use of basic language, cultural issues, and stimulation of student creativity and interest. (Author/VWL)

  20. Creating and decomposing vector Bessel beams

    CSIR Research Space (South Africa)

    Dudley, Angela L

    2013-07-01

    Full Text Available -1 58th Annual SAIP Conference, Richards Bay, 8-12 July 2013 Creating and decomposing vector Bessel beams Angela Dudley1,*, Yanming Li2, Thandeka Mhlanga1, Michael Escuti2 and Andrew Forbes1 1 CSIR National Laser Centre, Pretoria, South...

  1. Creating, Invigorating, and Sustaining Effective Teams.

    Science.gov (United States)

    Trimble, Susan; Miller, John W.

    1996-01-01

    Teams can boost creativity, morale, and communication, but they can also unleash disharmony, create tension, and waste time. To maximize teaming benefits, administrators must share authority, cultivate teacher leadership, train all team members, use situational leadership, model effective team leader behaviors, provide incentives, support each…

  2. Creating Music Environments in Early Childhood Programs.

    Science.gov (United States)

    Achilles, Elayne

    1999-01-01

    Describes how teachers and caregivers can create music environments in early childhood settings that connect to other areas of development. Discusses how music environments can accommodate free-choice participation, describes the caregiver's role, and suggests music activities. Includes definitions of musical concepts for young children, also tips…

  3. The Media Creates Us in Its Image

    Science.gov (United States)

    Stivers, Richard

    2012-01-01

    Propaganda in all its forms is the culture of a mass society. The media transmits propaganda to form public opinion and recreate the human being. Reversing the Western ideal of a rational and free individual, the media creates a childish conformist ensconced in the peer group, who acts unconsciously.

  4. Extending the "Knowledge Advantage": Creating Learning Chains

    Science.gov (United States)

    Maqsood, Tayyab; Walker, Derek; Finegan, Andrew

    2007-01-01

    Purpose: The purpose of this paper is to develop a synergy between the approaches of knowledge management in a learning organisation and supply chain management so that learning chains can be created in order to unleash innovation and creativity by managing knowledge in supply chains. Design/methodology/approach: Through extensive literature…

  5. Creating Future Memories: A Dialogue on Process

    DEFF Research Database (Denmark)

    Rehder, Mads Middelboe

    2016-01-01

    Desk of the Future” was created as a means of acting out how unhelpful many helpdesks actually are and to imagine how algorithms may be positioning our futures for us. The Museum of Random Memory functioned as a pop-up curatorial event where participants could offer up memories, experiences...

  6. Creating an Economically Enabling and Competitive Business ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Creating an Economically Enabling and Competitive Business Environment in the West Bank and Gaza Strip. The prospect of indefinite Israeli occupation of the Palestinian territories, and their extreme ... Country(s). Middle East, North of Sahara, South of Sahara, Central Asia, Far East Asia, South Asia, Palestine ...

  7. Creating a Data Warehouse using SQL Server

    DEFF Research Database (Denmark)

    Sørensen, Jens Otto; Alnor, Karl

    1999-01-01

    In this paper we construct a Star Join Schema and show how this schema can be created using the basic tools delivered with SQL Server 7.0. Major objectives are to keep the operational database unchanged so that data loading can be done with out disturbing the business logic of the operational...

  8. Introduction: Leadership and Diversity: Creating Inclusive Schools.

    Science.gov (United States)

    Madsen, Jean A.; Mabokela, Reitumetse Obakeng

    2002-01-01

    Introduces a theme issue that explores the perceptions of teachers toward African American school leaders as they seek to create inclusive school environments; the capacity of teachers and school leaders to negotiate intergroup conflict so they can work collaboratively on matters of race; and leaders' interpretation and implementation of policies…

  9. Creating social impact with sport events

    NARCIS (Netherlands)

    Hover, P.; Dijk, B.; Breedveld, K.; Eekeren, F.J.A. van; Slender, H.

    2016-01-01

    All over the world, sport events are seen as significant tools for creating positive social impact. This is understandable, as sport events have the power to attract enthusiastic participants, volunteers and to reach large audiences of visitors and followers via (social) media. Outbursts of

  10. Humanising education through technology: creating social presence ...

    African Journals Online (AJOL)

    While it is difficult to create social presence in large classes, educational technologies can enhance the social dimension of online learning if educators relinquish the use of technology as an instrument of control. This article argues the importance of social presence as a building block of successful learning environments ...

  11. Creating Teams Increases Extension Educator Productivity

    Science.gov (United States)

    Chalker-Scott, Linda; Daniels, Catherine H.; Martini, Nicole

    2016-01-01

    The Garden Team at Washington State University is a transdisciplinary group of faculty, staff, and students with expertise in applied plant and soil sciences and an interest in Extension education. The team's primary mission is to create current, relevant, and peer-reviewed materials as Extension publications for home gardeners. The average yearly…

  12. Green Energy Technologies Create Green Jobs

    Energy Technology Data Exchange (ETDEWEB)

    None

    2009-10-01

    The U.S. Department of Energy (DOE) is developing advanced energy technologies that can help address climate change and reduce U.S. dependence on oil. As these new technologies are launched into commercial use, they create new jobs for American workers.

  13. Engineering Encounters: Creating a Prosthetic Hand

    Science.gov (United States)

    Cook, Kristin Leigh; Bush, Sarah B.; Cox, Richard

    2015-01-01

    The power of 3D printing technology has grown exponentially in just the past few years--people around the world are using 3D printers to prepare food, create tailored clothing, build cars and homes, and advance the medical field in ways that never seemed possible. In classrooms across the nation, 3D printers have become increasingly common because…

  14. Creating Learning Communities in the Classroom

    Science.gov (United States)

    Saville, Bryan K.; Lawrence, Natalie Kerr; Jakobsen, Krisztina V.

    2012-01-01

    There are many ways to construct classroom-based learning communities. Nevertheless, the emphasis is always on cooperative learning. In this article, the authors focus on three teaching methods--interteaching, team-based learning, and cooperative learning in large, lecture-based courses--that they have used successfully to create classroom-based…

  15. Creating seamless connections: Intersecting the social and ...

    African Journals Online (AJOL)

    university's effort to create intimate learning communities for students within residence halls as a way of integrating students' academic experiences with their residential lives. Both examples illustrate how learning becomes seamless and continues beyond the classroom by allowing students to be organised into learning ...

  16. Creating Smart-er Cities: An Overview

    Science.gov (United States)

    Allwinkle, Sam; Cruickshank, Peter

    2011-01-01

    The following offers an overview of what it means for cities to be "smart." It draws the supporting definitions and critical insights into smart cities from a series of papers presented at the 2009 Trans-national Conference on Creating Smart(er) Cities. What the papers all have in common is their desire to overcome the all too often…

  17. Photocatalytic Solutions Create Self-Cleaning Surfaces

    Science.gov (United States)

    2013-01-01

    A Stennis Space Center researcher investigating the effectiveness of photocatalytic materials for keeping the Center's buildings free of grime turned to a solution created by PURETi Inc. of New York City. Testing proved successful, and NASA and the company now share a Dual Use Technology partnership. PURETi's coatings keep surfaces clean and purify surrounding air, eliminating pollution, odors, and microbes.

  18. Creating sustainable empowering learning environments through ...

    African Journals Online (AJOL)

    Creating sustainable empowering learning environments through scholarship of engagement. ... South African Journal of Higher Education ... Abstract. The assumption grounding this issue of SAJHE is that; a university or any institution of higher learning comes to its fullness through serious engagement with the community.

  19. Creating Self-Portraits. ERIC Digest.

    Science.gov (United States)

    Redekopp, Dave E.; And Others

    Creating Self-Portraits is an individual and/or group career development tool designed to assess without testing. Researchers have found that testing can be counter-productive; once clients were labelled, they frequently stopped self-examination. A tool was needed that would help people understand themselves in a way that would encourage further…

  20. Creating the networking enterprises - logistics determinants

    Directory of Open Access Journals (Sweden)

    Ewa Kulińska

    2014-06-01

    Full Text Available Background: The article describes the determinants of creating network enterprises with peculiar consideration of logistic factors which are conditioning the organization of processes, exchange of resources and competences. On the basis of literature analysis, there is proposed a model of creating network enterprises. A model is verified in the application part of the thesis. Methods: Within the publication a literature review of submitted scope of the interest was presented, as well as the empirical research. A research substance attaches the enterprises created on the basis of the reactivation of organizations which has collapsed due to bankruptcy proceeding. The research was based upon direct interviews with employees of the net-forming entities. Results and conclusions: Results of the research shows that taking up the cooperation and net-cooperation was the only possibility for new entities to come into existence, that were  based upon old assets and human resources liquidated during bankruptcy proceeding. There was indentified many determinants of enterprises network cooperation, however due to the research a conclusion draws, that basic factors of creating network cooperation are those which are profit-achieving oriented.

  1. Creating by Reusing Learning Design Solutions

    NARCIS (Netherlands)

    Hernández-Leo, Davinia; Harrer, Andreas; Dodero, Juan Manuel; Asensio-Pérez, Juan; Burgos, Daniel

    2006-01-01

    Hernández-Leo, D., Harrer, A., Dodero, J. M., Asension-Pérez, J. I., & Burgos, D. (2006). Creating by reusing Learning Design solutions. Proceedings of 8th Simposo Internacional de Informática Educativa, León, Spain: IEEE Technical Committee on Learning Technology. Retrieved October 3rd, 2006, from

  2. Creating Brand India: Strategies, Issues, and Challenges

    National Research Council Canada - National Science Library

    Alok Chakrawal; Pratibha Goyal

    2016-01-01

    .... Bureaucracy, corruption, delay in clearance of business proposals, ethical standards and work culture, tax reforms, political interventions, socio-economic barriers, regionalism, etc. are some of the challenges that must be coped with. This article examines these various issues and challenges that must be overcome in creating Brand India.

  3. Creating Appropriate Graphics for Business Situations

    Science.gov (United States)

    Katz, Susan M.

    2008-01-01

    Charts and graphs are ubiquitous in business documents, and most students in the author's business communication courses are well aware that they need to be able to create many different types of data representation. Most of them have had a great deal of experience working with spreadsheet applications, and they know how to manipulate data and…

  4. Towards Creating Sustainable Ecotourism Interventions: Practical ...

    African Journals Online (AJOL)

    2017-05-01

    May 1, 2017 ... Using the Sustainable Livelihoods Concept and a qualitative approach, this study sought to understand ... Towards Creating Sustainable Ecotourism Interventions: Practical Lessons from Mesomagoro, Ghana. Africa, was .... as mortars, pestles, stools, drums chewing sticks, sponges and material for houses;.

  5. Selection of Reliable Reference Genes for Gene Expression Analysis under Abiotic Stresses in the Desert Biomass Willow, Salix psammophila.

    Science.gov (United States)

    Li, Jianbo; Jia, Huixia; Han, Xiaojiao; Zhang, Jin; Sun, Pei; Lu, Mengzhu; Hu, Jianjun

    2016-01-01

    Salix psammophila is a desert shrub willow that has extraordinary adaptation to abiotic stresses and plays an important role in maintaining local ecosystems. Moreover, S. psammophila is regarded as a promising biomass feedstock because of its high biomass yields and short rotation coppice cycle. However, few suitable reference genes (RGs) for quantitative real-time polymerase chain reaction (qRT-PCR) constrain the study on normalization of gene expression in S. psammophila until now. Here, we investigated the expression stabilities of 14 candidate RGs across tissue types and under four abiotic stress treatments, including heat, cold, salt, and drought treatments. After calculation of PCR efficiencies, three different software, NormFinder, geNorm, and BestKeeper were employed to analyze systematically the qRT-PCR data, and the outputs were merged by RankAggreg software. The optimal RGs selected for gene expression analysis were EF1α (Elongation factor-1 alpha) and OTU (OTU-like cysteine protease family protein) for different tissue types, UBC (Ubiquitin-conjugating enzyme E2) and LTA4H (Leukotriene A-4 hydrolase homolog) for heat treatment, HIS (Histone superfamily protein H3) and ARF2 (ADP-ribosylation factor 2) for cold treatment, OTU and ACT7 (Actin 7) for salt treatment, UBC and LTA4H for drought treatment. The expression of UBC, ARF2, and VHAC (V-type proton ATPase subunit C) varied the least across tissue types and under abiotic stresses. Furthermore, the relative genes expression profiles of one tissue-specific gene WOX1a (WUSCHEL-related homeobox 1a), and four stress-inducible genes, including Hsf-A2 (Heat shock transcription factors A2), CBF3 (C-repeat binding factor 3), HKT1 (High-Affinity K+ Transporter 1), and GST (Glutathione S-transferase), were conducted to confirm the validity of the RGs in this study. These results provided an important RGs application guideline for gene expression characterization in S. psammophila.

  6. Association of HOXA10, ZFPM2, and MMP2 genes with scrotal hernias evaluated via biological candidate gene analyses in pigs.

    Science.gov (United States)

    Zhao, Xia; Du, Zhi-Qiang; Vukasinovic, Natascha; Rodriguez, Fernanda; Clutter, Archie C; Rothschild, Max F

    2009-08-01

    To evaluate the associations between 14 biological candidate genes and scrotal hernias in pigs. 1,534 Pietrain-based pigs, including 692 individuals from 298 pig families and 842 male pigs without family information. Pigs were classified as affected or unaffected for scrotal hernias. Single nucleotide polymorphisms of candidate genes were analyzed via PCR assays and genotyped. Statistical analyses were performed on the family-trio and the case-control data. 2 genes involved in collagen metabolism (homeobox A10 [HOXA10] and matrix metalloproteinases 2 [MMP2]) and 1 gene encoding zinc finger protein multitype 2 (ZFPM2, important in the development of diaphragmatic hernia) were significantly associated with hernias. Pigs with these genotypes had high odds of developing scrotal hernias in the case and control groups (2 ZFPM2 variants: odds ratio, 4.3 [95% confidence interval, 2.78 to 6.64] and 4.45[95%confidenceinterval,2.88to6.88]). Anothergene, collagentypeII A 1(COL2A1),was potentially involved in hernia development. HOXA10, ZFPM2, MMP2, and COL2A1 could have important roles in pig hernia development and potentially be useful for marker-assisted selection in the pig industry. Pigs are used for the study of many human diseases because of their physiologic similarities. Genes associated with scrotal hernias in this study may be directly used in understanding the molecular mechanisms underlying this defect in humans.

  7. A Pituitary Homeobox 2 (Pitx2):microRNA-200a-3p:β-catenin Pathway Converts Mesenchymal Cells to Amelogenin-expressing Dental Epithelial Cells*

    Science.gov (United States)

    Sharp, Thad; Wang, Jianbo; Li, Xiao; Cao, Huojun; Gao, Shan; Moreno, Myriam; Amendt, Brad A.

    2014-01-01

    Pitx2, Wnt/β-catenin signaling, and microRNAs (miRs) play a critical role in the regulation of dental stem cells during embryonic development. In this report, we have identified a Pitx2:β-catenin regulatory pathway involved in epithelial cell differentiation and conversion of mesenchymal cells to amelogenin expressing epithelial cells via miR-200a. Pitx2 and β-catenin are expressed in the labial incisor cervical loop or epithelial stem cell niche, with decreased expression in the differentiating ameloblast cells of the mouse lower incisor. Bioinformatics analyses reveal that miR-200a-3p expression is activated in the pre-ameloblast cells to enhance epithelial cell differentiation. We demonstrate that Pitx2 activates miR-200a-3p expression and miR-200a-3p reciprocally represses Pitx2 and β-catenin expression. Pitx2 and β-catenin interact to synergistically activate gene expression during odontogenesis and miR-200a-3p attenuates their expression and directs differentiation. To understand how this mechanism controls cell differentiation and cell fate, oral epithelial and odontoblast mesenchymal cells were reprogrammed by a two-step induction method using Pitx2 and miR-200a-3p. Conversion to amelogenin expressing dental epithelial cells involved an up-regulation of the stem cell marker Sox2 and proliferation genes and decreased expression of mesenchymal markers. E-cadherin expression was increased as well as ameloblast specific factors. The combination of Pitx2, a regulator of dental stem cells and miR-200a converts mesenchymal cells to a fully differentiated dental epithelial cell type. This pathway and reprogramming can be used to reprogram mesenchymal or oral epithelial cells to dental epithelial (ameloblast) cells, which can be used in tissue repair and regeneration studies. PMID:25122764

  8. A pituitary homeobox 2 (Pitx2):microRNA-200a-3p:β-catenin pathway converts mesenchymal cells to amelogenin-expressing dental epithelial cells.

