WorldWideScience

Sample records for critical region gene

  1. Critical Environmental Regions

    Directory of Open Access Journals (Sweden)

    VICTOR SOROCOVSCHI

    2005-01-01

    Full Text Available A short etymological interpretation of the notion of regions (Rette Lineatte, etc.. The region is: R= f (S+P, where S is space and P is power. There follows an evaluation of the characteristics of the region and the presentation of different approaches to the region. From the classic ideas (von Humboldt, 1885, Dokuceaev, 1899, Herbertson, 1905, and others we get to a wide interpretative array of what we accept as organizational spatial units of geographical reality. The environmental region has important connotations with regard to the system as a surrounded element (man, society and the adjacent system. Critical environmental regions are areas where there already exists interactive degradation. The critical character may be physical, hence the “geocritical regions” or the result of human impact, hence the “anthropocritical regions.” Critical situations are differentiated at the local, regional, and global level. In order to understand critical regional situations we must refer to the following characteristics: fragility, resilience, and vulnerability. Still there are few environmental studies on critical regions and work must be done in this field.

  2. Microphthalmia with linear skin defects syndrome (MLS): Characterization of the critical region and isolation of candidate genes

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    Schaefer, L.; Wapenaar, M.C.; Grillo, A. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Microphthalmia with linear skin defects syndrome (MLS) is an X-linked male-lethal disorder characterized by abnormalities in the development of the eye, skin, and brain. We defined the MLS critical region through analysis of hybrid cell lines retaining various deletion breakpoints in Xp22, including cell lines from 17 female patients showing features of MLS. Using a combination of YAC cloning and long-range restriction analysis, the MLS candidate region was estimated to be 450-550 kb. A minimally overlapping cosmid contig comprised of 20 cosmid clones was subsequently developed in this region. These cosmids are currently being used to isolate expressed sequences using cross-species conservation studies and exon-trapping. An evolutionarily conserved sequence isolated from a cosmid within the critical region has been used to isolate several overlapping cDNAs from a human embryonic library. Northern analysis using these cDNA clones identified a 5.2 kb transcript in all tissues examined. Sequence analysis revealed a 777 base pair open reading frame encoding a putative 258 amino acid protein. Using the exon-trapping method, fifty-four putative exons have been isolated from fourteen cosmids within the critical region. The expression patterns of the genes containing these exons are being analyzed by polymerase chain reaction (PCR) using reverse-transcribed mRNA from several human tissues and primers corresponding to the exon sequences. Using this approach in combination with exon connection, we determined the four of the trapped exons belong to the same cDNA transcript, which is expressed in adult retina, lymphoblast, skeletal muscle, and fetal brain. To date, we have isolated and sequenced 1 kilobase of this gene, all of which appears to be open reading frame. Both of the genes isolated from the critical region are being analyzed as possible candidates for MLS.

  3. A conserved region in the 3' untranslated region of the human LIMK1 gene is critical for proper expression of LIMK1 at the post-transcriptional level

    Institute of Scientific and Technical Information of China (English)

    Guang-Fei Deng; Shu-Jing Liu; Xun-Sha Sun; Wei-Wen Sun; Qi-Hua Zhao; Wei-Ping Liao; Yong-Hong Yi

    2013-01-01

    LIM kinase 1 (LIMK1),a cytosolic serine/threonine kinase,regulates actin filament dynamics and reorganization and is involved in neuronal development and brain function.Abnormal expression of LIMK1 is associated with several neurological disorders.In this study,we performed a conservation analysis using Vector NTI (8.0) software.The dualluciferase reporter assay and real-time quantitative RT-PCR were used to assess the protein and mRNA levels of the reporter gene,respectively.We found that a region ranging from nt +884 to +966 in the human LIMK1 3' untranslated region (UTR) was highly conserved in the mouse Limk1 3' UTR and formed a structure containing several loops and stems.Luciferase assay showed that the relative luciferase activity of the mutated construct with the conserved region deleted,pGL4-hLIMK1-3U-M,in SH-SY5Y and HEK-293 cells was only ~60% of that of the wild-type construct pGL4-hLIMK1-3U,indicating that the conserved region is critical for the reporter gene expression.Real-time quantitative RT-PCR analysis demonstrated that the relative Luc2 mRNA levels in SH-SY5Y and HEK293 cells transfected with pGL4-hLIMK1-3U-M decreased to ~50% of that in cells transfected with pGL4-hLIMK1-3U,suggesting an important role of the conserved region in maintaining Luc2 mRNA stability.Our study suggests that the conserved region in the LIMK1 3' UTR is involved in regulating LIMK1 expression at the post-transcriptional level,which may help reveal the mechanism underlying the regulation of LIMK1 expression in the central nervous system and explore the relationship between the 3'-UTR mutant and neurological disorders.

  4. Characterisation of the Angelman syndrome critical region

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    Gilbert, H.L.; Buxton, J.; Chan, C.T.J. [Univ. of London (United Kingdom)] [and others

    1994-09-01

    Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are distinct neurogenetic disorders associated with a deletion of 15q11-13, a region subject to genomic imprinting. The chromosomal deletions are either maternal (AS) or paternal (PWS) in origin. The AS critical region was previously defined by an inherited deletion of approximately 1.5 Mb, encompassing TD3-21, LS6-1 and GABRB3. An individual with classical AS has been identified whose deletion includes LS6-1 but not TD3-21 or GABRB3. Both maternal and paternal methylation patterns at ZNF127, PW71B and SNRPN are present, suggesting that the AS gene itself is a disrupted, rather than imprinting sequences, as proposed recently for some familial cases. Initially, the deletion was detected by (CA)n repeat analysis. Cosmids derived from a 260 kb LS6-1 YAC were then used to confirm the deletion by fluorescence in-situ hybridization (FISH). Neither end cosmid from the YAC is deleted, suggesting that the AS critical region is less than 200 kb. Fragments isolated from the cosmids which span the deletion were used to further delineate the AS critical region by Southern blot analysis. Single copy genomic fragments within this region were then used to search for differential parental methylation patterns and potential coding sequences. We have used cosmids from the region in exon-trapping experiments. Using this combination of approaches, we aim to identify candidate genes for AS.

  5. Two critical genes (HLA-DRB1 and ABCF1)in the HLA region are associated with the susceptibility to autoimmune pancreatitis.

    Science.gov (United States)

    Ota, Masao; Katsuyama, Yoshihiko; Hamano, Hideaki; Umemura, Takeji; Kimura, Akinori; Yoshizawa, Kaname; Kiyosawa, Kendo; Fukushima, Hirofumi; Bahram, Seiamak; Inoko, Hidetoshi; Kawa, Shigeyuki

    2007-01-01

    We have previously reported that autoimmune pancreatitis (AIP) is a bioclinical entity characterized by high serum immunoglobulin G4 concentrations and association with the HLA-DRB1*0405-DQB1*0401 haplotype. However, the precise identity of gene(s) within this haplotype directly responsible for AIP pathogenesis is yet to be established. To dissect the genetic contribution of the incriminated haplotype, we have now performed an association analysis within the human leukocyte antigen (HLA) region using various types of polymorphic markers. Genomic DNAs from 43 AIP patients and 213 unrelated Japanese controls were used in this analysis. In each DNA sample, we established the genotype of 25 microsatellite markers distributed throughout the HLA region, that of single nucleotide polymorphism within the 5'-flanking regions of the TNFA and IkBLI (also known as NFKBIL1) as well as HLA class I and II genes. The HLA-linked susceptibility regions for AIP were localized to two segments: HLA-DRB1 (*0405; OR = 3.20, P = 0.00063, Pc = 0.0016) -DQB1 (*0401; OR = 3.29, P = 0.00046, Pc = 0.0069) in the HLA class II and C3-2-11 microsatellite (allele 219; OR = 2.96, P = 0.0076, Pc = 0.099) in the HLA class I regions. Upon stratification analysis in search for a synergistic effect given the extensive linkage disequilibrium within the major histocompatibility complex, it was established that each segment contributed to disease pathogenesis. The two critical HLA regions for susceptibility to AIP are limited to the HLA-DRB1*0405-DQB1*0401 in the class II and the ABCF1 proximal to C3-2-11, telomeric of HLA-E, in the class I regions.

  6. The refinement of the critical region for the 2q31.2q32.3 deletion syndrome indicates candidate genes for mental retardation and speech impairment.

    Science.gov (United States)

    Cocchella, Alessandro; Malacarne, Michela; Forzano, Francesca; Marciano, Carmela; Pierluigi, Mauro; Perroni, Lucia; Faravelli, Francesca; Di Maria, Emilio

    2010-10-05

    Current literature provides more than 30 patients with interstitial deletions in chromosome 2q31q33. Only a few of them were studied using high-resolution methods. Among these, two patients had presented with a particular consistence of some clinical features associated to a deletion between bands q31.2 and q32.3 of chromosome 2. This clinical pattern, labeled as "2q31.2q32.3 syndrome," consists of multiple dysmorphisms, developmental delay, mental retardation and behavioural disturbances. We report an adult female patient with a 4.4 Mb deletion in the 2q31.2q32.3 region, showing facial dysmorphisms, mental retardation and absence of speech. The region overlaps with the deletion found in the two cases previously reported. The critical region points to a few genes, namely NEUROD1, ZNF804A, PDE1A, and ITGA4, which are good candidates to explain the cognitive and behavioural phenotype, as well as the severe speech impairment associated with the 2q31.2q32.3 deletion.

  7. Hexasomy of the Prader-Willi/Angelman critical region, including the OCA2 gene, in a patient with pigmentary dysplasia: case report.

    Science.gov (United States)

    Kraoua, Lilia; Chaabouni, Myriam; Ewers, Elisabeth; Chelly, Imen; Ouertani, Ines; Ben Jemaa, Lamia; Maazoul, Faouzi; Liehr, Thomas; Chaabouni, Habiba

    2011-01-01

    Derivatives of chromosome 15, often referred to as inv dup(15), represent the most common supernumerary marker chromosome (SMC). SMC(15)s can be classified into two major groups according to their length: small SMC(15) and large ones. Depending on the amount of euchromatin, the carriers may either present with a normal phenotype or with a recognizable syndrome. Here we describe a patient with severe mental retardation, epilepsy, dysmorphic features and pigmentary dysplasia. His karyotype was 47,XY,+mar[41]/46,XY[9]. Chromosomal fluorescence in situ hybridization (FISH) showed the SMC to be originating from chromosome 15, dicentric and containing four copies of the Prader-Willi/Angelman Syndrome Critical Region (PWACR), including the OCA2 gene. Molecular studies indicated that it is maternally derived. This report supports the previous observations assuming that severity of phenotype in patients with SMC(15) depends on the dosage of the PWACR and that skin pigmentation is correlated to OCA2 gene copy number. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  8. Construction of a YAC contig and STS map spanning 2.5 Mbp in Xq25, the critical region for the X-linked lymphoproliferative (XLP) gene

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    Lanyi, A.; Li, B.F.; Li, S. [Univ. of Nebraska Medical Center, Omaha, NE (United States)] [and others

    1994-09-01

    X-linked lymphoproliferative disease (XLP) is characterized by a marked vulnerability in Epstein-Barr virus (EBV) infection. Infection of XLP patients with EBV invariably results in fatal mononucleosis, agammaglobulinemia or B-cell lymphoma. The XLP gene lies within a 10 cM region in Xq25 between DXS42 and DXS10. Initial chromosome studies revealed an interstitial, cytogenetically visible deletion in Xq25 in one XLP family (43-004). We estimated the size of the Xq25 deletion by dual laser flow karyotyping to involve 2% of the X chromosome, or approximately 3 Mbp of DNA sequences. To further delineate the deletion we performed a series of pulsed field gel electrophoresis (PFGE) analyses which showed that DXS6 and DXS100, two Xq25-specific markers, are missing from 45-004 DNA. Five yeast artificial chromosomes (YACs) from a chromosome X specific YAC library containing sequences deleted in patient`s 43-004 DNA were isolated. These five YACs did not overlap, and their end fragments were used to screen the CEPH MegaYAC library. Seven YACs were isolated from the CEPH MegaYAC library. They could be arranged into a contig which spans between DXS6 and DXS100. The contig contains a minimum of 2.5 Mbp of human DNA. A total of 12 YAC end clone, lambda subclones and STS probes have been used to order clones within the contig. These reagents were also used in Southern blot and patients showed interstitial deletions in Xq25. The size of these deletions range between 0.5 and 2.5 Mbp. The shortest deletion probably represents the critical region for the XLP gene.

  9. Cloning and characterization of a putative human holocytochrome c-type synthetase gene (HCCS) isolated from the critical region for microphthalmia with linear skin defects (MLS)

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    Schaefer, L.; Ballabio, A.; Zoghbi, H.Y. [Baylor College of Medicine, Houston, TX (United States)

    1996-06-01

    Microphthalmia with linear skin defects syndrome (MLS) is an X-linked male-lethal disorder associated with X chromosomal rearrangements resulting in monosomy from Xpter to Xp22. Features include microphthalmia, sclerocornea, linear skin defects, and agenesis of the corpus callosum. Using a cross-species conservation strategy, an expressed sequence from the 450- to the 550-kb MLS critical region on Xp22 was identified by screening a human embryo cDNA library. Northern analysis revealed a transcript of {approx}2.6 kb in all tissues examined, with weaker expression of {approx}1.2- and {approx}5.2-kb transcripts. The strongest expression was observed in heart and skeletal muscle. Sequence analysis of a 3-kb cDNA contig revealed an 807-bp open reading frame encoding a putative 268-amino-acid-protein. Comparison of the sequence with sequences in the databases revealed homology with holocytochrome c-type synthetases, which catalyze the covalent addition of a heme group onto c-type cytochromes in the mitochondria. The c-type cytochromes are required for proper functioning of the electron transport pathway. The human gene (HGMW-approved symbol HCCS) and the corresponding murine gene characterized in this paper are the first mammalian holocytochrome c-type synthetases to be described in the literature. Because of the lack of a neuromuscular phenotype in MLS, it is uncertain whether the deletion of a mitochondrial holocytochrome synthetase would contribute to the phenotype seen in MLS. The expression pattern of this gene and knowledge about the function of holocytochrome synthetases, however, suggest that it is a good candidate for X-linked encephalomyopathies typically associated with mitochondrial dysfunction. 25 refs., 4 figs.

  10. The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease.

    Science.gov (United States)

    Kimura, Ryo; Kamino, Kouzin; Yamamoto, Mitsuko; Nuripa, Aidaralieva; Kida, Tomoyuki; Kazui, Hiroaki; Hashimoto, Ryota; Tanaka, Toshihisa; Kudo, Takashi; Yamagata, Hidehisa; Tabara, Yasuharu; Miki, Tetsuro; Akatsu, Hiroyasu; Kosaka, Kenji; Funakoshi, Eishi; Nishitomi, Kouhei; Sakaguchi, Gaku; Kato, Akira; Hattori, Hideyuki; Uema, Takeshi; Takeda, Masatoshi

    2007-01-01

    We scanned throughout chromosome 21 to assess genetic associations with late-onset Alzheimer disease (AD) using 374 Japanese patients and 375 population-based controls, because trisomy 21 is known to be associated with early deposition of beta-amyloid (Abeta) in the brain. Among 417 markers spanning 33 Mb, 22 markers showed associations with either the allele or the genotype frequency (P KCNJ6 genes. In logistic regression, the DYRK1A (dual-specificity tyrosine-regulated kinase 1A) gene, located in the Down syndrome critical region, showed the highest significance [OR = 2.99 (95% CI: 1.72-5.19), P = 0.001], whereas the RUNX1 gene showed a high odds ratio [OR = 23.3 (95% CI: 2.76-196.5), P = 0.038]. DYRK1A mRNA level in the hippocampus was significantly elevated in patients with AD when compared with pathological controls (P < 0.01). DYRK1A mRNA level was upregulated along with an increase in the Abeta-level in the brain of transgenic mice, overproducing Abeta at 9 months of age. In neuroblastoma cells, Abeta induced an increase in the DYRK1A transcript, which also led to tau phosphorylation at Thr212 under the overexpression of tau. Therefore, the upregulation of DYRK1A transcription results from Abeta loading, further leading to tau phosphorylation. Our result indicates that DYRK1A could be a key molecule bridging between beta-amyloid production and tau phosphorylation in AD.

  11. The human homologue of the Drosophila melanogaster flightless-I gene (fliI) maps within the Smith-Magenis microdeletion critical region in 17p11.2

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    Chen, K.S.; Gunaratne, P.H.; Greenberg, F.; Shaffer, L.G.; Lupski, J.R. [Baylor College of Medicine, Houston, TX (United States); Hoheisel, J.D. [German Cancer Research Center, Heidelberg (Germany); Young, I.G.; Miklos, G.L.G.; Campbell, H.D. [Australian National Univ., Canberra (Australia)

    1995-01-01

    The Smith-Magenis syndrome (SMS) appears to be a contiguous-gene-deletion syndrome associated with a proximal deletion of the short arm of chromosome 17 in band p11.2. The spectrum of clinical findings includes short stature, brachydactyly, developmental delay, dysmorphic features, sleep disturbances, and behavioral problems. The complex phenotypic features suggest deletion of several contiguous genes. However, to date, no protein-encoding gene has been mapped to the SMS critical region. Recently, the Drosophila melanogaster flightless-I gene, fliI, and the homologous human cDNA have been isolated. Mutations in fliI result in loss of flight ability and, when severe, cause lethality due to incomplete cellularization with subsequent abnormal gastrulation. Here, we demonstrate that the human homologue (FLI) maps within the SMS critical region. Genomic cosmids were used as probes for FISH, which localized this gene to the 17p11.2 region. Somatic-cell hybrid-panel mapping further localized this gene to the SMS critical region. Southern blot analysis of somatic-cell hybrids and/or FISH analysis of lymphoblastoid cell lines from 12 SMS patients demonstrates the deletion of one copy of FLI in all SMS patients analyzed. 47 refs., 4 figs., 1 tab.

  12. Injury modality, survival interval, and sample region are critical determinants of qRT-PCR reference gene selection during long-term recovery from brain trauma.

    Science.gov (United States)

    Harris, Janna L; Reeves, Thomas M; Phillips, Linda L

    2009-10-01

    In the present study we examined expression of four real-time quantitative RT-PCR reference genes commonly applied to rodent models of brain injury. Transcripts for beta-actin, cyclophilin A, GAPDH, and 18S rRNA were assessed at 2-15 days post-injury, focusing on the period of synaptic recovery. Diffuse moderate central fluid percussion injury (FPI) was contrasted with unilateral entorhinal cortex lesion (UEC), a model of targeted deafferentation. Expression in UEC hippocampus, as well as in FPI hippocampus and parietotemporal cortex was analyzed by qRT-PCR. Within-group variability of gene expression was assessed and change in expression relative to paired controls was determined. None of the four common reference genes tested was invariant across brain region, survival time, and type of injury. Cyclophilin A appeared appropriate as a reference gene in UEC hippocampus, while beta-actin was most stable for the hippocampus subjected to FPI. However, each gene may fail as a suitable reference with certain test genes whose RNA expression is targeted for measurement. In FPI cortex, all reference genes were significantly altered over time, compromising their utility for time-course studies. Despite such temporal variability, certain genes may be appropriate references if limited to single survival times. These data provide an extended baseline for identification of appropriate reference genes in rodent studies of recovery from brain injury. In this context, we outline additional considerations for selecting a qRT-PCR normalization strategy in such studies. As previously concluded for acute post-injury intervals, we stress the importance of reference gene validation for each brain injury paradigm and each set of experimental conditions.

  13. Microprocessor complex subunit DiGeorge syndrome critical region gene 8 (Dgcr8) is required for schwann cell myelination and myelin maintenance.

    Science.gov (United States)

    Lin, Hsin-Pin; Oksuz, Idil; Hurley, Edward; Wrabetz, Lawrence; Awatramani, Rajeshwar

    2015-10-02

    We investigated the role of a key component of the Microprocessor complex, DGCR8, in the regulation of myelin formation and maintenance. We found that conditionally ablating Dgcr8 in Schwann cells (SCs) during development results in an arrest of SC differentiation. Dgcr8 conditional knock-out (cKO) SCs fail to form 1:1 relationships with axons or, having achieved this, fail to form myelin sheaths. The expression of genes normally found in immature SCs, such as sex-determining region Y-box 2 (Sox2), is increased in Dgcr8 cKO SCs, whereas the expression of myelin-related genes, including the master regulatory transcription factor early growth response 2 (Egr2), is decreased. Additionally, expression of a novel gene expression program involving sonic hedgehog (Shh), activated de novo in injured nerves, is elevated in Dgcr8 cKOs but not in Egr2 null mice, a model of SC differentiation arrest, suggesting that the injury-related gene expression program in Dgcr8 cKOs cannot be attributed to differentiation arrest. Inducible ablation of Dgcr8 in adult SCs results in gene expression changes similar to those found in cKOs, including an increase in the expression of Sox2 and Shh. Analyses of these nerves mainly reveal normal myelin thickness and axon size distribution but some dedifferentiated SCs and increased macrophage infiltration. Together our data suggest that Dgcr8 is responsible for modulation of gene expression programs underlying myelin formation and maintenance as well as suppression of an injury-related gene expression program.

  14. The E6-Ap ubiquitin-protein ligase (UBE3A) gene is localized within a narrowed Angelman syndrome critical region.

    Science.gov (United States)

    Sutcliffe, J S; Jiang, Y H; Galijaard, R J; Matsuura, T; Fang, P; Kubota, T; Christian, S L; Bressler, J; Cattanach, B; Ledbetter, D H; Beaudet, A L

    1997-04-01

    Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are distinct clinical phenotypes resulting from maternal and paternal deficiencies, respectively, in human chromosome 15qll-q13. Although several imprinted, paternally expressed transcripts have been identified within the PWS candidate region, no maternally expressed gene has yet been identified within the AS candidate region. We have developed an integrated physical map spanning the PWS and AS candidate regions and localized two breakpoints, including a cryptic t(14;15) translocation associated with AS and a non-AS 15q deletion, which substantially narrow the AS candidate region to approximately 250 kb. Mapping data indicate that the entire transcriptional unit of the E6-AP ubiquitin-protein ligase (UBE3A) gene lies within the AS region. The UBE3A locus expresses a transcript of approximately 5 kb at low to moderate levels in all tissues tested. The mouse homolog of UBE3A was cloned and sequenced revealing a high degree of conservation at nucleotide and protein levels. Northern and RT-PCR analysis of Ube3a expression in mouse tissues from animals with segmental, paternal uniparental disomy failed to detect substantially reduced or absent expression compared to control animals, failing to provide any evidence for maternal-specific expression from this locus. Recent identification of de novo truncating mutations in UBE3A taken with these observations indicates that mutations in UBE3A can lead to AS and suggests that this locus may encode both imprinted and biallelically expressed products.

  15. Identifying candidate genes for X-linked hypophosphatemic rickets (HYP) in the critical region X(p22.1-p22.2)

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    Holm, L.A.; Freedner, N.L.; Maizoub, J.A. [Harvard Medical School, Boston, MA (United States)] [and others

    1994-09-01

    X-linked hypophosphatemic rickets (HYP) is the most common inherited form of rickets, characterized by a proximal renal tubular phosphate leak leading to phosphate-wasting and abnormal 1.25-dihydroxyvitamin D metabolism. The primary defect is unknown, and the candidate gene approach has thus far been unsuccessful in identifying the gene. The HYP locus has been mapped to X(p22.1-p22.2) and more recently to a 500,000 base pair region spanned by two YACs, E01138 and A0472. In an effort to identify the HYP gene in the 500 kb region, we are taking the direct selection approach. Since the tissue expressing the HYP gene is unknown, we are using cDNA libraries from a number of tissues for direct selection, including kidney, liver, thyroid, brain, spinal cord, total fetus, bone, and an osteosarcoma cell line. The tissue cDNA is hybridized to the YACs A0472 and EO1138 (obtained courtesy of Fiona Francis, Imperial Cancer Research Fund, London) in the presence of quenchers, which block repeated and ribosomal sequences on the YACs. A selected library is created from the tissues cDNAs that hybridize to the YACs. The selected cDNA library is first screened to eliminate inserts containing repeated and ribosomal sequences. The presence of the inserts on the YAC and on X(p22.1-p22.2) is then verified using mapping panels. Candidate cDNAs that make it through this analysis are sequenced. Our first attempts at making selected libraries resulted in a number of contaminants. Three separate libraries are currently under construction, using the following combinations of tissue cDNA libraries: (1) kidney, liver, and thyroid; (2) brain, spinal cord, and total fetus; and (3) bone and an osteosarcoma cell line. We will discuss transcripts obtained from these libraries.

  16. 19q13 microdeletion syndrome: Further refining the critical region.

    Science.gov (United States)

    Forzano, Francesca; Napoli, Flavia; Uliana, Vera; Malacarne, Michela; Viaggi, Chiara; Bloise, Raffaella; Coviello, Domenico; Di Maria, Emilio; Olivieri, Irene; Di Iorgi, Natascia; Faravelli, Francesca

    2012-06-01

    The 19q13 microdeletion syndrome is a recently identified disorder of which very few cases have been reported so far. Growth deficiency, microcephaly, ectodermal anomalies and intellectual disability are the major features reported in all the described cases. The critical region has been estimated to span 750 Kb. We report an Italian patient carrying a de novo 1.37 Mb deletion in chromosome 19q13, who presented all the cardinal features of the syndrome, and multiple pituitary hormone deficiency. Our findings might contribute to further refine the critical region to 460 Kb and restrict the list of candidate genes.

  17. Structure-function analysis of RBP-J-interacting and tubulin-associated (RITA) reveals regions critical for repression of Notch target genes.

    Science.gov (United States)

    Tabaja, Nassif; Yuan, Zhenyu; Oswald, Franz; Kovall, Rhett A

    2017-06-23

    The Notch pathway is a cell-to-cell signaling mechanism that is essential for tissue development and maintenance, and aberrant Notch signaling has been implicated in various cancers, congenital defects, and cardiovascular diseases. Notch signaling activates the expression of target genes, which are regulated by the transcription factor CSL (CBF1/RBP-J, Su(H), Lag-1). CSL interacts with both transcriptional corepressor and coactivator proteins, functioning as both a repressor and activator, respectively. Although Notch activation complexes are relatively well understood at the structural level, less is known about how CSL interacts with corepressors. Recently, a new RBP-J (mammalian CSL ortholog)-interacting protein termed RITA has been identified and shown to export RBP-J out of the nucleus, thereby leading to the down-regulation of Notch target gene expression. However, the molecular details of RBP-J/RITA interactions are unclear. Here, using a combination of biochemical/cellular, structural, and biophysical techniques, we demonstrate that endogenous RBP-J and RITA proteins interact in cells, map the binding regions necessary for RBP-J·RITA complex formation, and determine the X-ray structure of the RBP-J·RITA complex bound to DNA. To validate the structure and glean more insights into function, we tested structure-based RBP-J and RITA mutants with biochemical/cellular assays and isothermal titration calorimetry. Whereas our structural and biophysical studies demonstrate that RITA binds RBP-J similarly to the RAM (RBP-J-associated molecule) domain of Notch, our biochemical and cellular assays suggest that RITA interacts with additional regions in RBP-J. Taken together, these results provide molecular insights into the mechanism of RITA-mediated regulation of Notch signaling, contributing to our understanding of how CSL functions as a transcriptional repressor of Notch target genes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Regional analgesia in postsurgical critically ill patients.

    Science.gov (United States)

    Moliner Velázquez, S; Rubio Haro, R; De Andrés Serrano, C; De Andrés Ibáñez, J

    2017-03-01

    Regional analgesia intrinsically, based on its physiological effects, is routinely used for the perioperative treatment of pain associated with surgical procedures. However, in other areas such as the non-surgical treatment of acute pain for patients in a critical condition, it has not been subjected to specific prospective studies. If we confine ourselves to the physiological effects of the nerve block, in a situation of stress, the indications for regional anaesthesia in this group of patients extend to the management of a wide variety of medical as well as postsurgical conditions, of trauma patients and of other painful procedures performed in the patient's bed. The critical patient certainly must be analyzed individually as their own primary conditions is of vital importance, as well as any associated conditions they have developed that can potentially increase the risk of systemic toxicity or morbidity, such as, coagulopathies, infection, immunosuppressive states, sedation and problems associated with mechanical ventilation. This review aims to assess the role of regional analgesia in critically ill patients, placing it within the algorithm decision tree of the professional responsible for patients in critical care units, all based on the evidence of potential benefits according to the published literature. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. The human homologue of the Drosophila melanogaster flightless-I gene (fliI) maps within the Smith-Magenis microdeletion critical region in 17p11.2

    Energy Technology Data Exchange (ETDEWEB)

    Chen, K.S.; Nguyen, D.; Greenberg, F. [Baylor College of Medicing, Houston, TX (United States)] [and others

    1994-09-01

    The Smith-Magenis syndrome (SMS) appears to be a contiguous gene deletion syndrome associated with a proximal deletion of the short arm of chromosome 17 in band p11.2. The spectrum of clinical findings includes short stature, brachydactyly, developmental delay, dysmorphic features, sleep disturbances and behavioral problems. The complex phenotypic features suggest deletion of several contiguous genes. However, to date no protein encoding gene has been mapped to the SMS critical region. Recently, Campbell described the cloning and characterization of D. melanogaster fli cDNAs and of homologous cDNAs from caenorhabditis elegans and from humans. Mutations in fliI result in loss of flight ability and, when severe, cause lethality due to incomplete cellularization with subsequent abnormal gastrulation. The amino acid sequence deduced from the FLI cDNA has 52% similarity to the human gelsolin protein and also has a N-terminal leucine-rich domain with 16 consecutive leucine-rich repeats (LRR). Here, we demonstrate that the human homologue (FLI) maps within the SMS critical region. Genomic cosmids were used as probes for fluorescence in situ hybridization (FISH) and localized this gene to the 17p11.2 region. Somatic cell hybrids and/or FISH analysis of lymphoblastoid cell lines form 12 SMS patients demonstrate that one copy of the FLI gene is deleted in all SMS patients analyzed with the common deletion. Further studies are required to determine if haploinsufficiency of FLI or other as yet unidentified genes is important for the expression of the SMS phenotype.

  20. Mapping of the human dentin matrix acidic phosphoprotein gene (DMP1) to the dentinogenesis imperfecta type II critical region at chromosome 4q21

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    Aplin, H.M.; Hirst, K.L.; Crosby, A.H.; Dixon, M.J. [Univ. of Manchester (United Kingdom)

    1995-11-20

    Dentinogenesis imperfecta type II (DGI1) is an autosomal dominant disorder of dentin formation, which has been mapped to human chromosome 4q12-q21. The region most likely to contain the DGI1 locus is a 3.2-cM region surrounding the osteopontin (SPP1) locus. Recently, a novel dentin-specific acidic phosphoprotein (dmp1) has been cloned in the rat and mapped to mouse chromosome 5q21. In the current investigation, we have isolated a cosmid containing the human DMP1 gene. The isolation of a short tandem repeat polymorphism at this locus has allowed us to map the DMP1 locus to human chromosome 4q21 and demonstrate that it is tightly linked to DGI1 in two families (Z{sub max} = 11.01, {theta} = 0.001). The creation of a yeast artificial chromosome contig around SPP1 has further allowed us to demonstrate that DMP1 is located within 150 kb of the bone sialoprotein and 490 kb of the SPP1 loci, respectively. DMP1 is therefore a strong candidate for the DGI1 locus. 12 refs., 2 figs., 1 tab.

  1. The gene for human U2 snRNP auxiliary factor small 35-kDa subunit (U2AF1) maps to the progressive myoclonus epilepsy (EPM1) critical region on chromosome 21q22.3

    Energy Technology Data Exchange (ETDEWEB)

    Lalioti, M.D.; Rossier, C.; Antonarakis, S.E. [Univ. of Geneva Medical School (Switzerland)] [and others

    1996-04-15

    We used targeted exon trapping to clone portions of genes from human chromosome 21q22.3. One trapped sequence showed complete homology with the cDNA of human U2AF{sup 35} (M96982; HGM-approved nomenclature U2AF1), which encodes for the small 35-kDa subunit of the U2 snRNP auxiliary factor. Using the U2AF1 cDNA as a probe, we mapped this gene to cosmid Q15D2, a P1, and YAC 350F7 of the Chumakov et al. contig, close to the cystathionine-{beta}-synthase gene (CBS) on 21q22.3. This localization was confirmed by PCR using oligonucleotides from the 3{prime} UTR and by FISH. As U2AF1 associated with a number of different factors during mRNA splicing, overexpression in trisomy 21 individuals could contribute to some Down syndrome phenotypes by interfering with the splicing process. Furthermore, because this gene maps in the critical region for the progressive myoclonus epilepsy I locus (EPM1), mutation analysis will be carried out in patients to evaluate the potential role of U2AF1 as a candidate for EPM1. 24 refs., 1 fig.

  2. Genetic dissection of the Down syndrome critical region.

    Science.gov (United States)

    Jiang, Xiaoling; Liu, Chunhong; Yu, Tao; Zhang, Li; Meng, Kai; Xing, Zhuo; Belichenko, Pavel V; Kleschevnikov, Alexander M; Pao, Annie; Peresie, Jennifer; Wie, Sarah; Mobley, William C; Yu, Y Eugene

    2015-11-15

    Down syndrome (DS), caused by trisomy 21, is the most common chromosomal disorder associated with developmental cognitive deficits. Despite intensive efforts, the genetic mechanisms underlying developmental cognitive deficits remain poorly understood, and no treatment has been proven effective. The previous mouse-based experiments suggest that the so-called Down syndrome critical region of human chromosome 21 is an important region for this phenotype, which is demarcated by Setd4/Cbr1 and Fam3b/Mx2. We first confirmed the importance of the Cbr1-Fam3b region using compound mutant mice, which carry a duplication spanning the entire human chromosome 21 orthologous region on mouse chromosome 16 [Dp(16)1Yey] and Ms1Rhr. By dividing the Setd4-Mx2 region into complementary Setd4-Kcnj6 and Kcnj15-Mx2 intervals, we started an unbiased dissection through generating and analyzing Dp(16)1Yey/Df(16Setd4-Kcnj6)Yey and Dp(16)1Yey/Df(16Kcnj15-Mx2)Yey mice. Surprisingly, the Dp(16)1Yey-associated cognitive phenotypes were not rescued by either deletion in the compound mutants, suggesting the possible presence of at least one causative gene in each of the two regions. The partial rescue by a Dyrk1a mutation in a compound mutant carrying Dp(16)1Yey and the Dyrk1a mutation confirmed the causative role of Dyrk1a, whereas the absence of a similar rescue by Df(16Dyrk1a-Kcnj6)Yey in Dp(16)1Yey/Df(16Dyrk1a-Kcnj6)Yey mice demonstrated the importance of Kcnj6. Our results revealed the high levels of complexities of gene actions and interactions associated with the Setd4/Cbr1-Fam3b/Mx2 region as well as their relationship with developmental cognitive deficits in DS.

  3. Big-Think Regionalism: A Critical Survey

    OpenAIRE

    Richard Baldwin

    2008-01-01

    Economic thinking on regionalism has traditionally focused on the Vinerian question: Would a nation gain from joining a trade bloc? Since 1991, "Big Think Regionalism" considers the broader question of regionalism’s impact on the world trading system focusing on two questions: Does spreading regionalism harm world welfare? and Does regionalism help or hinder multilateralism? This paper syntheses and critiques the theoretical literature in an attempt to identify the insights that are useful fo...

  4. Migrant Cuisine, Critical Regionalism and Gastropoetics

    Directory of Open Access Journals (Sweden)

    Ben Highmore

    2013-02-01

    Full Text Available This essay is based around two sentences from Nadeem Alslam’s 2004 novel Maps for Lost Lovers. From this base comes an exploration of what aesthetics could mean for cultural studies, and what sorts of practices it could foster. The essay argues for the pertinence this may have for the study of food culture, while also taking up the project of ‘critical regionalism’ and ‘gastropoetics’ as a way of moving from the tightly figured frame of a fragment from a novel, to the histories, geographies and affects that impact on it.

  5. Teaching Critical Thinking in World Regional Geography through Stakeholder Debate

    Science.gov (United States)

    Sziarto, Kristin M.; McCarthy, Linda; Padilla, Nicholas L.

    2014-01-01

    Using a stakeholder debate based on a real-world case of regional construction--that of Turkey's application to join the European Union--improved students' critical thinking in an introductory world regional geography course. Such courses are a staple offering among US geography departments, and often the only exposure of non-majors to geographic…

  6. Holographic butterfly effect and diffusion in quantum critical region

    Science.gov (United States)

    Ling, Yi; Xian, Zhuo-Yu

    2017-09-01

    We investigate the butterfly effect and charge diffusion near the quantum phase transition in holographic approach. We argue that their criticality is controlled by the holographic scaling geometry with deformations induced by a relevant operator at finite temperature. Specifically, in the quantum critical region controlled by a single fixed point, the butterfly velocity decreases when deviating from the critical point. While, in the non-critical region, the behavior of the butterfly velocity depends on the specific phase at low temperature. Moreover, in the holographic Berezinskii-Kosterlitz-Thouless transition, the universal behavior of the butterfly velocity is absent. Finally, the tendency of our holographic results matches with the numerical results of Bose-Hubbard model. A comparison between our result and that in the O( N ) nonlinear sigma model is also given.

  7. Genetic dissection of the Down syndrome critical region

    OpenAIRE

    Jiang,Xiaoling; Liu, Chunhong; Yu, Tao; ZHANG Li; Meng, Kai; Xing, Zhuo; Belichenko, Pavel V.; Kleschevnikov, Alexander M.; Pao, Annie; Peresie, Jennifer; Wie, Sarah; Mobley, William C.; Yu, Y. Eugene

    2015-01-01

    Down syndrome (DS), caused by trisomy 21, is the most common chromosomal disorder associated with developmental cognitive deficits. Despite intensive efforts, the genetic mechanisms underlying developmental cognitive deficits remain poorly understood, and no treatment has been proven effective. The previous mouse-based experiments suggest that the so-called Down syndrome critical region of human chromosome 21 is an important region for this phenotype, which is demarcated by Setd4/Cbr1 and Fam...

  8. The ribosomal gene spacer region in archaebacteria

    Science.gov (United States)

    Achenbach-Richter, L.; Woese, C. R.

    1988-01-01

    Sequences for the spacer regions that separate the 16S and 23S ribosomal RNA genes have been determined for four more (strategically placed) archaebacteria. These confirm the general rule that methanogens and extreme halophiles have spacers that contain a single tRNAala gene, while tRNA genes are not found in the spacer region of the true extreme thermophiles. The present study also shows that the spacer regions from the sulfate reducing Archaeglobus and the extreme thermophile Thermococcus (both of which cluster phylogenetically with the methanogens and extreme halophiles) contain each a tRNAala gene. Thus, not only all methanogens and extreme halophiles show this characteristic, but all organisms on the "methanogen branch" of the archaebacterial tree appear to do so. The finding of a tRNA gene in the spacer region of the extreme thermophile Thermococcus celer is the first known phenotypic property that links this organism with its phylogenetic counterparts, the methanogens, rather than with its phenotypic counterparts, the sulfur-dependent extreme thermophiles.

  9. Gene Regions Responding to Skeletal Muscle Atrophy

    Science.gov (United States)

    Booth, Frank W.

    1997-01-01

    Our stated specific aims for this project were: 1) Identify the region(s) of the mouse IIb myosin heavy chain (MHC) promoter necessary for in vivo expression in mouse fast-twitch muscle, and 2) Identify the region(s) of the mouse IIb MHC promoter responsive to immobilization in mouse slow-twitch muscle in vivo. We sought to address these specific aims by introducing various MHC IIb promoter/reporter gene constructs directly into the tibialis anterior and gastrocnemius muscles of living mice. Although the method of somatic gene transfer into skeletal muscle by direct injection has been successfully used in our laboratory to study the regulation of the skeletal alpha actin gene in chicken skeletal muscle, we had many difficulties utilizing this procedure in the mouse. Because of the small size of the mouse soleus and the difficulty in obtaining consistent results, we elected not to study this muscle as first proposed. Rather, our MHC IIb promoter deletion experiments were performed in the gastrocnemius. Further, we decided to use hindlimb unloading via tail suspension to induce an upregulation of the MHC IIb gene, rather than immobilization of the hindlimbs via plaster casts. This change was made because tail suspension more closely mimics spaceflight, and this procedure in our lab results in a smaller loss of overall body mass than the mouse hindlimb immobilization procedure. This suggests that the stress level during tail suspension is less than during immobilization. This research has provided an important beginning point towards understanding the molecular regulation of the MHC lIb gene in response to unweighting of skeletal muscle Future work will focus on the regulation of MHC IIb mRNA stability in response to altered loading of skeletal muscle

  10. Axial dependence of optical weak measurements in the critical region

    CERN Document Server

    Araujo, Manoel P; Maia, Gabriel G

    2015-01-01

    The interference between optical beams of different polarizations plays a fundamental role in reproducing the optical analog of the electron spin weak measurement. The extraordinary point in optical weak measurements is represented by the possibility to estimate with great accuracy the Goos-Haenchen (GH) shift by measuring the distance between the peak of the outgoing beams for two opposite rotation angles of the polarizers located before and after the dielectric block. Starting from the numerical calculation of the GH shift, which clearly shows a frequency crossover for incidence near to the critical angle, we present a detailed study of the interference between s and p polarized waves in the critical region. This allows to determine in which conditions it is possible to avoid axial deformations and reproduce the GH curves. In view of a possible experimental implementation, we give the expected weak measurement curves for Gaussian lasers of different beam waist sizes propagating through borosilicate (BK7) an...

  11. Simple Model for Identifying Critical Regions in Atrial Fibrillation

    Science.gov (United States)

    Peters, Nicholas S.

    2015-01-01

    Atrial fibrillation (AF) is the most common abnormal heart rhythm and the single biggest cause of stroke. Ablation, destroying regions of the atria, is applied largely empirically and can be curative but with a disappointing clinical success rate. We design a simple model of activation wave front propagation on an anisotropic structure mimicking the branching network of heart muscle cells. This integration of phenomenological dynamics and pertinent structure shows how AF emerges spontaneously when the transverse cell-to-cell coupling decreases, as occurs with age, beyond a threshold value. We identify critical regions responsible for the initiation and maintenance of AF, the ablation of which terminates AF. The simplicity of the model allows us to calculate analytically the risk of arrhythmia and express the threshold value of transversal cell-to-cell coupling as a function of the model parameters. This threshold value decreases with increasing refractory period by reducing the number of critical regions which can initiate and sustain microreentrant circuits. These biologically testable predictions might inform ablation therapies and arrhythmic risk assessment. PMID:25635565

  12. Familial Angelman syndrome with a crossover in the critical deletion region

    Energy Technology Data Exchange (ETDEWEB)

    Nelen, M.R.; Van der Burgt, C.J.A.M.; Nillesen, W.N.; Smeets, H.J.M. [University Hospital Nijmegen (Netherlands); Vis, A. [Institute for Mentally Handicapped De Winckelsteegh, Nijmegen (Netherlands)

    1994-09-01

    More than two thirds of the patients with Angelman syndrome (AS) carry a deletion or other chromosomal abnormality in the 15q11-13 region. A much less frequent cause (4%) is paternal uniparental disomy of the entire chromosome. In general no abnormalities are detectable in familial cases and an inherited submicroscopic deletion was described only once. Here a familial case of 2 sibs with AS is reported. No major cytogenetic or molecular abnormality was identified, but a recombination event had occurred in the AS critical region. The AS locus, D15S113, D15S10, D15S11, and D15S18 mapped proximal and the GABRB3 gene, D15S97, and GABRA5 gene, and D15S12 distal to the crossover site. This recombination within the AS critical region confirmed the exclusion of GABRB3 as a candidate gene for AS. Other markers and candidate genes can be tested genetically as well for a possible role in AS. 36 refs., 4 figs.

  13. Molecular characterization of a serine/threonine kinase in the DiGeorge minimal critical region.

    Science.gov (United States)

    Goldmuntz, E; Fedon, J; Roe, B; Budarf, M L

    1997-10-01

    The majority of patients with DiGeorge, velocardiofacial or conotruncal anomaly facial syndromes share a common genetic etiology, deletion of chromosomal region 22q11.2. This report describes a computational approach toward the identification and molecular characterization of a newly identified serine/threonine kinase from the minimal critical deleted region (MDGCR). A cosmid contig of the minimal critical region has been assembled and sequenced in its entirety. Database searches and computer analysis of one cosmid (111f11) for coding sequences identified two regions with high similarity to the mouse serine/threonine kinase, Tsk1. Our investigations demonstrate that one of these regions contains a testis-specific gene that undergoes differential splicing, while the other region is most likely a pseudogene. Northern blot analysis and cDNA cloning demonstrate that there is alternate processing of the 3'UTR without altering the conserved kinase domains within the open reading frame. Serine/threonine kinases can play a regulatory role and have been found to be expressed during early embryogenesis. Based on its position in the MDGCR and possible function, the gene reported here is a candidate for the features seen in the 22q11 deletion syndrome.

  14. Gene therapy of inherited skin adhesion disorders: a critical overview.

    Science.gov (United States)

    De Luca, M; Pellegrini, G; Mavilio, F

    2009-07-01

    Gene therapy has the potential to treat devastating inherited diseases for which there is little hope of finding a conventional cure. These include lethal diseases, like immunodeficiencies or several metabolic disorders, or conditions associated with a relatively long life expectancy but poor quality of life and expensive and life-long symptomatic treatments, such as muscular dystrophy, cystic fibrosis and thalassaemia. Skin adhesion defects belong to both groups. For the nonlethal forms, gene therapy, or transplantation of cultured skin derived from genetically corrected epidermal stem cells, represents a very attractive therapeutic option, and potentially a definitive treatment. Recent advances in gene transfer and stem cell culture technology are making this option closer than ever. This paper critically reviews the progress and prospects of gene therapy for epidermolysis bullosa, and the technical and nontechnical factors currently limiting its development.

  15. Marker2sequence, mine your QTL regions for candidate genes

    NARCIS (Netherlands)

    Chibon, P.Y.F.R.P.; Schoof, H.; Visser, R.G.F.; Finkers, H.J.

    2012-01-01

    Marker2sequence (M2S) aims at mining quantitative trait loci (QTLs) for candidate genes. For each gene, within the QTL region, M2S uses data integration technology to integrate putative gene function with associated gene ontology terms, proteins, pathways and literature. As a typical QTL region

  16. Critical Exponents in Percolation Model of Track Region Critical Exponents in Percolation Model of Track Region Critical Exponents in Percolation Model of Track Region

    Directory of Open Access Journals (Sweden)

    A.B. Demchyshyn

    2012-03-01

    Full Text Available Differences between critical exponents of this model and the continuous percolation model indicate that the dependence of the modified structure area on the dose and the angle related with the correlation between individual tracks. It results in next effect: angular dependence of the surface area of the branched structure has maximum value at certain «critical» angle of ions incidence. Differences between critical exponents of this model and the continuous percolation model indicate that the dependence of the modified structure area on the dose and the angle related with the correlation between individual tracks. It results in next effect: angular dependence of the surface area of the branched structure has maximum value at certain «critical» angle of ions incidence. Differences between critical exponents of this model and the continuous percolation model indicate that the dependence of the modified structure area on the dose and the angle related with the correlation between individual tracks. It results in next effect: angular dependence of the surface area of the branched structure has maximum value at certain «critical» angle of ions incidence.

  17. The Prx1 Homeobox Gene is Critical for Molar Tooth Morphogenesis

    OpenAIRE

    Mitchell, J M; Hicklin, D.M.; Doughty, P.M.; Hicklin, J.H.; Dickert, J.W.; Tolbert, S.M.; Peterkova, R.; Kern, M.J.

    2006-01-01

    The paired-related homeobox genes, Prx1 and Prx2, encode transcription factors critical for orofacial development. Prx1-/-/Prx2-/- neonates have mandibular hypoplasia and malformed mandibular incisors. Although the mandibular incisor phenotype has been briefly described (ten Berge et al., 1998, 2001; Lu et al., 1999), very little is known about the role of Prx proteins during tooth morphogenesis. Since the posterior mandibular region was relatively normal, we examined molar tooth development ...

  18. Genome-wide analysis of regions similar to promoters of histone genes

    KAUST Repository

    Chowdhary, Rajesh

    2010-05-28

    Background: The purpose of this study is to: i) develop a computational model of promoters of human histone-encoding genes (shortly histone genes), an important class of genes that participate in various critical cellular processes, ii) use the model so developed to identify regions across the human genome that have similar structure as promoters of histone genes; such regions could represent potential genomic regulatory regions, e.g. promoters, of genes that may be coregulated with histone genes, and iii/ identify in this way genes that have high likelihood of being coregulated with the histone genes.Results: We successfully developed a histone promoter model using a comprehensive collection of histone genes. Based on leave-one-out cross-validation test, the model produced good prediction accuracy (94.1% sensitivity, 92.6% specificity, and 92.8% positive predictive value). We used this model to predict across the genome a number of genes that shared similar promoter structures with the histone gene promoters. We thus hypothesize that these predicted genes could be coregulated with histone genes. This hypothesis matches well with the available gene expression, gene ontology, and pathways data. Jointly with promoters of the above-mentioned genes, we found a large number of intergenic regions with similar structure as histone promoters.Conclusions: This study represents one of the most comprehensive computational analyses conducted thus far on a genome-wide scale of promoters of human histone genes. Our analysis suggests a number of other human genes that share a high similarity of promoter structure with the histone genes and thus are highly likely to be coregulated, and consequently coexpressed, with the histone genes. We also found that there are a large number of intergenic regions across the genome with their structures similar to promoters of histone genes. These regions may be promoters of yet unidentified genes, or may represent remote control regions that

  19. A YAC contig encompassing the Treacher Collins syndrome critical region at 5q31. 3-32

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, J.; Gladwin, A.J.; Perveen, R.; Dixon, M.J. (Univ. of Manchester (United Kingdom)); Loftus, S.K.; Wasmuth, J.J. (Univ. of California, Irvine, CA (United States)); Riley, J.H.; Anand, R.

    1994-08-01

    Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development the features of which include conductive hearing loss and cleft palate. Previous studies have localized the TCOF1 locus between D5S519 (proximal) and SPARC (distal), a region of 22 centirays as estimated by radiation hybrid mapping. In the current investigation the authors have created a contig across the TCOF1 critical region, using YAC clones. Isolation of a novel short tandem repeat polymorphism corresponding to the end of one of the YACs has allowed reduction of the size of the critical region to [approximately] 840 kb, which has been covered with three nonchimeric YACs. Restriction mapping has revealed that the region contains a high density of clustered rare-cutter restriction sites, suggesting that it may contain a number of different genes. The results of the present investigation have further allowed confirmation that the RPS14 locus lies proximal to the critical region and can thereby be excluded from a role in the pathogenesis of TCOF1, while ANX6 lies within the TCOF1 critical region and remains a potential candidate for the mutated gene. 26 refs., 4 figs., 1 tab.

  20. Narrowing the Duane syndrome critical region at chromosome 8q13 down to 40 kb.

    Science.gov (United States)

    Calabrese, G; Telvi, L; Capodiferro, F; Morizio, E; Pizzuti, A; Stuppia, L; Bordoni, R; Ion, A; Fantasia, D; Mingarelli, R; Palka, G

    2000-05-01

    Duane syndrome (MIM 126800) is an autosomal dominant disorder characterised by primary strabismus and other ocular anomalies, associated with variable deficiency of binocular sight. We have recently identified a syndrome carrying a reciprocal translation t(6;8)(q26;q13). FISH and PCR analyses using a YAC contig spanning the SRO narrowed the Duane region to a < 1 cM interval between markers SHGC37325 and W14901. In addition, the identification and mapping of two PAC clones flanking the translocation breakpoint, allowed us to further narrow the critical region to about 40 kb. As part of these mapping studies, we have also refined the map position of AMYB, a putative candidate gene, to 8q13, centromeric to Duane locus. AMYB is expressed in brain cortex and genital crests and has been previously mapped to 8q22.

  1. Genomic study of the critical region of chromosome 21 associated to Down syndrome

    Directory of Open Access Journals (Sweden)

    Julio César Montoya

    2011-03-01

    Full Text Available Introduction: Previous reports have identified a region of chromosome 21 known as Down ayndrome critical region (DSCR in which the expression of some genes would modulate the main clinical characteristics of this pathology. In this sense, there is currently limited information on the architecture of the DSCR associated.Objective: To obtain in silico a detailed vision of the chromatin structure associated with the evaluation of genomic covariables contained in public data bases.Methods: Taking as reference the information consigned in the National Center for Biotechnology Information, the Genome Browser from the University of California at Santa Cruz and from the HapMap project, a chromosome walk along 21 Mb of the distal portion of chromosome 21q arm was performed. In this distal portion, the number of single nucleotide polymorphisms (SNP, number of CpG islands, repetitive elements, recombination frequencies, and topographical state of that chromatin were recorded.Results: The frequency of CpG islands and Ref genes increased in the more distal 1.2 Mb DSCR that contrast with those localized near to the centromere. The highest level of recombination calculated for women was registered in the 21q22.12 to 22.3 bands. DSCR 6 and 9 genes showed a high percentage of methylation in CpG islands in DNA from normal and trisomic fibroblasts. The DSCR2 gene exhibited high levels of open chromatin and also methylation in some lysine residues of the histone H3 as relevant characteristics.Conclusion: The existence of a genomic environment characterized by high values of recombination frequencies and CpG methylation in DSCR 6 and 9 and also DSCR2 genes led us to postulate that in non-disjunction detected in Down syndrome, complex genomic, epigenetic and environmental relationships regulate some processes of meiosis.

  2. Genomic study of the critical region of chromosome 21 associated to Down syndrome

    Directory of Open Access Journals (Sweden)

    Julio César Montoya

    2011-04-01

    Full Text Available Introduction: Previous reports have identified a region of chromosome 21 known as Down ayndrome critical region (DSCR in which the expression of some genes would modulate the main clinical characteristics of this pathology. In this sense, there is currently limited information on the architecture of the DSCR associated. Objective: To obtain in silico a detailed vision of the chromatin structure associated with the evaluation of genomic covariables contained in public data bases. Methods: Taking as reference the information consigned in the National Center for Biotechnology Information, the Genome Browser from the University of California at Santa Cruz and from the HapMap project, a chromosome walk along 21 Mb of the distal portion of chromosome 21q arm was performed. In this distal portion, the number of single nucleotide polymorphisms (SNP, number of CpG islands, repetitive elements, recombination frequencies, and topographical state of that chromatin were recorded. Results: The frequency of CpG islands and Ref genes increased in the more distal 1.2 Mb DSCR that contrast with those localized near to the centromere. The highest level of recombination calculated for women was registered in the 21q22.12 to 22.3 bands. DSCR 6 and 9 genes showed a high percentage of methylation in CpG islands in DNA from normal and trisomic fibroblasts. The DSCR2 gene exhibited high levels of open chromatin and also methylation in some lysine residues of the histone H3 as relevant characteristics. Conclusion: The existence of a genomic environment characterized by high values of recombination frequencies and CpG methylation in DSCR 6 and 9 and also DSCR2 genes led us to postulate that in non-disjunction detected in Down syndrome, complex genomic, epigenetic and environmental relationships regulate some processes of meiosis.

  3. Mechanosensitive promoter region in the human HB-GAM gene

    DEFF Research Database (Denmark)

    Liedert, Astrid; Kassem, Moustapha; Claes, Lutz;

    2009-01-01

    expression through specific transcription factor binding sites in the promoter region of mechanosensitive genes. In the present study, we demonstrate that the expression of HB-GAM, which is known to have stimulating effects on osteogenic differentiation, is rapidly induced by mechanical loading in hMSC-TERT4...... cells. Analysis of the human HB-GAM gene upstream regulatory region with luciferase reporter gene assays revealed that the upregulation of HB-GAM expression occurred at the transcriptional level and was mainly dependent on the HB-GAM promoter region most upstream containing three potential AP-1 binding...

  4. Profiling critical cancer gene mutations in clinical tumor samples.

    Directory of Open Access Journals (Sweden)

    Laura E MacConaill

    Full Text Available BACKGROUND: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. METHODOLOGY: We developed and implemented an optimized mutation profiling platform ("OncoMap" to interrogate approximately 400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. CONCLUSIONS: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of "actionable" cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents.

  5. Regional innovation systems in Portugal: a critical evaluation

    Directory of Open Access Journals (Sweden)

    Domingos Santos

    2014-01-01

    Full Text Available La innovación ha pasado a primer plano en la política regional en las tres últimas décadas. Las políticas públicas han sido diseñadas por los «modelos de mejores prácticas» derivadas de las zonas urbano-metropolitanas de alta tecnología y regiones exitosas. Sin embargo, las lecciones aprendidas de estos ejemplos son raramente transferibles a otras partes. Los sistemas regionales de innovación en las regiones periféricas, y la posibilidad de su actuación como instrumentos de competitividad territorial, rara vez han sido objeto de discusión. El objetivo principal del artículo es, precisamente, tener a Portugal como un ejemplo para enriquecer este análisis. En la primera parte de este artículo se examina el concepto de sistemas de innovación regional en el contexto de las modernas teorías de la innovación y de las políticas regionales. Se argumenta que el papel del aprendizaje localizado es de importancia estratégica en la promoción del desarrollo regional endógeno. Luego, los autores discuten las barreras estructurales y oportunidades para promover estrategias regionales de innovación en el contexto político, económico y social portugués, y, por último, se señalan algunas especificidades que deben ser abordadas en el rediseño de las intervenciones públicas con el fin de mejorar la competitividad regional y la sostenibilidad.

  6. Regionalization in the Brazilian Healthcare System, SUS: a critical review.

    Science.gov (United States)

    Fernandes, Fernando Manuel Bessa

    2017-04-01

    to review the output and the use of the data to support managers in making decisions on the healthcare system, and analyze academic output on the theme. An online search of the SciELO database for articles using 'regionalization' and 'health/healthcare' as the keywords, and all indices as the 'scope of the study'. We found a total of 102 references, and after analyzing the abstracts selected 70 articles that effectively discuss regionalization of health/healthcare in Brazil. We also found four articles in non-health related journals. the institutional criteria (journal, theme area, date of publication, scope and number of authors), and the analytical criteria created by author - Type 1 - "Exploratory Studies" (26), "Evaluation Studies" (6), "Comparison Studies" (3); and "Reports of Experience" (5), Type 2 - "Theoretical-Analytical" papers (20) and "Historical-Conceptual Reviews" (4), and Type 3 - "Editorials (3) and "Book Reviews" (3). regionalization has become more important in journals published since 2010. Most of the articles fall in the Type 1 category.

  7. Superhelical destabilization in regulatory regions of stress response genes.

    Directory of Open Access Journals (Sweden)

    Huiquan Wang

    2008-01-01

    Full Text Available Stress-induced DNA duplex destabilization (SIDD analysis exploits the known structural and energetic properties of DNA to predict sites that are susceptible to strand separation under negative superhelical stress. When this approach was used to calculate the SIDD profile of the entire Escherichia coli K12 genome, it was found that strongly destabilized sites occur preferentially in intergenic regions that are either known or inferred to contain promoters, but rarely occur in coding regions. Here, we investigate whether the genes grouped in different functional categories have characteristic SIDD properties in their upstream flanks. We report that strong SIDD sites in the E. coli K12 genome are statistically significantly overrepresented in the upstream regions of genes encoding transcriptional regulators. In particular, the upstream regions of genes that directly respond to physiological and environmental stimuli are more destabilized than are those regions of genes that are not involved in these responses. Moreover, if a pathway is controlled by a transcriptional regulator whose gene has a destabilized 5' flank, then the genes (operons in that pathway also usually contain strongly destabilized SIDD sites in their 5' flanks. We observe this statistically significant association of SIDD sites with upstream regions of genes functioning in transcription in 38 of 43 genomes of free-living bacteria, but in only four of 18 genomes of endosymbionts or obligate parasitic bacteria. These results suggest that strong SIDD sites 5' to participating genes may be involved in transcriptional responses to environmental changes, which are known to transiently alter superhelicity. We propose that these SIDD sites are active and necessary participants in superhelically mediated regulatory mechanisms governing changes in the global pattern of gene expression in prokaryotes in response to physiological or environmental changes.

  8. Critical issues of alcohol safety in the region

    Directory of Open Access Journals (Sweden)

    Svetlana Vasil’evna Aksyutina

    2015-03-01

    Full Text Available The paper presents results of the research into the economic and socio-demographic indicators associated with the production and consumption of alcoholic beverages. It discloses the analysis of the alcoholic beverage market structure in the Vologda Oblast. The authors have identified the threshold of the safe alcohol production volume in the region taking into account the World Health Organization standards of alcohol consumption and the share of illegally produced goods. The article states that the increased alcohol production contributes to the rise in tax revenues, but the state fiscal policy to regulate the alcoholic beverage market leads to an increase in the share of shadow turnover. The authors have calculated the economic loss connected with the illegal production of alcoholic beverages in the Vologda Oblast. The alcohol consumption is a destructive socio-demographic process and one of the threats to the health of the nation. Excessive alcohol consumption leads to alcohol dependence, regression of the society and increases the threat to national and economic security. The study reveals a direct correlation between the consumption of alcoholic beverages per capita and mortality rates in men and women of working age from the causes related to the consumption of alcoholic beverages. The study of the international experience to regulate alcohol consumption has showed the need to tighten state control in the sphere of production and turnover of alcoholic products. The conduct of the unified state alcohol policy substantiates the selection of the alcohol industry in the all-Russian classifier of economic activity types. The authors have elaborated the concept and conditions of alcoholic security from the point of view of economic growth and social development. The article substantiates the necessity to monitor alcohol safety indicators when considering the regional development. It presents the complex system of socio-economic and demographic

  9. The distribution of SNPs in human gene regulatory regions

    Directory of Open Access Journals (Sweden)

    Guo Yongjian

    2005-10-01

    Full Text Available Abstract Background As a result of high-throughput genotyping methods, millions of human genetic variants have been reported in recent years. To efficiently identify those with significant biological functions, a practical strategy is to concentrate on variants located in important sequence regions such as gene regulatory regions. Results Analysis of the most common type of variant, single nucleotide polymorphisms (SNPs, shows that in gene promoter regions more SNPs occur in close proximity to transcriptional start sites than in regions further upstream, and a disproportionate number of those SNPs represent nucleotide transversions. Additionally, the number of SNPs found in the predicted transcription factor binding sites is higher than in non-binding site sequences. Conclusion Current information about transcription factor binding site sequence patterns may not be exhaustive, and SNPs may be actively involved in influencing gene expression by affecting the transcription factor binding sites.

  10. Evidence for gene conversion among immunoglobulin heavy chain variable region genes.

    Science.gov (United States)

    Clarke, S H; Rudikoff, S

    1984-03-01

    We have previously reported that the VH region amino acid sequence of a phosphocholine (PC)-binding hybridoma antibody of CBA/J origin, HP101 6G6 (6G6), differs extensively from the VH regions of other PC-binding antibodies. The sequence of 6G6 VH appears to be derived from a gene homologous to the BALB/c V11 gene, a member of the PC VH (T15 VH) gene family not normally used to encode PC-binding antibodies. The 6G6 VH sequence differs from the translated sequence of V11 by six amino acids, four of which occur at the same position in other members of this gene family. This coincidence led to the proposal that the 6G6 VH gene was derived by gene conversion involving three genes of the PC VH gene family. We report here the nucleic acid sequence of the rearranged VH gene of hybridoma 6G6. This sequence supports our previous suggestion of gene conversion by confirming those differences, relative to the BALB/c V11 gene sequence, that are encoded by other members of this gene family, and extends this correlation to include three silent base pair substitutions as well. In addition, 5' noncoding region sequence and Southern blot analysis using probes derived from the coding and 5' noncoding regions confirm that the 6G6 VH gene is likely to be derived from the V11 homologue in CBA/J mice, and suggest that all three genes believed to be involved in the generation of the 6G6 VH gene are present in the CBA/J genome, a prerequisite for their involvement in gene conversion.

  11. Characterization of 3'-untranslated region of the mouse GDNF gene

    Directory of Open Access Journals (Sweden)

    Oh-hashi Kentaro

    2012-01-01

    Full Text Available Abstract Background Glial cell line-derived neurotrophic factor (GDNF is a potent survival factor for many cell types, and its expression is widespread both within and outside of the nervous system. The regulation of GDNF expression has been extensively investigated but is not fully understood. Results Using a luciferase reporter assay, we identified the role of the 3'-untranslated region (3'-UTR of the mouse GDNF gene in the regulation of gene expression. We focused on a well-conserved A- and T-rich region (approximately 200 bp in length, which is located approximately 1000 bp downstream of the stop codon in exon 4 of the gene and contains three typical AU-rich elements (AREs, AUUUA. Interestingly, these AREs are well conserved in several GDNF genes. By testing reporter constructs containing various regions and lengths of the 3'-UTR fused to the end of the luciferase gene, we demonstrated that the ARE-induced decrease in luciferase activity correlates with the attenuation of the mRNA stability. Furthermore, we found that several regions around the AREs in the 3'-UTR suppressed the luciferase activity. Moreover, the expression level of the GDNF protein was negligible in C6 glioma cells transfected with the ARE-containing GDNF expression vector. Conclusions Our study is the first characterization of the possible role of AREs and other suppressive regions in the 3'-UTR in regulating the amounts of GDNF mRNA in C6 cells.

  12. Identification of genes from the Treacher Collins candidate region

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, M.; Dixon, J.; Edwards, S. [Univ. of California, Irvine, CA (United States)]|[Univ. of Manchester (United Kingdom)] [and others

    1994-09-01

    Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development. The TCOF1 locus has previously been mapped to chromosome 5q32-33. The candidate gene region has been defined as being between two flanking markers, ribosomal protein S14 (RPS14) and Annexin 6 (ANX6), by analyzing recombination events in affected individuals. It is estimated that the distance between these flanking markers is 500 kb by three separate analysis methods: (1) radiation hybrid mapping; (2) genetic linkage; and (3) YAC contig analysis. A cosmid contig which spans the candidate gene region for TCOF1 has been constructed by screening the Los Alamos National Laboratory flow-sorted chromosome 5 cosmid library. Cosmids were obtained by using a combination of probes generated from YAC end clones, Alu-PCR fragments from YACs, and asymmetric PCR fragments from both T7 and T3 cosmid ends. Exon amplifications, the selection of genomic coding sequences based upon the presence of functional splice acceptor and donor sites, was used to identify potential exon sequences. Sequences found to be conserved between species were then used to screen cDNA libraries in order to identify candidate genes. To date, four different cDNAs have been isolated from this region and are being analyzed as potential candidate genes for TCOF1. These include the genes encoding plasma glutathione peroxidase (GPX3), heparin sulfate sulfotransferase (HSST), a gene with homology to the ETS family of proteins and one which shows no homology to any known genes. Work is also in progress to identify and characterize additional cDNAs from the candidate gene region.

  13. Clinical manifestations of the deletion of Down syndrome critical region including DYRK1A and KCNJ6.

    Science.gov (United States)

    Yamamoto, Toshiyuki; Shimojima, Keiko; Nishizawa, Tsutomu; Matsuo, Mari; Ito, Masahiro; Imai, Katsumi

    2011-01-01

    A relatively small region of human chromosome 21 (Hsa21) is considered to play a major role in Down syndrome (DS) phenotypes, and the concept of a Down syndrome critical region (DSCR) has been proposed. The goal of the phenotype-genotype correlation study is to discover which genes are responsible for each DS phenotype. Loss of the genomic copy numbers of Hsa21 can give us important suggestion to understand the functions of the involved genes. Genomic copy number aberrations were analyzed by micro-array-based comparative genomic hybridization (aCGH) in 300 patients with developmental delay. Partial deletions of Hsa21 were identified in three patients with developmental delay, epilepsy, microcephaly, and distinctive manifestations. Two of the patients had mosaic deletions of 21q22-qter including a part of DSCR; one of whom whose mosaic ratio was higher than the other showed more severe brain morphogenic abnormality with colpocephaly, which was similar to the previously reported patients having pure deletions of 21q22-qter, indicating the critical region for cortical dysplasia at this region. The remaining patient had the smallest microdeletion with 480 kb in DSCR including DYRK1A and KCNJ6. Although we could not identify any nucleotide alteration in DYRK1A and KCNJ6 in our cohort study for 150 patients with mental retardation with/without epilepsy, this study underscores the clinical importance of DSCR not only for DS but also for developmental disorders.

  14. Bioethical conflicts of gene therapy: a brief critical review

    Directory of Open Access Journals (Sweden)

    José Ednésio da Cruz Freire

    2014-12-01

    Full Text Available Methods and techniques employed in gene therapy are reviewed in parallel with pertinent ethical conflicts. Clinical interventions based on gene therapy techniques preferentially use vectors for the transportation of therapeutic genes, however little is known about the potential risks and damages to the patient. Thus, attending carefully to the clinical complications arising as well as to security is essential. Despite the scientific and technological advances, there are still many uncertainties about the side effects of gene therapy. Moreover, there is a need, above all, to understand the principles of bioethics as both science and ethics, in accordance with its socioecological responsibility, in order to prioritize the health and welfare of man and nature, using properly natural resources and technology. Therefore, it is hard to determine objective results and to which extent the insertion of genes can affect the organism, as well as the ethical implication

  15. Transport and transformation of genetic information in the critical zone: The case of antibiotic resistance genes

    Science.gov (United States)

    Zhu, Y. G.

    2015-12-01

    In addition to material and energy flows, the dynamics and functions of the Earth's critical zone are intensively mediated by biological actions performed by diverse organisms. These biological actions are modulated by the expression of functional genes and their translation into enzymes that catalyze geochemical reactions, such as nutrient turnover and pollutant biodegradation. Although geobiology, as an interdisciplinary research area, is playing and vital role in linking biological and geochemical processes at different temporal and spatial scales, the distribution and transport of functional genes have rarely been investigated from the Earth's critical zone perspectives. To illustrate the framework of studies on the transport and transformation of genetic information in the critical zone, antibiotic resistance is taken as an example. Antibiotic resistance genes are considered as a group of emerging contaminants, and their emergence and spread within the critical zone on one hand are induced by anthropogenic activities, and on other hand are threatening human health worldwide. The transport and transformation of antibiotic resistance genes are controlled by both horizontal gene transfer between bacterial cells and the movement of bacteria harboring antibiotic resistance genes. In this paper, the fate and behavior of antibiotic resistance genes will be discussed in the following aspects: 1) general overview of environmental antibiotic resistance; 2) high through quantification of the resistome in various environmental media; 3) pathways of resistance gene flow within the critical zone; and 4) potential strategies in mitigating antibiotic resistance, particularly from the critical zone perspectives.

  16. Induced Pib Expression and Resistance to Magnaporthe grisea are Compromised by Cytosine Demethylation at Critical Promoter Regions in Rice.

    Science.gov (United States)

    Li, Yuan; Xia, Qiong; Kou, Hongping; Wang, Dan; Lin, Xiuyun; Wu, Ying; Xu, Chunming; Xing, Shaochen; Liu, Bao

    2011-10-01

    Pib is a well-characterized rice blast-resistance gene belonging to the nucleotide binding site (NBS) and leucine-rich repeat (LRR) superfamily. Expression of Pib was low under non-challenged conditions, but strongly induced by the blast-causing fungal pathogen Magnaporthe grisea, thereby conferring resistance to the pathogen. It is generally established that cytosine methylation of the promoter-region often plays a repressive role in modulating expression of the gene in question. We report here that two critical regions of the Pib promoter were heavily CG cytosine-methylated in both cultivars studied. Surprisingly, induced expression of Pib by M. grisea infection did not entail its promoter demethylation, and partial demethylation by 5-azacytidine-treatment actually reduced Pib expression relative to wild-type plants. Accordingly, the blast disease-resistance was compromised in the 5'-azaC-treated plants relative to wild-type. In contrast, the disease susceptibility was not affected by the 5'-azaC treatment in another two rice cultivars that did not contain the Pib gene, ruling out effects of other R genes and non-specific genotoxic effects by the drug-treatment as a cause for the compromised Pib-conditioned blast-resistance. Taken together, our results suggest that promoter DNA methylation plays a novel enhancing role in conditioning high-level of induced expression of the Pib gene in times of M. grisea infection, and its conferred resistance to the pathogen.

  17. Identifying hotspots and management of critical ecosystem services in rapidly urbanizing Yangtze River Delta Region, China.

    Science.gov (United States)

    Cai, Wenbo; Gibbs, David; Zhang, Lang; Ferrier, Graham; Cai, Yongli

    2017-04-15

    Rapid urbanization has altered many ecosystems, causing a decline in many ecosystem services, generating serious ecological crisis. To cope with these challenges, we presented a comprehensive framework comprising five core steps for identifying and managing hotspots of critical ecosystem services in a rapid urbanizing region. This framework was applied in the case study of the Yangtze River Delta (YRD) Region. The study showed that there was large spatial heterogeneity in the hotspots of ecosystem services in the region, hotspots of supporting services and regulating services aggregately distributing in the southwest mountainous areas while hotspots of provisioning services mainly in the northeast plain, and hotspots of cultural services widespread in the waterbodies and southwest mountainous areas. The regionalization of the critical ecosystem services was made through the hotspot analysis. This study provided valuable information for environmental planning and management in a rapid urbanizing region and helped improve China's ecological redlines policy at regional scale. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Gene recovery microdissection (GRM) a process for producing chromosome region-specific libraries of expressed genes

    Energy Technology Data Exchange (ETDEWEB)

    Christian, A T; Coleman, M A; Tucker, J D

    2001-02-08

    Gene Recovery Microdissection (GRM) is a unique and cost-effective process for producing chromosome region-specific libraries of expressed genes. It accelerates the pace, reduces the cost, and extends the capabilities of functional genomic research, the means by which scientists will put to life-saving, life-enhancing use their knowledge of any plant or animal genome.

