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Sample records for 6q 8p 9p

  1. West syndrome associated with a novel chromosomal anomaly; partial trisomy 8P together with partial monosomy 9P, resulting from a familial unbalanced reciprocal translocation.

    PubMed

    Erol, Ilknur; Saygı, Semra; Demir, Şenay; Alehan, Fusun; Sahin, Feride Iffet

    2015-01-01

    West syndrome is classified according to the underlying etiology into an acquired West syndrome, a congenital/developmental West syndrome, and West syndrome of unknown etiology. Causes of a congenital/developmental West syndrome are extensive and include chromosomal anomalies. We report on a patient carrying a derivative chromosome originating from the reciprocal unbalanced translocation t (8;9) (p11.2;p22) and presenting with macrocephaly, West syndrome, severe mental motor retardation and hypotonia. As far as we know, this is a new chromosomal anomaly associated with West syndrome.

  2. Monosomy 6q1: Syndrome delineation

    SciTech Connect

    Romie, S.S.; Hartsfield, J.K. Jr.; Sutcliffe, M.J.

    1996-03-15

    We report on a girl with a de novo 6q1 interstitial deletion. To our knowledge, this is the second reported case with a deletion of 6q11-q15. We review the phenotype of monosomy 6q1. Our patient has manifestations similar to others with monosomy 6q1 including mental deficiency, growth retardation, short neck, and minor facila anomalies. 18 refs., 5 figs., 3 tabs.

  3. Interstitial deletion (6)q13q15

    SciTech Connect

    Gershoni-Baruch, R.; Mandel, H.; Bar El, H.; Bar-Nizan, N.; Borochowitz, Z.; Dar, Hanna

    1996-04-24

    We report on a 2-year-old child with psychomotor retardation, facial and urogenital anomalies. His chromosome constitution was 46,XY,del(6)(q13q15). This case further contributes to the karyotype-phenotype correlation of proximal deletion 6q syndromes. 18 refs., 3 figs., 1 tab.

  4. Comparative proteome analysis of the hippocampus implicates chromosome 6q in schizophrenia.

    PubMed

    Edgar, P F; Douglas, J E; Cooper, G J; Dean, B; Kydd, R; Faull, R L

    2000-01-01

    Comparative brain proteome analysis is a new strategy to discover proteins and therefore genes whose altered expression may underlie schizophrenia. This strategy does not require an a priori theory of the pathogenesis or the mode of inheritance of schizophrenia. Using proteome analysis we previously compared the hippocampal proteome, that is, those proteins expressed by the hippocampal genome, of seven schizophrenic individuals with the hippocampal proteome of seven control individuals, matched for age and post mortem delay.1 We found 18 proteins that were significantly altered in concentration in the schizophrenic hippocampus (P < 0.05), when compared to control tissue. One of these proteins was characterised, by N-terminal sequencing, as diazepam binding inhibitor whose gene maps to 6q12-q21. Here we characterise a further three of the 18 proteins as: manganese superoxide dismutase, 6q25.3, T-complex protein 1, 6q25.3-q26 and collapsin response mediator protein 2, 8p21. That three of these four characterised proteins should map to the long arm of the same chromosome is significant (P < 0.002) and suggests the importance of chromosome 6q in schizophrenia. These results indicate that antioxidant defence is altered in the schizophrenic hippocampus and suggest that segregation distortion, of schizophrenia susceptibility genes, may be a possible causative factor in the high incidence of schizophrenia. Molecular Psychiatry (2000) 5, 85-90.

  5. Analysis of gains and losses of DNA sequences along all human chromosomes by comparative genomic hybridization implicates 6q and several other chromosomal sites as putative tumor suppressor gene loci in prostate cancer

    SciTech Connect

    Visakorpi, T.; Karhu, R.; Kallioniemi, A.

    1994-09-01

    Genetic changes associated with the development of prostate cancer are poorly known. We sought to identify regions that contain important genes for the development of prostate cancer by using comparative genomic hybridization (CGH) for genome-wide screening of gains and losses of DNA sequences. In CGH, differentially labeled tumor and normal DNAs are co-hybridized to normal metaphase spreads to visualize chromosomal regions with losses and gains of DNA sequences. Analysis of 31 uncultured primary prostate cancers showed that deletions predominated over gains with a ratio of 5:1. The most commonly deleted regions were 8p; 32% (minimal common region p12-pter), 13q; 32% (q21-q31), 6q; 22% (cen-q21), 16q; 19% (cen-q23), 18q; 19% (q22-qter) and 9p; 16%(p23-pter). Gain of the entire long arm of chromosome 8 was found in 6% of cases but no high-level amplifications were found in any of the specimens. Of the aberrations found by CGH, 6q represents a previously unreported, major site for deletion in prostate cancer. Analysis of loss of heterozygosity (LOH) was used to confirm the presence of 6q and other deletions found by CGH. LOH and CGH data showed an about 75% concordance. The significance of genetic aberrations in prostate cancer are being evaluated by correlating CGH findings with clinical outcome as well as by comparing genetic changes observed in the primary tumor with those found in recurrent lesions and metastases of the same patient.

  6. Novel Cleft Susceptibility Genes in Chromosome 6q

    PubMed Central

    Letra, A.; Menezes, R.; Fonseca, R.F.; Govil, M.; McHenry, T.; Murphy, M.J.; Hennebold, J.D.; Granjeiro, J.M.; Castilla, E.E.; Orioli, I.M.; Martin, R.; Marazita, M.L.; Bjork, B.C.; Vieira, A.R.

    2010-01-01

    Cleft lip/palate is a defect of craniofacial development. In previous reports, chromosome 6q has been suggested as a candidate region for cleft lip/palate. A multipoint posterior probability of linkage analysis of multiplex families from the Philippines attributed an 88% probability of harboring a cleft-susceptibility gene to a narrower region on bands 6q14.2-14.3. We genotyped 2732 individuals from families and unrelated individuals with and without clefts to investigate the existence of possible cleft-susceptibility genes in this region. We found association of PRSS35 and SNAP91 genes with cleft lip/palate in the case-control cohort and in Caucasian families. Haplotype analyses support the individual associations with PRSS35. We found Prss35 expression in the head and palate of mouse embryos at critical stages for palatogenesis, whereas Snap91 was expressed in the adult brain. We provide further evidence of the involvement of chromosome 6q in cleft lip/palate and suggest PRSS35 as a novel candidate gene. PMID:20511563

  7. Duplication/deletion of chromosome 8p

    SciTech Connect

    Priest, J.H.

    1995-09-11

    The article by Guo et al. provides evidence for deletion of D8S596 loci (assigned to 8p23) in at least some patients with inverted duplications of 8p. Cytogenetic break points forming the inverted duplication are remarkably similar among most of their patients and those reported previously, suggesting a common mechanism for this interesting rearrangement. Why should similar breaks occur in 8p and why is a FISH signal absent in the distal short arm when the ONCOR digoxigenin-labeled probe for loci D8S596 is used? Other studies also indicate that duplication for the region 8p12-p22 is associated with a deletion distal to the duplication itself. 4 refs.

  8. Dermatoglyphic Patterns in 9p Trisomy Syndrome

    ERIC Educational Resources Information Center

    Loesch, Danuta; Czyzewska, Jadwiga

    1978-01-01

    Thirty-seven palm prints and 30 sole prints of people with 9p trisomy (a chromosomal anomaly associated with abnormal limb development) were analysed with respect to frequency distribution of loops and triradii on palms, soles, and fingertips, as well as of the total pattern types. (Author)

  9. Interstitial deletion of 6q21-q23 associated with split hand

    SciTech Connect

    Tsukahara, Masato; Yoneda, Junko; Azuma, Reiko

    1997-03-31

    We report on a 7-month-old boy with interstitial deletion of 6q21-q23 and split-hand defect. He died at 7 months. This is the fifth patient with distal limb anomaly associated with a rearrangement of 6q21 region, and supports previous suggestions that there may be candidate gene(s) for distal limb development in the 6q21 region. 10 refs., 3 figs., 1 tab.

  10. 18 CFR 357.4 - FERC Form No. 6-Q, Quarterly report of oil pipeline companies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., Quarterly report of oil pipeline companies. 357.4 Section 357.4 Conservation of Power and Water Resources... No. 6-Q, Quarterly report of oil pipeline companies. (a) Prescription. The quarterly financial report form of oil pipeline companies, designated as FERC Form No. 6-Q, is prescribed for the...

  11. 18 CFR 357.4 - FERC Form No. 6-Q, Quarterly report of oil pipeline companies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., Quarterly report of oil pipeline companies. 357.4 Section 357.4 Conservation of Power and Water Resources... No. 6-Q, Quarterly report of oil pipeline companies. (a) Prescription. The quarterly financial report form of oil pipeline companies, designated as FERC Form No. 6-Q, is prescribed for the...

  12. 18 CFR 357.4 - FERC Form No. 6-Q, Quarterly report of oil pipeline companies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., Quarterly report of oil pipeline companies. 357.4 Section 357.4 Conservation of Power and Water Resources... No. 6-Q, Quarterly report of oil pipeline companies. (a) Prescription. The quarterly financial report form of oil pipeline companies, designated as FERC Form No. 6-Q, is prescribed for the...

  13. 18 CFR 357.4 - FERC Form No. 6-Q, Quarterly report of oil pipeline companies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., Quarterly report of oil pipeline companies. 357.4 Section 357.4 Conservation of Power and Water Resources... No. 6-Q, Quarterly report of oil pipeline companies. (a) Prescription. The quarterly financial report form of oil pipeline companies, designated as FERC Form No. 6-Q, is prescribed for the...

  14. 18 CFR 357.4 - FERC Form No. 6-Q, Quarterly report of oil pipeline companies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., Quarterly report of oil pipeline companies. 357.4 Section 357.4 Conservation of Power and Water Resources... No. 6-Q, Quarterly report of oil pipeline companies. (a) Prescription. The quarterly financial report form of oil pipeline companies, designated as FERC Form No. 6-Q, is prescribed for the...

  15. 78 FR 24187 - Commission Information Collection Activities (FERC Form 6-Q); Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-24

    ... Energy Regulatory Commission Commission Information Collection Activities (FERC Form 6-Q); Comment... Energy Regulatory Commission (Commission or FERC) is submitting the information collection FERC Form 6-Q... issued a Notice in the Federal Register (78 FR 8500, 2/6/2013) requesting public comments. FERC...

  16. Heterogeneity and chronology of 6q15 deletion and ERG-fusion in prostate cancer

    PubMed Central

    Krohn, Antje; Freudenthaler, Fabian; Bauer, Melanie; Salomon, Georg; Heinzer, Hans; Michl, Uwe; Steurer, Stefan; Simon, Ronald; Sauter, Guido; Schlomm, Thorsten; Minner, Sarah

    2016-01-01

    Prostate cancer is notorious for its heterogeneity, which poses a problem for the applicability of diagnostic molecular markers. However, heterogeneity analysis can provide valuable information on the chronology in which molecular alterations arise. Here, we constructed a heterogeneity tissue microarray (TMA) comprising samples from 10 different tumor areas of 189 prostate cancers each in order to study the sequence of two frequent molecular alterations, i.e. 6q15 deletion and TMPRSS2:ERG fusion. Previous work shows a marked inverse relationship between these alterations, suggesting that presence of one of these alterations might impact development of the other. 6q15 deletion was analyzed by fluorescence in situ hybridization and ERG-expression by immunohistochemistry. Only 6.6% of 334 ERG-positive but 28.4% of 440 ERG-negative TMA spots showed 6q15 deletions (p < 0.0001). A breakdown of these data to the level of tumor foci revealed 6q deletions in 138 tumor foci that were large enough to have at least 3 analyzable TMA spots. These included 42 tumor foci with homogeneous ERG positivity and 16 with homogeneous 6q15 deletions. Remarkably, six of the 42 homogeneously ERG-positive tumor foci (14.3%) harbored small 6q15-deleted areas, but none of the 34 6q15-deleted foci showed areas of ERG positivity (p = 0.022). In conclusion, our data suggest that ERG-fusion can precede 6q15 deletion, but not vice versa. The complete absence of ERG-positive tumor areas in 6q15-deleted tumor foci further suggest that the functional consequences of 6q15 deletions may prevent the development of TMPRSS2:ERG fusions. PMID:26684029

  17. Three cases of tetrasomy 9p.

    PubMed

    Dhandha, S; Hogge, W A; Surti, U; McPherson, E

    2002-12-15

    We report three cases of tetrasomy 9p, two of which were confirmed prenatally. All three had characteristic findings on ultrasound and at birth. We also present a review of the literature, which suggests that a recognizable phenotype for this condition is emerging. Common findings on prenatal ultrasound include intrauterine growth restriction, ventriculomegaly, cleft lip or palate, and renal anomalies. These findings can provide a clue toward the prenatal diagnosis of this condition. There is also a clearly recognizable phenotype at birth. Facial characteristics include hypertelorism, broad nasal bridge/bulbous or beaked nose, cleft lip/palate, ear anomalies, and micrognathia. The exact extent of the isochromosome does not seem to predict severity, but mosaic cases are less severe, or at least have a greater probability of survival. PMID:12457411

  18. 75 FR 5061 - Commission Information Collection Activities (FERC Form Nos. 6 and 6-Q); Comment Request; Extensions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-01

    ...''), ``Annual Report of Oil Pipeline Companies,'' implemented in 18 CFR Sections 357.1, 357.2, and 385.2011; OMB Control No. 1902-0022 and FERC Form 6-Q (``FERC-6Q'' or ``FERC-6-Q''), ``Quarterly Financial Report of Oil... ensure just and reasonable rates for transportation of crude oil and petroleum products by pipelines...

  19. 78 FR 8500 - Commission Information Collection Activities (FERC Form 6-Q); Comment Request; Extension

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-06

    ... Financial Report of Oil Pipeline Companies. DATES: Comments on the collection of information are due April 8...: Title: FERC Form 6-Q (Quarterly Financial Report of Oil Pipeline Companies). OMB Control No.: 1902-0206... profitability, efficiency, risk and in its overall monitoring. Type of Respondents: Oil Pipelines. Estimate...

  20. Magnetic turbulence and resistive MHD instabilities in a 0. 6 < q < 3 poloidal divertor tokamak

    SciTech Connect

    Agim, Y.Z.; Callen, J.D.; Chang, Z.; Dexter, R.N.; Goetz, J.A.; Graessle, D.E.; Haines, E.; Kortbawi, D.; LaPointe, M.A.; Moyer, R.A.

    1988-09-01

    Detailed statistical properties of internal magnetic turbulence, and internal disruptions in magnetically- and materially-limited discharges, are studied in the Tokapole II poloidal divertor tokamak over the safety factor range 0.6 < q{sub a} < 3. A nonlinear MHD code treats tearing modes in the divertor geometry. 9 refs., 2 figs.

  1. A de novo interstitial deletion of chromosome 6 (q22.2q23.1).

    PubMed

    Park, J P; Graham, J M; Berg, S Z; Wurster-Hill, D H

    1988-02-01

    A unique interstitial deletion of the long arm of chromosome 6 involving bands q22.2 and q23.1 was observed in a patient referred for craniostenosis and developmental delay. The associated phenotypic anomalies are compared with other reported cases of deletion 6q involving adjacent regions.

  2. Incomplete penetrance and phenotypic variability of 6q16 deletions including SIM1

    PubMed Central

    El Khattabi, Laïla; Guimiot, Fabien; Pipiras, Eva; Andrieux, Joris; Baumann, Clarisse; Bouquillon, Sonia; Delezoide, Anne-Lise; Delobel, Bruno; Demurger, Florence; Dessuant, Hélène; Drunat, Séverine; Dubourg, Christelle; Dupont, Céline; Faivre, Laurence; Holder-Espinasse, Muriel; Jaillard, Sylvie; Journel, Hubert; Lyonnet, Stanislas; Malan, Valérie; Masurel, Alice; Marle, Nathalie; Missirian, Chantal; Moerman, Alexandre; Moncla, Anne; Odent, Sylvie; Palumbo, Orazio; Palumbo, Pietro; Ravel, Aimé; Romana, Serge; Tabet, Anne-Claude; Valduga, Mylène; Vermelle, Marie; Carella, Massimo; Dupont, Jean-Michel; Verloes, Alain; Benzacken, Brigitte; Delahaye, Andrée

    2015-01-01

    6q16 deletions have been described in patients with a Prader–Willi-like (PWS-like) phenotype. Recent studies have shown that certain rare single-minded 1 (SIM1) loss-of-function variants were associated with a high intra-familial risk for obesity with or without features of PWS-like syndrome. Although SIM1 seems to have a key role in the phenotype of patients carrying 6q16 deletions, some data support a contribution of other genes, such as GRIK2, to explain associated behavioural problems. We describe 15 new patients in whom de novo 6q16 deletions were characterised by comparative genomic hybridisation or single-nucleotide polymorphism (SNP) array analysis, including the first patient with fetopathological data. This fetus showed dysmorphic facial features, cerebellar and cerebral migration defects with neuronal heterotopias, and fusion of brain nuclei. The size of the deletion in the 14 living patients ranged from 1.73 to 7.84 Mb, and the fetus had the largest deletion (14 Mb). Genotype–phenotype correlations confirmed the major role for SIM1 haploinsufficiency in obesity and the PWS-like phenotype. Nevertheless, only 8 of 13 patients with SIM1 deletion exhibited obesity, in agreement with incomplete penetrance of SIM1 haploinsufficiency. This study in the largest series reported to date confirms that the PWS-like phenotype is strongly linked to 6q16.2q16.3 deletions and varies considerably in its clinical expression. The possible involvement of other genes in the 6q16.2q16.3-deletion phenotype is discussed. PMID:25351778

  3. 6q22.33 microdeletion in a family with intellectual disability, variable major anomalies, and behavioral abnormalities.

    PubMed

    Mackenroth, Luisa; Hackmann, Karl; Beyer, Anke; Schallner, Jens; Novotna, Barbara; Klink, Barbara; Schröck, Evelin; Di Donato, Nataliya

    2015-11-01

    Interstitial deletions on the long arm of chromosome six have been described for several regions including 6q16, 6q22.1, and 6q21q22.1, and with variable phenotypes such as intellectual disability/developmental delay, growth retardation, major and minor facial anomalies. However, an isolated microdeletion of the sub-band 6q22.33 has not been reported so far and thus, no information about the specific phenotype associated with such a copy number variant is available. Here, we define the clinical picture of an isolated 6q22.33 microdeletion based on the phenotype of six members of one family with loss of approximately 1 Mb in this region. Main clinical features include mild intellectual disability and behavioral abnormalities as well as microcephaly, heart defect, and cleft lip and palate.

  4. Genetics Home Reference: 8p11 myeloproliferative syndrome

    MedlinePlus

    ... resources address the diagnosis or management of 8p11 myeloproliferative syndrome: Cancer.Net from the American Society of Clinical Oncology: ... Hodgkin's Lymphoma KidsHealth from Nemours: Leukemia MalaCards: 8p11 ... associated with FGFR1 rearrangement Patient Support and Advocacy ...

  5. A new myeloproliferative disorder associated with chromosomal translocations involving 8p11: a review.

    PubMed

    Macdonald, D; Aguiar, R C; Mason, P J; Goldman, J M; Cross, N C

    1995-10-01

    Chromosomal breakpoints associated with malignancy are known to cluster at particular regions of the karyotype. Based on a review of the literature we have identified a novel leukaemia syndrome associated with translocations involving 8p11. This syndrome is distinct from the previously described translocation t(8;16)(p11;p13) associated with acute monoblastic leukaemia. We have summarized the clinical and cytogenetic features of 13 case reports which describe a myeloproliferative syndrome with eosinophilia, lymphadenopathy and a high incidence of T cell non-Hodgkin's lymphoma with progression to acute myeloid leukaemia. The translocations involving 8p11 were: either t(8;13)(p11-12;q11-12), t(8;9) (p11;q32-34) or t(6;8)(q27;p12). In two cases of t(8;13) molecular studies have mapped the chromosome 13 breakpoint to a 1.5 Mbp region, but a full molecular characterization of these translocations is required. In view of the striking clinicopathological and karyotypic similarities between these cases we propose that they be considered a single nosological entity and termed '8p11 myeloproliferative syndrome'. PMID:7564500

  6. Characterizations of 9p21 candidate genes in familial melanoma

    SciTech Connect

    Walker, G.J.; Flores, J.F.; Glendening, J.M.

    1994-09-01

    We have previously collected and characterized 16 melanoma families for the inheritance of a familial melanoma predisposition gene on 9p21. Clear evidence for genetic linkage has been detected in 8 of these families with the 9p21 markers D9S126 and 1FNA, while linkage of the remaining families to this region is less certain. A candidate for the 9p21 familial melanoma gene, the cyclin kinase inhibitor gene p16 (also known as the multiple tumor suppressor 1 (MTS1) gene), has been recently indentified. Notably, a nonsense mutation within the p16 gene has been detected in the lymphoblastoid cell line DNA from a dysplastic nevus syndrome (DNS), or familial melanoma, patient. The p16 gene is also known to be frequently deleted or mutated in a variety of tumor cell lines (including melanoma) and resides within a region that has been defined as harboring the 9p21 melanoma predisposition locus. This region is delineated on the distal side by the marker D9S736 (which resides just distal to the p16 gene) and extends in a proximal direction to the marker D9S171. Overall, the entire distance between these two loci is estimated at 3-5Mb. Preliminary analysis of our two largest 9p21-linked melanoma kindreds (by direct sequencing of PCR products) has not yet revealed mutations within the coding region of the p16 gene. Others have reported that 8/11 unrelated 9p21-linked melanoma families do not appear to carry p16 mutations; thus the possibility exists that p16 is not a melanoma susceptibility gene per se, although it appears to play some role in melanoma tumor progression. Our melanoma kindred DNAs are currently being analyzed by SSCP using primers that amplify exons of other candidate genes from the 9p21 region implicated in familial melanoma. These novel genes reside within a distinct critical region of homozygous loss in melanoma which is located >2 Mb from the p16 gene on 9p21.