    Science.gov (United States)

    Sharp, Thad; Wang, Jianbo; Li, Xiao; Cao, Huojun; Gao, Shan; Moreno, Myriam; Amendt, Brad A

    2014-09-26

    Pitx2, Wnt/β-catenin signaling, and microRNAs (miRs) play a critical role in the regulation of dental stem cells during embryonic development. In this report, we have identified a Pitx2:β-catenin regulatory pathway involved in epithelial cell differentiation and conversion of mesenchymal cells to amelogenin expressing epithelial cells via miR-200a. Pitx2 and β-catenin are expressed in the labial incisor cervical loop or epithelial stem cell niche, with decreased expression in the differentiating ameloblast cells of the mouse lower incisor. Bioinformatics analyses reveal that miR-200a-3p expression is activated in the pre-ameloblast cells to enhance epithelial cell differentiation. We demonstrate that Pitx2 activates miR-200a-3p expression and miR-200a-3p reciprocally represses Pitx2 and β-catenin expression. Pitx2 and β-catenin interact to synergistically activate gene expression during odontogenesis and miR-200a-3p attenuates their expression and directs differentiation. To understand how this mechanism controls cell differentiation and cell fate, oral epithelial and odontoblast mesenchymal cells were reprogrammed by a two-step induction method using Pitx2 and miR-200a-3p. Conversion to amelogenin expressing dental epithelial cells involved an up-regulation of the stem cell marker Sox2 and proliferation genes and decreased expression of mesenchymal markers. E-cadherin expression was increased as well as ameloblast specific factors. The combination of Pitx2, a regulator of dental stem cells and miR-200a converts mesenchymal cells to a fully differentiated dental epithelial cell type. This pathway and reprogramming can be used to reprogram mesenchymal or oral epithelial cells to dental epithelial (ameloblast) cells, which can be used in tissue repair and regeneration studies. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. GENE EXPRESSION CHANGES AND ANTI-PROLIFERATIVE EFFECT OF NONI (Morinda citrifolia FRUIT EXTRACT ANALYSED BY REAL TIME-PCR

    Directory of Open Access Journals (Sweden)

    hermansyah hermansyah

    2017-05-01

    Full Text Available To elucidate the anti-proliferative effect of noni (Morinda citrifolia fruit extract for a Saccharomyces cerevisiae model organism, analysis of gene expression changes related to cell cycle associated with inhibition effect of noni fruit extract was carried out. Anti-proliferative of noni fruit extract was analyzed using gene expression changes of Saccharomyces cerevisiae (strains FY833 and BY4741.  Transcriptional analysis of genes that play a role in cell cycle was conducted by growing cells on YPDAde broth medium containing 1% (w/v noni fruit extract, and then subjected using quantitative real-time polymerase chain reaction (RT-PCR.  Transcriptional level of genes CDC6 (Cell Division Cycle-6, CDC20 (Cell Division Cycle-20, FAR1 (Factor ARrest-1, FUS3 (FUSsion-3, SIC1 (Substrate/Subunit Inhibitor of Cyclin-dependent protein kinase-1, WHI5 (WHIskey-5, YOX1 (Yeast homeobOX-1 and YHP1 (Yeast Homeo-Protein-1 increased, oppositely genes expression of DBF4 (DumbBell Forming, MCM1 (Mini Chromosome Maintenance-1 and TAH11 (Topo-A Hypersensitive-11 decreased, while the expression level of genes CDC7 (Cell Division Cycle-7, MBP1 (MIul-box Binding Protein-1 and SWI6 (SWItching deficient-6 relatively unchanged. These results indicated that gene expression changes might associate with anti-proliferative effect from noni fruit extract. These gene expressions changes lead to the growth inhibition of S.cerevisiae cell because of cell cycle defect.

  10. AUTOMATED TECHNIQUE FOR CREATING LITHOLOGIC LOG PLOTS

    Directory of Open Access Journals (Sweden)

    Kristijan Posavec

    2006-12-01

    Full Text Available Paper presents automated technique for creating lithologic log plots. Technique is based on three computer tools: Microsoft (MS Access program, LogPlot program, and Visual Basic (VB macros for MS Excel. MS Access ensures professional storage of lithologic data which can be in that way easier and faster entered, searched, updated, and also used for different purposes, while LogPlot provides tools for creating lithologic log plots. VB macros enable transfer of lithologic data from MS Access to LogPlot. Data stored in MS Access are exported in ASCII files which are later used by LogPlot for creation of lithologic log plots. Presented concept facilitates creation of lithologic log plots, and automated technique enables processing of a large number of data i.e. creation of lareg number lithologic log plots in a short period of time (the paper is published in Croatian.

  11. Creating a culture for information systems success

    CERN Document Server

    Belkhamza, Zakariya

    2015-01-01

    It has been widely reported that issues related to organizational context appear frequently in discussions of information systems success. The statement that the information system did not fit the behavioral context in an organization is often part of the explanation of why particular information system encountered unanticipated resistance and never met expectation. While this context has been intensively studied, we still lack evidence on how this organizational context is affecting the success of information system from a managerial action perspective. This type of managerial involvement is often neglected to the extent that it became an essential obstacle to organizational performance. The objective of Creating a Culture for Information Systems Success is to assist CIOs and IT managers on how to use their managerial actions to create a suitable cultural environment in the organization, which leads to a successful implementation of information systems. This  book will also provide guidelines fo...

  12. Creating and Editing Video to Accompany Manuscripts.

    Science.gov (United States)

    Gordon, Shayna L; Porto, Dennis A; Ozog, David M; Council, M Laurin

    2016-02-01

    The use of video can enhance the learning experience by demonstrating procedural techniques that are difficult to relay in writing. Several peer-reviewed journals allow publication of videos alongside articles to complement the written text. The purpose of this article is to instruct the dermatologic surgeon on how to create and edit a video using a smartphone, to accompany a article. The authors describe simple tips to optimize surgical videography. The video that accompanies this article further demonstrates the techniques described. Creating a surgical video requires little experience or equipment and can be completed in a modest amount of time. Making and editing a video to accompany a article can be accomplished by following the simple recommendations in this article. In addition, the increased use of video in dermatologic surgery education can enhance the learning opportunity.

  13. Novel device for creating continuous curvilinear capsulorhexis.

    Science.gov (United States)

    Soylak, Mustafa

    2016-01-01

    The purpose of this paper is to develop a novel capsulorhexis system. Mechatronics Laboratory, University of Erciyes and Kayseri Maya Eye Hospital. A 3D model was created and simulations were conducted to develop a new device which was designed, fabricated and tested for continuous curvilinear capsulorhexis (CCC). The name of this system is the electro-mechanical capsulorhexis system (EMCS). The 3D model was created by using a commercial design software and a 3D printer was used to fabricate the EMCS Finite element analysis and geometrical relation tests of the EMCS for different sized lenses were performed. The results show that the EMCS is a perfect solution for capsulorhexis surgeries, without mechanical or geometrical problems. The EMCS can open the anterior lens capsule more easily and effectively than manual CCC applications and needs less experience.

  14. How do entrepreneurs think they create value?

    DEFF Research Database (Denmark)

    Lyth Frederiksen, Dennis; Brem, Alexander

    2017-01-01

    The means with which entrepreneurs create and capture value can be difficult to get a comprehensive picture of. Looking at the tools they use can offer insights, and in this context, the book “The Lean Startup” by Eric Ries has received a tremendous amount of attention. Supposedly, many entrepren......The means with which entrepreneurs create and capture value can be difficult to get a comprehensive picture of. Looking at the tools they use can offer insights, and in this context, the book “The Lean Startup” by Eric Ries has received a tremendous amount of attention. Supposedly, many...... entrepreneurs have read the book and may have followed his advice. Hence, we investigate the merits and characteristics of the methods detailed by Ries through a comparison with leading theories and empirical evidence found in the scientific literature. The results indicate that overall the methods find...

  15. Designing value-creating supply chain networks

    CERN Document Server

    Martel, Alain

    2016-01-01

    Focusing on the design of robust value-creating supply chain networks (SCN) and key strategic issues related to the number; location, capacity and mission of supply chain facilities (plants, distribution centers) – as well as the network structure required to provide flexibility and resilience in an uncertain world – this book presents an innovative methodology for SCN reengineering that can be used to significantly improve the bottom line of supply chain dependent businesses. Providing readers with the tools needed to analyze and model value creation activities, Designing Value-Creating Supply Chain Networks examines the risks faced by modern supply chains, and shows how to develop plausible future scenarios to evaluate potential SCN designs. The design methods proposed are based on a visual representation formalism that facilitates the analysis and modeling of SCN design problems, book chapters incorporate several example problems and exercises which can be solved with Excel tools (Analysis tools and So...

  16. Creating interdisciplinary education within monodisciplinary structures

    DEFF Research Database (Denmark)

    Lindvig, Katrine; Lyall, Catherine; R. Meagher, Laura

    2017-01-01

    to the processes of creating interdisciplinary education initiatives within traditional monodisciplinary universities. In this study, we thus explore how interdisciplinary education and teaching emerge and develop within universities that have little or no established infrastructure to support interdisciplinarity......The literature on interdisciplinary higher education is influenced by two overall trends: one looks at the institutional level of specially designed interdisciplinary institutions, while the other assesses individual interdisciplinary educational activities. Much less attention is given....... Using qualitative data from a multi-part case study, we examine the development of diverse interdisciplinary educational efforts within a traditional faculty-structured university in order to map the ways in which interdisciplinary educational elements have been created, supported, challenged or even...

  17. Barriers to creating a secure MPI

    Energy Technology Data Exchange (ETDEWEB)

    Brightwell, R.; Greenberg, D.S.; Matt, B.J. [Sandia National Labs., Albuquerque, NM (United States); Davida, G.I. [Univ. of Wisconsin, Milwaukee, WI (United States). Dept. of Computer Sciences

    1997-08-01

    This paper explores some of the many issues in developing security enhanced MPI for embedded real-time systems supporting the Department of Defense`s Multi-level Security policy (DoD MLS) are presented along with the preliminary design for such an MPI variant. In addition some of the many issues that need to be addressed in creating security enhanced versions of MPI for other domains are discussed. 19 refs.

  18. Creating an Asthma-Friendly School

    Centers for Disease Control (CDC) Podcasts

    2007-11-08

    This podcast features real-life success stories of students with asthma who, thanks to their schools' implementation of asthma-friendly policies and programs, now have their asthma under control.  Created: 11/8/2007 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Adolescent and School Health (DASH).   Date Released: 5/20/2008.

  19. Climate Change Creates Trade Opportunity in India

    OpenAIRE

    Dinda, Soumyananda

    2013-01-01

    Climate change is an emerging challenge to developing economy like India however it also creates opportunity to grow through climate friendly goods production and new direction of trade. This paper focuses India’s potential export trade in climate friendly goods. The estimated gravity model is defined as the potential trade and potential trade gap is measured as how well a bilateral trade flow performs relative to the mean as predicted by the model. Potential trade gap means that actual trade...

  20. Cognitive abilities and creating metaphorical names

    Directory of Open Access Journals (Sweden)

    Avanesyan, Marina O.

    2016-06-01

    Full Text Available The cognitive processing of metaphor creation has been insufficiently investigated. Creating metaphors requires the ability to work in a fantastic, impossible context, using symbolic and associative means to express oneís thoughts. It has been shown recently that intelligence plays an important role in the creation of metaphors, but it is not the main factor in determining their success. The present research explores the roles of conceptual abilities, categorical abilities, and flexibility (as the factor creativity in metaphor creation. Participants (n = 38 young adults were asked to come up with names for three photos, without any special instruction to create metaphors. To classify conceptual abilities we used ìConceptual Synthesisî (M. A. Kholodnaya, 2012; to measure categorical ability we used the subtest ìSimilaritiesî (D. Wechsler, 1955; to identify the role of creativity in the metaphor process we used the test of ìUnusual Usesî (J. P. Guilford, 1960. The creation of complex metaphorical names was associated with a tendency to create highly organized mental structures and to retain them within the general semantic context (r = 0.344, p < 0.05. The tendency to create single-level situational connections was associated with a tendency to give specific names to photos (r = 0.475, p < 0.01. Photographic images proved out to be fruitful stimuli to investigate the processing of visual information. We developed a preliminary classification of names: 1 concrete; 2 situational; 3 abstract; 4 metaphorical (M1 and M2. We identified two types of metaphorical names — perceptual and complex metaphors — that relate to conceptual abilities in different ways. It is inaccurate to speak about a general concept of ìmetaphorical abilitiesî; we should differentiate the psychological mechanisms that lie at their base.

  1. How to create a UX story

    OpenAIRE

    Michailidou, Ioanna; von Saucken, Constantin; Kremer, Simon; Lindemann, Udo

    2014-01-01

    Narratives are a tool used in many disciplines. In the area of User Experience Design (UXD), in particular, a storytelling approach can be applied during the whole design process to improve the quality of developed concepts regarding user experience (UX). Furthermore stories support designers in ex-ploring and communicating their new concept ideas. However, the guidelines on how to create a story are either too abstract or do not focus on the experience elements of the interaction. This paper...

  2. Creating an international curriculum: why and how?

    OpenAIRE

    Magne, PJ

    2015-01-01

    Today’s globally interconnected world offers a vast array of new opportunities, but it has simultaneously created a need for greater intercultural understanding (Koehne, 2006). The current rise of internationalisation policy and strategy suggests that HEIs recognise the part they need to play to enable graduates to operate effectively in the 21st century (Bremer & Van-der-Wende, 1995; Knight & Yorke, 2003; Shiel, 2006) Whilst it is would be irresponsible to ignore the challenges posed by inte...

  3. Can cognitive science create a cognitive economics?

    Science.gov (United States)

    Chater, Nick

    2015-02-01

    Cognitive science can intersect with economics in at least three productive ways: by providing richer models of individual behaviour for use in economic analysis; by drawing from economic theory in order to model distributed cognition; and jointly to create more powerful 'rational' models of cognitive processes and social interaction. There is the prospect of moving from behavioural economics to a genuinely cognitive economics. Copyright © 2014. Published by Elsevier B.V.

  4. Creating an Online Training Module on RDM

    OpenAIRE

    Guy, Marieke; Cope, Jez; Pink, Catherine

    2013-01-01

    Creating an Online Training Module on Research Data Management for the University of BathResearch 360In 2011 the University of Bath was awarded funding by the JISC Managing Research Data Programme to support and develop Research Data Management across the institution.The Research 360: Managing data across the institutional research lifecycle project (Research360@Bath) will develop policies, infrastructure and training resources to help researchers at the University of Bath to get the most out...

  5. Creating social impact with sport events

    OpenAIRE

    Hover, P.; Dijk, B.; Breedveld, K.; Eekeren, F.J.A. van; Slender, H.

    2016-01-01

    All over the world, sport events are seen as significant tools for creating positive social impact. This is understandable, as sport events have the power to attract enthusiastic participants, volunteers and to reach large audiences of visitors and followers via (social) media. Outbursts of excitement, pleasure and feelings of camaraderie are experienced among millions of people in the case of mega events. Still, a fairly large section of the population does not care that much for sports. Som...

  6. Creating an Innovative Attitude at Work

    DEFF Research Database (Denmark)

    Eriksen, Kaare; Tollestrup, Christian

    2012-01-01

    or tacit knowledge among colleagues in a complex organization. The set-up of the project was organized as a series of workshops also involving design students, and the paper outlines the difficulties and results from the initiative. The project showed that designerly methods can be very effective...... in creating the participants’ positive innovative approach, but also that it is a challenge to translate such methods and vocabulary, and more trained designerly assistance might need to be applied in the process....

  7. Public libraries: places creating social capital?

    OpenAIRE

    Vårheim, Andreas

    2009-01-01

    Purpose – The purpose of this paper is to show why studies of public libraries, regarding their possible contribution in creating social capital, are important for social capital research in general, and are important for library practice in particular. Design/methodology/approach – Building on the latest theoretical developments and empirical findings of social capital research, the role of the public library as a potential creator of social capital is discussed. Findings from both quantita...

  8. Creating marketing strategies for higher education institutions

    OpenAIRE

    Lidia Białoń

    2015-01-01

    The article presents a thesis that the primary premise of creating marketing strategies for higher education institution is a three-dimensional notion of marketing. The first dimension lies in the theoretical notions of the essence of marketing, including the transactional marketing (1.0), relationship marketing (2.0) and spiritual marketing (3.0). The second dimension is formed by methods of marketing research and accurate notions of marketing, while the third are channels of marketing infor...