  19. A brain region-specific predictive gene map for autism derived by profiling a reference gene set.

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    Full Text Available Molecular underpinnings of complex psychiatric disorders such as autism spectrum disorders (ASD remain largely unresolved. Increasingly, structural variations in discrete chromosomal loci are implicated in ASD, expanding the search space for its disease etiology. We exploited the high genetic heterogeneity of ASD to derive a predictive map of candidate genes by an integrated bioinformatics approach. Using a reference set of 84 Rare and Syndromic candidate ASD genes (AutRef84, we built a composite reference profile based on both functional and expression analyses. First, we created a functional profile of AutRef84 by performing Gene Ontology (GO enrichment analysis which encompassed three main areas: 1 neurogenesis/projection, 2 cell adhesion, and 3 ion channel activity. Second, we constructed an expression profile of AutRef84 by conducting DAVID analysis which found enrichment in brain regions critical for sensory information processing (olfactory bulb, occipital lobe, executive function (prefrontal cortex, and hormone secretion (pituitary. Disease specificity of this dual AutRef84 profile was demonstrated by comparative analysis with control, diabetes, and non-specific gene sets. We then screened the human genome with the dual AutRef84 profile to derive a set of 460 potential ASD candidate genes. Importantly, the power of our predictive gene map was demonstrated by capturing 18 existing ASD-associated genes which were not part of the AutRef84 input dataset. The remaining 442 genes are entirely novel putative ASD risk genes. Together, we used a composite ASD reference profile to generate a predictive map of novel ASD candidate genes which should be prioritized for future research.

  20. Characterization of the promoter region of the mouse Xist gene.

    Science.gov (United States)

    Pillet, N; Bonny, C; Schorderet, D F

    1995-01-01

    The mouse Xist gene is expressed exclusively from the inactive X chromosome and may be implicated in initiating X inactivation. To better understand the mechanisms underlying the control of Xist expression, we investigated the upstream regulatory region of the mouse Xist promoter. A 1.2-kb upstream region of the Xist gene was sequenced and promoter activity was studied by chloramphenicol acetyltransferase (CAT) assays after transfection in murine XX and XY cell lines. The region analyzed (-1157 to +917 showed no in vitro sex-specific promoter activity. However, a minimal constitutional promoter was assigned to a region from -81 to +1, and a cis element from -41 to -15 regulates promoter activity. We showed that a nuclear factor binds to an element located at -30 to -25 (TTAAAG). A second sequence at -41 to -15 does not act as an enhancer and is unable to confer transcriptional activity to the Xist gene on its own. A third region from -82 to -41 is needed for correct expression. Deletion of the segment -441 to -231 is associated with an increase in CAT activity and may represent a silencer element. Images Fig. 3 PMID:8618932

  1. Gene expression profiles in rat brain disclose CNS signature genes and regional patterns of functional specialisation

    Directory of Open Access Journals (Sweden)

    Breilid Harald

    2007-04-01

    Full Text Available Abstract Background The mammalian brain is divided into distinct regions with structural and neurophysiological differences. As a result, gene expression is likely to vary between regions in relation to their cellular composition and neuronal function. In order to improve our knowledge and understanding of regional patterns of gene expression in the CNS, we have generated a global map of gene expression in selected regions of the adult rat brain (frontomedial-, temporal- and occipital cortex, hippocampus, striatum and cerebellum; both right and left sides as well as in three major non-neural tissues (spleen, liver and kidney using the Applied Biosystems Rat Genome Survey Microarray. Results By unsupervised hierarchical clustering, we found that the transcriptome within a region was highly conserved among individual rats and that there were no systematic differences between the two hemispheres (right versus left side. Further, we identified distinct sets of genes showing significant regional enrichment. Functional annotation of each of these gene sets clearly reflected several important physiological features of the region in question, including synaptic transmission within the cortex, neurogenesis in hippocampus and G-protein-mediated signalling in striatum. In addition, we were able to reveal potentially new regional features, such as mRNA transcription- and neurogenesis-annotated activities in cerebellum and differential use of glutamate signalling between regions. Finally, we determined a set of 'CNS-signature' genes that uncover characteristics of several common neuronal processes in the CNS, with marked over-representation of specific features of synaptic transmission, ion transport and cell communication, as well as numerous novel unclassified genes. Conclusion We have generated a global map of gene expression in the rat brain and used this to determine functional processes and pathways that have a regional preference or ubiquitous

  2. Calculation of critical fault recovery time for nonlinear systems based on region of attraction analysis

    DEFF Research Database (Denmark)

    Tabatabaeipour, Mojtaba; Blanke, Mogens

    2014-01-01

    In safety critical systems, the control system is composed of a core control system with a fault detection and isolation scheme together with a repair or a recovery strategy. The time that it takes to detect, isolate, and recover from the fault (fault recovery time) is a critical factor in safety...... of a system. It must be guaranteed that the trajectory of a system subject to fault remains in the region of attraction (ROA) of the post-fault system during this time. This paper proposes a new algorithm to compute the critical fault recovery time for nonlinear systems with polynomial vector elds using sum...

  3. Functional characterization of genetic polymorphisms identified in the promoter region of the bovine PEPS gene.

    Science.gov (United States)

    Ju, Zhihua; Zheng, Xue; Huang, Jinming; Qi, Chao; Zhang, Yan; Li, Jianbin; Zhong, Jifeng; Wang, Changfa

    2012-06-01

    Peptidase S (PEPS) is a metallopeptidase that cleaves N-terminal residues from proteins and peptides. PEPS is used as a cell maintenance enzyme with critical roles in peptide turnover. The promoter region located upstream of the initiation site plays an important role in regulating gene expression. Polymorphism in the promoter region can alter gene expression and lead to biological changes. In the current study, polymorphisms in the promoter region of the PEPS gene were investigated. Polymerase chain reaction (PCR)-restriction fragment length polymorphism and DNA sequencing methods were used to screen sequence variations in the promoter region of DNA samples from 743 Chinese Holstein cattle. Two polymorphisms (g. -534 T>C and g. -2545 G>A) were identified and eight haplotypes were classified by haplotype analysis. The two genetic polymorphisms and haplotypes were associated with fat percentage and somatic cell score in Chinese Holstein cattle. The results of real-time PCR showed that cow kidneys exhibit the highest PEPS expression level. Moreover, bioinformatics analysis predicted that the single-nucleotide polymorphism g. -534 T>C is located in the core promoter region and in the transcription factor binding sites. The promoter activities of the polymorphism of -543 T>C were measured by luciferase assay in the human kidney epithelial cell line 293T. Transcriptional activity is significantly lower in cell lines transfected with the reporter construct containing 2.5 kb upstream fragments with -543 C than in those with wild-type -543 T. The results indicated that genetic variation at locus -543 influences PEPS promoter activity. The genetic variation in the promoter region of PEPS gene may regulate PEPS gene transcription and might have consequences at a regulatory level.

  4. Regional variation in critical care evacuation needs for children after a mass casualty incident.

    Science.gov (United States)

    Kanter, Robert K

    2012-06-01

    To determine the ability of five New York statewide regions to accommodate 30 children needing critical care after a hypothetical mass casualty incident (MCI) and the duration to complete an evacuation to facilities in other regions if the surge exceeded local capacity. A quantitative model evaluated pediatric intensive care unit (PICU) vacancies for MCI patients, based on data on existing resources, historical average occupancy, and evidence on early discharges and transfers in a public health emergency. Evacuation of patients exceeding local capacity to the nearest PICU center with vacancies was modeled in discrete event chronological simulations for three scenarios in each region: pediatric critical care transport teams were considered to originate from other PICU hospitals statewide, using (1) ground ambulances or (2) helicopters, and (3) noncritical care teams were considered to originate from the local MCI region using ground ambulances. Chronology of key events was modeled. Across five regions, the number of children needing evacuation would vary from 0 to 23. The New York City (NYC) metropolitan area could accommodate all patients. The region closest to NYC could evacuate all excess patients to PICU hospitals in NYC within 12 hours using statewide critical care teams traveling by ground ambulance. Helicopters and local noncritical care teams would not shorten the evacuation. For other statewide regions, evacuation of excess patients by statewide critical care teams traveling by ground ambulance would require up to nearly 26 hours. Helicopter transport would reduce evacuation time by 40%-44%, while local noncritical care teams traveling by ground would reduce evacuation time by 16%-34%. The present study provides a quantitative, evidence-based approach to estimate regional pediatric critical care evacuation needs after an MCI. Large metropolitan areas with many PICU beds would be better able to accommodate patients in a local MCI, and would serve as a

  5. Urban land use limits regional bumble bee gene flow.

    Science.gov (United States)

    Jha, Shalene; Kremen, C

    2013-05-01

    Potential declines in native pollinator communities and increased reliance on pollinator-dependent crops have raised concerns about native pollinator conservation and dispersal across human-altered landscapes. Bumble bees are one of the most effective native pollinators and are often the first to be extirpated in human-altered habitats, yet little is known about how bumble bees move across fine spatial scales and what landscapes promote or limit their gene flow. In this study, we examine regional genetic differentiation and fine-scale relatedness patterns of the yellow-faced bumble bee, Bombus vosnesenskii, to investigate how current and historic habitat composition impact gene flow. We conducted our study across a landscape mosaic of natural, agricultural and urban/suburban habitats, and we show that B. vosnesenskii exhibits low but significant levels of differentiation across the study system (F(ST) = 0.019, D(est) = 0.049). Most importantly, we reveal significant relationships between pairwise F(ST) and resistance models created from contemporary land use maps. Specifically, B. vosnesenskii gene flow is most limited by commercial, industrial and transportation-related impervious cover. Finally, our fine-scale analysis reveals significant but declining relatedness between individuals at the 1-9 km spatial scale, most likely due to local queen dispersal. Overall, our results indicate that B. vosnesenskii exhibits considerable local dispersal and that regional gene flow is significantly limited by impervious cover associated with urbanization.

  6. In vivo analysis of Aicda gene regulation: a critical balance between upstream enhancers and intronic silencers governs appropriate expression.

    Directory of Open Access Journals (Sweden)

    Le Thi Huong

    Full Text Available The Aicda gene encodes activation-induced cytidine deaminase (AID. Aicda is strongly transcribed in activated B cells to diversify immunoglobulin genes, but expressed at low levels in various other cells in response to physiological or pathological stimuli. AID's mutagenic nature has been shown to be involved in tumor development. Here, we used a transgenic strategy with bacterial artificial chromosomes (BACs to examine the in vivo functions of Aicda regulatory elements, which cluster in two regions: in the first intron (region 2, and approximately 8-kb upstream of the transcription start site (region 4. Deleting either of these regions completely abolished the expression of Aicda-BAC reporters, demonstrating these elements' critical roles. Furthermore, we found that selectively deleting two C/EBP-binding sites in region 4 inactivated the enhancer activity of the region despite the presence of intact NF-κB-, STAT6- and Smad-binding sites. On the other hand, selectively deleting E2F- and c-Myb-binding sites in region 2 increased the frequency of germinal-center B cells in which the Aicda promoter was active, indicating that E2F and c-Myb act as silencers in vivo. Interestingly, the silencer deletion did not cause ectopic activation of the Aicda promoter, indicating that Aicda activation requires enhancer-specific stimulation. In summary, precise regulation of the Aicda promoter appears to depend on a coordinated balance of activities between enhancer and silencer elements.

  7. Universities and Regional Development: A Critical Assessment of Tensions and Contradictions. International Studies in Higher Education

    Science.gov (United States)

    Pinheiro, Romulo, Ed.; Benneworth, Paul, Ed.; Jones, Glen A., Ed.

    2012-01-01

    Universities are under increasing pressure to help promote socio-economic growth in their local communities. However until now, no systematic, critical attention has been paid to the factors and mechanisms that currently make this process so daunting. In Universities and Regional Development, scholars from Europe, the Americas, Africa, and Asia…

  8. Odd viscosity in the quantum critical region of a holographic Weyl semimetal

    CERN Document Server

    Landsteiner, Karl; Sun, Ya-Wen

    2016-01-01

    We study odd viscosity in a holographic model of a Weyl semimetal. The model is characterised by a quantum phase transition from a topological semimetal to a trivial semimetal state. Since the model is axisymmetric in three spatial dimensions there are two independent odd viscosities. Both odd viscosity coefficients are non-vanishing in the quantum critical region and non-zero only due to the mixed axial gravitational anomaly. It is therefore a novel example in which the mixed axial gravitational anomaly gives rise to a transport coefficient at first order in derivatives at finite temperature. We also compute anisotropic shear viscosities and show that one of them violates the KSS bound. In the quantum critical region, the physics of viscosities as well as conductivities is governed by the quantum critical point.

  9. Mutagenesis of tGCN5 core region reveals two critical surface residues F90 and R140

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, Kinjal Rajesh; Chan, Yan M.; Lee, Man X.; Yang, Ching Yao; Voloshchuk, Natalya [Department of Chemical and Biological Sciences, Polytechnic Institute of New York University, 6 MetroTech Center, Brooklyn, NY 11201 (United States); Montclare, Jin Kim, E-mail: jmontcla@poly.edu [Department of Chemical and Biological Sciences, Polytechnic Institute of New York University, 6 MetroTech Center, Brooklyn, NY 11201 (United States); Department of Biochemistry, SUNY-Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203 (United States)

    2010-09-24

    Research highlights: {yields} Mutagenesis of the tGCN5 core region reveals two residues important for function. {yields} Developed a fluorescent lysate-based activity assay to assess mutants. {yields} Surface-exposed residues F90 and R140 of tGCN5 are critical for H3 acetylation. -- Abstract: Tetrahymena General Control Non-Derepressor 5 (tGCN5) is a critical regulator of gene transcription via acetylation of histones. Since the acetylation ability has been attributed to the 'core region', we perform mutagenesis of residues within the tGCN5 'core region' in order to identify those critical for function and stability. Residues that do not participate in catalysis are identified, mutated and characterized for activity, structure and thermodynamic stability. Variants I107V, Q114L, A121T and A130S maintain the acetylation function relative to wild-type tGCN5, while variants F90Y, F112R and R140H completely abolish function. Of the three non-functional variants, since F112 is mutated into a non-homologous charged residue, a loss in function is expected. However, the remaining two variants are mutated into homologous residues, suggesting that F90 and R140 are critical for the activity of tGCN5. While mutation to homologous residue maintains acetylation of histone H3 for the majority of the variants, the two surface-exposed residues, F90 and R140, appear to be essential for tGCN5 function, structure or stability.

  10. Delineation of a deletion region critical for corpus callosal abnormalities in chromosome 1q43-q44.

    Science.gov (United States)

    Nagamani, Sandesh C Sreenath; Erez, Ayelet; Bay, Carolyn; Pettigrew, Anjana; Lalani, Seema R; Herman, Kristin; Graham, Brett H; Nowaczyk, Malgorzata Jm; Proud, Monica; Craigen, William J; Hopkins, Bobbi; Kozel, Beth; Plunkett, Katie; Hixson, Patricia; Stankiewicz, Pawel; Patel, Ankita; Cheung, Sau Wai

    2012-02-01

    Submicroscopic deletions involving chromosome 1q43-q44 result in cognitive impairment, microcephaly, growth restriction, dysmorphic features, and variable involvement of other organ systems. A consistently observed feature in patients with this deletion are the corpus callosal abnormalities (CCAs), ranging from thinning and hypoplasia to complete agenesis. Previous studies attempting to delineate the critical region for CCAs have yielded inconsistent results. We conducted a detailed clinical and molecular characterization of seven patients with deletions of chromosome 1q43-q44. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. Four patients had CCAs, and shared the smallest region of overlap that contains only three protein coding genes, CEP170, SDCCAG8, and ZNF238. One patient with a small deletion involving SDCCAG8 and AKT3, and another patient with an intragenic deletion of AKT3 did not have any CCA, implying that the loss of these two genes is unlikely to be the cause of CCA. CEP170 is expressed extensively in the brain, and encodes for a protein that is a component of the centrosomal complex. ZNF238 is involved in control of neuronal progenitor cells and survival of cortical neurons. Our results rule out the involvement of AKT3, and implicate CEP170 and/or ZNF238 as novel genes causative for CCA in patients with a terminal 1q deletion.

  11. Induced Pib Expression and Resistance to Magnaporthe grisea are Compromised by Cytosine Demethylation at Critical Promoter Regions in Rice

    Institute of Scientific and Technical Information of China (English)

    Yuan Li; Qiong Xia; Hongping Kou; Dan Wang; Xiuyun Lin; Ying Wu; Chunming Xu; Shaochen Xing

    2011-01-01

    Pib is a well-characterized rice blast-resistance gene belonging to the nucleotide binding site (NBS) and leucine-rich repeat (LRR) superfamily.Expression of Pib was low under non-challenged conditions,but strongly induced by the blast-causing fungal pathogen Magnaporthe grisea,thereby conferring resistance to the pathogen.It is generally established that cytosine methylation of the promoter-region often plays a repressive role in modulating expression of the gene in question.We report here that two critical regions of the Pib promoter were heavily CG cytosine-methylated in both cultivars studied.Surprisingly,induced expression of Pib by M.grisea infection did not entail its promoter demethylation,and partial demethylation by 5-azacytidine-treatment actually reduced Pib expression relative to wildtype plants.Accordingly,the blast disease-resistance was compromised in the 5’-azaC-treated plants relative to wild-type.In contrast,the disease susceptibility was not affected by the 5’-azaC treatment in another two rice cultivars that did not contain the Pib gene,ruling out effects of other R genes and non-specific genotoxic effects by the drug-treatment as a cause for the compromised Pib-conditioned blast-resistance.Taken together,our results suggest that promoter DNA methylation plays a novel enhancing role in conditioning high-level of induced expression of the Pib gene in times of M.grisea infection,and its conferred resistance to the pathogen.

  12. Critical pathways of change in fruit export regions at desert margin (Chile)

    DEFF Research Database (Denmark)

    Frederiksen, Peter

    change changed pathways. Pathways resulted from a combination of global value chains, the adoption of innovations, past climate change, and regional conditions at different scales. Main pathways of change were upgrade and downgrade of the fruit export region and irrigation systems, whereas the breaking......The purpose is to elucidate how critical pathways function in a fruit export region at the desert margin in Chile. The region was investigated at the system level as an open land system with managed fruit plantations in a geographically complex valley. Data collection procedures included total...... field surveys, semi-structured interviews, and library investigations. The main result is that no single variable could explain the pathways. Pathways were found to be explained by the functioning of the regional dynamic system. Pathways were found to vary in type, cause, relation and space-time. Global...

  13. A PROVISIONAL TRANSCRIPT MAP OF THE SPINAL MUSCULAR-ATROPHY (SMA) CRITICAL REGION

    NARCIS (Netherlands)

    VANDERSTEEGE, G; DRAAIJERS, TG; GROOTSCHOLTEN, PM; OSINGA, J; ANZEVINO, R; VELONA, [No Value; DENDUNNEN, JT; SCHEFFER, H; BRAHE, C; VANOMMEN, GJB; BUYS, CHCM

    1995-01-01

    YACs from the region containing the spinal muscular atrophy (SMA) locus at 5q12 have been used as probes in a direct screening of cDNA libraries to isolate 8 cDNAs, mapped to different YAC fragments. Three clones showed complete identity to the genes for cyclin B1 (CCNB1), the p44 subunit of the tra

  14. A PROVISIONAL TRANSCRIPT MAP OF THE SPINAL MUSCULAR-ATROPHY (SMA) CRITICAL REGION

    NARCIS (Netherlands)

    VANDERSTEEGE, G; DRAAIJERS, TG; GROOTSCHOLTEN, PM; OSINGA, J; ANZEVINO, R; VELONA, [No Value; DENDUNNEN, JT; SCHEFFER, H; BRAHE, C; VANOMMEN, GJB; BUYS, CHCM

    1995-01-01

    YACs from the region containing the spinal muscular atrophy (SMA) locus at 5q12 have been used as probes in a direct screening of cDNA libraries to isolate 8 cDNAs, mapped to different YAC fragments. Three clones showed complete identity to the genes for cyclin B1 (CCNB1), the p44 subunit of the

  15. CITA/NLRC5: A critical transcriptional regulator of MHC class I gene expression.

    Science.gov (United States)

    Downs, Isaac; Vijayan, Saptha; Sidiq, Tabasum; Kobayashi, Koichi S

    2016-07-08

    Major histocompatibility complex (MHC) class I and class II molecules play essential roles in the development and activation of the human adaptive immune system. An NLR protein, CIITA (MHC class II transactivator) has been recognized as a master regulator of MHC class II gene expression, albeit knowledge about the regulatory mechanism of MHC class I gene expression had been limited. Recently identified MHC class I transactivator (CITA), or NLRC5, also belongs to the NLR protein family and constitutes a critical regulator for the transcriptional activation of MHC class I genes. In addition to MHC class I genes, CITA/NLRC5 induces the expression of β2 -microglobulin, TAP1 and LMP2, essential components of the MHC class I antigen presentation pathway. Therefore, CITA/NLRC5 and CIITA are transcriptional regulators that orchestrate the concerted expression of critical components in the MHC class I and class II pathways, respectively. © 2016 BioFactors, 42(4):349-357, 2016.

  16. Identification and uniparental expression of a novel gene from the Prader-Willi region of chromosome 15

    Energy Technology Data Exchange (ETDEWEB)

    Wevrick, R.; Kerns, J.A.; Francke, U. [Stanford Univ., CA (United States)

    1994-09-01

    The Prader-Willi syndrome (PWS) is a neurobehavioral disorder which occurs at a frequency of about 1/25,000. Most patients ({approximately}70%) have a cytogentic deletion of their paternal 15q11-q13 region, while {approximately}30% have uniparental maternal disomy. The parent of origin dependence of the phenotype is thought to be reflective of the uniparental pattern of expression of genes in the region, a phenomenon known as genomic imprinting. A small subset of PWS patient with a typical cytogenetic rearrangements has defined a critical region for genes involved in PWS. We have used STSs from the region to construct a YAC contig including the entire PWS critical region, which is about 350 kb considering presently characterized deletions. We are now using these YACs to isolate and characterize novel genes potentially involved in PWS. Overlapping YACs from the critical region were subjected to the technique of cDNA selection. Gel-purified YAC DNA was biotinylated during PCR amplification and annealed in solution to amplified cDNA. cDNAs remaining after hybridization washing, and denaturation of the hybrids were tested for localization within the YAC contig. One such cDNA mapped back to the YAC contig and was further analyzed. A full length cDNA clone was isolated from a fetal brain library and sequenced. The pattern of expression was determined in cell lines derived from Prader-Willi and Angelman patients and in normal individuals. The gene was found to have monoallelic, paternal expression in normal individuals and is marginally or not expressed in cell lines derived form Prader-Willi individuals. Expression in cell lines from Angelman patients, who are deleted for the same region on the maternal chromosome 15, was normal. Thus this apparently maternally imprinted gene is a candidate for involvement in the Prader-Willi phenotype.

  17. Investigation of Surface Tensions for Pure Fluids outside and inside the Critical Region

    Institute of Scientific and Technical Information of China (English)

    FU Dong

    2006-01-01

    An equation of state (EOS) applicable for both the uniform and non-uniform fluids was established by using the density-gradient expansion, in which the influence parameter κ[ρ(r),T] was obtained by the use of direct correlation function. The density functional theory (DFT) provides a framework under which both the phase equilibria and interfacial properties can be investigated within a single set of molecular parameters. The phase equilibria inside the critical region can be improved by the renormalization group theory (RGT). However, the correction of interfacial properties by DFT and RGT is computationaily difficult. In the present work, the density gradient theory (DGT) in which κ[ρ(r),T] is treated as a constant is used to combine with the RGT for interfacial properties inside the critical region.

  18. Intersecting Itineraries Beyond the Strada Novissima: The Converging Authorship of Critical Regionalism

    Directory of Open Access Journals (Sweden)

    Stylianos Giamarelos

    2016-07-01

    Full Text Available While the 1980 Venice Biennale is usually understood as the exhibition that crystallised postmodernism as a style of historicist eclecticism, the event also acted as a catalyst for the eventual convergence of alternative architectural sensibilities and ideas. This article shows how critical regionalism emerged when the physical and intellectual trajectories of British historian Kenneth Frampton and the Greek architects Suzana Antonakaki and Dimitris Antonakakis intersected in the aftermath of the Biennale. Offering an alternative way out of the contemporaneous crisis of modernism, this open-ended and extrovert regionalism that opposed static cultural insularities is thus the discursive footprint of architectural sensibilities travelling through cultures.

  19. Cubic Polynomial Maps with Periodic Critical Orbit, Part II: Escape Regions

    CERN Document Server

    Bonifant, Araceli; Milnor, John

    2009-01-01

    The parameter space $\\mathcal{S}_p$ for monic centered cubic polynomial maps with a marked critical point of period $p$ is a smooth affine algebraic curve whose genus increases rapidly with $p$. Each $\\mathcal{S}_p$ consists of a compact connectedness locus together with finitely many escape regions, each of which is biholomorphic to a punctured disk and is characterized by an essentially unique Puiseux series. This note will describe the topology of $\\mathcal{S}_p$, and of its smooth compactification, in terms of these escape regions. It concludes with a discussion of the real sub-locus of $\\mathcal{S}_p$.

  20. A global fundamental equation of state for normal hexane in the critical region

    Energy Technology Data Exchange (ETDEWEB)

    Abbaci, Azzedine, E-mail: azzedine.abbaci@univ-annaba.org [Laboratoire de Synthèse et de Biocatalyse Organique, Unité Thermodynamique des Fluides et des Mélanges, Faculté des Sciences, Département de Chimie, Université Badji Mokhtar, BP 12, Sidi-Amar, Annaba 23000 (Algeria); Rizi, Aicha [Laboratoire de Synthèse et de Biocatalyse Organique, Unité Thermodynamique des Fluides et des Mélanges, Faculté des Sciences, Département de Chimie, Université Badji Mokhtar, BP 12, Sidi-Amar, Annaba 23000 (Algeria); Abdulagatov, Ilmutdin M. [Institute of Physics of the Dagestan Scientific Center of the Russian Academy of Sciences, 367005 Makhachkala, M. Yaragskogo Str. 94, Dagestan (Russian Federation)

    2013-09-10

    Highlights: ► The crossover Landau model is used to predict the thermodynamic properties of normal hexane. ► Thermodynamic properties of normal are studied. ► Comparison with different thermodynamic properties is done. - Abstract: In our previous work [S. Azzouz, A. Rizi, A. Acidi, A. Abbaci, St. Cerc. St. CICBIA 11 (2) (2010) 235–241], we developed an interim thermodynamic property formulation for the supercritical n-hexane which incorporates non-analytic scaling laws in the critical region and reproduces the thermodynamic properties of n-hexane far away from the critical region. However, it appears that this equation of state gives unphysical values for critical amplitudes such as that of the compressibility above the critical point. In this work, we present a modification of this equation of state based on the pressure data of Grigoriev et al. group and those of Abdulagatov, the isochoric specific heat data of Amirkhanov et al. as well as the isobaric specific heat of Gerasimov et al. Comparison with different sets of thermodynamic-property data available is given.

  1. Analysis and prediction of the critical regions of antimicrobial peptides based on conditional random fields.

    Directory of Open Access Journals (Sweden)

    Kuan Y Chang

    Full Text Available Antimicrobial peptides (AMPs are potent drug candidates against microbes such as bacteria, fungi, parasites, and viruses. The size of AMPs ranges from less than ten to hundreds of amino acids. Often only a few amino acids or the critical regions of antimicrobial proteins matter the functionality. Accurately predicting the AMP critical regions could benefit the experimental designs. However, no extensive analyses have been done specifically on the AMP critical regions and computational modeling on them is either non-existent or settled to other problems. With a focus on the AMP critical regions, we thus develop a computational model AMPcore by introducing a state-of-the-art machine learning method, conditional random fields. We generate a comprehensive dataset of 798 AMPs cores and a low similarity dataset of 510 representative AMP cores. AMPcore could reach a maximal accuracy of 90% and 0.79 Matthew's correlation coefficient on the comprehensive dataset and a maximal accuracy of 83% and 0.66 MCC on the low similarity dataset. Our analyses of AMP cores follow what we know about AMPs: High in glycine and lysine, but low in aspartic acid, glutamic acid, and methionine; the abundance of α-helical structures; the dominance of positive net charges; the peculiarity of amphipathicity. Two amphipathic sequence motifs within the AMP cores, an amphipathic α-helix and an amphipathic π-helix, are revealed. In addition, a short sequence motif at the N-terminal boundary of AMP cores is reported for the first time: arginine at the P(-1 coupling with glycine at the P1 of AMP cores occurs the most, which might link to microbial cell adhesion.

  2. Critical probability of percolation over bounded region in N-dimensional Euclidean space

    Science.gov (United States)

    Roubin, Emmanuel; Colliat, Jean-Baptiste

    2016-03-01

    Following Tomita and Murakami (Research of Pattern Formation ed R Takaki (Tokyo: KTK Scientific Publishers) pp 197-203) we propose an analytical model to predict the critical probability of percolation. It is based on the excursion set theory which allows us to consider N-dimensional bounded regions. Details are given for the three-dimensional (3D) case and statistically representative volume elements are calculated. Finally, generalisation to the N-dimensional case is made.

  3. Parallel evolution of genes and languages in the Caucasus region.

    Science.gov (United States)

    Balanovsky, Oleg; Dibirova, Khadizhat; Dybo, Anna; Mudrak, Oleg; Frolova, Svetlana; Pocheshkhova, Elvira; Haber, Marc; Platt, Daniel; Schurr, Theodore; Haak, Wolfgang; Kuznetsova, Marina; Radzhabov, Magomed; Balaganskaya, Olga; Romanov, Alexey; Zakharova, Tatiana; Soria Hernanz, David F; Zalloua, Pierre; Koshel, Sergey; Ruhlen, Merritt; Renfrew, Colin; Wells, R Spencer; Tyler-Smith, Chris; Balanovska, Elena

    2011-10-01

    We analyzed 40 single nucleotide polymorphism and 19 short tandem repeat Y-chromosomal markers in a large sample of 1,525 indigenous individuals from 14 populations in the Caucasus and 254 additional individuals representing potential source populations. We also employed a lexicostatistical approach to reconstruct the history of the languages of the North Caucasian family spoken by the Caucasus populations. We found a different major haplogroup to be prevalent in each of four sets of populations that occupy distinct geographic regions and belong to different linguistic branches. The haplogroup frequencies correlated with geography and, even more strongly, with language. Within haplogroups, a number of haplotype clusters were shown to be specific to individual populations and languages. The data suggested a direct origin of Caucasus male lineages from the Near East, followed by high levels of isolation, differentiation, and genetic drift in situ. Comparison of genetic and linguistic reconstructions covering the last few millennia showed striking correspondences between the topology and dates of the respective gene and language trees and with documented historical events. Overall, in the Caucasus region, unmatched levels of gene-language coevolution occurred within geographically isolated populations, probably due to its mountainous terrain.

  4. Self-Organizing Global Gene Expression Regulated through Criticality: Mechanism of the Cell-Fate Change

    Science.gov (United States)

    Tsuchiya, Masa; Giuliani, Alessandro; Hashimoto, Midori; Erenpreisa, Jekaterina; Yoshikawa, Kenichi

    2016-01-01

    Background A fundamental issue in bioscience is to understand the mechanism that underlies the dynamic control of genome-wide expression through the complex temporal-spatial self-organization of the genome to regulate the change in cell fate. We address this issue by elucidating a physically motivated mechanism of self-organization. Principal Findings Building upon transcriptome experimental data for seven distinct cell fates, including early embryonic development, we demonstrate that self-organized criticality (SOC) plays an essential role in the dynamic control of global gene expression regulation at both the population and single-cell levels. The novel findings are as follows: i) Mechanism of cell-fate changes: A sandpile-type critical transition self-organizes overall expression into a few transcription response domains (critical states). A cell-fate change occurs by means of a dissipative pulse-like global perturbation in self-organization through the erasure of initial-state critical behaviors (criticality). Most notably, the reprogramming of early embryo cells destroys the zygote SOC control to initiate self-organization in the new embryonal genome, which passes through a stochastic overall expression pattern. ii) Mechanism of perturbation of SOC controls: Global perturbations in self-organization involve the temporal regulation of critical states. Quantitative evaluation of this perturbation in terminal cell fates reveals that dynamic interactions between critical states determine the critical-state coherent regulation. The occurrence of a temporal change in criticality perturbs this between-states interaction, which directly affects the entire genomic system. Surprisingly, a sub-critical state, corresponding to an ensemble of genes that shows only marginal changes in expression and consequently are considered to be devoid of any interest, plays an essential role in generating a global perturbation in self-organization directed toward the cell-fate change

  5. Critical period of weed control in oilseed rape in two Moroccan regions.

    Science.gov (United States)

    Maataoui, A; Bouhache, M; Benbella, M; Talouizte, A

    2003-01-01

    The determination of critical period of weed control in oilseed rape is necessary to know the weed control period. To determine the critical period, two fields experiments were carried out during 1995-96 growth season in Loukkos and Saïs regions at two oilseed densities (D1 = 24 and D2 = 36 plants m(-2)). Ten treatments corresponding to plots left weed free or weeded plots until four leaves, flowers bud, flowering, puds formation, and maturity stages of oilseed rape were tested. Density and biomass of weeds were determined at each oilseed stages. Results showed that weed density and biomass were higher in Saïs than in Loukkos sites. For a 10% yield loss, critical period of weed control in Loukkos was from 458 to 720 degree days after emergence (D degrees AE) and from 480 to 720 D degrees AE in oilseed conducted at densities D1 and D2, respectively. In Saïs, critical period of weed control was from 474 to 738 D degrees AE and from 468 to 675 D degrees AE in oilseed conducted at D1 and D2, respectively. It was concluded that the length of the critical period of weed control in oilseed rape grain yield seems to be dependant of the level of the infestation.

  6. Regional genomic instability predisposes to complex dystrophin gene rearrangements.

    Science.gov (United States)

    Oshima, Junko; Magner, Daniel B; Lee, Jennifer A; Breman, Amy M; Schmitt, Eric S; White, Lisa D; Crowe, Carol A; Merrill, Michelle; Jayakar, Parul; Rajadhyaksha, Aparna; Eng, Christine M; del Gaudio, Daniela

    2009-09-01

    Mutations in the dystrophin gene (DMD) cause Duchenne and Becker muscular dystrophies and the majority of cases are due to DMD gene rearrangements. Despite the high incidence of these aberrations, little is known about their causative molecular mechanism(s). We examined 792 DMD/BMD clinical samples by oligonucleotide array-CGH and report on the junction sequence analysis of 15 unique deletion cases and three complex intragenic rearrangements to elucidate potential underlying mechanism(s). Furthermore, we present three cases with intergenic rearrangements involving DMD and neighboring loci. The cases with intragenic rearrangements include an inversion with flanking deleted sequences; a duplicated segment inserted in direct orientation into a deleted region; and a splicing mutation adjacent to a deletion. Bioinformatic analysis demonstrated that 7 of 12 breakpoints combined among 3 complex cases aligned with repetitive sequences, as compared to 4 of 30 breakpoints for the 15 deletion cases. Moreover, the inversion/deletion case may involve a stem-loop structure that has contributed to the initiation of this rearrangement. For the duplication/deletion and splicing mutation/deletion cases, the presence of the first mutation, either a duplication or point mutation, may have elicited the deletion events in an attempt to correct preexisting mutations. While NHEJ is one potential mechanism for these complex rearrangements, the highly complex junction sequence of the inversion/deletion case suggests the involvement of a replication-based mechanism. Our results support the notion that regional genomic instability, aided by the presence of repetitive elements, a stem-loop structure, and possibly preexisting mutations, may elicit complex rearrangements of the DMD gene.

  7. Anthropogenic antibiotic resistance genes mobilization to the polar regions

    Science.gov (United States)

    Hernández, Jorge; González-Acuña, Daniel

    2016-01-01

    Anthropogenic influences in the southern polar region have been rare, but lately microorganisms associated with humans have reached Antarctica, possibly from military bases, fishing boats, scientific expeditions, and/or ship-borne tourism. Studies of seawater in areas of human intervention and proximal to fresh penguin feces revealed the presence of Escherichia coli strains least resistant to antibiotics in penguins, whereas E. coli from seawater elsewhere showed resistance to one or more of the following antibiotics: ampicillin, tetracycline, streptomycin, and trim-sulfa. In seawater samples, bacteria were found carrying extended-spectrum β-lactamase (ESBL)-type CTX-M genes in which multilocus sequencing typing (MLST) showed different sequence types (STs), previously reported in humans. In the Arctic, on the contrary, people have been present for a long time, and the presence of antibiotic resistance genes (ARGs) appears to be much more wide-spread than was previously reported. Studies of E coli from Arctic birds (Bering Strait) revealed reduced susceptibility to antibiotics, but one globally spreading clone of E. coli genotype O25b-ST131, carrying genes of ESBL-type CTX-M, was identified. In the few years between sample collections in the same area, differences in resistance pattern were observed, with E. coli from birds showing resistance to a maximum of five different antibiotics. Presence of resistance-type ESBLs (TEM, SHV, and CTX-M) in E. coli and Klebsiella pneumoniae was also confirmed by specified PCR methods. MLST revealed that those bacteria carried STs that connect them to previously described strains in humans. In conclusion, bacteria previously related to humans could be found in relatively pristine environments, and presently human-associated, antibiotic-resistant bacteria have reached a high global level of distribution that they are now found even in the polar regions. PMID:27938628

  8. Rarity of DNA sequence alterations in the promoter region of the human androgen receptor gene

    Directory of Open Access Journals (Sweden)

    D.F. Cabral

    2004-12-01

    Full Text Available The human androgen receptor (AR gene promoter lies in a GC-rich region containing two principal sites of transcription initiation and a putative Sp1 protein-binding site, without typical "TATA" and "CAAT" boxes. It has been suggested that mutations within the 5'untranslated region (5'UTR may contribute to the development of prostate cancer by changing the rates of gene transcription and/or translation. In order to investigate this question, the aim of the present study was to search for the presence of mutations or polymorphisms at the AR-5'UTR in 92 prostate cancer patients, where histological diagnosis of adenocarcinoma was established in specimens obtained from transurethral resection or after prostatectomy. The AR-5'UTR was amplified by PCR from genomic DNA samples of the patients and of 100 healthy male blood donors, included as controls. Conformation-sensitive gel electrophoresis was used for DNA sequence alteration screening. Only one band shift was detected in one individual from the blood donor group. Sequencing revealed a new single nucleotide deletion (T in the most conserved portion of the promoter region at position +36 downstream from the transcription initiation site I. Although the effect of this specific mutation remains unknown, its rarity reveals the high degree of sequence conservation of the human androgen promoter region. Moreover, the absence of detectable variation within the critical 5'UTR in prostate cancer patients indicates a low probability of its involvement in prostate cancer etiology.

  9. DSCR2, a Down syndrome critical region protein, is localized to the endoplasmic reticulum of mammalian cells

    Directory of Open Access Journals (Sweden)

    PA Possik

    2009-06-01

    Full Text Available We used immunocytochemical and fluorescence assays to investigate the subcellular location of the protein encoded by Down syndrome critical region gene 2 (DSCR2 in transfected cells. It was previously suggested that DSCR2 is located in the plasma membrane as an integral membrane protein. Interestingly, we observed this protein in the endoplasmic reticulum (ER of cells.We also studied whether the truncated forms of DSCR2 showed different subcellular distributions. Our observations indicate that DSCR2 probably is not inserted into the membrane of the endoplasmic reticulum since the fragments lacking the predicted transmembrane (TM helices remained associated with the ER. Our analyses suggest that, although DSCR2 is associated with the endoplasmic reticulum, it is not an integral membrane protein and it is maintained on the cytoplasmic side of the ER by indirect interaction with the ER membrane or with another protein.

  10. Current status and future prospect of FSHD region gene 1

    Indian Academy of Sciences (India)

    ARMAN KUNWAR HANSDA; ANKIT TIWARI; MANJUSHA DIXIT

    2017-06-01

    FSHD region gene 1 (FRG1), as the name suggests, is the primary candidate gene for fascioscapulohumeral musculardystrophy disease. It seemingly affects muscle physiology in normal individuals but in FSHD, where it is found to behighly upregulated, might be involved in disruption of face, scapula and humeral skeletal muscle. Literature on FRG1,reviewed from 1996 to 2016, reveals that it is primarily associated with muscle development and maintenance.Approximately 75% of FSHD patients also show vascular abnormalities indicating that FRG1 might have some part toplay in these abnormalities. Research involving vasculature in X. laevis larvae shows that FRG1 positively affectsnormal vasculature. Few of the well-established angiogenic regulators seem to get affected by abnormal expressionlevel of FRG1. Its primary localization in sub nuclear structures like Cajal bodies and nuclear speckles indicatesregulation of the above-mentioned factors by transcriptional and post-transcriptional machineries, but in-depth studiesneed to be done to conclude a clear statement. In this review, we have attempted to present all the work done onFRG1, all the lacunas which need to be unraveled, and hypothesized a model for our readers to get an insight into itsmolecular mechanism.

  11. The bovine Mx1 gene: characterization of the gene structure, alternative splicing, and promoter region.

    Science.gov (United States)

    Kojima, Takatoshi; Oshima, Kazunaga; Watanabe, Hiroko; Komatsu, Masanori

    2003-12-01

    The Mx gene encodes an antiviral protein and is induced by type 1 interferons (IFNs). In this study, a new bovine Mx gene (designated Mx1B) was isolated from the endometrial cDNA library of the early pregnant cow. Although the Mx1B cDNA contained a single open reading frame (ORF) the same as the known Mx1, the 5' untranslated region (UTR) and 5' coding region of Mx1B were rather different from the corresponding regions of Mx1. Genomic structure analysis revealed that bovine Mx1B was an alternative splicing variant of Mx1 and had transcription regulatory sequences in the upstream region. RT-PCR and its sequencing identified another Mx1 splicing variant and demonstrated that these bovine Mx1 splicing variants were ubiquitously expressed in various tissues. Furthermore, it was found that all the bovine breeds investigated had identical splice sites of Mx1 and Mx1B. It is speculated that cattle have at least two functional Mx isoforms that might provide strong natural resistance to specific viruses.

  12. Characterisation of the promoter region of the zebrafish six7 gene.

    Science.gov (United States)

    Drivenes, O; Seo, H C; Fjose, A

    2000-04-25

    The Drosophila homeobox gene sine oculis and its murine homologue Six3 have both been shown to have regulatory functions in eye and brain development. In zebrafish, three Six3-related genes with conserved expression during early eye and head formation have been identified. One of these, six7, is first expressed at the gastrula stage in the involuting axial mesoderm, and later in the overlying neuroectoderm from which the forebrain and optic primordium develop. To elucidate the mechanisms regulating six7 expression, we isolated a 2.7-kb fragment of the 5'-flanking region. Three sequentially deleted fragments of this upstream region were used to produce GFP reporter constructs for analysis of tissue-specific expression in zebrafish embryos. The results show that a 625-bp upstream fragment is sufficient to direct strong expression of the reporter during gastrulation and early neurulation. The proximal part of the promoter contains binding sites for various constitutive transcription factors and an additional upstream element that was shown to be critical in directing expression to the anterior region of the zebrafish brain.

  13. Critical brain regions for tool-related and imitative actions: a componential analysis

    Science.gov (United States)

    Shapiro, Allison D.; Coslett, H. Branch

    2014-01-01

    Numerous functional neuroimaging studies suggest that widespread bilateral parietal, temporal, and frontal regions are involved in tool-related and pantomimed gesture performance, but the role of these regions in specific aspects of gestural tasks remains unclear. In the largest prospective study of apraxia-related lesions to date, we performed voxel-based lesion–symptom mapping with data from 71 left hemisphere stroke participants to assess the critical neural substrates of three types of actions: gestures produced in response to viewed tools, imitation of tool-specific gestures demonstrated by the examiner, and imitation of meaningless gestures. Thus, two of the three gesture types were tool-related, and two of the three were imitative, enabling pairwise comparisons designed to highlight commonalities and differences. Gestures were scored separately for postural (hand/arm positioning) and kinematic (amplitude/timing) accuracy. Lesioned voxels in the left posterior temporal gyrus were significantly associated with lower scores on the posture component for both of the tool-related gesture tasks. Poor performance on the kinematic component of all three gesture tasks was significantly associated with lesions in left inferior parietal and frontal regions. These data enable us to propose a componential neuroanatomic model of action that delineates the specific components required for different gestural action tasks. Thus, visual posture information and kinematic capacities are differentially critical to the three types of actions studied here: the kinematic aspect is particularly critical for imitation of meaningless movement, capacity for tool-action posture representations are particularly necessary for pantomimed gestures to the sight of tools, and both capacities inform imitation of tool-related movements. These distinctions enable us to advance traditional accounts of apraxia. PMID:24776969

  14. Endogenous retroviral LTRs as promoters for human genes: a critical assessment.

    Science.gov (United States)

    Cohen, Carla J; Lock, Wynne M; Mager, Dixie L

    2009-12-15

    Gene regulatory changes are thought to be major factors driving species evolution, with creation of new regulatory regions likely being instrumental in contributing to diversity among vertebrates. There is growing appreciation for the role of transposable elements (TEs) in gene regulation and, indeed, laboratory investigations have confirmed many specific examples of mammalian genes regulated by promoters donated by endogenous retroviruses (ERVs) or other TEs. Bioinformatics studies have revealed hundreds of additional instances where this is likely to be the case. Since the long terminal repeats (LTRs) of retroviruses naturally contain abundant transcriptional regulatory signals, roles for ERV LTRs in regulating mammalian genes are eminently plausible. Moreover, it seems reasonable that exaptation of an LTR regulatory module provides opportunities for evolution of new gene regulatory patterns. In this Review we summarize known examples of LTRs that function as human gene alternative promoters, as well as the evidence that LTR exaptation has resulted in a pattern of novel gene expression significantly different from the pattern before LTR insertion or from that of gene orthologs lacking the LTR. Available data suggest that, while new expression patterns can arise as a result of LTR usage, this situation is relatively rare and is largely restricted to the placenta. In many cases, the LTR appears to be a minor, alternative promoter with an expression pattern similar to that of the native promoter(s) and hence likely exerts a subtle overall effect on gene expression. We discuss these findings and offer evolutionary models to explain these trends.

  15. Regionalized care for time-critical conditions: lessons learned from existing networks.

    Science.gov (United States)

    Carr, Brendan G; Matthew Edwards, J; Martinez, Ricardo

    2010-12-01

    The 2010 Academic Emergency Medicine (AEM) consensus conference "Beyond Regionalization" aimed to place the design of a 21st century emergency care delivery system at the center of emergency medicine's (EM's) health policy research agenda. To examine the lessons learned from existing regional systems, consensus conference organizers convened a panel discussion made up of experts from the fields of acute care surgery, interventional cardiology, acute ischemic stroke, cardiac arrest, critical care medicine, pediatric EM, and medical toxicology. The organizers asked that each member provide insight into the barriers that slowed network creation and the solutions that allowed them to overcome barriers. For ST-segment elevation myocardial infarction (STEMI) management, the American Heart Association's (AHA's) Mission: Lifeline aims to increase compliance with existing guidelines through improvements in the chain of survival, including emergency medical services (EMS) protocols. Increasing use of therapeutic hypothermia post-cardiac arrest through a network of hospitals in Virginia has led to dramatic improvements in outcome. A regionalized network of acute stroke management in Cincinnati was discussed, in addition to the effect of pediatric referral centers on pediatric capabilities of surrounding facilities. The growing importance of telemedicine to a variety of emergencies, including trauma and critical care, was presented. Finally, the importance of establishing a robust reimbursement mechanism was illustrated by the threatened closure of poison control centers nationwide. The panel discussion added valuable insight into the possibilities of maximizing patient outcomes through regionalized systems of emergency care. A primary challenge remaining is for EM to help to integrate the existing and developing disease-based systems of care into a more comprehensive emergency care system.

  16. Sequencing analysis reveals a unique gene organization in the gyrB region of Mycoplasma hominis

    DEFF Research Database (Denmark)

    Ladefoged, Søren; Christiansen, Gunna

    1994-01-01

    of which showed similarity to that which encodes the LicA protein of Haemophilus influenzae. The organization of the genes in the region showed no resemblance to that in the corresponding regions of other bacteria sequenced so far. The gyrA gene was mapped 35 kb downstream from the gyrB gene....

  17. Head and neck squamous cell carcinoma susceptibility genes in the HLA region

    NARCIS (Netherlands)

    Reinders, Judith

    2006-01-01

    The Human Leukocyte Antigen (HLA) region on the short arm of chromosome 6 includes the classical HLA genes and in addition HLA-related and non-HLA related genes. The majority of the genes located in this region are directly or indirectly involved in the immune response. The polymorphic HLA molecules

  18. Influenza NA and PB1 Gene Segments Interact during the Formation of Viral Progeny: Localization of the Binding Region within the PB1 Gene

    Directory of Open Access Journals (Sweden)

    Brad Gilbertson

    2016-08-01

    Full Text Available The influenza A virus genome comprises eight negative-sense viral RNAs (vRNAs that form individual ribonucleoprotein (RNP complexes. In order to incorporate a complete set of each of these vRNAs, the virus uses a selective packaging mechanism that facilitates co-packaging of specific gene segments but whose molecular basis is still not fully understood. Recently, we used a competitive transfection model where plasmids encoding the A/Puerto Rico/8/34 (PR8 and A/Udorn/307/72 (Udorn PB1 gene segments were competed to show that the Udorn PB1 gene segment is preferentially co-packaged into progeny virions with the Udorn NA gene segment. Here we created chimeric PB1 genes combining both Udorn and PR8 PB1 sequences to further define the location within the Udorn PB1 gene that drives co-segregation of these genes and show that nucleotides 1776–2070 of the PB1 gene are crucial for preferential selection. In vitro assays examining specific interactions between Udorn NA vRNA and purified vRNAs transcribed from chimeric PB1 genes also supported the importance of this region in the PB1-NA interaction. Hence, this work identifies an association between viral genes that are co-selected during packaging. It also reveals a region potentially important in the RNP-RNP interactions within the supramolecular complex that is predicted to form prior to budding to allow one of each segment to be packaged in the viral progeny. Our study lays the foundation to understand the co-selection of specific genes, which may be critical to the emergence of new viruses with pandemic potential.

  19. Evidence for a critical role of gene occlusion in cell fate restriction

    Institute of Scientific and Technical Information of China (English)

    Jedidiah Gaetz; Wei-Hua Yu; Andy Peng Xiang; Bruce T Lahn; Kayla L Clift; Croydon J Fernandes; Frank Fuxiang Mao; Jae Hyun Lee; Li Zhang; Samuel W Baker; Timothy J Looney; Kara M Foshay

    2012-01-01

    The progressive restriction of cell fate during lineage differentiation is a poorly understood phenomenon despite its ubiquity in multicellular organisms.We recently used a cell fusion assay to define a mode of epigenetic silencing that we termed "occlusion",wherein affected genes are silenced by cis-acting chromatin mechanisms irrespective of whether trans-acting transcriptional activators are present.We hypothesized that occlusion of lineage-inappropriate genes could contribute to cell fate restriction.Here,we test this hypothesis by introducing bacterial artificial chromosomes (BACs),which are devoid of chromatin modifications necessary for occlusion,into mouse fibroblasts.We found that BAC transgenes corresponding to occluded endogenous genes are expressed in most eases,whereas BAC transgenes corresponding to silent but non-occluded endogenous genes are not expressed.This indicates that the cellular milieu in trans supports the expression of most occluded genes in fibroblasts,and that the silent state of these genes is solely the consequence of occlusion in cis.For the BAC corresponding to the occluded myogenic master regulator Myf5,expression of the Myf5 transgene on the BAC triggered fibroblasts to acquire a muscle-like phenotype.These results provide compelling evidence for a critical role of gene occlusion in cell fate restriction.

  20. Localizing F(ST) outliers on a QTL map reveals evidence for large genomic regions of reduced gene exchange during speciation-with-gene-flow.

    Science.gov (United States)

    Via, Sara; Conte, Gina; Mason-Foley, Casey; Mills, Kelly

    2012-11-01

    Populations that maintain phenotypic divergence in sympatry typically show a mosaic pattern of genomic divergence, requiring a corresponding mosaic of genomic isolation (reduced gene flow). However, mechanisms that could produce the genomic isolation required for divergence-with-gene-flow have barely been explored, apart from the traditional localized effects of selection and reduced recombination near centromeres or inversions. By localizing F(ST) outliers from a genome scan of wild pea aphid host races on a Quantitative Trait Locus (QTL) map of key traits, we test the hypothesis that between-population recombination and gene exchange are reduced over large 'divergence hitchhiking' (DH) regions. As expected under divergence hitchhiking, our map confirms that QTL and divergent markers cluster together in multiple large genomic regions. Under divergence hitchhiking, the nonoutlier markers within these regions should show signs of reduced gene exchange relative to nonoutlier markers in genomic regions where ongoing gene flow is expected. We use this predicted difference among nonoutliers to perform a critical test of divergence hitchhiking. Results show that nonoutlier markers within clusters of F(ST) outliers and QTL resolve the genetic population structure of the two host races nearly as well as the outliers themselves, while nonoutliers outside DH regions reveal no population structure, as expected if they experience more gene flow. These results provide clear evidence for divergence hitchhiking, a mechanism that may dramatically facilitate the process of speciation-with-gene-flow. They also show the power of integrating genome scans with genetic analyses of the phenotypic traits involved in local adaptation and population divergence. © 2012 Blackwell Publishing Ltd.

  1. Critical issues in implementing low vision care in the Asia-Pacific region

    Directory of Open Access Journals (Sweden)

    Peggy Pei-Chia Chiang

    2012-01-01

    Full Text Available Two-thirds of the world′s population with low vision resides in the Asia-Pacific region. Provision of comprehensive low vision services is important to improve vision-related quality of life (QoL for people with this condition. This review outlines the critical issues and challenges facing the provision of low vision services in the Asia-Pacific region. The review offers possible strategies to tackle these issues and challenges facing service providers and policy makers in lieu of Vision 2020 strategies in this area. Pertinent findings from the global survey of low vision services and extensive ground work conducted in the region are used; in addition, a discussion on the availability of services, human resources and training, and funding and the future sustainability of low vision care will be covered. In summary, current issues and challenges facing the region are the lack of specific evidence-based data, access, appropriate equipment and facilities, human resources, funding, and sustainability. These issues are inextricably interlinked and thus cannot be addressed in isolation. The solutions proposed cover all areas of the VISION 2020 strategy that include service delivery, human resources, infrastructure and equipment, advocacy and partnership; and include provision of comprehensive care via vertical and horizontal integration; strengthening primary level care in the community; providing formal and informal training to enable task shifting and capacity building; and promoting strong government and private sector partnership to achieve long-term service financial sustainability.

  2. Magnon-induced nuclear relaxation in the quantum critical region of a Heisenberg linear chain

    Science.gov (United States)

    Hoch, M. J. R.

    2017-07-01

    The low-temperature properties of spin-1/2 one-dimensional (1D) Heisenberg antiferromagnetic (HAF) chains which have relatively small exchange couplings between the spins can be tuned using laboratory-scale magnetic fields. Magnetization measurements, made as a function of temperature, provide phase diagrams for these systems and establish the quantum critical point (QCP). The evolution of the spin dynamics behavior with temperature and applied field in the quantum critical (QC) region, near the QCP, is of particular interest and has been experimentally investigated in a number of 1D HAFs using neutron scattering and nuclear magnetic resonance as the preferred techniques. In the QC phase both quantum and thermal spin fluctuations are present. As a result of extended spin correlations in the chains, magnon excitations are important at finite temperatures. An expression for the NMR spin-lattice relaxation rate 1 /T1 of probe nuclei in the QC phase of 1D HAFs is obtained by considering Raman scattering processes which induce nuclear spin flips. The relaxation rate expression, which involves the temperature and the chemical potential, predicts scaling behavior of 1 /T1 consistent with recent experimental findings for quasi-1D HAF systems. A simple relationship between 1 /T1 and the deviation of the magnetization from saturation (MS-M ) is predicted for the QC region.

  3. A 600 kb triplication in the cat eye syndrome critical region causes anorectal, renal and preauricular anomalies in a three-generation family.

    Science.gov (United States)

    Knijnenburg, Jeroen; van Bever, Yolande; Hulsman, Lorette O M; van Kempen, Chantal A P; Bolman, Galhana M; van Loon, Rosa Laura E; Beverloo, H Berna; van Zutven, Laura J C M

    2012-09-01

    Cat eye syndrome (CES) is caused by a gain of the proximal part of chromosome 22. Usually, a supernumerary marker chromosome is present, containing two extra copies of the chromosome 22q11.1q11.21 region. More sporadically, the gain is present intrachromosomally. The critical region for CES is currently estimated to be about 2.1 Mb and to contain at least 14 RefSeq genes. Gain of this region may cause ocular coloboma, preauricular, anorectal, urogenital and congenital heart malformations. We describe a family in which a 600 kb intrachromosomal triplication is present in at least three generations. The copy number alteration was detected using MLPA and further characterized with interphase and metaphase FISH and SNP-array. The amplified fragment is located in the distal part of the CES region. The family members show anal atresia and preauricular tags or pits, matching part of the phenotype of this syndrome. This finding suggests that amplification of the genes CECR2, SLC25A18 and ATP6V1E1, mapping within the critical region for CES, may be responsible for anorectal, renal and preauricular anomalies in patients with CES.

  4. Regional citrate anticoagulation in critically ill patients during continuous blood purification

    Institute of Scientific and Technical Information of China (English)

    龚德华; 季大玺; 徐斌; 谢红浪; 刘云; 黎磊石

    2003-01-01

    Objectives To evaluate the safety and define the contraindication of regional citrate anticoagulation treatment on various critically ill patients being treated by continuous blood purification, who also had bleeding tendencies. Methods Forty critically ill patients being treated by continuous blood purification (CBP) were involved in this study. Due to their bleeding tendencies, regional citrate anticoagulation treatment was given to all of them. Those with hepatic function impairment (n=10) were classified as Group A, those with hypoxemia were classified as Group B (n=10), and the others as Group C (n=20). Blood samples were collected before treatment, and at 4, 12, 24, 36, and 48 hour intervals during CBP. These samples then were used arterial blood gas analysis, whole blood activated clotting time (WBACT) pre- and post-filter, and serum ionized calcium examination. Results WBACT pre-filter showed little fluctuant through the 48hr period of CBP, and WBACT post-filter showed obvious prolongation than that of the pre-filter (P<0.05) at all time points. Metabolic acidosis was found in Group A patients before CBP, and improved during CBP. Normal acid-base conditions of patients were disturbed and deteriorated in Group B during CBP, but not in Group C. Serum ionized calcium was maintained at a normal range during CBP in Group A and C patients, but declined significantly in Group B patients (vs. pre-treatment, P<0.05). Conclusions Regional citrate anticoagulation can be safely used in conjunction with CBP treatment for patients with hepatic function impairment , but may induce acidosis and a decline in serum ionized calcium when used with hypoxemic patients.

  5. Comparative analysis of chromatin landscape in regulatory regions of human housekeeping and tissue specific genes

    Directory of Open Access Journals (Sweden)

    Dasgupta Dipayan

    2005-05-01

    Full Text Available Abstract Background Global regulatory mechanisms involving chromatin assembly and remodelling in the promoter regions of genes is implicated in eukaryotic transcription control especially for genes subjected to spatial and temporal regulation. The potential to utilise global regulatory mechanisms for controlling gene expression might depend upon the architecture of the chromatin in and around the gene. In-silico analysis can yield important insights into this aspect, facilitating comparison of two or more classes of genes comprising of a large number of genes within each group. Results In the present study, we carried out a comparative analysis of chromatin characteristics in terms of the scaffold/matrix attachment regions, nucleosome formation potential and the occurrence of repetitive sequences, in the upstream regulatory regions of housekeeping and tissue specific genes. Our data show that putative scaffold/matrix attachment regions are more abundant and nucleosome formation potential is higher in the 5' regions of tissue specific genes as compared to the housekeeping genes. Conclusion The differences in the chromatin features between the two groups of genes indicate the involvement of chromatin organisation in the control of gene expression. The presence of global regulatory mechanisms mediated through chromatin organisation can decrease the burden of invoking gene specific regulators for maintenance of the active/silenced state of gene expression. This could partially explain the lower number of genes estimated in the human genome.

  6. Correlation between ECT2 gene expression and methylation change of ECT2 promoter region in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Mang-Li Zhang; Sen Lu; Lin Zhou; Shu-Sen Zheng

    2008-01-01

    BACKGROUND: Pancreatic cancer is closely related to epigenetic abnormality. The epithelial cell transforming sequence 2 gene (ECT2) plays a critical role in Rho activation during cytokinesis, and thus may play a role in the pathogenesis of pancreatic cancer. In this study, we investigated the relationships between aberrant expression and epigenetic changes of the ECT2 gene in pancreatic cancer. METHODS: Four cell lines (PANC-1, Colo357, T3M-4 and PancTuⅠ) and pancreatic ductal adenocarcinoma (PDAC) tissues were used for mRNA detection. After restriction isoschizomer endonucleases (MspⅠ/HpaⅡ) were used to digest the DNA sequence (5'-CCGG-3'), PCR was made to amplify the product. And RT-PCR was applied to determine the expression of the gene. RESULTS: The mRNA expression of the ECT2 gene was higher in pancreatic tumor tissue than in normal tissue. The gene was also expressed in the 4 PDAC cell lines. The methylation states of the upstream regions of the ECT2 gene were almost identical in normal, tumor pancreatic tissues, and the 4 PDAC cell lines. Some of the 5'-CCGG-3' areas in the upstream region of ECT2 were methylated, while others were unmethylated. CONCLUSIONS: The oncogene ECT2 is overexpressed in pancreatic tumor tissues as veriifed by RT-PCR detection. The methylation status of DNA in promoter areas is involved in the gene expression, along with other factors, in pancreatic cancer.

  7. A critical analysis of the higher Pennsylvanian megafloras of the Appalachian region

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, R.H.; Lyons, P.C. [Jardin Botanico de Cordoba, Cordoba (Spain)

    1997-01-01

    Published records of Stephanian megafloras in eastern North America are critically reviewed and the results of personal investigations in the Appalachian region are reported. The analysis despite incomplete megafloral records, allows the conclusion that the succession in the Appalachian area hides a large stratigraphic gap, at the base of the Upper Pennsylvanian Series. This gap is in the same position and of similar magnitude to that below the Rotliegend of northwestern Europe. Analysis of the floral records in the Southern Anthracite field shows evidence of a similar gap. Megafloral data from the Narragansett basin are analysed, but are found insufficient for determining if there is a stratigraphic gap. Published data from the Maritime Provinces of Canada are used to suggest that the same pre-Rotliegend gap exists in this area. Recognition of this important regional unconformity in eastern North America, which is similar to that in the British Isles and throughout northwestern Europe, strengthens the view that the Appalachian region and the paralic coal belt of northwestern Europe constitute a single, major palaeogeographic area.

  8. Enhanced Stability and Controllability of an Ionic Diode Based on Funnel-Shaped Nanochannels with an Extended Critical Region.

    Science.gov (United States)

    Xiao, Kai; Xie, Ganhua; Zhang, Zhen; Kong, Xiang-Yu; Liu, Qian; Li, Pei; Wen, Liping; Jiang, Lei

    2016-05-01

    The enhanced stability and controllability of an ionic diode system based on funnel-shaped nanochannels with a much longer critical region is reported. The polarity of ion transport switching from anion/cation-selective to ambipolar can be controlled by tuning the length and charge of the critical region. This nanofluidic structure anticipates potential applications in single-molecule biosensing, water resource monitoring, and healthcare.

  9. Intrinsic noise and deviations from criticality in Boolean gene-regulatory networks

    Science.gov (United States)

    Villegas, Pablo; Ruiz-Franco, José; Hidalgo, Jorge; Muñoz, Miguel A.

    2016-10-01

    Gene regulatory networks can be successfully modeled as Boolean networks. A much discussed hypothesis says that such model networks reproduce empirical findings the best if they are tuned to operate at criticality, i.e. at the borderline between their ordered and disordered phases. Critical networks have been argued to lead to a number of functional advantages such as maximal dynamical range, maximal sensitivity to environmental changes, as well as to an excellent tradeoff between stability and flexibility. Here, we study the effect of noise within the context of Boolean networks trained to learn complex tasks under supervision. We verify that quasi-critical networks are the ones learning in the fastest possible way –even for asynchronous updating rules– and that the larger the task complexity the smaller the distance to criticality. On the other hand, when additional sources of intrinsic noise in the network states and/or in its wiring pattern are introduced, the optimally performing networks become clearly subcritical. These results suggest that in order to compensate for inherent stochasticity, regulatory and other type of biological networks might become subcritical rather than being critical, all the most if the task to be performed has limited complexity.

  10. Intrinsic noise and deviations from criticality in Boolean gene-regulatory networks

    Science.gov (United States)

    Villegas, Pablo; Ruiz-Franco, José; Hidalgo, Jorge; Muñoz, Miguel A.

    2016-01-01

    Gene regulatory networks can be successfully modeled as Boolean networks. A much discussed hypothesis says that such model networks reproduce empirical findings the best if they are tuned to operate at criticality, i.e. at the borderline between their ordered and disordered phases. Critical networks have been argued to lead to a number of functional advantages such as maximal dynamical range, maximal sensitivity to environmental changes, as well as to an excellent tradeoff between stability and flexibility. Here, we study the effect of noise within the context of Boolean networks trained to learn complex tasks under supervision. We verify that quasi-critical networks are the ones learning in the fastest possible way –even for asynchronous updating rules– and that the larger the task complexity the smaller the distance to criticality. On the other hand, when additional sources of intrinsic noise in the network states and/or in its wiring pattern are introduced, the optimally performing networks become clearly subcritical. These results suggest that in order to compensate for inherent stochasticity, regulatory and other type of biological networks might become subcritical rather than being critical, all the most if the task to be performed has limited complexity. PMID:27713479

  11. Emotional intelligence moderates the relationship between regional gray matter volume in the bilateral temporal pole and critical thinking disposition.

    Science.gov (United States)

    Yao, Xiaonan; Yuan, Shuge; Yang, Wenjing; Chen, Qunlin; Wei, Dongtao; Hou, Yuling; Zhang, Lijie; Qiu, Jiang; Yang, Dong

    2017-03-29

    Critical thinking enables people to form sound beliefs and provides a basis for emotional life. Research has indicated that individuals with better critical thinking disposition can better recognize and regulate their emotions, though the neuroanatomical mechanisms involved in this process remain to be elucidated. Further, the influence of emotional intelligence on the relationship between brain structure and critical thinking disposition has not been examined. The present study utilized voxel-based morphometry (VBM) to investigate the neural structures underlying critical thinking disposition in a large sample of college students (N = 296). Regional gray matter volume (rGMV) in the bilateral temporal pole, which reflects an individual's ability to process social and emotional information, was negatively correlated with critical thinking disposition. In addition, rGMV in bilateral para hippocampal regions -regions involved in contextual association/emotional regulation-exhibited negative correlation with critical thinking disposition. Further analysis revealed that emotional intelligence moderated the relationship between rGMV of the temporal pole and critical thinking disposition. Specifically, critical thinking disposition was associated with decreased GMV of the temporal pole for individuals who have relatively higher emotional intelligence rather than lower emotional intelligence. The results of the present study indicate that people who have higher emotional intelligence exhibit more effective and automatic processing of emotional information and tend to be strong critical thinkers.

  12. Engineered chromosome-based genetic mapping establishes a 3.7 Mb critical genomic region for Down syndrome-associated heart defects in mice.

    Science.gov (United States)

    Liu, Chunhong; Morishima, Masae; Jiang, Xiaoling; Yu, Tao; Meng, Kai; Ray, Debjit; Pao, Annie; Ye, Ping; Parmacek, Michael S; Yu, Y Eugene

    2014-06-01

    Trisomy 21 (Down syndrome, DS) is the most common human genetic anomaly associated with heart defects. Based on evolutionary conservation, DS-associated heart defects have been modeled in mice. By generating and analyzing mouse mutants carrying different genomic rearrangements in human chromosome 21 (Hsa21) syntenic regions, we found the triplication of the Tiam1-Kcnj6 region on mouse chromosome 16 (Mmu16) resulted in DS-related cardiovascular abnormalities. In this study, we developed two tandem duplications spanning the Tiam1-Kcnj6 genomic region on Mmu16 using recombinase-mediated genome engineering, Dp(16)3Yey and Dp(16)4Yey, spanning the 2.1 Mb Tiam1-Il10rb and 3.7 Mb Ifnar1-Kcnj6 regions, respectively. We found that Dp(16)4Yey/+, but not Dp(16)3Yey/+, led to heart defects, suggesting the triplication of the Ifnar1-Kcnj6 region is sufficient to cause DS-associated heart defects. Our transcriptional analysis of Dp(16)4Yey/+ embryos showed that the Hsa21 gene orthologs located within the duplicated interval were expressed at the elevated levels, reflecting the consequences of the gene dosage alterations. Therefore, we have identified a 3.7 Mb genomic region, the smallest critical genomic region, for DS-associated heart defects, and our results should set the stage for the final step to establish the identities of the causal gene(s), whose elevated expression(s) directly underlie this major DS phenotype.

  13. Effect of regional citrate anticoagulation on critical patients with continuous renal replacement therapy

    Institute of Scientific and Technical Information of China (English)

    Li-Li You

    2016-01-01

    Objective:To investigate the efficacy and safety of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT) for critical patients.Methods:A total of 83 critical patients need CRRT in the intensive care units of our hospital from July 2012 to June 2016 were recruited in the study, and the patients were divided into two groups randomly, the patients in observation group received the RCA treatment, and the patients in control group received traditional low molecular heparin anticoagulation. The difference of safety indicators, biochemical indicators, extracorporeal circulation blood coagulation condition and complications in patients were determined between two groups.Results: Compared with control group, the patients in observation group had an elevated level of iCa2+, the level of chloride ion reduced, the use time of filter increased, the bleeding cases reduced, the concentrations of urea nitrogen, creatinine TNF-α, IL-1β, IL-8 and NO were all significantly downregulated, the data have a significant difference (P < 0.05).Conclusions:RCA is a safe and effective method for CRRT in patients with a high risk of bleeding.

  14. Hydrogeochemistry of prairie pothole region wetlands: Role of long-term critical zone processes

    Science.gov (United States)

    Goldhaber, Martin B.; Mills, Christopher; Morrison, Jean M.; Stricker, Craig A.; Mushet, David M.; LaBaugh, James W.

    2014-01-01

    This study addresses the geologic and hydrogeochemical processes operating at a range of scales within the prairie pothole region (PPR). The PPR is a 750,000 km2portion of north central North America that hosts millions of small wetlands known to be critical habitat for waterfowl and other wildlife. At a local scale, we characterized the geochemical evolution of the 92-ha Cottonwood Lake study area (CWLSA), located in North Dakota, USA. Critical zone processes are the long-term determinant of wetland water and groundwater geochemistry via the interaction of oxygenated groundwater with pyrite in the underlying glacial till. Pyrite oxidation produced a brown, iron oxide-bearing surface layer locally over 13 m thick and an estimated minimum of 1.3 × 1010 g sulfate (SO42 −) at CWLSA. We show that the majority of this SO42− now resides in solid-phase gypsum (CaSO4•2H2O) and gypsum-saturated groundwater.

  15. Characterization of the cheetah serum amyloid A1 gene: critical role and functional polymorphism of a cis-acting element.

    Science.gov (United States)

    Zhang, Beiru; Une, Yumi; Ge, Fengxia; Fu, Xiaoying; Qian, Jinze; Zhang, Pengyao; Sawashita, Jinko; Higuchi, Keiichi; Mori, Masayuki

    2008-01-01

    Amyloid A (AA) amyloidosis is one of the principal causes of morbidity and mortality in captive cheetahs (Acinonyx jubatus), which are in danger of extinction. For practical conservation of this species, therefore, it is critical to elucidate the etiology of AA amyloidosis, especially to understand the mechanisms of transcriptional regulation of serum amyloid A (SAA), a precursor protein of the AA protein. In this study, the structure and nucleotide sequence of the cheetah SAA1 gene including the 5'-flanking promoter/enhancer region was determined. Putative nuclear factor kappa-B (NF-kappaB) and CCAAT/enhancer binding protein beta (C/EBPbeta) cis-acting elements, which play key roles in SAA1 transcriptional induction in response to inflammation, were identified in the 5'-flanking region of the cheetah SAA1 gene. Fortuitously, a single nucleotide polymorphism was identified in the captive cheetah cohort in the putative NF-kappaB cis-acting element and had a remarkable effect on SAA1 transcriptional induction. These results provide a foundation not only for clarifying the etiology of AA amyloidosis in the cheetah but also for contriving a strategy for conservation of this species.