  7. Genomewide scans of red cell indices suggest linkage on chromosome 6q23

    PubMed Central

    Iliadou, A; Evans, D M; Zhu, G; Duffy, D L; Frazer, I H; Montgomery, G W; Martin, N G

    2007-01-01

    Background The red cell indices quantify the size, number and oxygen‐carrying ability of erythrocytes. Although the genetic basis of many monogenic forms of anaemia is well understood, comparatively little is known about the genes responsible for variation in the red cell indices among healthy participants. Objective To identify quantitative trait loci (QTLs) responsible for normal variation in the red cell indices of 391 pairs of dizygotic twins who were measured longitudinally at 12, 14 and 16 years of age. Results Evidence suggesting linkage of red cell indices to haemoglobin concentration (LOD  = 3.03) and haematocrit (LOD  = 2.95) on chromosome 6q23, a region previously identified as possibly harbouring a QTL for haematocrit, was found. Evidence for linkage to several other regions of the genome, including chromosome 4q32 for red cell count and 7q for mean cell volume, was also found. In contrast, there was little evidence of linkage to the chromosomal regions containing the genes for erythropoietin (7q21) and its receptor (19p13.2), nor to the regions containing the genes for the haemoglobin α (16p13.3) and β chains (11p15.5). Conclusion Findings provide additional evidence for a QTL affecting haemoglobin and haematocrit on chromosome 6q23. In contrast, polymorphisms in the genes coding for erythropoietin, its receptor and the haemoglobin α and β chains do not appear to contribute substantially to variation in the red cell indices between healthy persons. PMID:16950815

  8. Tetrasomy 9p mosaicism associated with a normal phenotype.

    PubMed

    McAuliffe, Fionnuala; Winsor, Elizabeth J T; Chitayat, David

    2005-01-01

    Isochromosome (tetrasomy) 9p is a rare chromosomal aberration characterized by phenotypic abnormalities ranging from mild developmental delay to multiple anomalies including intrauterine growth retardation, cerebral ventriculomegaly, dysmorphic facial features, cleft lip or palate, abnormal genitalia and renal anomalies. We present a patient with isochromosome (tetrasomy) 9p mosaicism who is a healthy normal adult male with oligospermia who has fathered two normal children. This chromosomal abnormality may be tissue specific, with a higher detection rate in cultured lymphocytes compared with fibroblasts. Therefore, there is an increased chance of missing the abnormality prenatally by amniocentesis or chorionic villus sampling. We are aware of only one other patient in the literature with a normal phenotype associated with mosaicism for this chromosomal abnormality. PMID:15824502

  9. Congenital diaphragmatic hernia in a patient with tetrasomy 9p.

    PubMed

    Henriques-Coelho, Tiago; Oliva-Teles, Natália; Fonseca-Silva, M Luz; Tibboel, Dick; Guimarães, Hercília; Correia-Pinto, Jorge

    2005-10-01

    Tetrasomy of the short arm of chromosome 9 constitutes a rare condition resulting in a well clinically recognized syndrome. In our case, in addition to the characteristic phenotype at birth, the existence of a hernia-type Bochdalek diaphragmatic defect was found. Cytogenetic analysis revealed a nonmosaic case of an isochromosome of the entire short arm of chromosome 9 with no involvement of the heterochromatic region of the long arm: 47, XX, +i (9p). Because chromosome 9 contains several gene locus for enzymes and receptors of the retinoid pathway, this case potentially contributes to retinoid hypothesis in the etiology of congenital diaphragmatic hernia. PMID:16226972

  10. Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27

    PubMed Central

    Peddibhotla, Sirisha; Nagamani, Sandesh CS; Erez, Ayelet; Hunter, Jill V; Holder Jr, J Lloyd; Carlin, Mary E; Bader, Patricia I; Perras, Helene MF; Allanson, Judith E; Newman, Leslie; Simpson, Gayle; Immken, LaDonna; Powell, Erin; Mohanty, Aaron; Kang, Sung-Hae L; Stankiewicz, Pawel; Bacino, Carlos A; Bi, Weimin; Patel, Ankita; Cheung, Sau W

    2015-01-01

    Patients with terminal deletions of chromosome 6q present with structural brain abnormalities including agenesis of corpus callosum, hydrocephalus, periventricular nodular heterotopia, and cerebellar malformations. The 6q27 region harbors genes that are important for the normal development of brain and delineation of a critical deletion region for structural brain abnormalities may lead to a better genotype–phenotype correlation. We conducted a detailed clinical and molecular characterization of seven unrelated patients with deletions involving chromosome 6q27. All patients had structural brain abnormalities. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. The smallest region of overlap spans 1.7 Mb and contains DLL1, THBS2, PHF10, and C6orf70 (ERMARD) that are plausible candidates for the causation of structural brain abnormalities. Our study reiterates the importance of 6q27 region in normal development of brain and helps identify putative genes in causation of structural brain anomalies. PMID:24736736

  11. Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27.

    PubMed

    Peddibhotla, Sirisha; Nagamani, Sandesh C S; Erez, Ayelet; Hunter, Jill V; Holder, J Lloyd; Carlin, Mary E; Bader, Patricia I; Perras, Helene M F; Allanson, Judith E; Newman, Leslie; Simpson, Gayle; Immken, LaDonna; Powell, Erin; Mohanty, Aaron; Kang, Sung-Hae L; Stankiewicz, Pawel; Bacino, Carlos A; Bi, Weimin; Patel, Ankita; Cheung, Sau W

    2015-01-01

    Patients with terminal deletions of chromosome 6q present with structural brain abnormalities including agenesis of corpus callosum, hydrocephalus, periventricular nodular heterotopia, and cerebellar malformations. The 6q27 region harbors genes that are important for the normal development of brain and delineation of a critical deletion region for structural brain abnormalities may lead to a better genotype-phenotype correlation. We conducted a detailed clinical and molecular characterization of seven unrelated patients with deletions involving chromosome 6q27. All patients had structural brain abnormalities. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. The smallest region of overlap spans 1.7 Mb and contains DLL1, THBS2, PHF10, and C6orf70 (ERMARD) that are plausible candidates for the causation of structural brain abnormalities. Our study reiterates the importance of 6q27 region in normal development of brain and helps identify putative genes in causation of structural brain anomalies.

  12. inv(9)(p24q13) in three sterile brothers.

    PubMed

    Dávalos, I P; Rivas, F; Ramos, A L; Galaviz, C; Sandoval, L; Rivera, H

    2000-01-01

    Only nine non-polymorphic constitutional pericentric inversions of chromosome 9 have been described. We report on a familial inv(9)(p24q13) associated with sterility in three brothers. The mother's chromosomes were normal in blood lymphocytes (n=130); the father was already deceased and his karyotype unknown. However, the presence of any of the maternal chromosomes 9 (as assessed by C-banding) in her carrier children is inconsistent with the assumption of maternal mosaicism. Two single sisters were also carriers. The same rearranged chromosome 9 in the three sterile brothers can hardly be regarded as a fortuitous association, especially when the breakpoints are almost identical to those of the sole inversion previously found in an azoospermic male. If their father was a carrier, the observed sterility may be the result of 'chromosome anticipation', a phenomenon already invoked for certain familial chromosomal rearrangements.

  13. Comet 9P/Tempel 1: Evolution of the surface

    NASA Astrophysics Data System (ADS)

    Kossacki, Konrad J.

    2015-01-01

    Comet 9P/Tempel 1 was imaged during two consecutive perihelion passages. According to Thomas et al. (Thomas, et al. [2013]. Icarus 222, 453-466) one scarp located at 40°S receded up to 50 m. I attempted to use this observation to constrain local material properties of the nucleus. For this purpose I simulated recession of a model scarp due to sub-dust sublimation of ice. I have found, that the observed recession of the scarp can be reproduced when the dust mantle has high porosity about 0.8 and low thermal conductivity about 10 mW m-1 K-1, as found for artificial dust layers (Krause, M., Blum, J., Skorov, Yu.V., Trieloff, M. [2011]. Icarus 214, 286-296). Taking into account the temperature dependence of the sublimation coefficient of ice reduces the calculated recession rate of the scarp by about 40%.

  14. TERT promoter mutations and chromosome 8p loss are characteristic of nonalcoholic fatty liver disease-related hepatocellular carcinoma.

    PubMed

    Ki Kim, Soo; Ueda, Yoshihide; Hatano, Etsuro; Kakiuchi, Nobuyuki; Takeda, Haruhiko; Goto, Tomoyuki; Shimizu, Takahiro; Yoshida, Kenichi; Ikura, Yoshihiro; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Uemoto, Shinji; Chiba, Tsutomu; Ogawa, Seishi; Marusawa, Hiroyuki

    2016-12-01

    The number of patients with nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) is increasing. To understand the molecular features of the tumor phenotype, we aimed to clarify the overall landscape of genetic aberrations accumulated in NAFLD-related HCC. Of 247 HCC patients who underwent hepatectomy during 2010 to 2014 at a single center in Japan, 10 were diagnosed with NAFLD-HCC based on strict clinical and pathologic criteria. We analyzed the genetic aberrations of 11 NAFLD-HCC tumor samples from these 10 patients by whole-exome sequencing, targeted sequencing of the selected genes, and copy number variation studies. Whole-exome sequencing revealed a mean somatic mutation rate of 1.86 per megabase, and 12 genes were recurrently mutated in NAFLD-HCCs. Targeted sequencing of the 26 selected genes (12 recurrently mutated genes in whole-exome sequencing and 14 representative HCC-associated genes) revealed that TERT promoter mutations occurred in 9 of 11 HCCs (82%), followed by CTNNB1 (45%) and TP53 (36%) mutations. Array-based copy number variation studies identified recurrent gains at 1q and 8q, and recurrent losses at 1p, 4q, 6q, 8p, 13q, 16p, 17p, and 18q. Notably, chromosome 8p loss occurred in all of the NAFLD-HCC samples. The current study provided the characteristics of genetic aberrations in NAFLD-HCC and suggested that TERT promoter mutations and chromosome 8p loss mainly contribute to NAFLD-related liver carcinogenesis.

  15. TERT promoter mutations and chromosome 8p loss are characteristic of nonalcoholic fatty liver disease-related hepatocellular carcinoma.

    PubMed

    Ki Kim, Soo; Ueda, Yoshihide; Hatano, Etsuro; Kakiuchi, Nobuyuki; Takeda, Haruhiko; Goto, Tomoyuki; Shimizu, Takahiro; Yoshida, Kenichi; Ikura, Yoshihiro; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Uemoto, Shinji; Chiba, Tsutomu; Ogawa, Seishi; Marusawa, Hiroyuki

    2016-12-01

    The number of patients with nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) is increasing. To understand the molecular features of the tumor phenotype, we aimed to clarify the overall landscape of genetic aberrations accumulated in NAFLD-related HCC. Of 247 HCC patients who underwent hepatectomy during 2010 to 2014 at a single center in Japan, 10 were diagnosed with NAFLD-HCC based on strict clinical and pathologic criteria. We analyzed the genetic aberrations of 11 NAFLD-HCC tumor samples from these 10 patients by whole-exome sequencing, targeted sequencing of the selected genes, and copy number variation studies. Whole-exome sequencing revealed a mean somatic mutation rate of 1.86 per megabase, and 12 genes were recurrently mutated in NAFLD-HCCs. Targeted sequencing of the 26 selected genes (12 recurrently mutated genes in whole-exome sequencing and 14 representative HCC-associated genes) revealed that TERT promoter mutations occurred in 9 of 11 HCCs (82%), followed by CTNNB1 (45%) and TP53 (36%) mutations. Array-based copy number variation studies identified recurrent gains at 1q and 8q, and recurrent losses at 1p, 4q, 6q, 8p, 13q, 16p, 17p, and 18q. Notably, chromosome 8p loss occurred in all of the NAFLD-HCC samples. The current study provided the characteristics of genetic aberrations in NAFLD-HCC and suggested that TERT promoter mutations and chromosome 8p loss mainly contribute to NAFLD-related liver carcinogenesis. PMID:27511114

  16. Ulnar ray defect in an infant with a 6q21;7q31.2 translocation: Further evidence of the existence of a limb defect gene in 6q21

    SciTech Connect

    Gurrieri, F.; Genuardi, M.; Pomponi, M.G.

    1995-01-30

    Ectrodactyly is a developmental defect of the distal limbs characterized by marked clinical variability and genetic heterogeneity, also reflected in the observation of different chromosome abnormalities nonrandomly associated with longitudinal postaxial limb deficiencies. The one most frequently found in patients with split hand-split foot (SHSF) involves chromosome band 7q22. Recently, structural anomalies of chromosome 6q21 have been reported in 2 unrelated patients with SHSF, suggesting that this region may also contain genes responsible for limb development. We report on a third patient who had a de novo, apparently balanced t(6;7)(q21;q31.2) translocation and bilateral ulnar aplasia with postaxial oligodactyly. In spite of the different phenotypic effects observed in these 3 patients, we consider our case as further evidence that genes in 6q21 may play a role in distal limb development. 8 refs., 3 figs.

  17. 8p11 myeloproliferative syndrome: diagnostic challenges and pitfalls.

    PubMed

    Antic, Darko A; Vukovic, Vojin M; Milosevic Feenstra, Jelena D; Kralovics, Robert; Bogdanovic, Andrija D; Dencic Fekete, Marija S; Mihaljevic, Biljana S

    2016-01-01

    8p11 myeloproliferative syndrome (EMS) is a very rare clinicopathological entity which is characterized by the appearance of a myeloproliferative neoplasm in the bone marrow, peripheral lymphadenopathy, usually caused by T or B lymphoblastic lymphoma/leukemia, and a reciprocal translocation involving chromosome 8p11. Herein we describe a 22-year-old male patient with unusual clinical presentation of EMS. Namely, he initially presented with prolonged epistaxis. Complete blood count showed elevated hemoglobin (17.7g/dl), thrombocytopenia (98x109/l) and leukocytosis (57x109/l). Bone marrow aspirate and biopsy findings corresponded with the presence of a myeloproliferative neoplasm while cytogenetic analysis revealed t(8;13)(p11q12). After that ZMYM2-FGFR1 in-frame fusion was confirmed at the molecular level. Immediately after establishing the diagnosis of a myeloproliferative neoplasm (MPN) generalized lymphadenopathy was developed. Histopathologic examination of lymph node sample confirmed the diagnosis of a T cell lymphoblastic lymphoma without bone marrow involvement. Four cycles of Hyper CVAD chemotherapy were administered with complete morphological and cytogenetic remission. Four weeks after evaluation, patient developed peripheral blood monocytosis and eosinophilia without bone marrow criteria for acute leukemia. Cytogenetic analysis showed t(8;13) accompanied by complex numerical and structural aberrations. The patient underwent allogeneic stem cell transplantation (allo-SCT) from HLA matched sister and he subsequently achieved complete remission. In conclusion, patients with MPN and translocations involving chromosome 8 need to be carefully evaluated for EMS. However, having in mind the very aggressive clinical course of EMS allo-SCT is the only potential curative option. PMID:27569099

  18. A familial venous malformation locus is on chromosome 9p

    SciTech Connect

    Boon, L.M.; Mulliken, J.B.; Vikkula, M.

    1994-09-01

    Venous malformation is the most common vascular malformation affecting 0.2% of the population. Depending upon size and location, these slow-flow lesions may cause pain, anatomic distortion and threaten life. Most venous malformations occur sporadically and present as solitary lesions. For this reason, determining their pathogenic bases has proven elusive. However, venous malformations also occur in several rare syndromes, some of which demonstrate Mendelian inheritance. As a first step towards identifying the pathogenic bases for these lesions, we have mapped a locus for an autosomal dominant disorder in a three generation family that manifests as multiple cutaneous and mucosal venous malformations. This locus lies within a 24.5 cM interval on chromosome 9p, defined by the markers D9S157 and D9S163. A maximum LOD score of 4.11 at {theta} = 0.05 is obtained with several markers within the interval. The interferon gene cluster, which has previously been implicated in angiogenesis, and the multiple tumor suppressor gene, responsible for several types of malignant tumors, also lie within this interval and are potential candidates.

  19. Endocrine phenotype of 6q16.1-q21 deletion involving SIM1 and Prader-Willi syndrome-like features.

    PubMed

    Izumi, Kosuke; Housam, Ryan; Kapadia, Chirag; Stallings, Virginia A; Medne, Livija; Shaikh, Tamim H; Kublaoui, Bassil M; Zackai, Elaine H; Grimberg, Adda

    2013-12-01

    Proximal interstitial 6q deletion involving Single-minded 1 (SIM1) gene causes a syndromic form of obesity mimicking Prader-Willi syndrome. In addition to obesity, Prader-Willi syndrome includes several other endocrinopathies, such as hypothyroidism, growth hormone deficiency, and hypogonadotropic hypogonadism. The endocrine phenotype of interstitial 6q deletion remains largely unknown, although clinical similarities between Prader-Willi syndrome and interstitial 6q deletion suggest endocrine abnormalities also may contribute to the interstitial 6q deletion phenotype. This report describes the endocrine phenotype in a propositus with the Prader-Willi-like syndrome associated with an interstitial 6q deletion including the SIM1 gene. Detailed endocrine evaluation of the propositus during childhood and adolescence revealed hypopituitarism, though initial endocrine evaluations during infancy were unremarkable. Our patient raises the possibility that hypopituitarism may be part of the phenotype, especially short stature, caused by interstitial 6q deletion. SIM1 plays an important role in the development of neuroendocrine lineage cells, implicating SIM1 haploinsufficiency in the pathophysiology of hypopituitarism seen in our propositus. Early identification of endocrine abnormalities can improve clinical outcome by allowing timely introduction of hormone replacement therapy. Hence, we suggest that detailed endocrine evaluation and longitudinal endocrine follow up be performed in individuals with proximal interstitial 6q deletion involving SIM1.

  20. Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25

    PubMed Central

    Fejerman, Laura; Ahmadiyeh, Nasim; Hu, Donglei; Huntsman, Scott; Beckman, Kenneth B.; Caswell, Jennifer L.; Tsung, Karen; John, Esther M.; Torres-Mejia, Gabriela; Carvajal-Carmona, Luis; Echeverry, María Magdalena; Tuazon, Anna Marie D.; Ramirez, Carolina; Carvajal-Carmona, Luis; Echeverry, María Magdalena; Bohórquez, Mabel Elena; Prieto, Rodrigo; Criollo, Ángel; Ramírez, Carolina; Estrada, Ana Patricia; Suáres, John Jairo; Mateus, Gilbert; Castro, Jorge Mario; Sánchez, Yesid; Murillo, Raúl; Lucia Serrano, Martha; Sanabria, Carolina; Olaya, Justo Germán; Bolaños, Fernando; Vélez, Alejandro; Carmona, Jenny Andrea; Vélez, Alejandro; Rodríguez, Nancy Guerrero; Serón Sousa, Cristina; Mendez, Cesar Eduardo Alvarez; Galviz, Ana Isabel Orduz; Gignoux, Christopher R.; Eng, Celeste; Gonzalez-Burchard, Esteban; Henderson, Brian; Marchand, Loic Le; Kooperberg, Charles; Hou, Lifang; Agalliu, Ilir; Kraft, Peter; Lindström, Sara; Perez-Stable, Eliseo J.; Haiman, Christopher A.; Ziv, Elad

    2014-01-01

    The genetic contributions to breast cancer development among Latinas are not well understood. Here we carry out a genome-wide association study of breast cancer in Latinas and identify a genome-wide significant risk variant, located 5′ of the Estrogen Receptor 1 gene (ESR1; 6q25 region). The minor allele for this variant is strongly protective (rs140068132: odds ratio (OR) 0.60, 95% confidence interval (CI) 0.53–0.67, P=9 × 10−18), originates from Indigenous Americans and is uncorrelated with previously reported risk variants at 6q25. The association is stronger for oestrogen receptor-negative disease (OR 0.34, 95% CI 0.21–0.54) than oestrogen receptor-positive disease (OR 0.63, 95% CI 0.49–0.80; P heterogeneity=0.01) and is also associated with mammographic breast density, a strong risk factor for breast cancer (P=0.001). rs140068132 is located within several transcription factor-binding sites and electrophoretic mobility shift assays with MCF-7 nuclear protein demonstrate differential binding of the G/A alleles at this locus. These results highlight the importance of conducting research in diverse populations. PMID:25327703

  1. Genome-wide association study of breast cancer in Latinas identifies novel protective variants on 6q25.

    PubMed

    Fejerman, Laura; Ahmadiyeh, Nasim; Hu, Donglei; Huntsman, Scott; Beckman, Kenneth B; Caswell, Jennifer L; Tsung, Karen; John, Esther M; Torres-Mejia, Gabriela; Carvajal-Carmona, Luis; Echeverry, María Magdalena; Tuazon, Anna Marie D; Ramirez, Carolina; Gignoux, Christopher R; Eng, Celeste; Gonzalez-Burchard, Esteban; Henderson, Brian; Le Marchand, Loic; Kooperberg, Charles; Hou, Lifang; Agalliu, Ilir; Kraft, Peter; Lindström, Sara; Perez-Stable, Eliseo J; Haiman, Christopher A; Ziv, Elad

    2014-10-20

    The genetic contributions to breast cancer development among Latinas are not well understood. Here we carry out a genome-wide association study of breast cancer in Latinas and identify a genome-wide significant risk variant, located 5' of the Estrogen Receptor 1 gene (ESR1; 6q25 region). The minor allele for this variant is strongly protective (rs140068132: odds ratio (OR) 0.60, 95% confidence interval (CI) 0.53-0.67, P=9 × 10(-18)), originates from Indigenous Americans and is uncorrelated with previously reported risk variants at 6q25. The association is stronger for oestrogen receptor-negative disease (OR 0.34, 95% CI 0.21-0.54) than oestrogen receptor-positive disease (OR 0.63, 95% CI 0.49-0.80; P heterogeneity=0.01) and is also associated with mammographic breast density, a strong risk factor for breast cancer (P=0.001). rs140068132 is located within several transcription factor-binding sites and electrophoretic mobility shift assays with MCF-7 nuclear protein demonstrate differential binding of the G/A alleles at this locus. These results highlight the importance of conducting research in diverse populations.