  9. Digital gene expression tag profiling of bat digits provides robust candidates contributing to wing formation

    Directory of Open Access Journals (Sweden)

    Young Rebecca L

    2010-11-01

    Full Text Available Abstract Background As the only truly flying mammals, bats use their unique wing - consisting of four elongated digits (digits II-V connected by membranes - to power their flight. In addition to the elongated digits II-V, the forelimb contains one shorter digit (digit I that is morphologically similar to the hindlimb digits. Here, we capitalized on the morphological variation among the bat forelimb digits to investigate the molecular mechanisms underlying digit elongation and wing formation. Using next generation sequencing technology, we performed digital gene expression tag profiling (DGE-tag profiling of developing digits in a pooled sample of two Myotis ricketti and validated our sequencing results using real-time quantitative PCR (RT-qPCR of gene expression in the developing digits of two Hipposideros armiger. Results Among hundreds of genes exhibiting significant differences in expression between the short and long digits, we highlight 14 genes most related to digit elongation. These genes include two Tbx genes (Tbx3 and Tbx15, five BMP pathway genes (Bmp3, RGMB, Smad1, Smad4 and Nog, four Homeobox genes (Hoxd8, Hoxd9, Hoxa1 and Satb1, and three other genes (Twist1, Tmeff2 and Enpp2 related to digit malformations or cell proliferation. In addition, our results suggest that Tbx4 and Pitx2 contribute to the morphological similarity and five genes (Acta1, Tnnc2, Atp2a1, Hrc and Myoz1 contribute to the functional similarity between the thumb and hindlimb digits. Conclusions Results of this study not only implicate many developmental genes as robust candidates underlying digit elongation and wing formation in bats, but also provide a better understanding of the genes involved in autopodial development in general.

  10. Teleoperación Plataforma Móvil Irobot Create

    Directory of Open Access Journals (Sweden)

    William Quispe

    2013-11-01

    Full Text Available El tema de investigación está enfocado en la Teleoperación de la plataforma móvil Irobot Create, esta plataforma móvil es distribuida por iRobot Corporation. La teleoperación consiste en enviar comandos a dicha plataforma para la ejecución de movimientos, esto mediante la utilización de un HMI basada en PC, así también la interface de teleoperación es capaz de mostrar imágenes del entorno de la plataforma móvil con ayuda de una cámara analógica montada sobre esta.

  11. Oncogenes create a unique landscape of fragile sites.

    Science.gov (United States)

    Miron, Karin; Golan-Lev, Tamar; Dvir, Raz; Ben-David, Eyal; Kerem, Batsheva

    2015-05-11

    Recurrent genomic instability in cancer is attributed to positive selection and/or the sensitivity of specific genomic regions to breakage. Among these regions are fragile sites (FSs), genomic regions sensitive to replication stress conditions induced by the DNA polymerase inhibitor aphidicolin. However, the basis for the majority of cancer genomic instability hotspots remains unclear. Aberrant oncogene expression induces replication stress, leading to DNA breaks and genomic instability. Here we map the cytogenetic locations of oncogene-induced FSs and show that in the same cells, each oncogene creates a unique fragility landscape that only partially overlaps with aphidicolin-induced FSs. Oncogene-induced FSs colocalize with cancer breakpoints and large genes, similar to aphidicolin-induced FSs. The observed plasticity in the fragility landscape of the same cell type following oncogene expression highlights an additional level of complexity in the molecular basis for recurrent fragility in cancer.

  12. Gene Therapy

    Science.gov (United States)

    Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

  13. Gene duplication as a major force in evolution

    Indian Academy of Sciences (India)

    Gene duplication is an important mechanism for acquiring new genes and creating genetic novelty in organisms. Many new gene functions have evolved through gene duplication and it has contributed tremendously to the evolution of developmental programmes in various organisms. Gene duplication can result from ...

  14. Construction Of An Optimized Lentiviral Vector Containing Pdx-1 Gene For Transduction Of Stem Cells Towards Gene Therapy Diabetes Type 1

    Directory of Open Access Journals (Sweden)

    S Rahmati

    2013-02-01

    Full Text Available Abstract Background & aim: Nowadays, most of gene therapy protocols are performed by lentiviral vectors. One of the most important factors which is involved in pancreas development and transcription of insulin gene is pancreatic & duodenal homeobox 1 (PDX-1 transcription factor. The goal of this study was to optimize a lentiviral construct, containing pdx-1 gene, to transfect stem cells towards gene therapy of type-1 diabetes. Methods: In this experimental study, first, the pdx-1 gene was multiplied by PCR from pcDNA3.1-pdx-1 and cloned into pTG19-T vector. Then, pdx-1 was subcloned on upstream of IRES-EGFP gene into IRES2-EGFP vector. At the next step, the cloned parts of IRES-EGFP and pdx-1 were isolated and cloned into the lentiviral expression vector pSINTREM in upstream of TRE-CMV gene. After sequencing, final construct was transfected into HEK 293 cells and gene expression of pdx-1 was evaluated using flow cytometry analysis and reverse fluorescent microscopy. Results: Flow cytometry results and inverted fluorescent microscopy observing showed that pdx-1 and GFP genes are expressed in cells transfected with final recombinant construct. Conclusion: Regarding the design of this construct, to ensure long time expression with higher in vivo and in vitro expression efficiency for stem cells and also use of Tet on induced optimized system, it seems that the current construct can be among the best ones to transfect stem cells. Key words: Gene therapy, Diabetes, Stem cells

  15. Sequential Binding of MEIS1 and NKX2-5 on the Popdc2 Gene: A Mechanism for Spatiotemporal Regulation of Enhancers during Cardiogenesis

    Directory of Open Access Journals (Sweden)

    Laurent Dupays

    2015-10-01

    Full Text Available The homeobox transcription factors NKX2-5 and MEIS1 are essential for vertebrate heart development and normal physiology of the adult heart. We show that, during cardiac differentiation, the two transcription factors have partially overlapping expression patterns, with the result that as cardiac progenitors from the anterior heart field differentiate and migrate into the cardiac outflow tract, they sequentially experience high levels of MEIS1 and then increasing levels of NKX2-5. Using the Popdc2 gene as an example, we also show that a significant proportion of target genes for NKX2-5 contain a binding motif recognized by NKX2-5, which overlaps with a binding site for MEIS1. Binding of the two factors to such overlapping sites is mutually exclusive, and this provides a simple regulatory mechanism for spatial and temporal synchronization of a common pool of targets between NKX2-5 and MEIS1.

  16. Characterization of Transcriptional Repressor Gene MSX1 Variations for Possible Associations with Congenital Heart Diseases.

    Directory of Open Access Journals (Sweden)

    Fei-Feng Li

    Full Text Available The human heart consists of several cell types with distinct lineage origins. Interactions between these cardiac progenitors are very important for heart formation. The muscle segment homeobox gene family plays a key role in the cell morphogenesis and growth, controlled cellular proliferation, differentiation, and apoptosis, but the relationships between the genetic abnormalities and CHD phenotypes still remain largely unknown. The aim of this work was to evaluate variations in MSX1 and MSX2 for their possible associations with CHD.We sequenced the MSX1 and MSX2 genes for 300 Chinese Han CHD patients and 400 normal controls and identified the variations. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0. The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE.Six variations rs4647952, rs2048152, rs4242182, rs61739543, rs111542301 and rs3087539 were identified in the MSX2 gene, but the genetic heterozygosity of those SNPs was very low. In contrast, the genetic heterozygosity of two variations rs3821949 near the 5'UTR and rs12532 within 3'UTR of the MSX1 gene was considerably high. Statistical analyses showed that rs3821949 and rs12532 were associated with the risk of CHD (specifically VSD.The SNPs rs3821949 and rs12532 in the MSX1 gene were associated with CHD in Chinese Han populations.

  17. Differential gene expression patterns during embryonic development of sea urchin exposed to triclosan.

    Science.gov (United States)

    Hwang, Jinik; Suh, Sung-Suk; Park, Mirye; Park, So Yun; Lee, Sukchan; Lee, Taek-Kyun

    2017-02-01

    Triclosan (TCS; 2,4,4'-trichloro-2'-hydroxydiphenyl ether) is a broad-spectrum antibacterial agent used in common industrial, personal care and household products which are eventually rinsed down the drain and discharged with wastewater effluent. It is therefore commonly found in the aquatic environment, leading to the continual exposure of aquatic organisms to TCS and the accumulation of the antimicrobial and its harmful degradation products in their bodies. Toxic effects of TCS on reproductive and developmental progression of some aquatic organisms have been suggested but the underlying molecular mechanisms have not been defined. We investigated the expression patterns of genes involved in the early development of TCS-treated sea urchin Strongylocentrotus nudus using cDNA microarrays. We observed that the predominant consequence of TCS treatment in this model system was the widespread repression of TCS-modulated genes. In particular, empty spiracles homeobox 1 (EMX-1), bone morphogenic protein, and chromosomal binding protein genes showed a significant decrease in expression in response to TCS. These results suggest that TCS can induce abnormal development of sea urchin embryos through the concomitant suppression of a number of genes that are necessary for embryonic differentiation in the blastula stage. Our data provide new insight into the crucial role of genes associated with embryonic development in response to TCS. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 426-433, 2017. © 2016 Wiley Periodicals, Inc.

  18. Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sang-Keun; Yoon, Joonseon [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seou1 151-742 (Korea, Republic of); Choi, Gyung Ja [Screening Division, Korea Research Institute of Chemical Technology, Daejeon 305-600 (Korea, Republic of); Jang, Hyun A; Kwon, Suk-Yoon [Korea Research Institute of Bioscience and Biotechnology, Yusung, Daejeon 305-600 (Korea, Republic of); Choi, Doil, E-mail: doil@snu.ac.kr [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seou1 151-742 (Korea, Republic of)

    2013-12-06

    Highlights: •The CaHB1 is a nuclear factor, belonging to HD-Zip proteins. •SA and ET, as signal molecules, modulate CaHB1-mediated responses. •Overexpression of CaHB1 in tomato resulted in a thicker cell wall. •CaHB1-transgenic tomato confers resistance to Phytophthora infestans. •CaHB1 enhanced tolerance to saline stress in tomato. -- Abstract: Homeodomain-leucine zipper (HD-Zip) family proteins are unique to plants, but little is known about their role in defense responses. CaHB1 is a nuclear factor in peppers, belonging to subfamily II of HD-Zip proteins. Here, we determined the role of CaHB1 in the defense response. CaHB1 expression was induced when pepper plants were challenged with Phytophthora capsici, a plant pathogen to which peppers are susceptible, or environmental stresses such as drought and salt stimuli. CaHB1 was also highly expressed in pepper leaves following application of SA, whereas ethephon and MeJA had a moderate effect. To further investigate the function of CaHB1 in plants, we performed gain-of-function study by overexpression of CaHB1 in tomato. CaHB1-transgenic tomatoes showed significant growth enhancement including increased leaf thickness and enlarged cell size (1.8-fold larger than control plants). Microscopic analysis revealed that leaves from CaHB1-transgenic plants had thicker cell walls and cuticle layers than those from controls. Moreover, CaHB1-transgenic plants displayed enhanced resistance against Phytophthora infestans and increased tolerance to salt stress. Additionally, RT-PCR analysis of CaHB1-transgenic tomatoes revealed constitutive up-regulation of multiple genes involved in plant defense and osmotic stress. Therefore, our findings suggest roles for CaHB1 in development, salt stress, and pathogen defense.

  19. Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense.

    Science.gov (United States)

    Oh, Sang-Keun; Yoon, Joonseon; Choi, Gyung Ja; Jang, Hyun A; Kwon, Suk-Yoon; Choi, Doil

    2013-12-06

    Homeodomain-leucine zipper (HD-Zip) family proteins are unique to plants, but little is known about their role in defense responses. CaHB1 is a nuclear factor in peppers, belonging to subfamily II of HD-Zip proteins. Here, we determined the role of CaHB1 in the defense response. CaHB1 expression was induced when pepper plants were challenged with Phytophthora capsici, a plant pathogen to which peppers are susceptible, or environmental stresses such as drought and salt stimuli. CaHB1 was also highly expressed in pepper leaves following application of SA, whereas ethephon and MeJA had a moderate effect. To further investigate the function of CaHB1 in plants, we performed gain-of-function study by overexpression of CaHB1 in tomato. CaHB1-transgenic tomatoes showed significant growth enhancement including increased leaf thickness and enlarged cell size (1.8-fold larger than control plants). Microscopic analysis revealed that leaves from CaHB1-transgenic plants had thicker cell walls and cuticle layers than those from controls. Moreover, CaHB1-transgenic plants displayed enhanced resistance against Phytophthora infestans and increased tolerance to salt stress. Additionally, RT-PCR analysis of CaHB1-transgenic tomatoes revealed constitutive up-regulation of multiple genes involved in plant defense and osmotic stress. Therefore, our findings suggest roles for CaHB1 in development, salt stress, and pathogen defense. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Create a new vision for indigenous development

    Energy Technology Data Exchange (ETDEWEB)

    Chavez Alba, Rafael; Sanchez Arancibia, Oscar Armando [TRANSIERRA S.A., Santa Cruz (Bolivia)

    2009-07-01

    Transierra is a Bolivian company created in the year 2000 with the goal of transporting natural gas from the fields of San Alberto and San Antonio, in Tarija, to the Rio Grande Gas Compression Plant in Santa Cruz, for export to Brazil. Transierra has implemented a Social Action Plan, which allowed it to execute more than 800 community projects for the benefit of over 40 thousand families living in it's area of influence, with the presence of 146 indigenous communities, generally lagging behind in economic and productive life in the region and country. The Support Program to Guarani Development Plans (PA-PDG) is part of the Social Plan and is part of a long-term agreement signed between Transierra and indigenous organizations. The program has implemented more than one hundred projects for productive development, health, education, cultural revaluation, and strengthening organizational infrastructure, generating huge benefits in improving the living conditions of thousands of families of the Guarani people. This year a unique initiative was created with 4 Indigenous Captains and with the support of the International Finance Corporation (World Bank Group), including Business Plans to promote sustainable economic growth, created productive economic cycles involving improvements to the production and productivity to enter the commercial distribution of local and national markets. These four initiatives have meant a shift in the implementation and is helping to generate new dynamics in production, in addition to capturing significant resources from public and private investment, laying the groundwork for the improvement of the incomes and quality of life of its beneficiaries. (author)

  1. 10 ways to create shareholder value.

    Science.gov (United States)

    Rappaport, Alfred

    2006-09-01

    Executives have developed tunnel vision in their pursuit of shareholder value, focusing on short-term performance at the expense of investing in long-term growth. It's time to broaden that perspective and begin shaping business strategies in light of the competitive landscape, not the shareholder list. In this article, Alfred Rappaport offers ten basic principles to help executives create lasting shareholder value. For starters, companies should not manage earnings or provide earnings guidance; those that fail to embrace this first principle of shareholder value will almost certainly be unable to follow the rest. Additionally, leaders should make strategic decisions and acquisitions and carry assets that maximize expected value, even if near-term earnings are negatively affected as a result. During times when there are no credible value-creating opportunities to invest in the business, companies should avoid using excess cash to make investments that look good on the surface but might end up destroying value, such as ill-advised, overpriced acquisitions. It would be better to return the cash to shareholders in the form of dividends and buybacks. Rappaport also offers guidelines for establishing effective pay incentives at every level of management; emphasizes that senior executives need to lay their wealth on the line just as shareholders do; and urges companies to embrace full disclosure, an antidote to short-term earnings obsession that serves to lessen investor uncertainty, which could reduce the cost of capital and increase the share price. The author notes that a few types of companies--high-tech start-ups, for example, and severely capital-constrained organizations--cannot afford to ignore market pressures for short-term performance. Most companies with a sound, well-executed business model, however, could better realize their potential for creating shareholder value by adopting the ten principles.

  2. How leaders create and use networks.

    Science.gov (United States)

    Ibarra, Herman; Hunter, Mark

    2007-01-01

    Most people acknowledge that networking-creating a fabric of personal contacts to provide support, feedback, insight, and resources--is an essential activity for an ambitious manager. Indeed, it's a requirement even for those focused simply on doing their current jobs well. For some, this is a distasteful reality. Working through networks, they believe,means relying on "who you know" rather than "what you know"--a hypocritical, possibly unethical, way to get things done. But even people who understand that networking is a legitimate and necessary part of their jobs can be discouraged by the payoff--because they are doing it in too limited a fashion. On the basis of a close study of 30 emerging leaders, the authors outline three distinct forms of networking. Operational networking is geared toward doing one's assigned tasks more effectively. It involves cultivating stronger relationships with colleagues whose membership in the network is clear; their roles define them as stakeholders. Personal networking engages kindred spirits from outside an organization in an individual's efforts to learn and find opportunities for personal advancement. Strategic networking puts the tools of networking in the service of business goals. At this level, a manager creates the kind of network that will help uncover and capitalize on new opportunities for the company. The ability to move to this level of networking turns out to be a key test of leadership. Companies often recognize that networks are valuable, andthey create explicit programs to support them. But typically these programs facilitate only operational networking. Likewise, industry associations provide formal contexts for personal networking. The unfortunate effect is to give managers the impression that they know how to network and are doing so sufficiently. A sidebar notes the implication for companies' leadership development initiatives: that teaching strategic networking skills will serve their aspiring leaders and

  3. Workshop: Creating Your Institutional Research Repository

    KAUST Repository

    Grenz, Daryl M.