  16. A regional cohort study of the treatment of critically ill children with bronchiolitis.

    Science.gov (United States)

    Carroll, Christopher L; Faustino, Edward Vincent S; Pinto, Matthew G; Sala, Kathleen A; Canarie, Michael F; Li, Simon; Giuliano, John S; The Northeast Pediatric Critical Care Research Consortium

    2016-12-01

    To describe the treatment practices in critically ill children with RSV bronchiolitis across four regional PICUs in the northeastern United States, and to determine the factors associated with increased ICU length of stay in this population. We conducted a retrospective cohort study of children who were admitted with RSV bronchiolitis between July 2009 and July 2011 to the PICUs of Connecticut Children's Medical Center, Yale-New Haven Children's Hospital, Maria Fareri Children's Hospital, and Baystate Children's Hospital. Data were collected regarding clinical characteristics and intensive care course among these hospitals. During the study period, 323 children were admitted to one of the four ICUs with RSV bronchiolitis. Despite similar mortality risk scores among ICUs, there was considerable variation in the use of therapies, particularly intubation and mechanical ventilation, in which there was greater than a 3.5-fold increased risk of intubation between sites with the highest and lowest frequency of intubation (odds ratio: 3.8; 95% confidence interval: 2.2-6.4). Albuterol was the most commonly used respiratory treatment, followed by chest physiotherapy, high-flow nasal cannula, and hypertonic saline. Longer stays in the ICU were associated with more frequent use of therapies, specifically invasive mechanical ventilation, inhaled corticosteroids, intrapulmonary percussive ventilation, and chest physiotherapy. Even within a close geographic region, there is significant variation in the treatment provided to critically ill children with RSV bronchiolitis. None of these treatments were associated with shorter durations of hospitalization in this population and some, such as mechanical ventilation, were associated with longer ICU lengths of stay.

  17. Experimental evidence validating the computational inference of functional associations from gene fusion events: a critical survey.

    Science.gov (United States)

    Promponas, Vasilis J; Ouzounis, Christos A; Iliopoulos, Ioannis

    2014-05-01

    More than a decade ago, a number of methods were proposed for the inference of protein interactions, using whole-genome information from gene clusters, gene fusions and phylogenetic profiles. This structural and evolutionary view of entire genomes has provided a valuable approach for the functional characterization of proteins, especially those without sequence similarity to proteins of known function. Furthermore, this view has raised the real possibility to detect functional associations of genes and their corresponding proteins for any entire genome sequence. Yet, despite these exciting developments, there have been relatively few cases of real use of these methods outside the computational biology field, as reflected from citation analysis. These methods have the potential to be used in high-throughput experimental settings in functional genomics and proteomics to validate results with very high accuracy and good coverage. In this critical survey, we provide a comprehensive overview of 30 most prominent examples of single pairwise protein interaction cases in small-scale studies, where protein interactions have either been detected by gene fusion or yielded additional, corroborating evidence from biochemical observations. Our conclusion is that with the derivation of a validated gold-standard corpus and better data integration with big experiments, gene fusion detection can truly become a valuable tool for large-scale experimental biology.

  18. Cloning and functional characterization of the 5' regulatory region of ovine Hormone Sensitive Lipase (HSL) gene.

    Science.gov (United States)

    Lampidonis, Antonis D; Stravopodis, Dimitrios J; Voutsinas, Gerassimos E; Messini-Nikolaki, Niki; Stefos, George C; Margaritis, Lukas H; Argyrokastritis, Alexandros; Bizelis, Iosif; Rogdakis, Emmanuel

    2008-12-31

    Hormone Sensitive Lipase (HSL) catalyzes the rate-limiting step in the mobilization of fatty acids from adipose tissue, thus determining the supply of energy substrates in the body. HSL enzymatic activity is increased by adrenergic agonists, such as catecholamines and glucagons, which induce cyclic AMP (cAMP) intracellular production, subsequently followed by the activation of Protein Kinase A (PKA) and its downstream signaling cascade reactions. HSL constitutes the critical enzyme in the modulation of lipid stores and the only component being subjected to hormonal control in terms of the recently identified Adipose Triglyceride Lipase (ATGL). In order to acquire detailed knowledge with regard to the mechanisms regulating ovine HSL (ovHSL) gene transcription activity, we initially isolated and cloned the 5' proximal and distal promoter regions through a genome walking approach, with the utilization of the already characterized ovHSL cDNAs. As evinced by BLAST analysis and a multiple alignment procedure, the isolated genomic fragment of 2.744 kb appeared to contain the already specified 5'-untranslated region (5'-UTR), which was interrupted by a relatively large intron of 1.448 kb. Regarding the upstream remaining part of 1.224 kb, it was demonstrated to represent a TATA-less promoter area, harboring several cis-regulatory elements that could be putatively recognized by relatively more general transcription factors, mainly including Stimulating protein 1 (Sp1), CCAAT-box Binding Factors (CBFs), Activator Protein 2 (AP2) and Glucocorticoid Receptor (GR), as well as other cis-acting regions denominated as Insulin Response Element (IRE), Glucose Response Element (GRE), Fat Specific Element (FSE) and cAMP Response Element (CRE), which could likely function in a nourishment (i.e. glucose)-/hormone-dependent fashion. When different genomic fragments were directionally (5' to 3') cloned into a suitable reporter vector upstream of a promoter-less luciferase gene and

  19. Critical role of TCF-1 in repression of the IL-17 gene.

    Directory of Open Access Journals (Sweden)

    Jian Ma

    Full Text Available Overwhelming activation of IL-17, a gene involved in inflammation, leads to exaggerated Th17 responses associated with numerous autoimmune conditions, such as experimental autoimmune encephalomyelitis (EAE. Here we show that TCF-1 is a critical factor to repress IL-17 gene locus by chromatin modifications during T cell development. Deletion of TCF-1 resulted in increased IL-17 gene expression both in thymus and peripheral T cells, which led to enhanced Th17 differentiation. As a result, TCF-1(-/- mice were susceptible to Th17-dependent EAE induction. Rag1(-/- mice reconstituted with TCF-1(-/- T cells were also susceptible to EAE, indicating TCF-1 is intrinsically required to repress IL-17. However, expression of wild-type TCF-1 or dominant negative TCF-1 did not interfere with Th17 differentiation in mature T cells. Furthermore, expression of TCF-1 in TCF-1(-/- T cells could not restore Th17 differentiation to wild-type levels, indicating that TCF-1 cannot affect IL-17 production at the mature T cell stage. This is also supported by the normal up-regulation or activation in mature TCF-1(-/- T cells of factors known to regulate Th17 differentiation, including RORγt and Stat3. We observed hyperacetylation together with trimethylation of Lys-4 at the IL-17 locus in TCF-1(-/- thymocytes, two epigenetic modifications indicating an open active state of the gene. Such epigenetic modifications were preserved even when TCF-1(-/- T cells migrated out of thymus. Therefore, TCF-1 mediates an active process to repress IL-17 gene expression via epigenetic modifications during T cell development. This TCF-1-mediated repression of IL-17 is critical for peripheral T cells to generate balanced immune responses.

  20. Duplication of the Miller-Dieker Critical Region in a Patient with a Subtelomeric Unbalanced Translocation t(10;17)(p15.3;p13.3)

    Science.gov (United States)

    Ruiz Esparza-Garrido, R.; Velázquez-Wong, A.C.; Araujo-Solís, M.A.; Huicochea-Montiel, J.C.; Velázquez-Flores, M.Á.; Salamanca-Gómez, F.; Arenas-Aranda, D.J.

    2012-01-01

    Submicroscopic duplications in the Miller-Dieker critical region have been recently described as new genomic disorders. To date, only a few cases have been reported with overlapping 17p13.3 duplications in this region. Also, small deletions that affect chromosome region 10p14→pter are rarely described in the literature. In this study, we describe, to our knowledge for the first time, a 5-year-old female patient with intellectual disability who has an unbalanced 10;17 translocation inherited from the father. The girl was diagnosed by subtelomeric FISH and array-CGH, showing a 4.43-Mb heterozygous deletion on chromosome 10p that involved 14 genes and a 3.22-Mb single-copy gain on chromosome 17p, which includes the critical region of the Miller-Dieker syndrome and 61 genes. The patient's karyotype was established as 46,XX.arr 10p15.3p15.1(138,206–4,574,436)x1,17p13.3(87,009–3,312,600)x3. Because our patient exhibits a combination of 2 imbalances, she has phenotypic features of both chromosome abnormalities, which have been reported separately. Interestingly, the majority of patients who carry the deletion 10p have visual and auditory deficiencies that are attributed to loss of the GATA3 gene. However, our patient also presents severe hearing and visual problems even though GATA3 is present, suggesting the involvement of different genes that affect the development of the visual and auditory systems. PMID:23326253

  1. A differentially methylated region of the DAZ1 gene in spermatic and somatic cells

    Institute of Scientific and Technical Information of China (English)

    Zuo-Xiang Li; Xu Ma; Zhao-Hui Wang

    2006-01-01

    Aim: To investigate the methylation status of the deleted in azoospermia 1 (DAZ1) gene promoter region in different cell types. Methods: Using CpG island Searcher software, a CpG island was found in the promoter region of the DAZ1 gene. The methylation status of this region was analyzed in sperm and leukocytes by bisulfited sequencing.Results: The methylation status of the CpG island in the DAZ1 gene promoter region differed in leukocytes and sperm: it was methylated in leukocytes, but unmethylated in sperm. Conclusion: A differentially methylated region of the DAZ1 gene exists in spermatic and somatic cells, suggesting that methylation of this region may regulate DAZ1 gene expression in different tissues.

  2. Differences in economic development in rural regions of advanced countries: an overview and critical analysis of theories

    NARCIS (Netherlands)

    Terluin, I.J.

    2003-01-01

    This article provides an overview and critical analysis of theories on economic development in rural regions in advanced countries. For this purpose, we have consulted literature in regional economics and the multidisciplinary field of rural studies. In order to analyse to which extent these theorie

  3. Differences in economic development in rural regions of advanced countries: an overview and critical analysis of theories

    NARCIS (Netherlands)

    Terluin, I.J.

    2003-01-01

    This article provides an overview and critical analysis of theories on economic development in rural regions in advanced countries. For this purpose, we have consulted literature in regional economics and the multidisciplinary field of rural studies. In order to analyse to which extent these

  4. Experimental Study of the Isochoric Heat Capacity of Diethyl Ether (DEE) in the Critical and Supercritical Regions

    Science.gov (United States)

    Polikhronidi, N. G.; Abdulagatov, I. M.; Batyrova, R. G.; Stepanov, G. V.; Wu, J. T.; Ustuzhanin, E. E.

    2012-02-01

    Two- and one-phase liquid and vapor isochoric heat capacities ( C V ρ T relationship) of diethyl ether (DEE) in the critical and supercritical regions have been measured with a high-temperature and high-pressure nearly constant-volume adiabatic calorimeter. The measurements were carried out in the temperature range from 347 K to 575 K for 12 liquid and 5 vapor densities from 212.6 kg·m-3 to 534.6 kg·m-3. The expanded uncertainties (coverage factor k = 2, two-standard deviation estimate) for values of the heat capacity were 2% to 3% in the near-critical region, 1.0% to 1.5% for the liquid isochores, and 3% to 4% for the vapor isochores. The uncertainties of density ( ρ) and temperature ( T) measurements were 0.02% and 15 mK, respectively. The values of the internal energy, U( T, V), and second temperature derivative of pressure, (∂2 P/∂ T 2) ρ , were derived using the measured C V data near the critical point. The critical anomaly of the measured C V and derived values of U( T, V) and (∂2 P/∂ T 2) ρ in the critical and supercritical regions were interpreted in terms of the scaling theory of critical phenomena. The asymptotic critical amplitudes {({A_0^+} and {A_0^- )}} of the scaling power laws along the critical isochore for one- and two-phase C V were calculated from the measured values of C V . Experimentally derived values of the critical amplitude ratio for {CV left({A_0^+ /A_0^- = 0.521}right)} are in good agreement with the values predicted by scaling theory. The measured C V data for DEE were analyzed to study the behavior of loci of isothermal and isochoric C V maxima and minima in the critical and supercritical regions.

  5. Risk prediction of Critical Infrastructures against extreme natural hazards: local and regional scale analysis

    Science.gov (United States)

    Rosato, Vittorio; Hounjet, Micheline; Burzel, Andreas; Di Pietro, Antonio; Tofani, Alberto; Pollino, Maurizio; Giovinazzi, Sonia

    2016-04-01

    Natural hazard events can induce severe impacts on the built environment; they can hit wide and densely populated areas, where there is a large number of (inter)dependent technological systems whose damages could cause the failure or malfunctioning of further different services, spreading the impacts on wider geographical areas. The EU project CIPRNet (Critical Infrastructures Preparedness and Resilience Research Network) is realizing an unprecedented Decision Support System (DSS) which enables to operationally perform risk prediction on Critical Infrastructures (CI) by predicting the occurrence of natural events (from long term weather to short nowcast predictions, correlating intrinsic vulnerabilities of CI elements with the different events' manifestation strengths, and analysing the resulting Damage Scenario. The Damage Scenario is then transformed into an Impact Scenario, where punctual CI element damages are transformed into micro (local area) or meso (regional) scale Services Outages. At the smaller scale, the DSS simulates detailed city models (where CI dependencies are explicitly accounted for) that are of important input for crisis management organizations whereas, at the regional scale by using approximate System-of-Systems model describing systemic interactions, the focus is on raising awareness. The DSS has allowed to develop a novel simulation framework for predicting earthquakes shake maps originating from a given seismic event, considering the shock wave propagation in inhomogeneous media and the subsequent produced damages by estimating building vulnerabilities on the basis of a phenomenological model [1, 2]. Moreover, in presence of areas containing river basins, when abundant precipitations are expected, the DSS solves the hydrodynamic 1D/2D models of the river basins for predicting the flux runoff and the corresponding flood dynamics. This calculation allows the estimation of the Damage Scenario and triggers the evaluation of the Impact Scenario

  6. Gene-Based Analysis of Regionally Enriched Cortical Genes in GWAS Data Sets of Cognitive Traits and Psychiatric Disorders

    DEFF Research Database (Denmark)

    Ersland, Kari M; Christoforou, Andrea; Stansberg, Christine;

    2012-01-01

    the regionally enriched cortical genes to mine a genome-wide association study (GWAS) of the Norwegian Cognitive NeuroGenetics (NCNG) sample of healthy adults for association to nine psychometric tests measures. In addition, we explored GWAS data sets for the serious psychiatric disorders schizophrenia (SCZ) (n......Despite its estimated high heritability, the genetic architecture leading to differences in cognitive performance remains poorly understood. Different cortical regions play important roles in normal cognitive functioning and impairment. Recently, we reported on sets of regionally enriched genes...... in three different cortical areas (frontomedial, temporal and occipital cortices) of the adult rat brain. It has been suggested that genes preferentially, or specifically, expressed in one region or organ reflect functional specialisation. Employing a gene-based approach to the analysis, we used...

  7. Enhanced Vascular Endothelial Growth Factor Gene Expression in Ischaemic Skin of Critical Limb Ischaemia Patients

    Directory of Open Access Journals (Sweden)

    Silvia Bleda

    2012-01-01

    Full Text Available Objectives. To perform a quantitative analysis of the vascular endothelial growth factor (VEGF gene transcription in the skin of ischemic legs and provide information for VEGF in the pathogenesis in critical limb ischemia (CLI. Methods. Skin biopsies were obtained from 40 patients with CLI. Control samples came from 44 patients with chronic venous disease. VEGF gene expression was analysed using quantitative polymerase chain reaction. Results. Patients with CLI had higher skin VEGF expression than control group (RQ: 1.3 ± 0.1 versus 1, P=0.04. Conclusions. We found an association between ischemic skin and an elevated VEGF expression in legs from patients with CLI. These data support that the mechanism for VEGF upregulation in hypoxia conditions is intact and acts appropriately in the ischaemic limbs from patients with CLI.

  8. Gene-based analysis of regionally enriched cortical genes in GWAS data sets of cognitive traits and psychiatric disorders.

    Directory of Open Access Journals (Sweden)

    Kari M Ersland

    Full Text Available BACKGROUND: Despite its estimated high heritability, the genetic architecture leading to differences in cognitive performance remains poorly understood. Different cortical regions play important roles in normal cognitive functioning and impairment. Recently, we reported on sets of regionally enriched genes in three different cortical areas (frontomedial, temporal and occipital cortices of the adult rat brain. It has been suggested that genes preferentially, or specifically, expressed in one region or organ reflect functional specialisation. Employing a gene-based approach to the analysis, we used the regionally enriched cortical genes to mine a genome-wide association study (GWAS of the Norwegian Cognitive NeuroGenetics (NCNG sample of healthy adults for association to nine psychometric tests measures. In addition, we explored GWAS data sets for the serious psychiatric disorders schizophrenia (SCZ (n = 3 samples and bipolar affective disorder (BP (n = 3 samples, to which cognitive impairment is linked. PRINCIPAL FINDINGS: At the single gene level, the temporal cortex enriched gene RAR-related orphan receptor B (RORB showed the strongest overall association, namely to a test of verbal intelligence (Vocabulary, P = 7.7E-04. We also applied gene set enrichment analysis (GSEA to test the candidate genes, as gene sets, for enrichment of association signal in the NCNG GWAS and in GWASs of BP and of SCZ. We found that genes differentially expressed in the temporal cortex showed a significant enrichment of association signal in a test measure of non-verbal intelligence (Reasoning in the NCNG sample. CONCLUSION: Our gene-based approach suggests that RORB could be involved in verbal intelligence differences, while the genes enriched in the temporal cortex might be important to intellectual functions as measured by a test of reasoning in the healthy population. These findings warrant further replication in independent samples on cognitive traits.

  9. Determination of variants in the 3'-region of the Tyrosinase gene requires locus specific amplification.

    NARCIS (Netherlands)

    Chaki, M.; Mukhopadhyay, A.; Ray, K.

    2005-01-01

    Mutations in the Tyrosinase gene (TYR, 11q14-q21) cause oculocutaneous albinism type 1 (OCA1). The 3'-region of the TYR shows 98.55% sequence identity with a pseudogene, known as Tyrosinase-Like Gene (TYRL, 11p11.2-cen). A large number of publicly available nucleotide variants of TYR in this region

  10. Requirement of histone deacetylase activity for the expression of critical photoreceptor genes

    Directory of Open Access Journals (Sweden)

    Cepko Constance L

    2007-06-01

    Full Text Available Abstract Background Histone deacetylases (HDACs play a major role in the regulation of gene transcription, often leading to transcriptional repression, as well as other effects following deacetylation of non-histone proteins. Results To investigate the role of HDACs in the developing mammalian retina, a general inhibitor of HDACs, trichostatin-A (TSA, was used to treat newborn murine retinae in explant cultures. Inhibition of HDAC activity resulted in a reduction in RNA levels for genes that regulate retinal development, as well as cell cycle regulators. Several of the genes encode transcription factors essential for rod photoreceptor development, Otx2, Nrl, and Crx. Using luciferase reporter assays, the promoter activity of both Nrl and Crx was found to be compromised by HDAC inhibition. Furthermore, downregulation of gene expression by HDAC inhibition didn't require de novo protein synthesis, and was associated with hyperacetylation of histones and non-histone proteins. Finally, HDAC inhibition in retinal explant cultures resulted in increased cell death, reduction in proliferation, a complete loss of rod photoreceptors and Müller glial cells, and an increase in bipolar cells. Conclusion HDAC activity is required for the expression of critical pro-rod transcription factors and the development of rod photoreceptor cells.

  11. Polymorphism in transmembrane region of MICA gene and cholelithiasis

    Science.gov (United States)

    Shih, Shou-Chuan; Lee, Yann-Jinn; Liu, Hsin-Fu; Dang, Ching-Wen; Chang, Shih-Chuan; Lin, Shee-Chan; Kao, Chin-Roa

    2003-01-01

    AIM: To study the significance of polymorphism of MHC class I chain-related gene A (MICA) gene in patients with cholelithiasis. METHODS: Subjects included 170 unrelated adults (83 males) with cholelithiasis and 245 randomly selected unrelated adults (130 males) as controls. DNA was extracted from peripheral leukocytes and analyzed for polymorphism of 5 alleles (A4, A5, A5.1, A6 and A9) of the MICA gene. RESULTS: There was no significant difference in phenotype, allele, and genotype frequencies of any of the 5 alleles between cholelithiasis patients and controls. CONCLUSION: This study demonstrates that MICA alleles studied bear no relation to cholelithiasis. PMID:12854159

  12. Polymorphism in transmembrane region of MTCA gene and cholelithiasis

    Institute of Scientific and Technical Information of China (English)

    Shou-Chuan Shih; Yann-Jinn Lee; Hsin-Fu Liu; Ching-Wen Dang; Shih-Chuan Chang; Shee-Chan Lin; Chin-Roa Kao

    2003-01-01

    AIM: To study the significance of polymorphism of MHC class I chain-related gene A (MICA) gene in patients with cholelithiasis.METHODS: Subjects included 170 unrelated adults (83males) with cholelithiasis and 245 randomly selected unrelated adults (130 males) as controls. DNA was extracted from peripheral leukocytes and analyzed for polymorphism of 5 alleles (A4, A5, A5.1, A6 and A9) of the MICA gene.RESULTS: There was no significant difference in phenotype,allele, and genotype frequencies of any of the 5 alleles between cholelithiasis patients and controls.CONCLUSION: This study demonstrates that MICA allelesstudied bear no relation to cholelithiasis.

  13. A 1.5-Mb cosmid contig of the CMT1A duplication/HNPP deletion critical region in 17p11.2-p12

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, Tatsufumi; Lupski, J.R. [Baylor College of Medicine, Houston, TX (United States)

    1996-05-15

    Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with a 1.5-Mb tandem duplication in chromosome 17p11.2-p12, and hereditary neuropathy with liability to pressure palsies (HNPP) is associated with a 1.5-Mb deletion at this locus. Both diseases appear to result from an altered copy number of the peripheral myelin protein-22 gene, PMP22, which maps within the critical region. To identify additional genes and characterize chromosomal elements, a 1.5-Mb cosmid contig of the CMT1A duplication/HNPP deletion critical region was assembled using a yeast artificial chromosome (YAC)-based isolation and binning strategy. Whole YAC probes were used for screening a high-density arrayed chromosome 17-specific cosmid library. Selected cosmids were spotted on dot blots and assigned to bins defined by YACs. This binning of cosmids facilitated the subsequent fingerprint analysis. The 1.5-Mb region was covered by 137 cosmids with a minimum overlap set of 52 cosmids assigned to 17 bins and 9 contigs. 20 refs., 2 figs.

  14. Burkitt's lymphoma is a malignancy of mature B cells expressing somatically mutated V region genes.

    OpenAIRE

    Klein, U.; Klein, G.; Ehlin-Henriksson, B.; Rajewsky, K.; Küppers, R.

    1995-01-01

    BACKGROUND: The developmental stage from which stems the malignant B cell population in Burkitt's lymphoma (BL) is unclear. An approach to answering this question is provided by the sequence analysis of rear-ranged immunoglobulin (Ig) variable region (V) genes from BL for evidence of somatic mutations, together with a phenotypic characterization. As somatic hypermutation of Ig V region genes occurs in germinal center B cells, somatically mutated Ig genes are found in germinal center B cells a...

  15. Critical Reflectance Derived from MODIS: Application for the Retrieval of Aerosol Absorption over Desert Regions

    Science.gov (United States)

    Wells, Kelley C.; Martins, J. Vanderlei; Remer, Lorraine A.; Kreidenweis, Sonia M.; Stephens, Graeme L.

    2012-01-01

    Aerosols are tiny suspended particles in the atmosphere that scatter and absorb sunlight. Smoke particles are aerosols, as are sea salt, particulate pollution and airborne dust. When you look down at the earth from space sometimes you can see vast palls of whitish smoke or brownish dust being transported by winds. The reason that you can see these aerosols is because they are reflecting incoming sunlight back to the view in space. The reason for the difference in color between the different types of aerosol is that the particles arc also absorbing sunlight at different wavelengths. Dust appears brownish or reddish because it absorbs light in the blue wavelengths and scatters more reddish light to space, Knowing how much light is scattered versus how much is absorbed, and knowin that as a function of wavelength is essential to being able to quantify the role aerosols play in the energy balance of the earth and in climate change. It is not easy measuring the absorption properties of aerosols when they are suspended in the atmosphere. People have been doing this one substance at a time in the laboratory, but substances mix when they are in the atmosphere and the net absorption effect of all the particles in a column of air is a goal of remote sensing that has not yet been completely successful. In this paper we use a technique based on observing the point at which aerosols change from brightening the surface beneath to darkening it. If aerosols brighten a surface. they must scatter more light to space. If they darken the surface. they must be absorbing more. That cross over point is called the critical reflectance and in this paper we show that critical reflectance is a monotonic function of the intrinsic absorption properties of the particles. This parameter we call the single scattering albedo. We apply the technique to MODIS imagery over the Sahara and Sahel regions to retrieve the single scattering albedo in seven wavelengths, compare these retrievals to ground

  16. DNA immunization with fusion genes containing HCV core region and HBV core region

    Institute of Scientific and Technical Information of China (English)

    杨莉; 刘晶; 孔玉英; 汪垣; 李光地

    1999-01-01

    The eucaryotic expression plasmids were constructed to express the complete (HCc191) or the truncated (HCc69 and HCc40) HCV core genes, solely or fused with the HBV core gene (HBc144). These constructions were transiently expressed in COS cells under the control of the CMV promoter. The antigenicity of HBc and HCc could be detected in the expression products by ELISA and Western blot. The mice immunized with these expression plasmids efficiently produced the anti-HCc antibodies, and also anti-HBc antibodies when the plasmids contained the fusion genes. In addition, the antibodies induced by the fusion genes were more persistent than those induced by the non-fusion HCV core genes. These indicate that the fusion of HCc genes to HBc gene is in favor of the immunogenicity of HCc, while the immunogenicity of HBc is not affected.

  17. Clinical associations of host genetic variations in the genes of cytokines in critically ill patients.

    Science.gov (United States)

    Belopolskaya, O B; Smelaya, T V; Moroz, V V; Golubev, A M; Salnikova, L E

    2015-06-01

    Host genetic variations may influence a changing profile of biochemical markers and outcome in patients with trauma/injury. The objective of this study was to assess clinical associations of single nucleotide polymorphisms (SNPs) in the genes of cytokines in critically ill patients. A total of 430 patients were genotyped for SNPs in the genes of pro- (IL1B, IL6, IL8) and anti-inflammatory (IL4, IL10, IL13) cytokines. The main end-points were sepsis, mortality and adult respiratory distress syndrome (ARDS). We evaluated the dynamic levels of bilirubin, blood urea nitrogen, creatine kinase, creatinine and lactate dehydrogenase in five points of measurements (between 1 and 14 days after admission) and correlated them with SNPs. High-producing alleles of proinflammatory cytokines protected patients against sepsis (IL1B -511A and IL8 -251A) and mortality (IL1B -511A). High-producing alleles of anti-inflammatory cytokines IL4 -589T and IL13 431A (144Gln) were less frequent in ARDS patients. The carriers of IL6 -174C/C genotypes were prone to the increased levels of biochemical markers and acute kidney and liver insufficiency. Genotype-dependent differences in the levels of biochemical indicators gradually increased to a maximal value on the 14th day after admission. These findings suggest that genetic variability in pro- and anti-inflammatory cytokines may contribute to different clinical phenotypes in patients at high risk of critical illness.

  18. Characterization of a novel gene at the Gaucher disease locus spanning the region between the glucocerebrosidase (GC) pseudogene and thrombospondin (TSP)3

    Energy Technology Data Exchange (ETDEWEB)

    Ginns, E.I.; Winfield, S.; Sidransky, E. [NIMH, Bethesda, MD (United States)] [and others

    1994-09-01

    The human GC locus on chromosome 1q21 encompasses a 7 kb functional gene encoding the enzyme deficient in Gaucher disease, and a highly homologous sequence 16 Kb downstream that has the properties of a pseudogene. A novel gene, gene X, spanning the 6 kb region between the pseudogene and TSP3 has been identified and characterized in the mouse, and appears to be critical for normal embryonic development. As in the mouse, the human gene X is located 5{prime} to the TSP3 gene and two genes are transcribed divergently from a bidirectional promoter; the direction of transcription of gene X and GC is convergent. However, in the human, gene X and GC are separated by gene X and GC pseudogenes that are the consequence of a gene duplication. The gene X pseudogene lacks the first exon and part of the second exon of the functional gene and may not be transcribed. Northern blot analyses indicate that gene X is transcribed in both normal individuals and in patients with Gaucher disease, but the function of this gene is still unknown. The possibility that mutations in gene X could account for some of the diversity of symptoms encountered in individuals with the more atypical presentations of Gaucher disease is under investigation.

  19. Mutational analysis of Trypanosoma brucei RNA editing ligase reveals regions critical for interaction with KREPA2.

    Directory of Open Access Journals (Sweden)

    Vaibhav Mehta

    Full Text Available The Trypanosoma brucei parasite causes the vector-borne disease African sleeping sickness. Mitochondrial mRNAs of T. brucei undergo posttranscriptional RNA editing to make mature, functional mRNAs. The final step of this process is catalyzed by the essential ligase, T. brucei RNA Editing Ligase 1 (TbREL1 and the closely related T. brucei RNA Editing Ligase 2 (TbREL2. While other ligases such as T7 DNA ligase have both a catalytic and an oligonucleotide/oligosaccharide-binding (OB-fold domain, T. brucei RNA editing ligases contain only the catalytic domain. The OB-fold domain, which is required for interaction with the substrate RNA, is provided in trans by KREPA2 (for TbREL1 and KREPA1 (for TbREL2. KREPA2 enhancement of TbREL1 ligase activity is presumed to occur via an OB-fold-mediated increase in substrate specificity and catalysis. We characterized the interaction between TbREL1 and KREPA2 in vitro using full-length, truncated, and point-mutated ligases. As previously shown, our data indicate strong, specific stimulation of TbREL1 catalytic activity by KREPA2. We narrowed the region of contact to the final 59 C-terminal residues of TbREL1. Specifically, the TbREL1 C-terminal KWKE (441-444 sequence appear to coordinate the KREPA2-mediated enhancement of TbREL1 activities. N-terminal residues F206, T264 and Y275 are crucial for the overall activity of TbREL1, particularly for F206, a mutation of this residue also disrupts KREPA2 interaction. Thus, we have identified the critical TbREL1 regions and amino acids that mediate the KREPA2 interaction.

  20. Probabilistic map of critical functional regions of the human cerebral cortex: Broca's area revisited.

    Science.gov (United States)

    Tate, Matthew C; Herbet, Guillaume; Moritz-Gasser, Sylvie; Tate, Joseph E; Duffau, Hugues

    2014-10-01

    The organization of basic functions of the human brain, particularly in the right hemisphere, remains poorly understood. Recent advances in functional neuroimaging have improved our understanding of cortical organization but do not allow for direct interrogation or determination of essential (versus participatory) cortical regions. Direct cortical stimulation represents a unique opportunity to provide novel insights into the functional distribution of critical epicentres. Direct cortical stimulation (bipolar, 60 Hz, 1-ms pulse) was performed in 165 consecutive patients undergoing awake mapping for resection of low-grade gliomas. Tasks included motor, sensory, counting, and picture naming. Stimulation sites eliciting positive (sensory/motor) or negative (speech arrest, dysarthria, anomia, phonological and semantic paraphasias) findings were recorded and mapped onto a standard Montreal Neurological Institute brain atlas. Montreal Neurological Institute-space functional data were subjected to cluster analysis algorithms (K-means, partition around medioids, hierarchical Ward) to elucidate crucial network epicentres. Sensorimotor function was observed in the pre/post-central gyri as expected. Articulation epicentres were also found within the pre/post-central gyri. However, speech arrest localized to ventral premotor cortex, not the classical Broca's area. Anomia/paraphasia data demonstrated foci not only within classical Wernicke's area but also within the middle and inferior frontal gyri. We report the first bilateral probabilistic map for crucial cortical epicentres of human brain functions in the right and left hemispheres, including sensory, motor, and language (speech, articulation, phonology and semantics). These data challenge classical theories of brain organization (e.g. Broca's area as speech output region) and provide a distributed framework for future studies of neural networks.

  1. Perceived barriers to the regionalization of adult critical care in the United States: a qualitative preliminary study

    Directory of Open Access Journals (Sweden)

    Rubenfeld Gordon D

    2008-11-01

    Full Text Available Abstract Background Regionalization of adult critical care services may improve outcomes for critically ill patients. We sought to develop a framework for understanding clinician attitudes toward regionalization and potential barriers to developing a tiered, regionalized system of care in the United States. Methods We performed a qualitative study using semi-structured interviews of critical care stakeholders in the United States, including physicians, nurses and hospital administrators. Stakeholders were identified from a stratified-random sample of United States general medical and surgical hospitals. Key barriers and potential solutions were identified by performing content analysis of the interview transcriptions. Results We interviewed 30 stakeholders from 24 different hospitals, representing a broad range of hospital locations and sizes. Key barriers to regionalization included personal and economic strain on families, loss of autonomy on the part of referring physicians and hospitals, loss of revenue on the part of referring physicians and hospitals, the potential to worsen outcomes at small hospitals by limiting services, and the potential to overwhelm large hospitals. Improving communication between destination and source hospitals, provider education, instituting voluntary objective criteria to become a designated referral center, and mechanisms to feed back patients and revenue to source hospitals were identified as potential solutions to some of these barriers. Conclusion Regionalization efforts will be met with significant conceptual and structural barriers. These data provide a foundation for future research and can be used to inform policy decisions regarding the design and implementation of a regionalized system of critical care.

  2. An improved method for detecting and delineating genomic regions with altered gene expression in cancer

    OpenAIRE

    2008-01-01

    Genomic regions with altered gene expression are a characteristic feature of cancer cells. We present a novel method for identifying such regions in gene expression maps. This method is based on total variation minimization, a classical signal restoration technique. In systematic evaluations, we show that our method combines top-notch detection performance with an ability to delineate relevant regions without excessive over-segmentation, making it a significant advance over existing methods. ...

  3. Exclusion of Linkage to the CDL1 Gene Region on Chromosome 3q26.3 in Some Familial Cases of Cornelia de Lange Syndrome

    Science.gov (United States)

    Krantz, Ian D.; Tonkin, Emma; Smith, Melanie; Devoto, Marcella; Bottani, Armand; Simpson, Claire; Hofreiter, Mary; Abraham, Vinod; Jukofsky, Lori; Conti, Brian P.; Strachan, Tom; Jackson, Laird

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is a complex developmental disorder consisting of characteristic facial features, limb abnormalities, hirsutism, ophthalmologic involvement, gastroesophageal dysfunction, hearing loss, as well as growth and neuro-developmental retardation. Most cases of CdLS appear to be sporadic. Familial cases are rare and indicate autosomal dominant inheritance. Several individuals with CdLS have been reported with chromosomal abnormalities, suggesting candidate genomic regions within which the causative gene(s) may lie. A CdLS gene location (CDL1) has been assigned to 3q26.3 based on phenotypic overlap with the duplication 3q syndrome (critical region 3q26.2-q27) and the report of a CdLS individual with a balanced de novo t(3;17)(q26.3;q23.1). It has been postulated that a gene within the dup3q critical region results in the CdLS when deleted or mutated. We have performed a linkage analysis to the minimal critical region for the dup3q syndrome (that encompasses the translocation breakpoint) on chromosome 3q in 10 rare familial cases of CdLS. Nineteen markers spanning a region of approximately 40 Mb (37 cM) were used. Results of a multipoint linkage analysis demonstrated total lod-scores that were negative across the chromosome 3q26-q27 region. In 4/10 families, lod-scores were less than −2 in the 2 cM region encompassing the translocation, while in the remaining 6/10 families, lod-scores could not exclude linkage to this region. These studies indicate that in some multicase families, the disease gene does not map to the CDL1 region at 3q26.3. PMID:11391654

  4. Structure of the dimerization domain of DiGeorge critical region 8

    Energy Technology Data Exchange (ETDEWEB)

    Senturia, R.; Faller, M.; Yin, S.; Loo, J.A.; Cascio, D.; Sawaya, M.R.; Hwang, D.; Clubb, R.T.; Guo, F. (UCLA)

    2010-09-27

    Maturation of microRNAs (miRNAs, {approx}22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298-352) at 1.7 {angstrom} resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis.

  5. The involucrin genes of the white-fronted capuchin and cottontop tamarin: the platyrrhine middle region.

    Science.gov (United States)

    Phillips, M; Rice, R H; Djian, P; Green, H

    1991-09-01

    In all anthropoid species, the coding region of the involucrin gene contains a segment of short tandem repeats that were added sequentially, beginning in a common anthropoid ancestor. The involucrin coding region of each of two platyrrhine species, the white-fronted capuchin (Cebus albifrons) and the cottontop tamarin (Saguinus oedipus), has now been cloned and sequenced. These genes share with the genes of the catarrhines the repeats added in the common anthropoid lineage (the early region). After their divergence, the platyrrhines, like the catarrhines, continued to add repeats vectorially 5' of the early region, to form a middle region. The mechanism that was established in the common anthropoid lineage for the addition of repeats at a definite site in the coding region was transmitted to both platyrrhines and catarrhines, enabling each to generate its middle region independently. The process of vectorial repeat addition continued in two platyrrhine sublineages after their divergence from each other.

  6. Tapetum Degeneration Retardation is Critical for Aliphatic Metabolism and Gene Regulation during Rice Pollen Development

    Institute of Scientific and Technical Information of China (English)

    Da-Sheng Zhang; Wan-Qi Liang; Zheng Yuan; Na Li; Jing Shi; Jue Wang; Yu-Min Liu; Wen-Juan Yu; Da-Bing Zhang

    2008-01-01

    As a complex wall system in flowering plants,the pollen outer wall mainly contains aliphatic sporopollenin;however,the mechanism for synthesizing these lipidic precursors during pollen development remains less well under-stood.Here,we report on the function of the rice tapetum-expressing TDR(Tapetum Degeneration Retardation)gene in aliphatic metabolism and its regulatory role during rice pollen development.The observations of transmission electron microscopy (TEM) and scanning electron microscopy(SEM)analyses suggested that pollen wall formation was significantly altered in the tdr mutant.The contents of aliphatic compositions of anther were greatly changed in the tdr mutant revealed by GC-MS(gas chromatography-mass spectrometry)testing,particularly less accumulated in fatty acids, primary alcohols,alkanes and alkenes,and an abnormal increase in secondary alcohols with carbon Iengths from C29 to C35 in tdr.Microarray data revealed that a group of genes putatively involved in lipid transport and metabolism were significantly altered in the tdr mutant,indicating the critical role of TDR in the formation of the pollen wall.Also,a wide range of genes tween wild-type and tdr.In addition to its function in promoting tapetum PCD,TDR possibly plays crucial regulatory roles in several basic biological processes during rice pollen development.

  7. Strategies to regenerate hair cells: identification of progenitors and critical genes.

    Science.gov (United States)

    Breuskin, Ingrid; Bodson, Morgan; Thelen, Nicolas; Thiry, Marc; Nguyen, Laurent; Belachew, Shibeshih; Lefebvre, Philippe P; Malgrange, Brigitte

    2008-02-01

    Deafness commonly results from a lesion of the sensory cells and/or of the neurons of the auditory part of the inner ear. There are currently no treatments designed to halt or reverse the progression of hearing loss. A key goal in developing therapy for sensorineural deafness is the identification of strategies to replace lost hair cells. In amphibians and birds, a spontaneous post-injury regeneration of all inner ear sensory hair cells occurs. In contrast, in the mammalian cochlea, hair cells are only produced during embryogenesis. Many studies have been carried out in order to demonstrate the persistence of endogenous progenitors. The present review is first focused on the occurrence of spontaneous supernumerary hair cells and on nestin positive precursors found in the organ of Corti. A second approach to regenerating hair cells would be to find genes essential for their differentiation. This review will also focus on critical genes for embryonic hair cell formation such as the cell cycle related proteins, the Atoh1 gene and the Notch signaling pathway. Understanding mechanisms that underlie hair cell production is an essential prerequisite to defining therapeutic strategies to regenerate hair cells in the mature inner ear.

  8. Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival

    DEFF Research Database (Denmark)

    Thomassen, Mads; Jochumsen, Kirsten M; Mogensen, Ole;

    2009-01-01

    the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of *Gene Set Enrichment Analysis*, we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1......Ovarian cancer cells exhibit complex karyotypic alterations causing deregulation of numerous genes. Some of these genes are probably causal for cancer formation and local growth, whereas others are causal for metastasis and recurrence. By using publicly available data sets, we have investigated......-4 consecutive cytogenetic bands identified regions with increased expression for chromosome 5q12-14, and a very large region of chromosome 7 with the strongest signal at 7p15-13 among tumors from short-living patients. Reduced gene expression was identified at 4q26-32, 6p12-q15, 9p21-q32, and 11p14-11. We...

  9. Chronic ethanol exposure produces time- and brain region-dependent changes in gene coexpression networks.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Osterndorff-Kahanek

    Full Text Available Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY, nucleus accumbens (NAC, prefrontal cortex (PFC, and liver after four weekly cycles of chronic intermittent ethanol (CIE vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000 at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600. Within each region, there was little gene overlap across time (~20%. All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global 'rewiring' of coexpression systems involving glial and immune signaling as well as neuronal genes.

  10. Thyroid hormone receptors bind to defined regions of the growth hormone and placental lactogen genes.

    Science.gov (United States)

    Barlow, J W; Voz, M L; Eliard, P H; Mathy-Harter, M; De Nayer, P; Economidis, I V; Belayew, A; Martial, J A; Rousseau, G G

    1986-12-01

    The intracellular receptor for thyroid hormone is a protein found in chromatin. Since thyroid hormone stimulates transcription of the growth hormone gene through an unknown mechanism, the hypothesis that the thyroid hormone-receptor complex interacts with defined regions of this gene has been investigated in a cell-free system. Nuclear extracts from human lymphoblastoid IM-9 cells containing thyroid hormone receptors were incubated with L-3,5,3'-tri[125I]iodothyronine and calf thymus DNA-cellulose. Restriction fragments of the human growth hormone gene were added to determine their ability to inhibit labeled receptor binding to DNA-cellulose. These fragments encompassed nucleotide sequences from about three kilobase pairs upstream to about four kilobase pairs downstream from the transcription initiation site. The thyroid hormone-receptor complex bound preferentially to the 5'-flanking sequences of the growth hormone gene in a region between nucleotide coordinates -290 and -129. The receptor also bound to an analogous promoter region in the human placental lactogen gene, which has 92% nucleotide sequence homology with the growth hormone gene. These binding regions appear to be distinct from those that are recognized by the receptor for glucocorticoids, which stimulate growth hormone gene expression synergistically with thyroid hormone. The presence of thyroid hormone was required for binding of its receptor to the growth hormone gene promoter, suggesting that thyroid hormone renders the receptor capable of recognizing specific gene regions.

  11. Differential regulation of the period genes in striatal regions following cocaine exposure.

    Directory of Open Access Journals (Sweden)

    Edgardo Falcon

    Full Text Available Several studies have suggested that disruptions in circadian rhythms contribute to the pathophysiology of multiple psychiatric diseases, including drug addiction. In fact, a number of the genes involved in the regulation of circadian rhythms are also involved in modulating the reward value for drugs of abuse, like cocaine. Thus, we wanted to determine the effects of chronic cocaine on the expression of several circadian genes in the Nucleus Accumbens (NAc and Caudate Putamen (CP, regions of the brain known to be involved in the behavioral responses to drugs of abuse. Moreover, we wanted to explore the mechanism by which these genes are regulated following cocaine exposure. Here we find that after repeated cocaine exposure, expression of the Period (Per genes and Neuronal PAS Domain Protein 2 (Npas2 are elevated, in a somewhat regionally selective fashion. Moreover, NPAS2 (but not CLOCK (Circadian Locomotor Output Cycles Kaput protein binding at Per gene promoters was enhanced following cocaine treatment. Mice lacking a functional Npas2 gene failed to exhibit any induction of Per gene expression after cocaine, suggesting that NPAS2 is necessary for this cocaine-induced regulation. Examination of Per gene and Npas2 expression over twenty-four hours identified changes in diurnal rhythmicity of these genes following chronic cocaine, which were regionally specific. Taken together, these studies point to selective disruptions in Per gene rhythmicity in striatial regions following chronic cocaine treatment, which are mediated primarily by NPAS2.

  12. Hox genes and regional patterning of the vertebrate body plan

    NARCIS (Netherlands)

    Mallo, M.; Wellik, D.M.; Deschamps, J.

    2010-01-01

    Several decades have passed since the discovery of Hox genes in the fruit fly Drosophila melanogaster. Their unique ability to regulate morphologies along the anteroposterior (AP) axis (Lewis, 1978) earned them well-deserved attention as important regulators of embryonic development. Phenotypes due

  13. A new case of 8q22.1 microdeletion restricts the critical region for Nablus mask-like facial syndrome.

    Science.gov (United States)

    Debost-Legrand, Anne; Eymard-Pierre, Eleonore; Pebrel-Richard, Céline; Gouas, Laetitia; Goumy, Carole; Giollant, Michel; Ayed, Wiem; Tchirkov, Andreï; Francannet, Christine; Vago, Philippe

    2013-01-01

    Microdeletions of 8q21.3-8q22.1 have been identified in all patients with Nablus mask-like facial syndrome (NMLFS). A recent report of a patient without this specific phenotype presented a 1.6 Mb deletion in this region that partially overlapped with previously reported 8q21.3 microdeletions, thus restricting critical region for this syndrome. We report on another case of an 8q21.3 deletion revealed by array comparative genome hybridization (aCGH) in a 4-year-old child with global developmental delay, autism, microcephaly, but without Nablus phenotype. The size of the interstitial deletion was estimated to span 5.2 Mb. By combining the data from previous reports on 8q21.3-8q22.1 deletions and our case, we were able to narrow the critical region of Nablus syndrome to 0.5 Mb. The deleted region includes FAM92A1, which seems to be a potential candidate gene in NMLFS.

  14. Short 5'-flanking regions of the Amy gene of Drosophila kikkawai affect amylase gene expression and respond to food environments.

    Science.gov (United States)

    Inomata, Nobuyuki; Nakashima, Shuichi

    2008-04-15

    Evolution of the duplicated genes and regulation in gene expression is of great interest, especially in terms of adaptation. Molecular population genetic and evolutionary studies on the duplicated amylase genes of Drosophila species have suggested that their 5'-flanking (cis-regulatory) regions play an important role in evolution of these genes. For better understanding of evolution of the duplicated amylase genes and gene expression, we studied functional significance of the Amy1 gene of Drosophila kikkawai using in vitro deletion mutagenesis followed by P-element-mediated germline transformation. We found that a 1.6-kb of the 5'-flanking region can produce strikingly higher level of larval amylase activity on starch food compared with that on glucose food. We found two cis-regulatory elements, which increase larval amylase activity on starch food. We also found a larval cis-regulatory element, which responds to the food difference. This food-response element is necessary for the function of the element increasing larval activity on starch food. A 5-bp deletion in a putative GRE caused high amylase activity, indicating a cis-regulatory element decreasing amylase activity. These cis-regulatory elements identified in the 5'-flanking region could be the targets of natural selection.

  15. PCR primers for 30 novel gene regions in the nuclear genomes of Lepidoptera

    OpenAIRE

    Wahlberg, Niklas; Peña, Carlos; Ahola, Milla; Wheat, Christopher W.; Rota, Jadranka

    2016-01-01

    Abstract We report primer pairs for 30 new gene regions in the nuclear genomes of Lepidoptera that can be amplified using a standard PCR protocol. The new primers were tested across diverse Lepidoptera , including nonditrysians and a wide selection of ditrysians. These new gene regions give a total of 11,043 bp of DNA sequence data and they show similar variability to traditionally used nuclear gene regions in studies of Lepidoptera . We feel that a PCR-based approach still has its place in m...

  16. The critical region for Angelman syndrome lies between D15S122 and D15S113

    Energy Technology Data Exchange (ETDEWEB)

    Greger, V.; Lalande, M. [Harvard Medical School, Boston, MA (United States); Reis, A. [Free Univ., Berlin (Germany)

    1994-12-01

    This {open_quotes}Rapid Publication{close_quotes} present the results of analysis of previously described patients with newly developed microsatellite markers. The markers redefine and considerably reduce the critical deletion region on chromosome 15 which is involved in the manifestations of Angelman syndrome (AS). The findings reduce the smallest region of deletion overlap for AS from 1 Mb to approximately 0.3 Mb and will permit a more focused search for the defects causing the disorder. 11 refs., 1 fig.

  17. Regional rearrangements in chromosome 15q21 cause formation of cryptic promoters for the CYP19 (aromatase) gene.

    Science.gov (United States)

    Demura, Masashi; Martin, Regina M; Shozu, Makio; Sebastian, Siby; Takayama, Kazuto; Hsu, Wei-Tong; Schultz, Roger A; Neely, Kirk; Bryant, Michael; Mendonca, Berenice B; Hanaki, Keiichi; Kanzaki, Susumu; Rhoads, David B; Misra, Madhusmita; Bulun, Serdar E

    2007-11-01

    Production of appropriate quantities of estrogen in various tissues is essential for human physiology. A single gene (CYP19), regulated via tissue-specific promoters, encodes the enzyme aromatase, which catalyzes the key step in estrogen biosynthesis. Aromatase excess syndrome is inherited as autosomal dominant and characterized by high systemic estrogen levels, short stature, prepubertal gynecomastia and testicular failure in males, and premature breast development and uterine pathology in females. The underlying genetic mechanism is poorly understood. Here, we characterize five distinct heterozygous rearrangements responsible for aromatase excess syndrome in three unrelated families and two individuals (nine patients). The constitutively active promoter of one of five ubiquitously expressed genes located within the 11.2 Mb region telomeric to the CYP19 gene in chromosome 15q21 cryptically upregulated aromatase expression in several tissues. Four distinct inversions reversed the transcriptional direction of the promoter of a gene (CGNL1, TMOD3, MAPK6 or TLN2), placing it upstream of the CYP19 coding region in the opposite strand, whereas a deletion moved the promoter of a fifth gene (DMXL2), normally transcribed from the same strand, closer to CYP19. The proximal breakpoints of inversions were located 17-185 kb upstream of the CYP19 coding region. Sequences at the breakpoints suggested that the inversions were caused by intrachromosomal nonhomologous recombination. Splicing the untranslated exon downstream of each promoter onto the identical junction upstream of the translation initiation site created CYP19 mRNA encoding functional aromatase protein. Taken together, small rearrangements may create cryptic promoters that direct inappropriate transcription of CYP19 or other critical genes.

  18. Analysis of the sexual development-promoting region of Schizophyllum commune TRP1 gene.

    Science.gov (United States)

    Sen, Kikuo; Kinoshita, Hideki; Tazuke, Kazuyuki; Maki, Yoshinori; Yoshiura, Yumi; Yakushi, Toshiharu; Shibai, Hiroshiro; Kurosawa, Shin-Ichi

    2016-10-01

    This study aims to elucidate the mechanism of sexual development of basidiomycetous mushrooms from mating to fruit body formation. Sequencing analysis showed the TRP1 gene of basidiomycete Schizophyllum commune encoded an enzyme with three catalytic regions of GAT (glutamine amidotransferase), IGPS (indole-3-glycerol phosphate synthase), and PRAI (5-phosphoribosyl anthranilate isomerase); among these three regions, the trp1 mutant (Trp(-)) had a missense mutation (L→F) of a 338th amino acid residue of the TRP1 protein within the IGPS region. To investigate the function of IGPS region related to sexual development, dikaryons with high, usual, and no expression of the IGPS region of TRP1 gene were made. The dikaryotic mycelia with high expression of the IGPS formed mature fruit bodies earlier than those with usual and no expression of the IGPS. These results showed that the IGPS region in TRP1 gene promoted sexual development of S. commune.

  19. Mutations in the gene region of hepatitis B virus genotype in Turkish patients

    Indian Academy of Sciences (India)

    Mehmet Özaslan; Ersan Özaslan; Arzu Barsgan; Mehmet Koruk

    2007-12-01

    The gene region of the hepatitis B virus (HBV) is responsible for the expression of surface antigens and includes the ‘a’-determinant region. Thus, mutation(s) in this region would afford HBV variants a distinct survival advantage, permitting the mutant virus to escape from the immune system. The aim of this study was to search for mutations of the gene region in different patient groups infected with genotype variants of HBV, and to analyse the biological significance of these mutations. Moreover, we investigated gene mutation inductance among family members. Forty HBV-DNA-positive patients were determined among 132 hepatitis B surface antigen (HbsAg) carriers by the first stage of seminested PCR. Genotypes and subtypes were established by sequencing of the amplified S gene regions. Variants were compared with original sequences of these serotypes, and mutations were identified. All variants were designated as genotype and subtype ayw3. Ten kinds of point mutations were identified within the region. The highest rates of mutation were found in chronic hepatitis patients and their family members. The amino acid mutations 125 (M → T) and 127 (T → P) were found on the first loop of ‘a’-determinant. The other consequence was mutation inductance in a family member. We found some mutations in the S gene region known to be stable and observed that some of these mutations affected gene expression.

  20. Increase of Expression Levels of Reporter Gene in Transgenic Tobaccos by Matrix Attachment Regions

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The matrix attachment region (MAR) located downstream of Plastocyanin gene was isolated from the genome of pea. To study the effect of MARs on foreign gene expression in transgenic plants, T-DNA vector was constructed in which MARs flanked bothβ-glucuronidase(GUS) gene and selectable marker neomycin phosphotransferase (NPT-II) gene. The plant expression vectors were transferred into leaf discs via Agrobacterium-mediated transformation procedure. The result of GUS measurement showed that pea MAR could increase transgene expression level. The mean expression levels of GUS gene expression in population containing MARs could be increased twofold when compared with that of population without MARs.

  1. Zitkala-Sa and the Problem of Regionalism: Nations, Narratives, and Critical Traditions

    Science.gov (United States)

    Totten, Gary

    2005-01-01

    Although Yankton Sioux writer Zitkala-Sa (Gertrude Bonnin, 1876-1938) was, as P. Jane Hafen notes, "virtually unknown for many decades," much critical work has appeared since Dexter Fisher's 1979 article,"Zitkala-Sa: Evolution of a Writer." Some critics desiring to bring Zitkala-Sa into the conversation about turn-of-the-century American women…

  2. Rapid growth cost in "all-fish" growth hormone gene transgenic carp: Reduced critical swimming speed

    Institute of Scientific and Technical Information of China (English)

    LI DeLiang; FU CuiZhang; HU Wei; ZHONG Shan; WANG YaPing; ZHU ZuoYan

    2007-01-01

    Evidence has accumulated that there is a trade-off between benefits and costs associated with rapid growth. A trade-off between growth rates and critical swimming speed (Ucrit) had been also reported to be common in teleost fish. We hypothesize that growth acceleration in the F3 generation of "all-fish"growth hormone gene (GH) transgenic common carp (Cyprinus carpio L.) would reduce the swimming abilities. Growth and swimming performance between transgenic fish and non-transgenic controls were compared. The results showed that transgenic fish had a mean body weight 1.4-1.9-fold heavier,and a mean specific growth rate (SGR) value 6%-10% higher than the controls. Transgenic fish,however, had a mean absolute Ucrit (cm/s) value 22% or mean relative Ucrit (BL/s) value 24% lower than the controls. It suggested that fast-growing "all-fish" GH-transgenic carp were inferior swimmers. It is also supported that there was a trade-off between growth rates and swimming performance, i.e.faster-growing individuals had lower critical swimming speed.

  3. 4p16.3 microdeletions and microduplications detected by chromosomal microarray analysis: New insights into mechanisms and critical regions.

    Science.gov (United States)

    Bi, Weimin; Cheung, Sau-Wai; Breman, Amy M; Bacino, Carlos A

    2016-10-01

    Deletions in the 4p16.3 region cause Wolf-Hirschhorn syndrome, a well known contiguous microdeletion syndrome with the critical region for common phenotype mapped in WHSCR2. Recently, duplications in 4p16.3 were reported in three patients with developmental delay and dysmorphic features. Through chromosomal microarray analysis, we identified 156 patients with a deletion (n = 109) or duplication (n = 47) in 4p16.3 out of approximately 60,000 patients analyzed by Baylor Miraca Genetics Laboratories. Seventy-five of the postnatally detected deletions encompassed the entire critical region, 32 (43%) of which were associated with other chromosome rearrangements, including six patients (8%) that had a duplication adjacent to the terminal deletion. Our data indicate that Wolf-Hirschhorn syndrome deletions with an adjacent duplication occur at a higher frequency than previously appreciated. Pure deletions (n = 14) or duplications (n = 15) without other copy number changes distal to or inside the WHSCR2 were identified for mapping of critical regions. Our data suggest that deletion of the segment from 0.6 to 0.9 Mb from the terminus of 4p causes a seizure phenotype and duplications of a region distal to the previously defined smallest region of overlap for 4p16.3 microduplication syndrome are associated with neurodevelopmental problems. We detected seven Wolf-Hirschhorn syndrome deletions and one 4p16.3 duplication prenatally; all of the seven are either >8 Mb in size and/or associated with large duplications. In conclusion, our study provides deeper insight into the molecular mechanisms, the critical regions and effective prenatal diagnosis for 4p16.3 deletions/ duplications. © 2016 Wiley Periodicals, Inc.

  4. Four out of eight genes in a mouse chromosome 7 congenic donor region are candidate obesity genes

    Science.gov (United States)

    Sarahan, Kari A.; Fisler, Janis S.

    2011-01-01

    We previously identified a region of mouse chromosome 7 that influences body fat mass in F2 littermates of congenic × background intercrosses. Current analyses revealed that alleles in the donor region of the subcongenic B6.C-D7Mit318 (318) promoted a twofold increase in adiposity in homozygous lines of 318 compared with background C57BL/6ByJ (B6By) mice. Parent-of-origin effects were discounted through cross-fostering studies and an F1 reciprocal cross. Mapping of the donor region revealed that it has a maximal size of 2.8 Mb (minimum 1.8 Mb) and contains a maximum of eight protein coding genes. Quantitative PCR in whole brain, liver, and gonadal white adipose tissue (GWAT) revealed differential expression between genotypes for three genes in females and two genes in males. Alpha-2,8-sialyltransferase 8B (St8sia2) showed reduced 318 mRNA levels in brain for females and males and in GWAT for females only. Both sexes of 318 mice had reduced Repulsive guidance molecule-a (Rgma) expression in GWAT. In brain, Family with sequence similarity 174 member b (Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 (Chd2-2) had reduced expression in 318 males. No donor region genes were differentially expressed in liver. Sequence analysis of coding exons for all genes in the 318 donor region revealed only one single nucleotide polymorphism that produced a nonsynonymous missense mutation, Gln7Pro, in Fam174b. Our findings highlight the difficulty of using expression and sequence to identify quantitative trait genes underlying obesity even in small genomic regions. PMID:21730028

  5. Four out of eight genes in a mouse chromosome 7 congenic donor region are candidate obesity genes.

    Science.gov (United States)

    Sarahan, Kari A; Fisler, Janis S; Warden, Craig H

    2011-09-22

    We previously identified a region of mouse chromosome 7 that influences body fat mass in F2 littermates of congenic × background intercrosses. Current analyses revealed that alleles in the donor region of the subcongenic B6.C-D7Mit318 (318) promoted a twofold increase in adiposity in homozygous lines of 318 compared with background C57BL/6ByJ (B6By) mice. Parent-of-origin effects were discounted through cross-fostering studies and an F1 reciprocal cross. Mapping of the donor region revealed that it has a maximal size of 2.8 Mb (minimum 1.8 Mb) and contains a maximum of eight protein coding genes. Quantitative PCR in whole brain, liver, and gonadal white adipose tissue (GWAT) revealed differential expression between genotypes for three genes in females and two genes in males. Alpha-2,8-sialyltransferase 8B (St8sia2) showed reduced 318 mRNA levels in brain for females and males and in GWAT for females only. Both sexes of 318 mice had reduced Repulsive guidance molecule-a (Rgma) expression in GWAT. In brain, Family with sequence similarity 174 member b (Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 (Chd2-2) had reduced expression in 318 males. No donor region genes were differentially expressed in liver. Sequence analysis of coding exons for all genes in the 318 donor region revealed only one single nucleotide polymorphism that produced a nonsynonymous missense mutation, Gln7Pro, in Fam174b. Our findings highlight the difficulty of using expression and sequence to identify quantitative trait genes underlying obesity even in small genomic regions.

  6. A Novel Phytophthora sojae Resistance Rps12 Gene Mapped to a Genomic Region That Contains Several Rps Genes

    Science.gov (United States)

    Sahoo, Dipak K.; Abeysekara, Nilwala S.; Cianzio, Silvia R.; Robertson, Alison E.

    2017-01-01

    Phytophthora sojae Kaufmann and Gerdemann, which causes Phytophthora root rot, is a widespread pathogen that limits soybean production worldwide. Development of Phytophthora resistant cultivars carrying Phytophthora resistance Rps genes is a cost-effective approach in controlling this disease. For this mapping study of a novel Rps gene, 290 recombinant inbred lines (RILs) (F7 families) were developed by crossing the P. sojae resistant cultivar PI399036 with the P. sojae susceptible AR2 line, and were phenotyped for responses to a mixture of three P. sojae isolates that overcome most of the known Rps genes. Of these 290 RILs, 130 were homozygous resistant, 12 heterzygous and segregating for Phytophthora resistance, and 148 were recessive homozygous and susceptible. From this population, 59 RILs homozygous for Phytophthora sojae resistance and 61 susceptible to a mixture of P. sojae isolates R17 and Val12-11 or P7074 that overcome resistance encoded by known Rps genes mapped to Chromosome 18 were selected for mapping novel Rps gene. A single gene accounted for the 1:1 segregation of resistance and susceptibility among the RILs. The gene encoding the Phytophthora resistance mapped to a 5.8 cM interval between the SSR markers BARCSOYSSR_18_1840 and Sat_064 located in the lower arm of Chromosome 18. The gene is mapped 2.2 cM proximal to the NBSRps4/6-like sequence that was reported to co-segregate with the Phytophthora resistance genes Rps4 and Rps6. The gene is mapped to a highly recombinogenic, gene-rich genomic region carrying several nucleotide binding site-leucine rich repeat (NBS-LRR)-like genes. We named this novel gene as Rps12, which is expected to be an invaluable resource in breeding soybeans for Phytophthora resistance. PMID:28081566

  7. Gene expression in the rodent brain is associated with its regional connectivity.

    Directory of Open Access Journals (Sweden)

    Lior Wolf

    2011-05-01

    Full Text Available The putative link between gene expression of brain regions and their neural connectivity patterns is a fundamental question in neuroscience. Here this question is addressed in the first large scale study of a prototypical mammalian rodent brain, using a combination of rat brain regional connectivity data with gene expression of the mouse brain. Remarkably, even though this study uses data from two different rodent species (due to the data limitations, we still find that the connectivity of the majority of brain regions is highly predictable from their gene expression levels-the outgoing (incoming connectivity is successfully predicted for 73% (56% of brain regions, with an overall fairly marked accuracy level of 0.79 (0.83. Many genes are found to play a part in predicting both the incoming and outgoing connectivity (241 out of the 500 top selected genes, p-value<1e-5. Reassuringly, the genes previously known from the literature to be involved in axon guidance do carry significant information about regional brain connectivity. Surveying the genes known to be associated with the pathogenesis of several brain disorders, we find that those associated with schizophrenia, autism and attention deficit disorder are the most highly enriched in the connectivity-related genes identified here. Finally, we find that the profile of functional annotation groups that are associated with regional connectivity in the rodent is significantly correlated with the annotation profile of genes previously found to determine neural connectivity in C. elegans (Pearson correlation of 0.24, p<1e-6 for the outgoing connections and 0.27, p<1e-5 for the incoming. Overall, the association between connectivity and gene expression in a specific extant rodent species' brain is likely to be even stronger than found here, given the limitations of current data.

  8. Alarm setting for the critically ill patient: a descriptive pilot survey of nurses' perceptions of current practice in an Australian Regional Critical Care Unit.

    Science.gov (United States)

    Christensen, Martin; Dodds, Andrew; Sauer, Josh; Watts, Nigel

    2014-08-01

    The aim of this survey was to assess registered nurse's perceptions of alarm setting and management in an Australian Regional Critical Care Unit. The setting and management of alarms within the critical care environment is one of the key responsibilities of the nurse in this area. However, with up to 99% of alarms potentially being false-positives it is easy for the nurse to become desensitised or fatigued by incessant alarms; in some cases up to 400 per patient per day. Inadvertently ignoring, silencing or disabling alarms can have deleterious implications for the patient and nurse. A total population sample of 48 nursing staff from a 13 bedded ICU/HDU/CCU within regional Australia were asked to participate. A 10 item open-ended and multiple choice questionnaire was distributed to determine their perceptions and attitudes of alarm setting and management within this clinical area. Two key themes were identified from the open-ended questions: attitudes towards inappropriate alarm settings and annoyance at delayed responses to alarms. A significant number of respondents (93%) agreed that alarm fatigue can result in alarm desensitisation and the disabling of alarms, whilst 81% suggested the key factors are those associated with false-positive alarms and inappropriately set alarms. This study contributes to what is known about alarm fatigue, setting and management within a critical care environment. In addition it gives an insight as to what nurses' within a regional context consider the key factors which contribute to alarm fatigue. Clearly nursing burnout and potential patient harm are important considerations for practice especially when confronted with alarm fatigue and desensitisation. Therefore, promoting and maintaining an environment of ongoing intra-professional communication and alarm surveillance are crucial in alleviating these potential problems. Copyright © 2014. Published by Elsevier Ltd.

  9. Fine mapping of the human pentraxin gene region on chromosome 1q23

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, M.T.; Whitehead, A.S. [Univ. of Dublin (Ireland); Divane, A. [Univ. of Cambridge (United Kingdom)

    1996-12-31

    The 1q21 to 25 region of human chromosome 1 contains genes which encode proteins with immune- and inflammation-associated functions. These include the pentraxin genes, for C-reactive protein (CRP), serum amyloid P(SAP) protein (APCS), and a CRP pseudogene (CRPP1). The region of chromosome 1 containing this cluster is syntenic with distal mouse chromosome 1. We constructed an approximately 1.4 megabase yeast artificial chromosome (YAC) contig with the pentraxin genes at its core. This four-YAC contig includes other genes with immune functions including the FCER1A gene, which encodes the {alpha}-subunit of the IgE high-affinity Fc receptor and the 1F1-16 gene, an interferon-{gamma}-induced gene. In addition, it contains the histone H3F2 and H4F2 genes and the gene for erythroid {alpha}-spectrin (SPTA1). The gene order is cen.-SPTA1-H4F2-H3F2-1F1-16-CRP-CRPP1-APCS-FCERIA-tel. The contig thus consists of a cluster of genes whose products either have immunological importance, bind DNA, or both. 68 refs., 3 figs., 2 tabs.

  10. Cloning and Sequence Analysis of Light Variable Region Gene of Anti-human Retinoblastoma Monoclonal Antibody

    Institute of Scientific and Technical Information of China (English)

    Xiufeng Zhong; Yongping Li; Shuqi Huang; Bo Ning; Chunyan Zhang; Jianliang Zheng; Guanguang Feng

    2002-01-01

    Purpose: To clone the variable region gene of light chain of monoclonal antibody against human retinoblastoma and to analyze the characterization of its nucleotide sequence as well as amino acid sequence.Methods: Total RNA was extracted from 3C6 hybridoma cells secreting specific monoclonal antibody(McAb)against human retinoblastoma(RB), then transcripted reversely into cDNA with olig-dT primers.The variable region of the light chain (VL) gene fragments was amplified using polymeerase chain reaction(PCR) and further cloned into pGEM(R) -T Easy vector. Then, 3C6 VL cDNA was sequenced by Sanger's method.Homologous analysis was done by NCBI BLAST.Results: The complete nucleotide sequence of 3C6 VL cDNA consisted of 321 bp encoding 107 amino acid residues, containing four workframe regions(FRs)and three complementarity-determining regions (CDRs) as well as the typical structure of two cys residues. The sequence is most homological to a member of the Vk9 gene family, and its chain utilizes the Jkl gene segment.Conclusion: The light chain variable region gene of the McAb against human RB was amplified successfully , which belongs to the Vk9 gene family and utilizes Vk-Jk1 gene rearrangement. This study lays a good basis for constructing a recombinant antibody and for making a new targeted therapeutic agents against retinoblastoma.

  11. Identification of the transcriptional promoters in the proximal regions of human microRNA genes.

    Science.gov (United States)

    Long, Yue-Sheng; Deng, Guang-Fei; Sun, Xun-Sha; Yi, Yong-Hong; Su, Tao; Zhao, Qi-Hua; Liao, Wei-Ping

    2011-08-01

    To identify the transcriptional promoters in the proximal regions of human microRNA (miRNA) genes, we analyzed the 5' flanking regions of intergenic miRNAs and intronic miRNAs. With the TSSG program prediction, we found that the ratio of intronic-s miRNA genes with a least one promoter was significantly lower than those of intergenic miRNA genes and intronic-a miRNA genes. More than half of the miRNA genes have only one promoter and less than 20% of the miRNA genes have more than three promoters in the 5-kb upstream regions. All potential promoters are randomly distributed within these regions. Approximately 60% of the miRNA promoters have a TATA-like box, being significantly higher than that of all human promoters. Luciferase reporter assays showed that 22 of the 30 promoters drove gene expression in HEK-293 cells, indicating a high accuracy of the promoter prediction. This study lays a foundation for future investigation into the transcriptional regulatory mechanisms of human miRNA genes.

  12. Regional differences in gene expression and promoter usage in aged human brains

    KAUST Repository

    Pardo, Luba M.

    2013-02-19

    To characterize the promoterome of caudate and putamen regions (striatum), frontal and temporal cortices, and hippocampi from aged human brains, we used high-throughput cap analysis of gene expression to profile the transcription start sites and to quantify the differences in gene expression across the 5 brain regions. We also analyzed the extent to which methylation influenced the observed expression profiles. We sequenced more than 71 million cap analysis of gene expression tags corresponding to 70,202 promoter regions and 16,888 genes. More than 7000 transcripts were differentially expressed, mainly because of differential alternative promoter usage. Unexpectedly, 7% of differentially expressed genes were neurodevelopmental transcription factors. Functional pathway analysis on the differentially expressed genes revealed an overrepresentation of several signaling pathways (e.g., fibroblast growth factor and wnt signaling) in hippocampus and striatum. We also found that although 73% of methylation signals mapped within genes, the influence of methylation on the expression profile was small. Our study underscores alternative promoter usage as an important mechanism for determining the regional differences in gene expression at old age.

  13. Sequence breakpoints in the aflatoxin biosynthesis gene cluster and flanking regions in nonaflatoxigenic Aspergillus flavus isolates.

    Science.gov (United States)

    Chang, Perng-Kuang; Horn, Bruce W; Dorner, Joe W

    2005-11-01

    Aspergillus flavus populations are genetically diverse. Isolates that produce either, neither, or both aflatoxins and cyclopiazonic acid (CPA) are present in the field. We investigated defects in the aflatoxin gene cluster in 38 nonaflatoxigenic A. flavus isolates collected from southern United States. PCR assays using aflatoxin-gene-specific primers grouped these isolates into eight (A-H) deletion patterns. Patterns C, E, G, and H, which contain 40 kb deletions, were examined for their sequence breakpoints. Pattern C has one breakpoint in the cypA 3' untranslated region (UTR) and another in the verA coding region. Pattern E has a breakpoint in the amdA coding region and another in the ver1 5'UTR. Pattern G contains a deletion identical to the one found in pattern C and has another deletion that extends from the cypA coding region to one end of the chromosome as suggested by the presence of telomeric sequence repeats, CCCTAATGTTGA. Pattern H has a deletion of the entire aflatoxin gene cluster from the hexA coding region in the sugar utilization gene cluster to the telomeric region. Thus, deletions in the aflatoxin gene cluster among A. flavus isolates are not rare, and the patterns appear to be diverse. Genetic drift may be a driving force that is responsible for the loss of the entire aflatoxin gene cluster in nonaflatoxigenic A. flavus isolates when aflatoxins have lost their adaptive value in nature.

  14. Cloning and Analysis of the Promoter Region of Rat uPA Gene

    Institute of Scientific and Technical Information of China (English)

    Yan LIU; Jin-wen XIONG; Li-gang CHEN; Yong-hong TIAN; Cheng-liang XIONG

    2007-01-01

    Objective To clone and analyze the promoter sequence of rat urokinase plasminogen activator protein gene.Methods The genomic DNA was extracted from rat testicular tissue. According to urokinase plasminogen activator, the gene sense primer and antisense primer of uPA gene were designed and synthesized, then Touch-Down PCR were performed. After proper purification, the PCR product was sequenced, analyzed with the promoter prediction software and compared with the DNA sequence of rattuas urokinase plasminogen activator.Results The cloned uPA gene was about 1 572 bp in length, which contained a full open-reading frame with 21 bp in length exons, and the upper region of transcriptional start was 1 551 bp in length which was eucaryon transcriptional control area.The 5' UTR had a promoter region including a non-responsive TATA-box. Not only the GC-box binding region was found in this gene, but also active protein 1 (AP1) and SP1 were seen in other regions.Conclusion A 1 572 bp uPA gene fragment (GenBank accession No. X65651) was obtained from rat genomic DNA library, containing eucaryon transcriptional control area with a promoter region, non-conspicuous TATA-box, GC-box and an extron. A non-responsive TATA-box is located at the upper -30 region.

  15. Detection of chromosomal regions showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma

    Directory of Open Access Journals (Sweden)

    Bortoluzzi Stefania

    2004-06-01

    Full Text Available Abstract Background Rhabdomyosarcoma is a relatively common tumour of the soft tissue, probably due to regulatory disruption of growth and differentiation of skeletal muscle stem cells. Identification of genes differentially expressed in normal skeletal muscle and in rhabdomyosarcoma may help in understanding mechanisms of tumour development, in discovering diagnostic and prognostic markers and in identifying novel targets for drug therapy. Results A Perl-code web client was developed to automatically obtain genome map positions of large sets of genes. The software, based on automatic search on Human Genome Browser by sequence alignment, only requires availability of a single transcribed sequence for each gene. In this way, we obtained tissue-specific chromosomal maps of genes expressed in rhabdomyosarcoma or skeletal muscle. Subsequently, Perl software was developed to calculate gene density along chromosomes, by using a sliding window. Thirty-three chromosomal regions harbouring genes mostly expressed in rhabdomyosarcoma were identified. Similarly, 48 chromosomal regions were detected including genes possibly related to function of differentiated skeletal muscle, but silenced in rhabdomyosarcoma. Conclusion In this study we developed a method and the associated software for the comparative analysis of genomic expression in tissues and we identified chromosomal segments showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma, appearing as candidate regions for harbouring genes involved in origin of alveolar rhabdomyosarcoma representing possible targets for drug treatment and/or development of tumor markers.