  2. 20-Mb duplication of chromosome 9p in a girl with minimal physical findings and normal IQ: narrowing of the 9p duplication critical region to 6 Mb.

    PubMed

    Bonaglia, Maria Clara; Giorda, Roberto; Carrozzo, Romeo; Roncoroni, Maria Elena; Grasso, Rita; Borgatti, Renato; Zuffardi, Orsetta

    2002-10-01

    We studied the case of a girl with a partial 9p duplication, dup(9)(p22.1 --> p13.1). Molecular cytogenetics studies defined the chromosome 9 rearrangement as a direct duplication of 20 Mb from D9S1213 to D9S52. Microsatellite analysis demonstrated the presence of a double dosage of the paternal alleles and demonstrated that the duplication occurred between sister chromatids. The patient's phenotype was almost normal, with a few minor anomalies (dolichocephaly, crowded teeth, high arched palate) and normal IQ. The breakpoint's location in this patient and previously reported cases suggest that the critical region for the 9p duplication syndrome lies within a 6-Mb portion of chromosome 9p22 between markers D9S267 and D9S1213.

  3. Tetrasomy 6 and 6q14 deletion are associated with better survival in hepatocellular carcinomas. a fluorescence in situ hybridization study of 77 cases.

    PubMed

    Huang, Shiu Feng; Hsu, Hey Chi; Chen, Jeng Chang; Chie, Wei Chu; Lai, Polin

    2003-07-01

    We previously described frequent 6q14 deletion and polysomy 6 in 25 hepatocellular carcinomas (HCC) by fluorescence in situ hybridization (FISH). A more favorable prognosis was noted in patients with 6q14 deletions. To confirm this clinical association, a two-colored FISH study was carried out on 77 HCC using a combination of a yeast artificial chromosome probe (813_E_12) of the 6q14 region and a chromosome 6 centromeric probe (D6Z1) for simultaneous evaluation of the copy number change and chromosome arm deletion. The 77 HCC were divided into four groups according to the copy number of the centromeric signal: 26 with HCC (33.7%) were disomy for chromosome 6, 9 with HCC (11.7%) were trisomy, 29 with HCC (37.6%) were tetrasomy, and 13 with HCC (17%) were classified as hypersomy with presence of one major clone (>7%) of pentasomy or hexasomy of chromosome 6. Allelic loss at 6q14 was found in 40 with HCC (52%). The distribution of sex, age, stage, tumor size, tumor grade, and viral markers in each group showed no significant differences. An association with cirrhosis, however, was significantly lower in the hypersomy group (P = 0.001). The tetrasomy group had the best survival. An interaction between 6q14 deletion and numerical change of chromosome 6 on patients' survival were also noted. For patients with 6q14 deletion, both disomy and tetrasomy groups had significantly better survival rates than trisomy and hypersomy groups. In contrast, no differences in survival rates could be observed among these four groups for patients without the 6q14 deletion. The association with more favorable prognosis shown in this study indicates that tetrasomy 6 and 6q14 deletion may play an important role in the tumorigenesis of hepatocellular carcinoma and is worthy of further investigation. PMID:12810252

  4. Choanal atresia in a patient with the deletion (9p) syndrome

    SciTech Connect

    Shashi, V.; Golden, W.L.; Fryburg, J.S.

    1994-01-01

    The authors report on a child with choanal atresia and deletion 9p. A review of the literature documented one previous instance of choanal atresia in a patient with del(9p). Choanal atresia may be part of the spectrum of malformations in the deletion (9p) syndrome and its presence should prompt a search for this particular deletion as part of the differential diagnosis. 9 refs., 3 figs.

  5. Linkage disequilibrium utilized to establish a refined genetic position of the Salla disease locus on 6q14-q15

    SciTech Connect

    Schleutker, J.; Laine, A.P.; Haataja, L. |

    1995-05-20

    Salla disease (SD), an inherited free sialic acid storage disorder, is caused by impaired transport of free sialic acid across the lyosomal membrane. Clinical characteristics of the disease include severe psychomotor retardation and some neurological abnormalities. The authors report detailed linkage analyses of 50 Finnish SD families that localize the SD disease gene to a refined chromosomal area on 6q14-q15. The highest lod score of 17.30 was obtained with a microsatellite marker of locus D6S280. When linkage disequilibrium was adopted in the linkage analyses, they could further assign the SD locus to the immediate vicinity of marker locus D6S406. Linkage disequilibrium facilitated further restriction of the critical chromosomal region to approximately 80 kb, well within the limits of positional cloning techniques. 31 refs., 3 figs., 3 tabs.

  6. Developmental delay and connective tissue disorder in four patients sharing a common microdeletion at 6q13-14.

    PubMed

    Van Esch, Hilde; Rosser, Elisabeth M; Janssens, Sandra; Van Ingelghem, Ingrid; Loeys, Bart; Menten, Bjorn

    2010-10-01

    Interstitial deletions of the long arm of chromosome 6 are rare, and most reported cases represent large, cytogenetically detectable deletions. The implementation of array comparative genome hybridisation in the diagnostic work-up of patients presenting with congenital disorders, including developmental delay, has enabled identification of many patients with smaller chromosomal imbalances. In this report, the cases are presented of four patients with a de novo interstitial deletion of chromosome 6q13-14, resulting in a common microdeletion of 3.7 Mb. All presented with developmental delay, mild dysmorphism and signs of lax connective tissue. Interestingly, the common deleted region harbours 16 genes, of which COL12A1 is a good candidate for the connective tissue pathology.

  7. Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23.

    PubMed

    Orozco, Gisela; Hinks, Anne; Eyre, Steve; Ke, Xiayi; Gibbons, Laura J; Bowes, John; Flynn, Edward; Martin, Paul; Wilson, Anthony G; Bax, Deborah E; Morgan, Ann W; Emery, Paul; Steer, Sophia; Hocking, Lynne; Reid, David M; Wordsworth, Paul; Harrison, Pille; Thomson, Wendy; Barton, Anne; Worthington, Jane

    2009-07-15

    The most consistent finding derived from the WTCCC GWAS for rheumatoid arthritis (RA) was association to a SNP at 6q23. We performed a fine-mapping of the region in order to search the 6q23 region for additional disease variants. 3962 RA patients and 3531 healthy controls were included in the study. We found 18 SNPs associated with RA. The SNP showing the strongest association was rs6920220 [P = 2.6 x 10(-6), OR (95% CI) 1.22 (1.13-1.33)]. The next most strongly associated SNP was rs13207033 [P = 0.0001, OR (95% CI) 0.86 (0.8-0.93)] which was perfectly correlated with rs10499194, a SNP previously associated with RA in a US/European series. Additionally, we found a number of new potential RA markers, including rs5029937, located in the intron 2 of TNFAIP3. Of the 18 associated SNPs, three polymorphisms, rs6920220, rs13207033 and rs5029937, remained significant after conditional logistic regression analysis. The combination of the carriage of both risk alleles of rs6920220 and rs5029937 together with the absence of the protective allele of rs13207033 was strongly associated with RA when compared with carriage of none [OR of 1.86 (95% CI) (1.51-2.29)]. This equates to an effect size of 1.50 (95% CI 1.21-1.85) compared with controls and is higher than that obtained for any SNP individually. This is the first study to show that the confirmed loci from the GWA studies, that confer only a modest effect size, could harbour a significantly greater effect once the effect of additional risk variants are accounted for. PMID:19417005

  8. Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23

    PubMed Central

    Orozco, Gisela; Hinks, Anne; Eyre, Steve; Ke, Xiayi; Gibbons, Laura J.; Bowes, John; Flynn, Edward; Martin, Paul; Wilson, Anthony G.; Bax, Deborah E.; Morgan, Ann W.; Emery, Paul; Steer, Sophia; Hocking, Lynne; Reid, David M.; Wordsworth, Paul; Harrison, Pille; Thomson, Wendy; Barton, Anne; Worthington, Jane

    2009-01-01

    The most consistent finding derived from the WTCCC GWAS for rheumatoid arthritis (RA) was association to a SNP at 6q23. We performed a fine-mapping of the region in order to search the 6q23 region for additional disease variants. 3962 RA patients and 3531 healthy controls were included in the study. We found 18 SNPs associated with RA. The SNP showing the strongest association was rs6920220 [P = 2.6 × 10−6, OR (95% CI) 1.22 (1.13–1.33)]. The next most strongly associated SNP was rs13207033 [P = 0.0001, OR (95% CI) 0.86 (0.8–0.93)] which was perfectly correlated with rs10499194, a SNP previously associated with RA in a US/European series. Additionally, we found a number of new potential RA markers, including rs5029937, located in the intron 2 of TNFAIP3. Of the 18 associated SNPs, three polymorphisms, rs6920220, rs13207033 and rs5029937, remained significant after conditional logistic regression analysis. The combination of the carriage of both risk alleles of rs6920220 and rs5029937 together with the absence of the protective allele of rs13207033 was strongly associated with RA when compared with carriage of none [OR of 1.86 (95% CI) (1.51–2.29)]. This equates to an effect size of 1.50 (95% CI 1.21–1.85) compared with controls and is higher than that obtained for any SNP individually. This is the first study to show that the confirmed loci from the GWA studies, that confer only a modest effect size, could harbour a significantly greater effect once the effect of additional risk variants are accounted for. PMID:19417005

  9. Detection and characterization of a human G9P[4] rotavirus strain in Japan.

    PubMed

    Yamamoto, Seiji P; Kaida, Atsushi; Ono, Atsushi; Kubo, Hideyuki; Iritani, Nobuhiro

    2015-08-01

    In a surveillance system in Osaka City, Japan, 48 sporadic rotavirus A (RVA) infections were detected during 2008/2009-2011/2012 seasons. The G/P-genotypes of detected RVAs were G1P[8], G2P[4], G3P[8], G9P[4], and G9P[8]. Although G9P[4] is a rare genotype that had not been reported in Japan, it was the second most prevalent genotype, following G1P[8], and accounted for 35.3% of RVA cases in the 2011/2012 season. Further genotyping revealed that the G9P[4] strain had genotype 2 internal protein genes except for NSP3: G9-P[4]-I2-R2-C2-M2-A2-N2-T1-E2-H2. Among detected RVA strains, G9P[4] and some G9P[8] strains shared high nucleotide identity in VP7 and NSP3 genes. Phylogenetic and BLAST search analyses showed that the G9P[4] strain in Japan shared high nucleotide identity in genotype 2 genes with common G2P[4] strains circulating globally, but was distinct from other G9P[4] strains circulating worldwide. These results suggest that the G9P[4] strain in Japan may have emerged through an independent reassortment between G9P[8] and G2P[4]. Finally, the role of NSP3 protein in the circulating RVA from an amino acid comparison between T1- and T2-type NSP3 is discussed. These findings provide an important insight into less problematic combinations of circulating RVA genes derived from different genotypes.

  10. Allelotyping in mycosis fungoides and Sézary syndrome: common regions of allelic loss identified on 9p, 10q, and 17p.

    PubMed

    Scarisbrick, J J; Woolford, A J; Russell-Jones, R; Whittaker, S J

    2001-09-01

    Allelotyping studies have been extensively used in a wide variety of malignancies to define chromosomal regions of allelic loss and sites of putative tumor suppressor genes; however, until now this technique has not been used in cutaneous lymphoma. We have analyzed 51 samples from patients with mycosis fungoides and 15 with Sézary syndrome using methods to detect loss of heterozygosity. Micro satellite markers were selected on 15 chromosomal arms because of their proximity to either known tumor suppressor genes or chromosomal abnormalities identified in previous cytogenetic studies in cutaneous lymphoma. Allelic loss was present in 45% of patients with mycosis fungoides and 67% with Sézary syndrome. Loss of heterozygosity was found in over 10% of patients with mycosis fungoides on 9p, 10q, 1p, and 17p and was present in 37% with early stage (T1 and T2) and 57% with advanced disease (T3 and T4). Allelic loss on 1p and 9p were found in all stages of mycosis fungoides, whereas losses on 17p and 10q were limited to advanced disease. In Sézary syndrome high rates of loss of heterozygosity were detected on 9p (46%) and 17p (42%) with lower rates on 2p (12%), 6q (7%), and 10q (12%). There was no significant difference in the age at diagnosis or number of treatments received by those with loss of heterozygosity and those without, suggesting that increasing age and multiple treatments do not predispose to allelic loss. These results provide the basis for further studies defining more accurately chromosomal regions of deletions and candidate tumor suppressor genes involved in mycosis fungoides and Sézary syndrome.

  11. A case of 9p deletion syndrome with Duane retraction syndrome

    PubMed Central

    Sinha, Rahul; Dalal, Shamsher; Raju, Uma; John, Biju M.; Negi, Vandana

    2012-01-01

    The chromosome 9p deletion syndrome is a rare but specific clinical event. The clinical manifestations include dysmorphic facial features (trigonocephaly, midface hypoplasia, upward slanting palpebral fissures, and a long philtrum) and psychomotor retardation. Here we report a child with chromosome 9p deletion with Duane retraction syndrome, which has never been reported in the literature before.

  12. The distal 8p deletion (8)(p23.1): A common syndrome associated with cogenital heart defect and mental retardation?

    SciTech Connect

    Wu, B.L.; Schneider, G.H.; Sabatino, D.E.

    1994-09-01

    We describe the clinical manifestations and molecular cytogenetic analysis of three patients with a similar distal deletion: del(8)(p23.1). Case 1: A nine-year-old girl who was the product of a normal pregnancy, with family history of recurrent miscarriages. She has an ASD, development delay and dysmorphic features. Case 2: A three-month-old female who died with a hypoplastic left heart and dysmorphic features. Her non-identical twin sister is healthy. No further family history is available. Case 3: A four-year-old boy who was the product of a normal pregnancy with family history of mental retardation. He has bifid uvula, delayed speech and language, and no major malformations or dysmorphic features. High resolution G and R banding revealed in all three patients del(8)(p23.1), but the breakpoint for case 1 and 2 was proximal to 8p23.1 and for case 3 distal to 8p23.1. FISH studies with a chromosome 8 paint probe confirmed that no other rearrangement was involved. Chromosome analysis of the parents of case 3 and mother of case 1 were normal; the remaining parents were not available for study. Eight individual patients and three members in one family with del(8)(p23.1) have been reported in the past five years. Major congenital anomalies, especially congenital heart defect, is most often associated with a breakpoint proximal to 8p23.1 Three patients were detected within a three year period in this study and five cases were found within a four year period by another group, suggesting that the distal 8p deletion may be a relatively common syndrome. This small deletion is easily overlooked (i.e. case 1 and 3 were reported as normal at amniocentesis) and can be associated with few or no major congenital anomalies.

  13. Distal 8p deletion (8) (p23.1): An easily missed chromosomal abnormality that may be associated with congenital heart defect and mental retardation

    SciTech Connect

    Wu, Bai-Lin; Schneider, G.H.; Sabatino, D.E.

    1996-03-01

    We describe the clinical manifestations and molecular cytogenetic analyses of three patients with a similar distal deletion of chromosome 8. Each child had mild developmental delay and subtle minor anomalies. Two had cardiac anomalies but no other major congenital anomalies were present. High resolution G and R banding showed in all three patients del(8)(p23.1), but the breakpoint in case 1 was distal to 8p23.1, in case 2 was in the middle of 8p23.1, and in case 3 proximal to 8p23.1. Fluorescence in situ hybridization (FISH) studies with a chromosome 8 paint probe confirmed that no other rearrangement had occurred. FISH with a chromosome 8-specific telomere probe indicated that two patients had terminal deletions. Chromosome analysis of the parents of case 1 and mother of case 2 were normal; the remaining parents were not available for study. Thirteen individual patients including the three in this study, and three relatives in one family with del(8)(p23.1), have been reported in the past 5 years. Major congenital anomalies, especially congenital heart defects, are most often associated with a breakpoint proximal to 8p23.1. Three patients were found within a 3-year period in this study and five cases were found within 4 years by another group, indicating that distal 8p deletion might be a relatively common chromosomal abnormality. This small deletion is easily overlooked (i.e., cases 1 and 2 were reported as normal at amniocentesis) and can be associated with few or no major congenital anomalies. 31 refs., 4 figs., 2 tabs.

  14. Glassy Behavior and Isolated Spin Dimers in a New Frustrated Magnet BaCr9pGa12-9pO19

    NASA Astrophysics Data System (ADS)

    Yang, Junjie; Samarakoon, Anjana M.; Hong, Kyun Woo; Copley, John R. D.; Huang, Qingzhen; Tennant, Alan; Sato, Taku J.; Lee, Seung-Hun

    2016-09-01

    Using bulk susceptibility and neutron scattering techniques, we have studied a new frustrated magnet, BaCr9pGa12-9pO19 [BCGO(p)], with 0.4 ≲ p ≲ 0.9. This system is isostructural to SrCr9pGa12-9pO19 [SCGO(p)], in which the magnetic Cr3+ (3d3, s = 3/2) ions form a quasi-two-dimensional triangular lattice of bi-pyramids or kagome-triangle-kagome trilayers. Our bulk susceptibility data exhibit glassy behavior at temperatures much lower than the absolute values of the Curie-Weiss temperature ΘCW ≈ -695(1) K for BCGO(p = 0.902(8)). The frustration index |ΘCW|/Tf is as high as 190 for BCGO(p = 0.902(8)) indicating strong frustration. Our inelastic neutron scattering data on BCGO(p = 0.902(8)) reveal a dispersionless magnetic excitation centered at ħω = 16.5(1) meV, due to a singlet to triplet excitation of spin s = 3/2 dimers. The spin dimers are formed by Cr3+ ions in two 4fvi layers that lie between 12k-2a-12k (kagome-triangle-kagome) trilayers. These results indicate that BCGO(p) is another good candidate system for a strongly frustrated quasi-two-dimensional magnet.

  15. Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27

    SciTech Connect

    Matsumine, Hiroto; Shimoda-Matsubayashi, Satoe; Nakagawa-Hattori, Yuko

    1997-03-01

    An autosomal recessive form of juvenile Parkinsonism (AR-JP) (MIM 600116) is a levodopa-responsive Parkinsonism whose pathological finding is a highly selective degeneration of dopaminergic neurons in the zona compacta of the substantia nigra. By linkage analysis of diallelic polymorphism of the Mn-superoxide dismutase gene (SOD2), we found a family with AR-JP showing perfect segregation of the disease with the SOD2 locus. By extending the linkage analysis to 13 families with AR-JP, we discovered strong evidence for the localization of the AR-JP gene at chromosome 6q25.2-27, including the SOD2 locus, with the maximal cumulative pairwise LOD scores of 7.26 and 7.71 at D6S305 ({theta} = .03) and D6S253 ({theta} = .02), respectively. Observation of obligate recombination events, as well as multipoint linkage analysis, placed the AR-JP gene in a 17-cM interval between D6S437 and D6S264. Delineation of the AR-JP gene will be an important step toward our understanding of the molecular mechanism underlying selective degeneration of the nigral neurons. 38 refs., 4 figs., 1 tab.

  16. Genome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma

    PubMed Central

    Johnson, David C.; Weinhold, Niels; Mitchell, Jonathan S.; Chen, Bowang; Kaiser, Martin; Begum, Dil B.; Hillengass, Jens; Bertsch, Uta; Gregory, Walter A.; Cairns, David; Jackson, Graham H.; Försti, Asta; Nickel, Jolanta; Hoffmann, Per; Nöethen, Markus M.; Stephens, Owen W.; Barlogie, Bart; Davis, Faith E.; Hemminki, Kari; Goldschmidt, Hartmut; Houlston, Richard S.; Morgan, Gareth J.