    2016-11-08

    In 2002, the Scholarly Publishing and Academic Resources Coalition (SPARC) proposed the concept of an institutional repository to simultaneously disrupt and enhance the state of scholarly communications in the academic world. Thirteen years later, thousands of universities and other institutions have answered this call, but many more have not due to gaps in budgets, awareness and, most of all, practical guidance on creating an institutional repository. This workshop provides you with an essential primer on what it takes to establish a fully-functioning institutional repository. Every aspect of the process will be covered, including policies, procedures, staffing guidelines, workflows and repository technologies.

  4. Creating environments that foster academic integrity.

    Science.gov (United States)

    Tippitt, Michelle Pixley; Ard, Nell; Kline, Juanita Reese; Tilghman, Joan; Chamberlain, Barbara; Meagher, P Gail

    2009-01-01

    A number of studies related to academic dishonesty within the nursing student population have been published; however, little has been written in the nursing literature regarding academic integrity and means of promoting this value. In addition to the many short-term solutions to prevent cheating and dissuade academic misconduct that are offered, solutions that promote long-term affective changes underlying the acquisition of academic integrity are needed. This article provides a context for discussions related to academic integrity, explores issues facing faculty when dealing with this challenge, and offers short-term and long-term strategies for creating environments that foster academic integrity.

  5. Creating a Library Database Search using Drupal

    Directory of Open Access Journals (Sweden)

    Danielle M. Rosenthal

    2010-06-01

    Full Text Available When Florida Gulf Coast University Library was faced with having to replace its database locator, they needed to find a low-cost, non-staff intensive replacement for their 350 plus databases search tool. This article details the development of a library database locator, based on the methods described in Leo Klein’s “Creating a Library Database Page using Drupal” online presentation. The article describes how the library used Drupal along with several modules, such as CCK, Views, and FCKeditor. It also discusses various Drupal search modules that were evaluated during the process.

  6. Creating an organizational climate for multiculturalism.

    Science.gov (United States)

    Bruhn, J G

    1996-06-01

    Multiculturism is an ideal goal for our society, its organizations, and its institutions, involving a continuous process of education and change within organizations. Multiculturalism begins with diversity and requires various steps to achieve changes in attitudes, behaviors, and values. The leadership of organizations must not only commit to diversification, but they must participate in it and reward its efforts. Diversification should be managed by creating a climate of open participation, feedback, and control at the lower organizational levels. To micromanage the process of becoming diverse increases resistance and paranoia and counters educational efforts.

  7. Does the New Economy Create Higher Productivity?

    DEFF Research Database (Denmark)

    Dilling-Hansen, Mogens; Madsen, Erik Strøjer; Smith, Valdemar

    2002-01-01

    The rapid and continuous growth in the US in the 1990s and the simultaneous boom in the IT industry created the concept "The New Economy". What connects the two phenomena is that the IT industry alone is considered productive, and increased productivity in other industries, as a result of increased...... IT use, has brought focus on the IT industry as a catalyst for growth. The Danish Ministry of Finance (2001) points out general increased productivity in Denmark at macro level and this increase is said to be a result of increased IT use. The question is, however, if the influence of IT investments...

  8. Do Treasure Islands Create Firm Value?

    DEFF Research Database (Denmark)

    Lai, Tat-kei; Ng, Travis

    They do! Otherwise, their use would not have been so prevalent among firms. How much firm value they create, however, is still an open question. Exploiting a political event in the U.K. that suddenly raised the cost of using tax havens, we find that there was a 0.87% reduction in cumulative...... abnormal return (CAR) among the sampled firms, corresponding to about £532 million in market capitalization. The firms of stronger corporate governance registered a stronger reduction in CAR. A simple linear extrapolation suggests that the firm value contributed by tax havens can be as much as £31 billion....

  9. Green electronics manufacturing creating environmental sensible products

    CERN Document Server

    Wang, John X

    2012-01-01

    Going ""green"" is becoming a major component of the mission for electronics manufacturers worldwide. While this goal seems simplistic, it poses daunting dilemmas. Yet, to compete effectively in the global economy, manufacturers must take the initiative to drive this crucial movement. Green Electronics Manufacturing: Creating Environmental Sensible Products provides you with a complete reference to design, develop, build, and install an electronic product with special consideration for the product's environmental impacts during its whole life cycle. The author discusses how to integrate the st

  10. Creating Posters for Effective Scientific Communication.

    Science.gov (United States)

    Bavdekar, Sandeep B; Vyas, Shruti; Anand, Varun

    2017-08-01

    A scientific poster is a summary of one's research that is presented in a visually engaging manner. Posters are presented as a means of short and quick scientific communications at conferences and scientific meetings. Presenting posters has advantages for the presenters and for conference attendees and organizers. It also plays a part in dissemination of research findings and furthering science. An effective poster is the one that focuses on a single message and conveys it through a concise and artistically attractive manner. This communication intends to provide tips on creating an effective poster to young scientists. © Journal of the Association of Physicians of India 2011.

  11. Short stature homeobox-containing gene duplication on the der(X) chromosome in a female with 45,X/46,X, der(X), gonadal dysgenesis, and tall stature

    National Research Council Canada - National Science Library

    Ogata, T; Kosho, T; Wakui, K; Fukushima, Y; Yoshimoto, M; Miharu, N

    2000-01-01

    .... Growth assessment revealed that she had a low normal height until her early teens, but continued to grow with a nearly constant height velocity in her late teens, attaining a final height of 172 cm (+ 2.9 SD...

  12. Short Stature Homeobox-Containing Gene Duplication on the der(X) Chromosome in a Female with 45,X/46,X, der(X), Gonadal Dysgenesis, and Tall Stature1

    National Research Council Canada - National Science Library

    Ogata, Tsutomu; Kosho, Tomoki; Wakui, Keiko; Fukushima, Yoshimitsu; Yoshimoto, Manami; Miharu, Norio

    2000-01-01

    .... Growth assessment revealed that she had a low normal height until her early teens, but continued to grow with a nearly constant height velocity in her late teens, attaining a final height of 172 cm (+2.9 sd...

  13. Pathways of aging: comparative analysis of gene signatures in replicative senescence and stress induced premature senescence.

    Science.gov (United States)

    Kural, Kamil C; Tandon, Neetu; Skoblov, Mikhail; Kel-Margoulis, Olga V; Baranova, Ancha V

    2016-12-28

    In culturing normal diploid cells, senescence may either happen naturally, in the form of replicative senescence, or it may be a consequence of external challenges such as oxidative stress. Here we present a comparative analysis aimed at reconstruction of molecular cascades specific for replicative (RS) and stressinduced senescence (SIPS) in human fibroblasts. An involvement of caspase-3/keratin-18 pathway and serine/threonine kinase Aurora A/ MDM2 pathway was shared between RS and SIPS. Moreover, stromelysin/MMP3 and N-acetylglucosaminyltransferase enzyme MGAT1, which initiates the synthesis of hybrid and complex Nglycans, were identified as key orchestrating components in RS and SIPS, respectively. In RS only, Aurora-B driven cell cycle signaling was deregulated in concert with the suppression of anabolic branches of the fatty acids and estrogen metabolism. In SIPS, Aurora-B signaling is deprioritized, and the synthetic branches of cholesterol metabolism are upregulated, rather than downregulated. Moreover, in SIPS, proteasome/ubiquitin ligase pathways of protein degradation dominate the regulatory landscape. This picture indicates that SIPS proceeds in cells that are actively fighting stress which facilitates premature senescence while failing to completely activate the orderly program of RS. The promoters of genes differentially expressed in either RS or SIPS are unusually enriched by the binding sites for homeobox family proteins, with particular emphasis on HMX1, IRX2, HDX and HOXC13. Additionally, we identified Iroquois Homeobox 2 (IRX2) as a master regulator for the secretion of SPP1-encoded osteopontin, a stromal driver for tumor growth that is overexpressed by both RS and SIPS fibroblasts. The latter supports the hypothesis that senescence-specific de-repression of SPP1 aids in SIPS-dependent stromal activation. Reanalysis of previously published experimental data is cost-effective approach for extraction of additional insignts into the functioning of

  14. Creating the Medical Schools of the Future.

    Science.gov (United States)

    Skochelak, Susan E; Stack, Steven J

    2017-01-01

    Despite wide consensus on needed changes in medical education, experts agree that the gap continues to widen between how physicians are trained and the future needs of our health care system. A new model for medical education is needed to create the medical school of the future. The American Medical Association (AMA) is working to support innovative models through partnerships with medical schools, educators, professional organizations, and accreditors. In 2013, the AMA designed an initiative to support rapid innovation among medical schools and disseminate the ideas being tested to additional medical schools. Awards of $1 million were made to 11 medical schools to redesign curricula for flexible, individualized learning pathways, measure achievement of competencies, develop new assessment tools to test readiness for residency, and implement new models for clinical experiences within health care systems. The medical schools have partnered with the AMA to create the AMA Accelerating Change in Medical Education Consortium, working together to share prototypes and participate in a national evaluation plan. Most of the schools have embarked on major curriculum revisions, replacing as much as 25% of the curriculum with new content in health care delivery and health system science in all four years of training. Schools are developing new certification in quality and patient safety and population management. In 2015, the AMA invited 21 additional schools to join the 11 founding schools in testing and disseminating innovation through the consortium and beyond.

  15. Creating Sister Cities: An Exchange Across Hemispheres

    Science.gov (United States)

    Adams, M. T.; Cabezon, S. A.; Hardy, E.; Harrison, R. J.

    2008-06-01

    Sponsored by Associated Universities, Inc. (AUI) and the National Radio Astronomy Observatory (NRAO), this project creates a cultural and educational exchange program between communities in South and North America, linking San Pedro de Atacama in Chile and Magdalena, New Mexico in the United States. Both communities have similar demographics, are in relatively undeveloped regions of high-elevation desert, and are located near major international radio astronomy research facilities. The Atacama Large Millimeter/submillimeter Array (ALMA) is just 40 km east of San Pedro; the Very Large Array (VLA) is just 40 km west of Magdalena. In February 2007, the Mayor of San Pedro and two teachers visited Magdalena for two weeks; in July 2007 three teachers from Magdalena will visit San Pedro. These visits enable the communities to lay the foundation for a permanent, unique partnership. The teachers are sharing expertise and teaching methodologies for physics and astronomy. In addition to creating science education opportunities, this project offers students linguistic and cultural connections. The town of San Pedro, Chile, hosts nearly 100,000 tourists per year, and English language skills are highly valued by local students. Through exchanges enabled by email and distance conferencing, San Pedro and Magdalena students will improve English and Spanish language skills while teaching each other about science and their respective cultures. This poster describes the AUI/NRAO Sister Cities program, including the challenges of cross-cultural communication and the rewards of interpersonal exchanges between continents and cultures.

  16. Cell adhesion pattern created by OSTE polymers.

    Science.gov (United States)

    Liu, Wenjia; Li, Yiyang; Ding, Xianting

    2017-04-24

    Engineering surfaces with functional polymers is a crucial issue in the field of micro/nanofabrication and cell-material interface studies. For many applications of surface patterning, it does not need cells to attach on the whole surface. Herein, we introduce a novel polymer fabrication protocol of off-stoichiometry thiol-ene (OSTE) polymers to create heterogeneity on the surface by utilizing 3D printing and soft-lithography. By choosing two OSTE polymers with different functional groups, we create a pattern where only parts of the surface can facilitate cell adhesion. We also study the hydrophilic property of OSTE polymers by mixing poly(ethylene glycol) (PEG) directly with pre-polymers and plasma treatments afterwards. Moreover, we investigate the effect of functional groups' excess ratio and hydrophilic property on the cell adhesion ability of OSTE polymers. The results show that the cell adhesion ability of OSTE materials can be tuned within a wide range by the coupling effect of functional groups' excess ratio and hydrophilic property. Meanwhile, by mixing PEG with pre-polymers and undergoing oxygen plasma treatment afterward can significantly improve the hydrophilic property of OSTE polymers.

  17. Creating a culture where employee engagement Thrives

    Energy Technology Data Exchange (ETDEWEB)

    Don Groover, C.S.P. [Behavioral Science Technology, Ojai, CA (United States)

    2007-07-01

    Safety leaders across industries face a critical challenge: engaging employees. While engagement of a few people may be easy in short-term projects, it is significantly more difficult with long-term processes. In this session we show leaders how they can create a culture where workers are more open and even eager to be involved in safety efforts. Our experience with safety leaders in the nuclear industry has verified that when the factors that drive organizational functioning are understood, leaders are enabled to augment employee engagement and attain significant improvement in safety outcomes. The underlying factors that influence employee engagement, performance, outcomes, and organizational culture are the same the world over. We will also show how safety is capable, by its intrinsic value, of winning profound support and direct engagement of employees. In this session, we will examine how leaders can leverage their decisions and actions to win over employees to safety and support them in their endeavors to promote it. Using the safety leadership best practices Vision, Credibility, Accountability, Communication, Collaboration, Action Orientation, and Recognition and Feedback, leaders increase their impact on their organization in favor of a culture that supports safety and employee engagement. Leaders that create a climate and culture where employee engagement thrives, realize better safety results. Leadership is not exclusively an inborn talent; it can be developed and enhanced. To this end, we will also show the advantages of transformational leadership style by comparing it to more classical transactional leadership.

  18. DO ROMANIAN MERGERS REALLY CREATE VALUE?

    Directory of Open Access Journals (Sweden)

    Anca-Simona HROMEI

    2015-12-01

    Full Text Available The realities of our modern society demonstrate that businesses operate in a competitive environment, which requires continuous improvement and development of production and sales. In this context, for financial, economic and fiscal reasons, companies resort to a process of concentration, through the merger of all the factors involved in the fulfilment and diversification of their activities. Often, the reasons for engaging in a merger refer to the fact that two merged companies create, in terms of value, an entity that exceeds the individual values of the two participants if they were to continue to activate separately. This paper aims at analysing whether the well-known relationship ‘1+1=3’, which describes merger synergies, applies at the Romanian level. For this reason, each of the values of 77 merged companies were compared with the sum of the individual values of the firms that initially created them. It was found that 56% of the mergers analysed generated added value for shareholders.

  19. Our Lunar Destiny: Creating a Lunar Economy

    Science.gov (United States)

    Rohwer, Christopher J.

    2000-01-01

    "Our Lunar Destiny: Creating a Lunar Economy" supports a vision of people moving freely and economically between the earth and the Moon in an expansive space and lunar economy. It makes the economic case for the creation of a lunar space economy and projects the business plan that will make the venture an economic success. In addition, this paper argues that this vision can be created and sustained only by private enterprise and the legal right of private property in space and on the Moon. Finally, this paper advocates the use of lunar land grants as the key to unleashing the needed capital and the economic power of private enterprise in the creation of a 21st century lunar space economy. It is clear that the history of our United States economic system proves the value of private property rights in the creation of any new economy. It also teaches us that the successful development of new frontiers-those that provide economic opportunity for freedom-loving people-are frontiers that encourage, respect and protect the possession of private property and the fruits of labor and industry. Any new 21st century space and lunar economy should therefore be founded on this same principle.

  20. Creating quality improvement culture in public health agencies

    National Research Council Canada - National Science Library

    Davis, Mary V; Mahanna, Elizabeth; Joly, Brenda; Zelek, Michael; Riley, William; Verma, Pooja; Fisher, Jessica Solomon

    2014-01-01

    ...), or creating a quality improvement culture (n = 4). Agencies conducting formal quality improvement and creating a quality improvement culture had leadership support for quality improvement, participated in national...

  1. How to create high-performing teams.

    Science.gov (United States)

    Lam, Samuel M

    2010-02-01

    This article is intended to discuss inspirational aspects on how to lead a high-performance team. Cogent topics discussed include how to hire staff through methods of "topgrading" with reference to Geoff Smart and "getting the right people on the bus" referencing Jim Collins' work. In addition, once the staff is hired, this article covers how to separate the "eagles from the ducks" and how to inspire one's staff by creating the right culture with suggestions for further reading by Don Miguel Ruiz (The four agreements) and John Maxwell (21 Irrefutable laws of leadership). In addition, Simon Sinek's concept of "Start with Why" is elaborated to help a leader know what the core element should be with any superior culture. Thieme Medical Publishers.

  2. Creating marketing strategies for higher education institutions

    Directory of Open Access Journals (Sweden)

    Lidia Białoń

    2015-12-01

    Full Text Available The article presents a thesis that the primary premise of creating marketing strategies for higher education institution is a three-dimensional notion of marketing. The first dimension lies in the theoretical notions of the essence of marketing, including the transactional marketing (1.0, relationship marketing (2.0 and spiritual marketing (3.0. The second dimension is formed by methods of marketing research and accurate notions of marketing, while the third are channels of marketing information. Harmonizing these three dimensions is a precondition for effective marketing. Among other conditions for effective strategies there are: aligning goals of the chosen strategy with the mission of higher education institution, correct choice of targeted segments of the market and of marketing tools. The article also gives a sample classification of marketing strategies based on these criteria, with emphasis on the fact, that every higher education institution employs its own strategy.