  16. Cloning and analysing of 5‘ flanking region of Xenopus organizer gene noggin

    Institute of Scientific and Technical Information of China (English)

    TAOQINHUA; JINGYANG; 等

    1999-01-01

    Xenopus organizer specific gene noggin possesses nearly all the characterestic properties of the action of organizer to specify the embryonic body acis.To analyze how the maternal inherited factors control its expression pattern,we cloned the 5' regulatory region of noggin gene.The 1.5 kb upstream sequense could direct reporter gene to express in vivo and data from deletion analysis indicated that a 229 base pair fragmet is essential for activating noggin expression.We further demonstrated that the response elements within this regulatory region were indeed under the control of growth factor activin and Wnt signaling pathway components.

  17. ATRX promotes gene expression by facilitating transcriptional elongation through guanine-rich coding regions.

    Science.gov (United States)

    Levy, Michael A; Kernohan, Kristin D; Jiang, Yan; Bérubé, Nathalie G

    2015-04-01

    ATRX is a chromatin remodeling protein involved in deposition of the histone variant H3.3 at telomeres and pericentromeric heterochromatin. It also influences the expression level of specific genes; however, deposition of H3.3 at transcribed genes is currently thought to occur independently of ATRX. We focused on a set of genes, including the autism susceptibility gene Neuroligin 4 (Nlgn4), that exhibit decreased expression in ATRX-null cells to investigate the mechanisms used by ATRX to promote gene transcription. Overall TERRA levels, as well as DNA methylation and histone modifications at ATRX target genes are not altered and thus cannot explain transcriptional dysregulation. We found that ATRX does not associate with the promoter of these genes, but rather binds within regions of the gene body corresponding to high H3.3 occupancy. These intragenic regions consist of guanine-rich DNA sequences predicted to form non-B DNA structures called G-quadruplexes during transcriptional elongation. We demonstrate that ATRX deficiency corresponds to reduced H3.3 incorporation and stalling of RNA polymerase II at these G-rich intragenic sites. These findings suggest that ATRX promotes the incorporation of histone H3.3 at particular transcribed genes and facilitates transcriptional elongation through G-rich sequences. The inability to transcribe genes such as Nlgn4 could cause deficits in neuronal connectivity and cognition associated with ATRX mutations in humans.

  18. GeneRegionScan: a Bioconductor package for probe-level analysis of specific, small regions of the genome.

    Science.gov (United States)

    Folkersen, Lasse; Diez, Diego; Wheelock, Craig E; Haeggström, Jesper Z; Goto, Susumu; Eriksson, Per; Gabrielsen, Anders

    2009-08-01

    Whole-genome microarrays allow us to interrogate the entire transcriptome of a cell. Affymetrix microarrays are constructed using several probes that match to different regions of a gene and a summarization step reduces this complexity into a single value, representing the expression level of the gene or the expression level of an exon in the case of exon arrays. However, this simplification eliminates information that might be useful when focusing on specific genes of interest. To address these limitations, we present a software package for the R platform that allows detailed analysis of expression at the probe level. The package matches the probe sequences against a target gene sequence (either mRNA or DNA) and shows the expression levels of each probe along the gene. It also features functions to fit a linear regression based on several genetic models that enables study of the relationship between gene expression and genotype. The software is implemented as a platform-independent R package available through the Bioconductor repository at http://www.bioconductor.org/. It is licensed as GPL 2.0. Supplementary data are available at Bioinformatics online.

  19. Critical regions of the Vibrio fischeri luxR protein defined by mutational analysis.

    OpenAIRE

    1990-01-01

    Expression of Vibrio fischeri luminescence genes requires an inducer, termed autoinducer, and a positive regulatory element, the luxR gene product. A plasmid containing a tac promoter-controlled luxR was mutagenized in vitro with hydroxylamine, and luxR mutant plasmids were identified by their inability to complement a luxR deletion mutation in trans. Sixteen luxR mutant plasmids were obtained, ten of which encoded full-length but inactive luxR gene products as demonstrated by a Western immun...

  20. Molecular methods for bacterial genotyping and analyzed gene regions

    Directory of Open Access Journals (Sweden)

    İbrahim Halil Yıldırım1, Seval Cing Yıldırım2, Nadir Koçak3

    2011-06-01

    Full Text Available Bacterial strain typing is an important process for diagnosis, treatment and epidemiological investigations. Current bacterial strain typing methods may be classified into two main categories: phenotyping and genotyping. Phenotypic characters are the reflection of genetic contents. Genotyping, which refers discrimination of bacterial strains based on their genetic content, has recently become widely used for bacterial strain typing. The methods already used in genotypingof bacteria are quite different from each other. In this review we tried to summarize the basic principles of DNA-based methods used in genotyping of bacteria and describe some important DNA regions that are used in genotyping of bacteria. J Microbiol Infect Dis 2011;1(1:42-46.

  1. Gene expression in the rodent brain is associated with its regional connectivity.

    Science.gov (United States)

    Wolf, Lior; Goldberg, Chen; Manor, Nathan; Sharan, Roded; Ruppin, Eytan

    2011-05-01

    The putative link between gene expression of brain regions and their neural connectivity patterns is a fundamental question in neuroscience. Here this question is addressed in the first large scale study of a prototypical mammalian rodent brain, using a combination of rat brain regional connectivity data with gene expression of the mouse brain. Remarkably, even though this study uses data from two different rodent species (due to the data limitations), we still find that the connectivity of the majority of brain regions is highly predictable from their gene expression levels-the outgoing (incoming) connectivity is successfully predicted for 73% (56%) of brain regions, with an overall fairly marked accuracy level of 0.79 (0.83). Many genes are found to play a part in predicting both the incoming and outgoing connectivity (241 out of the 500 top selected genes, p-valueregional connectivity in the rodent is significantly correlated with the annotation profile of genes previously found to determine neural connectivity in C. elegans (Pearson correlation of 0.24, p<1e-6 for the outgoing connections and 0.27, p<1e-5 for the incoming). Overall, the association between connectivity and gene expression in a specific extant rodent species' brain is likely to be even stronger than found here, given the limitations of current data.

  2. Efficient construction of a physical map by Fiber-FISH of the CLN5 region: Refined assignment and long-range contig covering the critical region on 13q22

    Energy Technology Data Exchange (ETDEWEB)

    Klockars, T.; Savukoski, M.; Isosomppi, J. [National Public Health Institute, Helsinki (Finland)] [and others

    1996-07-01

    The variant form of late infantile neuronal ceroid lipofuscinosis (vLINCL, locus definition CLN5) represents a progressive brain disease with autosomal recessive inheritance. We have previously assigned the CLN5 locus to chromosome 13q21.1-132 between markers D13S160 and D13S162 by linkage analysis in Finnish families. The information on ancient recombination events obtained from linkage disequilibrium provided an efficient tool for further refining the assignment of the CLN5 locus. Isolation of two novel (CA){sub n} markers, COLAC1 and AC224, resulted in a dramatic restriction of the critical DNA region. We utilized the Fiber-FISH technique to orient and order the large DNA clones isolated by STSs and were able to eliminate almost totally the restriction digestion and PFGE step in the construction of the long-range DNA contig. Both linkage disequilibrium data and Fiber-FISH analyses assigned the CLN5 locus to a well-defined 200-kb region. Here we report a complete physical map of about 350 kb covering the critical chromosomal region of CLN5, which will facilitate the final isolation of the CLN5 gene. 31 refs., 4 figs., 2 tabs.

  3. Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor.

    Science.gov (United States)

    Ryan, J J; McReynolds, L J; Keegan, A; Wang, L H; Garfein, E; Rothman, P; Nelms, K; Paul, W E

    1996-02-01

    IL-4 causes hematopoietic cells to proliferate and express a series of genes, including CD23. We examined whether IL-4-mediated growth, as measured by 4PS phosphorylation, and gene induction were similarly controlled. Studies of M12.4.1 cells expressing human IL-4R truncation mutants indicated that the region between amino acids 557-657 is necessary for full gene expression, which correlated with Stat6 DNA binding activity. This region was not required for 4PS phosphorylation. Tyrosine-to-phenylalanine mutations in the interval between amino acids 557-657 revealed that as long as one tyrosine remained unmutated, CD23 was fully induced. When all three tyrosines were mutated, the receptor was unable to induce CD23. The results indicate that growth regulation and gene expression are principally controlled by distinct regions of IL-4R.

  4. Analysis of transcription regulatory regions of embryonic chicken pepsinogen (ECPg) gene.

    Science.gov (United States)

    Watanuki, Kumiko; Yasugi, Sadao

    2003-09-01

    Genes encoding pepsinogens, zymogens of digestive enzyme pepsins, are expressed specifically in the gland epithelial cells of the vertebrate stomach, and their expression is also developmentally regulated, therefore providing a good model for the analysis of transcriptional regulation of genes. In the development of chicken embryonic stomach, the epithelium invaginates into the mesenchyme and forms glands and gland epithelial cells then begin to express embryonic chicken pepsinogen (ECPg) gene. It has been shown that cGATA5 binds directly GATA binding sites located within 1.1-kbp upstream of ECPg gene and activates its transcription. To find more precisely the sequences necessary for ECPg gene transcription, we carried out deletion and mutation analysis with 1.1-kbp upstream region. The results suggest that binding of GATA factor to three GATA binding sites within the upstream region -656 to -419 synergistically regulates ECPg expression in the gland epithelial cells.

  5. Reverse engineering of modified genes by Bayesian network analysis defines molecular determinants critical to the development of glioblastoma.

    Directory of Open Access Journals (Sweden)

    Brian W Kunkle

    Full Text Available In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I-IV, and 'key genes' within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated. These 10 genes were able to predict tumor status with 96-100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential 'hubs of activity'. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several 'key genes' may be required for the development of glioblastoma. Further studies are needed to validate these 'key genes' as useful tools for early detection and novel therapeutic options for these tumors.

  6. Reverse engineering of modified genes by Bayesian network analysis defines molecular determinants critical to the development of glioblastoma.

    Science.gov (United States)

    Kunkle, Brian W; Yoo, Changwon; Roy, Deodutta

    2013-01-01

    In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I-IV), and 'key genes' within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96-100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential 'hubs of activity'. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several 'key genes' may be required for the development of glioblastoma. Further studies are needed to validate these 'key genes' as useful tools for early detection and novel therapeutic options for these tumors.

  7. CAGE-defined promoter regions of the genes implicated in Rett Syndrome

    DEFF Research Database (Denmark)

    Vitezic, Morana; Bertin, Nicolas; Andersson, Robin;

    2014-01-01

    BACKGROUND: Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other...... for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum CONCLUSIONS: Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett...... Syndrome....

  8. Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions.

    Directory of Open Access Journals (Sweden)

    Soumya Raychaudhuri

    2009-06-01

    Full Text Available Translating a set of disease regions into insight about pathogenic mechanisms requires not only the ability to identify the key disease genes within them, but also the biological relationships among those key genes. Here we describe a statistical method, Gene Relationships Among Implicated Loci (GRAIL, that takes a list of disease regions and automatically assesses the degree of relatedness of implicated genes using 250,000 PubMed abstracts. We first evaluated GRAIL by assessing its ability to identify subsets of highly related genes in common pathways from validated lipid and height SNP associations from recent genome-wide studies. We then tested GRAIL, by assessing its ability to separate true disease regions from many false positive disease regions in two separate practical applications in human genetics. First, we took 74 nominally associated Crohn's disease SNPs and applied GRAIL to identify a subset of 13 SNPs with highly related genes. Of these, ten convincingly validated in follow-up genotyping; genotyping results for the remaining three were inconclusive. Next, we applied GRAIL to 165 rare deletion events seen in schizophrenia cases (less than one-third of which are contributing to disease risk. We demonstrate that GRAIL is able to identify a subset of 16 deletions containing highly related genes; many of these genes are expressed in the central nervous system and play a role in neuronal synapses. GRAIL offers a statistically robust approach to identifying functionally related genes from across multiple disease regions--that likely represent key disease pathways. An online version of this method is available for public use (http://www.broad.mit.edu/mpg/grail/.

  9. Burkitt's lymphoma is a malignancy of mature B cells expressing somatically mutated V region genes.

    Science.gov (United States)

    Klein, U.; Klein, G.; Ehlin-Henriksson, B.; Rajewsky, K.; Küppers, R.

    1995-01-01

    BACKGROUND: The developmental stage from which stems the malignant B cell population in Burkitt's lymphoma (BL) is unclear. An approach to answering this question is provided by the sequence analysis of rear-ranged immunoglobulin (Ig) variable region (V) genes from BL for evidence of somatic mutations, together with a phenotypic characterization. As somatic hypermutation of Ig V region genes occurs in germinal center B cells, somatically mutated Ig genes are found in germinal center B cells and their descendents. MATERIALS AND METHODS: Rearranged V kappa region genes from 10 kappa-expressing sporadic and endemic BL-derived cell lines (9 IgM and 1 IgG positive) and three kappa-expressing endemic BL biopsy specimens were amplified by polymerase chain reaction and sequenced. In addition, VH region gene sequences from these cell lines were determined. RESULTS: All BL cell lines and the three biopsy specimens carried somatically mutated V region genes. The average mutation frequency of rearranged V kappa genes from eight BL cell lines established from sporadic BL was 1.8%. A higher frequency (6%) was found in five endemic cases (three biopsy specimens and two BL cell lines). CONCLUSIONS: The detection of somatic mutations in the rearranged V region genes suggests that both sporadic and endemic BL represent a B-cell malignancy originating from germinal center B cells or their descendants. Interestingly, the mutation frequency detected in sporadic BL is in a range similar to that characteristic for IgM-expressing B cells in the human peripheral blood and for mu chain-expressing germinal center B cells, whereas the mutation frequency found in endemic BL is significantly higher. PMID:8529116

  10. A 4.5-megabase YAC contig and physical map over the hemochromatosis gene region

    Energy Technology Data Exchange (ETDEWEB)

    Burt, M.J.; Smit, D.J.; Pyper, W.R.; Powell, L.W.; Jazwinska, E.C. [Univ. of Queensland, Brisbane (Australia)

    1996-04-15

    We have constructed a yeast artificial chromosome (YAC) contig over the candidate hemochromatosis gene region. This contig comprises hemochromatosis gene region. This contig comprises 16 YACs from the CEPH, Washington University, and ICI YAC libraries and covers 4.5 Mb at 6p21.3-6p22. The complete contig has been restriction mapped, enabling the precise relationship between the YACs to be determined and the mapping of a total of 12 STSs. Nine of these are highly polymorphic STSs that are closely linked to hemochromatosis; this series includes D6S265 and D6S1260, which comprise the most proximal and distal markers linked to HC. This is the first YAC contig that spans the hemochromatosis candidate region, and it provides valuable resource material for the cloning of this and other genes in the region distal to the MHC class I complex. 33 refs., 1 fig., 1 tab.

  11. The human SOX18 gene: Expression analysis and characterization of its 5’ flanking region

    Directory of Open Access Journals (Sweden)

    Petrović Isidora

    2007-01-01

    Full Text Available The aim of this study was to establish an adequate in vitro model system for studying transcriptional regulation of the human SOX18 gene. The paper presents an analysis of expression of this gene in cultured cell lines and characterization of its 5' flanking region. Using RT-PCR, Northern and Western blot analysis, we demonstrated SOX18 expression in HeLa cells, indicating that this cell line provides a suitable model system for studying transcriptional regulation of the given gene. We also cloned, sequenced and for the first time characterized the human SOX18 5’ flanking region. It is shown that the region 892 bp in size immediately upstream from the start codone harbors regulatory elements sufficient for transcription and represents an SOX18 promoter region.

  12. Myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7: corroboration and narrowing of the critical region on 10q22.3.

    Science.gov (United States)

    Kuhl, Angelika; Melberg, Atle; Meinl, Edgar; Nürnberg, Gudrun; Nürnberg, Peter; Kehrer-Sawatzki, Hildegard; Jenne, Dieter E

    2008-03-01

    Several years ago, autosomal dominant myofibrillar myopathy (MFM) in combination with arrhythmogenic right ventricular cardiomyopathy (ARVC7) was tentatively mapped to a 10.6-Mbp (million base pairs) region on chromosome 10q22.3 between D10S605 (78.9 Mbp) and D10S215 (89.5 Mbp) in a Swedish family assuming that ARVC7 was allelic with cardiomyopathy, dilated 1C (CMD1C). To date, neither the genetic defect in ARVC7 nor CMD1C has been reported. In a comprehensive follow-up study we re-examined and confirmed the previous linkage data for ARVC7 using a high-density single nucleotide polymorphism marker panel from Affymetrix (Human Mapping 10K Array). No other regions with significant evidence for linkage were discovered. The critical interval was narrowed down to 4.27 Mbp between D10S1645 and D10S1786. This reduced the total number of candidate genes to 18 of which 17 (RAI17, PPIF, C10ORF56, SFTPA1, SFTPA2, SFTPA1B, SFTPA2B, SFTPD, C10ORF57, PLAC9, ANXA11, MAT1A, DYDC1, DYDC2, C10ORF58, TSPAN14 and SH2D4B) are shared with the CMD1C region. No disease-causing mutation was found in their coding regions. Moreover, metavinculin (VCL) and ZASP/cypher (LDB3) proximal and distal to this linked region were excluded by sequence analysis. To search for submicroscopic and intragenic deletions by PCR, we generated hybrid cell lines carrying only the affected or normal chromosome 10 homolog. All sequence tagged sites and exons were present on both homologs. We speculate that regulatory mutations in 1 of the 18 genes from 10q22.3 are responsible for a heterogenous spectrum of clinically distinct myodegenerative disorders, affecting both skeletal and cardiac muscles to variable degrees.

  13. Integrated care through disease-oriented critical paths:experience from Japan’s regional health planning initiatives

    Directory of Open Access Journals (Sweden)

    Etsuji Okamoto

    2011-09-01

    Full Text Available Introduction: In April 2008, Japan launched a radical reform in regional health planning that emphasized the development of disease-oriented clinical care pathways. These 'inter-provider critical paths' have sought to ensure effective integration of various providers ranging among primary care practitioners, acute care hospitals, rehabilitation hospitals, long-term care facilities and home care.  Description of policy practice: All 47 prefectures in Japan developed their Regional Health Plans pursuant to the guideline requiring that these should include at least four diseases: diabetes, acute myocardial infarction, cerebrovascular accident and cancer.  To illustrate the care pathways developed, this paper describes the guideline referring to strokes and provides examples of the new Regional Health Plans as well as examples of disease-oriented inter-provider clinical paths. In particular, the paper examines the development of information sharing through electronic health records (EHR to enhance effective integration among providers is discussed.Discussion and conclusion: Japan's reform in 2008 is unique in that the concept of "disease-oriented regional inter-provider critical paths" was adopted as a national policy and all 47 prefectures developed their Regional Health Plans simultaneously. How much the new regional health planning policy has improved the quality and outcome of care remains to be seen and will be evaluated in 2013 after the five year planned period of implementation has concluded. Whilst electronic health records appear to be a useful tool in supporting care integration they do not guarantee success in the application of an inter-provider critical path.

  14. Integrated care through disease-oriented critical paths:experience from Japan’s regional health planning initiatives

    Directory of Open Access Journals (Sweden)

    Etsuji Okamoto

    2011-09-01

    Full Text Available Introduction: In April 2008, Japan launched a radical reform in regional health planning that emphasized the development of disease-oriented clinical care pathways. These 'inter-provider critical paths' have sought to ensure effective integration of various providers ranging among primary care practitioners, acute care hospitals, rehabilitation hospitals, long-term care facilities and home care.   Description of policy practice: All 47 prefectures in Japan developed their Regional Health Plans pursuant to the guideline requiring that these should include at least four diseases: diabetes, acute myocardial infarction, cerebrovascular accident and cancer.  To illustrate the care pathways developed, this paper describes the guideline referring to strokes and provides examples of the new Regional Health Plans as well as examples of disease-oriented inter-provider clinical paths. In particular, the paper examines the development of information sharing through electronic health records (EHR to enhance effective integration among providers is discussed. Discussion and conclusion: Japan's reform in 2008 is unique in that the concept of "disease-oriented regional inter-provider critical paths" was adopted as a national policy and all 47 prefectures developed their Regional Health Plans simultaneously. How much the new regional health planning policy has improved the quality and outcome of care remains to be seen and will be evaluated in 2013 after the five year planned period of implementation has concluded. Whilst electronic health records appear to be a useful tool in supporting care integration they do not guarantee success in the application of an inter-provider critical path.

  15. Genetic Architecture of MAPT Gene Region in Parkinson Disease Subtypes.

    Science.gov (United States)

    Pascale, Esterina; Di Battista, Maria Elena; Rubino, Alfonso; Purcaro, Carlo; Valente, Marcella; Fattapposta, Francesco; Ferraguti, Giampiero; Meco, Giuseppe

    2016-01-01

    The microtubule-associated protein tau (MAPT) region has been conceptualized as a model of the interaction between genetics and functional disease outcomes in neurodegenerative disorders, such as Parkinson disease (PD). Indeed, haplotype-specific differences in expression and alternative splicing of MAPT transcripts affect cellular functions at different levels, increasing susceptibility to a range of neurodegenerative processes. In order to evaluate a possible link between MAPT variants, PD risk and PD motor phenotype, we analyzed the genetic architecture of MAPT in a cohort of PD patients. We observed a statistically significant association between the H1 haplotype and PD risk (79.5 vs 69.5%; χ(2) = 9.9; OR, 1.7; 95% CI, 1.2-2.4; p = 0.002). The effect was more evident in non tremor dominant (TD) PD subjects (NTD-PD) (82 vs 69.5%; χ(2) = 13.6; OR, 2.03; 95% CI, 1.4-3; p = 0.0003), while no difference emerged between PD subgroup of tremor dominant patients (TD-PD) and control subjects. Examination of specific intra-H1 variations showed that the H1h subhaplotype was overrepresented in NTD-PD patients compared with controls (p = 0.007; OR, 2.9; 95% CI, 1.3-6.3). Although we cannot exclude that MAPT variation may be associated with ethnicity, our results may support the hypothesis that MAPT H1 clade and a specific H1 subhaplotype influence the risk of PD and modulate the clinical expression of the disease, including motor phenotype.

  16. Water Information System Platforms Addressing Critical Societal Needs in the Mena Region

    Science.gov (United States)

    Habib, Shahid; Kfouri, Claire; Peters, Mark

    2012-01-01

    The MENA region includes 18 countries, the occupied Palestinian territories and Western Sahara. However, the region of interest for this study has a strategic interest in countries adjacent to the Mediterranean Sea, which includes, Morocco, Tunisia, Egypt, Lebanon and Jordan. The 90% of the water in the MENA region is used for the agriculture use. By the end of this century. this region is projected to experience an increase of 3 C to 5 C in mean temperatures and a 20% decline in precipitation (lPCC, 2007). Due to lower precipitation, water run-off is projected to drop by 20% to 30% in most of MENA by 2050 Reduced stream flow and groundwater recharge might lead to a reduction in water supply of 10% or greater by 2050. Therefore, per IPCC projections in temperature rise and precipitation decline in the region, the scarcity of water will become more acute with population growth, and rising demand of food in the region. Additionally, the trans boundary water issues will continue to plague the region in terms of sharing data for better management of water resources. Such pressing issues have brought The World Bank, USAID and NASA to jointly collaborate for establishing integrated, modern, up to date NASA developed capabilities for countries in the MENA region for addressing water resource issues and adapting to climate change impacts for improved decision making and societal benefit. This initiative was launched in October 2011 and is schedule to be completed by the end of2015.

  17. Weak measurement og the composite Goo-Haenchen shift in the critical region

    CERN Document Server

    Santana, Octavio J S; De Leo, Stefano; de Araujo, Luis E E

    2016-01-01

    By using a weak measurement technique, we investigated the interplay between the angular and lateral Goos-Haenchen shift of a focused He-Ne laser beam for incidence near the critical angle. We verified that this interplay dramatically affects the composite Goos-Haenchen shift of the propagated beam. The experimental results confirm theoretical predictions that recently appeared in the literature.

  18. Weak measurement of the composite Goos-Hänchen shift in the critical region

    Science.gov (United States)

    Santana, Octávio J. S.; Carvalho, Silvânia A.; De Leo, Stefano; de Araujo, Luís E. E.

    2016-08-01

    By using a weak measurement technique, we investigated the interplay between the angular and lateral Goos-Haenchen shift of a focused He-Ne laser beam for incidence near the critical angle. We verified that this interplay dramatically affects the composite Goos-Haenchen shift of the propagated beam. The experimental results confirm theoretical predictions that recently appeared in the literature.

  19. A Fluorescent Probe for Detecting Mycobacterium tuberculosis and Identifying Genes Critical for Cell Entry

    Directory of Open Access Journals (Sweden)

    Dong Yang

    2016-12-01

    Full Text Available ABSTRACTThe conventional method for quantitating Mycobacterium tuberculosis (Mtb in vitro and in vivo relies on bacterial colony forming unit (CFU enumeration on agar plates. Due to the slow growth rate of Mtb, it takes 3-6 weeks to observe visible colonies on agar plates. Imaging technologies that are capable of quickly quantitating both active and dormant tubercle bacilli in vitro and in vivo would accelerate research towards the development of anti-TB chemotherapies and vaccines. We have developed a fluorescent probe that can directly label the Mtb cell wall components. The fluorescent probe, designated as DLF-1, has a strong affinity to the D-Ala-D-Ala unit of the late peptidoglycan intermediates in the bacterial cell wall. We demonstrate that DLF-1 is capable of detecting Mtb in both the active replicating and dormant states in vitro at 100 nM without inhibiting bacterial growth. The DLF-1 fluorescence signal correlated well with CFU of the labeled bacteria (R2=1 and 0.99 for active replicating and dormant Mtb, respectively. DLF-1 can also quantitate labeled Mtb inside of cells. The utility of DLF-1 probe to quantitate Mtb was also successfully applied to identify genes critical for cell invasion. In conclusion, this novel near infrared imaging probe provides a powerful new tool for enumerating Mtb with potential future use in bacterial virulence study.

  20. Assessing the Value of DNA Barcodes and Other Priority Gene Regions for Molecular Phylogenetics of Lepidoptera

    Science.gov (United States)

    Wilson, John James

    2010-01-01

    Background Despite apparently abundant amounts of observable variation and species diversity, the order Lepidoptera exhibits a morphological homogeneity that has provided only a limited number of taxonomic characters and led to widespread use of nucleotides for inferring relationships. This study aims to characterize and develop methods to quantify the value of priority gene regions designated for Lepidoptera molecular systematics. In particular, I assess how the DNA barcode segment of the mitochondrial COI gene performs across a broad temporal range given its number one position of priority, most sequenced status, and the conflicting opinions on its phylogenetic performance. Methodology/Principal Findings Gene regions commonly sequenced for Lepidoptera phylogenetics were scored using multiple measures across three categories: practicality, which includes universality of primers and sequence quality; phylogenetic utility; and phylogenetic signal. I found that alternative measures within a category often appeared correlated, but high scores in one category did not necessarily translate into high scores in another. The DNA barcode was easier to sequence than other genes, and had high scores for utility but low signal above the genus level. Conclusions/Significance Given limited financial resources and time constraints, careful selection of gene regions for molecular phylogenetics is crucial to avoid wasted effort producing partially informative data. This study introduces an approach to assessing the value of gene regions prior to the initiation of new studies and presents empirical results to help guide future selections. PMID:20479871

  1. Assessing the value of DNA barcodes and other priority gene regions for molecular phylogenetics of Lepidoptera.

    Directory of Open Access Journals (Sweden)

    John James Wilson

    Full Text Available BACKGROUND: Despite apparently abundant amounts of observable variation and species diversity, the order Lepidoptera exhibits a morphological homogeneity that has provided only a limited number of taxonomic characters and led to widespread use of nucleotides for inferring relationships. This study aims to characterize and develop methods to quantify the value of priority gene regions designated for Lepidoptera molecular systematics. In particular, I assess how the DNA barcode segment of the mitochondrial COI gene performs across a broad temporal range given its number one position of priority, most sequenced status, and the conflicting opinions on its phylogenetic performance. METHODOLOGY/PRINCIPAL FINDINGS: Gene regions commonly sequenced for lepidoptera phylogenetics were scored using multiple measures across three categories: practicality, which includes universality of primers and sequence quality; phylogenetic utility; and phylogenetic signal. I found that alternative measures within a category often appeared correlated, but high scores in one category did not necessarily translate into high scores in another. The DNA barcode was easier to sequence than other genes, and had high scores for utility but low signal above the genus level. CONCLUSIONS/SIGNIFICANCE: Given limited financial resources and time constraints, careful selection of gene regions for molecular phylogenetics is crucial to avoid wasted effort producing partially informative data. This study introduces an approach to assessing the value of gene regions prior to the initiation of new studies and presents empirical results to help guide future selections.

  2. Identification of a set of genes showing regionally enriched expression in the mouse brain

    Directory of Open Access Journals (Sweden)

    Marra Marco A

    2008-07-01

    Full Text Available Abstract Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters ( Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.

  3. Critical region in 2q31.2q32.3 deletion syndrome: Report of two phenotypically distinct patients, one with an additional deletion in Alagille syndrome region

    Directory of Open Access Journals (Sweden)

    Ferreira Susana

    2012-05-01

    Full Text Available Abstract Background Standard cytogenetic analysis has revealed to date more than 30 reported cases presenting interstitial deletions involving region 2q31-q32, but with poorly defined breakpoints. After the postulation of 2q31.2q32.3 deletion as a clinically recognizable disorder, more patients were reported with a critical region proposed and candidate genes pointed out. Results We report two female patients with de novo chromosome 2 cytogenetically visible deletions, one of them with an additional de novo deletion in chromosome 20p12.2p12.3. Patient I presents a 16.8 Mb deletion in 2q31.2q32.3 while patient II presents a smaller deletion of 7 Mb in 2q32.1q32.3, entirely contained within patient I deleted region, and a second 4 Mb deletion in Alagille syndrome region. Patient I clearly manifests symptoms associated with the 2q31.2q32.3 deletion syndrome, like the muscular phenotype and behavioral problems, while patient II phenotype is compatible with the 20p12 deletion since she manifests problems at the cardiac level, without significant dysmorphisms and an apparently normal psychomotor development. Conclusions Whereas Alagille syndrome is a well characterized condition mainly caused by haploinsufficiency of JAG1 gene, with manifestations that can range from slight clinical findings to major symptoms in different domains, the 2q31.2q32.3 deletion syndrome is still being delineated. The occurrence of both imbalances in reported patient II would be expected to cause a more severe phenotype compared to the individual phenotype associated with each imbalance, which is not the case, since there are no manifestations due to the 2q32 deletion. This, together with the fact that patient I deleted region overlaps previously reported cases and patient II deletion is outside this common region, reinforces the existence of a critical region in 2q31.3q32.1, between 181 to 185 Mb, responsible for the clinical phenotype.

  4. Extrapolation of IAPWS-IF97 data: The saturation pressure of H2O in the critical region

    Science.gov (United States)

    Ustyuzhanin, E. E.; Ochkov, V. F.; Shishakov, V. V.; Rykov, A. V.

    2015-11-01

    Some literature sources and web sites are analyzed in this report. These sources contain an information about thermophysical properties of H2O including the vapor pressure Ps. (Ps,T)-data have a form of the international standard tables named as “IAPWS-IF97 data”. Our analysis shows that traditional databases represent (Ps,T)-data at t > 0.002, here t = (Tc - T)/Tc is a reduced temperature. It is an interesting task to extrapolate IAPWS-IF97 data in to the critical region and to get (Ps,T)-data at t laws of the scaling theory (ST). A combined model (CM) is chosen as a form, F(t,D,B), to express a function ln(Ps/Pc) in the critical region including t laws of ST are taken into account to elaborate F(t, D, B). Adjustable coefficients (B) are determined by fitting CM to input (Ps,T)-points those belong to IAPWS-IF97 data. Application results are got with a help of CM in the critical region including values of the first and the second derivatives for Ps(T). Some models Ps(T) are compared with CM.

  5. Cloning,sequencing and analyzing of the heavy chain V region genes of human polyreactive antibodies

    Institute of Scientific and Technical Information of China (English)

    ZHANGJINSONG; MINGYEH

    1994-01-01

    The heavy chain variable region genes of 5 human polyreactive mAbs generated in our laboratory have been cloned and sequenced using polymerase chain reaction(PCR) technique.We found that 2 and 3 mAbs utilized genes of the VHIV and VHⅢ families,respectively.The former 2 VH segments were in germline configuration.A common VH segment,with the best similarity of 90.1% to the published VHⅢ germline genes,was utilized by 2 different rearranged genes encoding the V regions of other 3 mAbs.This strongly suggests that the common VH segment is a unmutated copy of an unidentified germline VHⅢ gene.All these polyreactive mAbs displayed a large NDN region(VH-D-JH junction).The entire H chain V regions of these polyreactive mAbs are unusually basic.The analysis of the charge properties of these mAbs as well as those of other poly-and mono-reactive mAbs from literatures prompts us to propose that the charged amino acids with a particular distribution along the H chain V region,especially the binding sites(CDRs),may be an important structural feature involved in antibody polyreactivity.

  6. Differential Expression of FosB Proteins and Potential Target Genes in Select Brain Regions of Addiction and Depression Patients.

    Science.gov (United States)

    Gajewski, Paula A; Turecki, Gustavo; Robison, Alfred J

    2016-01-01

    Chronic exposure to stress or drugs of abuse has been linked to altered gene expression throughout the body, and changes in gene expression in discrete brain regions are thought to underlie many psychiatric diseases, including major depressive disorder and drug addiction. Preclinical models of these disorders have provided evidence for mechanisms of this altered gene expression, including transcription factors, but evidence supporting a role for these factors in human patients has been slow to emerge. The transcription factor ΔFosB is induced in the prefrontal cortex (PFC) and hippocampus (HPC) of rodents in response to stress or cocaine, and its expression in these regions is thought to regulate their "top down" control of reward circuitry, including the nucleus accumbens (NAc). Here, we use biochemistry to examine the expression of the FosB family of transcription factors and their potential gene targets in PFC and HPC postmortem samples from depressed patients and cocaine addicts. We demonstrate that ΔFosB and other FosB isoforms are downregulated in the HPC but not the PFC in the brains of both depressed and addicted individuals. Further, we show that potential ΔFosB transcriptional targets, including GluA2, are also downregulated in the HPC but not PFC of cocaine addicts. Thus, we provide the first evidence of FosB gene expression in human HPC and PFC in these psychiatric disorders, and in light of recent findings demonstrating the critical role of HPC ΔFosB in rodent models of learning and memory, these data suggest that reduced ΔFosB in HPC could potentially underlie cognitive deficits accompanying chronic cocaine abuse or depression.

  7. Three Hsp70 genes are located in the C4-H-2D region: Possible candidates for the Orch-1 locus

    Energy Technology Data Exchange (ETDEWEB)

    Snoek, M.; Jansen, M.; Vugt, H. van (The Netherlands Cancer Inst., Amsterdam (Netherlands)); Olavensen, M.G.; Campbell, R.D. (MRC Immunochemistry Univ., Oxford (United Kingdom)); Teuscher, C. (Brigham Young Univ., Provo (United States))

    1993-02-01

    The central region of the mouse MHC harbors a recombinational hot spot area. Most recombinations in this part of the complex take place between the Hsp70.1 gene and the G7 gene. This interval is of interest since structurally indistinguishable recombinant haplotypes do differ in functional behavior. Susceptibility to experimental allergic orchitis, which is controlled by the Orch-1 locus, is one example. We have analyzed the hot spot region at the molecular level in order to understand the molecular organization of this chromosomal segment. From a C57BL genomic library we constructed a cosmid contig bridging the interval between Hsp70.1 and G7. The Orch-1 gene maps to a 60-kb segment of DNA and which we found a new Hsp70 homologue, Hsp 70.3. Thus, as in the human MHC, the central region of the mouse MHC harbors a cluster of three Hsp70 genes: Hsp 70.1, Hsp 70.3, and Hsc 70t. Two other genes are located in this critical interval (G7b and G7a/Bat-6), and there might still be other undetected genes present in the region. Heat shock proteins play an important role in a large number of physiological processes and it is tempting to speculate that Hcs70t, which exhibits testis-specific expression, may be identical to Orch-1. 32 refs., 2 figs., 2 tabs.

  8. Identification of true EST alignments and exon regions of gene sequences

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yanhong; JING Hui; LI Yanen; LIU Huailan

    2004-01-01

    Expressed sequence tags (ESTs), which have piled up considerably so far, provide a valuable resource for finding new genes, disease-relevant genes, and for recognizing alternative splicing variants, SNP sites, etc. The prerequisite for carrying out these researches is to correctly ascertain the gene-sequence-related ESTs. Based on analysis of the alignment results between some known gene sequences and ESTs in public database, several measures including Identity Check, Gap Check, Inclusion Check and Length Check have been introduced to judge whether an EST alignment is related to a gene sequence or not. A computational program EDSAc1.0 has been developed to identify true EST alignments and exon regions of query gene sequences. When tested with human gene sequences in the standard dataset HMR195 and evaluated with the standard measures of gene prediction performance, EDSAc1.0 can identify protein- coding regions with specificity of 0.997 and sensitivity of 0.88 at the nucleotide level, which outperform that of the counterpart TAP. A web server of EDSAc1.0 is available at http://infosci.hust.edu.cn.

  9. Refinement of the critical 2p25.3 deletion region

    DEFF Research Database (Denmark)

    De Rocker, Nina; Vergult, Sarah; Koolen, David

    2015-01-01

    and his three children and a 5' MYT1L overlapping duplication in a father and his two children. Expression analysis in zebrafish embryos shows specific myt1l expression in the developing brain. CONCLUSION: Our data strongly strengthen the hypothesis that MYT1L is the causal gene for the observed syndromal...

  10. Characterization of a gene from the EDM1-PSACH region of human chromosome 19p

    Energy Technology Data Exchange (ETDEWEB)

    Lennon, G.G.; Giorgi, D.; Martin, J.R. [Lawrence Livermore National Lab., CA (United States)] [and others

    1994-09-01

    Genetic linkage mapping has indicated that both multiple epiphyseal dysplasia (EDM1), a dominantly inherited chondrodysplasia, and pseudoachondroplasia (PSACH), a skeletal disorder associated with dwarfism, map to a 2-3 Mb region of human chromosome 19p. We have isolated a partial cDNA from this region using hybrid selection, and report on progress towards the characterization of the genomic structure and transcription of the corresponding gene. Sequence analysis of the cDNA to date indicates that this gene is likely to be expressed within extracellular matrix tissues. Defects in this gene or neighboring gene family members may therefore lead to EDM1, PSACH, or other connective tissue and skeletal disorders.

  11. Soil phosphorus dynamic, balance and critical P values in long-term fertilization experiment in Taihu Lake region, China

    Institute of Scientific and Technical Information of China (English)

    SHI Lin-lin; SHEN Ming-xing; LU Chang-yin; WANG Hai-hou; ZHOU Xin-wei; JIN Mei-juan; WU Tong-dong

    2015-01-01

    Phosphorus (P) is an important macronutrient for plant but can also cause potential environmental risk. In this paper, we studied the long-term fertilizer experiment (started 1980) to assess the soil P dynamic, balance, critical P value and the crop yield response in Taihu Lake region, China. To avoid the effect of nitrogen (N) and potassium (K), only the folowing treatments were chosen for subsequent discussion, including: C0 (control treatment without any fertilizer or organic manure), CNK treatment (mineral N and K only), CNPK (balanced fertilization with mineral N, P and K), MNK (integrated organic ma-nure and mineral N and K), and MNPK (organic manure plus balanced fertilization). The results revealed that the response of wheat yield was more sensitive than rice, and no signiifcant differences of crop yield had been detected among MNK, CNPK and MNPK until 2013. Dynamic and balance of soil total P (TP) and Olsen-P showed soil TP pool was enlarged signiifcantly over consistent fertilization. However, the diminishing marginal utility of soil Olsen-P was also found, indicating that high-level P application in the present condition could not increase soil Olsen-P contents anymore. Linear-linear and Mitscherlich models were used to estimate the critical value of Olsen-P for crops. The average critical P value for rice and wheat was 3.40 and 4.08 mg kg–1, respectively. The smaler critical P value than in uplands indicated a stronger ability of P supply for crops in this paddy soil. We concluded that no more mineral P should be applied in rice-wheat system in Taihu Lake region if soil Olsen-P is higher than the critical P value. The agricultural technique and management referring to acti-vate the plant-available P pool are also considerable, such as integrated use of low-P organic manure with mineral N and K.

  12. Submicroscopic deletions of 11q24-25 in individuals without Jacobsen syndrome: re-examination of the critical region by high-resolution array-CGH

    Directory of Open Access Journals (Sweden)

    VanAllen Margot I

    2008-11-01

    individuals with ID who did not have the typical clinical features of Jacobsen syndrome were found to have deletions within the JBS region at 11q24-25. Their rearrangements facilitate the refinement of the JBS critical region and suggest that a deletion of at least 3 of the 4 platelet function critical genes (ETS-1, FLI-1 and NFRKB and JAM3 is necessary for thrombocytopenia; b one of the critical regions for heart abnormalities (conotruncal heart defects may lie within 129.03 – 130.6 Mb; c deletions of KCNJ1 and ADAMTS15 may contribute to the renal anomalies in Jacobsen Syndrome; d the critical region for MRI abnormalities involves a region from 124.6 – 129.03 Mb. Our results reiterate the benefits of array-CGH for description of new phenotype/genotype associations and refinement of previously established ones.

  13. Expression of. Arabidopsis tryptophan biosynthetic pathway genes: effect of the 5’ coding region of phosphoribosylanthranilate isomerase gene

    Institute of Scientific and Technical Information of China (English)

    何奕昆; 刘新仿; 李家洋

    1999-01-01

    There are three non-allelic isogenes encoding phosphoribosylanthranilate isomerase (PAI) in Arabidopsis thaliana. The expression plasmids were constructed by fusion of the GUS reporter gene to the three PAI promoters with or without the 5’ region encoding PAI N-terminal polypeptides and transferred into Arabidopsis plants by Agrobacterium tumefaciens. Analysis of GUS activity revealed that the PAI 5’ coding region was necessary for high expression of GUS activity. GUS activity in transgenic plants transformed with the expression plasmids containing the 5’ coding region of PAI1 or PAI3 was 60—100-fold higher than that without the corresponding 5’ region. However, the effect of 5’ coding region of PAI2 gene on the GUS activity was very small (only about 1 time difference). The GUS histochemical staining showed a similar result as revealed by GUS activity assay. It was expressed in the mesophyll cells and guard cells, but not in the epidermic cells, indicating that the N-terminal polypeptides encoded by t

  14. Genetic interactions between Shox2 and Hox genes during the regional growth and development of the mouse limb.

    Science.gov (United States)

    Neufeld, Stanley J; Wang, Fan; Cobb, John

    2014-11-01

    The growth and development of the vertebrate limb relies on homeobox genes of the Hox and Shox families, with their independent mutation often giving dose-dependent effects. Here we investigate whether Shox2 and Hox genes function together during mouse limb development by modulating their relative dosage and examining the limb for nonadditive effects on growth. Using double mRNA fluorescence in situ hybridization (FISH) in single embryos, we first show that Shox2 and Hox genes have associated spatial expression dynamics, with Shox2 expression restricted to the proximal limb along with Hoxd9 and Hoxa11 expression, juxtaposing the distal expression of Hoxa13 and Hoxd13. By generating mice with all possible dosage combinations of mutant Shox2 alleles and HoxA/D cluster deletions, we then show that their coordinated proximal limb expression is critical to generate normally proportioned limb segments. These epistatic interactions tune limb length, where Shox2 underexpression enhances, and Shox2 overexpression suppresses, Hox-mutant phenotypes. Disruption of either Shox2 or Hox genes leads to a similar reduction in Runx2 expression in the developing humerus, suggesting their concerted action drives cartilage maturation during normal development. While we furthermore provide evidence that Hox gene function influences Shox2 expression, this regulation is limited in extent and is unlikely on its own to be a major explanation for their genetic interaction. Given the similar effect of human SHOX mutations on regional limb growth, Shox and Hox genes may generally function as genetic interaction partners during the growth and development of the proximal vertebrate limb.

  15. Core and region-enriched networks of behaviorally regulated genes and the singing genome

    Science.gov (United States)

    Whitney, Osceola; Pfenning, Andreas R.; Howard, Jason T.; Blatti, Charles A; Liu, Fang; Ward, James M.; Wang, Rui; Audet, Jean-Nicolas; Kellis, Manolis; Mukherjee, Sayan; Sinha, Saurabh; Hartemink, Alexander J.; West, Anne E.; Jarvis, Erich D.

    2015-01-01

    Songbirds represent an important model organism for elucidating molecular mechanisms that link genes with complex behaviors, in part because they have discrete vocal learning circuits that have parallels with those that mediate human speech. We found that ~10% of the genes in the avian genome were regulated by singing, and we found a striking regional diversity of both basal and singing-induced programs in the four key song nuclei of the zebra finch, a vocal learning songbird. The region-enriched patterns were a result of distinct combinations of region-enriched transcription factors (TFs), their binding motifs, and presinging acetylation of histone 3 at lysine 27 (H3K27ac) enhancer activity in the regulatory regions of the associated genes. RNA interference manipulations validated the role of the calcium-response transcription factor (CaRF) in regulating genes preferentially expressed in specific song nuclei in response to singing. Thus, differential combinatorial binding of a small group of activity-regulated TFs and predefined epigenetic enhancer activity influences the anatomical diversity of behaviorally regulated gene networks. PMID:25504732

  16. Hypermethylation of Syk gene in promoter region associated with oncogenesis and metastasis of gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Shui Wang; Yong-Bin Ding; Guo-Yu Chen; Jian-Guo Xia; Zhen-Yan Wu

    2004-01-01

    AIM: To investigate the rrelationship between methylation of Syk (spleen tyrosine kinase) gene in promoter region and oncogenesis, metastasis of gastric carcinoma. The relation between silencing of the Syk gene and methylation of Syk promoter region was also studied.METHODS: By using methylation-specific PCR (MSP)technique, the methylation of Syk promoter region in specimens from 61 gastric cancer patients (tumor tissues and adjacent normal tissues) was detected. Meanwhile, RTPCR was used to analyse syk expression exclusively.RESULTS: The expression of the Syk gene was detected in all normal gastric tissues. Syk expression in gastric carcinoma was lower in 14 out of 61 gastric cancer samples than in adjacent normal tissues (x2=72.3, P<0.05). No methylation of Syk promoter was found in adjacent normal tissues, hypermethylation of Syk gene in promoter was detected 21 cases in 61 gastric carcinoma patients. The rate of methylation of Syk promoter in gastric carcinoma was higher than that in adjacent normal tissues (x2=25.1,P<0.05). In 31 patients with lymph node metastasis, 17 were found with Syk promoter methylation. A significant difference was noted between two groups (x2=11.4, P<0.05).CONCLUSION: Hypermethylation leads to silencing of the Syk gene in human gastric carcinoma. Methylation of Syk promoter is correlated to oncogenesis and metastasis of gastric carcinoma. Syk is considered to be a potential tumor suppressor and anti-metastasis gene in human gastric cancer.

  17. Conserved gene arrangement in the origin region of the Streptomyces coelicolor chromosome.

    OpenAIRE

    1992-01-01

    A 23-kb fragment of the Streptomyces coelicolor chromosome spanning the dnaA region has been isolated as a cosmid clone. Nucleotide sequence analysis of a 5-kb portion shows that the genes for the RNase P protein (rnpA), ribosomal protein L34 (rpmH), the replication initiator protein (dnaA), and the beta subunit of DNA polymerase III (dnaN) are present in the highly conserved gene arrangement found in all eubacterial genomes studied so far. The dnaA-dnaN intergenic region is approximately 1 k...

  18. Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development.

    Directory of Open Access Journals (Sweden)

    Gunnar R Mair

    2010-02-01

    Full Text Available A universal feature of metazoan sexual development is the generation of oocyte P granules that withhold certain mRNA species from translation to provide coding potential for proteins during early post-fertilization development. Stabilisation of translationally quiescent mRNA pools in female Plasmodium gametocytes depends on the RNA helicase DOZI, but the molecular machinery involved in the silencing of transcripts in these protozoans is unknown. Using affinity purification coupled with mass-spectrometric analysis we identify a messenger ribonucleoprotein (mRNP from Plasmodium berghei gametocytes defined by DOZI and the Sm-like factor CITH (homolog of worm CAR-I and fly Trailer Hitch. This mRNP includes 16 major factors, including proteins with homologies to components of metazoan P granules and archaeal proteins. Containing translationally silent transcripts, this mRNP integrates eIF4E and poly(A-binding protein but excludes P body RNA degradation factors and translation-initiation promoting eIF4G. Gene deletion mutants of 2 core components of this mRNP (DOZI and CITH are fertilization-competent, but zygotes fail to develop into ookinetes in a female gametocyte-mutant fashion. Through RNA-immunoprecipitation and global expression profiling of CITH-KO mutants we highlight CITH as a crucial repressor of maternally supplied mRNAs. Our data define Plasmodium P granules as an ancient mRNP whose protein core has remained evolutionarily conserved from single-cell organisms to germ cells of multi-cellular animals and stores translationally silent mRNAs that are critical for early post-fertilization development during the initial stages of mosquito infection. Therefore, translational repression may offer avenues as a target for the generation of transmission blocking strategies and contribute to limiting the spread of malaria.

  19. Expression profile of critical genes involved in FGF signaling pathway in the developing human primary dentition.

    Science.gov (United States)

    Huang, Feng; Hu, Xiaoxiao; Fang, Chunni; Liu, Hong; Lin, Chensheng; Zhang, Yanding; Hu, Xuefeng

    2015-11-01

    Mammalian tooth development is regulated by paracrine signal molecules of several conserved family interactions between epithelium and mesenchyme. The expression patterns and regulative roles of FGF signaling have been extensively studied in the mouse odontogenesis; however, that is not well known in human tooth development. In order to unveil the molecular mechanisms that regulate human tooth morphogenesis, we examined the expression patterns of the critical molecules involved in FGF signaling pathway in the developing human tooth germ by in situ hybridization, immunohistochemistry, and real-time RT-PCR, including FGF ligands, receptors, and intracellular transducer. We found overlapping but distinct expression pattern of FGF ligands and receptors in the different stages and components. Expression of FGF4, FGF7, FGF8, and FGF9 persists widespread in human tooth mesenchyme, which is quite different to that of in mouse. FGFR1 may be the major receptor in regulate mechanisms of FGF signals in human tooth development. Real-time RT-PCR indeed confirmed the results of in situ hybridization. Results of K-Ras, p-ERK1/2, p-p38, p-JNK, and p-PDK1 expression reveal spatial and temporal patterns of FGF signaling during morphogenesis and organogenesis of human tooth germ. Activity of the FGF signaling transducer protein in human tooth germ was much higher than that of in mouse. Our results provided important FGF singling information in the developing process, pinpoint to the domains where the downstream target genes of FGF signaling can be sought, and enlightened our knowledge about the nature of FGF signaling in human tooth germ.

  20. The critical role of RNA processing and degradation in the control of gene expression.

    Science.gov (United States)

    Arraiano, Cecília M; Andrade, José M; Domingues, Susana; Guinote, Inês B; Malecki, Michal; Matos, Rute G; Moreira, Ricardo N; Pobre, Vânia; Reis, Filipa P; Saramago, Margarida; Silva, Inês J; Viegas, Sandra C

    2010-09-01

    The continuous degradation and synthesis of prokaryotic mRNAs not only give rise to the metabolic changes that are required as cells grow and divide but also rapid adaptation to new environmental conditions. In bacteria, RNAs can be degraded by mechanisms that act independently, but in parallel, and that target different sites with different efficiencies. The accessibility of sites for degradation depends on several factors, including RNA higher-order structure, protection by translating ribosomes and polyadenylation status. Furthermore, RNA degradation mechanisms have shown to be determinant for the post-transcriptional control of gene expression. RNases mediate the processing, decay and quality control of RNA. RNases can be divided into endonucleases that cleave the RNA internally or exonucleases that cleave the RNA from one of the extremities. Just in Escherichia coli there are >20 different RNases. RNase E is a single-strand-specific endonuclease critical for mRNA decay in E. coli. The enzyme interacts with the exonuclease polynucleotide phosphorylase (PNPase), enolase and RNA helicase B (RhlB) to form the degradosome. However, in Bacillus subtilis, this enzyme is absent, but it has other main endonucleases such as RNase J1 and RNase III. RNase III cleaves double-stranded RNA and family members are involved in RNA interference in eukaryotes. RNase II family members are ubiquitous exonucleases, and in eukaryotes, they can act as the catalytic subunit of the exosome. RNases act in different pathways to execute the maturation of rRNAs and tRNAs, and intervene in the decay of many different mRNAs and small noncoding RNAs. In general, RNases act as a global regulatory network extremely important for the regulation of RNA levels.

  1. Gas Bearing Control for Safe Operation in Critical Speed Regions - Experimental Verification

    DEFF Research Database (Denmark)

    Theisen, Lukas R. S.; Niemann, Hans H.; Galeazzi, Roberto

    2015-01-01

    Gas bearings are popular for their high speed capabilities, low friction and clean operation, but require low clearances and suffer from poor damping properties. The poor damping properties cause high disturbance amplification near the natural frequencies. These become critical when the rotation...... supported by gas bearings to extend their operating range. Using H∞-design methods, active lubrication techniques are proposed to enhance the damping, which in turn reduces the vibrations to a desired safe level. The control design is validated experimentally on a laboratory test rig, and shown to allow...

  2. Sequencing of 15 622 gene-bearing BACs clarifies the gene-dense regions of the barley genome.

    Science.gov (United States)

    Muñoz-Amatriaín, María; Lonardi, Stefano; Luo, MingCheng; Madishetty, Kavitha; Svensson, Jan T; Moscou, Matthew J; Wanamaker, Steve; Jiang, Tao; Kleinhofs, Andris; Muehlbauer, Gary J; Wise, Roger P; Stein, Nils; Ma, Yaqin; Rodriguez, Edmundo; Kudrna, Dave; Bhat, Prasanna R; Chao, Shiaoman; Condamine, Pascal; Heinen, Shane; Resnik, Josh; Wing, Rod; Witt, Heather N; Alpert, Matthew; Beccuti, Marco; Bozdag, Serdar; Cordero, Francesca; Mirebrahim, Hamid; Ounit, Rachid; Wu, Yonghui; You, Frank; Zheng, Jie; Simková, Hana; Dolezel, Jaroslav; Grimwood, Jane; Schmutz, Jeremy; Duma, Denisa; Altschmied, Lothar; Blake, Tom; Bregitzer, Phil; Cooper, Laurel; Dilbirligi, Muharrem; Falk, Anders; Feiz, Leila; Graner, Andreas; Gustafson, Perry; Hayes, Patrick M; Lemaux, Peggy; Mammadov, Jafar; Close, Timothy J

    2015-10-01

    Barley (Hordeum vulgare L.) possesses a large and highly repetitive genome of 5.1 Gb that has hindered the development of a complete sequence. In 2012, the International Barley Sequencing Consortium released a resource integrating whole-genome shotgun sequences with a physical and genetic framework. However, because only 6278 bacterial artificial chromosome (BACs) in the physical map were sequenced, fine structure was limited. To gain access to the gene-containing portion of the barley genome at high resolution, we identified and sequenced 15 622 BACs representing the minimal tiling path of 72 052 physical-mapped gene-bearing BACs. This generated ~1.7 Gb of genomic sequence containing an estimated 2/3 of all Morex barley genes. Exploration of these sequenced BACs revealed that although distal ends of chromosomes contain most of the gene-enriched BACs and are characterized by high recombination rates, there are also gene-dense regions with suppressed recombination. We made use of published map-anchored sequence data from Aegilops tauschii to develop a synteny viewer between barley and the ancestor of the wheat D-genome. Except for some notable inversions, there is a high level of collinearity between the two species. The software HarvEST:Barley provides facile access to BAC sequences and their annotations, along with the barley-Ae. tauschii synteny viewer. These BAC sequences constitute a resource to improve the efficiency of marker development, map-based cloning, and comparative genomics in barley and related crops. Additional knowledge about regions of the barley genome that are gene-dense but low recombination is particularly relevant.

  3. A new PKLR gene mutation in the R-type promoter region affects the gene transcription causing pyruvate kinase deficiency.

    Science.gov (United States)

    Manco, L; Ribeiro, M L; Máximo, V; Almeida, H; Costa, A; Freitas, O; Barbot, J; Abade, A; Tamagnini, G

    2000-09-01

    Mutations in the PKLR gene responsible for pyruvate kinase (PK)-deficient anaemia are mainly located in the coding regions: 11 are in the splicing sites and, recently, three mutations have been described in the promoter region. We now report a novel point mutation A-->G on nucleotide 72, upstream from the initiation codon of the PKLR gene, in four Portuguese PK-deficient patients. This new regulatory mutation occurs within the most proximal of the four GATA motifs (GATA-A element) in the R-type promoter region. In two patients who were homozygous for this mutation, a semiquantitative reverse transcription polymerase chain reaction (PCR) procedure was used to evaluate the amount of R-PK mRNA transcript in the reticulocytes. The mRNA level was about five times lower than in normal controls, demonstrating that the PKLR gene transcription is severely affected, most probably because the -72A-->G point mutation disables the binding of the erythroid transcription factor GATA-1 to the GATA-A element. Supporting these data, the two patients homozygous for the -72A-->G mutation had severe haemolytic anaemia and were transfusion dependent until splenectomy. Two other patients who were compound heterozygous for this mutation and the previously described missense mutation 1456C-->T had a mild condition.

  4. Analysis of spatial-temporal gene expression patterns reveals dynamics and regionalization in developing mouse brain.

    Science.gov (United States)

    Chou, Shen-Ju; Wang, Chindi; Sintupisut, Nardnisa; Niou, Zhen-Xian; Lin, Chih-Hsu; Li, Ker-Chau; Yeang, Chen-Hsiang

    2016-01-20

    Allen Brain Atlas (ABA) provides a valuable resource of spatial/temporal gene expressions in mammalian brains. Despite rich information extracted from this database, current analyses suffer from several limitations. First, most studies are either gene-centric or region-centric, thus are inadequate to capture the superposition of multiple spatial-temporal patterns. Second, standard tools of expression analysis such as matrix factorization can capture those patterns but do not explicitly incorporate spatial dependency. To overcome those limitations, we proposed a computational method to detect recurrent patterns in the spatial-temporal gene expression data of developing mouse brains. We demonstrated that regional distinction in brain development could be revealed by localized gene expression patterns. The patterns expressed in the forebrain, medullary and pontomedullary, and basal ganglia are enriched with genes involved in forebrain development, locomotory behavior, and dopamine metabolism respectively. In addition, the timing of global gene expression patterns reflects the general trends of molecular events in mouse brain development. Furthermore, we validated functional implications of the inferred patterns by showing genes sharing similar spatial-temporal expression patterns with Lhx2 exhibited differential expression in the embryonic forebrains of Lhx2 mutant mice. These analysis outcomes confirm the utility of recurrent expression patterns in studying brain development.

  5. Linkage disequilibrium in the region of the autosomal dominant polycystic kidney disease gene (PKD1)

    Energy Technology Data Exchange (ETDEWEB)

    Snarey, A. (Imperial Cancer Research Fund, London (United Kingdom)); Thomas, S.; Harris, P.C. (Institute of Molecular Medicine, Oxford (United Kingdom)); Schneider, M.C. (Brigham and Women' s Hospital, Boston, MA (United States)); Pound, S.E.; Wright, A.F. (Western General Hospital, Edinburgh (United Kingdom)); Barton, N.; Somlo, S.; Germino, G.G.; Reeders, S.T. (and others)

    1994-08-01

    The gene for autosomal dominant polycystic kidney disease (PKD1) is located on chromosome 16p, between the flanking markers D16S84 and D16S125 (26.6 prox). This region is 750 kb long and has been cloned. The authors have looked at the association of 10 polymorphic markers from the region, with the disease and with each other. This was done in a set of Scottish families that had previously shown association with D16S94, a marker proximal to the PKD1 region. They report significant association between two CA repeat markers and the disease but have not found evidence for a single founder haplotype in these families, indicating the presence of several mutations in this population. Their results favor a location of the PKD1 gene in the proximal part of the candidate region. 25 refs., 1 fig., 4 tabs.

  6. Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni

    Science.gov (United States)

    Anderson, Letícia; Gomes, Monete Rajão; daSilva, Lucas Ferreira; Pereira, Adriana da Silva Andrade; Mourão, Marina M.; Romier, Christophe; Pierce, Raymond

    2017-01-01

    Background Schistosomiasis is a parasitic disease infecting hundreds of millions of people worldwide. Treatment depends on a single drug, praziquantel, which kills the Schistosoma spp. parasite only at the adult stage. HDAC inhibitors (HDACi) such as Trichostatin A (TSA) induce parasite mortality in vitro (schistosomula and adult worms), however the downstream effects of histone hyperacetylation on the parasite are not known. Methodology/Principal findings TSA treatment of adult worms in vitro increased histone acetylation at H3K9ac and H3K14ac, which are transcription activation marks, not affecting the unrelated transcription repression mark H3K27me3. We investigated the effect of TSA HDACi on schistosomula gene expression at three different time points, finding a marked genome-wide change in the transcriptome profile. Gene transcription activity was correlated with changes on the chromatin acetylation mark at gene promoter regions. Moreover, combining expression data with ChIP-Seq public data for schistosomula, we found that differentially expressed genes having the H3K4me3 mark at their promoter region in general showed transcription activation upon HDACi treatment, compared with those without the mark, which showed transcription down-regulation. Affected genes are enriched for DNA replication processes, most of them being up-regulated. Twenty out of 22 genes encoding proteins involved in reducing reactive oxygen species accumulation were down-regulated. Dozens of genes encoding proteins with histone reader motifs were changed, including SmEED from the PRC2 complex. We targeted SmEZH2 methyltransferase PRC2 component with a new EZH2 inhibitor (GSK343) and showed a synergistic effect with TSA, significantly increasing schistosomula mortality. Conclusions/Significance Genome-wide gene expression analyses have identified important pathways and cellular functions that were affected and may explain the schistosomicidal effect of TSA HDACi. The change in expression

  7. The Gesneriaceae of Guiana. A critical revision with notes on species from Adjacent Regions

    NARCIS (Netherlands)

    Leeuwenberg, A.J.M.

    1958-01-01

    The present study was started as a revision of the Gesneriaceae of Suriname (Dutch Guiana). As it proved to be impossible to solve the taxonomic problems on the base of the scanty material from that country only and as the region of the three Guianas inclusive of the Brazilian territory “Amapá” and

  8. Applying Critical Discourse Analysis in Health Policy Research: Case Studies in Regional, Organizational, and Global Health.

    Science.gov (United States)

    Evans-Agnew, Robin A; Johnson, Susan; Liu, Fuqin; Boutain, Doris M

    2016-08-01

    Critical discourse analysis (CDA) is a promising methodology for policy research in nursing. As a critical theoretical methodology, researchers use CDA to analyze social practices and language use in policies to examine whether such policies may promote or impede social transformation. Despite the widespread use of CDA in other disciplines such as education and sociology, nursing policy research employing CDA methodology is sparse. To advance CDA use in nursing science, it is important to outline the overall research strategies and describe the steps of CDA in policy research. This article describes, using exemplar case studies, how nursing and health policy researchers can employ CDA as a methodology. Three case studies are provided to discuss the application of CDA research methodologies in nursing policy research: (a) implementation of preconception care policies in the Zhejiang province of China, (b) formation and enactment of statewide asthma policy in Washington state of the United States, and (c) organizational implementation of employee antibullying policies in hospital systems in the Pacific Northwest of the United States. Each exemplar details how CDA guided the examination of policy within specific contexts and social practices. The variations of the CDA approaches in the three exemplars demonstrated the flexibilities and potentials for conducting policy research grounded in CDA. CDA provides novel insights for nurse researchers examining health policy formation, enactment, and implementation. © The Author(s) 2016.

  9. Potential transcriptional regulatory regions exist upstream of the human ezrin gene promoter in esophageal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Shuying Gao; Yanpeng Dai; Meijun Yin; Jing Ye; Gang Li; Jie Yu

    2011-01-01

    We previously demonstrated that the region -87/+ 134 of the human ezrin gene (VIL2) exhibited promoter activity in human esophageal carcinoma EC109 cells, and a further upstream region -1324/-890 positively regulated transcription.In this study, to identify the transcriptional regulatory regions upstream of the VIL2 promoter, we cloned VIL2 - 1541/- 706 segment containing the -1324/-890, and investigated its transcriptional regulatory properties via luciferase assays in transiently transfected cells.In EC109 cells, it was found that VIL2 -1541/-706 possessed promoter and enhancer activities.We also localized transcriptional regulatory regions by fusing 5′- or 3′-deletion segments of VIL2 -1541/-706 to a luciferase reporter.We found that there were three positive and one negative transcriptional regulatory regions ithin VIL2 -1541/-706 in EC109 cells.When these regions were separately located upstream of the luciferase gene without promoter, or located upstream of the VIL2 promoter or SV40 promoter directing the luciferase gene, only VIL2 -1297/-1186 exhibited considerable promoter and enhancer activities, which were lower than those of -1541/-706.In addition, transient expression of Sp1 increased ezrin expression and the transcriptional activation of VIL2 -1297/-1186.Other three regions,although exhibiting significantly positive or negative transcriptional regulation in deletion experiments, showed a weaker or absent regulation.These data suggested that more than one region upstream of the VIL2 promoter participated in VIL2 transcription, and the VIL2 -1297/-1186, probably as a key transcriptional regulatory region, regulated VIL2 transcription in company with other potential regulatory regions.

  10. Probing the critical behavior in the evolution of GDR width at very low temperatures in A∼100 mass region

    Energy Technology Data Exchange (ETDEWEB)

    Dey, Balaram; Mondal, Debasish; Pandit, Deepak; Mukhopadhyay, S.; Pal, Surajit [Variable Energy Cyclotron Centre, 1/AF-Bidhannagar, Kolkata 700064 (India); Bhattacharya, Srijit [Department of Physics, Barasat Govt. College, Barasat, N 24 Pgs, Kolkata 700124 (India); De, A. [Department of Physics, Raniganj Girls' College, Raniganj 713358 (India); Banerjee, K. [Variable Energy Cyclotron Centre, 1/AF-Bidhannagar, Kolkata 700064 (India); Dinh Dang, N. [Theoretical Nuclear Physics Laboratory, RIKEN Nishina Center for Accelerator-Based Science, RIKEN, 2-1 Hirosawa, Wako city, Saitama 351-0198 (Japan); Quang Hung, N. [School of Engineering, Tan Tao University, Tan Tao University Avenue, Tan Duc Ecity, Duc Hoa, Long An Province (Viet Nam); Banerjee, S.R., E-mail: srb@vecc.gov.in [Variable Energy Cyclotron Centre, 1/AF-Bidhannagar, Kolkata 700064 (India)

    2014-04-04

    The influence of giant dipole resonance (GDR) induced quadrupole moment on GDR width at low temperatures is investigated experimentally by measuring GDR width systematically in the unexplored temperature range T=0.8–1.5 MeV, for the first time, in A∼100 mass region. The measured GDR widths, using alpha induced fusion reaction, for {sup 97}Tc confirm that the GDR width remains constant at the ground state value up to a critical temperature and increases sharply thereafter with increase in T. The data have been compared with the adiabatic Thermal Shape Fluctuation Model (TSFM), phenomenological Critical Temperature Fluctuation Model (CTFM) and microscopic Phonon Damping Model (PDM). Interestingly, CTFM and PDM give similar results and agree with the data, whereas the TSFM differs significantly even after incorporating the shell effects.

  11. Global Gene-Expression Analysis to Identify Differentially Expressed Genes Critical for the Heat Stress Response in Brassica rapa.

    Science.gov (United States)

    Dong, Xiangshu; Yi, Hankuil; Lee, Jeongyeo; Nou, Ill-Sup; Han, Ching-Tack; Hur, Yoonkang

    2015-01-01

    Genome-wide dissection of the heat stress response (HSR) is necessary to overcome problems in crop production caused by global warming. To identify HSR genes, we profiled gene expression in two Chinese cabbage inbred lines with different thermotolerances, Chiifu and Kenshin. Many genes exhibited >2-fold changes in expression upon exposure to 0.5- 4 h at 45°C (high temperature, HT): 5.2% (2,142 genes) in Chiifu and 3.7% (1,535 genes) in Kenshin. The most enriched GO (Gene Ontology) items included 'response to heat', 'response to reactive oxygen species (ROS)', 'response to temperature stimulus', 'response to abiotic stimulus', and 'MAPKKK cascade'. In both lines, the genes most highly induced by HT encoded small heat shock proteins (Hsps) and heat shock factor (Hsf)-like proteins such as HsfB2A (Bra029292), whereas high-molecular weight Hsps were constitutively expressed. Other upstream HSR components were also up-regulated: ROS-scavenging genes like glutathione peroxidase 2 (BrGPX2, Bra022853), protein kinases, and phosphatases. Among heat stress (HS) marker genes in Arabidopsis, only exportin 1A (XPO1A) (Bra008580, Bra006382) can be applied to B. rapa for basal thermotolerance (BT) and short-term acquired thermotolerance (SAT) gene. CYP707A3 (Bra025083, Bra021965), which is involved in the dehydration response in Arabidopsis, was associated with membrane leakage in both lines following HS. Although many transcription factors (TF) genes, including DREB2A (Bra005852), were involved in HS tolerance in both lines, Bra024224 (MYB41) and Bra021735 (a bZIP/AIR1 [Anthocyanin-Impaired-Response-1]) were specific to Kenshin. Several candidate TFs involved in thermotolerance were confirmed as HSR genes by real-time PCR, and these assignments were further supported by promoter analysis. Although some of our findings are similar to those obtained using other plant species, clear differences in Brassica rapa reveal a distinct HSR in this species. Our data could also provide a

  12. Invasive candidiasis in non neutropenic critically ill - need for region-specific management guidelines.

    Science.gov (United States)

    Ahmed, Armin; Azim, Afzal; Baronia, A K; Marak, Rungmei S K; Gurjar, Mohan

    2015-06-01

    Use of antifungal agents has increased over past few decades. A number of risk factors such as immunosuppression, broad spectrum antibiotics, dialysis, pancreatitis, surgery, etc., have been linked with the increased risk of invasive candidiasis. Though there are various guidelines available for the use of antifungal therapy, local/regional epidemiology plays an important role in determining the appropriate choice of agent in situations where the offending organism is not known (i.e. empirical, prophylactic or preemptive therapy). Developing countries like India need to generate their own epidemiological data to facilitate appropriate use of antifungal therapy. In this article, the authors have highlighted the need for region-specific policies/guidelines for treatment of invasive candidiasis. Currently available Indian literature on candidemia epidemiology has also been summarized here.

  13. Invasive candidiasis in non neutropenic critically ill - need for region-specific management guidelines

    Directory of Open Access Journals (Sweden)

    Armin Ahmed

    2015-01-01

    Full Text Available Use of antifungal agents has increased over past few decades. A number of risk factors such as immunosuppression, broad spectrum antibiotics, dialysis, pancreatitis, surgery, etc., have been linked with the increased risk of invasive candidiasis. Though there are various guidelines available for the use of antifungal therapy, local/regional epidemiology plays an important role in determining the appropriate choice of agent in situations where the offending organism is not known (i.e. empirical, prophylactic or preemptive therapy. Developing countries like India need to generate their own epidemiological data to facilitate appropriate use of antifungal therapy. In this article, the authors have highlighted the need for region-specific policies/guidelines for treatment of invasive candidiasis. Currently available Indian literature on candidemia epidemiology has also been summarized here.

  14. Conserved charged amino acid residues in the extracellular region of sodium/iodide symporter are critical for iodide transport activity

    Directory of Open Access Journals (Sweden)

    Liang Ji-An

    2010-11-01

    Full Text Available Abstract Background Sodium/iodide symporter (NIS mediates the active transport and accumulation of iodide from the blood into the thyroid gland. His-226 located in the extracellular region of NIS has been demonstrated to be critical for iodide transport in our previous study. The conserved charged amino acid residues in the extracellular region of NIS were therefore characterized in this study. Methods Fourteen charged residues (Arg-9, Glu-79, Arg-82, Lys-86, Asp-163, His-226, Arg-228, Asp-233, Asp-237, Arg-239, Arg-241, Asp-311, Asp-322, and Asp-331 were replaced by alanine. Iodide uptake abilities of mutants were evaluated by steady-state and kinetic analysis. The three-dimensional comparative protein structure of NIS was further modeled using sodium/glucose transporter as the reference protein. Results All the NIS mutants were expressed normally in the cells and targeted correctly to the plasma membrane. However, these mutants, except R9A, displayed severe defects on the iodide uptake. Further kinetic analysis revealed that mutations at conserved positively charged amino acid residues in the extracellular region of NIS led to decrease NIS-mediated iodide uptake activity by reducing the maximal rate of iodide transport, while mutations at conserved negatively charged residues led to decrease iodide transport by increasing dissociation between NIS mutants and iodide. Conclusions This is the first report characterizing thoroughly the functional significance of conserved charged amino acid residues in the extracellular region of NIS. Our data suggested that conserved charged amino acid residues, except Arg-9, in the extracellular region of NIS were critical for iodide transport.