    2016-01-01

    Survival following a diagnosis of multiple myeloma (MM) varies between patients and some of these differences may be a consequence of inherited genetic variation. In this study, to identify genetic markers associated with MM overall survival (MM-OS), we conduct a meta-analysis of four patient series of European ancestry, totalling 3,256 patients with 1,200 MM-associated deaths. Each series is genotyped for ∼600,000 single nucleotide polymorphisms across the genome; genotypes for six million common variants are imputed using 1000 Genomes Project and UK10K as the reference. The association between genotype and OS is assessed by Cox proportional hazards model adjusting for age, sex, International staging system and treatment. We identify a locus at 6q25.1 marked by rs12374648 associated with MM-OS (hazard ratio=1.34, 95% confidence interval=1.22–1.48, P=4.69 × 10–9). Our findings have potential clinical implications since they demonstrate that inherited genotypes can provide prognostic information in addition to conventional tumor acquired prognostic factors. PMID:26743840

  17. A girl with pervasive developmental disorder and complex chromosome rearrangement involving 8p and 10p.

    PubMed

    Zwaigenbaum, L; Sonnenberg, L K; Heshka, T; Eastwood, S; Xu, J

    2005-06-01

    We report a 4-year-old girl with a de novo, apparently balanced complex chromosome rearrangement. She initially presented for assessment of velopharyngeal insufficiency due to hypernasal speech. She has distinctive facial features (long face, broad nasal bridge, and protuberant ears with simplified helices), bifid uvula, strabismus, and joint laxity. She is developmentally delayed, with language and cognitive skills approximately 2 SD below the mean expected for her age, and meets ADI, ADOS, and DSM-IV criteria for pervasive developmental disorder. She has poor eye contact, atypical communication and social interaction, repetitive behaviours and significant difficulties with processing sensory input. Her karyotype is characterized by the presence of two derivative chromosomes; 46,XX, der(8)(10pter- >10pl2.32::8p12- >8qter), der(l0)(8pter- >8p21.3::10p12.32- >10p11.23::8p21.3- > 8p12::10p11.23- >l0qter). The der(8) is a result of translocation of the segment 10p12.32-pter onto 8p12. The der(l0) has two 8p segments collectively from 8p12-pter in that the segment 8p21.3-pter is translocated onto 10p12.32 and the segment 8p12-p21.3 is inserted at 10p11.23. FISH analysis showed no microdeletion of the major locus at 22q11.2 nor for the minor locus at 10p13p14. This case suggests that aberrations at 8p12, 8p21.3, 10p11.23 and/or 10p12.32 may result in pervasive developmental disorder, associated with mild cognitive delay and specific facial anomalies. PMID:16119480

  18. Tetrasomy 9p mosaicism associated with a normal phenotype in two cases.

    PubMed

    Papoulidis, I; Kontodiou, M; Tzimina, M; Saitis, I; Hamid, A B; Klein, E; Kosyakova, N; Kordass, U; Kunz, J; Siomou, E; Nicolaides, P; Orru, S; Thomaidis, L; Liehr, T; Petersen, M B; Manolakos, E

    2012-01-01

    Tetrasomy 9p is a rare chromosomal syndrome and about 30% of known cases exhibit mosaicism. Approximately 50 of the reported cases with tetrasomy 9p mosaicism show a characteristic facial appearance, growth failure, and developmental delay. However, 3 patients with mosaicism for isochromosome 9p and a normal phenotype have also been reported. We report 2 additional cases of clinically normal young females with tetrasomy 9p mosaicism, one of whom also exhibited X chromosome aneuploidy mosaicism leading to an overall of 6 different cell lines. STR analysis performed on this complex mosaic case indicated that the extra isochromosome was of maternal origin while the X chromosome aneuploidy was of paternal origin, indicating a postzygotic event. PMID:22487875

  19. Fractional spin textures in the frustrated magnet SrCr(9p)Ga(12-9p)O₁₉.

    PubMed

    Sen, Arnab; Damle, Kedar; Moessner, Roderich

    2011-03-25

    We consider the archetypal frustrated antiferromagnet SrCr(9p)Ga(12-9p)O₁₉ in its well-known spin-liquid state, and demonstrate that a Cr(3+) spin S=3/2 ion in direct proximity to a pair of vacancies (in disordered p<1 samples) is cloaked by a spatially extended spin texture that encodes the correlations of the parent spin liquid. In this spin-liquid regime, our analytic theory predicts that the combined object has a magnetic response identical to a classical spin of length S/2=3/4, which dominates over the small intrinsic susceptibility of the pure system. This fractional-spin texture leaves an unmistakable imprint on the measured ⁷¹Ga nuclear magnetic resonance line shapes, which we compute using Monte Carlo simulations and compare with experimental data. PMID:21517349

  20. A genome-wide association study identifies a novel locus at 6q22.1 associated with ulcerative colitis.

    PubMed

    Julià, Antonio; Domènech, Eugeni; Chaparro, María; García-Sánchez, Valle; Gomollón, Fernando; Panés, Julián; Mañosa, Míriam; Barreiro-De Acosta, Manuel; Gutiérrez, Ana; Garcia-Planella, Esther; Aguas, Mariam; Muñoz, Fernando; Esteve, Maria; Mendoza, Juan L; Vera, Maribel; Márquez, Lucía; Tortosa, Raül; López-Lasanta, María; Alonso, Arnald; Gelpí, Josep L; García-Montero, Andres C; Bertranpetit, Jaume; Absher, Devin; Myers, Richard M; Gisbert, Javier P; Marsal, Sara

    2014-12-20

    The genetic analysis of ulcerative colitis (UC) has provided new insights into the etiology of this prevalent inflammatory bowel disease. However, most of the heritability of UC (>70%) has still not been characterized. To identify new risk loci for UC we have performed the first genome-wide association study (GWAS) in a Southern European population and undertaken a meta-analysis study combining the newly genotyped 825 UC patients and 1525 healthy controls from Spain with the six previously published GWAS comprising 6687 cases and 19 718 controls from Northern-European ancestry. We identified a novel locus with genome-wide significance at 6q22.1 [rs2858829, P = 8.97 × 10(-9), odds ratio (OR) (95% confidence interval, CI] = 1.12 (1.08-1.16)] that was validated with genotype data from a replication cohort of the same Southern European ancestry consisting in 1073 cases and 1279 controls [combined P = 7.59 × 10(-10), OR (95% CI) = 1.12 (1.08-1.16)]. Furthermore, we confirmed the association of 33 reported associations with UC and we nominally validated the GWAS results of nine new risk loci (P < 0.05, same direction of effect). SNP rs2858829 lies in an intergenic region and is a strong cis-eQTL for FAM26F gene, a gene that is shown to be selectively upregulated in UC colonic mucosa with active inflammation. Our results provide new insight into the genetic risk background of UC, confirming that there is a genetic risk component that differentiates from Crohn's Disease, the other major form of inflammatory bowel disease.

  1. Independent post-zygotic breaks of a dicentric chromosome result in mosaicism for an inverted duplication deletion 9p and terminal deletion 9p.

    PubMed

    Schlade-Bartusiak, Kamilla; Tucker, Tracy; Safavi, Holly; Livingston, Janet; van Allen, Margot I; Eydoux, Patrice; Armstrong, Linlea

    2013-05-01

    Mosaicism with two cell lines having different rearrangements of the same chromosome is rare. Only a few cases of mosaicism have been described in association with chromosomal inverted duplication deletion (inv dup del) rearrangements. A well-established mechanism of formation of inv dup del rearrangements involves a dicentric intermediate, which undergoes breakage during cell division, generating cells with either an inv dup del or a simple deletion. A patient with developmental delay and dysmorphic features was found to carry two cell lines with rearrangements of 9p: an inv dup del 9p and a terminal deletion 9p. Microarray and FISH analysis showed that these cell lines do not constitute the reciprocal products of a single dicentric breakage event. We propose that independent post-zygotic breaks of a dicentric chromosome as a likely mechanism leading to the generation of the observed cell lines. The post-zygotic origin of the inv dup del rearrangements and the associated mosaicism can be a more frequent phenomenon than currently appreciated. Therefore, genotype-phenotype correlations in the inv dup del rearrangements need to take into account the possible presence of other abnormal cell lines during early development.

  2. ASK1 (MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14-q15 and 6q23 amplifications.

    PubMed

    Chibon, Frédéric; Mariani, Odette; Derré, Josette; Mairal, Aline; Coindre, Jean-Michel; Guillou, Louis; Sastre, Xavier; Pédeutour, Florence; Aurias, Alain

    2004-05-01

    Malignant fibrous histiocytomas (MFHs) are aggressive tumors without any definable line of differentiation. We recently demonstrated that about 20% of them are characterized by high-level amplifications of the 12q14-q15 chromosome region, associated with either 1p32 or 6q23 band amplification. This genetic finding, very similar to that in well-differentiated liposarcomas, strongly suggests that these tumors actually correspond to undifferentiated liposarcomas. It also suggests that the lack of differentiation could be the consequence of amplification of target genes localized in the 1p32 or 6q23 bands. We report here the characterization by array CGH of the 6q23 minimal region of amplification. Our findings demonstrate that amplification and overexpression of ASK1 (MAP3K5), a gene localized in the 6q23 band and encoding a mitogen-activated protein kinase kinase kinase of the JNK-MAPK signaling pathway, could inhibit the adipocytic differentiation process of the tumor cells. Treatment of a cell line with specific inhibitors of ASK1 protein resulted in the bypass of the differentiation block and induction of a strong adipocytic differentiation. These observations indicate that ASK1 is a target for new therapeutic management of these aggressive tumors. PMID:15034865

  3. Assignment of the human cytosolic acetoacetyl-coenzyme a thiolase (ACAT2) gene to chromosome 6q25.3-q26

    SciTech Connect

    Masuno, Mitsuo; Imaizumi, Kiyoshi; Kuroki, Yoshikazu

    1996-08-15

    This report describes the localization of the human cytosolic acetoacetyl-coenzyme A thiolase (ACAT2) gene to human chromosome 6q25.3-q26 using fluorescence in situ hybridization. ACAT2 is involved in steroid biosynthesis; deficiency of this coenzyme results in a phenotype which includes severe mental retardation. 11 refs., 1 fig.

  4. Tissue-specific mosaicism for tetrasomy 9p uncovered by array CGH.

    PubMed

    Shehab, Marwa I; Mazen, Inas; Bint, Susan

    2011-10-01

    We report on a patient with a mild clinical phenotype, including genital anomalies, with mosaic tetrasomy 9p. Karyotype analysis of peripheral blood lymphocytes detected a supernumerary isochromosome 9p present in every cell, with the initial result being reported as tetrasomy 9p in non-mosaic form. However,array Comparative Genomic Hybridization (aCGH) studies on DNA extracted from peripheral blood lymphocytes and saliva showed that the patient had tissue-specific mosaicism, with a lower level of abnormal cells in the saliva. These results correlate with the patient's clinical features as non-mosaic cases of tetrasomy 9p have a more severe, often lethal, clinical phenotype. If non-mosaic tetrasomy 9p is identified in a peripheral blood culture then examination of a different tissue type should be undertaken. Array CGH may be used as an alternative to karyotype analysis to estimate the level of mosaicism, and may eliminate the need for invasive skin biopsy as samples such as buccal smear and saliva can be used. Array CGH is able to detect mosaicism, establish the euchromatic content of supernumerary marker chromosomes, and identify imbalances elsewhere in the genome allowing more accurate counselling and prognosis for patients. PMID:21998854

  5. A stable acentric marker chromosome derived from distal 8p: Reactivation of a latent ancient centromere at 8p23.1?

    SciTech Connect

    Ohashi, H.; Wakui, K.; Ogawa, K.

    1994-09-01

    Centromere is considered to be an essential chromosomal component for faithful segregation, and acentric chromosomes are unstable and lost through cell divisions. We report a novel marker chromosome that was acentric but stable through cell divisions. The patient was a 2-year-old girl with mental retardation, patent ductus arteriosus and mild dysmorphic features. G-banded chromosome analysis revealed an additional small marker chromosome in all 100 cells examined. Using the targeted chromosome-band painting method, the marker was found to originate from the distal region of 8p, and subsequent two color FISH analysis with cosmid probes around the region revealed the marker was a rearranged chromosome interpreted as 8pter{r_arrow}p23.1{r_arrow}8pter. No centromeric region was involved in the marker. By FISH, no {alpha}-satellite sequence was detected on the marker, while telomere sequence was detected at each end. Antikinetochore immunostaining using a serum from a patient with CREST syndrome showed a pair of signals on the marker, which indicated that a functional kinetochore was present on the marker, presumably at 8p23.1-corresponding region. The patient may provide evidence that an ancient centromere sequence exists at 8p23.1 and was reactivated through the chromosome rearrangement in the patient.

  6. Two cases of tetrasomy 9p syndrome with tissue limited mosaicism.

    PubMed

    Lloveras, Elisabet; Pérez, C; Solé, F; Zamora, L; Lladonosa, A; Espinet, B; Silvestre, E; Serra, J; Vendrell, T; Fernández, B; Salido, M; Plaja, A

    2004-02-01

    Tetrasomy of short arm of chromosome 9 constitutes a clinically recognizable chromosomal syndrome. Isochromosome 9p shows a strong propensity to tissue-limited mosaicism. It occurs predominantly in peripheral blood cultures, often at a lower frequency or even absent in skin, amniotic fluid or chorionic villous cell cultures. Tissue-limited nature of mosaicism may render prenatal detection of this condition very difficult. Herein, we report two new cases of mosaic tetrasomy 9p. Conventional cytogenetics (CC) and FISH studies demonstrated a differential expression of the mosaicism in several tissues. We review the literature and discuss the implications of these findings in cytogenetic prenatal diagnosis. PMID:14735590

  7. Delineation of a 6 cM commonly deleted region in childhood acute lymphoblastic leukemia on the 6q chromosomal arm.

    PubMed

    Gérard, B; Cavé, H; Guidal, C; Dastugue, N; Vilmer, E; Grandchamp, B

    1997-02-01

    Deletion of the long arm of human chromosome 6 in acute lymphoblastic leukemia (ALL) has been shown by cytogenetic studies in 4-11% of cases. To characterize further the region of deletion and to precisely establish its frequency, we studied loss of heterozygosity (LOH) in 120 children with ALL using polymorphic markers located from the 6q14-15 chromosomal band to the telomere. LOH was detected in eight patients. A single region of LOH, flanked distally by D6S1594 and proximally by D6S301 was detected. These DNA markers are separated by 6 cM and are approximately located at the 6q21-22 band. Our present results delineate a region that is likely to contain a tumor-suppressor gene involved in a subset of childhood ALLs.

  8. The same molecular mechanism at the maternal meiosis I produces mono- and dicentric 8p duplications

    SciTech Connect

    Floridia, G.; Piantanida, M.; Minelli, A.; Dellavecchia, C.; Bonaglia, C.

    1996-04-01

    We studied 16 cases of 8p duplications, with a karyotype 46,XX or XY,dup(8p), associated with mental retardation, facial dysmorphisms, and brain defects. We demonstrate that these 8p rearrangements can be either dicentric (6 cases) with the second centromere at the tip of the short arm or monocentric (10 cases). The distal 8p23 region, from D8S349 to the telomere, including the defensin 1 locus, is deleted in all the cases. The region spanning from D8S252 to D8S265, at the proximal 8p23 region, is present in single copy, and the remaining part of the abnormal 8 short arm is duplicated in the dicentric cases and partially duplicated in the monocentric ones. The distal edge of the duplication always spans up to D8S552 (8p23.1), while its proximal edge includes the centromere in the dicentric cases and varies from case to case in the monocentric ones. The analysis of DNA polymorphisms indicates that the rearrangement is consistently of maternal origin. In the deleted region, only paternal alleles were present in the patient. In the duplicated region, besides one paternal allele, some loci showed two different maternal alleles, while others, which were duplicated by FISH analysis, showed only one maternal allele. We hypothesize that, at maternal meiosis I, there was abnormal pairing of chromosomes 8 followed by anomalous crossover at the regions delimited by D8S552 and D8S35 and by D8S252 and D8S349, which presumably contain inverted repeated sequences. The resulting dicentric chromosome, 8qter-8p23.1 (D8S552)::8p23.1-(D8S35)-8qter, due to the presence of two centromeres, breaks at anaphase I, generating an inverted duplicated 8p, dicentric if the breakage occurs at the centromere or monocentric if it occurs between centromeres. 44 refs., 7 figs., 2 tabs.

  9. Variants in 9p21 Predicts Severity of Coronary Artery Disease in a Chinese Han Population.

    PubMed

    Jing, Jinjin; Su, Li; Zeng, Ying; Tang, Xiaojun; Wei, Jie; Wang, Long; Zhou, Li

    2016-09-01

    Recent genome-wide association studies identified the common genetic variants in 9p21 were associated with the coronary artery disease (CAD). However, whether this locus could predict the severity of CAD in Chinese Han population is unclear. 499 CAD patients who underwent coronary angiography (CAG) have been enrolled for this study. The single-nucleotide polymorphisms rs2383207 and rs2383206 in 9p21 were genotyped in 499 CAG cases and 1519 controls in Chinese Han population. The gene dosage of 9p21 was stratified by the degree of vascular lesions and tested for association with the severity of CAD. Rs2383207 and rs2383206 demonstrated significant associations with 2-vessel and 3-vessel disease (P = 2.0×10(-3) and 1.9×10(-4) , respectively). GG genotypes of rs2383206 occurred higher proportion of left main trunk (LM) disease (P = 6.0×10(-3) ). GG genotypes of rs2383207 occurred higher proportion of left anterior descending artery disease (LAD) and right CAD (RCA) (P = 2.7×10(-6) and 1.6×10(-4) , respectively). The risk allele G of rs2383207 was associated with severity of CAD estimated by the Gensini score (P = 3.6×10(-5) ). Rs2383207 may strongly influence the development of CAD in Chinese Han population. The gene dosage in 9p21 could predict the severity of CAD. PMID:27461153

  10. Small 6q16.1 Deletions Encompassing POU3F2 Cause Susceptibility to Obesity and Variable Developmental Delay with Intellectual Disability.

    PubMed

    Kasher, Paul R; Schertz, Katherine E; Thomas, Megan; Jackson, Adam; Annunziata, Silvia; Ballesta-Martinez, María J; Campeau, Philippe M; Clayton, Peter E; Eaton, Jennifer L; Granata, Tiziana; Guillén-Navarro, Encarna; Hernando, Cristina; Laverriere, Caroline E; Liedén, Agne; Villa-Marcos, Olaya; McEntagart, Meriel; Nordgren, Ann; Pantaleoni, Chiara; Pebrel-Richard, Céline; Sarret, Catherine; Sciacca, Francesca L; Wright, Ronnie; Kerr, Bronwyn; Glasgow, Eric; Banka, Siddharth

    2016-02-01

    Genetic studies of intellectual disability and identification of monogenic causes of obesity in humans have made immense contribution toward the understanding of the brain and control of body mass. The leptin > melanocortin > SIM1 pathway is dysregulated in multiple monogenic human obesity syndromes but its downstream targets are still unknown. In ten individuals from six families, with overlapping 6q16.1 deletions, we describe a disorder of variable developmental delay, intellectual disability, and susceptibility to obesity and hyperphagia. The 6q16.1 deletions segregated with the phenotype in multiplex families and were shown to be de novo in four families, and there was dramatic phenotypic overlap among affected individuals who were independently ascertained without bias from clinical features. Analysis of the deletions revealed a ∼350 kb critical region on chromosome 6q16.1 that encompasses a gene for proneuronal transcription factor POU3F2, which is important for hypothalamic development and function. Using morpholino and mutant zebrafish models, we show that POU3F2 lies downstream of SIM1 and controls oxytocin expression in the hypothalamic neuroendocrine preoptic area. We show that this finding is consistent with the expression patterns of POU3F2 and related genes in the human brain. Our work helps to further delineate the neuro-endocrine control of energy balance/body mass and demonstrates that this molecular pathway is conserved across multiple species.

  11. Mosaic Tetrasomy 9p: A Mendelian Condition Associated With Pediatric-Onset Overlap Myositis.

    PubMed

    Frémond, Marie-Louise; Gitiaux, Cyril; Bonnet, Damien; Guiddir, Tamazoust; Crow, Yanick J; de Pontual, Loïc; Bader-Meunier, Brigitte

    2015-08-01

    Pediatric-onset inflammatory myositis (IM) and systemic lupus erythematosus (SLE) are rare inflammatory diseases. Both result from the complex interaction of genetic and environmental factors. An increasing number of Mendelian conditions predisposing to the development of SLE have been recently identified. These include monogenic conditions, referred to as the type I interferonopathies, associated with a primary upregulation of type I interferon (IFN), a key cytokine in the pathogenesis of SLE and some cases of IM. Here, we report on a pediatric-onset inflammatory overlap phenotype in a 6-year-old girl who was shown to carry mosaic tetrasomy 9p. The patient presented with myositis overlapping with lupuslike features. Myositis was characterized by a proximal muscular weakness and HLA class I antigen myofiber overexpression on muscle biopsy. Lupus-like manifestations consisted of pericarditis, pleuritis, and positive antinuclear and anti-SSA (Sjögren-syndrome A) antibodies. Complete remission was achieved with corticosteroids and mycophenolate mofetyl. Analysis of tetrasomy 9p showed mosaic tetrasomy in the 9p24.3q12 region, including the type I IFN cluster, and increased expression of IFN-stimulated genes. These data suggest that mosaic tetrasomy 9p can be associated with an upregulation of type I IFN signaling, predisposing to inflammatory myositis and lupus-like features. Thus, unexplained muscle or other organ involvement in patients carrying mosaic tetrasomy of the type IFN cluster of chromosome 9p should lead to the search for IM and/or lupuslike disease, and karyotype should be performed in patients with SLE or IM with mental retardation. PMID:26216333

  12. Identification and functional analysis of 9p24 amplified genes in human breast cancer

    PubMed Central

    Wu, J; Liu, S; Liu, G; Dombkowski, A; Abrams, J; Martin-Trevino, R; Wicha, MS; Ethier, SP; Yang, Z-Q

    2013-01-01

    Previously, our group identified a novel amplicon at chromosome 9p24 in human esophageal and breast cancers, and cloned the novel gene, GASC1 (gene amplified in squamous cell carcinoma 1, also known as JMJD2C/KDM4C), from this amplicon. GASC1 is a histone demethylase involved in the deregulation of histone methylation in cancer cells. In the current study, we aimed to comprehensively characterize the genes in the 9p24 amplicon in human breast cancer. We performed extensive genomic analyses on a panel of cancer cell lines and narrowed the shortest region of overlap to approximately 2 Mb. Based on statistical analysis of copy number increase and overexpression, the 9p24 amplicon contains six candidate oncogenes. Among these, four genes (GASC1 UHRF2, KIAA1432 and C9orf123) are overexpressed only in the context of gene amplification while two genes (ERMP1 and IL33) are overexpressed independent of the copy number increase. We then focused our studies on the UHRF2 gene, which has a potential involvement in both DNA methylation and histone modification. Knocking down UHRF2 expression inhibited the growth of breast cancer cells specifically with 9p24 amplification. Conversely, ectopic overexpression of UHRF2 in non-tumorigenic MCF10A cells promoted cell proliferation. Furthermore, we demonstrated that UHRF2 has the ability to suppress the expression of key cell-cycle inhibitors, such as p16INK4a, p21Waf1/Cip1 and p27Kip1. Taken together, our studies support the notion that the 9p24 amplicon contains multiple oncogenes that may integrate genetic and epigenetic codes and have important roles in human tumorigenesis. PMID:21666724