  3. Creating Effective Dialogue Around Climate Change

    Science.gov (United States)

    Kiehl, J. T.

    2015-12-01

    Communicating climate change to people from diverse sectors of society has proven to be difficult in the United States. It is widely recognized that difficulties arise from a number of sources, including: basic science understanding, the psychologically affect laden content surrounding climate change, and the diversity of value systems that exist in our society. I explore ways of working with the affect that arises around climate change and describe specific methods to work with the resistance often encountered when communicating this important issue. The techniques I describe are rooted in psychology and group process and provide means for creating more effective narratives to break through the barriers to communicating climate change science. Examples are given from personal experiences in presenting climate change to diverse groups.

  4. Creating Visual Design and Meaningful Audience Experiences

    DEFF Research Database (Denmark)

    Steijn, Arthur; Ion Wille, Jakob

    2014-01-01

    conditions. The most important being 1) the development in new technology creating new expectations in audiences attending cultural events, including classical concerts, 2) resent decline in audiences attending classical music and 3) a will to strengthen relations between cultural institutions, creative......The main purpose of the EU Interreg funded Classical Composition Music and Experience Design project, was to rethink audience experiences and develop knowledge of applied technologies connected to classical music and live concerts. The project and its main objectives was motivated by at least thee...... businesses and educational institutions in the Øresund region (including the city and surroundings of Malmø and Copenhagen). Therefore the project Classical Composition Music and Experience Design focused on developing new and meaningful audience experiences where live classical music meets new digital...

  5. Creating Inclusive Youth Programs for LGBTQ+ Communities

    Directory of Open Access Journals (Sweden)

    Katherine E. Soule

    2017-06-01

    Full Text Available It is vital for youth to experience inclusive programming that is welcoming. Extension has a responsibility and an obligation to provide youth with programs and spaces that are inclusive of all sexes, gender identities, gender expressions, and sexual orientations. This article provides an overview of appropriate terminology, as well as steps for creating inclusive Extension spaces and programs for youth who identify as members of lesbian, gay, bisexual, transgender, or queer/questioning (LGBTQ+ communities. With a focus on urban Extension audiences, this article uses accessible language, self-reflective prompts, and supporting visual aids to share lessons learned from ongoing inclusivity trainings with Extension personnel across the nation, as well as from research activities and inclusive programming.

  6. FoilSim: Basic Aerodynamics Software Created

    Science.gov (United States)

    Peterson, Ruth A.

    1999-01-01

    FoilSim is interactive software that simulates the airflow around various shapes of airfoils. The graphical user interface, which looks more like a video game than a learning tool, captures and holds the students interest. The software is a product of NASA Lewis Research Center s Learning Technologies Project, an educational outreach initiative within the High Performance Computing and Communications Program (HPCCP).This airfoil view panel is a simulated view of a wing being tested in a wind tunnel. As students create new wing shapes by moving slider controls that change parameters, the software calculates their lift. FoilSim also displays plots of pressure or airspeed above and below the airfoil surface.

  7. Co-Creating ‘Second Life’

    DEFF Research Database (Denmark)

    Gürsimsek, Remzi Ates

    2010-01-01

    Developments in digital communication technologies, emergence of Social Media and shifting of digital media landscape towards a more participatory platform are not only the driving forces behind the implication of new technologies to the market, but they also have significant effects on the ways...... that mediate communication in Second Life (SL). The outlined theoretical framework and methodological approach is intended to summarize impressions from my observations of Second Life ‘builders’ in order to understand who they are, how they collaborate, and how they make sense of their co-design experiences...... people communicate, interact, participate and create communicative content in social contexts. This PhD project aims to observe how residents of Second Life use the Virtual World as a collaborative tool for creativity and co-design of the world’s content; that is, virtual places and artifacts...

  8. Creating biological nanomaterials using synthetic biology.

    Science.gov (United States)

    Rice, MaryJoe K; Ruder, Warren C

    2014-02-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

  9. Creating a turnkey hierarchical geospatial data warehouse

    Science.gov (United States)

    Libbey, Clinton R.

    1999-12-01

    The components of a web based data warehouse capable of populating, storing, searching, previewing, and disseminating a variety of information products over a TCP/IP network can be achieved through the use of commercially available products. The ability to deploy a solution that provides a central archive as well as distributed local archives of products is desirable. This approach is necessary due to the amount of data products generated for the community as well as the generation of custom products by regional users and the subsequent creation of their own archive for such products. Users must be able to leverage a central archive as well as have the ability to create their own local archive of data. This will increase efficiency at multiple levels and provide users with a solution that satisfies both their global data access needs and local data management.

  10. Minkowski metrics in creating universal ranking algorithms

    Directory of Open Access Journals (Sweden)

    Andrzej Ameljańczyk

    2014-06-01

    Full Text Available The paper presents a general procedure for creating the rankings of a set of objects, while the relation of preference based on any ranking function. The analysis was possible to use the ranking functions began by showing the fundamental drawbacks of commonly used functions in the form of a weighted sum. As a special case of the ranking procedure in the space of a relation, the procedure based on the notion of an ideal element and generalized Minkowski distance from the element was proposed. This procedure, presented as universal ranking algorithm, eliminates most of the disadvantages of ranking functions in the form of a weighted sum.[b]Keywords[/b]: ranking functions, preference relation, ranking clusters, categories, ideal point, universal ranking algorithm

  11. Genetic Transformation of Transcription Factor (35S-oshox4 Gene into Rice Genome and Transformant Analysis of hpt Gene by PCR and Hygromycin Resistance Test

    Directory of Open Access Journals (Sweden)

    INEZ HORTENZE SLAMET-LOEDIN

    2009-04-01

    Full Text Available Global warming, climate change and crop extensification in marginal dryland areas are related to long dry season and water deficit. The water availability is an important factor in improving plant production. Application of drought tolerant rice cultivars is one of several options that might be used. Genetic engineering at the level of transcription factors is particularly promising strategy to develop drought tolerant rice varieties. Transcription factors regulate a wide range of target genes in which of them contribute to stress tolerance. HD Zip genes are transcription factor that potential in the adaptation of plants to some environment stresses including water deficit. HD-ZIP oshox4 (oryza sativa homeobox gene controlled by 35S promotor is inserted into pCAMBIA 1300 vector with hpt (hygromycin gene as a selectable marker. The aim of this research is to obtain transgenic rice plant from transformation with 35S-oshox4 plasmid, segregation analysis of marker gene (hpt by PCR method at T0 and T1 generation, and hygromycin resistance analysis of seeds. Recombinant plasmid was transformed into rice genome of IRAT 112 and rojolele cultivars using Agrobacterium tumefaciens. The results showed that transformation efficiency of IRAT 112 is 5.7-13.6% and 26-66,7% for rojolele. While regeneration efficiency for IRAT 112 is 4.7-43.7% and 23-44.1% for rojolele. The result of hygromycin resistance test at T1 seeds were obtained 14 lines cv. rojolele segregation Mendelian for hpt gene. The PCR analysis using specific primers for hpt gene at the parent (T0 from 14 lines showed that 7 lines contain the gene. At the second generation (T1, PCR analysis using hpt primers showed that 3 from 4 lines were followed Mendelian segregation pattern by the presence of specific band.

  12. Expression analyses of the genes harbored by the type 2 diabetes and pediatric BMI associated locus on 10q23

    Directory of Open Access Journals (Sweden)

    Zhao Jianhua

    2012-09-01

    Full Text Available Abstract Background There is evidence that one of the key type 2 diabetes (T2D loci identified by GWAS exerts its influence early on in life through its impact on pediatric BMI. This locus on 10q23 harbors three genes, encoding hematopoietically expressed homeobox (HHEX, insulin-degrading enzyme (IDE and kinesin family member 11 (KIF11, respectively. Methods We analyzed the impact of adipogeneis on the mRNA and protein expression levels of these genes in the human adipocyte Simpson-Golabi-Behmel syndrome (SGBS cell line in order to investigate which could be the culprit gene(s in this region of linkage disequilibrium. Results Following activation of differentiation with a PPARγ ligand, we observed ~20% decrease in IDE, ~40% decrease in HHEX and in excess of 80% decrease in KIF11 mRNA levels when comparing the adipocyte and pre-adipocyte states. We also observed decreases in KIF11 and IDE protein levels, but conversely we observed a dramatic increase in HHEX protein levels. Subsequent time course experiments revealed some marked changes in expression as early as three hours after activation of differentiation. Conclusion Our data suggest that the expression of all three genes at this locus are impacted during SGBS adipogenesis and provides insights in to the possible mechanisms of how the genes at this 10q23 locus could influence both adipocyte differentiation and susceptibility to T2D through insulin resistance.

  13. Enabling Reanalysis Intercomparison with the CREATE-IP and CREATE-V Projects

    Science.gov (United States)

    Carriere, L.; Potter, G. L.; Hertz, J.; Shen, Y.; Britzolakis, G.; Peters, J.; Maxwell, T. P.; Li, J.; Strong, S.; Schnase, J. L.

    2016-12-01

    NASA Goddard Space Flight Center's Office of Computational and Information Sciences and Technology, the NASA Center for Climate Simulation (NCCS), and the Earth System Grid Federation (ESGF) are working together to build a uniform environment for the comparative study and use of a group of reanalysis datasets of particular importance to the research community. This effort is called the Collaborative REAnalysis Technical Environment (CREATE) and it contains two components: the CREATE-Intercomparison Project (CREATE-IP) and CREATE-V. For CREATE-IP, our target reanalyses include ECMWF ERA-Interim, NASA/GMAO MERRA and MERRA2, NOAA/NCEP CFSR, NOAA/ESRL 20CR and 20CRv2, JMA JRA25, and JRA55. Each dataset is reformatted similarly to the models in the CMIP5 archive. By repackaging the reanalysis data into a common structure and format, it simplifies access, subsetting, and reanalysis comparison. Both monthly average data and a selection of high frequency data (6-hr) relevant to investigations such as the 2016 El Niño are provided. Much of the processing workflow has been automated and new data appear on a regular basis. In collaboration with the CLIVAR Global Synthesis and Observations Panel (GSOP), we are also processing and publishing eight ocean reanalyses, from 1980 to the present. Here, the data are regridded to a common 1° x 1° grid, vertically interpolated to the World Ocean Atlas 09 (WOA09) depths, and an ensemble is generated. CREATE-V is a web based visualization tool that allows the user to simultaneously view four reanalyses to facilitate comparison. The addition of a backend analytics engine, based on UV-CDAT and Scala provides the ability to generate a time series and anomaly for any given location on a map. The system enables scientists to identify data of interest and visualize, subset, and compare data without the need for download large volumes of data for local visualization.

  14. Non-Invasive Gene Therapy of Experimental Parkinson's Disease

    National Research Council Canada - National Science Library

    Pardridge, William M

    2005-01-01

    ... medicine without the use of viral vectors. The brain gene targeting technology developed in this work creates an "artificial virus" which is comprised of non-immunogenic lipids and proteins, wherein the therapeutic gene is packaged...

  15. A crowdsourcing model for creating preclinical medical education study tools.

    Science.gov (United States)

    Bow, Hansen C; Dattilo, Jonathan R; Jonas, Andrea M; Lehmann, Christoph U

    2013-06-01

    During their preclinical course work, medical students must memorize and recall substantial amounts of information. Recent trends in medical education emphasize collaboration through team-based learning. In the technology world, the trend toward collaboration has been characterized by the crowdsourcing movement. In 2011, the authors developed an innovative approach to team-based learning that combined students' use of flashcards to master large volumes of content with a crowdsourcing model, using a simple informatics system to enable those students to share in the effort of generating concise, high-yield study materials. The authors used Google Drive and developed a simple Java software program that enabled students to simultaneously access and edit sets of questions and answers in the form of flashcards. Through this crowdsourcing model, medical students in the class of 2014 at the Johns Hopkins University School of Medicine created a database of over 16,000 questions that corresponded to the Genes to Society basic science curriculum. An analysis of exam scores revealed that students in the class of 2014 outperformed those in the class of 2013, who did not have access to the flashcard system, and a survey of students demonstrated that users were generally satisfied with the system and found it a valuable study tool. In this article, the authors describe the development and implementation of their crowdsourcing model for creating study materials, emphasize its simplicity and user-friendliness, describe its impact on students' exam performance, and discuss how students in any educational discipline could implement a similar model of collaborative learning.

  16. Creating an organizational culture for medication safety.

    Science.gov (United States)

    Dennison, Robin Donohoe

    2005-03-01

    Medication errors are costly from human, economic, and societal perspectives. All patients are vulnerable to the detrimental effects of these errors. Recommendations regarding the problem of medication errors include: Prevention of error by learning from the nonpunitive reporting of errors and near misses; Evaluation of the system for potential causes of error through failure mode and effects analysis and encouragement of a questioning attitude; Elimination of system problems that increase the risk of error; Recognition that humans are fallible and that error will occur even in a perfect system; Minimization of the consequences of errors when they do occur. An important goal for healthcare organizations should be to create a culture that accepts the imperfection of human performance and solicits the assistance of team members in the development of safeguards for error prevention. Proposed interventions to prevent medication errors can be described by the PATIENT SAFE taxonomy, which includes: Patient participation; Adherence to established policy and procedures; Technology use; Information accessibility; Education regarding medication safety; Nonpunitive approach to reporting of errors and near misses; Teamwork, communication, and collaboration; Staffing: adequate number and staffing mix; Administration support for the clinical goal of patient safety; Failure mode and effects analysis with team member involvement; Environment and equipment to support patient safety

  17. Creating Affording Situations: Coaching through Animate Objects.

    Science.gov (United States)

    Baber, Chris; Khattab, Ahmad; Russell, Martin; Hermsdörfer, Joachim; Wing, Alan

    2017-10-11

    We explore the ways in which animate objects can be used to cue actions as part of coaching in Activities of Daily Living (ADL). In this case, changing the appearance or behavior of a physical object is intended to cue actions which are appropriate for a given context. The context is defined by the intention of the users, the state of the objects and the tasks for which these objects can be used. We present initial design prototypes and simple user trials which explore the impact of different cues on activity. It is shown that raising the handle of a jug, for example, not only cues the act of picking up the jug but also encourages use of the hand adjacent to the handle; that combinations of lights (on the objects) and auditory cues influence activity through reducing uncertainty; and that cueing can challenge pre-learned action sequences. We interpret these results in terms of the idea that the animate objects can be used to create affording situations, and discuss implications of this work to support relearning of ADL following brain damage or injury, such as might arise following a stroke.

  18. Creating Affording Situations: Coaching through Animate Objects

    Directory of Open Access Journals (Sweden)

    Chris Baber

    2017-10-01

    Full Text Available We explore the ways in which animate objects can be used to cue actions as part of coaching in Activities of Daily Living (ADL. In this case, changing the appearance or behavior of a physical object is intended to cue actions which are appropriate for a given context. The context is defined by the intention of the users, the state of the objects and the tasks for which these objects can be used. We present initial design prototypes and simple user trials which explore the impact of different cues on activity. It is shown that raising the handle of a jug, for example, not only cues the act of picking up the jug but also encourages use of the hand adjacent to the handle; that combinations of lights (on the objects and auditory cues influence activity through reducing uncertainty; and that cueing can challenge pre-learned action sequences. We interpret these results in terms of the idea that the animate objects can be used to create affording situations, and discuss implications of this work to support relearning of ADL following brain damage or injury, such as might arise following a stroke.

  19. Informational conflicts created by the waggle dance

    Science.gov (United States)

    Grüter, Christoph; Balbuena, M. Sol; Farina, Walter M

    2008-01-01

    The honeybee (Apis mellifera) waggle dance is one of the most intriguing animal communication signals. A dancing bee communicates the location of a profitable food source and its odour. Followers may often experience situations in which dancers indicate an unfamiliar location but carry the scent of a flower species the followers experienced previously at different locations. Food scents often reactivate bees to resume food collection at previously visited food patches. This double function of the dance creates a conflict between the social vector information and the private navigational information. We investigated which kind of information followers with field experience use in this situation and found that followers usually ignored the spatial information encoded by the waggle dance even if they followed a dance thoroughly (five waggle runs or more). They relied on private information about food source locations instead (in 93% of all cases). Furthermore, foragers preferred to follow dancers carrying food odours they knew from previous field trips, independently of the spatial information encoded in the dance. Surprisingly, neither odour identity nor the location indicated by the dancer was an important factor for the reactivation success of a dance. Our results contrast with the assumption that (i) followers usually try to decode the vector information and (ii) dances indicating an unfamiliar location are of little interest to experienced foragers. PMID:18331980

  20. Creating the Nurses' Environmental Awareness Tool (NEAT).

    Science.gov (United States)

    Schenk, Elizabeth; Butterfield, Patricia; Postma, Julie; Barbosa-Leiker, Celestina; Corbett, Cindy

    2015-09-01

    Acute care delivery creates secondary health risks to patients, health care workers, and the environment through a complex waste stream, intensive energy use, and frequent use of harmful chemicals. Nurses are among the most affected by these risks and are also pivotal change agents in reducing the negative impacts of health care delivery. Assessing nurses' understanding of health care-associated environmental health risks is essential if care is to be delivered in an environmentally safe and healthy manner, as indicated by published professional standards of nursing practice. However, psychometrically sound instruments that measure nurses' awareness of the environmental impacts of nursing practice are not available. To address this gap, a prototype of the Nurse's Environmental Awareness Tool (NEAT) was developed. Seven content experts in environmental health nursing and/or psychometrics were asked to review draft items. Comments were analyzed and applied to the scale items. Several revisions from the original item pool were made. The resulting draft NEAT includes six subscales, in three paired subsets. This article provides a summary of the process of item development and scale design. These findings, although preliminary, provide a foundation for subsequent psychometric testing. The result of this study is the creation of an instrument to measure nurses' awareness of and behaviors associated with the environmental impact of their practices. © 2015 The Author(s).