  15. Identification of conserved regions and residues within Hedgehog acyltransferase critical for palmitoylation of Sonic Hedgehog.

    Directory of Open Access Journals (Sweden)

    John A Buglino

    Full Text Available BACKGROUND: Sonic hedgehog (Shh is a palmitoylated protein that plays key roles in mammalian development and human cancers. Palmitoylation of Shh is required for effective long and short range Shh-mediated signaling. Attachment of palmitate to Shh is catalyzed by Hedgehog acyltransferase (Hhat, a member of the membrane bound O-acyl transferase (MBOAT family of multipass membrane proteins. The extremely hydrophobic composition of MBOAT proteins has limited their biochemical characterization. Except for mutagenesis of two conserved residues, there has been no structure-function analysis of Hhat, and the regions of the protein required for Shh palmitoylation are unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we undertake a systematic approach to identify residues within Hhat that are required for protein stability and/or enzymatic activity. We also identify a second, novel MBOAT homology region (residues 196-234 that is required for Hhat activity. In total, ten deletion mutants and eleven point mutants were generated and analyzed. Truncations at the N- and C-termini of Hhat yielded inactive proteins with reduced stability. Four Hhat mutants with deletions within predicted loop regions and five point mutants retained stability but lost palmitoylation activity. We purified two point mutants, W378A and H379A, with defective Hhat activity. Kinetic analyses revealed alterations in apparent K(m and V(max for Shh and/or palmitoyl CoA, changes that likely explain the catalytic defects observed for these mutants. CONCLUSIONS/SIGNIFICANCE: This study has pinpointed specific regions and multiple residues that regulate Hhat stability and catalysis. Our findings should be applicable to other MBOAT proteins that mediate lipid modification of Wnt proteins and ghrelin, and should serve as a model for understanding how secreted morphogens are modified by palmitoyl acyltransferases.

  16. Critical strain region evaluation of self-assembled semiconductor quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Sales, D L [Departamento de Ciencia de los Materiales e I. M. y Q. I., Universidad de Cadiz, Puerto Real, Cadiz (Spain); Pizarro, J [Departamento de Lenguajes y Sistemas Informaticos, Universidad de Cadiz, Puerto Real, Cadiz (Spain); Galindo, P L [Departamento de Lenguajes y Sistemas Informaticos, Universidad de Cadiz, Puerto Real, Cadiz (Spain); Garcia, R [Departamento de Ciencia de los Materiales e I. M. y Q. I., Universidad de Cadiz, Puerto Real, Cadiz (Spain); Trevisi, G [CNR-IMEM Institute, Parco delle Scienze 37a, 43100, Parma (Italy); Frigeri, P [CNR-IMEM Institute, Parco delle Scienze 37a, 43100, Parma (Italy); Nasi, L [CNR-IMEM Institute, Parco delle Scienze 37a, 43100, Parma (Italy); Franchi, S [CNR-IMEM Institute, Parco delle Scienze 37a, 43100, Parma (Italy); Molina, S I [Departamento de Ciencia de los Materiales e I. M. y Q. I., Universidad de Cadiz, Puerto Real, Cadiz (Spain)

    2007-11-28

    A novel peak finding method to map the strain from high resolution transmission electron micrographs, known as the Peak Pairs method, has been applied to In(Ga)As/AlGaAs quantum dot (QD) samples, which present stacking faults emerging from the QD edges. Moreover, strain distribution has been simulated by the finite element method applying the elastic theory on a 3D QD model. The agreement existing between determined and simulated strain values reveals that these techniques are consistent enough to qualitatively characterize the strain distribution of nanostructured materials. The correct application of both methods allows the localization of critical strain zones in semiconductor QDs, predicting the nucleation of defects, and being a very useful tool for the design of semiconductor devices.

  17. Genetic organisation of the capsule transport gene region from Haemophilus paragallinarum

    Directory of Open Access Journals (Sweden)

    O. De Smidt

    2004-11-01

    Full Text Available The region involved in export of the capsule polysaccharides to the cell surface of Haemophilus paragallinarum was cloned and the genetic organisation determined. Degenerate primers designed from sequence alignment of the capsule transport genes of Haemophilus influenzae, Pasteurella multocida and Actinobacillus pleuropneumoniae were used to amplify a 2.6 kb fragment containing a segment of the H. paragallinarum capsule transport gene locus. This fragment was used as a digoxigenin labelled probe to isolate the complete H. paragallinarum capsule transport gene locus from genomic DNA. The sequence of the cloned DNA was determined and analysis revealed the presence of four genes, each showing high homology with known capsule transport genes. The four genes were designated hctA, B, C and D (for H. paragallinarum capsule transport genes and the predicted products of these genes likely encode an ATP-dependent export system responsible for transport of the capsule polysaccharides to the cell surface, possibly a member of a super family designated ABC (ATP-binding cassette transporters.

  18. Characterization of the Helicoverpa assulta nucleopolyhedrovirus genome and sequence analysis of the polyhedrin gene region

    Indian Academy of Sciences (India)

    Soo-Dong Woo; Jae Young Choi; Yeon Ho Je; Byung Rae Jin

    2006-09-01

    A local strain of Helicoverpa assulta nucleopolyhedrovirus (HasNPV) was isolated from infected H. assulta larvae in Korea. Restriction endonuclease fragment analysis, using 4 restriction enzymes, estimated that the total genome size of HasNPV is about 138 kb. A degenerate polymerase chain reaction (PCR) primer set for the polyhedrin gene successfully amplified the partial polyhedrin gene of HasNPV. The sequencing results showed that the about 430 bp PCR product was a fragment of the corresponding polyhedrin gene. Using HasNPV partial predicted polyhedrin to probe the Southern blots, we identified the location of the polyhedrin gene within the 6 kb EcoRI, 15 kb NcoI, 20 kb XhoI, 17 kb BglII and 3 kb ClaI fragments, respectively. The 3 kb ClaI fragment was cloned and the nucleotide sequences of the polyhedrin coding region and its flaking regions were determined. Nucleotide sequence analysis indicated the presence of an open reading frame of 735 nucleotides which could encode 245 amino acids with a predicted molecular mass of 29 kDa. The nucleotide sequences within the coding region of HasNPV polyhedrin shared 73.7% identity with the polyhedrin gene from Autographa californica NPV but were most closely related to Helicoverpa and Heliothis species NPVs with over 99% sequence identity.

  19. A common deletion at D6S265 in the hemochromatosis gene region

    Energy Technology Data Exchange (ETDEWEB)

    Pyper, W.R.; Burt, M.J.; Powell, L.W. [Queensland Institute of Medical Research and Department of Medicine, Brisbane (Australia)] [and others

    1994-09-01

    Positional cloning of the hemochromatosis (HC) gene on chromosome 6p has utilized a number of highly polymorphic microsatellite markers. While the putative HC gene has been localized within 1 cM of HLA-A, definition of the genetic limits of the HC locus has been controversial. Isolation and characterization of additional markers within this region will enable construction of a physical map upon which the HC gene can located. D6S265 is one such microsatellite, physically mapped within 120 kb centromeric of HLA-A. Recombinant and linkage analysis of this dinucleotide repeat in 24 Australian families segregating for HC positioned D6S265 within 1 cM of the HC gene, while allele association analysis showed allele 1 to be significantly increased in HC patients ({chi}{sup 2}=41.4, p<0.001, RR=5.75). In 6 of the 24 HC families, a D6265 locus deletion was found to segregate with HLA-A25 and HLA-A26 alleles. The D6S265 locus deletion was not associated with expression of HC. This study enables us to exclude candidate HC genes from the deleted region involving D6S265, and gives further support for an area of instability in the HLA class I region.

  20. Sequence analysis of 21 genes located in the Kartagener syndrome linkage region on chromosome 15q.

    Science.gov (United States)

    Geremek, Maciej; Schoenmaker, Frederieke; Zietkiewicz, Ewa; Pogorzelski, Andrzej; Diehl, Scott; Wijmenga, Cisca; Witt, Michal

    2008-06-01

    Primary ciliary dyskinesia (PCD) is a rare genetic disorder, which shows extensive genetic heterogeneity and is mostly inherited in an autosomal recessive fashion. There are four genes with a proven pathogenetic role in PCD. DNAH5 and DNAI1 are involved in 28 and 10% of PCD cases, respectively, while two other genes, DNAH11 and TXNDC3, have been identified as causal in one PCD family each. We have previously identified a 3.5 cM (2.82 Mb) region on chromosome 15q linked to Kartagener syndrome (KS), a subtype of PCD characterized by the randomization of body organ positioning. We have now refined the KS candidate region to a 1.8 Mb segment containing 18 known genes. The coding regions of these genes and three neighboring genes were subjected to sequence analysis in seven KS probands, and we were able to identify 60 single nucleotide sequence variants, 35 of which resided in mRNA coding sequences. However, none of the variations alone could explain the occurrence of the disease in these patients.

  1. A Region-Based GeneSIS Segmentation Algorithm for the Classification of Remotely Sensed Images

    Directory of Open Access Journals (Sweden)

    Stelios K. Mylonas

    2015-03-01

    Full Text Available This paper proposes an object-based segmentation/classification scheme for remotely sensed images, based on a novel variant of the recently proposed Genetic Sequential Image Segmentation (GeneSIS algorithm. GeneSIS segments the image in an iterative manner, whereby at each iteration a single object is extracted via a genetic-based object extraction algorithm. Contrary to the previous pixel-based GeneSIS where the candidate objects to be extracted were evaluated through the fuzzy content of their included pixels, in the newly developed region-based GeneSIS algorithm, a watershed-driven fine segmentation map is initially obtained from the original image, which serves as the basis for the forthcoming GeneSIS segmentation. Furthermore, in order to enhance the spatial search capabilities, we introduce a more descriptive encoding scheme in the object extraction algorithm, where the structural search modules are represented by polygonal shapes. Our objectives in the new framework are posed as follows: enhance the flexibility of the algorithm in extracting more flexible object shapes, assure high level classification accuracies, and reduce the execution time of the segmentation, while at the same time preserving all the inherent attributes of the GeneSIS approach. Finally, exploiting the inherent attribute of GeneSIS to produce multiple segmentations, we also propose two segmentation fusion schemes that operate on the ensemble of segmentations generated by GeneSIS. Our approaches are tested on an urban and two agricultural images. The results show that region-based GeneSIS has considerably lower computational demands compared to the pixel-based one. Furthermore, the suggested methods achieve higher classification accuracies and good segmentation maps compared to a series of existing algorithms.

  2. Identification of 2 novel genes developmentally regulated in the mouse aorta-gonad-mesonephros region

    NARCIS (Netherlands)

    C. Orelio; E.A. Dzierzak (Elaine)

    2003-01-01

    textabstractThe first adult-repopulating hematopoietic stem cells (HSCs) emerge in the mouse aorta-gonad-mesonephros (AGM) region at embryonic day 10.5 prior to their appearance in the yolk sac and fetal liver. Although several genes are implicated in the regulation of HSCs, there

  3. The Rhodomonas salina mitochondrial genome: bacteria-like operons, compact gene arrangement and complex repeat region.

    Science.gov (United States)

    Hauth, Amy M; Maier, Uwe G; Lang, B Franz; Burger, Gertraud

    2005-01-01

    To gain insight into the mitochondrial genome structure and gene content of a putatively ancestral group of eukaryotes, the cryptophytes, we sequenced the complete mitochondrial DNA of Rhodomonas salina. The 48 063 bp circular-mapping molecule codes for 2 rRNAs, 27 tRNAs and 40 proteins including 23 components of oxidative phosphorylation, 15 ribosomal proteins and two subunits of tat translocase. One potential protein (ORF161) is without assigned function. Only two introns occur in the genome; both are present within cox1 belong to group II and contain RT open reading frames. Primitive genome features include bacteria-like rRNAs and tRNAs, ribosomal protein genes organized in large clusters resembling bacterial operons and the presence of the otherwise rare genes such as rps1 and tatA. The highly compact gene organization contrasts with the presence of a 4.7 kb long, repeat-containing intergenic region. Repeat motifs approximately 40-700 bp long occur up to 31 times, forming a complex repeat structure. Tandem repeats are the major arrangement but the region also includes a large, approximately 3 kb, inverted repeat and several potentially stable approximately 40-80 bp long hairpin structures. We provide evidence that the large repeat region is involved in replication and transcription initiation, predict a promoter motif that occurs in three locations and discuss two likely scenarios of how this highly structured repeat region might have evolved.

  4. The evolution of vertebrate somatostatin receptors and their gene regions involves extensive chromosomal rearrangements

    Directory of Open Access Journals (Sweden)

    Ocampo Daza Daniel

    2012-11-01

    Full Text Available Abstract Background Somatostatin and its related neuroendocrine peptides have a wide variety of physiological functions that are mediated by five somatostatin receptors with gene names SSTR1-5 in mammals. To resolve their evolution in vertebrates we have investigated the SSTR genes and a large number of adjacent gene families by phylogeny and conserved synteny analyses in a broad range of vertebrate species. Results We find that the SSTRs form two families that belong to distinct paralogons. We observe not only chromosomal similarities reflecting the paralogy relationships between the SSTR-bearing chromosome regions, but also extensive rearrangements between these regions in teleost fish genomes, including fusions and translocations followed by reshuffling through intrachromosomal rearrangements. These events obscure the paralogy relationships but are still tractable thanks to the many genomes now available. We have identified a previously unrecognized SSTR subtype, SSTR6, previously misidentified as either SSTR1 or SSTR4. Conclusions Two ancestral SSTR-bearing chromosome regions were duplicated in the two basal vertebrate tetraploidizations (2R. One of these ancestral SSTR genes generated SSTR2, -3 and -5, the other gave rise to SSTR1, -4 and -6. Subsequently SSTR6 was lost in tetrapods and SSTR4 in teleosts. Our study shows that extensive chromosomal rearrangements have taken place between related chromosome regions in teleosts, but that these events can be resolved by investigating several distantly related species.

  5. Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis

    Directory of Open Access Journals (Sweden)

    Mark Gerstein

    2013-07-01

    Full Text Available The West Nile virus (WNV is an emerging infection of biodefense concern and there are no available treatments or vaccines. Here we used a high-throughput method based on a novel gene expression analysis, RNA-Seq, to give a global picture of differential gene expression by primary human macrophages of 10 healthy donors infected in vitro with WNV. From a total of 28 million reads per sample, we identified 1,514 transcripts that were differentially expressed after infection. Both predicted and novel gene changes were detected, as were gene isoforms, and while many of the genes were expressed by all donors, some were unique. Knock-down of genes not previously known to be associated with WNV resistance identified their critical role in control of viral infection. Our study distinguishes both common gene pathways as well as novel cellular responses. Such analyses will be valuable for translational studies of susceptible and resistant individuals—and for targeting therapeutics—in multiple biological settings.

  6. The spinal muscular atrophy gene region at 5q13.1 has a paralogous chromosomal region at 6p21.3.

    Science.gov (United States)

    Banyer, J L; Goldwurm, S; Cullen, L; van der Griend, B; Zournazi, A; Smit, D J; Powell, L W; Jazwinska, E C

    1998-03-01

    Paralogous regions are duplicated segments of chromosomal DNA that have been acquired during the evolution of the genome. Subsequent divergent evolution of the genes within paralogous regions can lead to the formation of gene families. Here, we report the identification of a region on Chromosome (Chr) 6 at 6p21.3 that is paralogous with the Spinal Muscular Atrophy (SMA) gene region on Chr 5 at 5q13.1. Partial characterization of this region identified nine sequences all of which are highly homologous to DNA sequences of the SMA gene region at 5q13.1. These sequences include four beta-glucuronidase sequences, two retrotransposon sequences, a novel cDNA, a Sequence Tagged Site (STS), and one that is homologous to exon 9 of the Neuronal Apoptosis Inhibitor Protein (NAIP) gene. The 6p21.3 paralogous SMA region may contain genes that are related to those in the SMA region at 5q13.1; however, a direct association of this region with SMA is unlikely given that no linkage of SMA with Chr 6 has been reported.

  7. Cloning and Sequence Analysis on 3' Coding Region of Wild Boar and Cross Bred Pig Myostatin Gene

    Institute of Scientific and Technical Information of China (English)

    LIU Di; YANG Xiu-qin; YANG Jia-fang

    2004-01-01

    Myostatin, with a highly conservative gene among breeds is a negative regulator of muscle. The 3' coding regions of wild boar and crossbred pig myostatin were cloned by RT-PCR and sequenced respectively. The homology of the nucleotide sequence between wild boar and crossbred pig was 100% and there was no difference in this region compared with pig myostatin gene of Genbank. This indicated that there was not change of gene sequence in this region during the evolution processes.

  8. Refinement in localization and identification of gene regions associated with Crohn disease.

    Science.gov (United States)

    Elding, Heather; Lau, Winston; Swallow, Dallas M; Maniatis, Nikolas

    2013-01-10

    The risk of Crohn disease (CD) has a large genetic component. A recent meta-analysis of 6 genome-wide association studies reported 71 chromosomal intervals but does not account for all of the known genetic contribution. Here, we refine localization of the previously reported intervals and also identify additional CD susceptibility genes using a mapping approach that localizes causal variants based on genetic maps in linkage disequilibrium units (LDU maps). Using 2 of the 6 cohorts, 66 of the 71 previously reported loci are confirmed and more precise location estimates for these intervals are given. We identify 78 additional gene regions that pass genome-wide significance, providing strong evidence for 144 genes. Additionally, 56 nominally significant signals, but with more stringent and precise colocalization, are identified. In total, we provide evidence for 200 gene regions confirming that CD is truly multifactorial and complex in nature. Many identified genes have functions that are compatible with involvement in immune/inflammatory processes and seem to have a large effect in individuals with extra ileal as well as ileal inflammation. The precise locations and the evidence that some genes reflect phenotypic subgroups will help identify functional variants and will lead to greater insight of CD etiology. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  9. Immediate-early Inducible Function in Upstream Region of junB Gene

    Institute of Scientific and Technical Information of China (English)

    HONG WAN; HIROSHI ISHIHARA; IZUMI TANAKA

    2006-01-01

    Objective To analyze the upstream region of radiation-induced junB gene. Methods Four plasmids containing 250 bp, 590 bp, 900 bp and 1650 bp, and CAT reporter gene were constructed separately and introduced to L8704 cells. The cells were irradiated with 2 Gy X-rays and incubated at different intervals. Total RNA was extracted from the cells and fluctuation of the CAT mRNA level was assessed by the RNA ratio of CAT/β-actin measured by quantitative Northern blot hybridization. Results CAT mRNA expression containing 900 bp and 1560 bpjunB promoter remarkably and rapidly increased, and reached its peak 30 min after 2 Gy X-ray irradiation. Conclusions 590~900 bp fragments located in the upstream region ofjunB gene play an important role in the early process of cells against radiation.

  10. Intact coding region of the serotonin transporter gene in obsessive-compulsive disorder

    Energy Technology Data Exchange (ETDEWEB)

    Altemus, M.; Murphy, D.L.; Greenberg, B. [NIMH, NIH, Bethesda, MD (United States); Lesch, K.P. [Univ. of Wuerzburg (Germany)

    1996-07-26

    Epidemiologic studies indicate that obsessive-compulsive disorder is genetically transmitted in some families, although no genetic abnormalities have been identified in individuals with this disorder. The selective response of obsessive-compulsive disorder to treatment with agents which block serotonin reuptake suggests the gene coding for the serotonin transporter as a candidate gene. The primary structure of the serotonin-transporter coding region was sequenced in 22 patients with obsessive-compulsive disorder, using direct PCR sequencing of cDNA synthesized from platelet serotonin-transporter mRNA. No variations in amino acid sequence were found among the obsessive-compulsive disorder patients or healthy controls. These results do not support a role for alteration in the primary structure of the coding region of the serotonin-transporter gene in the pathogenesis of obsessive-compulsive disorder. 27 refs.

  11. A triple stranded G-quadruplex formation in the promoter region of human myosin β(Myh7) gene.

    Science.gov (United States)

    Singh, Anju; Kukreti, Shrikant

    2017-09-19

    Regulatory regions in human genome, enriched in guanine-rich DNA sequences have the propensity to fold into G-quadruplex structures. On exploring the genome for search of G-tracts, it was interesting to find that promoter of Human Myosin Gene (MYH7) contains a conserved 23-mer G-rich sequence (HM-23). Mutations in this gene are associated with familial cardiomyopathy. Enrichment of MYH7 gene in G-rich sequences could possibly play a critical role in its regulation. We used polyacrylamide gel electrophoresis (PAGE), UV-Thermal denaturation (UV-Tm) and Circular Dichroism (CD), to demonstrate the formation of a G-quadruplex by 23-mer G-rich sequence HM23 in promoter location of MYH7 gene. We observed that the wild G-rich sequence HM23 containing consecutive G5 stretch in two stacks adopt G-quadruplexes of diverse molecularity by involvement of four-strand, three-strand and two-strands with same parallel topology. Interestingly, the mutated sequence in the absence of continuous G5 stretch obstructs the formation of three-stranded G-quadruplex. We demonstrated that continuous G5 stretch is mandatory for the formation of a unique three-stranded G-quadruplex. Presence of various transcription factors (TF) in vicinity of the sequence HM23 leave fair possibility of recognition by TF binding sites, and so modulate gene expression. These findings may add on our understanding about the effect of base change in the formation of varied structural species in similar solution condition. This study may give insight about structural polymorphism arising due to recognition of non-Watson-Crick G-quadruplex structures by cellular proteins and designing structure specific molecules.

  12. Frequent gene conversion events between the X and Y homologous chromosomal regions in primates

    Directory of Open Access Journals (Sweden)

    Hirai Hirohisa

    2010-07-01

    Full Text Available Abstract Background Mammalian sex-chromosomes originated from a pair of autosomes. A step-wise cessation of recombination is necessary for the proper maintenance of sex-determination and, consequently, generates a four strata structure on the X chromosome. Each stratum shows a specific per-site nucleotide sequence difference (p-distance between the X and Y chromosomes, depending on the time of recombination arrest. Stratum 4 covers the distal half of the human X chromosome short arm and the p-distance of the stratum is ~10%, on average. However, a 100-kb region, which includes KALX and VCX, in the middle of stratum 4 shows a significantly lower p-distance (1-5%, suggesting frequent sequence exchanges or gene conversions between the X and Y chromosomes in humans. To examine the evolutionary mechanism for this low p-distance region, sequences of a corresponding region including KALX/Y from seven species of non-human primates were analyzed. Results Phylogenetic analysis of this low p-distance region in humans and non-human primate species revealed that gene conversion like events have taken place at least ten times after the divergence of New World monkeys and Catarrhini (i.e., Old World monkeys and hominoids. A KALY-converted KALX allele in white-handed gibbons also suggests a possible recent gene conversion between the X and Y chromosomes. In these primate sequences, the proximal boundary of this low p-distance region is located in a LINE element shared between the X and Y chromosomes, suggesting the involvement of this element in frequent gene conversions. Together with a palindrome on the Y chromosome, a segmental palindrome structure on the X chromosome at the distal boundary near VCX, in humans and chimpanzees, may mediate frequent sequence exchanges between X and Y chromosomes. Conclusion Gene conversion events between the X and Y homologous regions have been suggested, mainly in humans. Here, we found frequent gene conversions in the

  13. Aberrant DNA methylation in 5'regions of DNA methyltransferase genes in aborted bovine clones

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    High rate of abortion and developmental abnormalities is thought to be closely associated with inefficient epigenetic reprogramming of the transplanted nuclei during bovine cloning.It is known that one of the important mechanisms for epigenetic reprogramming is DNA methylation.DNA methylation is established and maintained by DNA methyltransferases(DNMTs),therefore,it is postulated that the inefficient epigenetic reprogramming of transplanted nuclei may be due to abnormal expression of DNMTs.Since DNA methylation can strongly inhibit gene expression,aberrant DNA methylation of DNMT genes may disturb gene expression.But presently,it is not clear whether the methylation abnormality of DNMT genes is related to developmental failure of somatic cell nuclear transfer embryos.In our study,we analyzed methylation patterns of the 5' regions of four DNMT genes including Dnmt3a,Dnmt3b,Dnmtl and Dnmt2 in four aborted bovine clones.Using bisulfite sequencing method,we found that 3 out of 4 aborted bovine clones(AF1,AF2 and AF3)showed either hypermethylation or hypomethylation in the 5' regions of Dnmt3a and Dnmt3b.indicating that Dnmt3a and Dnmt3b genes are not properly reprogrammed.However,the individual AF4 exhibited similar methylation level and pattern to age-matched in vitro fertilized (IVF)fetuses.Besides,we found that tle 5'regions of Dnmtl and Dnmt2 were nearly completely unmethylated in all normal adults.IVF fetuses,sperm and aborted clones.Together,our results suggest that the aberrant methylation of Dnmt3a and Dnmt3b 5' regions is probably associated with the high abortion of bovine clones.

  14. Characterization of the bovine pregnancy-associated glycoprotein gene family – analysis of gene sequences, regulatory regions within the promoter and expression of selected genes

    Directory of Open Access Journals (Sweden)

    Walker Angela M

    2009-04-01

    Full Text Available Abstract Background The Pregnancy-associated glycoproteins (PAGs belong to a large family of aspartic peptidases expressed exclusively in the placenta of species in the Artiodactyla order. In cattle, the PAG gene family is comprised of at least 22 transcribed genes, as well as some variants. Phylogenetic analyses have shown that the PAG family segregates into 'ancient' and 'modern' groupings. Along with sequence differences between family members, there are clear distinctions in their spatio-temporal distribution and in their relative level of expression. In this report, 1 we performed an in silico analysis of the bovine genome to further characterize the PAG gene family, 2 we scrutinized proximal promoter sequences of the PAG genes to evaluate the evolution pressures operating on them and to identify putative regulatory regions, 3 we determined relative transcript abundance of selected PAGs during pregnancy and, 4 we performed preliminary characterization of the putative regulatory elements for one of the candidate PAGs, bovine (bo PAG-2. Results From our analysis of the bovine genome, we identified 18 distinct PAG genes and 14 pseudogenes. We observed that the first 500 base pairs upstream of the translational start site contained multiple regions that are conserved among all boPAGs. However, a preponderance of conserved regions, that harbor recognition sites for putative transcriptional factors (TFs, were found to be unique to the modern boPAG grouping, but not the ancient boPAGs. We gathered evidence by means of Q-PCR and screening of EST databases to show that boPAG-2 is the most abundant of all boPAG transcripts. Finally, we provided preliminary evidence for the role of ETS- and DDVL-related TFs in the regulation of the boPAG-2 gene. Conclusion PAGs represent a relatively large gene family in the bovine genome. The proximal promoter regions of these genes display differences in putative TF binding sites, likely contributing to observed

  15. Critical role of conserved hydrophobic residues within the major homology region in mature retroviral capsid assembly.

    Science.gov (United States)

    Purdy, John G; Flanagan, John M; Ropson, Ira J; Rennoll-Bankert, Kristen E; Craven, Rebecca C

    2008-06-01

    During retroviral maturation, the CA protein undergoes dramatic structural changes and establishes unique intermolecular interfaces in the mature capsid shell that are different from those that existed in the immature precursor. The most conserved region of CA, the major homology region (MHR), has been implicated in both immature and mature assembly, although the precise contribution of the MHR residues to each event has been largely undefined. To test the roles of specific MHR residues in mature capsid assembly, an in vitro system was developed that allowed for the first-time formation of Rous sarcoma virus CA into structures resembling authentic capsids. The ability of CA to assemble organized structures was destroyed by substitutions of two conserved hydrophobic MHR residues and restored by second-site suppressors, demonstrating that these MHR residues are required for the proper assembly of mature capsids in addition to any role that these amino acids may play in immature particle assembly. The defect caused by the MHR mutations was identified as an early step in the capsid assembly process. The results provide strong evidence for a model in which the hydrophobic residues of the MHR control a conformational reorganization of CA that is needed to initiate capsid assembly and suggest that the formation of an interdomain interaction occurs early during maturation.

  16. Echo mappping of the broad line region of agns a critical appraisal

    CERN Document Server

    Maoz, D

    1994-01-01

    The results of recent AGN monitoring campaigns confirm the ``big picture'' of the echo paradigm, but the details of the emission-line light curves cannot be accurately reproduced with only the simplest assumptions, some of which must be invalid. I discuss possible solutions. I present some preliminary optical light curves from Wise Observatory for NGC 4151 during the December 1993 multi-satellite campaign. The optical data show a continuity with the complex behavior observed in the IUE data, and may explain the peculiarities in emission-line response seen in this and other AGNs. I review some recent results on quasar emission line variability from the Steward-Wise PG quasar monitoring program, which allow extension of the observed AGN BLR Radius--Luminosity relation to higher luminosities than previously feasible. Agreement with the expected R\\propto L^{1/2} relation is suggested. Finally, I criticize the trend to attribute significance to the details of transfer functions recovered by inversion techniques. I...

  17. Genetic Otx2 mis-localization delays critical period plasticity across brain regions.

    Science.gov (United States)

    Lee, H H C; Bernard, C; Ye, Z; Acampora, D; Simeone, A; Prochiantz, A; Di Nardo, A A; Hensch, T K

    2017-02-14

    Accumulation of non-cell autonomous Otx2 homeoprotein in postnatal mouse visual cortex (V1) has been implicated in both the onset and closure of critical period (CP) plasticity. Here, we show that a genetic point mutation in the glycosaminoglycan recognition motif of Otx2 broadly delays the maturation of pivotal parvalbumin-positive (PV+) interneurons not only in V1 but also in the primary auditory (A1) and medial prefrontal cortex (mPFC). Consequently, not only visual, but also auditory plasticity is delayed, including the experience-dependent expansion of tonotopic maps in A1 and the acquisition of acoustic preferences in mPFC, which mitigates anxious behavior. In addition, Otx2 mis-localization leads to dynamic turnover of selected perineuronal net (PNN) components well beyond the normal CP in V1 and mPFC. These findings reveal widespread actions of Otx2 signaling in the postnatal cortex controlling the maturational trajectory across modalities. Disrupted PV+ network function and deficits in PNN integrity are implicated in a variety of psychiatric illnesses, suggesting a potential global role for Otx2 function in establishing mental health.Molecular Psychiatry advance online publication, 14 February 2017; doi:10.1038/mp.2017.1.

  18. Comparison of gene expression in segregating families identifies genes and genomic regions involved in a novel adaptation, zinc hyperaccumulation.

    Science.gov (United States)

    Filatov, Victor; Dowdle, John; Smirnoff, Nicholas; Ford-Lloyd, Brian; Newbury, H John; Macnair, Mark R

    2006-09-01

    One of the challenges of comparative genomics is to identify specific genetic changes associated with the evolution of a novel adaptation or trait. We need to be able to disassociate the genes involved with a particular character from all the other genetic changes that take place as lineages diverge. Here we show that by comparing the transcriptional profile of segregating families with that of parent species differing in a novel trait, it is possible to narrow down substantially the list of potential target genes. In addition, by assuming synteny with a related model organism for which the complete genome sequence is available, it is possible to use the cosegregation of markers differing in transcription level to identify regions of the genome which probably contain quantitative trait loci (QTLs) for the character. This novel combination of genomics and classical genetics provides a very powerful tool to identify candidate genes. We use this methodology to investigate zinc hyperaccumulation in Arabidopsis halleri, the sister species to the model plant, Arabidopsis thaliana. We compare the transcriptional profile of A. halleri with that of its sister nonaccumulator species, Arabidopsis petraea, and between accumulator and nonaccumulator F(3)s derived from the cross between the two species. We identify eight genes which consistently show greater expression in accumulator phenotypes in both roots and shoots, including two metal transporter genes (NRAMP3 and ZIP6), and cytoplasmic aconitase, a gene involved in iron homeostasis in mammals. We also show that there appear to be two QTLs for zinc accumulation, on chromosomes 3 and 7.

  19. Model assessment of atmospheric pollution control schemes for critical emission regions

    Science.gov (United States)

    Zhai, Shixian; An, Xingqin; Liu, Zhao; Sun, Zhaobin; Hou, Qing

    2016-01-01

    In recent years, the atmospheric environment in portions of China has become significantly degraded and the need for emission controls has become urgent. Because more international events are being planned, it is important to implement air quality assurance targeted at significant events held over specific periods of time. This study sets Yanqihu (YQH), Beijing, the location of the 2014 Beijing APEC (Asia-Pacific Economic Cooperation) summit, as the target region. By using the atmospheric inversion model FLEXPART, we determined the sensitive source zones that had the greatest impact on the air quality of the YQH region in November 2012. We then used the air-quality model Models-3/CMAQ and a high-resolution emissions inventory of the Beijing-Tianjian-Hebei region to establish emission reduction tests for the entire source area and for specific sensitive source zones. This was achieved by initiating emission reduction schemes at different ratios and different times. The results showed that initiating a moderate reduction of emissions days prior to a potential event is more beneficial to the air quality of Beijing than initiating a high-strength reduction campaign on the day of the event. The sensitive source zone of Beijing (BJ-Sens) accounts for 54.2% of the total source area of Beijing (BJ), but its reduction effect reaches 89%-100% of the total area, with a reduction efficiency 1.6-1.9 times greater than that of the entire area. The sensitive source zone of Huabei (HuaB-Sens.) only represents 17.6% of the total area of Huabei (HuaB), but its emission reduction effect reaches 59%-97% of the entire area, with a reduction efficiency 4.2-5.5 times greater than that of the total area. The earlier that emission reduction measures are implemented, the greater the effect they have on preventing the transmission of pollutants. In addition, expanding the controlling areas to sensitive provinces and cities around Beijing (HuaB-sens) can significantly accelerate the reduction

  20. Histone H4 deacetylation plays a critical role in early gene silencing during neuronal apoptosis

    Directory of Open Access Journals (Sweden)

    Schlamp Cassandra L

    2010-05-01

    Full Text Available Abstract Background Silencing of normal gene expression occurs early in the apoptosis of neurons, well before the cell is committed to the death pathway, and has been extensively characterized in injured retinal ganglion cells. The causative mechanism of this widespread change in gene expression is unknown. We investigated whether an epigenetic change in active chromatin, specifically histone H4 deacetylation, was an underlying mechanism of gene silencing in apoptotic retinal ganglion cells (RGCs following an acute injury to the optic nerve. Results Histone deacetylase 3 (HDAC3 translocates to the nuclei of dying cells shortly after lesion of the optic nerve and is associated with an increase in nuclear HDAC activity and widespread histone deacetylation. H4 in promoters of representative genes was rapidly and indiscriminately deacetylated, regardless of the gene examined. As apoptosis progressed, H4 of silenced genes remained deacetylated, while H4 of newly activated genes regained, or even increased, its acetylated state. Inhibition of retinal HDAC activity with trichostatin A (TSA was able to both preserve the expression of a representative RGC-specific gene and attenuate cell loss in response to optic nerve damage. Conclusions These data indicate that histone deacetylation plays a central role in transcriptional dysregulation in dying RGCs. The data also suggests that HDAC3, in particular, may feature heavily in apoptotic gene silencing.

  1. Critical brain regions for action recognition: lesion symptom mapping in left hemisphere stroke.

    Science.gov (United States)

    Kalénine, Solène; Buxbaum, Laurel J; Coslett, Harry Branch

    2010-11-01

    A number of conflicting claims have been advanced regarding the role of the left inferior frontal gyrus, inferior parietal lobe and posterior middle temporal gyrus in action recognition, driven in part by an ongoing debate about the capacities of putative mirror systems that match observed and planned actions. We report data from 43 left hemisphere stroke patients in two action recognition tasks in which they heard and saw an action word ('hammering') and selected from two videoclips the one corresponding to the word. In the spatial recognition task, foils contained errors of body posture or movement amplitude/timing. In the semantic recognition task, foils were semantically related (sawing). Participants also performed a comprehension control task requiring matching of the same verbs to objects (hammer). Using regression analyses controlling for both the comprehension control task and lesion volume, we demonstrated that performance in the semantic gesture recognition task was predicted by per cent damage to the posterior temporal lobe, whereas the spatial gesture recognition task was predicted by per cent damage to the inferior parietal lobule. A whole-brain voxel-based lesion symptom-mapping analysis suggested that the semantic and spatial gesture recognition tasks were associated with lesioned voxels in the posterior middle temporal gyrus and inferior parietal lobule, respectively. The posterior middle temporal gyrus appears to serve as a central node in the association of actions and meanings. The inferior parietal lobule, held to be a homologue of the monkey parietal mirror neuron system, is critical for encoding object-related postures and movements, a relatively circumscribed aspect of gesture recognition. The inferior frontal gyrus, on the other hand, was not predictive of performance in any task, suggesting that previous claims regarding its role in action recognition may require refinement.

  2. Genic regions of a large salamander genome contain long introns and novel genes

    Directory of Open Access Journals (Sweden)

    Bryant Susan V

    2009-01-01

    Full Text Available Abstract Background The basis of genome size variation remains an outstanding question because DNA sequence data are lacking for organisms with large genomes. Sixteen BAC clones from the Mexican axolotl (Ambystoma mexicanum: c-value = 32 × 109 bp were isolated and sequenced to characterize the structure of genic regions. Results Annotation of genes within BACs showed that axolotl introns are on average 10× longer than orthologous vertebrate introns and they are predicted to contain more functional elements, including miRNAs and snoRNAs. Loci were discovered within BACs for two novel EST transcripts that are differentially expressed during spinal cord regeneration and skin metamorphosis. Unexpectedly, a third novel gene was also discovered while manually annotating BACs. Analysis of human-axolotl protein-coding sequences suggests there are 2% more lineage specific genes in the axolotl genome than the human genome, but the great majority (86% of genes between axolotl and human are predicted to be 1:1 orthologs. Considering that axolotl genes are on average 5× larger than human genes, the genic component of the salamander genome is estimated to be incredibly large, approximately 2.8 gigabases! Conclusion This study shows that a large salamander genome has a correspondingly large genic component, primarily because genes have incredibly long introns. These intronic sequences may harbor novel coding and non-coding sequences that regulate biological processes that are unique to salamanders.

  3. Proximal 15q familial euchromatic variant and PWS/AS critical region duplication in the same patient: a cytogenetic pitfall.

    Science.gov (United States)

    Carelle-Calmels, Nadège; Girard-Lemaire, Françoise; Guérin, Eric; Bieth, Eric; Rudolf, Gabrielle; Biancalana, Valérie; Pecheur, Hélène; Demil, Houria; Schneider, Thierry; de Saint-Martin, Anne; Caron, Olivier; Legrain, Michèle; Gaston, Valérie; Flori, Elisabeth

    2008-01-01

    Cytogenetically detectable elongation of the 15q proximal region can be associated with Prader-Willi/Angelman critical region interstitial duplications or with inherited juxtacentromeric euchromatic variants. The first category has been reported in association with developmental delay and autistic disorders. These pathogenic recurrent duplications are more frequently of maternal origin and originate from unequal meiotic crossovers between chromosome 15 low-copy repeats. 15q juxtacentromeric euchromatic variants reflect polymorphic copy number variations of segments containing pseudogenes and usually segregate without apparent phenotypic consequence. Pathogenic relevant 15q11-q13 duplications are not distinguishable from the innocuous euchromatic variants with conventional cytogenetic methods. We report cytogenetic and molecular studies of a patient with hypotonia, developmental delay and epilepsy, carrying, on the same chromosome 15, both a de novo 15q11-q13 interstitial duplication and an inherited 15q juxtacentromeric amplification from maternal origin. The duplication, initially suspected by fluorescent in situ hybridization (FISH), has been confirmed by molecular studies. The 15q juxtacentromeric region amplification, which segregates in the family for at least three generations, has been confirmed by FISH using BAC probes overlapping the NF1 and GABRA5 pseudogenes. This report emphasizes the importance to distinguish proximal 15q polymorphic variants from clinically significant duplications. In any patient with inherited 15q proximal variant but unexplained developmental delay suggesting 15q11-q13 pathology, a pathogenic rearrangement has to be searched with adapted strategies, in order to detect deletions as well as duplications of this region.

  4. Clone and Bioinformatics Analysis of Pig SRPK1 Gene 5' UTR Region

    Institute of Scientific and Technical Information of China (English)

    E Guangxin; LIU Di; YANG Xiuqin; ZHANG Dongjie; YU Cui

    2011-01-01

    Part 5' UTR region of pig SRPK1 gene was cloned by inverse PCR (I-PCR), then a 425 bp gene sequence was acquired. A promoter region in -1--309 bp was predicted by online tool (TFSEARCH) and 32 binding sites of transcription with scores higher than 85 were getten, of which scores of Spl, MyoD, and HSF2 were over 90. Some of these binding sites of transcription factors were connected with promoters, but TATA-box, which was important to gene expression, hadn't been found in this region. By using PCR-SSCP method to search SNPs this part (5' UTR of SRPK1 in pig), total of 40 Large White pigs were obtained as the research objects, but no polymorphism were found. Thus, 5' UTR of SRPK1 was speculated with a characteristic of high conservation, while it might have been directly or indirectly selected in commercial breeding. The paper provided a further feature of SRPK1 gene in molecular genetics.

  5. Geochemical characterization of critical dust source regions in the American West

    Science.gov (United States)

    Aarons, Sarah M.; Blakowski, Molly A.; Aciego, Sarah M.; Stevenson, Emily I.; Sims, Kenneth W. W.; Scott, Sean R.; Aarons, Charles

    2017-10-01

    The generation, transport, and deposition of mineral dust are detectable in paleoclimate records from land, ocean, and ice, providing valuable insight into earth surface conditions and cycles on a range of timescales. Dust deposited in marine and terrestrial ecosystems can provide critical nutrients to nutrient-limited ecosystems, and variations in dust provenance can indicate changes in dust production, sources and transport pathways as a function of climate variability and land use change. Thus, temporal changes in locations of dust source areas and transport pathways have implications for understanding interactions between mineral dust, global climate, and biogeochemical cycles. This work characterizes dust from areas in the American West known for dust events and/or affected by increasing human settlement and livestock grazing during the last 150 years. Dust generation and uplift from these dust source areas depends on climate and land use practices, and the relative contribution of dust has likely changed since the expansion of industrialization and agriculture into the western United States. We present elemental and isotopic analysis of 28 potential dust source area samples analyzed using Thermal Ionization Mass Spectrometry (TIMS) for 87Sr/86Sr and 143Nd/144Nd composition and Multi-Collector Inductively Coupled Plasma Mass Spectrometer (MC-ICPMS) for 176Hf/177Hf composition, and ICPMS for major and trace element concentrations. We find significant variability in the Sr, Nd, and Hf isotope compositions of potential source areas of dust throughout western North America, ranging from 87Sr/86Sr = 0.703699 to 0.740236, εNd = -26.6 to 2.4, and εHf = -21.7 to -0.1. We also report differences in the trace metal and phosphorus concentrations in the geologic provinces sampled. This research provides an important resource for the geochemical tracing of dust sources and sinks in western North America, and will aid in modeling the biogeochemical impacts of increased

  6. Conservation-based prediction of the transcription regulatory region of the SCN1A gene

    Institute of Scientific and Technical Information of China (English)

    Yue-Sheng Long; Yi-Wu Shi; Wei-Ping Liao

    2009-01-01

    A challenge in identifying the transcription regulatory region is that the locations of eukaryotic transcriptional elements are often diverse among different genes.SCN1A,a disease-related sodium channel gene,has a complex 5'-untranslated region and diverse mRNA transcripts,which might be driven by different promoters.By cross-species sequence comparison and bioinformatics analysis,human 5'-untranslated exons were found to be conserved within the region of 200 kb upstream of the 5' flanking regions of SCN1A in higher mammals,but not in lower mammals and non-mammals.The core promoter elements (INR,DPE,and TATA) were found in the regions flanking different 5'-untranslated exons,suggesting that these sequences (from-45 to+35) might be targeted as core promoters.The nucleotide identity rate of these core promoter sequences are different,and the conservation level of the upstream region of each core promoter varies distinctly,implicating different regulatory mechanisms of the four promoters which exist in the nervous system.

  7. Silencing of meiosis-critical genes for engineering male sterility in plants

    Science.gov (United States)

    Engineering sterile traits in plants through the tissue-specific expression of a cytotoxic gene provides an effective way for containing transgene flow; however, the microbial origin of cytotoxic genes has raised concerns. In an attempt to develop a safe alternative, we have chosen the meiosis-crit...

  8. Association analysis of PRNP gene region with chronic wasting disease in Rocky Mountain elk

    Directory of Open Access Journals (Sweden)

    Spraker Terry R

    2010-11-01

    Full Text Available Abstract Background Chronic wasting disease (CWD is a transmissible spongiform encephalopathy (TSE of cervids including white-tailed (Odocoileus virginianus and mule deer (Odocoileus hemionus, Rocky Mountain elk (Cervus elaphus nelsoni, and moose (Alces alces. A leucine variant at position 132 (132L in prion protein of Rocky Mountain elk confers a long incubation time with CWD, but not complete resistance. However, variants in regulatory regions outside the open reading frame of PRNP have been associated with varying degrees of susceptibility to prion disease in other species, and some variants have been observed in similar regions of Rocky Mountain elk PRNP. Thus, additional genetic variants might provide increased protection, either alone or in combination with 132L. Findings This study provided genomic sequence of all exons for PRNP of Rocky Mountain elk. Many functional sites in and around the PRNP gene region were sequenced, and this report approximately doubled (to 75 the number of known variants in this region. A haplotype-tagging approach was used to reduce the number of genetic variants required to survey this variation in the PRNP gene region of 559 Rocky Mountain elk. Eight haplotypes were observed with frequencies over 1.0%, and one haplotype was present at 71.2% frequency, reflecting limited genetic diversity in the PRNP gene region. Conclusions The presence of 132L cut odds of CWD by more than half (Odds Ratio = 0.43; P = 0.0031, which was similar to a previous report. However after accounting for 132L, no association with CWD was found for any additional variants in the PRNP region (P > 0.05.

  9. The role of critical zone processes in the evolution of the Prairie Pothole Region wetlands

    Science.gov (United States)

    Goldhaber, M.B.; Mills, C.; Stricker, C.A.; Morrison, J.M.

    2011-01-01

    The Prairie Pothole Region, which occupies 900,000 km2 of the north central USA and south central Canada, is one of the most important ecosystems in North America. It is characterized by millions of small wetlands whose chemistry is highly variable over short distances. The study involved the geochemistry of surface sediments, wetland water, and groundwater in the Cottonwood Lakes area of North Dakota, USA, whose 92 ha includes the dominant wetland hydrologic settings. The data show that oxygenated groundwater interacting with pyrite resident in a component of surficial glacial till derived from the marine Pierre Shale Formation has, over long periods of time, focused SO2-4-bearing fluids from upland areas to topographically low areas. In these low areas, SO2-4-enriched groundwater and wetlands have evolved, as has the CaSO4 mineral gypsum. Sulfur isotope data support the conclusion that isotopically light pyrite from marine shale is the source of SO2-4. Literature data on wetland water composition suggests that this process has taken place over a large area in North Dakota.

  10. Critical role of dendritic cells in T cell retention in the interfollicular region of Peyer's patches.

    Science.gov (United States)

    Obata, Takashi; Shibata, Naoko; Goto, Yoshiyuki; Ishikawa, Izumi; Sato, Shintaro; Kunisawa, Jun; Kiyono, Hiroshi

    2013-07-15

    Peyer's patches (PPs) simultaneously initiate active and quiescent immune responses in the gut. The immunological function is achieved by the rigid regulation of cell distribution and trafficking, but how the cell distribution is maintained remains to be elucidated. In this study, we show that binding of stromal cell-derived lymphoid chemokines to conventional dendritic cells (cDCs) is essential for the retention of naive CD4(+) T cells in the interfollicular region (IFR) of PPs. Transitory depletion of CD11c(high) cDCs in mice rapidly impaired the IFR structure in the PPs without affecting B cell follicles or germinal centers, lymphoid chemokine production from stromal cells, or the immigration of naive T cells into the IFRs of PPs. The cDC-orchestrated retention of naive T cells was mediated by heparinase-sensitive molecules that were expressed on cDCs and bound the lymphoid chemokine CCL21 produced from stromal cells. These data collectively reveal that interactions among cDCs, stromal cells, and naive T cells are necessary for the formation of IFRs in the PPs.

  11. The Global Burden of Disease: A critical resource for informed policy making in the Gulf region

    Directory of Open Access Journals (Sweden)

    Ali H Mokdad

    2016-01-01

    Full Text Available The Gulf countries have made tremendous improvements in their health systems in a short period of time due to extensive investments. However, during the same time period, rapid changes in lifestyle habits led to a changing burden of disease. In this manuscript, we report the burden of disease and risk factors for the Gulf countries (Bahrain, Kuwait, Oman, Qatar, Kingdom of Saudi Arabia, United Arab Emirates, and Yemen measured by causes of death, years of life lost due to premature mortality (YLLs, years of life lived with disability (YLDs, and disability-adjusted life years (DALYs for the years 1990 to 2013. Our findings showed a decline of infectious diseases and a rising burden of road traffic accidents and non-communicable diseases while Yemen is still facing a large burden from communicable diseases. Our findings call for the development and implementation of programmes to reduce these burdens and engage other sectors such as the Government and the community in these efforts. These programmes need to be developed and adopted locally since many of the programmes found in the literature may not succeed in the region. Moreover, there is an urgent need for a political will and legislations to ensure their success.

  12. Molecular cloning of rhamnose-binding lectin gene and its promoter region from snakehead Channa argus.

    Science.gov (United States)

    Jia, W Z; Shang, N; Guo, Q L

    2010-09-01

    Lectins are sugar-binding proteins that mediate pathogen recognition and cell-cell interactions. A rhamnose-binding lectin (RBL) gene and its promoter region have been cloned and characterized from snakehead Channa argus. From the transcription initiation site, snakehead rhamnose-binding lectin (SHL) gene extends 2,382 bp to the end of the 3' untranslated region (UTR), and contains nine exons and eight introns. The open reading frame (ORF) of the SHL transcript has 675 bp which encodes 224 amino acids. The molecular structure of SHL is composed of two tandem repeat carbohydrate recognition domains (CRD) with 35% internal identity. Analysis of the gene organization of SHL indicates that the ancestral gene of RBL may diverge and evolve by exon shuffling and gene duplication, producing new forms to play their own roles in various organisms. The characteristics of SHL gene 5' flanking region are the presence of consensus nuclear factor of interleukin 6 (NF-IL6) and IFN-gamma activation (GAS) sites. The results provide indirect evidence that up-regulation of SHL expression may be induced in response to inflammatory stimuli, such as lipopolysaccharide (LPS), interleukin 6 (IL-6), and interferon gamma (IFN-gamma). The transcript of SHL mRNA was expressed in the head kidney, posterior kidney, spleen, liver, intestine, heart, muscle, and ovary. No tissue-specific expressive pattern is different from reported STLs, WCLs, and PFLs, suggesting that different types of RBLs exist in species-specific fish that have evolved and adapted to their surroundings.

  13. Deletion of 3p25.3 in a patient with intellectual disability and dysmorphic features with further definition of a critical region.

    Science.gov (United States)

    Kellogg, Gregory; Sum, John; Wallerstein, Robert

    2013-06-01

    Several recent reports of interstitial deletions at the terminal end of the short arm of chromosome 3 have helped to define the critical region whose deletion causes 3p deletion syndrome. We report on an 11-year-old girl with intellectual disability, obsessive-compulsive tendencies, hypotonia, and dysmorphic facial features in whom a 684 kb interstitial 3p25.3 deletion was characterized using array-CGH. This deletion overlaps with interstitial 3p25 deletions reported in three recent case reports. These deletions share a 124 kb overlap region including only three RefSeq annotated genes, THUMPD3, SETD5, and LOC440944. The current patient had phenotypic similarities, including intellectual disability, hypotonia, depressed nasal bridge, and long philtrum, with previously reported patients, while she did not have the cardiac defects, seizures ormicrocephaly reported in patients with larger deletions. Therefore, this patient furthers our knowledge of the consequences of 3p deletions, while suggesting genotype-phenotype correlations. Copyright © 2013 Wiley Periodicals, Inc.

  14. Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype.

    Science.gov (United States)

    Pelleri, Maria Chiara; Cicchini, Elena; Locatelli, Chiara; Vitale, Lorenza; Caracausi, Maria; Piovesan, Allison; Rocca, Alessandro; Poletti, Giulia; Seri, Marco; Strippoli, Pierluigi; Cocchi, Guido

    2016-06-15

    A 'Down Syndrome critical region' (DSCR) sufficient to induce the most constant phenotypes of Down syndrome (DS) had been identified by studying partial (segmental) trisomy 21 (PT21) as an interval of 0.6-8.3 Mb within human chromosome 21 (Hsa21), although its existence was later questioned. We propose an innovative, systematic reanalysis of all described PT21 cases (from 1973 to 2015). In particular, we built an integrated, comparative map from 125 cases with or without DS fulfilling stringent cytogenetic and clinical criteria. The map allowed to define or exclude as candidates for DS fine Hsa21 sequence intervals, also integrating duplication copy number variants (CNVs) data. A highly restricted DSCR (HR-DSCR) of only 34 kb on distal 21q22.13 has been identified as the minimal region whose duplication is shared by all DS subjects and is absent in all non-DS subjects. Also being spared by any duplication CNV in healthy subjects, HR-DSCR is proposed as a candidate for the typical DS features, the intellectual disability and some facial phenotypes. HR-DSCR contains no known gene and has relevant homology only to the chimpanzee genome. Searching for HR-DSCR functional loci might become a priority for understanding the fundamental genotype-phenotype relationships in DS. © The Author 2016. Published by Oxford University Press.

  15. 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.

  16. The critical behavior of the dielectric constant in the polar + polar binary liquid mixture nitromethane + 3-pentanol: An unusual sign of its critical amplitude in the one-phase region

    Science.gov (United States)

    Leys, Jan; Losada-Pérez, Patricia; Troncoso, Jacobo; Glorieux, Christ; Thoen, Jan

    2011-07-01

    Dielectric constant measurements have been carried out in the one- and two-phase regions near the critical point of the polar + polar binary liquid mixture nitromethane + 3-pentanol. In the two-phase region, evidence for the |t|2β singularity in the coexistence-curve diameter has been detected, thus confirming the novel predictions of complete scaling theory for liquid-liquid criticality. In the one-phase region, an "unusual" negative sign for the amplitude of the |t|1 - α singularity has been encountered for the first time in an upper critical solution temperature type of binary liquid mixture at atmospheric pressure. Mass density measurements have also been carried out to provide additional information related to such experimental finding, which entails an increase of the critical temperature Tc under an electric field.

  17. Study on the Polymorphisms of Porcine Myostatin Gene in Promoter Region by PCR-RFLPS

    Institute of Scientific and Technical Information of China (English)

    YANG Xiu-qin; LIU Di

    2005-01-01

    In order to further study functions of the porcine myostatin gene, we analyzed the polymorphisms of porcine myostatin gene in promoter region among different breeds including Yorkshire, Landrace, Duroc, Junmu, Min pig and Sanjiang white pig by PCR-RFLPs. The allele T dominated in the imported lean-type pig breeds such as Yorkshire, Landrace and Duroc. No allele A was detected in Junmu and Sanjiang white pig, and the frequencies of three genotypes were about equal in Min pig. The result using X2 analysis showed that the distribution of three genotypes was related to pig breeds.

  18. Interferon gamma response region in the promoter of the human DPA gene.

    OpenAIRE

    1990-01-01

    The interferon gamma (IFN-gamma) response region of the human class II major histocompatibility complex gene, DPA, has been localized to a 52-base-pair (bp) DNA fragment in the proximal promotor at -107 to -55 bp after transfection into HeLa cells of a series of 5', 3', and gap deletion mutants linked to a reporter gene, human growth hormone, as well as of synthetic oligonucleotides fused to the heterologous promoter thymidine kinase. The 52-mer sequence contains the X and Y box elements cons...

  19. Priority persistent contaminants in people dwelling in critical areas of Campania Region, Italy (SEBIOREC biomonitoring study)

    Energy Technology Data Exchange (ETDEWEB)

    De Felip, Elena, E-mail: defelip@iss.it [Istituto Superiore di Sanità, Dipartimento Ambiente e connessa Prevenzione Primaria, Rome (Italy); Bianchi, Fabrizio [Consiglio Nazionale delle Ricerche, Istituto di Fisiologia Clinica, Pisa and Rome (Italy); Bove, Crescenzo [ASL CE, Servizio di Epidemiologia e Prevenzione, Caserta (Italy); Cori, Liliana [Consiglio Nazionale delle Ricerche, Istituto di Fisiologia Clinica, Pisa and Rome (Italy); D' Argenzio, Angelo [ASL CE, Servizio di Epidemiologia e Prevenzione, Caserta (Italy); D' Orsi, Giancarlo [ASL NA2 Nord, Servizio di Epidemiologia e Prevenzione, Naples (Italy); Fusco, Mario [Registro Tumori della Regione Campania, ASL NA3 Sud, Naples (Italy); Miniero, Roberto [Istituto Superiore di Sanità, Dipartimento Ambiente e connessa Prevenzione Primaria, Rome (Italy); Ortolani, Rosanna [ASL NA1 Centro, Servizio di Epidemiologia e Prevenzione, Naples (Italy); Palombino, Raffaele [ASL NA3 Sud, Servizio di Epidemiologia e Prevenzione, Distretto Sanitario 69, Naples (Italy); Parlato, Antonino; Pelliccia, Maria Grazia; Peluso, Filomena [ASL NA2 Nord, Servizio di Epidemiologia e Prevenzione, Naples (Italy); Piscopo, Giovanni [ASL NA3 Sud, Servizio di Epidemiologia e Prevenzione, Distretto Sanitario 69, Naples (Italy); Pizzuti, Renato [Regione Campania, Assessorato alla Sanità, Osservatorio Epidemiologico, Naples (Italy); Porpora, Maria Grazia [Dipartimento di Ginecologia e Ostetricia, Dipartimento di Scienze Ginecologiche, Perinatologia, e Puericultura, Policlinico Umberto I, Università “Sapienza”, Rome (Italy); Protano, Domenico [ASL CE, Servizio di Epidemiologia e Prevenzione, Caserta (Italy); Senofonte, Oreste [Istituto Superiore di Sanità, Dipartimento Ambiente e connessa Prevenzione Primaria, Rome (Italy); and others

    2014-07-01

    To investigate if protracted living in degraded environments of the Caserta and Naples provinces (Campania Region, Italy) had an impact on exposure of local people, highly toxic persistent contaminants were measured in blood, blood serum, and human milk of a large number of healthy donors. Sampling was carried out from 2008 to 2009. Blood was collected from over 850 20–64-year old donors; by pooling, 84 blood and 84 serum samples were obtained. Milk was donated by 52 mothers: specimens were pooled into six samples. Polychlorodibenzodioxins (PCDDs), polychlorodibenzofurans (PCDFs), and polychlorobiphenyls (PCBs, dioxin-like (DL) and non-dioxin-like (Σ{sub 6}PCBs)), arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) were measured in serum (organic biomarkers) and blood (metals); these chemicals and polybromobiphenyl ethers (Σ{sub 9}PBDEs) were analyzed in milk. PCDD + PCDF, DL-PCB, TEQ{sub TOT}, and Σ{sub 6}PCB concentration ranges (medians) in serum were 6.26–23.1 (12.4), 3.42–31.7 (11.5), 10.0–52.8 (23.9) pgTEQ{sub 97}/g fat, and 55.5–647 (219) ng/g fat, respectively, while in milk concentration ranges were 5.99–8.77, 4.02–6.15, 10.0–14.2 pgTEQ{sub 97}/g fat, and 48.7–74.2 ng/g fat. Likewise, As, Cd, Hg, and Pb findings in blood spanned 2.34–13.4 (5.83), 0.180–0.930 (0.475), 1.09–7.60 (2.60), 10.2–55.9 (28.8) μg/L, respectively; only Pb could be measured in milk (2.78–5.99 μg/L). Σ{sub 9}PBDE levels in milk samples were 0.965–6.05 ng/g fat. Biomarkers' concentrations were found to be compatible with their current values in European countries and in Italy, and consistent with an exposure primarily determined by consumption of commercial food from the large distribution system. Based on relatively higher biomarker values within the hematic biomonitoring database, the following municipalities were flagged as possibly deserving attention for health-oriented interventions: Brusciano and Caivano (As), Giugliano (Hg), Pianura

  20. An ABA-responsive DRE-binding protein gene from Setaria italica, SiARDP, the target gene of SiAREB, plays a critical role under drought stress.

    Science.gov (United States)

    Li, Cong; Yue, Jing; Wu, Xiaowei; Xu, Cong; Yu, Jingjuan

    2014-10-01

    The DREB (dehydration-responsive element binding)-type transcription factors regulate the expression of stress-inducible genes by binding the DRE/CRT cis-elements in promoter regions. The upstream transcription factors that regulate the transcription of DREB transcription factors have not been clearly defined, although the function of DREB transcription factors in abiotic stress is known. In this study, an abscisic acid (ABA)-responsive DREB-binding protein gene (SiARDP) was cloned from foxtail millet (Setaria italica). The transcript level of SiARDP increased not only after drought, high salt, and low temperature stresses, but also after an ABA treatment in foxtail millet seedlings. Two ABA-responsive elements (ABRE1: ACGTGTC; ABRE2: ACGTGGC) exist in the promoter of SiARDP. Further analyses showed that two ABA-responsive element binding (AREB)-type transcription factors, SiAREB1 and SiAREB2, could physically bind to the ABRE core element in vitro and in vivo. The constitutive expression of SiARDP in Arabidopsis thaliana enhanced drought and salt tolerance during seed germination and seedling development, and overexpression of SiARDP in foxtail millet improved drought tolerance. The expression levels of target genes of SiARDP were upregulated in transgenic Arabidopsis and foxtail millet. These results reveal that SiARDP, one of the target genes of SiAREB, is involved in ABA-dependent signal pathways and plays a critical role in the abiotic stress response in plants.

  1. Reverse Engineering of Modified Genes by Bayesian Network Analysis Defines Molecular Determinants Critical to the Development of Glioblastoma

    Science.gov (United States)

    Kunkle, Brian W.; Yoo, Changwon; Roy, Deodutta

    2013-01-01

    In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I–IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96–100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential ‘hubs of activity’. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several ‘key genes’ may be required for the development of glioblastoma. Further studies are needed to validate these ‘key genes’ as useful tools for early detection and novel therapeutic options for these tumors. PMID:23737970

  2. Two pedigrees of autosomal dominant atrioventricular canal defect (AVCD): Exclusion from the critical region on 8p

    Energy Technology Data Exchange (ETDEWEB)

    Amati, F.; Mari, A.; Mingarelli, R. [Universita Tor Vergata, Rome (Italy)] [and others

    1995-07-03

    Atrioventricular canal defects (AVCD) constitute the predominant congenital heart defect in Down`s syndrome. For this reason, a candidate gene involved in atrioventricular canal development was previously searched and excluded in dominant pedigrees of AVCD, using linkage analysis of polymorphisms from chromosome 21. Because of the striking association between 8p deletion and AVCD, a search for an AVCD gene was carried out in two pedigrees of individuals with autosomal dominant AVCD using a set of DNA markers of the 8pter{r_arrow}q12 region. These two families include affected individuals and subjects who have transmitted the defect but are not clinically affected. Two-point lod scores were significantly negative for all markers at penetrance levels of 90% and 50%. Multipoint analysis excluded the region covered by the markers LPL-D8S262 and 30 cM to either side of this area. This result corroborates heterogeneity of this heart defect and indicates that the genetic basis of familial AVCD is different from AVCD associated to either trisomy 21 or 8p deletion. 25 refs., 3 figs., 2 tabs.

  3. Priority persistent contaminants in people dwelling in critical areas of Campania Region, Italy (SEBIOREC biomonitoring study).

    Science.gov (United States)

    De Felip, Elena; Bianchi, Fabrizio; Bove, Crescenzo; Cori, Liliana; D'Argenzio, Angelo; D'Orsi, Giancarlo; Fusco, Mario; Miniero, Roberto; Ortolani, Rosanna; Palombino, Raffaele; Parlato, Antonino; Pelliccia, Maria Grazia; Peluso, Filomena; Piscopo, Giovanni; Pizzuti, Renato; Porpora, Maria Grazia; Protano, Domenico; Senofonte, Oreste; Spena, Silvana Russo; Simonetti, Andrea; di Domenico, Alessandro

    2014-07-15

    To investigate if protracted living in degraded environments of the Caserta and Naples provinces (Campania Region, Italy) had an impact on exposure of local people, highly toxic persistent contaminants were measured in blood, blood serum, and human milk of a large number of healthy donors. Sampling was carried out from 2008 to 2009. Blood was collected from over 850 20-64-year old donors; by pooling, 84 blood and 84 serum samples were obtained. Milk was donated by 52 mothers: specimens were pooled into six samples. Polychlorodibenzodioxins (PCDDs), polychlorodibenzofurans (PCDFs), and polychlorobiphenyls (PCBs, dioxin-like (DL) and non-dioxin-like (Σ6PCBs)), arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) were measured in serum (organic biomarkers) and blood (metals); these chemicals and polybromobiphenyl ethers (Σ9PBDEs) were analyzed in milk. PCDD+PCDF, DL-PCB, TEQTOT, and Σ6PCB concentration ranges (medians) in serum were 6.26-23.1 (12.4), 3.42-31.7 (11.5), 10.0-52.8 (23.9) pgTEQ97/g fat, and 55.5-647 (219) ng/g fat, respectively, while in milk concentration ranges were 5.99-8.77, 4.02-6.15, 10.0-14.2 pgTEQ97/g fat, and 48.7-74.2 ng/g fat. Likewise, As, Cd, Hg, and Pb findings in blood spanned 2.34-13.4 (5.83), 0.180-0.930 (0.475), 1.09-7.60 (2.60), 10.2-55.9 (28.8) μg/L, respectively; only Pb could be measured in milk (2.78-5.99 μg/L). Σ9PBDE levels in milk samples were 0.965-6.05 ng/g fat. Biomarkers' concentrations were found to be compatible with their current values in European countries and in Italy, and consistent with an exposure primarily determined by consumption of commercial food from the large distribution system. Based on relatively higher biomarker values within the hematic biomonitoring database, the following municipalities were flagged as possibly deserving attention for health-oriented interventions: Brusciano and Caivano (As), Giugliano (Hg), Pianura (PCDDs+PCDFs), and Qualiano-Villaricca (As, Hg). The analysis of samples

  4. Comparison of regional gene expression differences in the brains of the domestic dog and human

    Directory of Open Access Journals (Sweden)

    Kennerly Erin

    2004-11-01

    Full Text Available Abstract Comparison of the expression profiles of 2,721 genes in the cerebellum, cortex and pituitary gland of three American Staffordshire terriers, one beagle and one fox hound revealed regional expression differences in the brain but failed to reveal marked differences among breeds, or even individual dogs. Approximately 85 per cent (42 of 49 orthologue comparisons of the regional differences in the dog are similar to those that differentiate the analogous human brain regions. A smaller percentage of human differences were replicated in the dog, particularly in the cortex, which may generally be evolving more rapidly than other brain regions in mammals. This study lays the foundation for detailed analysis of the population structure of transcriptional variation as it relates to cognitive and neurological phenotypes in the domestic dog.

  5. Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Natalie A Twine

    Full Text Available Recent studies strongly indicate that aberrations in the control of gene expression might contribute to the initiation and progression of Alzheimer's disease (AD. In particular, alternative splicing has been suggested to play a role in spontaneous cases of AD. Previous transcriptome profiling of AD models and patient samples using microarrays delivered conflicting results. This study provides, for the first time, transcriptomic analysis for distinct regions of the AD brain using RNA-Seq next-generation sequencing technology. Illumina RNA-Seq analysis was used to survey transcriptome profiles from total brain, frontal and temporal lobe of healthy and AD post-mortem tissue. We quantified gene expression levels, splicing isoforms and alternative transcript start sites. Gene Ontology term enrichment analysis revealed an overrepresentation of genes associated with a neuron's cytological structure and synapse function in AD brain samples. Analysis of the temporal lobe with the Cufflinks tool revealed that transcriptional isoforms of the apolipoprotein E gene, APOE-001, -002 and -005, are under the control of different promoters in normal and AD brain tissue. We also observed differing expression levels of APOE-001 and -002 splice variants in the AD temporal lobe. Our results indicate that alternative splicing and promoter usage of the APOE gene in AD brain tissue might reflect the progression of neurodegeneration.

  6. Possible deletion of a developmentally regulated heavy-chain variable region gene in autoimmune diseases

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Pei-Ming; Olee, Tsaiwei; Kozin, F.; Carson, D.A.; Chen, P.P. (Research Institute of Scripps Clinic, La Jolla, CA (USA)); Olsen, N.J. (Vanderbilt Univ., Nashville, TN (USA)); Siminovitch, K.A. (Univ. of Toronto (Canada))

    1990-10-01

    Several autoantibody-associated variable region (V) genes are preferentially expressed during early ontogenic development, suggesting strongly that they are of developmental and physiological importance. As such, it is possible that polymorphisms in one or more of these genes may alter susceptibility to autoimmune disease. The authors have searched extensively for a probe related to a developmentally regulated V gene that has the power to differentiate among highly homologous V genes in human populations. Using such a probe (i.e., Humhv3005/P1) related to both anti-DNA and anti-IgG autoantibodies, they studied restriction fragment length polymorphisms in patients with rheumatoid arthritis and systemic lupus erythematosus and found an apparent heavy-chain V (V{sub H}) gene deletion that was nearly restricted to the autoimmune patients. These data suggest that deletions of physiologically important V{sub H} genes may increase the risk of autoimmunity through indirect effects on the development and homeostasis of the B-cell repertoire.

  7. The highly recombinogenic bz locus lies in an unusually gene-rich region of the maize genome.

    Science.gov (United States)

    Fu, H; Park, W; Yan, X; Zheng, Z; Shen, B; Dooner, H K

    2001-07-17

    The bronze (bz) locus exhibits the highest rate of recombination of any gene in higher plants. To investigate the possible basis of this high rate of recombination, we have analyzed the physical organization of the region around the bz locus. Two adjacent bacterial artificial chromosome clones, comprising a 240-kb contig centered around the Bz-McC allele, were isolated, and 60 kb of contiguous DNA spanning the two bacterial artificial chromosome clones was sequenced. We find that the bz locus lies in an unusually gene-rich region of the maize genome. Ten genes, at least eight of which are shown to be transcribed, are contained in a 32-kb stretch of DNA that is uninterrupted by retrotransposons. We have isolated nearly full length cDNAs corresponding to the five proximal genes in the cluster. The average intertranscript distance between them is just 1 kb, revealing a surprisingly compact packaging of adjacent genes in this part of the genome. At least 11 small insertions, including several previously described miniature inverted repeat transposable elements, were detected in the introns and 3' untranslated regions of genes and between genes. The gene-rich region is flanked at the proximal and distal ends by retrotransposon blocks. Thus, the maize genome appears to have scattered regions of high gene density similar to those found in other plants. The unusually high rate of intragenic recombination seen in bz may be related to the very high gene density of the region.

  8. A GENE FROM HUMAN-CHROMOSOME REGION-3P21 WITH REDUCED EXPRESSION IN SMALL-CELL LUNG-CANCER

    NARCIS (Netherlands)

    CARRITT, B; KOK, K; van den Berg, Anke; OSINGA, J; PILZ, A; HOFSTRA, RMW; DAVIS, MB; VANDERVEEN, AY; RABBITTS, PH; GULATI, K; BUYS, CHCM

    1992-01-01

    A combination of cytogenetic and molecular studies has implicated the p21 region of human chromosome 3 as the probable site of a gene the loss of which contributes to the development of small cell lung cancer. We report here the isolation of a gene from this region which is expressed in normal lung

  9. Association of HLA-C and HCP5 gene regions with the clinical course of HIV-1 infection

    NARCIS (Netherlands)

    D. van Manen; N.A. Kootstra; B. Boeser-Nunnink; M.A. Handulle; A.B. van 't Wout; H. Schuitemaker

    2009-01-01

    Background: Recently, a genome-wide association analysis revealed single-nucleotide polymorphisms (SNPs) in the gene regions of HLA-C and HCP5 to be associated with viral load at set point and SNPs in the RNF39/ZNRD1 gene region to be associated with HIV-1 disease course. Methods: We Studied whether

  10. Early B-cell factor 1 (EBF1) is critical for transcriptional control of SLAMF1 gene in human B cells.

    Science.gov (United States)

    Schwartz, Anton M; Putlyaeva, Lidia V; Covich, Milica; Klepikova, Anna V; Akulich, Kseniya A; Vorontsov, Ilya E; Korneev, Kirill V; Dmitriev, Sergey E; Polanovsky, Oleg L; Sidorenko, Svetlana P; Kulakovskiy, Ivan V; Kuprash, Dmitry V

    2016-10-01

    Signaling lymphocytic activation molecule family member 1 (SLAMF1)/CD150 is a co-stimulatory receptor expressed on a variety of hematopoietic cells, in particular on mature lymphocytes activated by specific antigen, costimulation and cytokines. Changes in CD150 expression level have been reported in association with autoimmunity and with B-cell chronic lymphocytic leukemia. We characterized the core promoter for SLAMF1 gene in human B-cell lines and explored binding sites for a number of transcription factors involved in B cell differentiation and activation. Mutations of SP1, STAT6, IRF4, NF-kB, ELF1, TCF3, and SPI1/PU.1 sites resulted in significantly decreased promoter activity of varying magnitude, depending on the cell line tested. The most profound effect on the promoter strength was observed upon mutation of the binding site for Early B-cell factor 1 (EBF1). This mutation produced a 10-20 fold drop in promoter activity and pinpointed EBF1 as the master regulator of human SLAMF1 gene in B cells. We also identified three potent transcriptional enhancers in human SLAMF1 locus, each containing functional EBF1 binding sites. Thus, EBF1 interacts with specific binding sites located both in the promoter and in the enhancer regions of the SLAMF1 gene and is critical for its expression in human B cells.