  13. Ehlers-Danlos Syndrome, Hypermobility Type, Is Linked to Chromosome 8p22-8p21.1 in an Extended Belgian Family

    PubMed Central

    Syx, Delfien; Symoens, Sofie; Steyaert, Wouter; De Paepe, Anne; Coucke, Paul J.; Malfait, Fransiska

    2015-01-01

    Joint hypermobility is a common, mostly benign, finding in the general population. In a subset of individuals, however, it causes a range of clinical problems, mainly affecting the musculoskeletal system. Joint hypermobility often appears as a familial trait and is shared by several heritable connective tissue disorders, including the hypermobility subtype of the Ehlers-Danlos syndrome (EDS-HT) or benign joint hypermobility syndrome (BJHS). These hereditary conditions provide unique models for the study of the genetic basis of joint hypermobility. Nevertheless, these studies are largely hampered by the great variability in clinical presentation and the often vague mode of inheritance in many families. Here, we performed a genome-wide linkage scan in a unique three-generation family with an autosomal dominant EDS-HT phenotype and identified a linkage interval on chromosome 8p22-8p21.1, with a maximum two-point LOD score of 4.73. Subsequent whole exome sequencing revealed the presence of a unique missense variant in the LZTS1 gene, located within the candidate region. Subsequent analysis of 230 EDS-HT/BJHS patients resulted in the identification of three additional rare variants. This is the first reported genome-wide linkage analysis in an EDS-HT family, thereby providing an opportunity to identify a new disease gene for this condition. PMID:26504261

  14. Ehlers-Danlos Syndrome, Hypermobility Type, Is Linked to Chromosome 8p22-8p21.1 in an Extended Belgian Family.

    PubMed

    Syx, Delfien; Symoens, Sofie; Steyaert, Wouter; De Paepe, Anne; Coucke, Paul J; Malfait, Fransiska

    2015-01-01

    Joint hypermobility is a common, mostly benign, finding in the general population. In a subset of individuals, however, it causes a range of clinical problems, mainly affecting the musculoskeletal system. Joint hypermobility often appears as a familial trait and is shared by several heritable connective tissue disorders, including the hypermobility subtype of the Ehlers-Danlos syndrome (EDS-HT) or benign joint hypermobility syndrome (BJHS). These hereditary conditions provide unique models for the study of the genetic basis of joint hypermobility. Nevertheless, these studies are largely hampered by the great variability in clinical presentation and the often vague mode of inheritance in many families. Here, we performed a genome-wide linkage scan in a unique three-generation family with an autosomal dominant EDS-HT phenotype and identified a linkage interval on chromosome 8p22-8p21.1, with a maximum two-point LOD score of 4.73. Subsequent whole exome sequencing revealed the presence of a unique missense variant in the LZTS1 gene, located within the candidate region. Subsequent analysis of 230 EDS-HT/BJHS patients resulted in the identification of three additional rare variants. This is the first reported genome-wide linkage analysis in an EDS-HT family, thereby providing an opportunity to identify a new disease gene for this condition. PMID:26504261

  15. Clinical and molecular delineation of Tetrasomy 9p syndrome: report of 12 new cases and literature review.

    PubMed

    El Khattabi, Laïla; Jaillard, Sylvie; Andrieux, Joris; Pasquier, Laurent; Perrin, Laurence; Capri, Yline; Benmansour, Abdelmadjid; Toutain, Annick; Marcorelles, Pascale; Vincent-Delorme, Catherine; Journel, Hubert; Henry, Catherine; De Barace, Claire; Devisme, Louise; Dubourg, Christèle; Demurger, Florence; Lucas, Josette; Belaud-Rotureau, Marc-Antoine; Amiel, Jeanne; Malan, Valérie; De Blois, Marie-Christine; De Pontual, Loïc; Lebbar, Aziza; Le Dû, Nathalie; Germain, Dominique P; Pinard, Jean-Marc; Pipiras, Eva; Tabet, Anne-Claude; Aboura, Azzedine; Verloes, Alain

    2015-06-01

    Tetrasomy 9p is a generic term describing the presence of a supernumerary chromosome incorporating two copies of the 9p arm. Two varieties exist: isodicentric chromosome 9p (i(9p)), where the two 9p arms are linked by a single centromeric region, and pseudodicentric 9p (idic(9p)), where one active and one inactive centromere are linked together by a proximal segment of 9q that may incorporate euchromatic material. In living patients, i(9p) and idic(9p) are usually present in a mosaic state. Fifty-four cases, including fetuses, have been reported, of which only two have been molecularly characterized using array-CGH. Tetrasomy 9p leads to a variable phenotype ranging from multiple congenital anomalies with severe intellectual disability and growth delay to subnormal cognitive and physical developments. Hypertelorism, abnormal ears, microretrognathia and bulbous nose are the most common dysmorphic traits. Microcephaly, growth retardation, joint dislocation, scoliosis, cardiac and renal anomalies were reported in several cases. Those physical anomalies are often, but not universally, accompanied by intellectual disability. The most recurrent breakpoints, defined by conventional cytogenetics, are 9p10, 9q12 and 9q13. We report on 12 new patients with tetrasomy 9p (3 i(9p), 8 idic(9p) and one structurally uncharacterized), including the first case of parental germline mosaicism. All rearrangements have been characterized by DNA microarray. Based on our results and a review of the literature, we further delineate the prenatal and postnatal clinical spectrum of this imbalance. Our results show poor genotype-phenotype correlations and underline the need of precise molecular characterization of the supernumerary marker. PMID:25847481

  16. Lifetimes of the 9s and 8p levels of atomic francium

    SciTech Connect

    Aubin, S.; Gomez, E.; Orozco, L.A.; Sprouse, G.D.

    2004-10-01

    We use time-correlated single-photon counting techniques on a sample of {sup 210}Fr atoms confined and cooled in a magneto-optical trap to measure the lifetimes of the 9S{sub 1/2}, 8P{sub 3/2}, and 8P{sub 1/2} excited levels. We populate the 9S{sub 1/2} level by two-photon resonant excitation through the 7P{sub 1/2} level. The direct measurement of the 9S{sub 1/2} decay through the 7P{sub 3/2} level at 851 nm gives a lifetime of 107.53{+-}0.90 ns. We observe the decay of the 9S{sub 1/2} level through the 8P{sub 3/2} level at 423 nm and the 8P{sub 1/2} level at 433 nm down to the 7S{sub 1/2} ground level, and indirectly determine the lifetimes of these to be 83.5{+-}1.5 ns and 149.3{+-}3.5 ns, respectively.

  17. The origin, global distribution, and functional impact of the human 8p23 inversion polymorphism.

    PubMed

    Salm, Maximilian P A; Horswell, Stuart D; Hutchison, Claire E; Speedy, Helen E; Yang, Xia; Liang, Liming; Schadt, Eric E; Cookson, William O; Wierzbicki, Anthony S; Naoumova, Rossi P; Shoulders, Carol C

    2012-06-01

    Genomic inversions are an increasingly recognized source of genetic variation. However, a lack of reliable high-throughput genotyping assays for these structures has precluded a full understanding of an inversion's phylogenetic, phenotypic, and population genetic properties. We characterize these properties for one of the largest polymorphic inversions in man (the ∼4.5-Mb 8p23.1 inversion), a structure that encompasses numerous signals of natural selection and disease association. We developed and validated a flexible bioinformatics tool that utilizes SNP data to enable accurate, high-throughput genotyping of the 8p23.1 inversion. This tool was applied retrospectively to diverse genome-wide data sets, revealing significant population stratification that largely follows a clinal "serial founder effect" distribution model. Phylogenetic analyses establish the inversion's ancestral origin within the Homo lineage, indicating that 8p23.1 inversion has occurred independently in the Pan lineage. The human inversion breakpoint was localized to an inverted pair of human endogenous retrovirus elements within the large, flanking low-copy repeats; experimental validation of this breakpoint confirmed these elements as the likely intermediary substrates that sponsored inversion formation. In five data sets, mRNA levels of disease-associated genes were robustly associated with inversion genotype. Moreover, a haplotype associated with systemic lupus erythematosus was restricted to the derived inversion state. We conclude that the 8p23.1 inversion is an evolutionarily dynamic structure that can now be accommodated into the understanding of human genetic and phenotypic diversity.

  18. A Case of Partial Trisomy of Chromosome 8p Associated with Autism

    ERIC Educational Resources Information Center

    Papanikolaou, Katerina; Paliokosta, Elena; Gyftodimou, Jolanda; Kolaitis, Gerassimos; Vgenopoulou, Sofia; Sarri, Catherine; Tsiantis, John

    2006-01-01

    We report on a case of a 6-year-old female with partial trisomy 8p(21-23) associated with autism, mild dysmorphic features, and moderate learning disability. Although mental retardation is a common finding in patients with mosaic trisomy 8 or partial trisomy of various regions of chromosome 8, only two cases associated with autism have been…

  19. Dandy-Walker malformation in an infant with tetrasomy 9p.

    PubMed

    Cazorla Calleja, María R; Verdú, Alfonso; Félix, Valentin

    2003-04-01

    An infant with Dandy-Walker malformation and prenatally diagnosed tetrasomy 9p is reported. Chromosomal analysis of primary amniocyte culture revealed true mosaicism for two cell lines: 50% of the cells had an isochromosome 9p (pter-q13::q13-pter), and the other 50% showed a normal female karyotype (46,XX). After birth the same chromosomal abnormality was found in 75% of peripheral blood lymphocytes. Phenotypic features included intrauterine growth retardation, hypotrophy of the left side of the body with left microphthalmus, and progressive hydrocephalus secondary to Dandy-Walker malformation. Although most cases of Dandy-Walker malformation are not associated with chromosomal abnormalities, our case, together with two previously reported cases of the same association, indicates that this chromosomal disorder should be looked for in children with Dandy-Walker malformation and abnormal somatic development. PMID:12689705

  20. Bulk Density of Comet 9P/Tempel 1 Based on Orbital and Rotational Nongravitational Effects

    NASA Astrophysics Data System (ADS)

    Samarasinha, Nalin H.; Belton, M.; Farnham, T.; Gutierrez, P.; Mueller, B.; Chesley, S.

    2009-09-01

    The accurate determination of bulk densities of cometary nuclei provides a strong indicator of their interior structure and will furnish insights into the conditions in the early solar system. The primary technique to determine cometary bulk densities is by correlating the secular orbital changes of the comet with the corresponding forces due to outgassing. However, significant uncertainties persist in these determinations as the accurate assessment of forces due to outgassing is difficult. Davidsson et al. (2007) derived a bulk density of 200-700 kg m-3 for comet 9P/Tempel 1 based on the orbital nongravitational forces. Richardson and colleagues (e.g,, Richardson et al. 2007) independently determined a density of 200-1000 kg m-3 for comet 9P/Tempel 1 based on the analysis of the ejecta fallback caused by the impactor of the Deep Impact mission. These density determinations based on widely different techniques yield consistent results; however, the allowed density range is relatively large. A simultaneous modeling of orbital and rotational changes in 9P/Tempel 1 is expected to yield more constraining results for the bulk density. Accurate determinations of the rotational changes (Belton et al. 2009) and the localized activity (cf. Farnham et al. 2007, Feaga et al. 2007, Schleicher 2006) of comet 9P/Tempel 1 allow us to simultaneously model the orbital and rotational changes caused by outgassing in a self-consistent manner. Initial results from this study will be presented at the meeting. We thank NASA Outer Planets Research Program. References: Belton, M.J.S. et al. 2009. Icarus, in preparation. Davidsson, B.J.R. et al. 2007, Icarus, 187, 306-320. Farnham, T.L. et al. 2007. Icarus, 187, 26-40. Feaga, L.M. et al. 2007. Icarus, 190, 345-356. Richardson, J.E. et al. 2007. Icarus, 190, 357-390. Schleicher D.G. 2006. Icarus, 181, 442-457.

  1. Liveborn with both partial trisomy of 3q and partial monosomy of 9p

    SciTech Connect

    Farren-Chavez, D.M.; Guzman, E.R.; Peters, T.L.

    1994-09-01

    A 32-year-old G{sub 3}P{sub 2002} Hispanic female presented at 14 weeks gestation for routine dating ultrasound. At that time ultrasonography revealed a septated cystic hygroma, omphalocele, bilateral talipes equinovarus, and hydrops. Amniocentesis was performed at 15 weeks and revealed a 46,XX,9p+ chromosome complement. The origin of the extra material on the terminal short arm of chromosome 9 could not be identified. Chromosome analysis was performed on the parents and the mother was found to carry the balanced translocation 46,XX,p(3;9)(q23;p13). Further analysis revealed that the fetus had inherited the derivative 9 chromosome. The fetus was therefore monosomic for 9p13-9pter and trisomic for 3q23-3pter. The patient chose to continue the pregnancy. Serial ultrasonography later demonstrated a sloping forehead, small nose, micrognathia, ventriculomegaly, possible VSD, micropenis, hypospadias, cryptorchidism and post-axial polydactyly of the hands. The fetus was delivered prematurely at 31 weeks and survived one hour. Post-mortem examination confirmed the ultrasound findings and revealed additional stigmata consistent with both 9p monosomy and 3q trisomy. A review of the literature indicates no previous report of both syndromes concurrently.

  2. The gas production of Comet 9P/Tempel 1 around the Deep Impact date

    NASA Astrophysics Data System (ADS)

    Weiler, M.; Rauer, H.; Knollenberg, J.; Sterken, C.

    The target of the Deep Impact space mission (NASA), Comet 9P/Tempel 1, was observed from two nights before impact to eight nights after impact using the FORS spectrographs at the ESO VLT UT1 and UT2 telescopes. Low resolution optical long-slit spectra were obtained to study the evolution of the gas coma around the Deep Impact event. Following first results of this observing campaign on the CN and dust activity [Rauer, H., Weiler, M., Sterken, C., Jehin, E., Knollenberg, J., Hainaut, O., 2006. Astron. Astrophys. 459, 257 263], this work presents a study of the complete dataset on CN, C2, C3, and NH2 activity of Comet 9P/Tempel 1. An extended impact gas cloud was observed moving radially outwards. No compositional differences between this impact cloud and the undisturbed coma were found as far as the observed radicals are concerned. The gas production rates before and well after impact indicate no change in the cometary activity on an intermediate time scale. Over the observing period, the activity of Comet 9P/Tempel 1 was found to be related to the rotation of the cometary nucleus. The rotational lightcurve for different gaseous species provides indications for compositional differences among different parts of the nucleus surface.

  3. The gas production of Comet 9P/Tempel 1 around the Deep Impact date

    NASA Astrophysics Data System (ADS)

    Weiler, M.; Rauer, H.; Knollenberg, J.; Sterken, C.

    2007-10-01

    The target of the Deep Impact space mission (NASA), Comet 9P/Tempel 1, was observed from two nights before impact to eight nights after impact using the FORS spectrographs at the ESO VLT UT1 and UT2 telescopes. Low resolution optical long-slit spectra were obtained to study the evolution of the gas coma around the Deep Impact event. Following first results of this observing campaign on the CN and dust activity [Rauer, H., Weiler, M., Sterken, C., Jehin, E., Knollenberg, J., Hainaut, O., 2006. Astron. Astrophys. 459, 257-263], this work presents a study of the complete dataset on CN, C 2, C 3, and NH 2 activity of Comet 9P/Tempel 1. An extended impact gas cloud was observed moving radially outwards. No compositional differences between this impact cloud and the undisturbed coma were found as far as the observed radicals are concerned. The gas production rates before and well after impact indicate no change in the cometary activity on an intermediate time scale. Over the observing period, the activity of Comet 9P/Tempel 1 was found to be related to the rotation of the cometary nucleus. The rotational lightcurve for different gaseous species provides indications for compositional differences among different parts of the nucleus surface.

  4. 7q36 deletion and 9p22 duplication: effects of a double imbalance

    PubMed Central

    2013-01-01

    The etiology of mental retardation/developmental delay (MRDD) remains a challenge to geneticists and clinicians and can be correlated to environmental and genetic factors. Chromosomal aberrations are common causes of moderate to severe mental retardation and may represent 10% of these occurrences. Here we report the case of a boy with development delay, hypoplasia of corpus callosum, microcephaly, muscular hypotonia, and facial dysmorphisms. A deletion of 7q36.1 → 36.3 and duplication of 9p22.3 → 23 was detected as a result of an unbalanced translocation of paternal origin. Breakpoint delimitation was achieved with array comparative genomic hybridization assay. Additional multiplex ligation dependent probe amplification (MLPA) analyzes confirmed one copy loss of 7q36.3 region and one copy gain of 9p24.3 region. Patient resultant phenotype is consistent with the already described findings for both 7q deletion and 9p duplication syndromes. PMID:23317051

  5. Multiple independent variants in 6q21-22 associated with susceptibility to celiac disease in the Dutch, Finnish and Hungarian populations

    PubMed Central

    Einarsdottir, Elisabet; Bevova, Marianna R; Zhernakova, Alexandra; Monsuur, Alienke; Koskinen, Lotta LE; Slot, Ruben van't; Mulder, Chris; Mearin, M Luisa; Korponay-Szabo, Ilma R; Kaukinen, Katri; Kurppa, Kalle; Kere, Juha; Mäki, Markku; Wijmenga, Cisca; Saavalainen, Päivi

    2011-01-01

    Celiac disease is an inflammatory enteropathy caused by intolerance to gluten. Previous linkage studies in the Dutch, Finnish and Hungarian populations have revealed a locus on chromosome 6q21-22 conferring susceptibility to celiac disease. This locus has previously been implicated in susceptibility to other autoimmune diseases such as Crohn's disease and type 1 diabetes. We performed fine mapping on 446 independent individuals with celiac disease and 641 controls of Dutch origin, testing 872 tagging SNPs in a 22 Mb region of chromosome 6. The 12 most promising SNPs were followed up in 2071 individuals from 284 Finnish and 357 Hungarian celiac disease families to identify risk variants in this region. Multiple markers in the region were significantly associated with celiac disease in the Dutch material. Two SNPs, rs9391227 and rs4946111, were significantly associated with celiac disease in the Finnish population. The association to rs9391227 represents the strongest association signal found in the Finnish (P=0.003, OR 0.66) as well as the combined Dutch, Finnish and Hungarian populations (P=3.6 × 10−5, OR 0.76). The rs9391227 is situated downstream of the HECT domain and ankyrin repeat containing, E3 ubiquitin protein ligase 1 (HACE1) gene and is contained within a region of strong linkage disequilibrium enclosing HACE1. Two additional, independent, susceptibility variants in the 6q21-22 region were also found in a meta-analysis of the three populations. The 6q21-22 region was confirmed as a celiac disease susceptibility locus and harbors multiple independent associations, some of which may implicate ubiquitin-pathways in celiac disease susceptibility. PMID:21326284

  6. Selections from 2015: EGSY8p7, the Galaxy Far, Far Away

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2015-12-01

    Editors Note:In these last two weeks of 2015, well be looking at a few selections from among the most-downloaded paperspublished in AAS journals this year. The usual posting schedule will resume after the AAS winter meeting.Ly Emission from a Luminous z = 8.68 Galaxy: Implications for Galaxies as Tracers of Cosmic ReionizationPublished August 2015Main takeaway:A team led by Adi Zitrin (Hubble Fellow at California Institute of Technology) detected Ly emission in the bright galaxy EGSY8p7 using the MOSFIRE spectrograph at Keck Observatory. From this emission line, they calculated that the galaxy has an astonishing redshift of z=8.68.Why its interesting:This spectroscopic confirmation crowned EGSY8p7 as the record-holder for the farthest-known (and therefore oldest) galaxy. Its redshift shattered the previous record, a galaxy at z=7.73.Why its even more interesting than that:Spectroscopic detection of emission in EGSY8p7 with MOSFIRE. The black line is the raw data; the red line shows the best-fit model to the data. [Zitrin et al. 2015]Based on our understanding of how the universe evolved, the detection of Ly emission from this galaxy came as a surprise. At EGSY8p7s redshift of 8.68, the universe was still full of clouds of neutral hydrogen that should have absorbed the galaxys Ly emission long before it reached us. So what does it mean that we do see Ly emission from EGSY8p7? The reionization of the universe through which the neutral hydrogen clouds were made transparent may have been a patchy process. In particular, EGSY8p7 might have emitted an unusual amount of ionizing radiation, creating an early ionized bubble around it that allowed the Ly emission to escape.CitationAdi Zitrin et al 2015 ApJ 810 L12. doi:10.1088/2041-8205/810/1/L12

  7. Localization of the gene (LAMA4) to chromosome 6q21 and isolation of a partial cDNA encoding a variant laminin A chain

    SciTech Connect

    Richards, A.J.; Al-Imara, L.; Carter, N.P.

    1994-07-01

    Laminin is a basement membrane glycoprotein composed of three nonidentical chains, A, B1, and B2. Variant chains such as merosin and S-laminin have been found in different tissues. The authors have isolated a cDNA encoding a novel laminin A variant that hybridizes to a 6.45-kb mRNA. Using amplification of genomic DNA and flow-sorted chromosomes they have assigned the gene (LAMA4) for this new laminin A variant to chromosome 6. Fluorescence in situ hybridization of a YAC clone further localized the gene to 6q21. 19 refs., 2 figs.