  1. Creating the optimal conditions for rehabilitation research.

    Science.gov (United States)

    Bakheit, Abdel Magid

    2009-09-01

    Current evidence suggests that productivity in biomedical research depends on the support that the research group enjoys from its parent institution, the composition of the group and the personal attributes of its members and leader. Supportive institutions provide adequate physical resources and allow substantial uninterrupted time for research. The effectiveness of the research group asa whole is also strongly influenced by the group's structure, the professional competence of the group leader, his leadership style and his ability to foster collaboration with other research groups and organizations. There is a good case for a flexible leadership style that is modelled on the situational theory of leadership. In addition, the personal characteristics of the individual members of the research group influence the quality and quantity of the research output. Effective groups are made of motivated individuals with research training and skills that are relevant to the objectives of the research group. Rehabilitation research is fundamentally different from traditional biomedical research. This study discusses how the factors that influence productivity of biomedical research relate to rehabilitation science and practice and examines the conditions that are necessary to create and maintain an academic environment that is conducive to large volume,high-quality research in rehabilitation medicine.

  2. Creating a Universe, a Conceptual Model

    Directory of Open Access Journals (Sweden)

    James R. Johnson

    2016-10-01

    Full Text Available Space is something. Space inherently contains laws of nature: universal rules (mathematics, space dimensions, types of forces, types of fields, and particle species, laws (relativity, quantum mechanics, thermodynamics, and electromagnetism and symmetries (Lorentz, Gauge, and symmetry breaking. We have significant knowledge about these laws of nature because all our scientific theories assume their presence. Their existence is critical for developing either a unique theory of our universe or more speculative multiverse theories. Scientists generally ignore the laws of nature because they “are what they are” and because visualizing different laws of nature challenges the imagination. This article defines a conceptual model separating space (laws of nature from the universe’s energy source (initial conditions and expansion (big bang. By considering the ramifications of changing the laws of nature, initial condition parameters, and two variables in the big bang theory, the model demonstrates that traditional fine tuning is not the whole story when creating a universe. Supporting the model, space and “nothing” are related to the laws of nature, mathematics and multiverse possibilities. Speculation on the beginning of time completes the model.

  3. Creating the optimized international marketing mix

    Directory of Open Access Journals (Sweden)

    Grubor Aleksandar

    2005-01-01

    Full Text Available In the international practice of Serbian companies still dominant approach is based on traditional foreign trade approach, which in the significant dimension ballast effective inclusion of domestic companies in the contemporary business. Such practice is a result of the modality of international trading evolved and stimulated recently including long lasting period of self managing socialism-business as well international orientation in trading was originated by the state support, which procured in the edification of so-called national corporations as a chief exporter. Long-time existing of that modality of the international trading procured in the shrinking and limitation possibilities for comprehensive development of the international orientation of domestic i.e local companies, which is an argument of objectively difficult international position of Serbian firms in the moment. Paper discuss different issues including assessment that incoming presence of regional or international investors on the domestic market will proffer possibilities for enhancement a domestic management and marketing know - how among others. So, this is a way how local management circles could make substantial progress in creating the optimized international marketing mix within domestic companies following on-going business experience.

  4. Creating healthy work environments: a strategic perspective.

    Science.gov (United States)

    Adamson, Bonnie J

    2010-01-01

    Although I find Graham Lowe and Ben Chan's logic model and work environment metrics thought provoking, a healthy work environment framework must be more comprehensive and consider the addition of recommended diagnostic tools, vehicles to deliver the necessary change and a sustainability strategy that allows for the tweaking and refinement of ideas. Basic structure is required to frame and initiate an effective process, while allowing creativity and enhancements to be made by organizations as they learn. I support the construction of a suggested Canadian health sector framework for measuring the health of an organization, but I feel that organizations need to have some freedom in that design and the ability to incorporate their own indicators within the established proven drivers. Reflecting on my organization's experience with large-scale transformation efforts, I find that emotional intelligence along with formal leadership development and front-line engagement in Lean process improvement activities are essential for creating healthy work environments that produce the balanced set of outcomes listed in my hospital's Balanced Scorecard.

  5. Creating a national home visiting research network.

    Science.gov (United States)

    Duggan, Anne; Minkovitz, Cynthia S; Chaffin, Mark; Korfmacher, Jon; Brooks-Gunn, Jeanne; Crowne, Sarah; Filene, Jill; Gonsalves, Kay; Landsverk, John; Harwood, Robin

    2013-11-01

    Home visiting can play a key role in the early childhood system of services. For home visiting to achieve its potential, decision-makers must make informed choices regarding adoption, adaptation, coordination, scale-up, and sustainment. We need a coordinated, focused, and theory-based home visiting research infrastructure to inform such decisions. The transdisciplinary Home Visiting Research Network (HVRN) was established in July 2012 with funding from the Health Resources and Services Administration. Its goal is to promote the translation of research findings into policy and practice. Its objectives are to (1) develop a national home visiting research agenda, (2) advance the use of innovative research methods; and (3) provide a research environment that is supportive of the professional development of emerging researchers interested in home visiting. A Management Team designs and directs activities to achieve these objectives through Work Teams. A Steering Committee of national leaders representing stakeholder groups oversees progress. HVRN's Coordinating Center supports the Work Teams and HVRN's Home visiting Applied Research Collaborative, a practice-based research network of home visiting programs. This article describes HVRN's rationale, approach, and anticipated products. We use home visiting-primary care coordination as an illustration, noting potential roles for pediatric practices and pediatric researchers and research educators in HVRN activities. HVRN creates the infrastructure for a rigorous program of research to inform policy and practice on home visiting as part of the system of services to improve family functioning, parenting, and child outcomes.

  6. Creating better superconductors by periodic nanopatterning

    Directory of Open Access Journals (Sweden)

    Milan P. Allan, Mark H. Fischer, Oliver Ostojic, Arjo Andringa

    2017-08-01

    Full Text Available The quest to create superconductors with higher transition temperatures is as old as superconductivity itself. One strategy, popular after the realization that (conventional superconductivity is mediated by phonons, is to chemically combine different elements within the crystalline unit cell to maximize the electron-phonon coupling. This led to the discovery of NbTi and Nb3Sn, to name just the most technologically relevant examples. Here, we propose a radically different approach to transform a `pristine' material into a better (meta- superconductor by making use of modern fabrication techniques: designing and engineering the electronic properties of thin films via periodic patterning on the nanoscale. We present a model calculation to explore the key effects of different supercells that could be fabricated using nanofabrication or deliberate lattice mismatch, and demonstrate that specific pattern will enhance the coupling and the transition temperature. We also discuss how numerical methods could predict the correct design parameters to improve superconductivity in materials including Al, NbTi, and MgB2

  7. Dancing Lights: Creating the Aurora Story

    Science.gov (United States)

    Wood, E. L.; Cobabe-Ammann, E. A.

    2009-12-01

    Science tells a story about our world, our existence, our history, and the larger environment our planet occupies. Bearing this in mind, we created a series of lessons for 3rd-5th grades using a cross-disciplinary approach to teaching about the aurora by incorporating stories, photos, movies, and geography into the science in order to paint a broad picture and answer the question, “why do we care?” The fundamental backbone of the program is literacy. Students write and illustrate fiction and non-fiction work, poetry, and brochures that solidify both language arts skills and science content. In a time when elementary teachers relegate science to less than one hour per week, we have developed a novel science program that can be easily integrated with other topics during the typical school day to increase the amount of science taught in a school year. We are inspiring students to take an interest in the natural world with this program, a stepping-stone for larger things.

  8. Creating cultures of excellence: Strategies and outcomes

    Directory of Open Access Journals (Sweden)

    Michael Mintrom

    2014-12-01

    Full Text Available Research findings on effective support for learning, the development of expertise, and the psychology of success suggest that the pursuit of excellence is teachable. Within the emerging field of research and practice termed “the scholarship of teaching and learning,” considerable effort has been made to document the practices of teachers who, by various measures, have been deemed excellent. In contrast, no effort has been made to codify how students can be trained to self-consciously build behaviors that generate excellent outcomes. This article reports on a multi-year effort to create cultures of excellence among cohorts of graduate students. A statistical analysis of subsequent student performance on a significant, related task indicates that explicitly promoting a culture of excellence among course participants can have a positive and sustained impact on their individual practices. Comments from subsequent student reflections further support this claim. The teaching strategies reported here could be refined, replicated, and reinvented to good effect across higher education. They are also of special relevance to those delivering professional development training to early- and mid-career professionals.

  9. Creating conditions for cooperative learning: Basic elements

    Directory of Open Access Journals (Sweden)

    Ševkušić-Mandić Slavica G.

    2003-01-01

    Full Text Available Although a large number of research evidence speak out in favor of cooperative learning, its effectiveness in teaching does not depend only on teacher’s and students’ enthusiasm and willingness to work in such a manner. Creating cooperative situations in learning demands a serious preparation and engagement on the part of teacher who is structuring various aspects of work in the classroom. Although there exist a large number of models and techniques of cooperative learning, which vary in the way in which students work together, in the structure of learning tasks as well as in the degree to which cooperative efforts of students are coupled with competition among groups, some elements should be present in the structure of conditions irrespective of the type of group work in question. Potential effects of cooperation are not likely to emerge unless teachers apply five basic elements of cooperative structure: 1. structuring of the learning task and students’ positive interdependence, 2. individual responsibility, 3. upgrading of "face to face" interaction, 4. training of students’ social skills, and 5. evaluation of group processes. The paper discusses various strategies for establishing the mentioned elements and concrete examples for teaching practice are provided, which should be of assistance to teachers for as much successful cooperative learning application as possible in work with children.

  10. Creating Web Services from Community Sourced Data

    Science.gov (United States)

    Siegel, D.; Scopel, C.; Boghici, E.

    2013-12-01

    In order to extend the World Hydro Basemap and build watershed delineation and river tracing services that cover the entire planet, we are integrating community-contributed data into a global hydrographic dataset. This dataset is the engine behind a foundational set of tools and services intended to enable hydrologic analysis on the web. However, each organization that collects hydrography uses a workflow and data model unique to their mission, which makes synthesizing their data difficult. Furthermore, these data are collected at different resolutions, so running analytics across regions with multiple contributors is not necessarily valid. Thus, instead of merging contributed data into a seamless geodatabase, the goal of our Community Maps for Hydrology program is to create workflows for converting any arbitrary dataset into the Arc Hydro Data Model. This way, tools and services can be pointed towards different contributions interchangeably while still maintaining the autonomy of each dataset. Contributors retain ownership of their data and are responsible for updates and edits, but the tools and services work identically across all contributions. HydroSHEDs data, contributed by the World Wildlife Fund, is used at the smallest scales to ensure global coverage, and national datasets extend our services to the medium-scales where available. A workflow to incorporate LIDAR and other large scale data is being developed as well, so that local governments and engineering companies can contribute to the program. Watershed Delineation Tool The World Hydro Basemap

  11. Mutations in the SRY, DAX1, SF1 and WNT4 genes in Brazilian sex-reversed patients

    Directory of Open Access Journals (Sweden)

    S. Domenice

    2004-01-01

    Full Text Available In most mammals, male development is triggered by the transient expression of the SRY gene, which initiates a cascade of gene interactions ultimately leading to the formation of a testis from the indifferent fetal gonad. Mutation studies have identified several genes essential for early gonadal development. We report here a molecular study of the SRY, DAX1, SF1 and WNT4 genes, mainly involved in sexual determination, in Brazilian 46,XX and 46,XY sex-reversed patients. The group of 46,XX sex-reversed patients consisted of thirteen 46,XX true hermaphrodites and four 46,XX males, and was examined for the presence of the SRY gene and for the loss of function (inactivating mutations and deletions of DAX1 and WNT4 genes. In the second group consisting of thirty-three 46,XY sex-reversed patients we investigated the presence of inactivating mutations in the SRY and SF1 genes as well as the overexpression (duplication of the DAX1 and WNT4 genes. The SRY gene was present in two 46,XX male patients and in none of the true hermaphrodites. Only one mutation, located outside homeobox domain of the 5' region of the HMG box of SRY (S18N, was identified in a patient with 46,XY sex reversal. A novel 8-bp microdeletion of the SF1 gene was identified in a 46,XY sex-reversed patient without adrenal insufficiency. The dosage of DAX1 and WNT4 was normal in the sex-reversed patients studied. We conclude that these genes are rarely involved in the etiology of male gonadal development in sex-reversed patients, a fact suggesting the presence of other genes in the sex determination cascade.

  12. gene structure, gene expression

    Indian Academy of Sciences (India)

    Primer 5.0 software. To adjust for RNA quality and diffe- rences in cDNA concentration, we amplified actin as an internal control with the following primers: PtActin-F (5′-TG. AAGGAGAAACTTGCGTAT-3′) and PtActin-R (5′-GCA. CAATGTTACCGTACAGAT-3′). These genes were ampli- fied from first-strand cDNA using ...

  13. Creating supportive environments for AIDS prevention.

    Science.gov (United States)

    1995-01-01

    The World Health Organization's Global Programme on AIDS (GPA) argues that AIDS prevention requires a supportive environment, but that discriminatory laws make marginalized people even more vulnerable to sexually transmitted diseases (STDs). A country's legal, economic, and social environments can influence the pandemic. A short-term measure could be prostitutes collectively insisting that their clients wear condoms. Long-term measures of AIDS prevention require the improvement of the legal status of women and their access to education. Societies repress or tolerate drug use, prostitution, homosexuality, and casual sex, but often ministries forbid condom advertising, and condom possession by women can be used as evidence of prostitution. Fear of mandatory testing and detention prevents sex workers and drug users from accepting condoms and needles. A recent review of policies in 22 locations around the world found low seroprevalence of HIV among IV drug users in only 5 countries -- exactly the same countries where IV drug users had legal access to sterile needles. In Zambia a national condom promotion campaign was launched only after a 2-year debate, while free condoms had been distributed surreptitiously by a nongovernmental organization. Sex discrimination in many countries forces women to trade sex for money to make a living, and women in sex work are very vulnerable to HIV infection. Overcoming the subordination of women is a long-term undertaking, but an example of successful short-term empowerment of women is a credit scheme operated by a bank for rural women in Bangladesh. Socially, culturally, and economically male infidelity is often condoned, creating the risk of HIV infection and of passing the infection on to wives. Information campaigns stressing shared responsibility can be effective in changing social norms. Some traditional practices, e.g., ritual cleansing in Uganda and Zambia, also expose participants to the risk of HIV infection.

  14. DOES CIVIL SOCIETY CREATE SOCIAL ENTREPRENEURS?

    Directory of Open Access Journals (Sweden)

    Gauca Oana

    2013-07-01

    Full Text Available The purpose of this paper is to analyze whether civil society itself can enhance or stimulate the creation of social entrepreneurs, by studying the traits of the civil society and the various definitions attributed to it. The main question that the paper wants to answer to is Does civil society create social entrepreneurs and the main approach used in this research paper is the theoretical one. By studying existing articles and books on the topic, the paper tries to emphasize the various dimensions that civil society can embrace, as pictured by various authors, as well as how these dimensions can relate to social entrepreneurs and the emergence of social businesses. The paper is not meant to be a breakthrough in the field, but rather to launch a question that is related to very important topics these days, social entrepreneurship, social innovation, social businesses and their connection to a very much debated topic-civil society. The paper is work-in progress and wants to stimulate research regarding the search of the sources of social entrepreneurship, in order to analyze them and better establish them as incubators for the future. It wants to be of use to whoever is researching the concepts illustrated above, as well as for those who want to get in touch with the new buzz words of the academic and entrepreneurial fields. The hereby paper stands, as previously stated, in a theoretical framework and the findings represent a mere analysis of the cause-effect relationship between the characteristics of civil society and those of social entrepreneurs. However, we are of the opinion that it can be a very good starting point for the ones interested in the domain, to analyze more sources of social entrepreneurship or further refine the answer to the question addressed in this article.