  11. Aberrant Expression of Critical Genes during Secondary Cell Wall Biogenesis in a Cotton Mutant, Ligon Lintless-1 (Li-1

    Directory of Open Access Journals (Sweden)

    James J. Bolton

    2009-01-01

    Full Text Available Over ninety percent of the value of cotton comes from its fiber; however, the genetic mechanisms governing fiber development are poorly understood. Due to their biochemical and morphological diversity in fiber cells cotton fiber mutants have been useful in examining fiber development; therefore, using the Ligon Lintless (Li-1 mutant, a monogenic dominant cotton mutant with very short fibers, we employed the high throughput approaches of microarray technology and real time PCR to gain insights into what genes were critical during the secondary cell wall synthesis stage. Comparative transcriptome analysis of the normal TM-1 genotype and the near isogenic Li-1 revealed that over 100 transcripts were differentially expressed at least 2-fold during secondary wall biogenesis, although the genetic profile of the expansion phase showed no significant differences in the isolines. Of particular note, we identified three candidate gene families-expansin, sucrose synthase, and tubulin—whose expression in Li-1 deviates from normal expression patterns of its parent, TM-1. These genes may contribute to retarded growth of fibers in Li-1 since they are fiber-expressed structural and metabolic genes. This work provides more details into the mechanisms of fiber development, and suggests the Li gene is active during the later stages of fiber development.

  12. Fractionation of Synteny in a Genomic Region Containing Tandemly Duplicated Genes Across Glycine max, Medicago truncatula and Arabidopsis thaliana

    Science.gov (United States)

    Extended comparison of gene sequences found on homeologous soybean BACs to Medicago truncatula and Arabidopsis thaliana genomic sequences demonstrated a network of synteny within conserved regions interrupted by gene addition and/or deletions. Consolidation of gene order among all three species prov...

  13. Variation in the sequence and modification state of the human insulin gene flanking regions.

    Science.gov (United States)

    Ullrich, A; Dull, T J; Gray, A; Philips, J A; Peter, S

    1982-04-10

    The nucleotide sequence of a highly repetitive sequence region upstream from the human insulin gene is reported. The length of this region varies between alleles in the population, and appears to be stably transmitted to the next generation in a Mendelian fashion. There is no significant correlation between the length of this sequence and two types of diabetes mellitus. We observe variation in the cleavability of a BglI recognition site downstream from the human insulin gene, which is probably due to variable nucleotide modification. This presumed modification state appears not to be inherited, and varies between tissues within an individual and between individuals for a given tissue. Both alleles in a given tissue DNA sample are modified to the same extent.

  14. [Association between single nucleotide polymorphisms of 5'-untranslated region of GPx4 gene and male infertility].

    Science.gov (United States)

    Liu, Shu-yuan; Zhang, Chang-jun; Si, Xiao-min; Yao, Yu-feng; Shi, Lei; Ke, Jin-kun; Yu, Liang; Shi, Li; Yang, Zhao-qin; Huang, Xiao-qin; Sun, Hao; Chu, Jia-you

    2011-06-01

    To study the association between the single nucleotide polymorphisms (SNPs) of the 5'-untranslated region (5'-UTR) of phospholipid hydroperoxide glutathione peroxidase (GPx4 or PHGPx) gene and oligo- or asthenozoospermic male infertility. The 5'-UTR region of the GPx4 gene was amplified from infertile men and controls using the polymerase chain reaction and was analyzed for polymorphisms by direct sequencing. A total of 9 SNPs were present in the cohort, however there were no significant differences in these 9 SNPs between the case and control groups. According to the results of linkage disequilibrium analysis and haplotype construction, one haplotype (rs757229-rs757230-rs4588110-rs3746165-rs3746166: C-G-G-T-A) was present only in the control men, and significant difference was detected(Pinfertility. However, the haplotype (rs757229-rs757230-rs4588110- rs3746165-rs3746166: C-G-G-T-A) might be a protective haplotype.

  15. Genes involved in complex adaptive processes tend to have highly conserved upstream regions in mammalian genomes

    Directory of Open Access Journals (Sweden)

    Kohane Isaac

    2005-11-01

    Full Text Available Abstract Background Recent advances in genome sequencing suggest a remarkable conservation in gene content of mammalian organisms. The similarity in gene repertoire present in different organisms has increased interest in studying regulatory mechanisms of gene expression aimed at elucidating the differences in phenotypes. In particular, a proximal promoter region contains a large number of regulatory elements that control the expression of its downstream gene. Although many studies have focused on identification of these elements, a broader picture on the complexity of transcriptional regulation of different biological processes has not been addressed in mammals. The regulatory complexity may strongly correlate with gene function, as different evolutionary forces must act on the regulatory systems under different biological conditions. We investigate this hypothesis by comparing the conservation of promoters upstream of genes classified in different functional categories. Results By conducting a rank correlation analysis between functional annotation and upstream sequence alignment scores obtained by human-mouse and human-dog comparison, we found a significantly greater conservation of the upstream sequence of genes involved in development, cell communication, neural functions and signaling processes than those involved in more basic processes shared with unicellular organisms such as metabolism and ribosomal function. This observation persists after controlling for G+C content. Considering conservation as a functional signature, we hypothesize a higher density of cis-regulatory elements upstream of genes participating in complex and adaptive processes. Conclusion We identified a class of functions that are associated with either high or low promoter conservation in mammals. We detected a significant tendency that points to complex and adaptive processes were associated with higher promoter conservation, despite the fact that they have emerged

  16. Localization of candidate regions for a novel gene for Kartagener syndrome.

    Science.gov (United States)

    Gutierrez-Roelens, Ilse; Sluysmans, Thierry; Jorissen, Mark; Amyere, Mustapha; Vikkula, Miikka

    2006-07-01

    Asymmetric positioning of internal organs is a characteristics of vertebrates. The normal left-right anatomic positioning, situs solitus, sometimes does not occur normaly, leading to laterality defects. Studies in animal models have shown that laterality decisions are mediated by a cascade of genes that lead to the asymmetric expression of Nodal, LEFTA, LEFTB and PITX2 in the lateral plate mesoderm. A search for mutations in genes implicated in left-right patterning in animal models allowed genes associated with heterotaxia defects in humans to be identified. However, these genes explain only a small percentage of human situs defects, suggesting that other genes must play a role. In this study, we report a consanguineous family of Turkish origin, composed of two unaffected parents and three children, two of whom presented Kartagener syndrome. On the basis of their family history, we hypothesize autosomal recessive mode of inheritance. A genotype analysis with polymorphic markers did not show linkage with any known genes or loci causing laterality disorders. Array CGH did not detect a duplication or microdeletion greater than 1 Mb as a possible cause. Genome wide screening using 10 K Affymetrix SNP chips was performed, allowing the identification of two regions of autozygosity, one in chromosome 1 and the other on chromosome 7. In the chromosome 1 locus, a strong candidate gene, encoding the kinesin-associated protein 3 (KIF3AP) was not mutated, based on SSCP/heteroduplex analysis and direct sequencing. These data provide a basis for the identification of a novel gene implicated in Kartagener syndrome.

  17. Recombination events near the immunoglobulin Cmu gene join variable and constant region genes, switch heavy-chain expression, or inactivate the locus.

    Science.gov (United States)

    Cory, S; Webb, E; Gough, J; Adams, J M

    1981-04-28

    Immunoglobulin heavy-chain expression is initiated by recombination between a variable region (VH) gene and one of several joining region (JH) genes located near the mu constant region (Cmu) gene, and the active VH gene can subsequently switch to another CH gene. That the general mechanism for CH switching involves recombination between sites within the JH-Cmu intervening sequence and the 5' flanking region of another CH gene is supported here by Southern blot hybridization analysis of eight IgG- and IgA-secreting plasmacytomas. An alternative model requiring successive VH linkage to similar JH clusters near each CH gene is shown to be very unlikely since the mouse genome appears to contain only one complement of the JH locus and no JH gene was detectable within large cloned sequences flanking germline C gamma 3 and C gamma 1 genes. Thus, VH-JH joining and CH switching are mediated by separate regions of "the joining-switch" or J-S element. In each plasmacytoma examined, the J-S element had undergone recombination within both the JH locus and the switch region and was shown to be linked to the functional CH gene in an IgG3, and IgG1, and three IgA secretors. Both JH joining and CH switching occurred by deletion of DNA. Switch recombination occurred at more than one site within the J-S element in different lines, even for recombination with the same CH gene. Significantly, although heavy-chain expression is restricted to one allele ("allelic exclusion"), all rearranged in each plasmacytoma. Some rearrangements were aberrant, involving, for example, deletion of all JH genes from the allele. Hence, an error-prone recombination machinery may account for allelic exclusion in many plasmacytomas.

  18. Organization and evolution of a gene-rich region of the mouse genome: a 12.7-Mb region deleted in the Del(13)Svea36H mouse.

    Science.gov (United States)

    Mallon, Ann-Marie; Wilming, Laurens; Weekes, Joseph; Gilbert, James G R; Ashurst, Jennifer; Peyrefitte, Sandrine; Matthews, Lucy; Cadman, Matthew; McKeone, Richard; Sellick, Chris A; Arkell, Ruth; Botcherby, Marc R M; Strivens, Mark A; Campbell, R Duncan; Gregory, Simon; Denny, Paul; Hancock, John M; Rogers, Jane; Brown, Steve D M

    2004-10-01

    Del(13)Svea36H (Del36H) is a deletion of approximately 20% of mouse chromosome 13 showing conserved synteny with human chromosome 6p22.1-6p22.3/6p25. The human region is lost in some deletion syndromes and is the site of several disease loci. Heterozygous Del36H mice show numerous phenotypes and may model aspects of human genetic disease. We describe 12.7 Mb of finished, annotated sequence from Del36H. Del36H has a higher gene density than the draft mouse genome, reflecting high local densities of three gene families (vomeronasal receptors, serpins, and prolactins) which are greatly expanded relative to human. Transposable elements are concentrated near these gene families. We therefore suggest that their neighborhoods are gene factories, regions of frequent recombination in which gene duplication is more frequent. The gene families show different proportions of pseudogenes, likely reflecting different strengths of purifying selection and/or gene conversion. They are also associated with relatively low simple sequence concentrations, which vary across the region with a periodicity of approximately 5 Mb. Del36H contains numerous evolutionarily conserved regions (ECRs). Many lie in noncoding regions, are detectable in species as distant as Ciona intestinalis, and therefore are candidate regulatory sequences. This analysis will facilitate functional genomic analysis of Del36H and provides insights into mouse genome evolution.

  19. Candidate genes within a 143 kb region of the flower sex locus in Vitis.

    Science.gov (United States)

    Fechter, Iris; Hausmann, Ludger; Daum, Margrit; Sörensen, Thomas Rosleff; Viehöver, Prisca; Weisshaar, Bernd; Töpfer, Reinhard

    2012-03-01

    Wild Vitis species are dioecious plants, while the cultivated counterpart, Vitis vinifera subspec. vinifera, generally shows hermaphroditic flowers. In Vitis the genetic determinants of flower sex have previously been mapped to a region on chromosome 2. In a combined strategy of map-based cloning and the use of the publicly available grapevine reference genome sequence, the structure of the grapevine flower sex locus has been elucidated with the subsequent identification of candidate genes which might be involved in the development of the different flower sex types. In a fine mapping approach, the sex locus in grapevine was narrowed down using a population derived from a cross of a genotype with a Vitis vinifera background ('Schiava Grossa' × 'Riesling') with the male rootstock cv. 'Börner' (V. riparia × V. cinerea). A physical map of 143 kb was established from BAC clones spanning the 0.5 cM region defined by the closest flanking recombination break points. Sequencing and gene annotation of the entire region revealed several candidate genes with a potential impact on flower sex formation. One of the presumed candidate genes, an adenine phosphoribosyltransferase, was analysed in more detail. The results led to the development of a marker for the presence or absence of the female alleles, while the male and hermaphroditic alleles are still to be differentiated. The impact of other candidate genes is discussed, especially with regard to plant hormone actions. The markers developed will permit the selection of female breeding lines which do not require laborious emasculation thus considerably simplifying grapevine breeding. The genetic finger prints displayed that our cultivated grapevines frequently carry a female allele while homozygous hermaphrodites are rare.

  20. Dual DNA methylation patterns in the CNS reveal developmentally poised chromatin and monoallelic expression of critical genes.

    Science.gov (United States)

    Wang, Jinhui; Valo, Zuzana; Bowers, Chauncey W; Smith, David D; Liu, Zheng; Singer-Sam, Judith

    2010-11-04

    As a first step towards discovery of genes expressed from only one allele in the CNS, we used a tiling array assay for DNA sequences that are both methylated and unmethylated (the MAUD assay). We analyzed regulatory regions of the entire mouse brain transcriptome, and found that approximately 10% of the genes assayed showed dual DNA methylation patterns. They include a large subset of genes that display marks of both active and silent, i.e., poised, chromatin during development, consistent with a link between differential DNA methylation and lineage-specific differentiation within the CNS. Sixty-five of the MAUD hits and 57 other genes whose function is of relevance to CNS development and/or disorders were tested for allele-specific expression in F(1) hybrid clonal neural stem cell (NSC) lines. Eight MAUD hits and one additional gene showed such expression. They include Lgi1, which causes a subtype of inherited epilepsy that displays autosomal dominance with incomplete penetrance; Gfra2, a receptor for glial cell line-derived neurotrophic factor GDNF that has been linked to kindling epilepsy; Unc5a, a netrin-1 receptor important in neurodevelopment; and Cspg4, a membrane chondroitin sulfate proteoglycan associated with malignant melanoma and astrocytoma in human. Three of the genes, Camk2a, Kcnc4, and Unc5a, show preferential expression of the same allele in all clonal NSC lines tested. The other six genes show a stochastic pattern of monoallelic expression in some NSC lines and bi-allelic expression in others. These results support the estimate that 1-2% of genes expressed in the CNS may be subject to allelic exclusion, and demonstrate that the group includes genes implicated in major disorders of the CNS as well as neurodevelopment.

  1. Dual DNA methylation patterns in the CNS reveal developmentally poised chromatin and monoallelic expression of critical genes.

    Directory of Open Access Journals (Sweden)

    Jinhui Wang

    Full Text Available As a first step towards discovery of genes expressed from only one allele in the CNS, we used a tiling array assay for DNA sequences that are both methylated and unmethylated (the MAUD assay. We analyzed regulatory regions of the entire mouse brain transcriptome, and found that approximately 10% of the genes assayed showed dual DNA methylation patterns. They include a large subset of genes that display marks of both active and silent, i.e., poised, chromatin during development, consistent with a link between differential DNA methylation and lineage-specific differentiation within the CNS. Sixty-five of the MAUD hits and 57 other genes whose function is of relevance to CNS development and/or disorders were tested for allele-specific expression in F(1 hybrid clonal neural stem cell (NSC lines. Eight MAUD hits and one additional gene showed such expression. They include Lgi1, which causes a subtype of inherited epilepsy that displays autosomal dominance with incomplete penetrance; Gfra2, a receptor for glial cell line-derived neurotrophic factor GDNF that has been linked to kindling epilepsy; Unc5a, a netrin-1 receptor important in neurodevelopment; and Cspg4, a membrane chondroitin sulfate proteoglycan associated with malignant melanoma and astrocytoma in human. Three of the genes, Camk2a, Kcnc4, and Unc5a, show preferential expression of the same allele in all clonal NSC lines tested. The other six genes show a stochastic pattern of monoallelic expression in some NSC lines and bi-allelic expression in others. These results support the estimate that 1-2% of genes expressed in the CNS may be subject to allelic exclusion, and demonstrate that the group includes genes implicated in major disorders of the CNS as well as neurodevelopment.

  2. Complete structure and organization of immunoglobulin heavy chain constant region genes in a phylogenetically primitive vertebrate.

    OpenAIRE

    Kokubu, F; Hinds, K.; Litman, R.; Shamblott, M J; Litman, G. W.

    1988-01-01

    Immunoglobulin (Ig) gene organization in Heterodontus francisci (horned shark), a phylogenetically primitive vertebrate, is unique. Homologous Ig heavy chain variable (VH) and constant region (CH) specific probes were used to screen a spleen cDNA library constructed in lambda gt11. Both secretory (SEC) and transmembrane (TM) cDNA clones were recovered; the latter were identified by a negative selection strategy. The complete sequence of the CH portion of a Heterodontus genomic DNA-lambda clon...

  3. Mutations in the Translated Region of the Lactase Gene (LCT) Underlie Congenital Lactase Deficiency

    OpenAIRE

    Kuokkanen, Mikko; Kokkonen, Jorma; Enattah, Nabil Sabri; Ylisaukko-oja, Tero; Komu, Hanna; Varilo, Teppo; Peltonen, Leena; Savilahti, Erkki; Järvelä, Irma

    2005-01-01

    Congenital lactase deficiency (CLD) is a severe gastrointestinal disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. We initially assigned the CLD locus by linkage and linkage disequilibrium on 2q21 in 19 Finnish families. Here we report the molecular background of CLD via characterization of five distinct mutations in the coding region of the lactase (LCT) gene. Twenty-seven patients out of 32 (84%) were homozygous for a nonsense mu...

  4. Seasonal and regional differences in gene expression in the brain of a hibernating mammal.

    Directory of Open Access Journals (Sweden)

    Christine Schwartz

    Full Text Available Mammalian hibernation presents a unique opportunity to study naturally occurring neuroprotection. Hibernating ground squirrels undergo rapid and extreme physiological changes in body temperature, oxygen consumption, and heart rate without suffering neurological damage from ischemia and reperfusion injury. Different brain regions show markedly different activity during the torpor/arousal cycle: the cerebral cortex shows activity only during the periodic returns to normothermia, while the hypothalamus is active over the entire temperature range. Therefore, region-specific neuroprotective strategies must exist to permit this compartmentalized spectrum of activity. In this study, we use the Illumina HiSeq platform to compare the transcriptomes of these two brain regions at four collection points across the hibernation season: April Active, October Active, Torpor, and IBA. In the cerebral cortex, 1,085 genes were found to be differentially expressed across collection points, while 1,063 genes were differentially expressed in the hypothalamus. Comparison of these transcripts indicates that the cerebral cortex and hypothalamus implement very different strategies during hibernation, showing less than 20% of these differentially expressed genes in common. The cerebral cortex transcriptome shows evidence of remodeling and plasticity during hibernation, including transcripts for the presynaptic cytomatrix proteins bassoon and piccolo, and extracellular matrix components, including laminins and collagens. Conversely, the hypothalamic transcriptome displays upregulation of transcripts involved in damage response signaling and protein turnover during hibernation, including the DNA damage repair gene RAD50 and ubiquitin E3 ligases UBR1 and UBR5. Additionally, the hypothalamus transcriptome also provides evidence of potential mechanisms underlying the hibernation phenotype, including feeding and satiety signaling, seasonal timing mechanisms, and fuel

  5. Phenotype of mutations in the promoter region of the β-globin gene.

    Science.gov (United States)

    Ropero, Paloma; Erquiaga, Sara; Arrizabalaga, Beatriz; Pérez, Germán; de la Iglesia, Silvia; Torrejón, María José; Gil, Celia; Elena, Cela; Tenorio, María; Nieto, Jorge M; de la Fuente-Gonzalo, Félix; Villegas, Ana; González Fernández, Fernando-Ataúlfo; Martínez, Rafael

    2017-10-01

    β(+)-Thalassaemia is characterised by reduced production of β chains, which decrease can be caused by mutations in the promoter region (CACCC or TATA box), and is classified as mild or silent depending on the extent of β-globin chain reduction. In both cases, homozygotes or compound heterozygotes for these mutations usually have thalassaemia intermedia. Frequently the diagnosis is made in adulthood or even in old age. A total of 37 alterations in the promoter region have been described so far. In this report we describe the mutations found in the promoter region of the β-globin gene in a single hospital in Madrid. Between 1998 and 2015, more than 9000 blood samples were analysed for full blood count and underwent haemoglobin electrophoresis and high performance liquid chromatography. Genetic analysis of the β and Gγ-globin genes was carried out by automatic sequencing and, in the case of α genes, by multiplex PCR. 35 samples showed mutation in the promoter region of the β-globin gene, with a total of six different mutations identified: one in the distal CACCC box, two in the proximal CACCC box, three in the ATA box. Any alterations in the proximal CACCC and TATA boxes lead to a moderate decrease in synthesis of the β-globin chain, which has been demonstrated in cases of thalassaemia intermedia that have presented in the second decade of life with a moderate clinical course. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. Transmission test for linkage disequilibrium: The insulin gene region and insulin-dependent diabetes mellitus (IDDM)

    Energy Technology Data Exchange (ETDEWEB)

    Spielman, R.S.; McGinnis, R.E. (Univ. of Pennsylvania School of Medicine, Philadelphia (United States)); Ewens, W.J. (Univ. of Pennsylvania, Philadelphia (United States))

    1993-03-01

    A population association has consistently been observed between insulin-dependent diabetes mellitus (IDDM) and the class 1 alleles of the region of tandem-repeat DNA (5[prime] flanking polymorphism [5[prime]FP])adjacent to the insulin gene on chromosome 11p. This finding suggests that the insulin gene region contains a gene or genes contributing to IDDM susceptibility. However, several studies that have sought to show linkage with IDDM by testing for cosegregation in affected sib pairs have failed to find evidence for linkage. As means for identifying genes for complex diseases, both the association and the affected-sib-pairs approaches have limitations. It is well known that population association between a disease and a genetic marker can arise as an artifact of population structure, even in the absence of linkage. On the other hand, linkage studies with modest numbers of affected sib pairs may fail to detect linkage, especially if there is linkage heterogeneity. The authors consider an alternative method to test for linkage with a genetic marker when population association has been found. Using data from families with at least one affected child, they evaluate the transmission of the associated marker allele from a heterozygous parent to an affected offspring. This approach has been used by several investigators, but the statistical properties of the method as a test for linkage have not been investigated. In the present paper they describe the statistical basis for this transmission test for linkage disequilibrium (transmission/disequilibrium test [TDT]). They then show the relationship of this test to tests of cosegregation that are based on the proportion of haplotypes or genes identical by descent in affected sibs. The TDT provides strong evidence for linkage between the 5[prime]FP and susceptibility to IDDM. 27 refs., 6 tabs.

  7. Localisation of the gene for achondroplasia to the telomeric region of chromosome 4p

    Energy Technology Data Exchange (ETDEWEB)

    Stoilov, I.; Velinov, M.; Kilpatrick, M.W. [and others

    1994-09-01

    Achondroplasia (ACH), the most common type of genetic dwarfism, is characterized by a variety of skeletal anomalies including disproportionate short stature and rhizomelic shortening of the extremities. The disorder is inherited as an autosomal dominant trait, with a prevalence of 1-15 per 100,000 live births. The etiology of ACH remains unknown, although evidence points to a defect in the maturation of the chondrocytes in the growth plate of the cartilage. To determine the location of the gene responsible for ACH, a panel of 14 families with a total of 43 meioses was genotyped for 40 polymorphic markers for loci randomly distributed throughout the genome. The first significant positive Lod score was obtained for the locus D4S127 (Zmax=3.65 at {theta}=0.03). A series of 20 markers for chromosome 4p16.3 loci were then used to determine the most likely position of the ACH gene. Two additional loci, D4S412 and IDUA, showed strong linkage to the disease (Zmax=3.34 at {theta}=0.03 and Zmax=3.35 at {theta}=0.0, respectively). Multipoint analysis and direct counting of recombinants places the ACH gene in a 2.5 cM region between the marker D4S43 and the chromosome 4p telomere. No evidence was found for genetic heterogeneity. The ACH region contains a number of genes, including that for the fibroblast growth factor receptor FGFR3, which are being evaluated as candidates for the ACH gene. This identification of tightly linked polymorphic markers, as well as being the first step in the characterization of the ACH gene, offers the possibility of DNA based prenatal diagnosis of this disorder.

  8. Molecular characterization of genes encoding the quinolone resistance determining regions of Malaysian Streptococcus pneumoniae strains

    Directory of Open Access Journals (Sweden)

    Kumari N

    2008-01-01

    Full Text Available Genes encoding the quinolones resistance determining regions (QRDRs in Streptococcus pneumoniae were detected by PCR and the sequence analysis was carried out to identify point mutations within these regions. The study was carried out to observe mutation patterns among S. pneumoniae strains in Malaysia. Antimicrobial susceptibility testing of 100 isolates was determined against various antibiotics, out of which 56 strains were categorised to have reduced susceptibility to ciprofloxacin (≥2 μg/mL. These strains were subjected to PCR amplification for presence of the gyrA, parC , gyrB and parE genes. Eight representative strains with various susceptibilities to fluoroquinolones were sequenced. Two out of the eight isolates that were sequenced were shown to have a point mutation in the gyrA gene at position Ser81. The detection of mutation at codon Ser81 of the gyrA gene suggested the potential of developing fluoroquinolone resistance among S. pneumoniae isolates in Malaysia. However, further experimental work is required to confirm the involvement of this mutation in the development of fluoroquinolone resistance in Malaysia.

  9. Disruption of Imprinted Genes at Chromosome Region 11p15.5 in Paediatric Rhabdomyosarcoma

    Directory of Open Access Journals (Sweden)

    John Anderson

    1999-10-01

    Full Text Available Rhabdomyosarcomas are characterized by loss of heterozygosity (LOH at chromosome region 11pl5.5, a region known to contain several imprinted genes including insulin-like growth factor 2 (IGF2, H19, p57KIP2. We analyzed 48 primary tumour samples and found distinct genetic changes at 11p15.5 in alveolar and embryonal histological subtypes. LOH was a feature of embryonal tumours, but at a lower frequency than previous studies. Loss of imprinting (LOI of the IGF2 gene was detected in 6 of 13 informative cases, all harbouring PAX3—FKHR or PAX7—FKHR fusion genes characteristic of alveolar histology. In contrast, H19 imprinting was maintained in 14 of 15 informative cases and the case with H19 LOI had maintenance of the IGF2 imprint indicating separate mechanisms controlling imprinting of IGF2 and H19. The adult promoter of IGF2, P1, was used in 5 of 14 tumours and its expression was unrelated to IGF2 imprinting status implying a further mechanism of altered IGF2 regulation. The putative tumour suppressor gene p57KIP2 was expressed in 15 of 29 tumours and expression was unrelated to allele status. Moreover, in tumours with p57KIP2 expression, there was no evidence for inactivating mutations, suggesting that p57KIP2 is not a tumour suppressor in rhabdomyosarcoma.

  10. Genetic Diversity and Balancing Selection within the Human Phenylalanine Hydroxylase (PAH Gene Region in Iranian Population

    Directory of Open Access Journals (Sweden)

    J Mowla

    2012-04-01

    Full Text Available Background:Genetic diversity of three polymorphic markers in the phenylalanine hydroxylase(PAH gene region including PvuII(a, PAHSTR and MspI were investigated.Methods:Unrelated individuals (n=139 from the Iranian populations were genotyped using primers specific to PAH gene markers including PvuII(a,MspI and PAHSTR. The amplified products for PvuII(a,MspI were digested using the appropriate restriction enzymes and separated on 1.5% agarose. The PAHSTR alleles were identified using polyacrylamide gel electrophoresis followed by silver staining. The exact size of the STR alleles was determined by sequencing. The allele frequency and population status of the alleles were estimated using PHASE, FBAT and GENEPOP software.Results: The estimated degree of heterozygosity for PAHSTR, MspI and PvuII (a was 66%, 56% and 58%, respectively. The haplotype estimation analysis of the markers resulted in nine informative haplotypes with frequencies ≥5%.Moreover,the results obtained from Ewens-Watterson test for neutrality suggested that the markers were under balancing selection in the Iranian population.Conclusion:These findings suggested the presence of genetic diversity at these three markers in the PAH gene region. Therefore, the markers could be considered as functional markers for linkage analysis of the PAH gene mutations in the Iranian families with the PKU disease.

  11. [Regional features of obesity-associated gene polymorphism (rs9939609 FTO gene and gene Trp64Arg ADRB3) in Russian population].

    Science.gov (United States)

    Baturin, A K; Sorokina, E Iu; Pogozheva, A V; Peskova, E V; Makurina, O N; Tutel'ian, V A

    2014-01-01

    Recent studies have shown a significant association with obesity polymorphisms: rs9939609 gene due to fat mass and obesity FTO in European and some Asian and African American populations Trp64Arg ADRB3 gene in several European populations. Association of variants rs9939609 and Trp64Arg obesity was studied in 1244 the inhabitants of Moscow and Sverdlovsk regions. Genotyping was performed using allele-specific amplification, detection results in real time using TaqMan-probes complementary DNA polymorphic sites. The frequency of the mutant allele of the FTO gene in the population of Moscow and Sverdlovsk region was 45.1%, with the TT genotype was detected in 30.2% of cases, AT--49.5%, AA--20.3%. Women had the presence of the mutant allele more likely than men (48.4 vs. 42.5%). People with obesity were more genotypes AA (26.3%) and AT (52.8%) compared to the surveyed with a BMI of less than 30 kg/m2 (respectively 18.1 and 50.7%). A significantly higher incidence of risk allele A was found in individuals with obesity (52.6 and 43.4%). The presence of the mutant allele of the gene ADRB3 among the population of Moscow and Sverdlovsk regions was noted in 7.4% of cases. While 15.5% of patients had a heterozygous genotype Trp64Arg ADRB3, that is consistent with international research. The frequency of the risk allele and genotype Arg64 Trp64Arg in women (9.3 and 18.5%) was significantly higher than men (6.2 and 12.2%). The presence of the mutant allele and genotype Trp64Arg ADRB3 (respectively, 9.1 and 18.1%) were significantly more marked in the examined obese compared with those with a body mass index less than 30 kg/m2 (7.4 and 14.9%), but these differences were not statistically significant. The results of these studies suggest that genetic variants of the FTO gene rs9939609 genotype and Trp64Arg ADRB3 contribute to the development of obesity among residents of Moscow and Sverdlovsk Region of Russia. The risk of obesity increases in the case of combined polymorphisms in

  12. Acetylcholinesterase (AChE) gene modification in transgenic animals: functional consequences of selected exon and regulatory region deletion.

    Science.gov (United States)

    Camp, Shelley; Zhang, Limin; Marquez, Michael; de la Torre, Brian; Long, Jeffery M; Bucht, Goran; Taylor, Palmer

    2005-12-15

    AChE is an alternatively spliced gene. Exons 2, 3 and 4 are invariantly spliced, and this sequence is responsible for catalytic function. The 3' alternatively spliced exons, 5 and 6, are responsible for AChE disposition in tissue [J. Massoulie, The origin of the molecular diversity and functional anchoring of cholinesterases. Neurosignals 11 (3) (2002) 130-143; Y. Li, S. Camp, P. Taylor, Tissue-specific expression and alternative mRNA processing of the mammalian acetylcholinesterase gene. J. Biol. Chem. 268 (8) (1993) 5790-5797]. The splice to exon 5 produces the GPI anchored form of AChE found in the hematopoietic system, whereas the splice to exon 6 produces a sequence that binds to the structural subunits PRiMA and ColQ, producing AChE expression in brain and muscle. A third alternative RNA species is present that is not spliced at the 3' end; the intron 3' of exon 4 is used as coding sequence and produces the read-through, unanchored form of AChE. In order to further understand the role of alternative splicing in the expression of the AChE gene, we have used homologous recombination in stem cells to produce gene specific deletions in mice. Alternatively and together exon 5 and exon 6 were deleted. A cassette containing the neomycin gene flanked by loxP sites was used to replace the exon(s) of interest. Tissue analysis of mice with exon 5 deleted and the neomycin cassette retained showed very low levels of AChE expression, far less than would have been anticipated. Only the read-through species of the enzyme was produced; clearly the inclusion of the selection cassette disrupted splicing of exon 4 to exon 6. The selection cassette was then deleted in exon 5, exon 6 and exons 5 + 6 deleted mice by breeding to Ella-cre transgenic mice. AChE expression in serum, brain and muscle has been analyzed. Another AChE gene targeted mouse strain involving a region in the first intron, found to be critical for AChE expression in muscle cells [S. Camp, L. Zhang, M. Marquez, B

  13. Radiation hybrid mapping of a cytokine gene cluster located in the proximal region of 5q

    Energy Technology Data Exchange (ETDEWEB)

    Segal, A.L.; McPherson, J.D.; Wasmuth, J.J. [Univ. of California, Irvine (United States)

    1994-09-01

    The long (q) arm of chromosome 5 has been shown to contain a large number of genes encoding growth factors, growth factor receptors, hormone receptors and neurotransmitter receptors. IL-3, IL-4, IL-5, IL-9, IL-13, GM-CSF and IRF-1 are located in the 5q22-31.1 interval, while three GABA receptors map to 5q33-34. A number of receptors, including the prolactin and growth hormone receptors, the IL-7 receptor and the leukemia inhibitory factor receptor, map to proximal 5p. Genes encoding three of the complement components, C6, C7 and C9, are also located in the same region. YAC data indicates that C6 and C7 lie within 170 kb of each other. We have used a panel of 180 Chinese hamster-human radiation hybrids possessing fragments of human chromosome 5 to construct a physical map of this region of 5q. Two-point and multi-point analyses were done on the data and significant LOD scores (from 3 to 30) were observed. LIFR, PRLR, GHR, IL-7R, C6, C7, C9, TARS, and a number of CEPH-Genethon dinucleotide repeat markers were ordered and mapped. Yeast artificial chromosomes and cosmids have been isolated and inter-Alu PCR products from them are being used to construct a contig and to improve the physical map. The long term goal of this work is to identify and characterize new genes in the region.

  14. Point mutation of 5' noncoding region of BCL-6 gene in primary gastric lymphomas

    Institute of Scientific and Technical Information of China (English)

    Da-Liu Min; Xiao-Yan Zhou; Wen-Tao Yang; Hong-Fen Lu; Tai-Ming Zhang; Ai-Hua Zhen; Pei-Zheng Cao; Da-Ren Shi

    2005-01-01

    AIM: To investigate the mutations of the 5' noncoding region of BCL-6 gene in Chinese patients with primary gastric lymphomas.METHODS: PCR and direct DNA sequencing were used to identify BCL-6 gene mutations in the 5' noncoding region in 29 cases of gastric diffuse large B-cell lymphoma (DLBCL)and 18 cases of gastric mucosa-associated lymphoid tissue (MALT) lymphoma as well as 10 cases of reactive hyperplasia of lymph node (LRH).RESULTS: Six of 29 gastric DLBCLs (20.7%), 4 of 18 gastric MALT lymphomas (22.2%) and 1 of 10 LRHs(10%) were found to have mutations. All mutations were single-base substitutions and the frequency of single-base changes was 0.20x10-2-1.02x10-2 per bp.CONCLUSION: Point mutations in the 5' noncoding region of BCL-6gene are found in Chinese patients with primary gastric DLBCLs and MALT lymphomas, suggesting that they may, in some extent, participate in the pathogenesis of primary gastric DLBCLs and MALT lymphomas.

  15. Cloning and characterizing of the murine IRF-3 gene promoter region.

    Science.gov (United States)

    Xu, Hua-Guo; Liu, Lifei; Gao, Shan; Jin, Rui; Ren, Wei; Zhou, Guo-Ping

    2016-08-01

    The interferon regulatory factor 3 (IRF-3) plays essential roles in inflammation and immune response. Here, we cloned the nucleotide sequence of the 5'-flanking region of the murine IRF-3 gene (mIRF-3) and characterized the molecular mechanisms controlling the mIRF-3 transcriptional activity in NIH3T3 cells. Analyses of a series of 5' deletion constructs demonstrated that a 301 bp region (-255/+46) of the mIRF-3 gene is sufficient for full promoter activity. This region contains IK1, Egr2, Cmyb, E2F1 and YY1 putative transcription factor binding sites. Mutation of Egr2 or YY1 site led to 52-68 % decrease of the mIRF-3 promoter activity, and double Egr2 and YY1 mutation reduced the promoter activity to 20 % of the wild-type promoter activity. Furthermore, knockingdown of endogenous Egr2 or YY1 by a siRNA strategy markedly inhibited the mIRF-3 promoter activity. Chromatin immunoprecipitation assays showed that Egr2 and YY1 interact with the mIRF-3 promoter in vivo. These results suggested that the basal promoter activity of the mIRF-3 gene is regulated by transcription factors Egr2 and YY1 in NIH3T3 cells.

  16. A critical assessment of cross-species detection of gene duplicates using comparative genomic hybridization

    Directory of Open Access Journals (Sweden)

    Renn Suzy CP

    2010-05-01

    Full Text Available Abstract Background Comparison of genomic DNA among closely related strains or species is a powerful approach for identifying variation in evolutionary processes. One potent source of genomic variation is gene duplication, which is prevalent among individuals and species. Array comparative genomic hybridization (aCGH has been successfully utilized to detect this variation among lineages. Here, beyond the demonstration that gene duplicates among species can be quantified with aCGH, we consider the effect of sequence divergence on the ability to detect gene duplicates. Results Using the X chromosome genomic content difference between male D. melanogaster and female D. yakuba and D. simulans, we describe a decrease in the ability to accurately measure genomic content (copy number for orthologs that are only 90% identical. We demonstrate that genome characteristics (e.g. chromatin environment and non-orthologous sequence similarity can also affect the ability to accurately measure genomic content. We describe a normalization strategy and statistical criteria to be used for the identification of gene duplicates among any species group for which an array platform is available from a closely related species. Conclusions Array CGH can be used to effectively identify gene duplication and genome content; however, certain biases are present due to sequence divergence and other genome characteristics resulting from the divergence between lineages. Highly conserved gene duplicates will be more readily recovered by aCGH. Duplicates that have been retained for a selective advantage due to directional selection acting on many loci in one or both gene copies are likely to be under-represented. The results of this study should inform the interpretation of both previously published and future work that employs this powerful technique.

  17. Amygdala nuclei critical for emotional learning exhibit unique gene expression patterns.

    Science.gov (United States)

    Partin, Alexander C; Hosek, Matthew P; Luong, Jonathan A; Lella, Srihari K; Sharma, Sachein A R; Ploski, Jonathan E

    2013-09-01

    The amygdala is a heterogeneous, medial temporal lobe structure that has been implicated in the formation, expression and extinction of emotional memories. This structure is composed of numerous nuclei that vary in cytoarchitectonics and neural connections. In particular the lateral nucleus of the amygdala (LA), central nucleus of the amygdala (CeA), and the basal (B) nucleus contribute an essential role to emotional learning. However, to date it is still unclear to what extent these nuclei differ at the molecular level. Therefore we have performed whole genome gene expression analysis on these nuclei to gain a better understanding of the molecular differences and similarities among these nuclei. Specifically the LA, CeA and B nuclei were laser microdissected from the rat brain, and total RNA was isolated from these nuclei and subjected to RNA amplification. Amplified RNA was analyzed by whole genome microarray analysis which revealed that 129 genes are differentially expressed among these nuclei. Notably gene expression patterns differed between the CeA nucleus and the LA and B nuclei. However gene expression differences were not considerably different between the LA and B nuclei. Secondary confirmation of numerous genes was performed by in situ hybridization to validate the microarray findings, which also revealed that for many genes, expression differences among these nuclei were consistent with the embryological origins of these nuclei. Knowing the stable gene expression differences among these nuclei will provide novel avenues of investigation into how these nuclei contribute to emotional arousal and emotional learning, and potentially offer new genetic targets to manipulate emotional learning and memory.

  18. Post Windstorm Evaluation of Critical Aspects Causing Damage to Rural Houses in the Northern Region of Peninsular Malaysia

    Directory of Open Access Journals (Sweden)

    Shah Zaini Shaharudin

    2017-01-01

    Full Text Available Rural houses are susceptible to roof blown off and severe damage during a windstorm event due to the lack of engineering considerations. The aim of this paper is to conduct a post windstorm evaluation on the damaged rural houses located in the northern region of Peninsula Malaysia. Several activities were involved during the post windstorm survey including site visualization, site measurement and interview. Critical aspects including types of damages, types of houses, gap height, overhang length, roof geometry, roof pitch, roof cladding and terrain category were analysed using a simple bar chart. It is anticipated that the presence of kitchen house influences the overall stability of the rural houses due to the formation of gap height.

  19. Equivalent dose, effective dose and risk assessment from panoramic radiography to the critical organs of head and neck region

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Bong Hae; Nah, Kyung Soo [Dept. of Dental Radiology, College of Dentistry, Pusan National University, Pusan (Korea, Republic of); Lee, Ae Ryeon [Dept. of Pediatric Dentistry, College of Dentistry, Pusan National University, Pusan (Korea, Republic of)

    1995-08-15

    The purpose of this study was to evaluate the equivalent and effective dose, and estimate radiation risk to the critical organs of head and neck region from the use of adult and child mode in panoramic radiography. The results were as follows. 1. The salivary glands showed the highest equivalent and effective dose in adult and child mode. The equivalent and effective dose in adult mode were 837 {mu}Sv and 20.93 {mu}Sv, those in child mode were 462 {mu}Sv and 11.54 {mu}Sv, respectively. 2. Total effective doses to the critical head and neck organs were estimated 34.2l {mu}Sv in adult mode, 20.14 {mu}Sv in child mode. From these data, the probabilities of stochastic effect from adult and child mode were 2.50xl0{sup -6} and 1.47x10{sup -6} 3. The other remainder showed the greatest risk of fatal cancer. The risk estimate were 4.5 and 2.7 fatal malignancies in adult and child mode from million examinations. The bone marrow and thyroid gland showed about 0.1 fatal cancer in adult. and child mode from these examinations.

  20. A 32 kb critical region excluding Y402H in CFH mediates risk for age-related macular degeneration.

    Science.gov (United States)

    Sivakumaran, Theru A; Igo, Robert P; Kidd, Jeffrey M; Itsara, Andy; Kopplin, Laura J; Chen, Wei; Hagstrom, Stephanie A; Peachey, Neal S; Francis, Peter J; Klein, Michael L; Chew, Emily Y; Ramprasad, Vedam L; Tay, Wan-Ting; Mitchell, Paul; Seielstad, Mark; Stambolian, Dwight E; Edwards, Albert O; Lee, Kristine E; Leontiev, Dmitry V; Jun, Gyungah; Wang, Yang; Tian, Liping; Qiu, Feiyou; Henning, Alice K; LaFramboise, Thomas; Sen, Parveen; Aarthi, Manoharan; George, Ronnie; Raman, Rajiv; Das, Manmath Kumar; Vijaya, Lingam; Kumaramanickavel, Govindasamy; Wong, Tien Y; Swaroop, Anand; Abecasis, Goncalo R; Klein, Ronald; Klein, Barbara E K; Nickerson, Deborah A; Eichler, Evan E; Iyengar, Sudha K

    2011-01-01

    Complement factor H shows very strong association with Age-related Macular Degeneration (AMD), and recent data suggest that multiple causal variants are associated with disease. To refine the location of the disease associated variants, we characterized in detail the structural variation at CFH and its paralogs, including two copy number polymorphisms (CNP), CNP147 and CNP148, and several rare deletions and duplications. Examination of 34 AMD-enriched extended families (N = 293) and AMD cases (White N = 4210 Indian = 134; Malay = 140) and controls (White N = 3229; Indian = 117; Malay = 2390) demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH. Regression analysis of seven common haplotypes showed three haplotypes, H1, H6 and H7, as conferring risk for AMD development. Being the most common haplotype H1 confers the greatest risk by increasing the odds of AMD by 2.75-fold (95% CI = [2.51, 3.01]; p = 8.31×10(-109)); Caucasian (H6) and Indian-specific (H7) recombinant haplotypes increase the odds of AMD by 1.85-fold (p = 3.52×10(-9)) and by 15.57-fold (P = 0.007), respectively. We identified a 32-kb region downstream of Y402H (rs1061170), shared by all three risk haplotypes, suggesting that this region may be critical for AMD development. Further analysis showed that two SNPs within the 32 kb block, rs1329428 and rs203687, optimally explain disease association. rs1329428 resides in 20 kb unique sequence block, but rs203687 resides in a 12 kb block that is 89% similar to a noncoding region contained in ΔCNP148. We conclude that causal variation in this region potentially encompasses both regulatory effects at single markers and copy number.

  1. A 32 kb critical region excluding Y402H in CFH mediates risk for age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Theru A Sivakumaran

    Full Text Available Complement factor H shows very strong association with Age-related Macular Degeneration (AMD, and recent data suggest that multiple causal variants are associated with disease. To refine the location of the disease associated variants, we characterized in detail the structural variation at CFH and its paralogs, including two copy number polymorphisms (CNP, CNP147 and CNP148, and several rare deletions and duplications. Examination of 34 AMD-enriched extended families (N = 293 and AMD cases (White N = 4210 Indian = 134; Malay = 140 and controls (White N = 3229; Indian = 117; Malay = 2390 demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH. Regression analysis of seven common haplotypes showed three haplotypes, H1, H6 and H7, as conferring risk for AMD development. Being the most common haplotype H1 confers the greatest risk by increasing the odds of AMD by 2.75-fold (95% CI = [2.51, 3.01]; p = 8.31×10(-109; Caucasian (H6 and Indian-specific (H7 recombinant haplotypes increase the odds of AMD by 1.85-fold (p = 3.52×10(-9 and by 15.57-fold (P = 0.007, respectively. We identified a 32-kb region downstream of Y402H (rs1061170, shared by all three risk haplotypes, suggesting that this region may be critical for AMD development. Further analysis showed that two SNPs within the 32 kb block, rs1329428 and rs203687, optimally explain disease association. rs1329428 resides in 20 kb unique sequence block, but rs203687 resides in a 12 kb block that is 89% similar to a noncoding region contained in ΔCNP148. We conclude that causal variation in this region potentially encompasses both regulatory effects at single markers and copy number.

  2. The brain finger protein gene (ZNF179), a member of the RING finger family, maps within the Smith-Magenis syndrome region at 17p11.2

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Toshiyuki; Arakawa, Yoshiki; Inazawa, Johji [Kyoto Prefectural Univ. of Medicine, Kyoto (Japan)] [and others

    1997-03-31

    Smith-Magenis syndrome (SAIS) is caused by a microdeletion of 17p11.2 and comprises developmental and growth delay, facial abnormalities, unusual behavior and sleep problems. This phenotype may be due to haploinsufficiency of several contiguous genes. The human brain finger protein gene (ZNF179), a member of the RING finger protein family, has been isolated and mapped to l7p11.2. FISH analyses of metaphase or interphase chromosomes of 6 patients with SMS show that ZNF179 was deleted in one of the 2 homologs (17p11.2), indicating a possible association of the defect of this gene with the pathogenesis of SMS. Furthermore, using a prophase FISH ordering system, we sublocalized ZNF179 proximally to LLGL which lies on the critical region for SMS. 27 refs., 2 figs.

  3. Genomic Characterization of Esophageal Squamous Cell Carcinoma Reveals Critical Genes Underlying Tumorigenesis and Poor Prognosis

    Science.gov (United States)

    Qin, Hai-De; Liao, Xiao-Yu; Chen, Yuan-Bin; Huang, Shao-Yi; Xue, Wen-Qiong; Li, Fang-Fang; Ge, Xiao-Song; Liu, De-Qing; Cai, Qiuyin; Long, Jirong; Li, Xi-Zhao; Hu, Ye-Zhu; Zhang, Shao-Dan; Zhang, Lan-Jun; Lehrman, Benjamin; Scott, Alan F.; Lin, Dongxin; Zeng, Yi-Xin; Shugart, Yin Yao; Jia, Wei-Hua

    2016-01-01

    The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. Here, we report somatic mutations found in ESCC from sequencing 10 whole-genome and 57 whole-exome matched tumor-normal sample pairs. Among the identified genes, we characterized mutations in VANGL1 and showed that they accelerated cell growth in vitro. We also found that five other genes, including three coding genes (SHANK2, MYBL2, FADD) and two non-coding genes (miR-4707-5p, PCAT1), were involved in somatic copy-number alterations (SCNAs) or structural variants (SVs). A survival analysis based on the expression profiles of 321 individuals with ESCC indicated that these genes were significantly associated with poorer survival. Subsequently, we performed functional studies, which showed that miR-4707-5p and MYBL2 promoted proliferation and metastasis. Together, our results shed light on somatic mutations and genomic events that contribute to ESCC tumorigenesis and prognosis and might suggest therapeutic targets. PMID:27058444

  4. SINGLE NUCLEOTIDE POLYMORPHISM IN THE CODING REGION OF MYF5 GENE OF THE CAMEL (CAMELUS DROMEDARIUS

    Directory of Open Access Journals (Sweden)

    M. G. SHAH, A. S. QURESHI1, M. REISSMANN2 AND H. J. SCHWARTZ3

    2007-10-01

    Full Text Available The myogenic factors (MYF 5 and 6 are integral to the initiation and development of skeletal muscles and to the maintenance of their phenotypes. Thus, they are candidate genes for growth and meat quality-related traits. The MYF5 gene is expressed during proliferation of myoblasts and comprises 3 exons: 500, 76 and 191 bp long. Genomic DNA was isolated from the camel hair using NucleoSpin Tissue kit. Two animals of each of the six breeds namely, Marecha, Dhatti, Larri, Kohi, Sakrai and Cambelpuri were used for sequencing. For PCR amplification of the gene, a primer pair was designed from homolog regions of already published sequences of farm animals from GenBank. Results showed that exon 1 comprising of 422 bp of the dromedary MYF5 gene was more homologous (94% to the cattle than the dog and human. However, phylogram showed that a small number of mutations had been experienced by dromedary camels at their MYF5 gene and was more near to human than other farm animals.

  5. Regulation of noncoding region for expression of Sendai virus hemagglutinin-neuraminidase (HN) gene

    Institute of Scientific and Technical Information of China (English)

    胡建红; 齐义鹏

    1999-01-01

    Hemagglutinin-neuraminidase (HN) protein was expressed in COS-7 cells, indicating that the expression of HN protein driven by SRα promoter is higher than that driven by chicken β-actin promoter. Moreover, with 5’ noncoding region (NCR) of HN gene, the expression was enhanced. Northern blotting demonstrated that this phenomenon was caused by the difference of HN mRNA transcription. To know the regulatory function of 5’ NCR, HN gene 5’ NCR was replaced by 5’ NCR of keratin gene or cytochrome P-450 gene and the 3’ NCR was deleted by site-directed mutagenesis. By using CAT gene as a reporter, S1 nuclease assay was done to quantitate the HN mRNA transcript in the COS-7 cells co-transfected with the reporter and mutated plasmids, indicating that 5’ NCR is non-specific to the enhancement of HN protein expression, and the 3’ NCR also has a special regulatory function.

  6. Complete structure and organization of immunoglobulin heavy chain constant region genes in a phylogenetically primitive vertebrate.

    Science.gov (United States)

    Kokubu, F; Hinds, K; Litman, R; Shamblott, M J; Litman, G W

    1988-07-01

    Immunoglobulin (Ig) gene organization in Heterodontus francisci (horned shark), a phylogenetically primitive vertebrate, is unique. Homologous Ig heavy chain variable (VH) and constant region (CH) specific probes were used to screen a spleen cDNA library constructed in lambda gt11. Both secretory (SEC) and transmembrane (TM) cDNA clones were recovered; the latter were identified by a negative selection strategy. The complete sequence of the CH portion of a Heterodontus genomic DNA-lambda clone also was determined. The sequences of the individual CH genes differ from each other in all exons. When compared to mammalian prototypes, similarities in exon and intron organization as well as conservation of sequences involved with differential splicing of SEC and TM mRNA indicate that Heterodontus heavy chain genes are of the mu type, although intron lengths are uniformly longer in Heterodontus. Heterodontus genes are not associated, however, with the family of DNA sequences that have been implicated in heavy chain class switching in mammals. Spleen cDNA library screening and RNA blot analyses indicate that mRNAs encoding TM Ig are exceedingly rare. The relationship between this quantitative difference and the distribution of polyadenylation signal sequences suggests that regulation of Ig gene expression in Heterodontus may be highly dependent on position effects.

  7. Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer's disease.

    Science.gov (United States)

    Berchtold, Nicole C; Coleman, Paul D; Cribbs, David H; Rogers, Joseph; Gillen, Daniel L; Cotman, Carl W

    2013-06-01

    Synapses are essential for transmitting, processing, and storing information, all of which decline in aging and Alzheimer's disease (AD). Because synapse loss only partially accounts for the cognitive declines seen in aging and AD, we hypothesized that existing synapses might undergo molecular changes that reduce their functional capacity. Microarrays were used to evaluate expression profiles of 340 synaptic genes in aging (20-99 years) and AD across 4 brain regions from 81 cases. The analysis revealed an unexpectedly large number of significant expression changes in synapse-related genes in aging, with many undergoing progressive downregulation across aging and AD. Functional classification of the genes showing altered expression revealed that multiple aspects of synaptic function are affected, notably synaptic vesicle trafficking and release, neurotransmitter receptors and receptor trafficking, postsynaptic density scaffolding, cell adhesion regulating synaptic stability, and neuromodulatory systems. The widespread declines in synaptic gene expression in normal aging suggests that function of existing synapses might be impaired, and that a common set of synaptic genes are vulnerable to change in aging and AD.

  8. Intervene: a tool for intersection and visualization of multiple gene or genomic region sets.

    Science.gov (United States)

    Khan, Aziz; Mathelier, Anthony

    2017-05-31

    A common task for scientists relies on comparing lists of genes or genomic regions derived from high-throughput sequencing experiments. While several tools exist to intersect and visualize sets of genes, similar tools dedicated to the visualization of genomic region sets are currently limited. To address this gap, we have developed the Intervene tool, which provides an easy and automated interface for the effective intersection and visualization of genomic region or list sets, thus facilitating their analysis and interpretation. Intervene contains three modules: venn to generate Venn diagrams of up to six sets, upset to generate UpSet plots of multiple sets, and pairwise to compute and visualize intersections of multiple sets as clustered heat maps. Intervene, and its interactive web ShinyApp companion, generate publication-quality figures for the interpretation of genomic region and list sets. Intervene and its web application companion provide an easy command line and an interactive web interface to compute intersections of multiple genomic and list sets. They have the capacity to plot intersections using easy-to-interpret visual approaches. Intervene is developed and designed to meet the needs of both computer scientists and biologists. The source code is freely available at https://bitbucket.org/CBGR/intervene , with the web application available at https://asntech.shinyapps.io/intervene .

  9. Crossing the threshold: gene flow, dominance and the critical level of standing genetic variation required for adaptation to novel environments.

    Science.gov (United States)

    Nuismer, S L; MacPherson, A; Rosenblum, E B

    2012-12-01

    Genetic architecture plays an important role in the process of adaptation to novel environments. One example is the role of allelic dominance, where advantageous recessive mutations have a lower probability of fixation than advantageous dominant mutations. This classic observation, termed 'Haldane's sieve', has been well explored theoretically for single isolated populations adapting to new selective regimes. However, the role of dominance is less well understood for peripheral populations adapting to novel environments in the face of recurrent and maladaptive gene flow. Here, we use a combination of analytical approximations and individual-based simulations to explore how dominance influences the likelihood of adaptation to novel peripheral environments. We demonstrate that in the face of recurrent maladaptive gene flow, recessive alleles can fuel adaptation only when their frequency exceeds a critical threshold within the ancestral range.

  10. Specific amplification by PCR of rearranged genomic variable regions of immunoglobulin genes from mouse hybridoma cells.

    Science.gov (United States)

    Berdoz, J; Monath, T P; Kraehenbuhl, J P

    1995-04-01

    We have designed a novel strategy for the isolation of the rearranged genomic fragments encoding the L-VH-D-JH and L-V kappa/lambda-J kappa/lambda regions of mouse immunoglobulin genes. This strategy is based on the PCR amplification of genomic DNA from mouse hybridomas using multiple specific primers chosen in the 5'-untranslated region and in the intron downstream of the rearranged JH/J kappa/lambda sequences. Variable regions with intact coding sequences, including full-length leader peptides (L) can be obtained without previous DNA sequencing. Our strategy is based on a genomic template that produces fragments that do not need to be adapted for recombinant antibody expression, thus facilitating the generation of chimeric and isotype-switched immunoglobulins.

  11. Selection of reference genes in different myocardial regions of an in vivo ischemia/reperfusion rat model for normalization of antioxidant gene expression.

    Science.gov (United States)

    Vesentini, Nicoletta; Barsanti, Cristina; Martino, Alessandro; Kusmic, Claudia; Ripoli, Andrea; Rossi, AnnaMaria; L'Abbate, Antonio

    2012-02-29

    Changes in cardiac gene expression due to myocardial injury are usually assessed in whole heart tissue. However, as the heart is a heterogeneous system, spatial and temporal heterogeneity is expected in gene expression. In an ischemia/reperfusion (I/R) rat model we evaluated gene expression of mitochondrial and cytoplasmatic superoxide dismutase (MnSod, Cu-ZnSod) and thioredoxin reductase (trxr1) upon short (4 h) and long (72 h) reperfusion times in the right ventricle (RV), and in the ischemic/reperfused (IRR) and the remote region (RR) of the left ventricle. Gene expression was assessed by Real-time reverse-transcription quantitative PCR (RT-qPCR). In order to select most stable reference genes suitable for normalization purposes, in each myocardial region we tested nine putative reference genes by geNorm analysis. The genes investigated were: Actin beta (actb), Glyceraldehyde-3-P-dehydrogenase (gapdh), Ribosomal protein L13A (rpl13a), Tyrosine 3-monooxygenase (ywhaz), Beta-glucuronidase (gusb), Hypoxanthine guanine Phosphoribosyltransferase 1 (hprt), TATA binding box protein (tbp), Hydroxymethylbilane synthase (hmbs), Polyadenylate-binding protein 1 (papbn1). According to our findings, most stable reference genes in the RV and RR were hmbs/hprt and hmbs/tbp/hprt respectively. In the IRR, six reference genes were recommended for normalization purposes; however, in view of experimental feasibility limitations, target gene expression could be normalized against the three most stable reference genes (ywhaz/pabp/hmbs) without loss of sensitivity. In all cases MnSod and Cu-ZnSod expression decreased upon long reperfusion, the former in all myocardial regions and the latter in IRR alone. trxr1 expression did not vary. This study provides a validation of reference genes in the RV and in the anterior and posterior wall of the LV of cardiac ischemia/reperfusion model and shows that gene expression should be assessed separately in each region.

  12. Selection of reference genes in different myocardial regions of an in vivo ischemia/reperfusion rat model for normalization of antioxidant gene expression

    Directory of Open Access Journals (Sweden)

    Vesentini Nicoletta

    2012-02-01

    Full Text Available Abstract Background Changes in cardiac gene expression due to myocardial injury are usually assessed in whole heart tissue. However, as the heart is a heterogeneous system, spatial and temporal heterogeneity is expected in gene expression. Results In an ischemia/reperfusion (I/R rat model we evaluated gene expression of mitochondrial and cytoplasmatic superoxide dismutase (MnSod, Cu-ZnSod and thioredoxin reductase (trxr1 upon short (4 h and long (72 h reperfusion times in the right ventricle (RV, and in the ischemic/reperfused (IRR and the remote region (RR of the left ventricle. Gene expression was assessed by Real-time reverse-transcription quantitative PCR (RT-qPCR. In order to select most stable reference genes suitable for normalization purposes, in each myocardial region we tested nine putative reference genes by geNorm analysis. The genes investigated were: Actin beta (actb, Glyceraldehyde-3-P-dehydrogenase (gapdh, Ribosomal protein L13A (rpl13a, Tyrosine 3-monooxygenase (ywhaz, Beta-glucuronidase (gusb, Hypoxanthine guanine Phosphoribosyltransferase 1 (hprt, TATA binding box protein (tbp, Hydroxymethylbilane synthase (hmbs, Polyadenylate-binding protein 1 (papbn1. According to our findings, most stable reference genes in the RV and RR were hmbs/hprt and hmbs/tbp/hprt respectively. In the IRR, six reference genes were recommended for normalization purposes; however, in view of experimental feasibility limitations, target gene expression could be normalized against the three most stable reference genes (ywhaz/pabp/hmbs without loss of sensitivity. In all cases MnSod and Cu-ZnSod expression decreased upon long reperfusion, the former in all myocardial regions and the latter in IRR alone. trxr1 expression did not vary. Conclusions This study provides a validation of reference genes in the RV and in the anterior and posterior wall of the LV of cardiac ischemia/reperfusion model and shows that gene expression should be assessed separately in

  13. Human transcription factor genes involved in neuronal development tend to have high GC content and CpG elements in the proximal promoter region

    Institute of Scientific and Technical Information of China (English)

    Yue-Sheng Long; Jia-Ming Qin; Tao Su; Qi-Hua Zhao; Yong-Hong Yi; Wei-Ping Liao

    2011-01-01

    Transcription factors (TFs) play critical roles in the development of the nervous system, but the transcriptional regulatory mechanisms of these genes are poorly understood. Here we analyzed 5-kb of the 5' flanking genomic DNA sequences of 41 TF genes involved in neuronal development. The results showed that the TF genes tend to have higher GC contents in the proximal region and most of the TF genes have at least one proximal GC-rich (GC content > 60%) promoter with a CpG island. The promoter distribution analysis showed that the GC-poor promoters were sporadically distributed within the 5-kb flanking genomic sequence (FGS); however, more than half (37 of 70) of the GC-rich promoters were located in the proximal region between nucleotides -1 and -500. Luciferase assays showed that partial GC-rich promoters increased gene expression in SH-SY5Y cells and that CpG methylation repressed the promoter activity. This study suggests a potential general mechanism for regulation of TF expression.

  14. Early vertebrate chromosome duplications and the evolution of the neuropeptide Y receptor gene regions

    Directory of Open Access Journals (Sweden)

    Brenner Sydney

    2008-06-01

    Full Text Available Abstract Background One of the many gene families that expanded in early vertebrate evolution is the neuropeptide (NPY receptor family of G-protein coupled receptors. Earlier work by our lab suggested that several of the NPY receptor genes found in extant vertebrates resulted from two genome duplications before the origin of jawed vertebrates (gnathostomes and one additional genome duplication in the actinopterygian lineage, based on their location on chromosomes sharing several gene families. In this study we have investigated, in five vertebrate genomes, 45 gene families with members close to the NPY receptor genes in the compact genomes of the teleost fishes Tetraodon nigroviridis and Takifugu rubripes. These correspond to Homo sapiens chromosomes 4, 5, 8 and 10. Results Chromosome regions with conserved synteny were identified and confirmed by phylogenetic analyses in H. sapiens, M. musculus, D. rerio, T. rubripes and T. nigroviridis. 26 gene families, including the NPY receptor genes, (plus 3 described recently by other labs showed a tree topology consistent with duplications in early vertebrate evolution and in the actinopterygian lineage, thereby supporting expansion through block duplications. Eight gene families had complications that precluded analysis (such as short sequence length or variable number of repeated domains and another eight families did not support block duplications (because the paralogs in these families seem to have originated in another time window than the proposed genome duplication events. RT-PCR carried out with several tissues in T. rubripes revealed that all five NPY receptors were expressed in the brain and subtypes Y2, Y4 and Y8 were also expressed in peripheral organs. Conclusion We conclude that the phylogenetic analyses and chromosomal locations of these gene families support duplications of large blocks of genes or even entire chromosomes. Thus, these results are consistent with two early vertebrate

  15. The variations of ionosphere critical frequency of E layer over the equatorial geomagnetic region in Southeast Asia

    Science.gov (United States)

    Kenpankho, Prasert; Ishii, Mamoru; Supnithi, Pornchai

    2016-07-01

    We investigate the values of the critical frequency of the ionospheric E layer, foE, obtained at Chumphon ionospheric observatory station, Thailand. For a declining phase of the solar cycle 23 during the year 2005-2008 and an inclining phase of the solar cycle 24 during the year 2009-2013, the foE data have been used to investigate the foE variations over the equatorial geomagnetic region in Southeast Asia. A comparison between the observation data and International Reference Ionosphere (IRI) 2012 model has also been investigated and studied. The results show that the foE obtained from IRI 2012 model underestimates foE from Chumphon station especially during the period of 7-11 am and after 6 pm for each day and all seasons. As the results combining with the previous investigations, we suggest that the underestimation of ionospheric foE by IRI 2012 model is helpful for the correction and improvement of IRI model in an equatorial Asia region.

  16. Klf4 Is a Transcriptional Regulator of Genes Critical for EMT, Including Jnk1 (Mapk8)

    Science.gov (United States)

    Tiwari, Neha; Meyer-Schaller, Nathalie; Arnold, Phil; Antoniadis, Helena; Pachkov, Mikhail; van Nimwegen, Erik; Christofori, Gerhard

    2013-01-01

    We have identified the zinc-finger transcription factor Kruppel-like factor 4 (Klf4) among the transcription factors that are significantly downregulated in their expression during epithelial-mesenchymal transition (EMT) in mammary epithelial cells and in breast cancer cells. Loss and gain of function experiments demonstrate that the down-regulation of Klf4 expression is required for the induction of EMT in vitro and for metastasis in vivo. In addition, reduced Klf4 expression correlates with shorter disease-free survival of subsets of breast cancer patients. Yet, reduced expression of Klf4 also induces apoptosis in cells undergoing TGFβ-induced EMT. Chromatin immunoprecipitation/deep-sequencing in combination with gene expression profiling reveals direct Klf4 target genes, including E-cadherin (Cdh1), N-cadherin (Cdh2), vimentin (Vim), β-catenin (Ctnnb1), VEGF-A (Vegfa), endothelin-1 (Edn1) and Jnk1 (Mapk8). Thereby, Klf4 acts as a transcriptional activator of epithelial genes and as a repressor of mesenchymal genes. Specifically, increased expression of Jnk1 (Mapk8) upon down-regulation of its transcriptional repressor Klf4 is required for EMT cell migration and for the induction of apoptosis. The data demonstrate a central role of Klf4 in the maintenance of epithelial cell differentiation and the prevention of EMT and metastasis. PMID:23451207

  17. Molecular structural and functional characterization of STAT1 gene regulatory region in teleost Channa argus.

    Science.gov (United States)

    Jia, Weizhang; Zhou, Xiuxia

    2010-05-15

    The transcription factor STAT1 is involved in signal transduction of type I and II interferons (IFNs). However, the molecular characteristics of the STAT1 regulatory region still remain to be elucidated in teleosts. In the present study, the complete cDNA and the regulatory region of the STAT1 gene were isolated from snakehead (Channa argus). More than 2.4kb 5'-flanking region of STAT1 shares the regulatory elements of IFN-stimulated response element (ISRE) and IFN-gamma activation site (GAS). Consensus ISRE and GAS were located from -373 to -361 and -716 to -724 in the promoter region, respectively. Moreover, it is noticeable that the crucial elements of ISRE (+698 to +710) and GAS (+294 and +301) are present in the first intron of snakehead STAT1. Comparisons of six vertebrate STAT1 5'-flanking regions all present the common sequence characteristics of IFN-induced gene promoter, which include ISRE, GAS and Sp1 sites. In order to further characterize the snakehead STAT1 regulatory region, six reporter constructs of snakehead STAT1 promoter and first intron were generated to examine the specificity to human interferon-gamma (hIFN-gamma). Only those constructs containing the ISRE element showed notable reporter activity after stimulation of Hela cells with hIFN-gamma. However, sequential deletions of putative transcription factor binding sites indicated that GAS elements have little effect on the promoter and intronic activity in response to hIFN-gamma. Taken together, these results suggest that the regulatory mechanisms of IFN-signalling appear to be mediated in a similar manner in fish and mammals.

  18. Reciprocal and nonreciprocal recombination at the glucocerebrosidase gene region: implications for complexity in Gaucher disease.

    Science.gov (United States)

    Tayebi, Nahid; Stubblefield, Barbara K; Park, Joseph K; Orvisky, Eduard; Walker, Jamie M; LaMarca, Mary E; Sidransky, Ellen

    2003-03-01

    Gaucher disease results from an autosomal recessive deficiency of the lysosomal enzyme glucocerebrosidase. The glucocerebrosidase gene is located in a gene-rich region of 1q21 that contains six genes and two pseudogenes within 75 kb. The presence of contiguous, highly homologous pseudogenes for both glucocerebrosidase and metaxin at the locus increases the likelihood of DNA rearrangements in this region. These recombinations can complicate genotyping in patients with Gaucher disease and contribute to the difficulty in interpreting genotype-phenotype correlations in this disorder. In the present study, DNA samples from 240 patients with Gaucher disease were examined using several complementary approaches to identify and characterize recombinant alleles, including direct sequencing, long-template polymerase chain reaction, polymorphic microsatellite repeats, and Southern blots. Among the 480 alleles studied, 59 recombinant alleles were identified, including 34 gene conversions, 18 fusions, and 7 downstream duplications. Twenty-two percent of the patients evaluated had at least one recombinant allele. Twenty-six recombinant alleles were found among 310 alleles from patients with type 1 disease, 18 among 74 alleles from patients with type 2 disease, and 15 among 96 alleles from patients with type 3 disease. Several patients carried two recombinations or mutations on the same allele. Generally, alleles resulting from nonreciprocal recombination (gene conversion) could be distinguished from those arising by reciprocal recombination (crossover and exchange), and the length of the converted sequence was determined. Homozygosity for a recombinant allele was associated with early lethality. Ten different sites of crossover and a shared pentamer motif sequence (CACCA) that could be a hotspot for recombination were identified. These findings contribute to a better understanding of genotype-phenotype relationships in Gaucher disease and may provide insights into the mechanisms

  19. Characterization of the promoter region of biosynthetic enzyme genes involved in berberine biosynthesis in Coptis japonica

    Directory of Open Access Journals (Sweden)

    Yasuyuki Yamada

    2016-09-01

    Full Text Available The presence of alkaloids is rather specific to certain plant species. However, berberine, an isoquinoline alkaloid, is relatively broadly distributed in the plant kingdom. Thus, berberine biosynthesis has been intensively investigated, especially using Coptis japonica cell cultures. Almost all biosynthetic enzyme genes have already been characterized at the molecular level. Particularly, two transcription factors (TFs, a plant-specific WRKY-type transcription factor, CjWRKY1, and a basic helix-loop-helix (bHLH transcription factor, CjbHLH1, were shown to comprehensively regulate berberine biosynthesis in C. japonica cells. In this study, we characterized the promoter region of some biosynthetic enzyme genes and associated cis-acting elements involved in the transcriptional regulation via two TFs. The promoter regions of three berberine biosynthetic enzyme genes (CYP80B2, 4’OMT and CYP719A1 were isolated, and their promoter activities were dissected by a transient assay involving the sequentially truncated promoter::luciferase (LUC reporter constructs. Furthermore, transactivation activities of CjWRKY1 were determined using the truncated promoter::LUC reporter constructs or constructs with mutated cis-elements. These results suggest the involvement of a putative W-box in the regulation of biosynthetic enzyme genes. Direct binding of CjWRKY1 to the W-box DNA sequence was also confirmed by an electrophoresis mobility shift assay (EMSA and by a chromatin immunoprecipitation (ChIP assay. In addition, CjbHLH1 also activated transcription from truncated 4’OMT and CYP719A1 promoters independently of CjWRKY1, suggesting the involvement of a putative E-box. Unexpected transcriptional activation of biosynthetic enzyme genes via a non-W-box sequence and by CjWRKY1 as well as the possible involvement of a GCC-box in berberine biosynthesis in C. japonica are discussed.

  20. Yeast artificial chromosome contigs reveal that distal variable-region genes reside at least 3 megabases from the joining regions in the murine immunoglobulin kappa locus.

    Science.gov (United States)

    George, J B; Li, S; Garrard, W T

    1995-01-01

    The immunoglobulin kappa gene locus encodes 95% of the light chains of murine antibody molecules and is thought to contain up to 300 variable (V kappa)-region genes generally considered to comprise 20 families. To delineate the locus we have isolated 29 yeast artificial chromosome genomic clones that form two contigs, span > 3.5 megabases, and contain two known non-immunoglobulin kappa markers. Using PCR primers specific for 19 V kappa gene families and Southern analysis, we have refined the genetically defined order of these V kappa gene families. Of these, V kappa 2 maps at least 3.0 Mb from the joining (J kappa) region and appears to be the most distal V kappa gene segment. Images Fig. 3 Fig. 4 PMID:8618913

  1. Critical evaluation of HPV16 gene copy number quantification by SYBR green PCR.

    Science.gov (United States)

    Roberts, Ian; Ng, Grace; Foster, Nicola; Stanley, Margaret; Herdman, Michael T; Pett, Mark R; Teschendorff, Andrew; Coleman, Nicholas

    2008-07-24

    Human papilloma virus (HPV) load and physical status are considered useful parameters for clinical evaluation of cervical squamous cell neoplasia. However, the errors implicit in HPV gene quantification by PCR are not well documented. We have undertaken the first rigorous evaluation of the errors that can be expected when using SYBR green qPCR for quantification of HPV type 16 gene copy numbers. We assessed a modified method, in which external calibration curves were generated from a single construct containing HPV16 E2, HPV16 E6 and the host gene hydroxymethylbilane synthase in a 1:1:1 ratio. When testing dilutions of mixed HPV/host DNA in replicate runs, we observed errors in quantifying E2 and E6 amplicons of 5-40%, with greatest error at the lowest DNA template concentration (3 ng/microl). Errors in determining viral copy numbers per diploid genome were 13-53%. Nevertheless, in cervical keratinocyte cell lines we observed reasonable agreement between viral loads determined by qPCR and Southern blotting. The mean E2/E6 ratio in episome-only cells was 1.04, but with a range of 0.76-1.32. In three integrant-only lines the mean E2/E6 ratios were 0.20, 0.72 and 2.61 (values confirmed by gene-specific Southern blotting). When E2/E6 ratios in fourteen HPV16-positive cervical carcinomas were analysed, conclusions regarding viral physical state could only be made in three cases, where the E2/E6 ratio was unavoidable inaccuracies that should be allowed for when quantifying HPV gene copy number. While E6 copy numbers can be considered to provide a useable indication of viral loads, the E2/E6 ratio is of limited value. Previous studies may have overestimated the frequency of mixed episomal/integrant HPV infections.