  8. Microarray Analysis of 8p23.1 Deletion in New Patients with Atypical Phenotypical Traits.

    PubMed

    Khelifa, Hela Ben; Kammoun, Molka; Hannachi, Hanene; Soyah, Najla; Hammami, Saber; Elghezal, Hatem; Sanlaville, Damien; Saad, Ali; Mougou-Zerelli, Soumaya

    2015-12-01

    We describe two patients carrying deletions of chromosome 8p23.1 with a commonly critical region identified by means of oligonucleotide array comparative genomic hybridization (array CGH). They didn't present congenital heart defects or behavioral problems. Only one patient presented with intellectual disability and carrying deletion of TNKS gene. We presumed the inclusion of TNKS gene in the mental impairment. PMID:27617130

  9. A stable acentric marker chromosome: Possible existence of an intercalary ancient centromere at distal 8p

    SciTech Connect

    Ohashi, Hirofumi; Fukushima, Yoshimitsu; Wakui, Keiko; Ogawa, Kioyshi; Okano, Tetsuroh; Niikawa, Norio

    1994-12-01

    A centromere is considered to be an essential chromosomal component where microtubule-kinetochore interaction occurs to segregate sister chromatids faithfully and acentric chromosomes are unstable and lost through cell divisions. We report a novel marker chromosome that was acentric but stable through cell divisions. The patient was a 2-year-old girl with mental retardation, patent ductus arteriosus, and mild dysmorphic features. G-banded chromosome analysis revealed that an additional small marker chromosome was observed in all 100 cells examined. By the reverse-chromosome-painting method, the marker was found to originate from the distal region of 8p, and a subsequent two-color FISH analysis with cosmid probes around the region revealed that the marker was an inverted duplication interpreted as 8pter {yields} p23.1::p23.1 {yields} 8pter. No centromeric region was involved in the marker. By FISH, no {alpha}-satellite sequence was detected on the marker, while a telomere sequence was detected at each end. Anti-kinetochore immunostaining, using a serum from a patient with CREST (calcinosis, Raynaud syndrome, esophageal dismotility, sclerodactyly, and telangiectasia) syndrome, showed a pair of signals on the marker, which indicated that a functional kinetochore was present on the marker. The analysis of this patient might suggest the possibility that an ancient centromere sequence exists at distal 8p (8p23.1-pter) and was activated through the chromosome rearrangement in the patient.

  10. Hyperfine Quantum Beat Spectroscopy of the Cs 8p level with Pulsed Pump-Probe Technique

    NASA Astrophysics Data System (ADS)

    Bayram, Burcin; Popov, Oleg; Kelly, Stephen; Boyle, Patrick; Salsman, Andrew

    2013-05-01

    Quantum beats arising from the hyperfine interaction were measured in a three-level excitation (lambda) scheme: pump for the 6s2S1 / 2 --> 8p2P3 / 2 and stimulated emission pump (probe) for the 8p2P3 / 2 --> 5d2D5 / 2 transitions of atomic cesium. In the technique, pump laser instantaneously excites the hot atomic vapor and creates anisotropy in the 8p2P3 / 2 level, and probe laser comes after some time delay. Delaying the probe time allows us to map out the motion of the polarized atoms like a stroboscope. According to the observed evolution of the hyperfine structure dependent parameters, e.g. alignment and atomic polarization, by delaying the arrival time of the stimulated emission pump laser (SEP), precise values of the magnetic dipole and electric quadrupole coefficients are obtained with an improved precision over previous results. The usefulness of the PUMP-SEP excitation scheme for the polarization hyperfine quantum beat measurements without complications from the Doppler effect will also be discussed. The financial support of the Research Corporation under the Grant number CC7133 and MiamiUniversity, College of the Arts and Sciences are acknowledged.

  11. COMMON BASIS FOR THE MECHANISM OF METALLO AND NON-METALLO KDO8P SYNTHASES

    PubMed Central

    Tao, Peng; Schlegel, H. Bernhard; Gatti, Domenico L.

    2010-01-01

    The three-dimensional structures of metal and non-metal enzymes that catalyze the same reaction are often quite different, a clear indication of convergent evolution. However, there are interesting cases in which the same scaffold supports both a metal and a non-metal catalyzed reaction. One of these is 3-deoxy-D-manno-octulosonate 8-phosphate (KDO8P) synthase (KDO8PS), a bacterial enzyme that catalyzes the synthesis of KDO8P and inorganic phosphate (Pi) from phosphoenolpyruvate (PEP), arabinose 5-phosphate (A5P), and water. This reaction is one of the key steps in the biosynthesis of bacterial endotoxins. The evolutionary tree of KDO8PS is evenly divided between metal and non-metal forms, both having essentially identical structures. Mutagenesis and crystallographic studies suggests that one or two residues at most determine whether or not KDO8PS requires a metal for function, a clear example of “minimalist evolution”. Quantum mechanical/molecular mechanical (QM/MM) simulations of both the enzymatic and non-enzymatic synthesis of KDO8P have revealed the mechanism underlying the switch between metal and non-metal dependent catalysis. The principle emerging from these studies is that this conversion is possible in KDO8PS because the metal is not involved in an activation process, but primarily contributes to orienting properly the reactants to lower the activation energy, an action easily mimicked by amino acid side-chains. PMID:20825995

  12. Genetic polymorphisms in the 9p21 region associated with risk of multiple cancers.

    PubMed

    Li, Wen-Qing; Pfeiffer, Ruth M; Hyland, Paula L; Shi, Jianxin; Gu, Fangyi; Wang, Zhaoming; Bhattacharjee, Samsiddhi; Luo, Jun; Xiong, Xiaoqin; Yeager, Meredith; Deng, Xiang; Hu, Nan; Taylor, Philip R; Albanes, Demetrius; Caporaso, Neil E; Gapstur, Susan M; Amundadottir, Laufey; Chanock, Stephen J; Chatterjee, Nilanjan; Landi, Maria Teresa; Tucker, Margaret A; Goldstein, Alisa M; Yang, Xiaohong R

    2014-12-01

    The chromosome 9p21 region has been implicated in the pathogenesis of multiple cancers. We analyzed 9p21 single nucleotide polymorphisms (SNPs) from eight genome-wide association studies (GWAS) with data deposited in dbGaP, including studies of esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), pancreatic cancer, renal cell carcinoma (RCC), lung cancer (LC), breast cancer (BrC), bladder cancer (BC) and prostate cancer (PrC). The number of subjects ranged from 2252 (PrC) to 7619 (LC). SNP-level analyses for each cancer were conducted by logistic regression or random-effects meta-analysis. A subset-based statistical approach (ASSET) was performed to combine SNP-level P values across multiple cancers. We calculated gene-level P values using the adaptive rank truncated product method. We identified that rs1063192 and rs2157719 in the CDKN2A/2B region were significantly associated with ESCC and rs2764736 (3' of TUSC1) was associated with BC (P ≤ 2.59 × 10(-6)). ASSET analyses identified four SNPs significantly associated with multiple cancers: rs3731239 (CDKN2A intronic) with ESCC, GC and BC (P = 3.96 × 10(-) (4)); rs10811474 (3' of IFNW1) with RCC and BrC (P = 0.001); rs12683422 (LINGO2 intronic) with RCC and BC (P = 5.93 × 10(-) (4)) and rs10511729 (3' of ELAVL2) with LC and BrC (P = 8.63 × 10(-) (4)). At gene level, CDKN2B, CDKN2A and CDKN2B-AS1 were significantly associated with ESCC (P ≤ 4.70 × 10(-) (5)). Rs10511729 and rs10811474 were associated with cis-expression of 9p21 genes in corresponding cancer tissues in the expression quantitative trait loci analysis. In conclusion, we identified several genetic variants in the 9p21 region associated with the risk of multiple cancers, suggesting that this region may contribute to a shared susceptibility across different cancer types. PMID:25239644

  13. Deep Impact 9P/TEMPEL Encounter - Raw MRI Nav Images V1.1

    NASA Astrophysics Data System (ADS)

    Carcich, B.; Shaw, A. S.; Desnoyer, M.; McLaughlin, S. A.; Mastrodemos, N.; Klaasen, K. P.

    2010-01-01

    This data set contains raw 9P/Tempel 1 and calibration images acquired by the Deep Impact Medium Resolution Instrument Visible CCD during the encounter phase of the mission. These observations were used for optical and autonomous navigation (NAV) of the flyby spacecraft as well as for scientific investigations. These data were collected from 1 May to 4 July 2005. In this version 1.1 of the data set, the values for the INTEGRATION_DURATION keyword in the PDS data labels were corrected. This revised data set supersedes version 1.0.

  14. Deep Impact 9P/TEMPEL Encounter - Raw its Nav Images V1.1

    NASA Astrophysics Data System (ADS)

    Carcich, B.; Shaw, A. S.; Desnoyer, M.; McLaughlin, S. A.; Mastrodemos, N.; Klaasen, K. P.

    2010-01-01

    This data set contains raw comet 9P/Tempel 1 and calibration images acquired by the Deep Impact Impactor Targeting Sensor Visible CCD during the encounter phase of the mission. These observations were used for optical and autonomous navigation (NAV) of the impactor spacecraft as well as for scientific investigations. These data were collected from 6 May to 4 July 2005. In this version 1.1 of the data set, the values for the INTEGRATION_DURATION keyword in the PDS data labels were corrected. This revised data set supersedes version 1.0.

  15. Deep Impact 9P/TEMPEL Cruise - Raw MRI Nav Images V1.1

    NASA Astrophysics Data System (ADS)

    Carcich, B.; Shaw, A. S.; Desnoyer, M.; McLaughlin, S. A.; Mastrodemos, N.; Klaasen, K. P.

    2010-01-01

    This data set contains raw calibration and test images acquired by the Deep Impact Medium Resolution Instrument Visible CCD during the cruise phase of the mission. These observations were used for optical and autonomous navigation (NAV) of the flyby spacecraft. These data were collected from 14 January to 25 April 2005. Test images of comet 9P/Tempel 1 were acquired on 25 April. In this version 1.1 of the data set, the values for the INTEGRATION_DURATION keyword in the PDS data labels were corrected. This revised data set supersedes version 1.0.

  16. Identification of multiple complex rearrangements associated with deletions in the 6q23-27 region in Sézary syndrome.

    PubMed

    Iżykowska, Katarzyna; Zawada, Mariola; Nowicka, Karina; Grabarczyk, Piotr; Braun, Floriane C M; Delin, Martin; Möbs, Markus; Beyer, Marc; Sterry, Wolfram; Schmidt, Christian A; Przybylski, Grzegorz K

    2013-11-01

    The 6q23-27 region, recurrently deleted in Sézary syndrome (SS), was characterized at the molecular level in 13 SS patients and SS cell line SeAx. Using fine-tiling comparative genomic hybridization, deletions within the 6q23-27 region were detected in half of the samples (six patients and SeAx). All samples with deletions were further analyzed by ligation-mediated PCR. In addition, in one patient sample and in SeAx, paired-end next-generation sequencing was performed on the HiSeq2000 Illumina platform. Using those techniques, 23 rearrangements associated with the deletions were identified. The majority of rearrangements showed enormous complexity and diversity, including eight inversions, three transpositions, and four translocations (with chromosomes 3, 17, 10, and 12). Fifteen genes were disrupted by those rearrangements, the MYB proto-oncogene three times and the interleukin-22 receptor subunit alpha-2 gene (IL22RA2) twice. All three patients with MYB alterations showed low MYB expression, whereas seven of the remaining patients showed overexpression. Most patients overexpressing MYB also presented increased expression of MYC, HSPA8, and BCL2. Five gene fusions were identified, of which two, CCDC28A-IL22RA2 and AIG1-GOSR1, both in SeAx, were in the same orientation and were expressed at the messenger RNA level.

  17. The First Genomewide Interaction and Locus-Heterogeneity Linkage Scan in Bipolar Affective Disorder: Strong Evidence of Epistatic Effects between Loci on Chromosomes 2q and 6q

    PubMed Central

    Abou Jamra, Rami ; Fuerst, Robert ; Kaneva, Radka ; Orozco Diaz, Guillermo ; Rivas, Fabio ; Mayoral, Fermin ; Gay, Eudoxia ; Sans, Sebastian ; González, Maria Jose ; Gil, Susana ; Cabaleiro, Francisco ; del Rio, Francisco ; Perez, Fermin ; Haro, Jesus ; Auburger, Georg ; Milanova, Vihra ; Kostov, Christian ; Chorbov, Vesselin ; Stoyanova, Vessela ; Nikolova-Hill, Amelia ; Onchev, George ; Kremensky, Ivo ; Jablensky, Assen ; Schulze, Thomas G. ; Propping, Peter ; Rietschel, Marcella ; Nöthen, Markus M. ; Cichon, Sven ; Wienker, Thomas F. ; Schumacher, Johannes 

    2007-01-01

    We present the first genomewide interaction and locus-heterogeneity linkage scan in bipolar affective disorder (BPAD), using a large linkage data set (52 families of European descent; 448 participants and 259 affected individuals). Our results provide the strongest interaction evidence between BPAD genes on chromosomes 2q22-q24 and 6q23-q24, which was observed symmetrically in both directions (nonparametric LOD [NPL] scores of 7.55 on 2q and 7.63 on 6q; P<.0001 and P=.0001, respectively, after a genomewide permutation procedure). The second-best BPAD interaction evidence was observed between chromosomes 2q22-q24 and 15q26. Here, we also observed a symmetrical interaction (NPL scores of 6.26 on 2q and 4.59 on 15q; P=.0057 and .0022, respectively). We covered the implicated regions by genotyping additional marker sets and performed a detailed interaction linkage analysis, which narrowed the susceptibility intervals. Although the heterogeneity analysis produced less impressive results (highest NPL score of 3.32) and a less consistent picture, we achieved evidence of locus heterogeneity at chromosomes 2q, 6p, 11p, 13q, and 22q, which was supported by adjacent markers within each region and by previously reported BPAD linkage findings. Our results provide systematic insights in the framework of BPAD epistasis and locus heterogeneity, which should facilitate gene identification by the use of more-comprehensive cloning strategies. PMID:17924339

  18. Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus.

    PubMed

    Fung, E Y M G; Smyth, D J; Howson, J M M; Cooper, J D; Walker, N M; Stevens, H; Wicker, L S; Todd, J A

    2009-03-01

    As a result of genome-wide association studies in larger sample sets, there has been an increase in identifying genes that influence susceptibility to individual immune-mediated diseases, as well as evidence that some genes are associated with more than one disease. In this study, we tested 17 single nucleotide polymorphisms (SNP) from 16 gene regions that have been reported in several autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), ankylosing spondylitis (AS) and Crohn's disease (CD) to determine whether the variants are also associated with type 1 diabetes (T1D). In up to 8010 cases and 9733 controls we found some evidence for an association with T1D in the regions containing genes: 2q32/STAT4, 17q21/STAT3, 5p15/ERAP1 (ARTS1), 6q23/TNFAIP3 and 12q13/KIF5A/PIP4K2C with allelic P-values ranging from 3.70 x 10(-3) to 3.20 x 10(-5). These findings extend our knowledge of susceptibility locus sharing across different autoimmune diseases, and provide convincing evidence that the RA/SLE locus 6q23/TNFAIP3 is a newly identified T1D locus. PMID:19110536

  19. Secular variation of activity in comets 2P/Encke and 9P/Tempel 1

    NASA Technical Reports Server (NTRS)

    Haken, Michael; AHearn, Michael F.; Feldman, Paul D.; Budzien, Scott A.

    1995-01-01

    We compare production rates of H20 derived from International Ultraviolet Explorer (IUE) spectra from multiple apparitions of 2 comets, 2P/Encke and 9P/Tempel 1, whose orbits are in near-resonance with that of the Earth. Since model-induced errors are primarily a function of observing geometry, the close geometrical matches afforded by the resonance condition results in the cancellation of such errors when taking ratios of production rates. Giving careful attention to the variation of model parameters with solar activity, we find marginal evidence of change in 2P/Encke: a 1-sigma pre-perihelion decrease averaging 4%/revolution over 4 apparitions from 1980-1994, and a 1-sigma post-perihelion increase of 16%/revolution for 2 successive apparitions in 1984 and 1987. We find for 9P/Tempel 1, however, a 7-sigma decrease of 29%/revolution over 3 apparitions from 1983-1994, even after correcting for a tracking problem which made the fluxes systematically low. We speculate on a possible association of the character of long-term brightness variations with physical properties of the nucleus, and discuss implications for future research.

  20. Spondylocostal dysostosis in a pregnancy complicated by confined placental mosaicism for tetrasomy 9p.

    PubMed

    Coman, David; Bacic, Sonya; Boys, Amber; Sparrow, Duncan B; Dunwoodie, Sally L; Savarirayan, Ravi; Amor, David J

    2008-08-01

    The spondylocostal dysostoses (SCD) are a clinically and genetically heterogeneous group of disorders characterized by defects of vertebral segmentation and rib abnormalities. We report on the diagnosis of two siblings with SCD. Diagnosis was first made in a female infant following a pregnancy that was complicated by early fetal hydrops and a nuchal translucency of 8.2 mm in the first trimester. The clinical picture was complicated by the co-existent diagnosis of confined placental mosaicism (CPM) for tetrasomy 9p. To our knowledge, this is the first report of CPM for tetrasomy 9p. Postnatally the diagnosis of SCD was made on the basis of radiographic findings comprising multiple anomalies of the cervical and thoracic vertebrae and multiple fused and dysplastic ribs. Radiographic investigation of other family members showed that the infant's 4-year-old sibling had fusion of four ribs on the right side, indicating a less severe form of SCD. Testing of the genes DLL3, MESP2, and LFNG did not identify a mutation, suggesting that the siblings may have a new molecular subtype of SCD. PMID:18627039

  1. 4p- syndrome and 9p tetrasomy mosaicism with cleft lip and palate.

    PubMed

    Kobayashi, J; Kimijima, Y; Yamada, S; Amagasa, T; Saito-Ohara, F

    2000-06-01

    Chromosome 4p- syndrome is a multiple malformation syndrome associated with partial deletion of the short arm of chromosome 4 (4p-). It is characterized by dysmorphic features and retarded development. Cleft lip and/or palate are the major clinical manifestations. Cases of tetrasomy 9p are extremely rare; the principal clinical manifestations of this condition are characteristic craniofacial abnormalities, generalized hypotonia and severe mental retardation. We present the first case of a female infant with 4p deletion and tetrasomy 9p mosaicism, exhibiting a left-sided cleft lip, alveolus and soft palate. Karyotype analysis of lymphocytes cultured from the patient revealed that she was mosaic: 86% of the cells were 46, XX, add (4) (p15.32) and 14% were 47, XX, add (4) (p15.32), +idic (9)(q12). The G-banding pattern appeared consistent with either translocation or partial proximal deletion of 4p. In order to make a definitive cytogenetic diagnosis of isodicentric chromosome 9, fluorescence in situ hybridization (FISH) was applied. At 8 months, when the patient weighed 4.3 kg, her cleft lip was repaired. Before and after surgery there were no seizures, and the postoperative course was uneventful. PMID:10964553

  2. CHANDRA OBSERVATIONS OF COMETS 8P/TUTTLE AND 17P/HOLMES DURING SOLAR MINIMUM

    SciTech Connect

    Christian, D. J.; Bodewits, D.; Lisse, C. M.; Dennerl, K.; Wolk, S. J.; Hsieh, H.; Zurbuchen, T. H.; Zhao, L. E-mail: damian.christian@csun.edu E-mail: carey.lisse@jhuapl.edu E-mail: swolk@cfa.harvard.edu E-mail: thomasz@umich.edu

    2010-04-01

    We present results for Chandra X-ray Observatory observations of two comets made during the minimum of solar cycle 24. The two comets, 17P/Holmes (17P) and 8P/Tuttle (8P), were very different in their activity and geometry. 17P was observed, for 30 ks right after its major outburst, on 2007 October 31 (10:07 UT), and comet 8P/Tuttle was observed in 2008 January for 47 ks. During the two Chandra observations, 17P was producing at least 100 times more water than 8P but was 2.2 times further away from the Sun. Also, 17P was at a relatively high solar latitude (+19.{sup 0}1) while 8P was observed at a lower solar latitude (3.{sup 0}4). The X-ray spectrum of 17P is unusually soft with little significant emission at energies above 500 eV. Depending on our choice of background, we derive a 300-1000 eV flux of 0.5-4.5 x 10{sup -13} erg cm{sup -2} s{sup -1}, with over 90% of the emission in the 300-400 eV range. This corresponds to an X-ray luminosity between 0.4 and 3.3 x 10{sup 15} erg s{sup -1}. However, we cannot distinguish between this significant excess emission and possible instrumental effects, such as incomplete charge transfer across the CCD. 17P is the first comet observed at high latitude during solar minimum. Its lack of X-rays in the 400-1000 eV range, in a simple picture, may be attributed to the polar solar wind, which is depleted in highly charged ions. 8P/Tuttle was much brighter, with an average count rate of 0.20 counts s{sup -1} in the 300-1000 eV range. We derive an average X-ray flux in this range of 9.4 x 10{sup -13} erg cm{sup -2} s{sup -1} and an X-ray luminosity for the comet of 1.7 x 10{sup 14} erg s{sup -1}. The light curve showed a dramatic decrease in flux of over 60% between observations on January 1 and 4. When comparing outer regions of the coma to inner regions, its spectra showed a decrease in ratios of C VI/C V, O VIII/O VII, as predicted by recent solar wind charge exchange (SWCX) emission models. There are remarkable differences

  3. A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

    PubMed Central

    Siddiq, Afshan; Couch, Fergus J.; Chen, Gary K.; Lindström, Sara; Eccles, Diana; Millikan, Robert C.; Michailidou, Kyriaki; Stram, Daniel O.; Beckmann, Lars; Rhie, Suhn Kyong; Ambrosone, Christine B.; Aittomäki, Kristiina; Amiano, Pilar; Apicella, Carmel; Baglietto, Laura; Bandera, Elisa V.; Beckmann, Matthias W.; Berg, Christine D.; Bernstein, Leslie; Blomqvist, Carl; Brauch, Hiltrud; Brinton, Louise; Bui, Quang M.; Buring, Julie E.; Buys, Saundra S.; Campa, Daniele; Carpenter, Jane E.; Chasman, Daniel I.; Chang-Claude, Jenny; Chen, Constance; Clavel-Chapelon, Françoise; Cox, Angela; Cross, Simon S.; Czene, Kamila; Deming, Sandra L.; Diasio, Robert B.; Diver, W. Ryan; Dunning, Alison M.; Durcan, Lorraine; Ekici, Arif B.; Fasching, Peter A.; Feigelson, Heather Spencer; Fejerman, Laura; Figueroa, Jonine D.; Fletcher, Olivia; Flesch-Janys, Dieter; Gaudet, Mia M.; Gerty, Susan M.; Rodriguez-Gil, Jorge L.; Giles, Graham G.; van Gils, Carla H.; Godwin, Andrew K.; Graham, Nikki; Greco, Dario; Hall, Per; Hankinson, Susan E.; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Hoover, Robert N.; Hopper, John L.; Hu, Jennifer J.; Huntsman, Scott; Ingles, Sue A.; Irwanto, Astrid; Isaacs, Claudine; Jacobs, Kevin B.; John, Esther M.; Justenhoven, Christina; Kaaks, Rudolf; Kolonel, Laurence N.; Coetzee, Gerhard A.; Lathrop, Mark; Le Marchand, Loic; Lee, Adam M.; Lee, I-Min; Lesnick, Timothy; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Martin, Nicholas G.; McLean, Catriona A.; Meijers-Heijboer, Hanne; Meindl, Alfons; Miron, Penelope; Monroe, Kristine R.; Montgomery, Grant W.; Müller-Myhsok, Bertram; Nickels, Stefan; Nyante, Sarah J.; Olswold, Curtis; Overvad, Kim; Palli, Domenico; Park, Daniel J.; Palmer, Julie R.; Pathak, Harsh; Peto, Julian; Pharoah, Paul; Rahman, Nazneen; Rivadeneira, Fernando; Schmidt, Daniel F.; Schmutzler, Rita K.; Slager, Susan; Southey, Melissa C.; Stevens, Kristen N.; Sinn, Hans-Peter; Press, Michael F.; Ross, Eric; Riboli, Elio; Ridker, Paul M.; Schumacher, Fredrick R.; Severi, Gianluca; dos Santos Silva, Isabel; Stone, Jennifer; Sund, Malin; Tapper, William J.; Thun, Michael J.; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Waisfisz, Quinten; Wang, Xianshu; Wang, Zhaoming; Weaver, JoEllen; Schulz-Wendtland, Rüdiger; Wilkens, Lynne R.; Van Den Berg, David; Zheng, Wei; Ziegler, Regina G.; Ziv, Elad; Nevanlinna, Heli; Easton, Douglas F.; Hunter, David J.; Henderson, Brian E.; Chanock, Stephen J.; Garcia-Closas, Montserrat; Kraft, Peter; Haiman, Christopher A.; Vachon, Celine M.