  15. Defectors Can Create Conditions That Rescue Cooperation.

    Directory of Open Access Journals (Sweden)

    Adam James Waite

    2015-12-01

    Full Text Available Cooperation based on the production of costly common goods is observed throughout nature. This is puzzling, as cooperation is vulnerable to exploitation by defectors which enjoy a fitness advantage by consuming the common good without contributing fairly. Depletion of the common good can lead to population collapse and the destruction of cooperation. However, population collapse implies small population size, which, in a structured population, is known to favor cooperation. This happens because small population size increases variability in cooperator frequency across different locations. Since individuals in cooperator-dominated locations (which are most likely cooperators will grow more than those in defector-dominated locations (which are most likely defectors, cooperators can outgrow defectors globally despite defectors outgrowing cooperators in each location. This raises the possibility that defectors can lead to conditions that sometimes rescue cooperation from defector-induced destruction. We demonstrate multiple mechanisms through which this can occur, using an individual-based approach to model stochastic birth, death, migration, and mutation events. First, during defector-induced population collapse, defectors occasionally go extinct before cooperators by chance, which allows cooperators to grow. Second, empty locations, either preexisting or created by defector-induced population extinction, can favor cooperation because they allow cooperator but not defector migrants to grow. These factors lead to the counterintuitive result that the initial presence of defectors sometimes allows better survival of cooperation compared to when defectors are initially absent. Finally, we find that resource limitation, inducible by defectors, can select for mutations adaptive to resource limitation. When these mutations are initially present at low levels or continuously generated at a moderate rate, they can favor cooperation by further reducing local

  16. Peculiarities of Creating Foreign Students’ Lexical Competence

    Directory of Open Access Journals (Sweden)

    Aigul Eskermesovna Sadenova

    2016-11-01

    Full Text Available Teaching of vocabulary includes several aspects of teaching content: linguistic, methodological and psychological. Teaching of vocabulary is a process which is inextricably entwined with understanding relations between new words and phonetic and grammar aspects of the language. On the one hand, simultaneous learning of two languages complicates the tasks set to the students, but, on the other hand, it simplifies the process. The complexity is in the scope of vocabulary to be remembered, as well as in the differences between grammar structures used in Russian and Kazakh. The simplification is in the fact that students are fully aware that lexical competence is formed gradually, and that every language has its lexical base required at the initial stage, and that such base is to be developed for mastering a specific language. Before identifying the methods of vocabulary semantization in the course of teaching a language to foreign students, students shall be offered active vocabulary, used to express their ideas orally and in written form, and passive vocabulary, used to perceive oral and written information. It is not possible to teach semantics only. It is necessary to create paradigmatic, syntactic and associative relations. The formation of lexical skills is connected with the solidity of vocabulary retention. In order to ensure reinforcement of the vocabulary learnt, the students shall be offered exercises contributing to the development of their skills of using vocabulary in listening, speaking, reading and writing. All above mentioned types of vocabulary semantization constitute a unified whole. Different ways of semantization are set forth for methodological purposes, to facilitate the achievement of the desired result. Translation and non-translation techniques for vocabulary presentation, as well as some tips and exercises, are given. The use of basic vocabulary at elementary and advanced levels is suggested. Certain methods for the

  17. In vivo genome-wide analysis of multiple tissues identifies gene regulatory networks, novel functions and downstream regulatory genes for Bapx1 and its co-regulation with Sox9 in the mammalian vertebral column.

    Science.gov (United States)

    Chatterjee, Sumantra; Sivakamasundari, V; Yap, Sook Peng; Kraus, Petra; Kumar, Vibhor; Xing, Xing; Lim, Siew Lan; Sng, Joel; Prabhakar, Shyam; Lufkin, Thomas

    2014-12-05

    Vertebrate organogenesis is a highly complex process involving sequential cascades of transcription factor activation or repression. Interestingly a single developmental control gene can occasionally be essential for the morphogenesis and differentiation of tissues and organs arising from vastly disparate embryological lineages. Here we elucidated the role of the mammalian homeobox gene Bapx1 during the embryogenesis of five distinct organs at E12.5 - vertebral column, spleen, gut, forelimb and hindlimb - using expression profiling of sorted wildtype and mutant cells combined with genome wide binding site analysis. Furthermore we analyzed the development of the vertebral column at the molecular level by combining transcriptional profiling and genome wide binding data for Bapx1 with similarly generated data sets for Sox9 to assemble a detailed gene regulatory network revealing genes previously not reported to be controlled by either of these two transcription factors. The gene regulatory network appears to control cell fate decisions and morphogenesis in the vertebral column along with the prevention of premature chondrocyte differentiation thus providing a detailed molecular view of vertebral column development.

  18. Creating Single-Copy Genetic Circuits.

    Science.gov (United States)

    Lee, Jeong Wook; Gyorgy, Andras; Cameron, D Ewen; Pyenson, Nora; Choi, Kyeong Rok; Way, Jeffrey C; Silver, Pamela A; Del Vecchio, Domitilla; Collins, James J

    2016-07-21

    Synthetic biology is increasingly used to develop sophisticated living devices for basic and applied research. Many of these genetic devices are engineered using multi-copy plasmids, but as the field progresses from proof-of-principle demonstrations to practical applications, it is important to develop single-copy synthetic modules that minimize consumption of cellular resources and can be stably maintained as genomic integrants. Here we use empirical design, mathematical modeling, and iterative construction and testing to build single-copy, bistable toggle switches with improved performance and reduced metabolic load that can be stably integrated into the host genome. Deterministic and stochastic models led us to focus on basal transcription to optimize circuit performance and helped to explain the resulting circuit robustness across a large range of component expression levels. The design parameters developed here provide important guidance for future efforts to convert functional multi-copy gene circuits into optimized single-copy circuits for practical, real-world use. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridization.

    Science.gov (United States)

    Yokota, Naoki; Mainprize, Todd G; Taylor, Michael D; Kohata, Tomohiko; Loreto, Michael; Ueda, Shigeo; Dura, Wieslaw; Grajkowska, Wiesia; Kuo, John S; Rutka, James T

    2004-04-22

    To increase our understanding of the molecular pathogenesis of medulloblastoma (MB), we utilized the technique of suppression subtractive hybridization (SSH) to identify genes that are dysregulated in MB when compared to cerebellum. SSH-enriched cDNA libraries from both human and Ptch+/- heterozygous murine MBs were generated by subtracting common cDNAs from corresponding non-neoplastic cerebellum. For the human classic MB library, total human cerebellar RNA was used as control tissue; for the Ptch+/- heterozygous MB, non-neoplastic cerebellum from an unaffected Ptch+/- littermate was used as the control. Through differential screening of these libraries, over 100 upregulated tumor cDNA fragments were isolated, sequenced and identified with the NCBI BLAST program. From these, we selected genes involved in cellular proliferation, antiapoptosis, and cerebellar differentiation for further analysis. Upregulated genes identified in the human MB library included Unc33-like protein (ULIP), SOX4, Neuronatin (NNAT), the mammalian homologue of Drosophila BarH-like 1(BARHL1), the nuclear matix protein NRP/B (ENC1), and the homeobox OTX2 gene. Genes found to be upregulated in the murine MB library included cyclin D2 (Ccnd2), thymopoietin (Tmpo), Musashi-1 (Msh1), protein phosphatase 2A inhibitor-2 (I-2pp2a), and Unc5h4(D). Using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), the mRNA expression levels for these genes were markedly higher in human MBs than in cerebellum. Western blot analysis was used to further confirm the overexpression of a subset of these genes at the protein level. Notch pathway overactivity was demonstrated in the TE671 MB cell line expressing high levels of MSH1 through HES1-Luciferase transfections. This study has revealed a panel of developmentally regulated genes that may be involved in the pathogenesis of MB. Copyright 2004 Nature Publishing Group

  20. Analysis of the VSX1 gene in sporadic keratoconus patients from China.

    Science.gov (United States)

    Guan, Tao; Wang, Xue; Zheng, Li-Bin; Wu, Hai-Jian; Yao, Yu-Feng

    2017-09-26

    Keratoconus normally presents as a sporadic disease. Although different studies have found sequence variants of the visual system homeobox 1 (VSX1) gene associated with keratoconus in humans, no research has detected such variants in sporadic keratoconus patients from China. To investigate the possibility of VSX1 being a candidate susceptibility gene for Chinese patients with sporadic keratoconus, we performed sequence screening of this gene in such patients. Whole DNA was obtained from the leukocytes in the peripheral venous blood of 50 patients with sporadic keratoconus and 50 control subjects without this ocular disorder. Polymerase chain reaction single-strand conformation polymorphism analysis and direct DNA sequencing technology were used to detect sequence variation in the five exons and splicing regions of the introns of the VSX1 gene. The sequencing results were analyzed using DNAstar software. One novel missense heterozygous sequence variant (p.Arg131Pro) was found in the first exon of the VSX1 gene in one keratoconus patient. Another heterozygous sequence variant (p.Gly160Val) in the second exon was found in two keratoconus patients. These variants were not detected in the control subjects. In the third intron of the VSX1 gene, c.8326G > A nucleotide substitution (including heterozygous and homozygous change) was also discovered. The frequency of this variation did not differ significantly between patients and controls, it should belong to single-nucleotide polymorphism of the VSX1 gene. Bioinformatic analysis also predicted that one missense sequence variation (p.Arg131Pro) may not cause a pathogenic change. In this study, we added one novel missense sequence variation (p.Arg131Pro) in the coding region of the VSX1 gene to the range of VSX1 coding region variations observed in patients with sporadic keratoconus from China. Our work suggests that VSX1 sequence variants might be involved in the pathogenesis of sporadic keratoconus, but their precise

  1. Melonet-DB, A Grand RNA-seq Gene Expression Atlas in Melon (Cucumis melo L.).

    Science.gov (United States)

    Yano, Ryoichi; Nonaka, Satoko; Ezura, Hiroshi

    2017-12-04

    Melon (Cucumis melo L.) is an important Cucurbitaceae crop produced world-wide, exhibiting wide genetic variations and comprising both climacteric and non-climacteric fruit types. The muskmelon cultivar "Earl's favorite Harukei-3 (Harukei-3)" known for its sweetness and rich aroma is used for breeding of high-grade muskmelon in Japan. We conducted RNA-seq transcriptome studies in 30 different tissues of the 'Harukei-3' melon. These included root, stems, leaves, flowers, regenerating callus, and ovaries, in addition to the flesh and peel sampled at 7 stages of fruit development. The expression patterns of 20,752 genes were determined with FPKM > 1 in at least one tissue. Principal component analysis distinguished 30 melon tissues based on the global gene expression profile, and further, the weighted gene correlation network analysis classified melon genes into 45 distinct co-expression groups. Some co-expression groups exhibited tissue-specific gene expression. Furthermore, we developed and published web-application tools designated "Gene expression map viewer" and "Coexpression viewer" on our website Melonet-DB (http://melonet-db.agbi.tsukuba.ac.jp/) to promote functional genomics research in melon. By using both the tools, we analyzed melon homologs of tomato fruit ripening regulators such as E8, RIPENING-INHIBITOR (RIN) and NON-RIPENING (NOR). The "Coexpression viewer" clearly distinguished fruit ripening-associated melon RIN/NOR/CNR homologs from those expressed in other tissues. In addition, several other MADS-box, NAM/ATAF/CUC (NAC), and homeobox transcription factor genes were identified as fruit ripening-associated genes. Our tools provide useful information not only for research on melon but also on other fleshy fruit plants. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. High-throughput analysis of promoter occupancy reveals new targets for Arx, a gene mutated in mental retardation and interneuronopathies.

    Directory of Open Access Journals (Sweden)

    Marie-Lise Quillé

    Full Text Available Genetic investigations of X-linked intellectual disabilities have implicated the ARX (Aristaless-related homeobox gene in a wide spectrum of disorders extending from phenotypes characterised by severe neuronal migration defects such as lissencephaly, to mild or moderate forms of mental retardation without apparent brain abnormalities but with associated features of dystonia and epilepsy. Analysis of Arx spatio-temporal localisation profile in mouse revealed expression in telencephalic structures, mainly restricted to populations of GABAergic neurons at all stages of development. Furthermore, studies of the effects of ARX loss of function in humans and animal models revealed varying defects, suggesting multiple roles of this gene during brain development. However, to date, little is known about how ARX functions as a transcription factor and the nature of its targets. To better understand its role, we combined chromatin immunoprecipitation and mRNA expression with microarray analysis and identified a total of 1006 gene promoters bound by Arx in transfected neuroblastoma (N2a cells and in mouse embryonic brain. Approximately 24% of Arx-bound genes were found to show expression changes following Arx overexpression or knock-down. Several of the Arx target genes we identified are known to be important for a variety of functions in brain development and some of them suggest new functions for Arx. Overall, these results identified multiple new candidate targets for Arx and should help to better understand the pathophysiological mechanisms of intellectual disability and epilepsy associated with ARX mutations.

  3. Genes2FANs: connecting genes through functional association networks

    Directory of Open Access Journals (Sweden)

    Dannenfelser Ruth

    2012-07-01

    Full Text Available Abstract Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs, researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our

  4. Genome-Wide Analysis Suggests the Relaxed Purifying Selection Affect the Evolution of WOX Genes in Pyrus bretschneideri, Prunus persica, Prunus mume, and Fragaria vesca.

    Science.gov (United States)

    Cao, Yunpeng; Han, Yahui; Meng, Dandan; Li, Guohui; Li, Dahui; Abdullah, Muhammad; Jin, Qing; Lin, Yi; Cai, Yongping

    2017-01-01

    WUSCHEL-related homeobox (WOX) family is one of the largest group of transcription factors (TFs) specifically found in plant kingdom. WOX TFs play an important role in plant development processes and evolutionary novelties. Although the roles of WOXs in Arabidopsis and rice have been well-studied, however, little are known about the relationships among the main clades in the molecular evolution of these genes in Rosaceae. Here, we carried out a genome-wide analysis and identified 14, 10, 10, and 9 of WOX genes from four Rosaceae species (Fragaria vesca, Prunus persica, Prunus mume, and Pyrus bretschneideri, respectively). According to evolutionary analysis, as well as amino acid sequences of their homodomains, these genes were divided into three clades with nine subgroups. Furthermore, due to the conserved structural patterns among these WOX genes, it was proposed that there should exist some highly conserved regions of microsynteny in the four Rosaceae species. Moreover, most of WOX gene pairs were presented with the conserved orientation among syntenic genome regions. In addition, according to substitution models analysis using PMAL software, no significant positive selection was detected, but type I functional divergence was identified among certain amino acids in WOX protein. These results revealed that the relaxed purifying selection might be the main driving force during the evolution of WOX genes in the tested Rosaceae species. Our result will be useful for further precise research on evolution of the WOX genes in family Rosaceae.

  5. Genome-Wide Analysis Suggests the Relaxed Purifying Selection Affect the Evolution of WOX Genes in Pyrus bretschneideri, Prunus persica, Prunus mume, and Fragaria vesca

    Directory of Open Access Journals (Sweden)

    Yunpeng Cao

    2017-06-01

    Full Text Available WUSCHEL-related homeobox (WOX family is one of the largest group of transcription factors (TFs specifically found in plant kingdom. WOX TFs play an important role in plant development processes and evolutionary novelties. Although the roles of WOXs in Arabidopsis and rice have been well-studied, however, little are known about the relationships among the main clades in the molecular evolution of these genes in Rosaceae. Here, we carried out a genome-wide analysis and identified 14, 10, 10, and 9 of WOX genes from four Rosaceae species (Fragaria vesca, Prunus persica, Prunus mume, and Pyrus bretschneideri, respectively. According to evolutionary analysis, as well as amino acid sequences of their homodomains, these genes were divided into three clades with nine subgroups. Furthermore, due to the conserved structural patterns among these WOX genes, it was proposed that there should exist some highly conserved regions of microsynteny in the four Rosaceae species. Moreover, most of WOX gene pairs were presented with the conserved orientation among syntenic genome regions. In addition, according to substitution models analysis using PMAL software, no significant positive selection was detected, but type I functional divergence was identified among certain amino acids in WOX protein. These results revealed that the relaxed purifying selection might be the main driving force during the evolution of WOX genes in the tested Rosaceae species. Our result will be useful for further precise research on evolution of the WOX genes in family Rosaceae.