  2. Accelerated evolution in the protein-coding regions is universal in crotalinae snake venom gland phospholipase A2 isozyme genes.

    Science.gov (United States)

    Nakashima, K; Nobuhisa, I; Deshimaru, M; Nakai, M; Ogawa, T; Shimohigashi, Y; Fukumaki, Y; Hattori, M; Sakaki, Y; Hattori, S

    1995-06-06

    The nucleotide sequences of four genes encoding Trimeresurus gramineus (green habu snake, crotalinae) venom gland phospholipase A2 (PLA2; phosphatidylcholine 2-acylhydrolase, EC 3.1.1.4) isozymes were compared internally and externally with those of six genes encoding Trimeresurus flavoviridis (habu snake, crotalinae) venom gland PLA2 isozymes. The numbers of nucleotide substitutions per site (KN) for the noncoding regions including introns were one-third to one-eighth of the numbers of nucleotide substitutions per synonymous site (KS) for the protein-coding regions of exons, indicating that the noncoding regions are much more conserved than the protein-coding regions. The KN values for the introns were found to be nearly equivalent to those of introns of T. gramineus and T. flavoviridis TATA box-binding protein genes, which are assumed to be a general (nonvenomous) gene. Thus, it is evident that the introns of venom gland PLA2 isozyme genes have evolved at a similar rate to those of nonvenomous genes. The numbers of nucleotide substitutions per nonsynonymous site (KA) were close to or larger than the KS values for the protein-coding regions in venom gland PLA2 isozyme genes. All of the data combined reveal that Darwinian-type accelerated evolution has universally occurred only in the protein-coding regions of crotalinae snake venom PLA2 isozyme genes.

  3. A brain-specific gene cluster isolated from the region of the mouse obesity locus is expressed in the adult hypothalamus and during mouse development

    Energy Technology Data Exchange (ETDEWEB)

    Laig-Webster, M.; Lim, M.E.; Chehab, F.F. [Univ. of California, San Francisco, CA (United States)

    1994-09-01

    The molecular defect underlying an autosomal recessive form of genetic obesity in a classical mouse model C57 BL/6J-ob/ob has not yet been elucidated. Whereas metabolic and physiological disturbances such as diabetes and hypertension are associated with obesity, the site of expression and the nature of the primary lesion responsible for this cascade of events remains elusive. Our efforts aimed at the positional cloning of the ob gene by YAC contig mapping and gene identification have resulted in the cloning of a brain-specific gene cluster from the ob critical region. The expression of this gene cluster is remarkably complex owing to the multitude of brain-specific mRNA transcripts detected on Northern blots. cDNA cloning of these transcripts suggests that they are expressed from different genes as well as by alternate splicing mechanisms. Furthermore, the genomic organization of the cluster appears to consist of at least two identical promoters displaying CpG islands characteristic of housekeeping genes, yet clearly involving tissue-specific expression. Sense and anti-sense synthetic RNA probes were derived from a common DNA sequence on 3 cDNA clones and hybridized to 8-16 days mouse embryonic stages and mouse adult brain sections. Expression in development was noticeable as of the 11th day of gestation and confined to the central nervous system mainly in the telencephalon and spinal cord. Coronal and sagittal sections of the adult mouse brain showed expression only in 3 different regions of the brain stem. In situ hybridization to mouse hypothalamus sections revealed the presence of a localized and specialized group of cells expressing high levels of mRNA, suggesting that this gene cluster may also be involved in the regulation of hypothalamic activities. The hypothalamus has long been hypothesized as a primary candidate tissue for the expression of the obesity gene mainly because of its well-established role in the regulation of energy metabolism and food intake.

  4. The core microprocessor component DiGeorge syndrome critical region 8 (DGCR8) is a nonspecific RNA-binding protein.

    Science.gov (United States)

    Roth, Braden M; Ishimaru, Daniella; Hennig, Mirko

    2013-09-13

    MicroRNA (miRNA) biogenesis follows a conserved succession of processing steps, beginning with the recognition and liberation of an miRNA-containing precursor miRNA hairpin from a large primary miRNA transcript (pri-miRNA) by the Microprocessor, which consists of the nuclear RNase III Drosha and the double-stranded RNA-binding domain protein DGCR8 (DiGeorge syndrome critical region protein 8). Current models suggest that specific recognition is driven by DGCR8 detection of single-stranded elements of the pri-miRNA stem-loop followed by Drosha recruitment and pri-miRNA cleavage. Because countless RNA transcripts feature single-stranded-dsRNA junctions and DGCR8 can bind hundreds of mRNAs, we explored correlations between RNA binding properties of DGCR8 and specific pri-miRNA substrate processing. We found that DGCR8 bound single-stranded, double-stranded, and random hairpin transcripts with similar affinity. Further investigation of DGCR8/pri-mir-16 interactions by NMR detected intermediate exchange regimes over a wide range of stoichiometric ratios. Diffusion analysis of DGCR8/pri-mir-16 interactions by pulsed field gradient NMR lent further support to dynamic complex formation involving free components in exchange with complexes of varying stoichiometry, although in vitro processing assays showed exclusive cleavage of pri-mir-16 variants bearing single-stranded flanking regions. Our results indicate that DGCR8 binds RNA nonspecifically. Therefore, a sequential model of DGCR8 recognition followed by Drosha recruitment is unlikely. Known RNA substrate requirements are broad and include 70-nucleotide hairpins with unpaired flanking regions. Thus, specific RNA processing is likely facilitated by preformed DGCR8-Drosha heterodimers that can discriminate between authentic substrates and other hairpins.

  5. Design Theory and Practice of Critical Regionalism%批判地域主义的设计理论与设计实践

    Institute of Scientific and Technical Information of China (English)

    苏依; 王传东

    2014-01-01

    This paper briefly introduces the historical backg-round of the critical regionalism, at the same time in the dim-ension of time combs the process of critical regionalism from germination to explore to the rectification, explores the core idea of critical regionalism, commonness and difference of ot-her regionalism.%本文简单地介绍了批判的地域主义产生的历史背景,同时在时间维度上梳理了批判性地域主义从萌芽到探索再到正名的过程,并对批判性地域主义的核心思想和与其他地域主义的共性与区别进行了探究。

  6. Adsorption and Diffusion Properties of Ethylene, Benzene and Ethylbenzene in the Cylindrical Pore under Alkylation Reaction near Critical Regions by DCV-GCMD Simulation

    Institute of Scientific and Technical Information of China (English)

    刘涛; 刘洪来; 袁渭康

    2005-01-01

    A cylindrical pore model was used to represent approximately the pore of β-zeolite catalyst that had been used in the alkylation of benzene with ethylene and spherical Lennard-Jones molecules represented the components of the reaction system-ethylene, benzene and ethylbenzene. The dual control volume-grand canonical molecular dynamics (DCV-GCMD) method was used to simulate the adsorption and transport properties of three components under reaction in the cylindrical pore at 250℃ and 270℃ in the pressure range from 1 MPa to 8 MPa. The state map of the reactant mixture in the bulk phase could be divided into several different regions around its critical points. The simulated adsorption and transport properties in the pore were compared between the different near-critical regions. The thorough analysis suggested that the high pressure liquid region is the most suitable region for the alkylation reaction of benzene under the near-critical condition.

  7. A mathematical recursive model for accurate description of the phase behavior in the near-critical region by Generalized van der Waals Equation

    Science.gov (United States)

    Kim, Jibeom; Jeon, Joonhyeon

    2015-01-01

    Recently, related studies on Equation Of State (EOS) have reported that generalized van der Waals (GvdW) shows poor representations in the near critical region for non-polar and non-sphere molecules. Hence, there are still remains a problem of GvdW parameters to minimize loss in describing saturated vapor densities and vice versa. This paper describes a recursive model GvdW (rGvdW) for an accurate representation of pure fluid materials in the near critical region. For the performance evaluation of rGvdW in the near critical region, other EOS models are also applied together with two pure molecule group: alkane and amine. The comparison results show rGvdW provides much more accurate and reliable predictions of pressure than the others. The calculating model of EOS through this approach gives an additional insight into the physical significance of accurate prediction of pressure in the nearcritical region.

  8. Investigation of QTL regions on Chromosome 17 for genes associated with meat color in the pig.

    Science.gov (United States)

    Fan, B; Glenn, K L; Geiger, B; Mileham, A; Rothschild, M F

    2008-08-01

    Previous studies have uncovered several significant quantitative trait loci (QTL) relevant to meat colour traits mapped at the end of SSC17 in the pig. Furthermore, results released from the porcine genome sequencing project have identified genes underlying the entire QTL regions and can further contribute to mining the region for likely causative genes. Ten protein coding genes or novel transcripts located within the QTL regions were screened for single nucleotide polymorphisms (SNPs). Linkage mapping and association studies were carried out in the ISU Berkshire x Yorkshire (B x Y) pig resource family. The total length of the new SSC17 linkage map was 126.6 cM and additional markers including endothelin 3 (EDN3) and phosphatase and actin regulator 3 (PHACTR3) genes were assigned at positions 119.4 cM and 122.9 cM, respectively. A new QTL peak was noted at approximately 120 cM, close to the EDN3 gene, and for some colour traits QTL exceeded the 5% chromosome-wise significance threshold. The association analyses in the B x Y family showed that the EDN3 BslI and PHACTR3 PstI polymorphisms were strongly associated with the subjective colour score and objective colour reflectance measures in the loin, as well as average drip loss percentage and pH value. The RNPC1 DpnII and CTCFL HpyCH4III polymorphisms were associated with some meat colour traits. No significant association between CBLN4, TFAP2C, and four novel transcripts and meat colour traits were detected. The association analyses conducted in one commercial pig line found that both EDN3 BslI and PHACTR3 PstI polymorphisms were associated with meat colour reflectance traits such as centre loin hue angle and Minolta Lightness score. The present findings suggested that the EDN3 and PHACTR3 genes might have potential effects on meat colour in pigs, and molecular mechanisms of their functions are worth exploring.

  9. Absence of mutation at the 5'-upstream promoter region of the TPM4 gene from cardiac mutant axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Denz, Christopher R; Zhang, Chi; Jia, Pingping; Du, Jianfeng; Huang, Xupei; Dube, Syamalima; Thomas, Anish; Poiesz, Bernard J; Dube, Dipak K

    2011-09-01

    Tropomyosins are a family of actin-binding proteins that show cell-specific diversity by a combination of multiple genes and alternative RNA splicing. Of the 4 different tropomyosin genes, TPM4 plays a pivotal role in myofibrillogenesis as well as cardiac contractility in amphibians. In this study, we amplified and sequenced the upstream regulatory region of the TPM4 gene from both normal and mutant axolotl hearts. To identify the cis-elements that are essential for the expression of the TPM4, we created various deletion mutants of the TPM4 promoter DNA, inserted the deleted segments into PGL3 vector, and performed promoter-reporter assay using luciferase as the reporter gene. Comparison of sequences of the promoter region of the TPM4 gene from normal and mutant axolotl revealed no mutations in the promoter sequence of the mutant TPM4 gene. CArG box elements that are generally involved in controlling the expression of several other muscle-specific gene promoters were not found in the upstream regulatory region of the TPM4 gene. In deletion experiments, loss of activity of the reporter gene was noted upon deletion which was then restored upon further deletion suggesting the presence of both positive and negative cis-elements in the upstream regulatory region of the TPM4 gene. We believe that this is the first axolotl promoter that has ever been cloned and studied with clear evidence that it functions in mammalian cell lines. Although striated muscle-specific cis-acting elements are absent from the promoter region of TPM4 gene, our results suggest the presence of positive and negative cis-elements in the promoter region, which in conjunction with positive and negative trans-elements may be involved in regulating the expression of TPM4 gene in a tissue-specific manner.

  10. Genomic Regions Associated With Interspecies Communication in Dogs Contain Genes Related to Human Social Disorders

    Science.gov (United States)

    Persson, Mia E.; Wright, Dominic; Roth, Lina S. V.; Batakis, Petros; Jensen, Per

    2016-01-01

    Unlike their wolf ancestors, dogs have unique social skills for communicating and cooperating with humans. Previously, significant heritabilities for human-directed social behaviors have been found in laboratory beagles. Here, a Genome-Wide Association Study identified two genomic regions associated with dog’s human-directed social behaviors. We recorded the propensity of laboratory beagles, bred, kept and handled under standardized conditions, to initiate physical interactions with a human during an unsolvable problem-task, and 190 individuals were genotyped with an HD Canine SNP-chip. One genetic marker on chromosome 26 within the SEZ6L gene was significantly associated with time spent close to, and in physical contact with, the human. Two suggestive markers on chromosome 26, located within the ARVCF gene, were also associated with human contact seeking. Strikingly, four additional genes present in the same linkage blocks affect social abilities in humans, e.g., SEZ6L has been associated with autism and COMT affects aggression in adolescents with ADHD. This is, to our knowledge, the first genome-wide study presenting candidate genomic regions for dog sociability and inter-species communication. These results advance our understanding of dog domestication and raise the use of the dog as a novel model system for human social disorders. PMID:27685260

  11. [Gene geography of Chile: regional distribution of American, European and African genetic contributions].

    Science.gov (United States)

    Fuentes, Macarena; Pulgar, Iván; Gallo, Carla; Bortolini, María-Cátira; Canizales-Quinteros, Samuel; Bedoya, Gabriel; González-José, Rolando; Ruiz-Linares, Andrés; Rothhammer, Francisco

    2014-03-01

    The geographical distribution of genes plays a key role in genetic epidemiology. The Chilean population has three major stem groups (Native American, European and African). To estimate the regional rate of American, European and African admixture of the Chilean population. Forty single nucleotide polymorphisms (SNP´s) which exhibit substantially different frequencies between Amerindian populations (ancestry-informative markers or AIM´s), were genotyped in a sample of 923 Chilean participants to estimate individual genetic ancestry. The American, European and African individual average admixture estimates for the 15 Chilean Regions were relatively homogeneous and not statistically different. However, higher American components were found in northern and southern Chile and higher European components were found in central Chile. A negative correlation between African admixture and latitude was observed. On the average, American and European genetic contributions were similar and significantly higher than the African contribution. Weighted mean American, European and African genetic contributions of 44.34% ± 3 9%, 51.85% ± 5.44% and 3.81% ± 0.45%, were estimated. Fifty two percent of subjects harbor African genes. Individuals with Aymara and Mapuche surnames have an American admixture of 58.64% and 68.33%, respectively. Half of the Chilean population harbors African genes. Participants with Aymara and Mapuche surnames had a higher American genetic contribution than the general Chilean population. These results confirm the usefulness of surnames as a first approximation to determine genetic ancestry.

  12. Genomic Regions Associated With Interspecies Communication in Dogs Contain Genes Related to Human Social Disorders.

    Science.gov (United States)

    Persson, Mia E; Wright, Dominic; Roth, Lina S V; Batakis, Petros; Jensen, Per

    2016-09-29

    Unlike their wolf ancestors, dogs have unique social skills for communicating and cooperating with humans. Previously, significant heritabilities for human-directed social behaviors have been found in laboratory beagles. Here, a Genome-Wide Association Study identified two genomic regions associated with dog's human-directed social behaviors. We recorded the propensity of laboratory beagles, bred, kept and handled under standardized conditions, to initiate physical interactions with a human during an unsolvable problem-task, and 190 individuals were genotyped with an HD Canine SNP-chip. One genetic marker on chromosome 26 within the SEZ6L gene was significantly associated with time spent close to, and in physical contact with, the human. Two suggestive markers on chromosome 26, located within the ARVCF gene, were also associated with human contact seeking. Strikingly, four additional genes present in the same linkage blocks affect social abilities in humans, e.g., SEZ6L has been associated with autism and COMT affects aggression in adolescents with ADHD. This is, to our knowledge, the first genome-wide study presenting candidate genomic regions for dog sociability and inter-species communication. These results advance our understanding of dog domestication and raise the use of the dog as a novel model system for human social disorders.

  13. Determination of the promoter region of an early vaccinia virus gene encoding thymidine kinase.

    Science.gov (United States)

    Weir, J P; Moss, B

    1987-05-01

    Nine recombinant vaccinia viruses that contain overlapping segments of the putative promoter region of the vaccinia virus thymidine kinase (TK) gene linked to DNA coding for the prokaryotic enzyme chloramphenicol acetyltransferase (CAT) were constructed. In each case, the RNA start site and 5 bp of DNA downstream were retained. No significant difference in CAT expression occurred as the deletion was extended from 352 to 32 bp before the RNA start site. Deletion of a further 10 bp, however, led to complete cessation of early promoter activity. Primer extension analysis of the 5' ends of the transcripts verified that the natural TK RNA start site was still used when only 32 bp of upstream DNA remained. Loss of early promoter activity was previously found when deletions were extended from 31 to 24 bp before the RNA start site of another vaccinia gene that is expressed constitutively throughout infection (M.A. Cochran, C. Puckett, and B. Moss, 1985, Proc. Natl. Acad. Sci. USA 82, 19-23). Sequence similarities in the promoter regions of these two genes were noted.

  14. Early life adversity and serotonin transporter gene variation interact to affect DNA methylation of the corticotropin-releasing factor gene promoter region in the adult rat brain

    NARCIS (Netherlands)

    Doelen, R.H. van der; Arnoldussen, I.A.C.; Ghareh, H.; Och, L. van; Homberg, J.R.; Kozicz, L.T.

    2015-01-01

    The interaction between childhood maltreatment and the serotonin transporter (5-HTT) gene linked polymorphic region has been associated with increased risk to develop major depression. This Gene x Environment interaction has furthermore been linked with increased levels of anxiety and glucocorticoid

  15. An acute dose of gamma-hydroxybutyric acid alters gene expression in multiple mouse brain regions.

    Science.gov (United States)

    Schnackenberg, B J; Saini, U T; Robinson, B L; Ali, S F; Patterson, T A

    2010-10-13

    Gamma-hydroxybutyric acid (GHB) is normally found in the brain in low concentrations and may function as a neurotransmitter, although the mechanism of action has not been completely elucidated. GHB has been used as a general anesthetic and is currently used to treat narcolepsy and alcoholism. Recreational use of GHB is primarily as a "club drug" and a "date rape drug," due to its amnesic effects. For this study, the hypothesis was that behavioral and neurochemical alterations may parallel gene expression changes in the brain after GHB administration. Adult male C57/B6N mice (n=5/group) were administered a single dose of 500 mg/kg GHB (i.p.) and were sacrificed 1, 2 and 4 h after treatment. Control mice were administered saline. Brains were removed and regionally dissected on ice. Total RNA from the hippocampus, cortex and striatum was extracted, amplified and labeled. Gene expression was evaluated using Agilent whole mouse genome 4x44K oligonucleotide microarrays. Microarray data were analyzed by ArrayTrack and differentially expressed genes (DEGs) were identified using P or = 1.7 as the criteria for significance. Principal component analysis (PCA) and Hierarchical Cluster Analysis (HCA) showed that samples from each time point clustered into distinct treatment groups with respect to sacrifice time. Ingenuity pathways analysis (IPA) was used to identify involved pathways. The results show that GHB induces gene expression alterations in hundreds of genes in the hippocampus, cortex and striatum, and the number of affected genes increases throughout a 4-h time course. Many of these DEGs are involved in neurological disease, apoptosis, and oxidative stress.

  16. Identifying Regulatory Patterns at the 3'end Regions of Over-expressed and Under-expressed Genes

    KAUST Repository

    Othoum, Ghofran K

    2013-05-01

    Promoters, neighboring regulatory regions and those extending further upstream of the 5’end of genes, are considered one of the main components affecting the expression status of genes in a specific phenotype. More recently research by Chen et al. (2006, 2012) and Mapendano et al. (2010) demonstrated that the 3’end regulatory regions of genes also influence gene expression. However, the association between the regulatory regions surrounding 3’end of genes and their over- or under-expression status in a particular phenotype has not been systematically studied. The aim of this study is to ascertain if regulatory regions surrounding the 3’end of genes contain sufficient regulatory information to correlate genes with their expression status in a particular phenotype. Over- and under-expressed ovarian cancer (OC) genes were used as a model. Exploratory analysis of the 3’end regions were performed by transforming the annotated regions using principal component analysis (PCA), followed by clustering the transformed data thereby achieving a clear separation of genes with different expression status. Additionally, several classification algorithms such as Naïve Bayes, Random Forest and Support Vector Machine (SVM) were tested with different parameter settings to analyze the discriminatory capacity of the 3’end regions of genes related to their gene expression status. The best performance was achieved using the SVM classification model with 10-fold cross-validation that yielded an accuracy of 98.4%, sensitivity of 99.5% and specificity of 92.5%. For gene expression status for newly available instances, based on information derived from the 3’end regions, an SVM predictive model was developed with 10-fold cross-validation that yielded an accuracy of 67.0%, sensitivity of 73.2% and specificity of 61.0%. Moreover, building an SVM with polynomial kernel model to PCA transformed data yielded an accuracy of 83.1%, sensitivity of 92.5% and specificity of 74.8% using

  17. Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism.

    Science.gov (United States)

    Liu, Qingqing; Yuan, Bingbing; Lo, Kinyui Alice; Patterson, Heide Christine; Sun, Yutong; Lodish, Harvey F

    2012-09-04

    The effects of adiponectin on hepatic glucose and lipid metabolism at transcriptional level are largely unknown. We profiled hepatic gene expression in adiponectin knockout (KO) and wild-type (WT) mice by RNA sequencing. Compared with WT mice, adiponectin KO mice fed a chow diet exhibited decreased mRNA expression of rate-limiting enzymes in several important glucose and lipid metabolic pathways, including glycolysis, tricarboxylic acid cycle, fatty-acid activation and synthesis, triglyceride synthesis, and cholesterol synthesis. In addition, binding of the transcription factor Hnf4a to DNAs encoding several key metabolic enzymes was reduced in KO mice, suggesting that adiponectin might regulate hepatic gene expression via Hnf4a. Phenotypically, adiponectin KO mice possessed smaller epididymal fat pads and showed reduced body weight compared with WT mice. When fed a high-fat diet, adiponectin KO mice showed significantly reduced lipid accumulation in the liver. These lipogenic defects are consistent with the down-regulation of lipogenic genes in the KO mice.

  18. 2p24 Gain Region Harboring MYCN Gene Compared with MYCN Amplified and Nonamplified Neuroblastoma

    Science.gov (United States)

    Jeison, Marta; Ash, Shifra; Halevy-Berko, Gili; Mardoukh, Jacques; Luria, Drorit; Avigad, Smadar; Feinberg-Gorenshtein, Galina; Goshen, Yacov; Hertzel, Gabriel; Kapelushnik, Joseph; Barak, Ayelet Ben; Attias, Dina; Steinberg, Ran; Stein, Jerry; Stark, Batia; Yaniv, Isaac

    2010-01-01

    Although the role of MYCN amplification in neuroblastoma is well established, the biological and clinical characteristics of the 2p gain region harboring the MYCN gene remain unclear. The aim of this study was to compare the biological and clinical characteristics of these tumors with MYCN amplified and nonamplified neuroblastoma and to determine their impact on disease outcome. Samples from 177 patients were analyzed by fluorescence in situ hybridization, including MYCN, 1p, 17q, and 11q regions; 2p gain was identified in 25 patients, MYCN amplification in 31, and no amplification in 121 patients. Patients with 2p gain had a significantly worse 5-year event-free survival rate than patients with no MYCN amplified (P < 0.001), and an intermediate 5-year overall survival rate difference existed between the MYCN amplified tumors (P = 0.025) and nonamplified (P = 0.003) groups. All of the 2p gain samples were associated with segmental and/or numerical alterations in the other tested regions. The presence of segmental alterations with or without MYCN amplification was recently found to be the strongest predictor of relapse in a multivariate analysis. The results of the present study suggest that the determination of MYCN gene copy number relative to chromosome 2, when evaluating MYCN status at diagnosis, may help to reveal the underlying genetic pattern of these tumors and better understand their clinical behavior. PMID:20395439

  19. The myotonic dystrophy kinase 3{prime}-untranslated region and its effect on gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Ang, C.W.Y.; Sabourin, L.A.; Narang, M.A. [Univ. of Ottawa, Ontario (Canada)] [and others

    1994-09-01

    Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease involving the expansion of an unstable CTG repeat in the 3{prime}-untranslated (3{prime}-UTR) region of the DM kinase (DMK) gene. Increased levels of mRNA in congenital compared to normal tissue have been shown, suggesting elevated DMK levels may be responsible for the disease phenotype. To study the effect of the DMK 3{prime}UTR on gene expression, a reporter gene system was constructed using the constitutive CMV promoter with the chloramphenicol acetyl transferase (CAT) open reading frame and the DMK 3{prime}UTR containing from 5 repeats up to 90 repeats. Transient transfection into a rhabdomyosarcoma cell line shows a three-fold increase in CAT activity from constructs containing a wildtype 3{prime}UTR (5 and 20 repeats) compared to a control construct containing only a poly(A) signal. Reporter constructs with repeats in the protomutation (50 repeats) and mutation (90 repeats) range show a greater than 10-fold increase over control CAT activity. These results suggest the presence of elements in the DMK 3{prime}UTR capable of conferring increased gene expression. We are currently investigating cell-specific activity of the constructs and conducting deletion mapping to identify regulatory elements in the 3{prime}-UTR.

  20. Cloning and functional analysis of SEL1L promoter region, a pancreas-specific gene.

    Science.gov (United States)

    Cattaneo, M; Sorio, C; Malferrari, G; Rogozin, I B; Bernard, L; Scarpa, A; Zollo, M; Biunno, I

    2001-01-01

    We examined the promoter activity of SEL1L, the human ortholog of the C. elegans gene sel-1, a negative regulator of LIN-12/NOTCH receptor proteins. To understand the relation in SEL1L transcription pattern observed in different epithelial cells, we determined the transcription start site and sequenced the 5' flanking region. Sequence analysis revealed the presence of consensus promoter elements--GC boxes and a CAAT box--but the absence of a TATA motif. Potential binding sites for transcription factors that are involved in tissue-specific gene expression were identified, including: activator protein-2 (AP-2), hepatocyte nuclear factor-3 (HNF3 beta), homeobox Nkx2-5 and GATA-1. Transcription activity of the TATA-less SEL1L promoter was analyzed by transient transfection using luciferase reporter gene constructs. A core basal promoter of 302 bp was sufficient for constitutive promoter activity in all the cell types studied. This genomic fragment contains a CAAT and several GC boxes. The activity of the SEL1L promoter was considerably higher in mouse pancreatic beta cells (beta TC3) than in several human pancreatic neoplastic cell lines; an even greater reduction of its activity was observed in cells of nonpancreatic origin. These results suggest that SEL1L promoter may be a useful tool in gene therapy applications for pancreatic pathologies.

  1. Structural characteristics of the variable regions of immunoglobulin genes encoding a pathogenic autoantibody in murine lupus.

    Science.gov (United States)

    Tsao, B P; Ebling, F M; Roman, C; Panosian-Sahakian, N; Calame, K; Hahn, B H

    1990-02-01

    We have studied several monoclonal anti-double-stranded (ds) DNA antibodies for their ability to accelerate lupus nephritis in young NZB X NZW F1 female mice and to induce it in BALB/c mice. Two identified as pathogens in both strains have characteristics previously associated with nephritogenicity: expression of IgG2a isotype and IdGN2 idiotype. Both pathogenic antibodies used the combination of genes from the VHJ558 and VK9 subfamilies. Two weak pathogens failed to accelerate nephritis in young BW mice, but induced lupus nephritis in BALB/c mice. They both express IdGN2; one is cationic and an IgG3, the other is an IgG2a. Additional MAbs (some IgG2a, one IdGN2-positive) did not accelerate or induce nephritis. We have cloned and sequenced the variable regions of the immunoglobulin genes of one pathogenic autoantibody. No unique V, D, or J gene segments and no evidence of unusual mechanisms in generating diversity were used to construct this antibody. These data argue against use of unique abnormal Ig genes by systemic lupus erythematosus individuals to construct pathogenic autoantibody subsets. Instead, the major abnormality may be immunoregulatory.

  2. The role of RNA structure at 5' untranslated region in microRNA-mediated gene regulation.

    Science.gov (United States)

    Gu, Wanjun; Xu, Yuming; Xie, Xueying; Wang, Ting; Ko, Jae-Hong; Zhou, Tong

    2014-09-01

    Recent studies have suggested that the secondary structure of the 5' untranslated region (5' UTR) of messenger RNA (mRNA) is important for microRNA (miRNA)-mediated gene regulation in humans. mRNAs that are targeted by miRNA tend to have a higher degree of local secondary structure in their 5' UTR; however, the general role of the 5' UTR in miRNA-mediated gene regulation remains unknown. We systematically surveyed the secondary structure of 5' UTRs in both plant and animal species and found a universal trend of increased mRNA stability near the 5' cap in mRNAs that are regulated by miRNA in animals, but not in plants. Intra-genome comparison showed that gene expression level, GC content of the 5' UTR, number of miRNA target sites, and 5' UTR length may influence mRNA structure near the 5' cap. Our results suggest that the 5' UTR secondary structure performs multiple functions in regulating post-transcriptional processes. Although the local structure immediately upstream of the start codon is involved in translation initiation, RNA structure near the 5' cap site, rather than the structure of the full-length 5' UTR sequences, plays an important role in miRNA-mediated gene regulation.

  3. An antisense transcript in the human cytomegalovirus UL87 gene region

    Directory of Open Access Journals (Sweden)

    Ma Yanping

    2011-11-01

    Full Text Available Abstract Background Rapid advances in research on antisense transcripts are gradually changing our comprehension of genomic and gene expression aspects of the Herpesviridae. One such herpesvirus is the human cytomegalovirus (HCMV. Although transcription of the HCMV UL87 gene has not been specifically investigated, cDNA clones of UL87 antisense transcripts were found in HCMV cDNA libraries previously. In this study, the transcription of the UL87 antisense strand was investigated in three clinically isolated HCMV strains. Results First, an 800 nucleotides transcript having an antisense orientation to the UL87 gene was found in a late HCMV cDNA library. Then, the UL87 antisense transcript was confirmed by Rapid amplification of cDNA ends (RACE and Northern blot in three HCMV clinical strains. Two ORFs were predicted in the antisense transcript. The putative protein of ORF 1 showed a high degree of conservation among HCMV and other CMV strains. Conclusion An 800nt antisense transcript in the UL87 gene region exists in HCMV clinical strains.

  4. Critical evaluation of HPV16 gene copy number quantification by SYBR green PCR

    Directory of Open Access Journals (Sweden)

    Pett Mark R

    2008-07-01

    Full Text Available Abstract Background Human papilloma virus (HPV load and physical status are considered useful parameters for clinical evaluation of cervical squamous cell neoplasia. However, the errors implicit in HPV gene quantification by PCR are not well documented. We have undertaken the first rigorous evaluation of the errors that can be expected when using SYBR green qPCR for quantification of HPV type 16 gene copy numbers. We assessed a modified method, in which external calibration curves were generated from a single construct containing HPV16 E2, HPV16 E6 and the host gene hydroxymethylbilane synthase in a 1:1:1 ratio. Results When testing dilutions of mixed HPV/host DNA in replicate runs, we observed errors in quantifying E2 and E6 amplicons of 5–40%, with greatest error at the lowest DNA template concentration (3 ng/μl. Errors in determining viral copy numbers per diploid genome were 13–53%. Nevertheless, in cervical keratinocyte cell lines we observed reasonable agreement between viral loads determined by qPCR and Southern blotting. The mean E2/E6 ratio in episome-only cells was 1.04, but with a range of 0.76–1.32. In three integrant-only lines the mean E2/E6 ratios were 0.20, 0.72 and 2.61 (values confirmed by gene-specific Southern blotting. When E2/E6 ratios in fourteen HPV16-positive cervical carcinomas were analysed, conclusions regarding viral physical state could only be made in three cases, where the E2/E6 ratio was ≤ 0.06. Conclusion Run-to-run variation in SYBR green qPCR produces unavoidable inaccuracies that should be allowed for when quantifying HPV gene copy number. While E6 copy numbers can be considered to provide a useable indication of viral loads, the E2/E6 ratio is of limited value. Previous studies may have overestimated the frequency of mixed episomal/integrant HPV infections.

  5. Functional Characterization of a Single Nucleotide Polymorphism in the 3' Untranslated Region of Sheep DLX3 Gene.

    Directory of Open Access Journals (Sweden)

    Enguang Rong

    Full Text Available The Distal-less 3 (homeobox protein DLX-3, a transcription factor, is critical for the development of hair follicle and hair formation and regeneration. We previously identified and found that four SNPs (c. *118T>C, c. *228T>C, c. *688A>G and c. *1,038_1,039 insC in 3' untranslated region (UTR of sheep DLX3 were in high linkage disequilibrium with each other and significantly associated with wool crimp (P<0.05, however, the underlying mechanisms by which these SNPs affect the wool crimp remains unknown. In the present study, we performed association analysis between these four identified SNPs and DLX3 gene expression in sheep skin using quantitative real-time RT-PCR. The results showed that these SNPs were significantly associated with sheep skin DLX3 mRNA expression levels. Then, we constructed DLX3 3'UTR luciferase reporters and validated the association. The reporter assays showed that the three major haplotypes, derived from the four SNPs, had significantly different effects on luciferase reporter activity and the four SNPs also had significantly different allelic effects on the luciferase reporter activity (p < 0.05. Bioinformatics analysis showed that the SNP (c. *1,038_1,039 insC was located within a potential miR-188 binding site of the 3'UTR of sheep DLX3 mRNA. This SNP may affect miR-188-mediated DLX3 gene expression and result in phenotypic variation. To test the hypothesis, we investigated the effects of miR-188 mimic and inhibitor on the activity of the DLX3 3'UTR luciferase reporter with different SNP alleles. The results showed that in both sheep fetal fibroblasts (SFFs and human HaCaT cells, miR-188 mimic could significantly decrease the allele D (deletion luciferase reporter activity (p < 0.05, but miR-188 inhibitor could increased the reporter activitiy. However, neither miR-188 mimc nor inhibitor could influence the allele I (insertion reporter activity. In addition, transfection of miR-188 mimic dramatically decreased the

  6. Polymorphism and gene organization of water buffalo MHC-DQB genes show homology to the BoLA DQB region.

    Science.gov (United States)

    Sena, L; Schneider, M P C; Brenig, B B; Honeycutt, R L; Honeycutt, D A; Womack, J E; Skow, L C

    2011-08-01

    In cattle (Bos taurus), there is evidence of more than 50 alleles of BoLA-DQB (bovine lymphocyte antigen DQB) that are distributed across at least five DQB loci, making this region one of the most complex in the BoLA gene family. In this study, DQB alleles were analysed for the water buffalo (Bubalus bubalis), another economically important bovine species. Twelve alleles for Bubu-DQB (Bubalis bubalis DQB) were determined by nucleotide sequence analysis. A phylogenetic analysis revealed numerous trans-species polymorphisms, with alleles from water buffalo assigned to at least three different loci (BoLA-DQB1, BoLA-DQB3 and BoLA-DQB4) that are also found in cattle. These presumptive loci were analysed for patterns of synonymous (d(S)) and non-synonymous (d(N)) substitution. Like BoLA-DQB1, Bubu-DQB1 was observed to be under strong positive selection for polymorphism. We conclude that water buffalo and cattle share the current arrangement of their DQB region because of their common ancestry. © 2011 The Authors, Animal Genetics © 2011 Stichting International Foundation for Animal Genetics.

  7. Evidence for a novel exon in the coding region of the adenomatous polyposis coli (APC) gene

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Ling; St. Denis, K.A.; Bapat, B. [Univ. of Toronto (Canada)

    1995-08-10

    Germline mutations of the tumor suppressor gene APC cause familial adenomatous polyposis. Somatic APC alterations are involved in several sporadic neoplasma, including colorectal, duodenal, gastric, and esophageal carcinoma. The APC mRNA is encoded by 15 exons. Additional transcripts have been reported, due to alternative splicing of coding as well as noncoding regions. Two mRNA isoforms occur due to a deletion of exon 7 or a partial deletion of exon 9. We have identified a novel exon, flanked by APC exons 10 and 11, which is expressed as an alternatively transcribed product of the gene. Further, we have shown that the novel exon consists of a heptad repeat motif and is conserved across species. 18 refs., 2 figs.

  8. The clinical impact of hypoxia-regulated gene expression in loco-regional gastroesophageal cancer

    DEFF Research Database (Denmark)

    Winther, M.; Alsner, J.; Tramm, T.

    2015-01-01

    squamous cell carcinomas (ESCC) compared with adenocarcinomas of the esophago-gastric junction and the stomach (AC), and was a potential prognostic marker in patients with ESCC. The purpose of the present study was to confirm these results. Materials and Methods: The study population consisted of 152......Purpose/Objective: In a former study (1), the hypoxia gene expression classifier, developed in head and neck squamous cell carcinomas, was applied in 89 patients with loco-regional gastroesophageal cancer (GC). Analysis of the 15 genes was indicative of hypoxia being more profound in esophagus...... were available in 135 patients; ESCC: 89 patients (66%), AC: 43 patients (32%) and other carcinomas: 3 patients (2%). Comparing the cohorts of the original and present study, patient characteristics were similar except for a significantly lower T- and N-stage in the present cohort. Tumor specimens were...

  9. The phase transition of the first order in the critical region of the gas-liquid system

    Directory of Open Access Journals (Sweden)

    I.R. Yukhnovskii

    2014-12-01

    Full Text Available This is a summarising investigation of the events of the phase transition of the first order that occur in the critical region below the liquid-gas critical point. The grand partition function has been completely integrated in the phase-space of the collective variables. The basic density measure is the quartic one. It has the form of the exponent function with the first, second, third and fourth degree of the collective variables. The problem has been reduced to the Ising model in an external field, the role of which is played by the generalised chemical potential μ*. The line μ*(η =0, where η is the density, is the line of the phase transition. We consider the isothermal compression of the gas till the point where the phase transition on the line μ*(η =0 is reached. When the path of the pressing reaches the line μ* =0 in the gas medium, a droplet of liquid springs up. The work for its formation is obtained, the surface-tension energy is calculated. On the line μ* =0 we have a two-phase system: the gas and the liquid (the droplet one. The equality of the gas and of the liquid chemical potentials is proved. The process of pressing is going on. But the pressure inside the system has stopped, two fixed densities have arisen: one for the gas-phase ηG=ηc(1-d/2 and the other for the liquid-phase ηL=ηc(1+d/2 (symmetrically to the rectlinear diameter, where ηc=0.13044 is the critical density. Starting from that moment the external pressure works as a latent work of pressure. Its value is obtained. As a result, the gas-phase disappears and the whole system turns into liquid. The jump of the density is equal to ηc d, where d=(D/2G1/2 ~ τν/2. D and G are coefficients of the Hamiltonian in the last cell connected with the renormalisation-group symmetry. The equation of state is written.

  10. Whorl-specific expression of the SUPERMAN gene of Arabidopsis is mediated by cis elements in the transcribed region.

    Science.gov (United States)

    Ito, Toshiro; Sakai, Hajime; Meyerowitz, Elliot M

    2003-09-02

    The SUPERMAN (SUP) gene of Arabidopsis is involved in controlling cell proliferation in stamen and carpel primordia and in ovules during flower development. The SUP gene encodes a transcription factor with a C2H2-type zinc finger motif, a serine/proline-rich domain, a basic domain, and a leucine-zipper-like domain and is expressed in a very limited region in stamen primordia and in the developing ovary during flower development. The SUP gene is susceptible to methylation, resulting in epigenetic gene silencing. To understand how the SUP gene is expressed spatially and temporally in its restricted domain, and why methylation of the transcribed region affects early-stage SUP expression, we have identified the SUP cis regulatory elements by characterizing SUP gene fusions. These studies show that the SUP gene has discrete upstream promoter elements required for expression in stamen primordia in early stages and in the ovary in later stages. The promoter activity for stamen primordia is modulated by several positive and negative elements located in the transcribed and translated regions. Several regulatory elements in the transcribed region correlate with the areas of the gene that are heavily methylated in epigenetic alleles; these data provide a possible explanation of how methylation of the transcribed region represses transcription.

  11. Restriction mapping of a YAC contig in the hemochromatosis gene region

    Energy Technology Data Exchange (ETDEWEB)

    Burt, M.J.; Smit, D.J.; Pyper, W.R. [Univ. of Queensland, Brisbane (Australia)

    1994-09-01

    Hemochromatosis is a common inherited disorder of iron metabolism that can lead to cirrhosis, hepatocellular carcinoma, cardiomyopathy, diabetes and anthropathy. We have mapped the hemochromatosis gene to within 1 cM of HLA-A and the microsatellite D6S105, and our allele association studies have shown that D6S105 is the marker most closely associated with the hemochromatosis gene. We are currently constructing a YAC contig and restriction map of this region as part of a positional cloning strategy to identify the hemochromatosis gene. YACs containing HLA-A or D6S105 were selected, and fluorescent-in-situ-hybridization (FISH) was performed to confirm chromosomal location and exclude chimerism. YAC DNA was digested with a panel of rare cutters, separated by pulsed field gel electrophoresis, Southern blotted and probed with the vector arms to create restriction maps. YAC insert terminal ends were isolated using vectorette methodology. A contig extending 600 kb centromeric and 350 kb telomeric of HLA-A has been established. HLA-A, HLA-F and the microsatellite D6S265 have been positioned on this map. The contig does not yet overlap any D6S105 positive YACs but the telomeric end of the contig has been sequenced and is being used to identify additional YACs to bridge this interval. Restriction mapping of three D6S105 YACs has shown the presence of several CpG islands in this region. As these CpG islands are in close proximity to D6S105, they are being used to isolate coding sequences to determine whether any of these mark the position of the hemochromatosis gene.

  12. Mutational analysis of the promoter and the coding region of the 5-HT1A gene

    Energy Technology Data Exchange (ETDEWEB)

    Erdmann, J.; Noethen, M.M.; Shimron-Abarbanell, D. [Univ. of Bonn (Germany)] [and others

    1994-09-01

    Disturbances of serotonergic pathways have been implicated in many neuropsychiatric disorders. Serotonin (5HT) receptors can be subdivided into at least three major families (5HT1, 5HT2, and 5HT3). Five human 5HT1 receptor subtypes have been cloned, namely 1A, 1D{alpha}, 1D{beta}, 1E, and 1F. Of these, the 5HT1A receptor is the best characterized subtype. In the present study we sought to identify genetic variation in the 5HT1A receptor gene which through alteration of protein function or level of expression might contribute to the genetics of neuropsychiatric diseases. The coding region and the 5{prime} promoter region of the 5HT1A gene from 159 unrelated subjects (45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette`s syndrome, as well as 25 controls) were analyzed using SSCA. SSCA revealed the presence of two mutations both located in the coding region of the 5HT1A receptor gene. The first mutation is a rare silent C{r_arrow}T substitution at nucleotide position 549. The second mutation is characterized by a base pair substitution (A{r_arrow}G) at the first position of codon 28 and results in an amino acid exchange (Ile{r_arrow}Val). Since Val28 was found only in a single schizophrenic patient and in none of the other patients or controls, we decided to extend our samples and to use a restriction assay for screening a further 74 schizophrenic, 95 bipolar affective, and 49 patients with Tourette`s syndrome, as well as 185 controls, for the presence of the mutation. In total, the mutation was found in 2 schizophrenic patients, in 3 bipolars, in 1 Tourette patient, and in 5 controls. To our knowledge the Ile-28-Val substitution reported here is the first natural occuring molecular variant which has been identified for a serotonin receptor so far.

  13. Regional Association Analysis of MetaQTLs Delineates Candidate Grain Size Genes in Rice

    Directory of Open Access Journals (Sweden)

    Anurag V. Daware

    2017-05-01

    Full Text Available Molecular mapping studies which aim to identify genetic basis of diverse agronomic traits are vital for marker-assisted crop improvement. Numerous Quantitative Trait Loci (QTLs mapped in rice span long genomic intervals with hundreds to thousands of genes, which limits their utilization for marker-assisted genetic enhancement of rice. Although potent, fine mapping of QTLs is challenging task as it requires screening of large number of segregants to identify suitable recombination events. Association mapping offers much higher resolution as compared to QTL mapping, but detects considerable number of spurious QTLs. Therefore, combined use of QTL and association mapping strategies can provide advantages associated with both these methods. In the current study, we utilized meta-analysis approach to identify metaQTLs associated with grain size/weight in diverse Indian indica and aromatic rice accessions. Subsequently, attempt has been made to narrow-down identified grain size/weight metaQTLs through individual SNP- as well as haplotype-based regional association analysis. The study identified six different metaQTL regions, three of which were successfully revalidated, and substantially scaled-down along with GS3 QTL interval (positive control by regional association analysis. Consequently, two potential candidate genes within two reduced metaQTLs were identified based on their differential expression profiles in different tissues/stages of rice accessions during seed development. The developed strategy has broader practical utility for rapid delineation of candidate genes and natural alleles underlying QTLs associated with complex agronomic traits in rice as well as major crop plants enriched with useful genetic and genomic information.

  14. Differentially methylated regions of imprinted genes in prenatal, perinatal and postnatal human tissues.

    Directory of Open Access Journals (Sweden)

    Susan K Murphy

    Full Text Available Epigenetic plasticity in relation to in utero exposures may mechanistically explain observed differences in the likelihood of developing common complex diseases including hypertension, diabetes and cardiovascular disease through the cumulative effects of subtle alterations in gene expression. Imprinted genes are essential mediators of growth and development and are characterized by differentially methylated regulatory regions (DMRs that carry parental allele-specific methylation profiles. This theoretical 50% level of methylation provides a baseline from which endogenously- or exogenously-induced deviations in methylation can be detected. We quantified DNA methylation at imprinted gene DMRs in a large panel of human conceptal tissues, in matched buccal cell specimens collected at birth and at one year of age, and in the major cell fractions of umbilical cord blood to assess the stability of methylation at these regions. DNA methylation was measured using validated pyrosequencing assays at seven DMRs regulating the IGF2/H19, DLK1/MEG3, MEST, NNAT and SGCE/PEG10 imprinted domains. DMR methylation did not significantly differ for the H19, MEST and SGCE/PEG10 DMRs across all conceptal tissues analyzed (ANOVA p>0.10. Methylation differences at several DMRs were observed in tissues from brain (IGF2 and MEG3-IG DMRs, liver (IGF2 and MEG3 DMRs and placenta (both DLK1/MEG3 DMRs and NNAT DMR. In most infants, methylation profiles in buccal cells at birth and at one year of age were comparable, as was methylation in the major cell fractions of umbilical cord blood. Several infants showed temporal deviations in methylation at multiple DMRs. Similarity of inter-individual and intra-individual methylation at some, but not all of the DMRs analyzed supports the possibility that methylation of these regions can serve as useful biosensors of exposure.

  15. Genomic imprinting variations in the mouse type 3 deiodinase gene between tissues and brain regions.

    Science.gov (United States)

    Martinez, M Elena; Charalambous, Marika; Saferali, Aabida; Fiering, Steven; Naumova, Anna K; St Germain, Donald; Ferguson-Smith, Anne C; Hernandez, Arturo

    2014-11-01

    The Dio3 gene, which encodes for the type 3 deiodinase (D3), controls thyroid hormone (TH) availability. The lack of D3 in mice results in tissue overexposure to TH and a broad neuroendocrine phenotype. Dio3 is an imprinted gene, preferentially expressed from the paternally inherited allele in the mouse fetus. However, heterozygous mice with paternal inheritance of the inactivating Dio3 mutation exhibit an attenuated phenotype when compared with that of Dio3 null mice. To investigate this milder phenotype, the allelic expression of Dio3 was evaluated in different mouse tissues. Preferential allelic expression of Dio3 from the paternal allele was observed in fetal tissues and neonatal brain regions, whereas the biallelic Dio3 expression occurred in the developing eye, testes, and cerebellum and in the postnatal brain neocortex, which expresses a larger Dio3 mRNA transcript. The newborn hypothalamus manifests the highest degree of Dio3 expression from the paternal allele, compared with other brain regions, and preferential allelic expression of Dio3 in the brain relaxed in late neonatal life. A methylation analysis of two regulatory regions of the Dio3 imprinted domain revealed modest but significant differences between tissues, but these did not consistently correlate with the observed patterns of Dio3 allelic expression. Deletion of the Dio3 gene and promoter did not result in significant changes in the tissue-specific patterns of Dio3 allelic expression. These results suggest the existence of unidentified epigenetic determinants of tissue-specific Dio3 imprinting. The resulting variation in the Dio3 allelic expression between tissues likely explains the phenotypic variation that results from paternal Dio3 haploinsufficiency.

  16. Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity

    NARCIS (Netherlands)

    Rocker, N. de; Vergult, S.; Koolen, D.A.; Jacobs, E.; Hoischen, A.; Zeesman, S.; Bang, B.; Bena, F.; Bockaert, N.; Bongers, E.M.H.F.; Ravel, T. de; Devriendt, K.; Giglio, S.; Faivre, L.; Joss, S.; Maas, S.; Marle, N.; Novara, F.; Nowaczyk, M.J.; Peeters, H.; Polstra, A.; Roelens, F.; Rosenberg, C.; Thevenon, J.; Tumer, Z.; Vanhauwaert, S.; Varvagiannis, K.; Willaert, A.; Willemsen, M.H.; Willems, M.; Zuffardi, O.; Coucke, P.; Speleman, F.; Eichler, E.E.; Kleefstra, T.; Menten, B.

    2015-01-01

    PURPOSE: Submicroscopic deletions of chromosome band 2p25.3 are associated with intellectual disability and/or central obesity. Although MYT1L is believed to be a critical gene responsible for intellectual disability, so far no unequivocal data have confirmed this hypothesis. METHODS: In this study

  17. Two regulators of Vibrio parahaemolyticus play important roles in enterotoxicity by controlling the expression of genes in the Vp-PAI region.

    Directory of Open Access Journals (Sweden)

    Toshio Kodama

    Full Text Available Vibrio parahaemolyticus is an important pathogen causing food-borne disease worldwide. An 80-kb pathogenicity island (Vp-PAI, which contains two tdh (thermostable direct hemolysin genes and a set of genes for the type III secretion system (T3SS2, is closely related to the pathogenicity of this bacterium. However, the regulatory mechanisms of Vp-PAI's gene expression are poorly understood. Here we report that two novel ToxR-like transcriptional regulatory proteins (VtrA and VtrB regulate the expression of the genes encoded within the Vp-PAI region, including those for TDH and T3SS2-related proteins. Expression of vtrB was under control of the VtrA, as vector-expressed vtrB was able to recover a functional protein secretory capacity for T3SS2, independent of VtrA. Moreover, these regulatory proteins were essential for T3SS2-dependent biological activities, such as in vitro cytotoxicity and in vivo enterotoxicity. Enterotoxic activities of vtrA and/or vtrB deletion strains derived from the wild-type strain were almost absent, showing fluid accumulation similar to non-infected control. Whole genome transcriptional profiling of vtrA or vtrB deletion strains revealed that the expression levels of over 60 genes were downregulated significantly in these deletion mutant strains and that such genes were almost exclusively located in the Vp-PAI region. These results strongly suggest that VtrA and VtrB are master regulators for virulence gene expression in the Vp-PAI and play critical roles in the pathogenicity of this bacterium.

  18. Gene expression analysis of a critical enzyme in intermediary metabolism in oyster pathogen Perkinsus marinus .

    Science.gov (United States)

    Noell, K.

    2016-02-01

    A key regulatory component in the Krebs cycle pathway is the mitochondrial aconitase enzyme which has been posited to balance energy needs and oxidative growth total storage via citrate utilization. The presence of a cytosolic aconitase (cAcon) activity which serves as a competitor for citrate substrate has been recognized for years. cAcon is a dual function protein with mutually exclusive roles as a post transcriptional regulator of animal cell iron metabolism or as the cytosolic isoform of the iron sulfur enzyme aconitase. We are interested in establishing the role of this orthologue in Perkinsus marnius metabolism through demonstrating its function as aconitase, by looking at gene expression under certain environmental conditions. P. marinus is a close evolutionary relative of the dinoflagellates and is the causative agent of Dermo disease, which has significantly impacted oyster populations along the eastern seaboard. An understanding of intermediary metabolism will yield important insights into how c-aconitase may be involved in stress response systems such as oxidative tension and metabolite deficiency, which could be used to help aquaculturists alleviate the severe impact of "dermo" on the on the oyster population. This study will present data regarding our preliminary analysis of the gene aconitase and its role in intermediary metabolism.

  19. A gene for distal arthrogryposis Type I maps to the pericentromeric region of chromosome 9

    Energy Technology Data Exchange (ETDEWEB)

    Bamshad, M.; Watkins, W.S.; Zenger, R.K.; Bohnsack, J.F.; Carey, J.C.; Otterud, B.; Krakowiak, P.A.; Robertson, M.; Jorde, L.B. [Univ. of Utah Health Sciences Center, Salt Lake City, UT (United States)

    1994-12-01

    Club foot is one of the most common human congenital malformations. Distal arthrogryposis type I (DA-1) is a frequent cause of dominantly inherited club foot. Performing a genomewide search using short tandem repeat (STR) polymorphisms, we have mapped a DA-1 gene to the pericentromeric region of chromosome 9 in a large kindred. Linkage analysis has generated a positive lod score of 5.90 at {theta} = 0, with the marker GS-4. Multiple recombinants bracketing the region have been identified. Analysis of an additional family demonstrated no linkage to the same locus, indicating likely locus heterogeneity. Of the autosomal congenital contracture disorders causing positional foot deformities, this is the first to be mapped.

  20. Cloning and characterizing of the ovine MX1 gene promoter/enhancer region.

    Science.gov (United States)

    Assiri, A M; Ott, T L

    2007-01-01

    Ovine MX1 (MX1) is expressed in the uterus during the estrous cycle and is strongly up-regulated during early pregnancy in the uterus and peripheral blood leukocytes. In this study we cloned the MX1 gene promoter/enhancer, and tested its response to interferon tau (IFN-tau). To address the role of IFN tau in regulating MX1 expression, serial deletion mutants were prepared along with a clone that contained a full-length promoter including the two proximal ISREs but lacking an intronic ISRE site. Promoter deletions showed the two proximal ISRE sites, but not the intronic ISRE site, were required for maximal response to IFN tau. Interestingly, MX1 promoter deletion mutants revealed the presence of distal positive (-920 to -715) and negative (-715 to -437) regulatory regions. Identifying positive and negative regulatory regions in MX1 promoter will help define the complex regulation of MX1 during early pregnancy in ruminants.

  1. Novel region within the V kappa gene promoter is responsible for tissue and stage-specific expression of immunoglobulin genes in human lymphoid neoplasms.

    Science.gov (United States)

    Kossakowska, A E; Urbanski, S J

    1989-03-01

    Immunoglobulin gene-specific transacting factors have been shown to play a role in lymphoid tissue-specific expression of immunoglobulin genes. The role of these factors in B-cell differentiation and stage-specific expression of these genes is, however, not fully understood. We have used a model of human lymphoid neoplasia to address this question. Different fragments of unrearranged human variable region of immunoglobulin kappa gene (V kappa) were used for cell-free in vitro transcription and DNA mobility shift assays. Previously described enhancement of in vitro transcription that was only seen with nuclear extracts derived from B-cell neoplasms corresponding to the late stages of B-cell differentiation was shown to be dependent on the actions of these factor(s) on the DNA region within the V kappa gene promoter. This region is located within the 920 bp fragment located 210 bp upstream from the coding region and this fragment represents a possible novel DNA region, which plays a role in the stage- and tissue-specific expression of immunoglobulin genes.

  2. Exon organization of the mouse entactin gene corresponds to the structural domains of the polypeptide and has regional homology to the low-density lipoprotein receptor gene

    DEFF Research Database (Denmark)

    Durkin, M E; Wewer, U M; Chung, A E

    1995-01-01

    Entactin is a widespread basement membrane protein of 150 kDa that binds to type IV collagen and laminin. The complete exon-intron structure of the mouse entactin gene has been determined from lambda genomic DNA clones. The gene spans at least 65 kb and contains 20 exons. The exon organization...... of the mouse entactin gene closely corresponds to the organization of the polypeptide into distinct structural and functional domains. The two amino-terminal globular domains are encoded by three exons each. Single exons encode the two protease-sensitive, O-glycosylated linking regions. The six EGF......-like repeats and the single thyroglobulin-type repeat are each encoded by separate exons. The carboxyl-terminal half of entactin displays sequence homology to the growth factor-like region of the low-density lipoprotein receptor, and in both genes this region is encoded by eight exons. The positions of four...

  3. BF integrase genes of HIV-1 circulating in Sao Paulo, Brazil, with a recurrent recombination region.

    Directory of Open Access Journals (Sweden)

    Atila Iamarino

    Full Text Available Although some studies have shown diversity in HIV integrase (IN genes, none has focused particularly on the gene evolving in epidemics in the context of recombination. The IN gene in 157 HIV-1 integrase inhibitor-naïve patients from the São Paulo State, Brazil, were sequenced tallying 128 of subtype B (23 of which were found in non-B genomes, 17 of subtype F (8 of which were found in recombinant genomes, 11 integrases were BF recombinants, and 1 from subtype C. Crucially, we found that 4 BF recombinant viruses shared a recurrent recombination breakpoint region between positions 4900 and 4924 (relative to the HXB2 that includes 2 gRNA loops, where the RT may stutter. Since these recombinants had independent phylogenetic origin, we argue that these results suggest a possible recombination hotspot not observed so far in BF CRF in particular, or in any other HIV-1 CRF in general. Additionally, 40% of the drug-naïve and 45% of the drug-treated patients had at least 1 raltegravir (RAL or elvitegravir (EVG resistance-associated amino acid change, but no major resistance mutations were found, in line with other studies. Importantly, V151I was the most common minor resistance mutation among B, F, and BF IN genes. Most codon sites of the IN genes had higher rates of synonymous substitutions (dS indicative of a strong negative selection. Nevertheless, several codon sites mainly in the subtype B were found under positive selection. Consequently, we observed a higher genetic diversity in the B portions of the mosaics, possibly due to the more recent introduction of subtype F on top of an ongoing subtype B epidemics and a fast spread of subtype F alleles among the B population.

  4. Evolution of the DAZ gene and the AZFc region on primate Y chromosomes

    Directory of Open Access Journals (Sweden)

    Yu Jane-Fang

    2008-03-01

    Full Text Available Abstract Background The Azoospermia Factor c (AZFc region of the human Y chromosome is a unique product of segmental duplication. It consists almost entirely of very long amplicons, represented by different colors, and is frequently deleted in subfertile men. Most of the AZFc amplicons have high sequence similarity with autosomal segments, indicating recent duplication and transposition to the Y chromosome. The Deleted in Azoospermia (DAZ gene within the red-amplicon arose from an ancestral autosomal DAZ-like (DAZL gene. It varies significantly between different men regarding to its copy number and the numbers of RNA recognition motif and DAZ repeat it encodes. We used Southern analyses to study the evolution of DAZ and AZFc amplicons on the Y chromosomes of primates. Results The Old World monkey rhesus macaque has only one DAZ gene. In contrast, the great apes have multiple copies of DAZ, ranging from 2 copies in bonobos and gorillas to at least 6 copies in orangutans, and these DAZ genes have polymorphic structures similar to those of their human counterparts. Sequences homologous to the various AZFc amplicons are present on the Y chromosomes of some but not all primates, indicating that they arrived on the Y chromosome at different times during primate evolution. Conclusion The duplication and transposition of AZFc amplicons to the human Y chromosome occurred in three waves, i.e., after the branching of the New World monkey, the gorilla, and the chimpanzee/bonobo lineages, respectively. The red-amplicon, one of the first to arrive on the Y chromosome, amplified by inverted duplication followed by direct duplication after the separation of the Old World monkey and the great ape lineages. Subsequent duplication/deletion in the various lineages gave rise to a spectrum of DAZ gene structure and copy number found in today's great apes.

  5. Study on constructive system of green cave dwelling in Loess Plateau-Interpretation with the "regional gene" theory

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This article reveals the inherent evolution adjusting mechanism of regional architecture by means of considering the concept and method of "regional gene" as the research approach of regional architecture construction system, and in the meanwhile establishes the "gene database" of regional architecture and optimum technology, on the basis of the principle of sustainable development and scientific evaluation system. In addition, this article chooses the planning of model villages of cave dwellings in Loess Plateau and the construction of ecological cave dwellings for case study to prove the feasibility of the research approach.

  6. Faulting in the Yucca Mountain region: Critical review and analyses of tectonic data from the central Basin and Range

    Energy Technology Data Exchange (ETDEWEB)

    Ferrill, D.A.; Stirewalt, G.L.; Henderson, D.B.; Stamatakos, J.; Morris, A.P.; Spivey, K.H. [Southwest Research Inst., San Antonio, TX (United States). Center for Nuclear Waste Regulatory Analyses; Wernicke, B.P. [California Inst. of Tech., Pasadena, CA (United States). Div. of Geological and Planetary Sciences

    1996-03-01

    Yucca Mountain, Nevada, has been proposed as the potential site for a high-level waste (HLW) repository. The tectonic setting of Yucca Mountain presents several potential hazards for a proposed repository, such as potential for earthquake seismicity, fault disruption, basaltic volcanism, magma channeling along pre-existing faults, and faults and fractures that may serve as barriers or conduits for groundwater flow. Characterization of geologic structures and tectonic processes will be necessary to assess compliance with regulatory requirements for the proposed high level waste repository. In this report, we specifically investigate fault slip, seismicity, contemporary stain, and fault-slip potential in the Yucca Mountain region with regard to Key Technical Uncertainties outlined in the License Application Review Plan (Sections 3.2.1.5 through 3.2.1.9 and 3.2.2.8). These investigations center on (i) alternative methods of determining the slip history of the Bare Mountain Fault, (ii) cluster analysis of historic earthquakes, (iii) crustal strain determinations from Global Positioning System measurements, and (iv) three-dimensional slip-tendency analysis. The goal of this work is to assess uncertainties associated with neotectonic data sets critical to the Nuclear Regulatory Commission and the Center for Nuclear Waste Regulatory Analyses` ability to provide prelicensing guidance and perform license application review with respect to the proposed HLW repository at Yucca Mountain.

  7. Partial hexasomy for the Prader-Willi-Angelman syndrome critical region due to a maternally inherited large supernumerary marker chromosome.

    Science.gov (United States)

    Hoppman-Chaney, Nicole L; Dawson, D Brian; Nguyen, Lai; Sengupta, Sunanda; Reynolds, Kara; McPherson, Elizabeth; Velagaleti, Gopalrao

    2010-08-01

    Extra copies of the Prader-Willi-Angelman syndrome critical region (PWASCR) have been shown to have detrimental phenotypic effects depending on the parent of origin. Hexasomy for the PWASCR is rare; only 6 cases have been described to date. We report on a 15-year-old girl referred for developmental delay and seizures with a mosaic tricentric small marker chromosome (SMC) 15 identified by routine G-banding chromosome studies. C-banding and FISH confirmed the presence of three chromosome 15 centromeres as well as four copies of the PWASCR on the SMC in approximately 60% of interphase cells. Microsatellite genotyping documented maternal inheritance of the SMC, and methylation-sensitive multiplex ligation-dependent PCR amplification (MS-MLPA) showed that the extra copies of the PWASCR contained on the marker chromosome bear a methylation pattern similar to a normal maternal chromosome, implying maternal inheritance. These findings are consistent with the patient's phenotype as paternal inheritance of such a marker chromosome is thought to be benign. However, this patient's phenotype is the mildest described to date and may be a result of mosaicism for the SMC.

  8. Observation of parametric instabilities in the quarter critical density region driven by the Nike KrF laser

    Science.gov (United States)

    Weaver, J. L.; Oh, J.; Phillips, L.; Afeyan, B.; Seely, J.; Kehne, D.; Brown, C. M.; Obenschain, S. P.; Serlin, V.; Schmitt, A. J.; Feldman, U.; Lehmberg, R. H.; Mclean, E.; Manka, C.

    2013-02-01

    The krypton-fluoride (KrF) laser is an attractive choice for inertial confinement fusion due to its combination of short wavelength (λ =248 nm), large bandwidth (up to 3 THz), and superior beam smoothing by induced spatial incoherence. These qualities improve the overall hydrodynamics of directly driven pellet implosions and should allow use of increased laser intensity due to higher thresholds for laser plasma instabilities when compared to frequency tripled Nd:glass lasers (λ =351 nm). Here, we report the first observations of the two-plasmon decay instability using a KrF laser. The experiments utilized the Nike laser facility to irradiate solid plastic planar targets over a range of pulse lengths (0.35 ns≤τ≤1.25 ns) and intensities (up to 2×1015 W/cm2). Variation of the laser pulse created different combinations of electron temperature and electron density scale length. The observed onset of instability growth was consistent with the expected scaling that KrF lasers have a higher intensity threshold for instabilities in the quarter critical density region.

  9. Observation of parametric instabilities in the quarter critical density region driven by the Nike KrF laser

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, J. L.; Kehne, D.; Brown, C. M.; Obenschain, S. P.; Serlin, V.; Schmitt, A. J. [U.S. Naval Research Laboratory, Washington DC 20375 (United States); Oh, J.; Lehmberg, R. H.; Mclean, E.; Manka, C. [Research Support Instruments, Lanham, Maryland 20905 (United States); Phillips, L. [Alogus Research Corporation, McLean, Virginia 22101 (United States); Afeyan, B. [Polymath Research, Inc., Pleasanton, California 94566 (United States); Seely, J.; Feldman, U. [Berkeley Research Associates, Inc., Beltsville, Maryland 20705 (United States)

    2013-02-15

    The krypton-fluoride (KrF) laser is an attractive choice for inertial confinement fusion due to its combination of short wavelength ({lambda}=248 nm), large bandwidth (up to 3 THz), and superior beam smoothing by induced spatial incoherence. These qualities improve the overall hydrodynamics of directly driven pellet implosions and should allow use of increased laser intensity due to higher thresholds for laser plasma instabilities when compared to frequency tripled Nd:glass lasers ({lambda}=351 nm). Here, we report the first observations of the two-plasmon decay instability using a KrF laser. The experiments utilized the Nike laser facility to irradiate solid plastic planar targets over a range of pulse lengths (0.35 ns{<=}{tau}{<=}1.25 ns) and intensities (up to 2 Multiplication-Sign 10{sup 15} W/cm{sup 2}). Variation of the laser pulse created different combinations of electron temperature and electron density scale length. The observed onset of instability growth was consistent with the expected scaling that KrF lasers have a higher intensity threshold for instabilities in the quarter critical density region.

  10. Sequence analysis of the inversion region containing the pilin genes of Moraxella bovis.

    Science.gov (United States)

    Fulks, K A; Marrs, C F; Stevens, S P; Green, M R

    1990-01-01

    Moraxella bovis EPP63 is able to produce two antigenically distinct pili called Q and I pili (previously called beta and alpha pili). Hybridization studies have shown that the transition between the types is due to inversion of a 2.1-kilobase segment of chromosomal DNA. We present the sequence of a 4.1-kilobase region of cloned DNA spanning the entire inversion region in orientation 1 (Q pilin expressed). Comparison of this sequence with the sequence of the polymerase chain reaction-amplified genomic DNA from orientation 2 (I pilin expressed) allows the site-specific region of recombination to be localized to a 26-base-pair region in which sequence similarity to the left inverted repeat of the Salmonella typhimurium hin system was previously noted. In addition, 50% sequence similarity was seen in a 60-base-pair segment of our sequence to the recombinational enhancer of bacteriophage P1, an inversion system related to the hin system of S. typhimurium. Finally, two open reading frames representing potential genes were identified.

  11. Transcriptional analysis of the 5'-noncoding region of the human involucrin gene.

    Science.gov (United States)

    Lopez-Bayghen, E; Vega, A; Cadena, A; Granados, S E; Jave, L F; Gariglio, P; Alvarez-Salas, L M

    1996-01-01

    Human involucrin whose gene transcription is directed by a 2456-nucleotide (nt) 5'-noncoding region is a structural component of the epithelial cornified layer. Transient transfection assays demonstrated that this region is transcriptionally active in multiplying keratinocytes and is enhanced by 2 mM CaCl2 treatment. Calcium-independent transcriptional activity and the interaction with the AP-1 transcriptional factor was located on the proximal part (nt -159 to -1) of the 5'-noncoding region. However, CaCl2 responsiveness was mapped to a distal 1185-nt fragment (nt -2456 to -1272). Moreover, this fragment potentiated the Herpes simplex thymidine kinase promoter in normal keratinocytes and is responsive to calcium treatment in a cell type-specific manner. Interestingly, the absence of a 491-nt fragment located between the two enhancer domains (nt -651 to -160) resulted in transcriptional activation in multiplying keratinocytes. This fragment interacts with AP-1 and the YY1 transcriptional silencer. It is concluded that human involucrin 5'-noncoding region contains at least three regulatory domains, a distal CaCl2-responsive enhancer, a putative transcriptional silencer (that interacts with AP-1 and YY1), and a proximal enhancer/promoter (that interacts with AP-1). Thus, this study demonstrates the presence of particular transcriptional factors can potentially regulate the human involucrin expression.

  12. A new model approach for the near-critical point region: 1. Construction of the generalized van der Waals equation of state.

    Science.gov (United States)

    Lee, Sukbae; Jeon, Joonhyeon; Kim, Wonsoo; Chair, Tong-Seek

    2008-12-11

    To date, it has been considered that all classical equations of state (EOS) have failed to describe the properties of fluids near the critical region, where the density fluctuations have a significant influence on fluid properties. In this paper, we suggest a newly constructed equation for fluid states, the generalized van der Waals (GvdW) EOS with the highly simplified Dieterici's form P = [RT/(V - b)] - a(b/V)c by a new model potential construction describing intermolecular interactions. On the basis of the model potential construction, it is shown that the a, b, and c parameters have physical interpretations as an internal pressure, a void volume, and a dimensionless value that represents an inharmonic intermolecular cell potential, respectively. As an illustration of our model approach, we initially apply it to near the critical point (cp) region, where all classical EOS descriptions have been incorporated with experimental thermodynamic data, and we obtain a table of three parameters for 12 pure normal fluids, which precisely describes thermodynamic critical values. On the basis of the basic relations between pressure and volume at the critical point, we express the corresponding EOS in terms of the c parameter, and by this means, we also obtain a theoretical vapor-liquid equilibrium (VLE) line, which closely coincides with the experimental data for several pure normal fluids near the critical region. As a result, we show that thermodynamic properties near the critical region can be described analytically by only three parameters. In addition, to validate our EOS for the temperature-differential derivatives, we show that the calculated isochoric heat capacity (Cv) of saturated argon closely coincides with the experimental data. Moreover, the possibility of a precise description with respect to the entire fluid region is also argued, in terms of the physical cases from the triple point to the ideal gas region.

  13. Analysis of carbon source-regulated gene expression by the upstream region of the Candida tropicalis malate synthase gene in Saccharomyces cerevisiae.

    Science.gov (United States)

    Umemura, K; Atomi, H; Izuta, M; Kanai, T; Takeshita, S; Ueda, M; Tanaka, A

    1997-01-03

    We investigated the regulation of expression of a gene encoding malate synthase (MS) of an n-alkane-utilizable yeast Candida tropicalis in the yeast Saccharomyces cerevisiae, where its expression is highly induced by acetate. By comparing levels of gene expression in cells grown on glucose, acetate, lactate, and oleic acid, we found that the increase in gene expression was due to a glucose repression-derepression mechanism. In order to obtain information concerning the regulation of the gene expression, a fusion gene which consists of the 5'-upstream region of MS-2 (UPR-MS-2) and the lacZ gene (encoding Escherichia coli beta-galactosidase), was introduced into S. cerevisiae, and beta-galactosidase activities were measured with cells grown on glucose or acetate. Deletion analysis of UPR-MS-2 revealed that the region between -777 and -448 (against the translation initiation codon) enhanced the level of gene expression in both glucose- and acetate-grown cells. In this region, sequences which resemble binding sites of Rap1p/Grf1p/Tufp, a global transcription activator, were found at seven locations and one was found for another pleiotropic activator Abf1p. The result also suggested the presence of multiple upstream repression sequences (URSs), which function specifically in glucose-grown cells, in the region between -368 and -126. In the repressing region, there were three tandem C(A/T)CTCCC sequences and also a putative binding site of Mig1p, a transcriptional repressor which mediates glucose repression of several other genes. When MIG1 gene of S. cerevisiae was disrupted, the expression of the UPR-MS-2-lacZ gene in glucose-grown cells increased approx. 10-fold. Furthermore, the effect of deletion of a putative Mig1p binding site was abolished in the MIG1-disrupted strain, suggesting Mig1p binds to this site and brings about glucose repression. When the SNF1 gene was disrupted, the high level gene expression observed in acetate-grown cells bearing UPR-MS-2 was

  14. Functional analysis of genes differentially expressed in the Drosophila wing disc: role of transcripts enriched in the wing region.