    2012-01-01

    Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10-5 in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10−8) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10–6) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10−9), and with both ER-positive (OR = 1.09; P = 1.5 × 10−5) and ER-negative (OR = 1.16, P = 2.5 × 10−7) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci. PMID:22976474

  4. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

    PubMed Central

    Antoniou, Antonis C; Kartsonaki, Christiana; Sinilnikova, Olga M.; Soucy, Penny; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Cattaneo, Elisa; Barile, Monica; Pensotti, Valeria; Pasini, Barbara; Dolcetti, Riccardo; Giannini, Giuseppe; Laura Putignano, Anna; Varesco, Liliana; Radice, Paolo; Mai, Phuong L.; Greene, Mark H.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A.; Birk Jensen, Uffe; Crüger, Dorthe G.; Caligo, Maria A.; Laitman, Yael; Milgrom, Roni; Kaufman, Bella; Paluch-Shimon, Shani; Friedman, Eitan; Loman, Niklas; Harbst, Katja; Lindblom, Annika; Arver, Brita; Ehrencrona, Hans; Melin, Beatrice; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy; Jakubowska, Ania; Lubinski, Jan; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Gorski, Bohdan; Osorio, Ana; Ramón y Cajal, Teresa; Fostira, Florentia; Andrés, Raquel; Benitez, Javier; Hamann, Ute; Hogervorst, Frans B.; Rookus, Matti A.; Hooning, Maartje J.; Nelen, Marcel R.; van der Luijt, Rob B.; van Os, Theo A.M.; van Asperen, Christi J.; Devilee, Peter; Meijers-Heijboer, Hanne E.J.; Gómez Garcia, Encarna B.; Peock, Susan; Cook, Margaret; Frost, Debra; Platte, Radka; Leyland, Jean; Gareth Evans, D.; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Ong, Kai-ren; Cook, Jackie; Douglas, Fiona; Paterson, Joan; John Kennedy, M.; Miedzybrodzka, Zosia; Godwin, Andrew; Stoppa-Lyonnet, Dominique; Buecher, Bruno; Belotti, Muriel; Tirapo, Carole; Mazoyer, Sylvie; Barjhoux, Laure; Lasset, Christine; Leroux, Dominique; Faivre, Laurence; Bronner, Myriam; Prieur, Fabienne; Nogues, Catherine; Rouleau, Etienne; Pujol, Pascal; Coupier, Isabelle; Frénay, Marc; Hopper, John L.; Daly, Mary B.; Terry, Mary B.; John, Esther M.; Buys, Saundra S.; Yassin, Yosuf; Miron, Alexander; Goldgar, David; Singer, Christian F.; Tea, Muy-Kheng; Pfeiler, Georg; Catharina Dressler, Anne; Hansen, Thomas v.O.; Jønson, Lars; Ejlertsen, Bent; Bjork Barkardottir, Rosa; Kirchhoff, Tomas; Offit, Kenneth; Piedmonte, Marion; Rodriguez, Gustavo; Small, Laurie; Boggess, John; Blank, Stephanie; Basil, Jack; Azodi, Masoud; Ewart Toland, Amanda; Montagna, Marco; Tognazzo, Silvia; Agata, Simona; Imyanitov, Evgeny; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Pharoah, Paul D.P.; Sucheston, Lara; Karlan, Beth Y.; Walsh, Christine S.; Olah, Edith; Bozsik, Aniko; Teo, Soo-Hwang; Seldon, Joyce L.; Beattie, Mary S.; van Rensburg, Elizabeth J.; Sluiter, Michelle D.; Diez, Orland; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ruehl, Ina; Varon-Mateeva, Raymonda; Kast, Karin; Deissler, Helmut; Niederacher, Dieter; Arnold, Norbert; Gadzicki, Dorothea; Schönbuchner, Ines; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Dumont, Martine; Chiquette, Jocelyne; Tischkowitz, Marc; Chen, Xiaoqing; Beesley, Jonathan; Spurdle, Amanda B.; Neuhausen, Susan L.; Chun Ding, Yuan; Fredericksen, Zachary; Wang, Xianshu; Pankratz, Vernon S.; Couch, Fergus; Simard, Jacques; Easton, Douglas F.; Chenevix-Trench, Georgia

    2011-01-01

    Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r2 = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11–1.23, P-trend = 4.5 × 10−9 for rs2046210; HR = 1.28, 95% CI: 1.18–1.40, P-trend = 1.3 × 10−8 for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01–1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02–1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92–1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women. PMID:21593217

  5. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers.

    PubMed

    Antoniou, Antonis C; Kartsonaki, Christiana; Sinilnikova, Olga M; Soucy, Penny; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Cattaneo, Elisa; Barile, Monica; Pensotti, Valeria; Pasini, Barbara; Dolcetti, Riccardo; Giannini, Giuseppe; Putignano, Anna Laura; Varesco, Liliana; Radice, Paolo; Mai, Phuong L; Greene, Mark H; Andrulis, Irene L; Glendon, Gord; Ozcelik, Hilmi; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A; Birk Jensen, Uffe; Crüger, Dorthe G; Caligo, Maria A; Laitman, Yael; Milgrom, Roni; Kaufman, Bella; Paluch-Shimon, Shani; Friedman, Eitan; Loman, Niklas; Harbst, Katja; Lindblom, Annika; Arver, Brita; Ehrencrona, Hans; Melin, Beatrice; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy; Jakubowska, Ania; Lubinski, Jan; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Gorski, Bohdan; Osorio, Ana; Ramón y Cajal, Teresa; Fostira, Florentia; Andrés, Raquel; Benitez, Javier; Hamann, Ute; Hogervorst, Frans B; Rookus, Matti A; Hooning, Maartje J; Nelen, Marcel R; van der Luijt, Rob B; van Os, Theo A M; van Asperen, Christi J; Devilee, Peter; Meijers-Heijboer, Hanne E J; Gómez Garcia, Encarna B; Peock, Susan; Cook, Margaret; Frost, Debra; Platte, Radka; Leyland, Jean; Evans, D Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Ong, Kai-ren; Cook, Jackie; Douglas, Fiona; Paterson, Joan; Kennedy, M John; Miedzybrodzka, Zosia; Godwin, Andrew; Stoppa-Lyonnet, Dominique; Buecher, Bruno; Belotti, Muriel; Tirapo, Carole; Mazoyer, Sylvie; Barjhoux, Laure; Lasset, Christine; Leroux, Dominique; Faivre, Laurence; Bronner, Myriam; Prieur, Fabienne; Nogues, Catherine; Rouleau, Etienne; Pujol, Pascal; Coupier, Isabelle; Frénay, Marc; Hopper, John L; Daly, Mary B; Terry, Mary B; John, Esther M; Buys, Saundra S; Yassin, Yosuf; Miron, Alexander; Goldgar, David; Singer, Christian F; Tea, Muy-Kheng; Pfeiler, Georg; Dressler, Anne Catharina; Hansen, Thomas v O; Jønson, Lars; Ejlertsen, Bent; Barkardottir, Rosa Bjork; Kirchhoff, Tomas; Offit, Kenneth; Piedmonte, Marion; Rodriguez, Gustavo; Small, Laurie; Boggess, John; Blank, Stephanie; Basil, Jack; Azodi, Masoud; Toland, Amanda Ewart; Montagna, Marco; Tognazzo, Silvia; Agata, Simona; Imyanitov, Evgeny; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Pharoah, Paul D P; Sucheston, Lara; Karlan, Beth Y; Walsh, Christine S; Olah, Edith; Bozsik, Aniko; Teo, Soo-Hwang; Seldon, Joyce L; Beattie, Mary S; van Rensburg, Elizabeth J; Sluiter, Michelle D; Diez, Orland; Schmutzler, Rita K; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ruehl, Ina; Varon-Mateeva, Raymonda; Kast, Karin; Deissler, Helmut; Niederacher, Dieter; Arnold, Norbert; Gadzicki, Dorothea; Schönbuchner, Ines; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Dumont, Martine; Chiquette, Jocelyne; Tischkowitz, Marc; Chen, Xiaoqing; Beesley, Jonathan; Spurdle, Amanda B; Neuhausen, Susan L; Chun Ding, Yuan; Fredericksen, Zachary; Wang, Xianshu; Pankratz, Vernon S; Couch, Fergus; Simard, Jacques; Easton, Douglas F; Chenevix-Trench, Georgia

    2011-08-15

    Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 × 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.

  6. A common variant on chromosome 9p21 affects the risk of myocardial infarction.

    PubMed

    Helgadottir, Anna; Thorleifsson, Gudmar; Manolescu, Andrei; Gretarsdottir, Solveig; Blondal, Thorarinn; Jonasdottir, Aslaug; Jonasdottir, Adalbjorg; Sigurdsson, Asgeir; Baker, Adam; Palsson, Arnar; Masson, Gisli; Gudbjartsson, Daniel F; Magnusson, Kristinn P; Andersen, Karl; Levey, Allan I; Backman, Valgerdur M; Matthiasdottir, Sigurborg; Jonsdottir, Thorbjorg; Palsson, Stefan; Einarsdottir, Helga; Gunnarsdottir, Steinunn; Gylfason, Arnaldur; Vaccarino, Viola; Hooper, W Craig; Reilly, Muredach P; Granger, Christopher B; Austin, Harland; Rader, Daniel J; Shah, Svati H; Quyyumi, Arshed A; Gulcher, Jeffrey R; Thorgeirsson, Gudmundur; Thorsteinsdottir, Unnur; Kong, Augustine; Stefansson, Kari

    2007-06-01

    The global endemic of cardiovascular diseases calls for improved risk assessment and treatment. Here, we describe an association between myocardial infarction (MI) and a common sequence variant on chromosome 9p21. This study included a total of 4587 cases and 12,767 controls. The identified variant, adjacent to the tumor suppressor genes CDKN2A and CDKN2B, was associated with the disease with high significance. Approximately 21% of individuals in the population are homozygous for this variant, and their estimated risk of suffering myocardial infarction is 1.64 times as great as that of noncarriers. The corresponding risk is 2.02 times as great for early-onset cases. The population attributable risk is 21% for MI in general and 31% for early-onset cases.

  7. Preparation and crystal structure of the semiconducting compound Sn 4.2Si 9P 16

    NASA Astrophysics Data System (ADS)

    Pivan, Jean-Yves; Guerin, Roland; Padiou, Jean; Sergent, Marcel

    1988-09-01

    The phosphide Sn 4.2Si 9P 16 has been grown as single crystals using tin as a flux. The unit cell is rhombohedral, space group R3, with a = 9.504(2) Å, α = 111.00(2)°, and Z = 1. The X-ray structure was solved from three-dimensional single-crystal counter data and refined down the final R indices 0.027 and 0.033 for 854 independent reflections. It consists of |SiP 4| tetrahedra linked together by common apices which generate a tridimensional framework into which tin atoms, in a distorted tetrahedral phosphorus coordination, are inserted. This new compound was found to be semiconducting with a band gap of 0.2 eV.

  8. [A case of 9p partial monosomy caused by paternal translocation. Clinical and cytogenetic aspects].

    PubMed

    Calzolari, C; Seracini, D; Burgio, G; Gaeta, G; Pacini, M; Giovannucci-Uzielli, M L; Mainardi, A

    1988-01-01

    The authors describe a case of partial monosomy 9p in a newborn infant, with breakpoint in the region p221, due to a father's balanced translocation with karyotype 46 XY t(9;16)(p221;q224). The phenotypical features of our patient reproduce those reported in other 35 cases described up to now in the literature: trigonocephaly, upward slanting palpebral fistures, little and horizontal mouth, disproportionally long fingers and toes. Some peculiar clinical and cytogenetical features of the case are discussed, particularly the early closure of the sternal body ossification centers (already detected during the prenatal life), the partial agenesia of the splenium corporis callosi and the partial anomalous pulmonary venous return. The Authors point out the importance of an early diagnosis, based on the awareness to the clinical abnormalities and dysmorphisms, in order to provide for an adequate and opportune genetic counseling. PMID:3241758

  9. DLC1 is a chromosome 8p tumor suppressor whose loss promotes hepatocellular carcinoma

    PubMed Central

    Xue, Wen; Krasnitz, Alexander; Lucito, Robert; Sordella, Raffaella; VanAelst, Linda; Cordon-Cardo, Carlos; Singer, Stephan; Kuehnel, Florian; Wigler, Michael; Powers, Scott; Zender, Lars; Lowe, Scott W.

    2008-01-01

    Deletions on chromosome 8p are common in human tumors, suggesting that one or more tumor suppressor genes reside in this region. Deleted in Liver Cancer 1 (DLC1) encodes a Rho-GTPase activating protein and is a candidate 8p tumor suppressor. We show that DLC1 knockdown cooperates with Myc to promote hepatocellular carcinoma in mice, and that reintroduction of wild-type DLC1 into hepatoma cells with low DLC1 levels suppresses tumor growth in situ. Cells with reduced DLC1 protein contain increased GTP-bound RhoA, and enforced expression a constitutively activated RhoA allele mimics DLC1 loss in promoting hepatocellular carcinogenesis. Conversely, down-regulation of RhoA selectively inhibits tumor growth of hepatoma cells with disabled DLC1. Our data validate DLC1 as a potent tumor suppressor gene and suggest that its loss creates a dependence on the RhoA pathway that may be targeted therapeutically. PMID:18519636

  10. A bovine G8P[1] group A rotavirus isolated from an asymptomatically infected dog.

    PubMed

    Sieg, Michael; Rückner, Antje; Köhler, Christian; Burgener, Iwan; Vahlenkamp, Thomas W

    2015-01-01

    Group A rotaviruses (RVAs) are enteric pathogens with well-documented zoonotic transmissions to humans. The segmented genome of the virus enables reassortment events which might alter host susceptibility and/or disease course. Genetic analysis of rotavirus in dogs has so far only revealed RVAs with the VP7 and VP4 genome constellation G3P[3]. RVA G3P[3] have also been found in cats, humans, monkeys and bats. In the present study, we described an unusual RVA of genotype G8P[1] which was isolated from an asymptomatically infected young dog. The dog did not show signs of diarrhoea. Analysis of full-length segments of VP2, VP6 and VP7 as well as NSP1-NSP5 revealed a typical bovine-like genotype constellation G8-P[1]-I2-Rx-C2-Mx-A3-N2-T6-E2-H3. Phylogenetic analysis supported the hypothesis of an interspecies transmission from a bovine/artiodactyl species or from humans to the young dog. The isolate was likely to represent a multiple reassortant virus. PMID:25304653

  11. Genome annotation of a 1.5 Mb region of human chromosome 6q23 encompassing a quantitative trait locus for fetal hemoglobin expression in adults

    PubMed Central

    Close, James; Game, Laurence; Clark, Barnaby; Bergounioux, Jean; Gerovassili, Ageliki; Thein, Swee Lay

    2004-01-01

    Background Heterocellular hereditary persistence of fetal hemoglobin (HPFH) is a common multifactorial trait characterized by a modest increase of fetal hemoglobin levels in adults. We previously localized a Quantitative Trait Locus for HPFH in an extensive Asian-Indian kindred to chromosome 6q23. As part of the strategy of positional cloning and a means towards identification of the specific genetic alteration in this family, a thorough annotation of the candidate interval based on a strategy of in silico / wet biology approach with comparative genomics was conducted. Results The ~1.5 Mb candidate region was shown to contain five protein-coding genes. We discovered a very large uncharacterized gene containing WD40 and SH3 domains (AHI1), and extended the annotation of four previously characterized genes (MYB, ALDH8A1, HBS1L and PDE7B). We also identified several genes that do not appear to be protein coding, and generated 17 kb of novel transcript sequence data from re-sequencing 97 EST clones. Conclusion Detailed and thorough annotation of this 1.5 Mb interval in 6q confirms a high level of aberrant transcripts in testicular tissue. The candidate interval was shown to exhibit an extraordinary level of alternate splicing – 19 transcripts were identified for the 5 protein coding genes, but it appears that a significant portion (14/19) of these alternate transcripts did not have an open reading frame, hence their functional role is questionable. These transcripts may result from aberrant rather than regulated splicing. PMID:15169551

  12. Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2.

    PubMed

    Kirchhoff, Tomas; Gaudet, Mia M; Antoniou, Antonis C; McGuffog, Lesley; Humphreys, Manjeet K; Dunning, Alison M; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Dork, Thilo; Schürmann, Peter; Karstens, Johann H; Hillemanns, Peter; Couch, Fergus J; Olson, Janet; Vachon, Celine; Wang, Xianshu; Cox, Angela; Brock, Ian; Elliott, Graeme; Reed, Malcolm W R; Burwinkel, Barbara; Meindl, Alfons; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Broeks, Annegien; Schmidt, Marjanka K; Van 't Veer, Laura J; Braaf, Linde M; Johnson, Nichola; Fletcher, Olivia; Gibson, Lorna; Peto, Julian; Turnbull, Clare; Seal, Sheila; Renwick, Anthony; Rahman, Nazneen; Wu, Pei-Ei; Yu, Jyh-Cherng; Hsiung, Chia-Ni; Shen, Chen-Yang; Southey, Melissa C; Hopper, John L; Hammet, Fleur; Van Dorpe, Thijs; Dieudonne, Anne-Sophie; Hatse, Sigrid; Lambrechts, Diether; Andrulis, Irene L; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Juri I; Prokofieva, Daria; Bermisheva, Marina; Khusnutdinova, Elza; van Asperen, Christi J; Tollenaar, Robert A E M; Hooning, Maartje J; Devilee, Peter; Margolin, Sara; Lindblom, Annika; Milne, Roger L; Arias, José Ignacio; Zamora, M Pilar; Benítez, Javier; Severi, Gianluca; Baglietto, Laura; Giles, Graham G; Spurdle, Amanda B; Beesley, Jonathan; Chen, Xiaoqing; Holland, Helene; Healey, Sue; Wang-Gohrke, Shan; Chang-Claude, Jenny; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Agnarsson, Bjarni A; Caligo, Maria A; Godwin, Andrew K; Nevanlinna, Heli; Heikkinen, Tuomas; Fredericksen, Zachary; Lindor, Noralane; Nathanson, Katherine L; Domchek, Susan M; Loman, Niklas; Karlsson, Per; Stenmark Askmalm, Marie; Melin, Beatrice; von Wachenfeldt, Anna; Hogervorst, Frans B L; Verheus, Martijn; Rookus, Matti A; Seynaeve, Caroline; Oldenburg, Rogier A; Ligtenberg, Marjolijn J; Ausems, Margreet G E M; Aalfs, Cora M; Gille, Hans J P; Wijnen, Juul T; Gómez García, Encarna B; Peock, Susan; Cook, Margaret; Oliver, Clare T; Frost, Debra; Luccarini, Craig; Pichert, Gabriella; Davidson, Rosemarie; Chu, Carol; Eccles, Diana; Ong, Kai-Ren; Cook, Jackie; Douglas, Fiona; Hodgson, Shirley; Evans, D Gareth; Eeles, Rosalind; Gold, Bert; Pharoah, Paul D P; Offit, Kenneth; Chenevix-Trench, Georgia; Easton, Douglas F

    2012-01-01

    Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.