  6. Gene decay in archaea

    Directory of Open Access Journals (Sweden)

    M. W. J. van Passel

    2007-01-01

    Full Text Available The gene-dense chromosomes of archaea and bacteria were long thought to be devoid of pseudogenes, but with the massive increase in available genome sequences, whole genome comparisons between closely related species have identified mutations that have rendered numerous genes inactive. Comparative analyses of sequenced archaeal genomes revealed numerous pseudogenes, which can constitute up to 8.6% of the annotated coding sequences in some genomes. The largest proportion of pseudogenes is created by gene truncations, followed by frameshift mutations. Within archaeal genomes, large numbers of pseudogenes contain more than one inactivating mutation, suggesting that pseudogenes are deleted from the genome more slowly in archaea than in bacteria. Although archaea seem to retain pseudogenes longer than do bacteria, most archaeal genomes have unique repertoires of pseudogenes.

  7. MSX1 gene and nonsyndromic oral clefts in a Southern Brazilian population

    Energy Technology Data Exchange (ETDEWEB)

    Souza, L.T. [Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS (Brazil); Programa de Pós-Graduaçãoo em Saúde da Criança e do Adolescente, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Kowalski, T.W. [Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS (Brazil); Collares, M.V.M. [Universidade Federal do Rio Grande do Sul, Departamento de Cirurgia, Porto Alegre, RS, Brasil, Departamento de Cirurgia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Félix, T.M. [Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS (Brazil); Programa de Pós-Graduaçãoo em Saúde da Criança e do Adolescente, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre, RS, Brasil, Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS (Brazil)

    2013-08-10

    Nonsyndromic oral clefts (NSOC) are the most common craniofacial birth defects in humans. The etiology of NSOC is complex, involving both genetic and environmental factors. Several genes that play a role in cellular proliferation, differentiation, and apoptosis have been associated with clefting. For example, variations in the homeobox gene family member MSX1, including a CA repeat located within its single intron, may play a role in clefting. The aim of this study was to investigate the association between MSX1 CA repeat polymorphism and NSOC in a Southern Brazilian population using a case-parent triad design. We studied 182 nuclear families with NSOC recruited from the Hospital de Clínicas de Porto Alegre in Southern Brazil. The polymorphic region was amplified by the polymerase chain reaction and analyzed by using an automated sequencer. Among the 182 families studied, four different alleles were observed, at frequencies of 0.057 (175 bp), 0.169 (173 bp), 0.096 (171 bp) and 0.67 (169 bp). A transmission disequilibrium test with a family-based association test (FBAT) software program was used for analysis. FBAT analysis showed overtransmission of the 169 bp allele in NSOC (P=0.0005). These results suggest that the CA repeat polymorphism of the MSX1 gene may play a role in risk of NSOC in populations from Southern Brazil.

  8. Expression of cartilage developmental genes in Hoxc8- and Hoxd4-transgenic mice.

    Directory of Open Access Journals (Sweden)

    Claudia Kruger

    2010-02-01

    Full Text Available Hox genes encode transcription factors, which regulate skeletal patterning and chondrocyte differentiation during the development of cartilage, the precursor to mature bone. Overexpression of the homeobox transcription factors Hoxc8 and Hoxd4 causes severe cartilage defects due to delay in cartilage maturation. Matrix metalloproteinases (MMPs, bone morphogenetic proteins (BMPs and fibroblastic growth factors (FGFs are known to play important roles in skeletal development and endochondral bone formation and remodeling. In order to investigate whether these molecules are aberrantly expressed in Hoxc8- and/or Hoxd4-transgenic cartilage, we performed quantitative RT-PCR on chondrocytes from Hox-transgenic mice. Gene expression levels of Bmp4, Fgf8, Fgf10, Mmp9, Mmp13, Nos3, Timp3, Wnt3a and Wnt5a were altered in Hoxc8-transgenic chondrocytes, and Fgfr3, Ihh, Mmp8, and Wnt3a expression levels were altered in Hoxd4-transgenic chondrocytes, respectively. Notably, Wnt3a expression was elevated in Hoxc8- and reduced in Hoxd4-transgenic cartilage. These results suggest that both transcription factors affect cartilage maturation through different molecular mechanisms, and provide the basis for future studies into the role of these genes and possible interactions in pathogenesis of cartilage defects in Hoxc8- and Hoxd4-transgenic mice.

  9. Gene divergence of homeologous regions associated with a major seed protein content QTL in soybean

    Directory of Open Access Journals (Sweden)

    Puji eLestari

    2013-06-01

    Full Text Available Understanding several modes of duplication contributing on the present genome structure is getting an attention because it could be related to numerous agronomically important traits. Since soybean serves as a rich protein source for animal feeds and human consumption, breeding efforts in soybean have been directed toward enhancing seed protein content. The publicly available soybean sequences and its genomically featured elements facilitate comprehending of quantitative trait loci (QTL for seed protein content in concordance with homeologous regions in soybean genome. Although parts of chromosome (Chr 20 and Chr 10 showed synteny, QTLs for seed protein content present only on Chr 20. Using comparative analysis of gene contents in recently duplicated genomic regions harboring QTL for protein/oil content on Chrs 20 and 10, a total of 27 genes are present in duplicated regions of both chromosomes. Notably, 4 tandem duplicates of the putative homeobox protein 22 (HB22 are present only on Chr 20 and this Medicago truncatula homolog expressed in endosperm at seed filling stage. These tandem duplicates could contribute on the protein/oil QTL of Chr 20. Our study suggests that non-shared gene contents within the duplicated genomic regions might lead to absence/presence of QTL related to protein/oil content.

  10. MSX1 gene and nonsyndromic oral clefts in a Southern Brazilian population

    Directory of Open Access Journals (Sweden)

    L.T. Souza

    2013-08-01

    Full Text Available Nonsyndromic oral clefts (NSOC are the most common craniofacial birth defects in humans. The etiology of NSOC is complex, involving both genetic and environmental factors. Several genes that play a role in cellular proliferation, differentiation, and apoptosis have been associated with clefting. For example, variations in the homeobox gene family member MSX1, including a CA repeat located within its single intron, may play a role in clefting. The aim of this study was to investigate the association between MSX1 CA repeat polymorphism and NSOC in a Southern Brazilian population using a case-parent triad design. We studied 182 nuclear families with NSOC recruited from the Hospital de Clínicas de Porto Alegre in Southern Brazil. The polymorphic region was amplified by the polymerase chain reaction and analyzed by using an automated sequencer. Among the 182 families studied, four different alleles were observed, at frequencies of 0.057 (175 bp, 0.169 (173 bp, 0.096 (171 bp and 0.67 (169 bp. A transmission disequilibrium test with a family-based association test (FBAT software program was used for analysis. FBAT analysis showed overtransmission of the 169 bp allele in NSOC (P=0.0005. These results suggest that the CA repeat polymorphism of the MSX1 gene may play a role in risk of NSOC in populations from Southern Brazil.

  11. Identification of SNPs in growth-related genes in Colombian creole cattle.

    Science.gov (United States)

    Martinez, R; Rocha, J F; Bejarano, D; Gomez, Y; Abuabara, Y; Gallego, J

    2016-09-19

    Colombian creole cattle have important adaptation traits related to heat tolerance and reproductive and productive efficiency. Romosinuano (ROMO) and Blanco Orejinegro (BON) are the most common breeds used by Colombian cattle breeders. Growth traits are of prime importance in these animals, which are mainly raised for beef production. Genes encoding growth hormone, growth hormone receptor, homeobox protein, insulin growth factor binding protein 3, leptin, and myostatin have been associated with physiological growth pathways in cattle and other species. We therefore aimed to identify single nucleotide polymorphisms (SNPs) within these genes in ROMO, BON, and Zebu cattle. DNA regions of these genes were sequenced in 386 animals; 47 new SNPs were found, of which 14 were located in the exonic regions, thereby changing the protein sequence. An association of SNPs with weaning weight (WW), daily weight gain at weaning (DWG), and weight at 16 months (W16M) traits was deduced. The genetic analysis revealed several SNPs related to these traits. The SNP GhRE06.2 had a significant association with WW and the SNP Lep03.4 was highly associated with DWG and W16M. Other polymorphisms were significantly associated with WW and DWG, although they did not surpass the Bonferroni significance threshold. The new mutations identified may indicate important points of genetic control in the DNA that could be responsible for changes in the expression of the analyzed traits. These SNPs might be used in future breeding programs to improve the productive performance of cattle in beef farms.

  12. Analysis of a candidate gene associated with growth suppression of choriocarcinoma and differentiation of trophoblasts.

    Science.gov (United States)

    Asanoma, Kazuo; Kato, Hidenori; Inoue, Takafumi; Matsuda, Takao; Wake, Norio

    2004-08-01

    To isolate a choriocarcinoma suppressor gene and analyze its structure and function. We constructed a polymerase chain reaction-based subtracted fragmentary cDNA library between normal placental villi and choriocarcinoma cell line CC1. A novel homeobox gene, designated NECC1 (not expressed in differ choriocarcinoma clone 1), is included in this library. We analyzed the structure and function of NECC1 with molecular biology. NECC1 comprises an open reading frame of 219 nucleotides encoding 73 amino acids and contains a homeodomain as a consensus motif. NECC1 is located on human chromosome 4q11-q12, and its expression is ubiquitous in the brain, placenta, lung, smooth muscle, uterus, bladder, kidney and spleen. Normal placental villi abundantly expressed NECC1, but all choriocarcinoma cell lines examined and most surgically removed choriocarcinoma tissue samples failed to express it. We transfected this gene into choriocarcinoma cell lines and observed remarkable alterations in cell morphology and suppression of in vivo tumorigenesis. Induction of chorionic somatomammotropin hormone 1 by NECC1 transfection suggested differentiation of choriocarcinoma cells to syncytiotrophoblast-like cells. Our results suggest that loss of NECC1 expression is involved in malignant conversion of placental trophoblasts.

  13. Selection of reliable reference genes for gene expression analysis under abiotic stresses in the desert biomass willow, Salix psammophila

    Directory of Open Access Journals (Sweden)

    Jianbo Li

    2016-10-01

    Full Text Available Salix psammophila is a desert shrub willow that has extraordinary adaptation to abiotic stresses and plays an important role in maintaining local ecosystems. Moreover, S. psammophila is regarded as a promising biomass feedstock because of its high biomass yields and short rotation coppice cycle. However, few suitable reference genes (RGs for quantitative real-time polymerase chain reaction (qRT-PCR constrain the study on normalization of gene expression in S. psammophila until now. Here, we investigated the expression stabilities of 14 candidate RGs across tissue types and under four abiotic stress treatments, including heat, cold, salt and drought treatments. After calculation of PCR efficiencies, three different software, NormFinder, geNorm, and BestKeeper were employed to analyze systematically the qRT-PCR data, and the outputs were merged by RankAggreg software. The optimal reference genes selected for gene expression analysis were EF1□□ (Elongation factor-1 alpha and OTU (OTU-like cysteine protease family protein for different tissue types, UBC (Ubiquitin-conjugating enzyme E2 and LTA4H (Leukotriene A-4 hydrolase homologue for heat treatment, HIS (Histone superfamily protein H3 and ARF2 (ADP-ribosylation factor 2 for cold treatment, OTU and ACT7 (Actin 7 for salt treatment, UBC and LTA4H for drought treatment. The expression of UBC, ARF2 and VHAC (V-type proton ATPase subunit C varied the least across tissue types and under abiotic stresses. Furthermore, the relative genes expression profiles of one tissue-specific gene WOX1a (WUSCHEL-related homeobox 1a, and four stress-inducible genes, including Hsf-A2 (Heat shock transcription factors A2, CBF3 (C-repeat binding factor 3, HKT1 (High-Affinity K+ Transporter 1 and GST (Glutathione S-transferase, were conducted to confirm the validity of the reference genes in this study. These results provided an important RGs application guideline for gene expression characterization in S. psammophila.

  14. Generation of a human induced pluripotent stem cell (iPSC line from a patient carrying a P33T mutation in the PDX1 gene

    Directory of Open Access Journals (Sweden)

    Xianming Wang

    2016-09-01

    Full Text Available Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor PDX1 leads to pancreatic agenesis, whereas certain heterozygous point mutations are associated with Maturity-Onset Diabetes of the Young 4 (MODY4 and Type 2 Diabetes Mellitus (T2DM. To understand the pathomechanism of MODY4 and T2DM, we have generated iPSCs from a woman with a P33T heterozygous mutation in the transactivation domain of PDX1. The resulting PDX1 P33T iPSCs generated by episomal reprogramming are integration-free, have a normal karyotype and are pluripotent in vitro and in vivo. Taken together, this iPSC line will be useful to study diabetes pathomechanisms.

  15. Creating a Servitude to solve an encroachment Dispute: A Solution or creating another Problem?

    Directory of Open Access Journals (Sweden)

    Zsa-Zsa Temmers Boggenpoel

    2013-12-01

    Full Text Available The main focus of this note is the case of Roseveare v Katmer, Katmer v Roseveare 2013 ZAGPJHC 18, which provides an interesting (though possibly constitutionally problematic perspective to the encroachment problem. The decision in this case has opened the door for courts to create servitudes in instances where encroachments are left intact based on policy reasons. Concerning these policy reasons, the note investigates the reasonableness standard as it was applied in the case. It is argued that it is important to differentiate between the applications of reasonableness in encroachment cases and alleged nuisance disputes. The decision in this case creates the impression that courts may now order that a servitude be registered in favour of the encroacher against the affected landowner’s property. It seems as though the court had in mind the creation of a praedial servitude to justify the continued existence of the encroachment. The servitude is created by court order against the will of the affected landowner. At common law, the creation of a servitude in this respect does not exist, and the authority from which the power derives to make an order like this is not entirely clear. The court also does not provide any authority for the creation of the servitude in favour of the encroacher. Consequently, it is argued that this may have serious constitutional implications. For one, lack of authority for the deprivation that results may be unconstitutional because there is no law of general application that authorises the deprivation in terms of section 25(1. The creation of a servitude to explain the continued existence of the encroachment is not automatically included in the general discretion to replace removal with compensation. It is contended that an order that forces the affected landowner to register a servitude in favour of the encroacher to preserve the existing encroachment situation will be in conflict with section 25(1 as far as the common

  16. Merging Galaxies Create a Binary Quasar

    Science.gov (United States)

    2010-02-01

    Astronomers have found the first clear evidence of a binary quasar within a pair of actively merging galaxies. Quasars are the extremely bright centers of galaxies surrounding super-massive black holes, and binary quasars are pairs of quasars bound together by gravity. Binary quasars, like other quasars, are thought to be the product of galaxy mergers. Until now, however, binary quasars have not been seen in galaxies that are unambiguously in the act of merging. But images of a new binary quasar from the Carnegie Institution's Magellan telescope in Chile show two distinct galaxies with "tails" produced by tidal forces from their mutual gravitational attraction. "This is really the first case in which you see two separate galaxies, both with quasars, that are clearly interacting," says Carnegie astronomer John Mulchaey who made observations crucial to understanding the galaxy merger. Most, if not all, large galaxies, such as our galaxy the Milky Way, host super-massive black holes at their centers. Because galaxies regularly interact and merge, astronomers have assumed that binary super-massive black holes have been common in the Universe, especially during its early history. Black holes can only be detected as quasars when they are actively accreting matter, a process that releases vast amounts of energy. A leading theory is that galaxy mergers trigger accretion, creating quasars in both galaxies. Because most such mergers would have happened in the distant past, binary quasars and their associated galaxies are very far away and therefore difficult for most telescopes to resolve. The binary quasar, labeled SDSS J1254+0846, was initially detected by the Sloan Digital Sky Survey, a large scale astronomical survey of galaxies and over 120,000 quasars. Further observations by Paul Green of the Harvard-Smithsonian Center for Astrophysics and colleagues* using NASA's Chandra's X-ray Observatory and telescopes at Kitt Peak National Observatory in Arizona and Palomar

  17. Creating Partnerships on Campus to Facilitate Practical Experiences

    Science.gov (United States)

    Becker, Craig M.; Johnson, Hans; McNeil, Michael P.; Warren, Karen

    2006-01-01

    College campuses create small communities where mutually beneficial partnerships can be used to create practical work experiences for students. The procedure outlined in this article outlines how to create a partnership between the campus health and recreation center and an academic department to evaluate the implementation of a new smoking…

  18. Download - CREATE portal | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available .6 KB) Simple search and download 3 InCeP create_portal_incep.zip (1 KB) Simple search and download 4 InCeP images create_portal_imag...es.zip (13.4 MB) - 5 KeyMolnet data create_portal_keymolnet.zip (7.1 MB) - 6 Mascot

  19. 31 CFR 900.8 - No private rights created.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false No private rights created. 900.8... No private rights created. The standards in this chapter do not create any right or benefit, substantive or procedural, enforceable at law or in equity by a party against the United States, its agencies...

  20. 45 CFR 30.9 - No private rights created.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false No private rights created. 30.9 Section 30.9... Provisions § 30.9 No private rights created. The standards in this part do not create any right or benefit, substantive or procedural, enforceable at law or in equity by a party against the United States, the...