    Science.gov (United States)

    Jacobsen, Thomas L; Cain, Donna; Paul, Litty; Justiniano, Steven; Alli, Anwar; Mullins, Jeremi S; Wang, Chun Ping; Butchar, Jon P; Simcox, Amanda

    2006-12-01

    Differential gene expression is the major mechanism underlying the development of specific body regions. Here we assessed the role of genes differentially expressed in the Drosophila wing imaginal disc, which gives rise to two distinct adult structures: the body wall and the wing. Reverse genetics was used to test the function of uncharacterized genes first identified in a microarray screen as having high levels of expression in the presumptive wing. Such genes could participate in elaborating the specific morphological characteristics of the wing. The activity of the genes was modulated using misexpression and RNAi-mediated silencing. Misexpression of eight of nine genes tested caused phenotypes. Of 12 genes tested, 10 showed effective silencing with RNAi transgenes, but only 3 of these had resulting phenotypes. The wing phenotypes resulting from RNAi suggest that CG8780 is involved in patterning the veins in the proximal region of the wing blade and that CG17278 and CG30069 are required for adhesion of wing surfaces. Venation and apposition of the wing surfaces are processes specific to wing development providing a correlation between the expression and function of these genes. The results show that a combination of expression profiling and tissue-specific gene silencing has the potential to identify new genes involved in wing development and hence to contribute to our understanding of this process. However, there are both technical and biological limitations to this approach, including the efficacy of RNAi and the role that gene redundancy may play in masking phenotypes.

  15. Differential Expression of FosB Proteins and Potential Target Genes in Select Brain Regions of Addiction and Depression Patients

    OpenAIRE

    Gajewski, Paula A.; Turecki, Gustavo; Robison, Alfred J.

    2016-01-01

    Chronic exposure to stress or drugs of abuse has been linked to altered gene expression throughout the body, and changes in gene expression in discrete brain regions are thought to underlie many psychiatric diseases, including major depressive disorder and drug addiction. Preclinical models of these disorders have provided evidence for mechanisms of this altered gene expression, including transcription factors, but evidence supporting a role for these factors in human patients has been slow t...

  16. Gene Expression in Archaea: Studies of Transcriptional Promoters, Messenger RNA Processing, and Five Prime Untranslated Regions in "Methanocaldococcus Jannashchii"

    Science.gov (United States)

    Zhang, Jian

    2009-01-01

    Gene expression in Archaea is less understood than those in Bacteria and Eucarya. In general, three steps are involved in gene expression--transcription, RNA processing, and translation. To expand our knowledge of these processes in Archaea, I have studied transcriptional promoters, messenger RNA processing, and 5'-untranslated regions in…

  17. Identification of T1D susceptibility genes within the MHC region by combining protein interaction networks and SNP genotyping data

    DEFF Research Database (Denmark)

    Brorsson, C.; Hansen, Niclas Tue; Hansen, Kasper Lage;

    2009-01-01

    region were analysed in 1000 affected offspring trios generated by the Type 1 Diabetes Genetics Consortium (T1DGC). The most associated SNP in each gene was chosen and genes were mapped to ppi networks for identification of interaction partners. The association testing and resulting interacting protein...

  18. Gene Expression in Archaea: Studies of Transcriptional Promoters, Messenger RNA Processing, and Five Prime Untranslated Regions in "Methanocaldococcus Jannashchii"

    Science.gov (United States)

    Zhang, Jian

    2009-01-01

    Gene expression in Archaea is less understood than those in Bacteria and Eucarya. In general, three steps are involved in gene expression--transcription, RNA processing, and translation. To expand our knowledge of these processes in Archaea, I have studied transcriptional promoters, messenger RNA processing, and 5'-untranslated regions in…

  19. Extensive families of constant region genes in a phylogenetically primitive vertebrate indicate an additional level of immunoglobulin complexity.

    Science.gov (United States)

    Kokubu, F; Hinds, K; Litman, R; Shamblott, M J; Litman, G W

    1987-01-01

    A homologous probe for the constant region of the Heterodontus francisci (horned shark) immunoglobulin heavy chain was used to screen a genomic DNA library constructed in bacteriophage lambda, and a large number of independent clones were recovered. Their hybridization patterns with segment-specific probes are consistent with the close linkage of heavy-chain constant (CH), joining (JH), and variable (VH) gene segments. Differences in the nucleotide sequences of the first CH exon of five genes primarily are localized to 5' positions; extended regions of sequence identity are noted at 3' positions. The predicted amino acid sequences of each gene are different and are related distantly to the corresponding regions of higher vertebrate immunoglobulins. Gene-specific oligodeoxynucleotide probes were used to establish that at least three of the five genes are transcriptionally active. Quantitative gene titration data are consistent with the large numbers of genes suggested by the library screening analyses. In this representative early vertebrate, it appears that (VH-diversity-JH) segments are associated with individual constant region genes that can differ at the predicted protein level. Images PMID:3475706

  20. TLR9 gene region polymorphisms and susceptibility to tuberculosis in Vietnam.

    Science.gov (United States)

    Graustein, A D; Horne, D J; Arentz, M; Bang, N D; Chau, T T H; Thwaites, G E; Caws, M; Thuong, N T T; Dunstan, S J; Hawn, T R

    2015-03-01

    Humans exposed to Mycobacterium tuberculosis (Mtb) show variation in susceptibility to infection and differences in tuberculosis (TB) disease outcome. Toll-like receptor 9 (TLR9) is a pattern recognition receptor that mediates recognition of Mtb and modulates Mtb-specific T-cell responses. Using a case-population design, we evaluated whether single nucleotide polymorphisms (SNPs) in the TLR9 gene region are associated with susceptibility to pulmonary or meningeal TB as well as neurologic presentation and mortality in the meningeal TB group. In a discovery cohort (n = 352 cases, 382 controls), three SNPs were associated with TB (all forms, p meningeal tuberculosis (dominant model; p = 0.0002, OR 2.36, CI 1.43-3.87) while rs352143 was associated with pulmonary tuberculosis (recessive model; p = 0.006, OR 5.3, CI 1.26-31.13). None of the SNPs were associated with mortality. This is the first demonstration of an association between a TLR9 gene region SNP and tuberculous meningitis. In addition, this extends previous findings that support associations of TLR9 SNPs with pulmonary tuberculosis.

  1. Conserved gene arrangement in the origin region of the Streptomyces coelicolor chromosome.

    Science.gov (United States)

    Calcutt, M J; Schmidt, F J

    1992-01-01

    A 23-kb fragment of the Streptomyces coelicolor chromosome spanning the dnaA region has been isolated as a cosmid clone. Nucleotide sequence analysis of a 5-kb portion shows that the genes for the RNase P protein (rnpA), ribosomal protein L34 (rpmH), the replication initiator protein (dnaA), and the beta subunit of DNA polymerase III (dnaN) are present in the highly conserved gene arrangement found in all eubacterial genomes studied so far. The dnaA-dnaN intergenic region is approximately 1 kb and contains a cluster of at least 12 DnaA boxes with a consensus sequence of TTGTCCACA matching the consensus DnaA box in the phylogenetically related Micrococcus luteus. Two DnaA boxes precede the dnaA sequence. We propose that the chromosomal origin (oriC) of S. coelicolor lies between dnaA and dnaN. In related work, J. Zakrzewska-Czerwinska and H. Schrempf (J. Bacteriol. 174:2688-2693, 1992) have identified the homologous sequence from the closely-related Streptomyces lividans as capable of self-replication. PMID:1577691

  2. Characterisation of the promoter region of the human DNA-repair gene Rad51.

    Science.gov (United States)

    Hasselbach, L; Haase, S; Fischer, D; Kolberg, H C; Stürzbecher, H W

    2005-01-01

    Regulatory elements of the 5'-flanking region of the DNA-repair gene Rad51 were analysed to characterise pathological alterations of Rad51 mRNA expression during tumour development. Various fragments of the Rad51 promoter were cloned into the pGL3 reporter vector and the respective promoter activity was determined by luciferase assays in transfected U2-OS cells. Transcription factor binding was identified using Protein/DNA arrays. The region encompassing base pairs -204 to -58 was identified as crucial for Rad51 gene transcription. Down regulator sequences are present upstream (-305 to -204) and downstream (-48 and +204) of this core promoter element. Promoter activity is significantly enhanced by substituting G at the polymorphic positions +135 and +172 for C and T, respectively. Transcription factors Ets1/PEA3, E2F1, p53, EGR1, and Stat5 were identified as relevant for regulating expression of Rad51. We identified three separate cis-sequence elements within the Rad51 transcriptional promoter, one ensuring basal levels of expression and two elements limiting expression to relatively low levels. The characterisation of transcription factor binding might help to explain high-level expression of Rad51 in a variety of solid tumours. The polymorphic sites appear important for the increased risk of breast and/or ovarian cancer for BRCA2 mutation carriers.

  3. The genetic polymorphism ofPlasmodium vivax genes in endemic regions of Thailand

    Institute of Scientific and Technical Information of China (English)

    Varakorn Kosaisavee; Ian Hastings; Alister Craig; Usa Lek-Uthai

    2011-01-01

    Objective:To investigate the genetic polymorphism ofPlasmodium vivax (P. vivax)PvCSP andPvMSP1 genes from field isolates at four endemic regions (North, East, West and South) of Thailand.Methods:The152P. vivax infected cases from dried blood spots wereDNA extracted and confirmed by species-specific primer sets using multiplexPCR method.PvMSP1 fragments F2 andF3; PvCSPwere genotyped usingRFLP-PCR method.Results: Totally amplified DNA which was multiple genotypes for PvMSP1 F2 andPvMSP1 F3 were12.50% and8.55%, respectively while PvCSP was3.95%. The overall frequency of multiple genotypes was25%. There were 12 allele types ofPvMSP1 F2 using AluI enzyme digestion and 8 size variations were found in PvMSP1 F3. The isolates from western region was highly genetic diverse when compare among all isolates. The predominant variant type of PvCSP gene wasVK210 type.Conclusions:The multiple genotypes are common found in Thailand and it might hide the real genotype.PvCSP does not have extensive genetic diversity in this study. However, PvMSP1marker due to multiple genotypes is difficult to be analyzed. The multiple genotypes findings might stem from population migration and vector species findings.

  4. PCR-based panel for regional localization of genes on chromosome 15

    Energy Technology Data Exchange (ETDEWEB)

    McDaniel, L.D.; Zhang, B.; Schultz, R.A. [Univ. of Texas Southwestern Medical Center, Dallas (United States)

    1994-09-01

    As the number of genes mapped to specific human chromosomes continues to increase, the feasibility of identifying the gene involved in a human genetic disease via a `candidate gene` approach will continue to improve. Although fluorescence in situ hybridization offers one approach to achieve refined mapping, results are dependent on the size of the probe used, which is not optimal for cDNAs or ESTs. In contrast, a PCR-based approach can achieve mapping for clones <100 bp in size. Through the use of a previously described deletion of chromosome 15 and the 15/17 translocation common to acute promyelocytic leukemia, we have assembled a small panel of somatic cell hybrids that can be used to assign probes to the regions 15p-q15, 15q15-q22, and 15q22-ter. Primers specific for unique cDNA sequences were used to amplify genomic DNA through the polymerase chain reaction. With this approach, we have assigned hexosaminidase A and aggrecan1 to 15q22-qter and leukocyte tyrosine kinase to 15q15-22.

  5. Prioritization of candidate genes in "QTL-hotspot" region for drought tolerance in chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Kale, Sandip M; Jaganathan, Deepa; Ruperao, Pradeep; Chen, Charles; Punna, Ramu; Kudapa, Himabindu; Thudi, Mahendar; Roorkiwal, Manish; Katta, Mohan A V S K; Doddamani, Dadakhalandar; Garg, Vanika; Kishor, P B Kavi; Gaur, Pooran M; Nguyen, Henry T; Batley, Jacqueline; Edwards, David; Sutton, Tim; Varshney, Rajeev K

    2015-10-19

    A combination of two approaches, namely QTL analysis and gene enrichment analysis were used to identify candidate genes in the "QTL-hotspot" region for drought tolerance present on the Ca4 pseudomolecule in chickpea. In the first approach, a high-density bin map was developed using 53,223 single nucleotide polymorphisms (SNPs) identified in the recombinant inbred line (RIL) population of ICC 4958 (drought tolerant) and ICC 1882 (drought sensitive) cross. QTL analysis using recombination bins as markers along with the phenotyping data for 17 drought tolerance related traits obtained over 1-5 seasons and 1-5 locations split the "QTL-hotspot" region into two subregions namely "QTL-hotspot_a" (15 genes) and "QTL-hotspot_b" (11 genes). In the second approach, gene enrichment analysis using significant marker trait associations based on SNPs from the Ca4 pseudomolecule with the above mentioned phenotyping data, and the candidate genes from the refined "QTL-hotspot" region showed enrichment for 23 genes. Twelve genes were found common in both approaches. Functional validation using quantitative real-time PCR (qRT-PCR) indicated four promising candidate genes having functional implications on the effect of "QTL-hotspot" for drought tolerance in chickpea.

  6. A synthetic luciferin improves in vivo bioluminescence imaging of gene expression in cardiovascular brain regions.

    Science.gov (United States)

    Simonyan, Hayk; Hurr, Chansol; Young, Colin N

    2016-10-01

    Bioluminescence imaging is an effective tool for in vivo investigation of molecular processes. We have demonstrated the applicability of bioluminescence imaging to spatiotemporally monitor gene expression in cardioregulatory brain nuclei during the development of cardiovascular disease, via incorporation of firefly luciferase into living animals, combined with exogenous d-luciferin substrate administration. Nevertheless, d-luciferin uptake into the brain tissue is low, which decreases the sensitivity of bioluminescence detection, particularly when considering small changes in gene expression in tiny central areas. Here, we tested the hypothesis that a synthetic luciferin, cyclic alkylaminoluciferin (CycLuc1), would be superior to d-luciferin for in vivo bioluminescence imaging in cardiovascular brain regions. Male C57B1/6 mice underwent targeted delivery of an adenovirus encoding the luciferase gene downstream of the CMV promoter to the subfornical organ (SFO) or paraventricular nucleus of hypothalamus (PVN), two crucial cardioregulatory neural regions. While bioluminescent signals could be obtained following d-luciferin injection (150 mg/kg), CycLuc1 administration resulted in a three- to fourfold greater bioluminescent emission from the SFO and PVN, at 10- to 20-fold lower substrate concentrations (7.5-15 mg/kg). This CycLuc1-mediated enhancement in bioluminescent emission was evident early following substrate administration (i.e., 6-10 min) and persisted for up to 1 h. When the exposure time was reduced from 60 s to 1,500 ms, minimal signal in the PVN was detectable with d-luciferin, whereas bioluminescent images could be reliably captured with CycLuc1. These findings demonstrate that bioluminescent imaging with the synthetic luciferin CycLuc1 provides an improved physiological genomics tool to investigate molecular events in discrete cardioregulatory brain nuclei.

  7. [Analysis of the structure and expression of the cluster of Drosophila melanogaster genes DIP1, CG32500, CG32819, and CG14476 in the flamenco gene region].

    Science.gov (United States)

    Potapova, M V; Nefedova, L N; Kim, A I

    2009-10-01

    The flamenco gene controlling transpositions of the gypsy retrovirus is localized in the 20A1-3 region, in which eight open reading frames organized in a cluster were discovered: DIP1, three repeats of CG32500 and CG32819, and CG14476. Analysis of the genes composing the cluster indicates that their transcription in Drosophila melanogaster is a stage-specific process. Comparison of the expression of these genes in the strains OreR, SS, and MS having the flamenco phenotype and in the strain 413 having the flamenco+ phenotype revealed differences only for the DIP1 gene, transcription of this gene being altered only in the OreR strain. Thus, mutant flamenco alleles are differently expressed in different strains. The structural organization of the flamenco gene region was studied in different Drosophila species: D. sechellia, D. simulans, D. mauritiana, D. yakuba, D. erecta, D. virilis, D. ananassae, D. grimshawi, and D. pseudoobscura. The genes of the cluster were found to be highly conserved in genomes of different species, but in none of them, except D. sechellia, the structural organization of the region repeats the structure of the D. melanogaster cluster.

  8. Gene expression profiling in C57BL/6J and A/J mouse inbred strains reveals gene networks specific for brain regions independent of genetic background

    Directory of Open Access Journals (Sweden)

    Horvath Steve

    2010-01-01

    Full Text Available Abstract Background We performed gene expression profiling of the amygdala and hippocampus taken from inbred mouse strains C57BL/6J and A/J. The selected brain areas are implicated in neurobehavioral traits while these mouse strains are known to differ widely in behavior. Consequently, we hypothesized that comparing gene expression profiles for specific brain regions in these strains might provide insight into the molecular mechanisms of human neuropsychiatric traits. We performed a whole-genome gene expression experiment and applied a systems biology approach using weighted gene co-expression network analysis. Results We were able to identify modules of co-expressed genes that distinguish a strain or brain region. Analysis of the networks that are most informative for hippocampus and amygdala revealed enrichment in neurologically, genetically and psychologically related pathways. Close examination of the strain-specific gene expression profiles, however, revealed no functional relevance but a significant enrichment of single nucleotide polymorphisms in the probe sequences used for array hybridization. This artifact was not observed for the modules of co-expressed genes that distinguish amygdala and hippocampus. Conclusions The brain-region specific modules were found to be independent of genetic background and are therefore likely to represent biologically relevant molecular networks that can be studied to complement our knowledge about pathways in neuropsychiatric disease.

  9. [Sequence characterization of the 5'-Flanking region of the GHR gene in Tibetan sheep].

    Science.gov (United States)

    Ma, Zhi-Jie; Wei, Ya-Ping; Zhong, Jin-Cheng; Chen, Zhi-Hua; Lu, Hong; Tong, Zi-Bao

    2007-08-01

    The 5'-Flanking sequence (including the P1 promotor and exon 1A) of the GHR gene in Oura-type Tibetan sheep (O. aries) was cloned by T-A method and sequenced (GenBank accession No. EF116490). Characterization and comparison of this sequence with mouflons (O. musimon), goat (C. hircus), cattle (B. taurus) and European bison (B. bonasus) orthologues were also conducted. Results showed that: 1) The 5'-flanking region contained many potential transcriptional factor binding sites such as those for C/EBPb, C/EBP, SP1, Cap, USF, HFH-2, HNF-3b, and Oct-1, which might have an important effect on transcription activation and regulation as well as tissue-specific expression. The rate of repetitive sequences was 2.55% and no SINEs, LINEs, LTR anti-transcription elements or DNA transposon elements were found, although one (TG)11 microsatellite was found. 2) In the P1 promotor region, sequence homology between the Tibetan sheep and mouflon, goat, cattle and European bison was 99.7%, 94.2%, 85.9% and 86.5%, respectively, while that for exon 1A was 99.0%, 97.0%, 92.7% and 94.6%, respectively. 3) The molecular phylogenetic tree among these species, constructed by the neighborhood joining method based on the sequences of no-coding region of the GHR genes, placed the two Bovinae species on one branch and the three Caprinae species on the other. Tibetan sheep and mouflons were joined first, followed by the goat, and then the Bovinae species, including the cattle and European bison. This result of phylogenetic clustering was not only identical to the taxonomy, but also to the phylogenetic clustering using the mitochondrial DNA of these species.

  10. Inter-ethnic polymorphism of the beta-globin gene locus control region (LCR) in sickle-cell anemia patients.

    Science.gov (United States)

    Périchon, B; Ragusa, A; Lapouméroulie, C; Romand, A; Moi, P; Ikuta, T; Labie, D; Elion, J; Krishnamoorthy, R

    1993-06-01

    Sequence polymorphisms within the 5'HS2 segment of human locus control region is described among sickle cell anemia patients. Distinct polymorphic patterns of a simple sequence repeat are observed in strong linkage disequilibrium with each of the five major beta s haplotypes. Potential functional relevance of this polymorphic region in globin gene expression is discussed.

  11. The preferential codon usages in variable and constant regions of immunoglobulin genes are quite distinct from each other.

    Science.gov (United States)

    Miyata, T; Hayashida, H; Yasunaga, T; Hasegawa, M

    1979-12-20

    The pattern of codon utilization in the variable and constant regions of immunoglobulin genes are compared. It is shown that, in these regions, codon utilizations are quite distinct from one another: For most degenerate codons, there is a selective bias that prefers C and/or G ending codons to U and/or A ending codons in the constant region compared with the bias in the variable region. This would strongly suggest that, in immunoglobulin genes, the bias in code word usage is determined by other factors than those concerning with the translational mechanism such as tRNA availability and codon-anticodon interaction. A possibility is also suggested that this differance of code word usage between them is due to the existence of secondary structure in the constant region but not in the variable region.

  12. Cloning of the human heparan sulfate-N-deacetylase/N-sulfotransferase gene from the Treacher Collins syndrome candidate region at 5q32-q33.1

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, J.; Loftus, S.K.; Gladwin, A.J. [Univ. of Manchester (United Kingdom)] [and others

    1995-03-20

    Treacher Collins syndrome is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. Previous studies have shown that the Treacher Collins syndrome locus is flanked by D5S519 and SPARC, and a yeast artificial chromosome contig encompassing this {open_quotes}critical region{close_quotes} has been completed. In the current investigation a cosmid containing D5S519 has been used to screen a human placental cDNA library. This has resulted in the cloning of the human heparan sulfate-N-deacetylase/N-sulfotransferase gene. Two different mRNA species that have identical protein coding sequences but that differ in the size and sequence of the 3{prime} untranslated regions (3{prime}UTR) have been identified. The smaller species has a 3{prime}UTR of 1035 bp, whereas that of the larger is 4878 bp. 24 refs., 3 figs.

  13. Identification and genetic mapping of a homeobox gene to the 4p16. 1 region of human chromosome 4

    Energy Technology Data Exchange (ETDEWEB)

    Stadler, H.S.; Padanilam, B.J.; Solursh, M. (Univ. of Iowa, Iowa City (United States)); Buetow, K. (Fox Chase Cancer Center, Philadelphia, PA (United States)); Murray, J.C. (Univ. of Iowa Hospitals and Clinics, Iowa City (United States))

    1992-12-01

    A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4P16.1 region by using somatic cell hybrids containing specific deletions of human chromosome 4. Linkage data from a single-stranded conformational polymorphism derived from the 3[prime] untranslated region of the H6 cDNA placed this homeobox gene more than 20 centimorgans proximal of the previously mapped HOX7 gene on chromosome 4. Identity comparisons of the H6 Homeodomain with previously reported homeodomains reveal the highest identities to be with the Nk class of homeobox genes in Drosophila melanogaster. 53 refs., 5 figs., 2 tabs.

  14. Identification and genetic mapping of a homeobox gene to the 4p16.1 region of human chromosome 4.

    Science.gov (United States)

    Stadler, H S; Padanilam, B J; Buetow, K; Murray, J C; Solursh, M

    1992-12-01

    A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4p16.1 region by using somatic cell hybrids containing specific deletions of human chromosome 4. Linkage data from a single-stranded conformational polymorphism derived from the 3' untranslated region of the H6 cDNA placed this homeobox gene more than 20 centimorgans proximal of the previously mapped HOX7 gene on chromosome 4. Identity comparisons of the H6 homeodomain with previously reported homeodomains reveal the highest identities to be with the Nk class of homeobox genes in Drosophila melanogaster.

  15. A group of Giardia lamblia variant-specific surface protein (VSP) genes with nearly identical 5' regions.

    Science.gov (United States)

    Yang, Y; Adam, R D

    1995-12-01

    The surfaces of Giardia lamblia trophozoites contain one of a set of variant-specific surface proteins. The genes encoding these proteins are highly conserved at the 3' terminus, but frequently demonstrate little similarity in the remainder of the coding region. This report describes a family of vsp genes highly similar to a repeat-containing vsp gene (vspC5) at the 5' coding and flanking regions, but which diverge abruptly from vspC5 in the first repeat and do not themselves contain full copies of the repeat. This observation suggests the possibility that recombination among different vsp genes may have played a role in development of the vsp gene repertoire.

  16. Dissecting inflammatory complications in critically injured patients by within-patient gene expression changes: a longitudinal clinical genomics study.

    Directory of Open Access Journals (Sweden)

    Keyur H Desai

    2011-09-01

    Full Text Available BACKGROUND: Trauma is the number one killer of individuals 1-44 y of age in the United States. The prognosis and treatment of inflammatory complications in critically injured patients continue to be challenging, with a history of failed clinical trials and poorly understood biology. New approaches are therefore needed to improve our ability to diagnose and treat this clinical condition. METHODS AND FINDINGS: We conducted a large-scale study on 168 blunt-force trauma patients over 28 d, measuring ∼400 clinical variables and longitudinally profiling leukocyte gene expression with ∼800 microarrays. Marshall MOF (multiple organ failure clinical score trajectories were first utilized to organize the patients into five categories of increasingly poor outcomes. We then developed an analysis framework modeling early within-patient expression changes to produce a robust characterization of the genomic response to trauma. A quarter of the genome shows early expression changes associated with longer-term post-injury complications, captured by at least five dynamic co-expression modules of functionally related genes. In particular, early down-regulation of MHC-class II genes and up-regulation of p38 MAPK signaling pathway were found to strongly associate with longer-term post-injury complications, providing discrimination among patient outcomes from expression changes during the 40-80 h window post-injury. CONCLUSIONS: The genomic characterization provided here substantially expands the scope by which the molecular response to trauma may be characterized and understood. These results may be instrumental in furthering our understanding of the disease process and identifying potential targets for therapeutic intervention. Additionally, the quantitative approach we have introduced is potentially applicable to future genomics studies of rapidly progressing clinical conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT00257231

  17. Human lambda light-chain constant region gene CMor lambda: the primary structure of lambda VI Bence Jones protein Mor.

    OpenAIRE

    Frangione, B.; Moloshok, T; Prelli, F; Solomon, A

    1985-01-01

    Serologic, structural, and genetic analyses have shown that the constant (C) region of human kappa light chains is encoded by a single gene, whereas that of lambda chains is encoded by multiple genes. We have determined the complete C region amino acid sequence of two monoclonal lambda VI light chains, Bence Jones proteins Sut and Mor. The C region of lambda chains Sut and Mor consists of 105 residues, as is characteristic for human lambda light chains, of which 102 are identical in sequence....

  18. High diversity due to balancing selection in the promoter region of the Medea gene in Arabidopsis lyrata.

    Science.gov (United States)

    Kawabe, Akira; Fujimoto, Ryo; Charlesworth, Deborah

    2007-11-06

    Molecular imprinting is the differential expression and/or silencing of alleles according to their parent of origin [1, 2]. Conflicts between parents, or parents and offspring, should cause "arms races," with accelerated evolution of the genes involved in imprinting. This should be detectable in the evolution of imprinting genes' protein sequences and in the promoter regions of imprinted genes. Previous studies, however, found no evidence of more amino acid substitutions in imprinting genes [1, 3]. We have analyzed sequence diversity of the Arabidopsis lyrata Medea (MEA) gene and divergence from the A. thaliana sequence, including the first study of the promoter region. In A. thaliana, MEA is imprinted, with paternal alleles silenced in endosperm cells [4, 5], and also functions in the imprinting machinery [4, 6]; MEA protein binding at the MEA promoter region indicates self-regulated imprinting [7-9]. We find the same paternal MEA allele silencing in A. lyrata endosperm but no evidence for adaptive evolution in the coding region, whereas the 5' flanking region displays high diversity, with distinct haplotypes, suggesting balancing selection in the promoter region.

  19. Genes from the exo-xis region of λ and Shiga toxin-converting bacteriophages influence lysogenization and prophage induction.

    Science.gov (United States)

    Bloch, Sylwia; Nejman-Faleńczyk, Bożena; Łoś, Joanna M; Barańska, Sylwia; Łepek, Krzysztof; Felczykowska, Agnieszka; Łoś, Marcin; Węgrzyn, Grzegorz; Węgrzyn, Alicja

    2013-11-01

    The exo-xis region, present in genomes of lambdoid bacteriophages, contains highly conserved genes of largely unknown functions. In this report, using bacteriophage λ and Shiga toxin-converting bacteriophage ϕ24Β, we demonstrate that the presence of this region on a multicopy plasmid results in impaired lysogenization of Escherichia coli and delayed, while more effective, induction of prophages following stimulation by various agents (mitomycin C, hydrogen peroxide, UV irradiation). Spontaneous induction of λ and ϕ24Β prophages was also more efficient in bacteria carrying additional copies of the corresponding exo-xis region on plasmids. No significant effects of an increased copy number of genes located between exo and xis on both efficiency of adsorption on the host cells and lytic development inside the host cell of these bacteriophages were found. We conclude that genes from the exo-xis region of lambdoid bacteriophages participate in the regulation of lysogenization and prophage maintenance.

  20. RISSC: a novel database for ribosomal 16S-23S RNA genes spacer regions.

    Science.gov (United States)

    García-Martínez, J; Bescós, I; Rodríguez-Sala, J J; Rodríguez-Valera, F

    2001-01-01

    A novel database, under the acronym RISSC (Ribosomal Intergenic Spacer Sequence Collection), has been created. It compiles more than 1600 entries of edited DNA sequence data from the 16S-23S ribosomal spacers present in most prokaryotes and organelles (e.g. mitochondria and chloroplasts) and is accessible through the Internet (http://ulises.umh.es/RISSC), where systematic searches for specific words can be conducted, as well as BLAST-type sequence searches. Additionally, a characteristic feature of this region, the presence/absence and nature of tRNA genes within the spacer, is included in all the entries, even when not previously indicated in the original database. All these combined features could provide a useful documentation tool for studies on evolution, identification, typing and strain characterization, among others.

  1. Role of Interleukin-10 Gene Promoter Region Polymorphism in the Development of Chronic Lymphoid Leukemia.

    Science.gov (United States)

    Ovsepyan, V A; Gabdulkhakova, A Kh; Shubenkiva, A A; Zotina, E N

    2015-12-01

    Relationship between interleukin-10 (IL-10) gene G-1082A (rs1800896) polymorphism and the risk of development and stages of chronic lymphoid leukemia is studied in ethnic Russian residents of the Kirov region of Russia. Associations of allele -1082A and genotypes (-1082AA/-1082AG) with the risk of chronic lymphoid leukemia are detected (OR=1.39, 95%CI=1.09-1.78 and OR=1.66, 95%CI=1.09-2.54, respectively). In addition, association of 1082AA genotype with late stages of the disease by the moment of diagnosis is detected. These data indicate that IL-10 polymorphism G-1082A may be involved in the pathogenesis of chronic lymphoid leukemia.

  2. Comparative analysis of chicken chromosome 28 provides new clues to the evolutionary fragility of gene-rich vertebrate regions.

    Science.gov (United States)

    Gordon, Laurie; Yang, Shan; Tran-Gyamfi, Mary; Baggott, Dan; Christensen, Mari; Hamilton, Aaron; Crooijmans, Richard; Groenen, Martien; Lucas, Susan; Ovcharenko, Ivan; Stubbs, Lisa

    2007-11-01

    The chicken genome draft sequence has provided a valuable resource for studies of an important agricultural and experimental model species and an important data set for comparative analysis. However, some of the most gene-rich segments are missing from chicken genome draft assemblies, limiting the analysis of a substantial number of genes and preventing a closer look at regions that are especially prone to syntenic rearrangements. To facilitate the functional and evolutionary analysis of one especially gene-rich, rearrangement-prone genomic region, we analyzed sequence from BAC clones spanning chicken microchromosome GGA28; as a complement we also analyzed a gene-sparse, stable region from GGA11. In these two regions we documented the conservation and lineage-specific gain and loss of protein-coding genes and precisely mapped the locations of 31 major human-chicken syntenic breakpoints. Altogether, we identified 72 lineage-specific genes, many of which are found at or near syntenic breaks, implicating evolutionary breakpoint regions as major sites of genetic innovation and change. Twenty-two of the 31 breakpoint regions have been reused repeatedly as rearrangement breakpoints in vertebrate evolution. Compared with stable GC-matched regions, GGA28 is highly enriched in CpG islands, as are break-prone intervals identified elsewhere in the chicken genome; evolutionary breakpoints are further enriched in GC content and CpG islands, highlighting a potential role for these features in genome instability. These data support the hypothesis that chromosome rearrangements have not occurred randomly over the course of vertebrate evolution but are focused preferentially within "fragile" regions with unusual DNA sequence characteristics.

  3. Gene Map of the HLA Region, Graves' Disease and Hashimoto Thyroiditis, and Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Sasazuki, Takehiko; Inoko, Hidetoshi; Morishima, Satoko; Morishima, Yasuo

    2016-01-01

    The human leukocyte antigen (HLA) genomic region spanning about 4 Mb is the most gene dense and the polymorphic stretches in the human genome. A total of the 269 loci were identified, including 145 protein coding genes mostly important for immunity and 50 noncoding RNAs (ncRNAs). Biological function of these ncRNAs remains unknown, becoming hot spot in the studies of HLA-associated diseases. The genomic diversity analysis in the HLA region facilitated by next-generation sequencing will pave the way to molecular understanding of linkage disequilibrium structure, population diversity, histocompatibility in transplantation, and associations with autoimmune diseases. The 4-digit DNA genotyping of HLA for six HLA loci, HLA-A through DP, in the patients with Graves' disease (GD) and Hashimoto thyroiditis (HT) identified six susceptible and three resistant HLA alleles. Their epistatic interactions in controlling the development of these diseases are shown. Four susceptible and one resistant HLA alleles are shared by GD and HT. Two HLA alleles associated with GD or HT control the titers of autoantibodies to thyroid antigens. All these observations led us to propose a new model for the development of GD and HT. Hematopoietic stem cell transplantation from unrelated donor (UR-HSCT) provides a natural experiment to elucidate the role of allogenic HLA molecules in immune response. Large cohort studies using HLA allele and clinical outcome data have elucidated that (1) HLA locus, allele, and haplotype mismatches between donor and patient, (2) specific amino acid substitution at specific positions of HLA molecules, and (3) ethnic background are all responsible for the immunological events related to UR-HSCT including acute graft-versus-host disease (GVHD), chronic GVHD, graft-versus-leukemia (GvL) effect, and graft failure.

  4. MicroRNA genes and their target 3'-untranslated regions are infrequently somatically mutated in ovarian cancers.

    Directory of Open Access Journals (Sweden)

    Georgina L Ryland

    Full Text Available MicroRNAs are key regulators of gene expression and have been shown to have altered expression in a variety of cancer types, including epithelial ovarian cancer. MiRNA function is most often achieved through binding to the 3'-untranslated region of the target protein coding gene. Mutation screening using massively-parallel sequencing of 712 miRNA genes in 86 ovarian cancer cases identified only 5 mutated miRNA genes, each in a different case. One mutation was located in the mature miRNA, and three mutations were predicted to alter the secondary structure of the miRNA transcript. Screening of the 3'-untranslated region of 18 candidate cancer genes identified one mutation in each of AKT2, EGFR, ERRB2 and CTNNB1. The functional effect of these mutations is unclear, as expression data available for AKT2 and EGFR showed no increase in gene transcript. Mutations in miRNA genes and 3'-untranslated regions are thus uncommon in ovarian cancer.

  5. MicroRNA genes and their target 3'-untranslated regions are infrequently somatically mutated in ovarian cancers.

    Science.gov (United States)

    Ryland, Georgina L; Bearfoot, Jennifer L; Doyle, Maria A; Boyle, Samantha E; Choong, David Y H; Rowley, Simone M; Tothill, Richard W; Gorringe, Kylie L; Campbell, Ian G

    2012-01-01

    MicroRNAs are key regulators of gene expression and have been shown to have altered expression in a variety of cancer types, including epithelial ovarian cancer. MiRNA function is most often achieved through binding to the 3'-untranslated region of the target protein coding gene. Mutation screening using massively-parallel sequencing of 712 miRNA genes in 86 ovarian cancer cases identified only 5 mutated miRNA genes, each in a different case. One mutation was located in the mature miRNA, and three mutations were predicted to alter the secondary structure of the miRNA transcript. Screening of the 3'-untranslated region of 18 candidate cancer genes identified one mutation in each of AKT2, EGFR, ERRB2 and CTNNB1. The functional effect of these mutations is unclear, as expression data available for AKT2 and EGFR showed no increase in gene transcript. Mutations in miRNA genes and 3'-untranslated regions are thus uncommon in ovarian cancer.

  6. MicroRNA Genes and Their Target 3′-Untranslated Regions Are Infrequently Somatically Mutated in Ovarian Cancers

    Science.gov (United States)

    Doyle, Maria A.; Boyle, Samantha E.; Choong, David Y. H.; Rowley, Simone M.; Tothill, Richard W.; Gorringe, Kylie L.; Campbell, Ian G.

    2012-01-01

    MicroRNAs are key regulators of gene expression and have been shown to have altered expression in a variety of cancer types, including epithelial ovarian cancer. MiRNA function is most often achieved through binding to the 3′-untranslated region of the target protein coding gene. Mutation screening using massively-parallel sequencing of 712 miRNA genes in 86 ovarian cancer cases identified only 5 mutated miRNA genes, each in a different case. One mutation was located in the mature miRNA, and three mutations were predicted to alter the secondary structure of the miRNA transcript. Screening of the 3′-untranslated region of 18 candidate cancer genes identified one mutation in each of AKT2, EGFR, ERRB2 and CTNNB1. The functional effect of these mutations is unclear, as expression data available for AKT2 and EGFR showed no increase in gene transcript. Mutations in miRNA genes and 3′-untranslated regions are thus uncommon in ovarian cancer. PMID:22536442

  7. Single nucleotide polymorphism mining and nucleotide sequence analysis of Mx1 gene in exonic regions of Japanese quail

    Directory of Open Access Journals (Sweden)

    Diwesh Kumar Niraj

    2015-12-01

    Full Text Available Aim: An attempt has been made to study the Myxovirus resistant (Mx1 gene polymorphism in Japanese quail. Materials and Methods: In the present, investigation four fragments viz. Fragment I of 185 bp (Exon 3 region, Fragment II of 148 bp (Exon 5 region, Fragment III of 161 bp (Exon 7 region, and Fragment IV of 176 bp (Exon 13 region of Mx1 gene were amplified and screened for polymorphism by polymerase chain reaction-single-strand conformation polymorphism technique in 170 Japanese quail birds. Results: Out of the four fragments, one fragment (Fragment II was found to be polymorphic. Remaining three fragments (Fragment I, III, and IV were found to be monomorphic which was confirmed by custom sequencing. Overall nucleotide sequence analysis of Mx1 gene of Japanese quail showed 100% homology with common quail and more than 80% homology with reported sequence of chicken breeds. Conclusion: The Mx1 gene is mostly conserved in Japanese quail. There is an urgent need of comprehensive analysis of other regions of Mx1 gene along with its possible association with the traits of economic importance in Japanese quail.

  8. Enrichment of short interspersed transposable elements to embryonic stem cell-specific hypomethylated gene regions.

    Science.gov (United States)

    Muramoto, Hiroki; Yagi, Shintaro; Hirabayashi, Keiji; Sato, Shinya; Ohgane, Jun; Tanaka, Satoshi; Shiota, Kunio

    2010-08-01

    Embryonic stem cells (ESCs) have a distinctive epigenome, which includes their genome-wide DNA methylation modification status, as represented by the ESC-specific hypomethylation of tissue-dependent and differentially methylated regions (T-DMRs) of Pou5f1 and Nanog. Here, we conducted a genome-wide investigation of sequence characteristics associated with T-DMRs that were differentially methylated between ESCs and somatic cells, by focusing on transposable elements including short interspersed elements (SINEs), long interspersed elements (LINEs) and long terminal repeats (LTRs). We found that hypomethylated T-DMRs were predominantly present in SINE-rich/LINE-poor genomic loci. The enrichment for SINEs spread over 300 kb in cis and there existed SINE-rich genomic domains spreading continuously over 1 Mb, which contained multiple hypomethylated T-DMRs. The characterization of sequence information showed that the enriched SINEs were relatively CpG rich and belonged to specific subfamilies. A subset of the enriched SINEs were hypomethylated T-DMRs in ESCs at Dppa3 gene locus, although SINEs are overall methylated in both ESCs and the liver. In conclusion, we propose that SINE enrichment is the genomic property of regions harboring hypomethylated T-DMRs in ESCs, which is a novel aspect of the ESC-specific epigenomic information.

  9. Performance of genotype imputation for rare variants identified in exons and flanking regions of genes.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available Genotype imputation has the potential to assess human genetic variation at a lower cost than assaying the variants using laboratory techniques. The performance of imputation for rare variants has not been comprehensively studied. We utilized 8865 human samples with high depth resequencing data for the exons and flanking regions of 202 genes and Genome-Wide Association Study (GWAS data to characterize the performance of genotype imputation for rare variants. We evaluated reference sets ranging from 100 to 3713 subjects for imputing into samples typed for the Affymetrix (500K and 6.0 and Illumina 550K GWAS panels. The proportion of variants that could be well imputed (true r(2>0.7 with a reference panel of 3713 individuals was: 31% (Illumina 550K or 25% (Affymetrix 500K with MAF (Minor Allele Frequency less than or equal 0.001, 48% or 35% with 0.0010.05. The performance for common SNPs (MAF>0.05 within exons and flanking regions is comparable to imputation of more uniformly distributed SNPs. The performance for rare SNPs (0.01

  10. Analysis of Alzheimer's disease severity across brain regions by topological analysis of gene co-expression networks

    Directory of Open Access Journals (Sweden)

    Zhang Weixiong

    2010-10-01

    Full Text Available Abstract Background Alzheimer's disease (AD is a progressive neurodegenerative disorder involving variations in the transcriptome of many genes. AD does not affect all brain regions simultaneously. Identifying the differences among the affected regions may shed more light onto the disease progression. We developed a novel method involving the differential topology of gene coexpression networks to understand the association among affected regions and disease severity. Methods We analysed microarray data of four regions - entorhinal cortex (EC, hippocampus (HIP, posterior cingulate cortex (PCC and middle temporal gyrus (MTG from AD affected and normal subjects. A coexpression network was built for each region and the topological overlap between them was examined. Genes with zero topological overlap between two region-specific networks were used to characterise the differences between the two regions. Results and conclusion Results indicate that MTG shows early AD pathology compared to the other regions. We postulate that if the MTG gets affected later in the disease, post-mortem analyses of individuals with end-stage AD will show signs of early AD in the MTG, while the EC, HIP and PCC will have severe pathology. Such knowledge is useful for data collection in clinical studies where sample selection is a limiting factor as well as highlighting the underlying biology of disease progression.

  11. Characterization of promoter region and genomic structure of the murine and human genes encoding Src like adapter protein.

    Science.gov (United States)

    Kratchmarova, I; Sosinowski, T; Weiss, A; Witter, K; Vincenz, C; Pandey, A

    2001-01-10

    Src-like adapter protein (SLAP) was identified as a signaling molecule in a yeast two-hybrid system using the cytoplasmic domain of EphA2, a receptor protein tyrosine kinase (Pandey et al., 1995. Characterization of a novel Src-like adapter protein that associates with the Eck receptor tyrosine kinase. J. Biol. Chem. 270, 19201-19204). It is very similar to members of the Src family of cytoplasmic tyrosine kinases in that it contains very homologous SH3 and SH2 domains (Abram and Courtneidge, 2000. Src family tyrosine kinases and growth factor signaling. Exp. Cell. Res. 254, 1-13.). However, instead of a kinase domain at the C-terminus, it contains a unique C-terminal region. In order to exclude the possibility that an alternative form exists, we have isolated genomic clones containing the murine Slap gene as well as the human SLA gene. The coding regions of murine Slap and human SLA genes contain seven exons and six introns. Absence of any kinase domain in the genomic region confirm its designation as an adapter protein. Additionally, we have cloned and sequenced approximately 2.6 kb of the region 5' to the initiator methionine of the murine Slap gene. When subcloned upstream of a luciferase gene, this fragment increased the transcriptional activity about 6-fold in a human Jurkat T cell line and approximately 52-fold in a murine T cell line indicating that this region contains promoter elements that dictate SLAP expression. We have also cloned the promoter region of the human SLA gene. Since SLAP is transcriptionally regulated by retinoic acid and by activation of B cells, the cloning of its promoter region will permit a detailed analysis of the elements required for its transcriptional regulation.

  12. Insertion of part of an intron into the 5[prime] untranslated region of a Caenorhabditis elegans gene converts it into a trans-spliced gene

    Energy Technology Data Exchange (ETDEWEB)

    Conrad, R.; Thomas, J.; Spieth, J.; Blumenthal, T. (Indiana University, Bloomington (United States))

    1991-04-01

    In nematodes, the RNA products of some genes are trans-spliced to a 22-nucleotide spliced leader (SL), while the RNA products of other genes are not. In Caenorhabditis elegans, there are two SLs, Sl1 and SL2, donated by two distinct small nuclear ribonucleoprotein particles in a process functionally quite similar to nuclear intron removal. The authors demonstrate here that it is possible to convert a non-trans-spliced gene into a trans-spliced gene by placement of an intron missing only the 5[prime] splice site into the 5[prime] untranslated region. Stable transgenic strains were isolated expressing a gene in which 69 nucleotides of a vit-5 intron, including the 3[prime] splice site, were inserted into the 5[prime] untranslated region of a vit-2/vit-6 fusion gene. The RNA product of this gene was examined by primer extension and PCR amplification. Although the vit-2/vit-6 transgene product is not normally trans-spliced, the majority of transcripts from this altered gene were trans-spliced to SL1. They termed the region of a trans-spliced mRNA precursor between the 5[prime] end and the first 3[prime] splice site an 'outrun'. The results suggest that if a transcript begins with intronlike sequence followed by a 3[prime] splice site, this alone may constitute an outrun and be sufficient to demarcate a transcript as a trans-splice acceptor. These findings leave open the possibility that specific sequences are required to increase the efficiency of trans-splicing.

  13. Microarray and comparative genomics-based identification of genes and gene regulatory regions of the mouse immune system

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    Katz Jonathan D

    2004-10-01

    Full Text Available Abstract Background In this study we have built and mined a gene expression database composed of 65 diverse mouse tissues for genes preferentially expressed in immune tissues and cell types. Using expression pattern criteria, we identified 360 genes with preferential expression in thymus, spleen, peripheral blood mononuclear cells, lymph nodes (unstimulated or stimulated, or in vitro activated T-cells. Results Gene clusters, formed based on similarity of expression-pattern across either all tissues or the immune tissues only, had highly significant associations both with immunological processes such as chemokine-mediated response, antigen processing, receptor-related signal transduction, and transcriptional regulation, and also with more general processes such as replication and cell cycle control. Within-cluster gene correlations implicated known associations of known genes, as well as immune process-related roles for poorly described genes. To characterize regulatory mechanisms and cis-elements of genes with similar patterns of expression, we used a new version of a comparative genomics-based cis-element analysis tool to identify clusters of cis-elements with compositional similarity among multiple genes. Several clusters contained genes that shared 5–6 cis-elements that included ETS and zinc-finger binding sites. cis-Elements AP2 EGRF ETSF MAZF SP1F ZF5F and AREB ETSF MZF1 PAX5 STAT were shared in a thymus-expressed set; AP4R E2FF EBOX ETSF MAZF SP1F ZF5F and CREB E2FF MAZF PCAT SP1F STAT cis-clusters occurred in activated T-cells; CEBP CREB NFKB SORY and GATA NKXH OCT1 RBIT occurred in stimulated lymph nodes. Conclusion This study demonstrates a series of analytic approaches that have allowed the implication of genes and regulatory elements that participate in the differentiation, maintenance, and function of the immune system. Polymorphism or mutation of these could adversely impact immune system functions.

  14. Association between 5-hydroxytryptamine transporter gene-linked polymorphic region and smoking behavior in Chinese males

    Institute of Scientific and Technical Information of China (English)

    CHU Shui-lian; XIAO Dan; WANG Chen; JING Hang

    2009-01-01

    Background Tobacco use is the major risk factor for numerous health problems. However, only 5% of smokers can successfully quit without therapy owing to the highly addictive properties of nicotine. The serotoninergic system may be involved in smoking behavior because nicotine increases brain serotonin secretion, nicotine withdrawal decreases serotonin levels, and a selective serotonin reuptake inhibitor antagonizes the response to nicotine withdrawal. Serotonin transporter (5-HTT) is the most important protein, as it adjusts the serotonin concentration in the synaptic cleft. There is a polymorphism in the upstream regulatory region of the 5-HTT gene, named 5-hydroxytryptamine transporter gene-Iinked poyymorphic region (5-HTTLPR). Compared with the L allele, the S allele of the polymorphism is associated with decreased transcription efficiency of the 5-HTT gene. In this study, we investigated the relationship between this gene polymorphism and smoking behavior in Chinese males.Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find 5-HTTLPR gene polymorphisms in 144 smokers and 135 age-matched healthy non-smokers. A questionnaire was completed in all recruited subjects.Results The proportion of L/L (15.3% vs 5.2%) and S/L (50.0% vs 33.3%) genotypes was significantly higher in the smokers than that in the non-smokers (χ2=21.9; P <0.01). The odds ratio (OR) adjusted by age, education, effects of family members and friends who smoke, and alcohol intake was 2.9 (95%CI 1.78-4.80). In smokers, the number of cigarettes/day (L/L vs S/L vs S/S: 28+12 vs 20±8 vs 16±6, χ2=18.5, P <0.01), smoking index (L/L vs S/L vs S/S.. 561±446vs 393±341 vs 237+901, χ2=12.5, P <0.01) and score on the Fagerstrom test for nicotine dependence (FTND) (L/L vs S/L vs S/S. 7.8±1.6 vs 6.2±9.5 vs 3.5±9.1, χ2=48.3, P <0.01) were significantly higher in smokers with an L/L or S/L genotype than that in the smokers with the S/S genotype

  15. Critical success factors for govering public goods in rural delevopment of two Dutch regions, Winterwijk and Het Groene Woud

    NARCIS (Netherlands)

    Blom, M.; Korevaar, H.; Stuiver, M.; Groot, A.M.E.

    2012-01-01

    Sustainable regional development is a complex multi-stakeholder process that involves social and physical processes at different scales. The study aimed to provide adequate knowledge on the underlying mechanisms of regional development and the way actors in the region act upon these. Through two emp

  16. Association of MICA gene polymorphisms with liver fibrosis in schistosomiasis patients in the Dongting Lake region

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    Zheng Gong

    2012-03-01

    Full Text Available Major histocompatibility complex class I chain-related A (MICA is a highly polymorphic gene located within the MHC class I region of the human genome. Expressed as a cell surface glycoprotein, MICA modulates immune surveillance by binding to its cognate receptor on natural killer cells, NKG2D, and its genetic polymorphisms have been recently associated with susceptibility to some infectious diseases. We determined whether MICA polymorphisms were associated with the high rate of Schistosoma parasitic worm infection or severity of disease outcome in the Dongting Lake region of Hunan Province, China. Polymerase chain reaction-sequence specific priming (PCR-SSP and sequencing-based typing (SBT were applied for high-resolution allele typing of schistosomiasis cases (N = 103, age range = 36.2-80.5 years, 64 males and 39 females and healthy controls (N = 141, age range = 28.6-73.3 years, 73 males and 68 females. Fourteen MICA alleles and five short-tandem repeat (STR alleles were identified among the two populations. Three (MICA*012:01/02, MICA*017 and MICA*027 showed a higher frequency in healthy controls than in schistosomiasis patients, but the difference was not significantly correlated with susceptibility to S. japonicum infection (Pc > 0.05. In contrast, higher MICA*A5 allele frequency was significantly correlated with advanced liver fibrosis (Pc 0.05. This study provides the initial evidence that MICA genetic polymorphisms may underlie the severity of liver fibrosis occurring in schistosomiasis patients from the Dongting Lake region.

  17. Epigenetic changes within the promoter region of the HLA-G gene in ovarian tumors

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    Matyunina Lilya V

    2008-05-01

    Full Text Available Abstract Background Previous findings have suggested that epigenetic-mediated HLA-G expression in tumor cells may be associated with resistance to host immunosurveillance. To explore the potential role of DNA methylation on HLA-G expression in ovarian cancer, we correlated differences in HLA-G expression with methylation changes within the HLA-G regulatory region in an ovarian cancer cell line treated with 5-aza-deoxycytidine (5-aza-dC and in malignant and benign ovarian tumor samples and ovarian surface epithelial cells (OSE isolated from patients with normal ovaries. Results A region containing an intact hypoxia response element (HRE remained completely methylated in the cell line after treatment with 5-aza-dC and was completely methylated in all of the ovarian tumor (malignant and benign samples examined, but only variably methylated in normal OSE samples. HLA-G expression was significantly increased in the 5-aza-dC treated cell line but no significant difference was detected between the tumor and OSE samples examined. Conclusion Since HRE is the binding site of a known repressor of HLA-G expression (HIF-1, we hypothesize that methylation of the region surrounding the HRE may help maintain the potential for expression of HLA-G in ovarian tumors. The fact that no correlation exists between methylation and HLA-G gene expression between ovarian tumor samples and OSE, suggests that changes in methylation may be necessary but not sufficient for HLA-G expression in ovarian cancer.

  18. Association of MICA gene polymorphisms with liver fibrosis in schistosomiasis patients in the Dongting Lake region

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Zheng; Luo, Qi-Zhi; Lin, Lin [Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, Hunan Province (China); Su, Yu-Ping; Peng, Hai-Bo [Central Blood Bank in Yueyang, Yueyang, Hunan Province (China); Du, Kun; Yu, Ping [Department of Immunology, College of Basic Medical Sciences, Central South University, Changsha, Hunan Province (China); Wang, Shi-Ping [Key Laboratory of Schistosomiasis in Hunan, Department of Parasitology, College of Basic Medical Sciences, Central South University, Changsha, Hunan Province (China)

    2012-03-02

    Major histocompatibility complex class I chain-related A (MICA) is a highly polymorphic gene located within the MHC class I region of the human genome. Expressed as a cell surface glycoprotein, MICA modulates immune surveillance by binding to its cognate receptor on natural killer cells, NKG2D, and its genetic polymorphisms have been recently associated with susceptibility to some infectious diseases. We determined whether MICA polymorphisms were associated with the high rate of Schistosoma parasitic worm infection or severity of disease outcome in the Dongting Lake region of Hunan Province, China. Polymerase chain reaction-sequence specific priming (PCR-SSP) and sequencing-based typing (SBT) were applied for high-resolution allele typing of schistosomiasis cases (N = 103, age range = 36.2-80.5 years, 64 males and 39 females) and healthy controls (N = 141, age range = 28.6-73.3 years, 73 males and 68 females). Fourteen MICA alleles and five short-tandem repeat (STR) alleles were identified among the two populations. Three (MICA*012:01/02, MICA*017 and MICA*027) showed a higher frequency in healthy controls than in schistosomiasis patients, but the difference was not significantly correlated with susceptibility to S. japonicum infection (Pc > 0.05). In contrast, higher MICA*A5 allele frequency was significantly correlated with advanced liver fibrosis (Pc < 0.05). Furthermore, the distribution profile of MICA alleles in this Hunan Han population was significantly different from those published for Korean, Thai, American-Caucasian, and Afro-American populations (P < 0.01), but similar to other Han populations within China (P > 0.05). This study provides the initial evidence that MICA genetic polymorphisms may underlie the severity of liver fibrosis occurring in schistosomiasis patients from the Dongting Lake region.

  19. Evidence for a rapid rate of molecular evolution at the hypervariable and immunogenic Mycobacterium tuberculosis PPE38 gene region

    Directory of Open Access Journals (Sweden)

    van Pittius Nicolaas

    2009-09-01

    Full Text Available Abstract Background PPE38 (Rv2352c is a member of the large PPE gene family of Mycobacterium tuberculosis and related mycobacteria. The function of PPE proteins is unknown but evidence suggests that many are cell-surface associated and recognised by the host immune system. Previous studies targeting other PPE gene members suggest that some display high levels of polymorphism and it is thought that this might represent a means of providing antigenic variation. We have analysed the genetic variability of the PPE38 genomic region on a cohort of M. tuberculosis clinical isolates representing all of the major phylogenetic lineages, along with the ancestral M. tuberculosis complex (MTBC member M. canettii, and supplemented this with analysis of publicly available whole genome sequences representing additional M. tuberculosis clinical isolates, other MTBC members and non tuberculous mycobacteria (NTM. Where possible we have extended this analysis to include the adjacent plcABC and PPE39/40 genomic regions. Results We show that the ancestral MTBC PPE38 region comprises 2 homologous PPE genes (PPE38 and PPE71, separated by 2 esat-6 (esx-like genes and that this structure derives from an esx/esx/PPE duplication in the common ancestor of M. tuberculosis and M. marinum. We also demonstrate that this region of the genome is hypervariable due to frequent IS6110 integration, IS6110-associated recombination, and homologous recombination and gene conversion events between PPE38 and PPE71. These mutations result in combinations of gene deletion, gene truncation and gene disruption in the majority of clinical isolates. These mutations were generally found to be IS6110 strain lineage-specific, although examples of additional within-lineage and even within-cluster mutations were observed. Furthermore, we provide evidence that the published M. tuberculosis H37Rv whole genome sequence is inaccurate regarding this region. Conclusion Our results show that this antigen

  20. Countries, Within-Country Regions, and Multiple-Country Regions in International Management: A Functional, Institutional, and Critical Event (FICE) Perspective

    DEFF Research Database (Denmark)

    Søndergaard, Mikael; Peterson, Mark F.

    2014-01-01

    We introduce the focused issue by offering a functional, institutional and critical event or FICE perspective on the relationship between cultural boundaries and the boundaries of modern nation states (termed countries here). Our perspective draws from three kinds of theory that suggest how...

  1. Plasticity Region Genes jhp0940, jhp0945, jhp0947, and jhp0949 of Helicobacter pylori in Isolates from Mexican Children.

    Science.gov (United States)

    Romo-González, Carolina; Consuelo-Sánchez, Alejandra; Camorlinga-Ponce, Margarita; Velázquez-Guadarrama, Norma; García-Zúñiga, Magdalena; Burgueño-Ferreira, Juan; Coria-Jiménez, Rafael

    2015-06-01

    The genes jhp0940, jhp0945, jhp0947, and jhp0949 belong to the plasticity region of the Helicobacter pylori genome. Due to their prevalence in isolates from patients with gastritis, duodenal ulcer, and gastric cancer, they have been proposed as markers of gastroduodenal diseases. These genes are associated with pro-inflammatory cytokine induction through the NF-κB activation pathway. Nevertheless, the status of these genes is unknown in H. pylori isolates from children. The aim of the present work was to determine the frequency of the jhp0940-jhp0945-jhp0947-jhp0949 genes in H. pylori isolates from children. We identified the jhp0940, jhp0945, jhp0947, and jhp0949 genes and the relationship of each with the virulence factors cagA, cagPAI, and dupA by PCR in 49 isolates of H. pylori from children. The results were corroborated using dot blots. In addition, we compared the prevalence of these genes with the prevalence in adults. The prevalence of jhp0940 (53.1%), jhp0945 (44.9%), jhp0947 (77.6%), and jhp0949 (83.7%) was determined in the isolates from children, as was the prevalence of the virulence genes cagA (63.3%), cagPAI (71.4%), and dupA (37.5%). No association was found between the four genes of the plasticity region and the virulence genes. The presence of the intact locus integrated by jhp0940-jhp0945-jhp0947-jhp0949 was very common among the isolates from children. The genes jhp0940, jhp0947, and jhp0949 were present in more than 50% of the H. pylori isolates, and the joint presence of jhp0940-jhp0945-jhp0947-jhp0949 was very frequent. The frequency of these genes in isolates from children could contribute to the virulence of H. pylori and the evolution of the infection. © 2015 John Wiley & Sons Ltd.

  2. Genetic effects of polymorphisms in candidate genes and the QTL region on chicken age at first egg

    Directory of Open Access Journals (Sweden)

    Zhou Min

    2011-04-01

    Full Text Available Abstract Background The age at first egg (AFE, an important indicator for sexual maturation in female chickens, is controlled by polygenes. Based on our knowledge of reproductive physiology, 6 genes including gonadotrophin releasing hormone-I (GnRH-I, neuropeptide Y (NPY, dopamine D2 receptor (DRD2, vasoactive intestinal polypeptide (VIP, VIP receptor-1 (VIPR-1, and prolactin (PRL, were selected as candidates for influencing AFE. Additionally, the region between ADL0201 and MCW0241 of chromosome Z was chosen as the candidate QTL region according to some QTL databases. The objective of the present study was to investigate the effects of mutations in candidate genes and the QTL region on chicken AFE. Results Marker-trait association analysis of 8 mutations in those 6 genes in a Chinese native population found a highly significant association (P G840327C of the GnRH-I gene with AFE, and it remained significant even with Bonferroni correction. Based on the results of the 2-tailed χ2 test, mutations T32742394C, T32742468C, G32742603A, and C33379782T in the candidate QTL region of chromosome Z were selected for marker-trait association analysis. The haplotypes of T32742394C and T32742468C were significantly associated (P T32742394C and T32742468C were located in the intron region of the SH3-domain GRB2-like 2 (SH3GL2 gene, which appeared to be associated in the endocytosis and development of the oocyte. Conclusion This study found that G840327C of the GnRH-I gene and the haplotypes of T32742394C-T32742468C of the SH3GL2 gene were associated with the chicken AFE.

  3. Imaging brain gene expression profiles by antipsychotics: region-specific action of amisulpride on postsynaptic density transcripts compared to haloperidol.

    Science.gov (United States)

    de Bartolomeis, Andrea; Marmo, Federica; Buonaguro, Elisabetta Filomena; Rossi, Rodolfo; Tomasetti, Carmine; Iasevoli, Felice

    2013-11-01

    Induction of motor disorders is considered the clinical landmark differentiating typical from atypical antipsychotics, and has been mainly correlated to dopamine D2 receptors blockade in striatum. This view is challenged by benzamides, such as amisulpride, which display low liability for motor side effects despite being D2/D3 receptors high-affinity blocking agents. These effects have been explained with the prominent presynaptic action of amisulpride or with the fast dissociation at D2 receptors, but there is scarce information on the effects of amisulpride on postsynaptic signaling. We carried out a molecular imaging study of gene expression after acute administration of haloperidol (0.8 mg/kg), amisulpride (10 or 35 mg/kg), or vehicle, focusing on postsynaptic genes that are key regulators of synaptic plasticity, such as Arc, c-fos, Zif-268, Norbin, Homer. The last one has been associated to schizophrenia both in clinical and preclinical studies, and is differentially induced by antipsychotics with different D2 receptors affinity. Topography of gene expression revealed that amisulpride, unlike haloperidol, triggers transcripts expression peak in medial striatal regions. Correlation analysis of gene expression revealed a prevalent correlated gene induction within motor corticostriatal regions by haloperidol and a more balanced gene induction within limbic and motor corticostriatal regions by amisulpride. Despite the selective dopaminergic profile of both compounds, our results demonstrated a differential modulation of postsynaptic molecules by amisulpride and haloperidol, the former impacting preferentially medial regions of striatum whereas the latter inducing strong gene expression in lateral regions. Thus, we provided a possible molecular profile of amisulpride, putatively explaining its "atypical atypicality".

  4. Structural and functional characterization of the 5' upstream region of a glutamine synthetase gene from Scots pine

    OpenAIRE

    Avila, Concepción; Cantón, Francisco; Barnestein, Pilar; Suárez, María-Fernanda; Marraccini, Pierre; Rey, Manuel; Humara, Jaime; Ordás, Ricardo; Cánovas, Francisco

    2002-01-01

    International audience; We report here the isolation and characterization of a genomic clone encoding Scots pine (P. sylvestris) cytosolic glutamine synthetase GS1a. The clone contains the 5' half of the gene including part of the coding region organized in seven exons, interrupted by 6 introns and 980 bp upstream of the translation initiation codon. Earlier experiments carried out in our lab have shown that the GS1a gene is expressed in a light dependent fashion during the initial stages of ...

  5. Construction of chimeric antibodies: cloning of immunoglobulin genes including their promoter regions by PCR.

    Science.gov (United States)

    Mocikat, R; Kütemeier, G; Harloff, C

    1992-03-01

    In the production of recombinant antibodies, it is necessary to have an immunoglobulin gene promoter for driving the expression of the antibody genes. Here we describe a simple PCR method that allows cloning of the immunoglobulin genes together with their own promoters despite the fact that the sequence of the upstream part of the gene is unknown.

  6. Characterization of the Promoter Regions of Two Sheep Keratin-Associated Protein Genes for Hair Cortex-Specific Expression.

    Science.gov (United States)

    Zhao, Zhichao; Liu, Guangbin; Li, Xinyun; Huang, Ji; Xiao, Yujing; Du, Xiaoyong; Yu, Mei

    2016-01-01

    The keratin-associated proteins (KAPs) are the structural proteins of hair fibers and are thought to play an important role in determining the physical properties of hair fibers. These proteins are activated in a striking sequential and spatial pattern in the keratinocytes of hair fibers. Thus, it is important to elucidate the mechanism that underlies the specific transcriptional activity of these genes. In this study, sheep KRTAP 3-3 and KRTAP11-1 genes were found to be highly expressed in wool follicles in a tissue-specific manner. Subsequently, the promoter regions of the two genes that contained the 5' flanking/5' untranslated regions and the coding regions were cloned. Using an in vivo transgenic approach, we found that the promoter regions from the two genes exhibited transcriptional activity in hair fibers. A much stronger and more uniformly expressed green fluorescent signal was observed in the KRTAP11-1-ZsGreen1 transgenic mice. In situ hybridization revealed the symmetrical expression of sheep KRTAP11-1 in the entire wool cortex. Consistently, immunohistochemical analysis demonstrated that the pattern of ZsGreen1 expression in the hair cortex of transgenic mice matches that of the endogenous KRTAP11-1 gene, indicating that the cloned promoter region contains elements that are sufficient to govern the wool cortex-specific transcription of KRTAP11-1. Furthermore, regulatory regions in the 5' upstream sequence of the sheep KRTAP11-1 gene that may regulate the observed hair keratinocyte specificity were identified using in vivo reporter assays.

  7. Hybridization study of developmental plastid gene expression in mustard (Sinapsis alba L.) with cloned probes for most plastid DNA regions.

    Science.gov (United States)

    Link, G

    1984-07-01

    An approach to assess the extent of developmental gene expression of various regions of plastid (pt)DNA in mustard (Sinapis alba L.) is described. It involves cloning of most ptDNA regions. The cloned regions then serve as hybridization probes to detect and assess the abundance of complementary RNA sequences represented in total plastid RNA. By comparison of the hybridization pattern observed with plastid RNA from either dark-grown or light-grown plants it was found that many ptDNA regions are constitutively expressed, while several 'inducible' regions account for much higher transcript levels in the chloroplast than in the etioplast stage. The reverse situation, i.e. 'repressed' regions which would account for higher transcript levels in the etioplast, was not observed. The hybridization results obtained with RNA from 'intermediatetype' plastids suggest that transient gene expression is a common feature during light-induced chloroplast development. The time-course of gene expression differs for various ptDNA regions.

  8. Structural feature of sorghum chloroplast psbA gene and regulation effects of its 5’-noncoding region

    Institute of Scientific and Technical Information of China (English)

    吴乃虎; 方晓华; 施晓梅; 张晓武; 周立; 黄美娟

    1999-01-01

    Comparative analysis reveals remarkable homology between the sequences of both psbA gene nucleotides and the inferred amino acids of sorghum, a C4 plant, and those of rice, a C3 plant. The 5’-noncoding region of sorghum psbA gene contains the conservative promoter elements, "-35" element and "-10" element, like the prokaryote and the promoter element, TATA box, like the eukaryote. As compared with that of the rice, an extra sequence of 7 bp is found in the leader sequence of the mRNA in the former. Using an in vitro system, it has been demonstrated that protein factor exists in sorghum chloroplast protein extract which specifically binds to the 5’-noncoding region of psbA gene. Measurement of the expression of luciferase shows a 2—5 time greater reaction of the expression plasmids pALqs which contain leader region of sorghum psbA gene than that of the expression plasmids pALqr which contain leader region of rice psbA gene in E. coli.

  9. Chick homeobox gene cDlx expression demarcates the forebrain anlage, indicating the onset of forebrain regional specification at gastrulation.

    Science.gov (United States)

    Borghjid, S; Siddiqui, M A

    2000-01-01

    Here we describe the isolation and characterization of a chick homeobox-containing gene, cDlx, which shows greater than 85% homology to the homeodomain of other vertebrate Distal-less genes. Northern blot analysis and in situ hybridization studies reveal that cDlx expression is developmentally regulated and is tissue specific. In particular, the developmental expression pattern is characterized by an early appearance of cDlx transcript in the prospective forebrain region of gastrulating embryos. During neurulation, cDlx is consistently expressed in a spatially restricted domain in the presumptive ventral forebrain region of the neural plate that will give rise to the hypothalamus and the adenohypophysis. Our data support the notion that members of the Dlx gene family are part of a homeobox gene code in forebrain pattern formation and suggest that regional specification of the forebrain occurs at much earlier stages than previously thought. The homeobox gene cDlx may thus play a role in defining forebrain regional identity as early as gastrulation.

  10. Mapping of the human bradikinin B2 receptor gene and GALC gene at 14q31-32.1, the region of the Machado Joseph disease locus

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, V.T.T.; Cox, D.W. [Hospital for Sick Children, Toronto (Canada)]|[Univ. of Toronto (Canada)

    1994-09-01

    Bradykinin is a nine amino acid peptide liberated from the {alpha}2 globulin, kininogen, during inflammatory responses. Substantial evidence shows that bradikinin is involved in human inflammatory disorders. There are two types of kinin receptors: B1 and B2. The human bradikinin B2 receptor (BKRB2) gene was previously localized to chromosome 14 by somatic cell hybrids. Krabbe disease is an autosomal recessive disorder caused by deficiency of galactocerebrosidase (GALC). GALC has been previously localized to chromosome 14 at q31 by in situ hybridization. We have further defined the localization of the BKRB2 and GALC genes by physical and genetic linkage mapping. Primers were designed from the 3{prime} untranslated region of each gene. PCR was performed on human/rodent somatic cell hybrid carrying portions of chromosome 14, and on flow sorted chromosome DNA of patients with a deletion or translocation on chromosome 14. Results place the two genes between D14S48 and Pl, the same region as the Machado Joseph disease (MJD) gene. The genomic chromosome 14-specific cosmid library (DOE, Los Alamos) was screened using PCR products obtained from both sets of primers as probes. Positive clones for each gene were screened for di, tri and tetranucleotide repeats. A polymorphic CA repeat marker was obtained from the BKRB2 clones. CEPH families which show recombinants between D14S48 and Pl were typed with this marker and other published markers, which we have mapped in the region: D14S140, D14S68, D14S73, D14S67, D14S256 and D14S81. This positions BDRB2 more precisely and also provides an important map for further localization of the MJD gene.

  11. Association between SNP rs10569304 on the Second Expressed Region of Hole Gene and the Congenital Heart Disease

    Institute of Scientific and Technical Information of China (English)

    张亚莉; 徐琳; 邱健; 李志梁; 李林海; 任广立; 董爱荣; 李炳玲; 葛明晓; 蒙仕仁; 王剑青

    2010-01-01

    The correlation of single nucleotide polymorphism (SNP) rs10569304 on the second expressed region of hole gene and congenital heart disease (CHD) of human being, and the effect of hole gene on CHD were investigated. 179 patients with CHD as CHD group and 183 healthy people as control group were selected in the case-control study. DNA was abstracted from the peripheral blood by phenol-chloroform method. Primer was designed for the flanking sequence of SNP rs10569304 on the second expressed region of hole gen...

  12. Interleukin 10.G microsatellite in the promoter region of the interleukin-10 gene in severe sepsis

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background The highly polymorphic interleukin 10.G (IL10.G) microsatellite located in the promoter region of the interleukin-10 (IL-10) gene exerts a positive transcriptional regulatory effect on IL-10 gene expression and correlates with the in vitro IL-10 secretion. This study was conducted to investigate whether IL10.G microsatellite is associated with the incidence and /or the outcome of severe sepsis.Methods One hundred and fifteen patients with severe sepsis who had been treated at the intensive care unit of the university hospital were studied. One hundred and forty-one healthy individuals served as controls. IL10.G microsatellite genotyping was performed with the following two methods: fluorescent based polymerase chain reaction (PCR) techniques and silver staining of the amplified DNA fragment in polyacrylamide gel. Alleles were defined according to the size of the amplified DNA product.Results Ten alleles and 36 genotypes were detected both in the patients with severe sepsis and in the healthy controls. Allele IL10.G9 and allele IL10.G13 were the commonest alleles with the frequencies of 32.6% and 21.3% respectively in the patients with severe sepsis, and 34% and 27% respectively in the healthy controls. The allele frequencies of IL10.G microsatellite were neither different between the patients with severe sepsis and the healthy controls (P > 0.05), nor between survivors and non-survivors (P > 0.05). However, the frequency of one common allele IL10.G13 was slightly lower in the patients with severe sepsis than in the healthy controls (21.3% vs 27%, P > 0.05), and the frequency of allele IL10.G9 was slightly higher in the non-survivors than in the survivors (37.1% vs 28.1%, P > 0.05).Conclusion IL10.G microsatellite may neither contribute to the susceptibility to severe sepsis nor to the fatal outcome of severe sepsis.

  13. Frameshift mutation of WISP3 gene and its regional heterogeneity in gastric and colorectal cancers.

    Science.gov (United States)

    Lee, Ju Hwa; Choi, Youn Jin; Je, Eun Mi; Kim, Ho Shik; Yoo, Nam Jin; Lee, Sug Hyung

    2016-04-01

    WISP3 is involved in many cancer-related processes including epithelial-mesenchymal transition, cell death, invasion, and metastasis and is considered a tumor suppressor. The aim of our study was to find whether WISP3 gene was mutated and expressionally altered in gastric (GC) and colorectal cancers (CRCs). WISP3 gene possesses a mononucleotide repeat in the coding sequence that could be mutated in cancers with high microsatellite instability (MSI-H). We analyzed 79 GCs and 156 CRCs, and found that GCs (8.8%) and CRCs (10.5%) with MSI-H, but not those with microsatellite stable/low MSI, harbored a frameshift mutation. We also analyzed intratumoral heterogeneity (IT