  13. Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: schizophrenia linkage collaborative group III.

    PubMed

    Levinson, D F; Holmans, P; Straub, R E; Owen, M J; Wildenauer, D B; Gejman, P V; Pulver, A E; Laurent, C; Kendler, K S; Walsh, D; Norton, N; Williams, N M; Schwab, S G; Lerer, B; Mowry, B J; Sanders, A R; Antonarakis, S E; Blouin, J L; DeLeuze, J F; Mallet, J

    2000-09-01

    Schizophrenia candidate regions 33-51 cM in length on chromosomes 5q, 6q, 10p, and 13q were investigated for genetic linkage with mapped markers with an average spacing of 5.64 cM. We studied 734 informative multiplex pedigrees (824 independent affected sibling pairs [ASPs], or 1,003 ASPs when all possible pairs are counted), which were collected in eight centers. Cases with diagnoses of schizophrenia or schizoaffective disorder (DSM-IIIR criteria) were considered affected (n=1,937). Data were analyzed with multipoint methods, including nonparametric linkage (NPL), ASP analysis using the possible-triangle method, and logistic-regression analysis of identity-by-descent (IBD) sharing in ASPs with sample as a covariate, in a test for intersample heterogeneity and for linkage with allowance for intersample heterogeneity. The data most supportive for linkage to schizophrenia were from chromosome 6q; logistic-regression analysis of linkage allowing for intersample heterogeneity produced an empirical P value <.0002 with, or P=.0004 without, inclusion of the sample that produced the first positive report in this region; the maximum NPL score in this region was 2.47 (P=.0046), the maximum LOD score (MLS) from ASP analysis was 3.10 (empirical P=.0036), and there was significant evidence for intersample heterogeneity (empirical P=.0038). More-modest support for linkage was observed for chromosome 10p, with logistic-regression analysis of linkage producing an empirical P=. 045 and with significant evidence for intersample heterogeneity (empirical P=.0096). PMID:10924404

  14. Chromosome 8p23.1 Deletions as a Cause of Complex Congenital Heart Defects and Diaphragmatic Hernia

    PubMed Central

    Wat, Margaret J.; Shchelochkov, Oleg A.; Holder, Ashley M.; Breman, Amy M.; Dagli, Aditi; Bacino, Carlos; Scaglia, Fernando; Zori, Roberto T.; Cheung, Sau Wai; Scott, Daryl A.; Kang, Sung-Hae Lee

    2009-01-01

    Recurrent interstitial deletion of a region of 8p23.1 flanked by the low copy repeats 8p-OR-REPD and 8p-OR-REPP is associated with a spectrum of anomalies that can include congenital heart malformations and congenital diaphragmatic hernia (CDH). Haploinsufficiency of GATA4 is thought to play a critical role in the development of these birth defects. We describe two individuals and a monozygotic twin pair discordant for anterior CDH all of whom have complex congenital heart defects caused by this recurrent interstitial deletion as demonstrated by array comparative genome hybridization. To better define the genotype/phenotype relationships associated with alterations of genes on 8p23.1, we review the spectrum of congenital heart and diaphragmatic defects that have been reported in individuals with isolated GATA4 mutations and interstitial, terminal, and complex chromosomal rearrangements involving the 8p23.1 region. Our findings allow us to clearly define the CDH minimal deleted region on chromosome 8p23.1 and suggest that haploinsufficiency of other genes, in addition to GATA4, may play a role in the severe cardiac and diaphragmatic defects associated with 8p23.1 deletions. These findings also underscore the importance of conducting a careful cytogenetic/molecular analysis of the 8p23.1 region in all prenatal and postnatal cases involving congenital defects of the heart and/or diaphragm. PMID:19606479

  15. Chromosome 8p23.1 deletions as a cause of complex congenital heart defects and diaphragmatic hernia.

    PubMed

    Wat, Margaret J; Shchelochkov, Oleg A; Holder, Ashley M; Breman, Amy M; Dagli, Aditi; Bacino, Carlos; Scaglia, Fernando; Zori, Roberto T; Cheung, Sau Wai; Scott, Daryl A; Kang, Sung-Hae Lee

    2009-08-01

    Recurrent interstitial deletion of a region of 8p23.1 flanked by the low copy repeats 8p-OR-REPD and 8p-OR-REPP is associated with a spectrum of anomalies that can include congenital heart malformations and congenital diaphragmatic hernia (CDH). Haploinsufficiency of GATA4 is thought to play a critical role in the development of these birth defects. We describe two individuals and a monozygotic twin pair discordant for anterior CDH all of whom have complex congenital heart defects caused by this recurrent interstitial deletion as demonstrated by array comparative genomic hybridization. To better define the genotype/phenotype relationships associated with alterations of genes on 8p23.1, we review the spectrum of congenital heart and diaphragmatic defects that have been reported in individuals with isolated GATA4 mutations and interstitial, terminal, and complex chromosomal rearrangements involving the 8p23.1 region. Our findings allow us to clearly define the CDH minimal deleted region on chromosome 8p23.1 and suggest that haploinsufficiency of other genes, in addition to GATA4, may play a role in the severe cardiac and diaphragmatic defects associated with 8p23.1 deletions. These findings also underscore the importance of conducting a careful cytogenetic/molecular analysis of the 8p23.1 region in all prenatal and postnatal cases involving congenital defects of the heart and/or diaphragm.

  16. Trisomy 8 syndrome owing to isodicentric 8p chromosomes: regional assignment of a presumptive gene involved in corpus callosum development.

    PubMed Central

    Digilio, M C; Giannotti, A; Floridia, G; Uccellatore, F; Mingarelli, R; Danesino, C; Dallapiccola, B; Zuffardi, O

    1994-01-01

    Two patients with trisomy 8 syndrome owing to an isodicentric 8p;8p chromosome are described. Case 1 had a 46,XX/46,XX,-8,+idic(8)(p23) karyotype while case 2, a male, had the same abnormal karyotype without evidence of mosaicism. In situ hybridisation, performed in case 1, showed that the isochromosome was asymmetrical. Agenesis of the corpus callosum (ACC), which is a feature of trisomy 8 syndrome, was found in both patients. Although ACC is associated with aneuploidies for different chromosomes, a review of published reports indicates that, when associated with chromosome 8, this defect is the result of duplication of a gene located within 8p21-pter. Molecular analysis in one of our patients led us to exclude the distal 23 Mb of 8p from this ACC region. Images PMID:8014974

  17. Whole genomic characterization of Korean porcine G8P[7] reassortant rotaviruses.

    PubMed

    Park, Jun-Gyu; Park, Sang-Ik; Woo, Nam-Il; Kim, Deok-Song; Seo, Ja-Young; Alfajaro, Mia Madel; Kim, Ji-Yun; Soliman, Mahmoud; Baek, Yeong-Bin; Cho, Eun-Hyo; Kwon, Joseph; Choi, Jong-Soon; Kang, Mun-Il; Matthijnssens, Jelle; Cho, Kyoung-Oh

    2016-10-01

    This study analyzed eleven genomic segments of three Korean porcine G8P[7] group A rotavirus (RVA) strains. Phylogenetically, these strains contained two bovine-like and nine porcine-like genomic segments. Eight genes (VP1, VP2, VP6 and NSP1-NSP5) of strains 156-1 and 42-1 and seven genes (VP1, VP2, VP6 and NSP2-NSP5) of strain C-1 clustered closely with porcine and porcine-like animal strains and distantly from typical human Wa-like strains. The VP3-M2 genotype of these strains clustered closely with bovine-like strains, but distantly with typical human DS-1-like strains. These data indicate that multiple reassortments involving porcine and bovine RVA strains in Korea must have occurred. PMID:27393603

  18. An unusual haplotype structure on human chromosome 8p23 derived from the inversion polymorphism.

    PubMed

    Deng, Libin; Zhang, Yuezheng; Kang, Jian; Liu, Tao; Zhao, Hongbin; Gao, Yang; Li, Chaohua; Pan, Hao; Tang, Xiaoli; Wang, Dunmei; Niu, Tianhua; Yang, Huanming; Zeng, Changqing

    2008-10-01

    Chromosomal inversion is an important type of genomic variations involved in both evolution and disease pathogenesis. Here, we describe the refined genetic structure of a 3.8-Mb inversion polymorphism at chromosome 8p23. Using HapMap data of 1,073 SNPs generated from 209 unrelated samples from CEPH-Utah residents with ancestry from northern and western Europe (CEU); Yoruba in Ibadan, Nigeria (YRI); and Asian (ASN) samples, which were comprised of Han Chinese from Beijing, China (CHB) and Japanese from Tokyo, Japan (JPT)-we successfully deduced the inversion orientations of all their 418 haplotypes. In particular, distinct haplotype subgroups were identified based on principal component analysis (PCA). Such genetic substructures were consistent with clustering patterns based on neighbor-joining tree reconstruction, which revealed a total of four haplotype clades across all samples. Metaphase fluorescence in situ hybridization (FISH) in a subset of 10 HapMap samples verified their inversion orientations predicted by PCA or phylogenetic tree reconstruction. Positioning of the outgroup haplotype within one of YRI clades suggested that Human NCBI Build 36-inverted order is most likely the ancestral orientation. Furthermore, the population differentiation test and the relative extended haplotype homozygosity (REHH) analysis in this region discovered multiple selection signals, also in a population-specific manner. A positive selection signal was detected at XKR6 in the ASN population. These results revealed the correlation of inversion polymorphisms to population-specific genetic structures, and various selection patterns as possible mechanisms for the maintenance of a large chromosomal rearrangement at 8p23 region during evolution. In addition, our study also showed that haplotype-based clustering methods, such as PCA, can be applied in scanning for cryptic inversion polymorphisms at a genome-wide scale.

  19. Inside the 8p23.1 duplication syndrome; eight microduplications of likely or uncertain clinical significance.

    PubMed

    Barber, John C K; Rosenfeld, Jill A; Graham, John M; Kramer, Nancy; Lachlan, Katherine L; Bateman, Mark S; Collinson, Morag N; Stadheim, Barbro Fossøy; Turner, Claire L S; Gauthier, Jacqueline N; Reimschisel, Tyler E; Qureshi, Athar M; Dabir, Tabib A; Humphreys, Mervyn W; Marble, Michael; Huang, Taosheng; Beal, Sarah J; Massiah, Joanne; Taylor, Emma-Jane; Wynn, Sarah L

    2015-09-01

    The 8p23.1 duplication syndrome (8p23.1 DS) is a recurrent genomic condition with an estimated prevalence of 1 in 58,000. The core 3.68 Mb duplication contains 32 genes of which five are currently candidates for the phenotypic features. Here we describe four patients and five families with eight microduplications of 8p23.1 ranging from 187 to 1082 kb in size and one atypical duplication of 4 Mb. These indicate that a minimal region of overlap (MRO) in medial 8p23.1 can give rise to features of 8p23.1 DS including developmental delay, dysmorphism, macrocephaly and otitis media, but not congenital heart disease (CHD). This MRO spans 776 kb (chr8:10,167,881-10,943,836 hg19) and contains SOX7 and seven of the other 32 core 8p23.1 DS genes. In centromeric 8p23.1, microduplications including GATA4 can give rise to non-syndromic CHD but the clinical significance of two smaller centromeric microduplications without GATA4 was uncertain due to severe neurological profiles not usually found in 8p23.1 DS. The clinical significance of three further 8p23.1 microduplications was uncertain due to additional genetic factors without which the probands might not have come to medical attention. Variable expressivity was indicated by the almost entirely unaffected parents in all five families and the mildly affected sibling in one. Intronic interruptions of six genes by microduplication breakpoint intervals had no apparent additional clinical consequences. Our results suggest that 8p23.1 DS is an oligogenetic condition largely caused by the duplication and interactions of the SOX7 and GATA4 transcription factors.

  20. Pre-impact monitoring of Comet 9P/Tempel 1, the Deep Impact target

    NASA Astrophysics Data System (ADS)

    Lara, L. M.; Boehnhardt, H.; Gredel, R.; Gutiérrez, P. J.; Ortiz, J. L.; Rodrigo, R.; Vidal-Nuñez, M. J.

    2006-01-01

    Comet 9P/Tempel 1, the target of the Deep Impact Mission, has been monitored for 6 months aiming at its characterization before the impact experiment. During this period of time, the coma has gone through a slow morphological evolution from a wide structure in the south-western quadrant in mid-February to a porcupine pattern in mid-April and up to seven features identified in June. In addition to this evolution, an arclet in the western coma hemisphere was detected on June 14, related to an outburst event. Interpretation of these features and their evolution seems to indicate the presence of at least 3 or 4 very active regions on the nucleus, consistent with the rotation axis being oriented close to previous solutions found by Belton et al. (2005), or close to the angular momentum vector of the orbital motion of the comet. The value of Afρ varies with heliocentric distance as r_h-6.71; slightly enhanced Afρ (above the r_h-6.71 curve) was observed from mid-February until the end of March, when fan-shaped structures appeared in the coma for the first time. Somewhere between mid-April to mid-May (i.e. 80 to 60 days before perihelion), the comet peaked in activity. In terms of gas production rates, CN, C2 and C3 have been obtained at rh ˜ 1.7, 1.60 and 1.51 AU, being slightly below those derived from previous passages. Abundance ratios of these species indicate that comet 9P/Tempel 1 is classified as typical in terms of C2 abundance. The surface brightness profiles of the continuum, either azimuthally averaged profiles from the broadband images or in north-south direction from the long-slit spectra can be well fit with -1.9 ≤ m ≤ -1.14 in log B - log ρ representation. Steeper slopes are obtained at larger rh which might be related to variable dust size distribution with distance from the nucleus due to the radiation pressure dynamics and/or physical processing of the dust grains (sublimation, fragmentation). Normalized color of the dust inside the coma in the

  1. Mosaic tetrasomy 9p case with the phenotype mimicking Klinefelter syndrome and hyporesponse of gonadotropin-stimulated testosterone production.

    PubMed

    Ogino, Wakako; Takeshima, Yasuhiro; Nishiyama, Atsushi; Yagi, Mariko; Oka, Nobutoshi; Matsuo, Masafumi

    2007-01-01

    Tetrasomy 9p is a rare clinical syndrome and about 30% of known cases exhibit chromosome mosaicism. The cases with tetrasomy 9p mosaicism have been reported to show the various phenotypes. On the other hand, Klinefelter syndrome is well recognized chromosomal abnormality caused by an additional X chromosome in males (47,XXY), and the characteristic clinical findings include tall stature, immaturity of external genitalia, testicular dysfunction. Here, we report a 10-year-old male with tetrasomy of 9p mosaicism, whose phenotypic feature is mimicking Klinefelter syndrome. He was referred to our hospital for inconspicuous penis. He showed tall height (+2.5 SD). Endocrinological examination revealed the poor testosterone response to human chorionic gonadotropin administration, which indicated the testicular hypofunction, whereas MRI revealed concealed penis as a cause of inconspicuous penis. Because of the phenotype mimicking Klinefelter syndrome, karyotype of his blood lymphocytes was analyzed, and an additional marker chromosome was detected in 6% of the investigated metaphases. Fluorescence in situ hybridization analysis revealed that the marker chromosome was an isochromosome 9p, which resulted in tetrasomy 9p. Chromosome analysis of buccal smear also showed mosaicism for two karyotypes: 5% of cells had the isochromosome of 9p, and the other cells showed normal. This case is the second case with tetrasomy 9p mosaicism mimicking Klinefelter syndrome phenotype in the world. Our case, together with previously reported cases with the same association, indicates the possibility of testicular hypofunction and urogenital anomalies induced by overexpression of some genes on chromosome 9p. PMID:17932453

  2. [Information behavior of 7 STR loci on chromosome 9p in gene scanning].

    PubMed

    Zeng, Zhao-Yang; Xiong, Wei; Xiong, Fang; Shen, Shou-Rong; Li, Xiao-Ling; Li, Wei-Fang; Wang, Rong; Xiao, Bing-Yi; Fan, Song-Qing; Huang, He; Zhou, Ming; Li, Gui-Yuan

    2003-09-01

    To get genotype and allele frequency distributions of seven short tandem repeat (STR) loci of chromosome 9p,D9S288,D9S157,D9S1748,D9S171,D9S161,D9S1817 and D9S1805 in Chinese Han population in Hunan area,blood samples were collected from the random Han individual in Hunan and the whole genomic DNA was extracted.STR loci were amplified by multiplex-PCR technique and genotyped by ABI 377 sequencer.Seventy-five alleles were detected,with frequencies ranging from 0.002 to 0.800,and constituted 243 genotypes. All the seven loci met Hardy-Weinberg equilibrium. The statistical analysis of seven STR loci showed H(heterozygosity) ranging from 0.347 to 0.844,DP(discrimination power) ranging from 0.346 to 0.841,PPE(probabilities of paternity exclusion) ranging from 0.308 to 0.738 and PIC(polymorphic information content) ranging from 0.328 to 0.822. The result indicated that there was a significant difference between Han ethnic group and the white and the black.

  3. The Deep Impact crater on 9P/Tempel-1 from Stardust-NExT

    NASA Astrophysics Data System (ADS)

    Schultz, Peter H.; Hermalyn, Brendan; Veverka, Joe

    2013-02-01

    The Stardust-NExT (SdN) mission returned to Comet 9P/Tempel-1 and viewed the site of the Deep Impact (DI) collision just over one comet year later. Comparisons between pre-impact images from the ITS camera on the DI probe and SdN images reveal a 50 m-diameter crater surrounded by a low rim about 180 m in diameter. The removal of a small mound uprange (but offset from the trajectory) from the impact site can be related to changes in the evolution of ejecta. A narrow (6°) gap in the ejecta curtain downrange indicates that a ridge extending from the impact-facing scarp downrange interrupted the final stages of cratering in one small region. Together, these observations indicate that the DI excavation crater diameter was about 200 m (±20 m), a value consistent with the ejected mass derived from Earth- and space-based observations with the assumption that this mass represents only 10-20% of the total ejected mass. As a result, the DI crater visible today is consistent with either a larger transient crater, which collapsed, or a central crater of a nested crater resembling an inverted sombrero. The latter alternative would be expected from a layered target: a loose particulate surface about 1-2 m deep over a slightly more competent substrate.

  4. Deep Impact: Working Properties for the Target Nucleus Comet 9P/Tempel 1

    NASA Astrophysics Data System (ADS)

    Belton, Michael J. S.; Meech, Karen J.; A'Hearn, Michael F.; Groussin, Olivier; McFadden, Lucy; Lisse, Carey; Fernández, Yanga R.; Pittichová, Jana; Hsieh, Henry; Kissel, Jochen; Klaasen, Kenneth; Lamy, Philippe; Prialnik, Dina; Sunshine, Jessica; Thomas, Peter; Toth, Imre

    2005-03-01

    In 1998, Comet 9P/Tempel 1 was chosen as the target of the Deep Impact mission (A’Hearn, M. F., Belton, M. J. S., and Delamere, A., Space Sci. Rev., 2005) even though very little was known about its physical properties. Efforts were immediately begun to improve this situation by the Deep Impact Science Team leading to the founding of a worldwide observing campaign (Meech et al., Space Sci. Rev., 2005a). This campaign has already produced a great deal of information on the global properties of the comet’s nucleus (summarized in Table I) that is vital to the planning and the assessment of the chances of success at the impact and encounter. Since the mission was begun the successful encounters of the Deep Space 1 spacecraft at Comet 19P/Borrelly and the Stardust spacecraft at Comet 81P/Wild 2 have occurred yielding new information on the state of the nuclei of these two comets. This information, together with earlier results on the nucleus of comet 1P/Halley from the European Space Agency’s Giotto, the Soviet Vega mission, and various ground-based observational and theoretical studies, is used as a basis for conjectures on the morphological, geological, mechanical, and compositional properties of the surface and subsurface that Deep Impact may find at 9P/Tempel 1. We adopt the following working values (circa December 2004) for the nucleus parameters of prime importance to Deep Impact as follows: mean effective radius = 3.25± 0.2 km, shape irregular triaxial ellipsoid with a/b = 3.2± 0.4 and overall dimensions of ˜14.4 × 4.4 × 4.4 km, principal axis rotation with period = 41.85± 0.1 hr, pole directions (RA, Dec, J2000) = 46± 10, 73± 10 deg (Pole 1) or 287± 14, 16.5± 10 deg (Pole 2) (the two poles are photometrically, but not geometrically, equivalent), Kron-Cousins (V-R) color = 0.56± 0.02, V-band geometric albedo = 0.04± 0.01, R-band geometric albedo = 0.05± 0.01, R-band H(1,1,0) = 14.441± 0.067, and mass ˜7×1013 kg assuming a bulk density of 500

  5. Targeted deletion of the 9p21 noncoding coronary artery disease risk interval in mice

    SciTech Connect

    Visel, Axel; Zhu, Yiwen; May, Dalit; Afzal, Veena; Gong, Elaine; Attanasio, Catia; Blow, Matthew J.; Cohen, Jonathan C.; Rubin, Edward M.; Pennacchio, Len A.

    2010-01-01

    Sequence polymorphisms in a 58kb interval on chromosome 9p21 confer a markedly increased risk for coronary artery disease (CAD), the leading cause of death worldwide 1,2. The variants have a substantial impact on the epidemiology of CAD and other life?threatening vascular conditions since nearly a quarter of Caucasians are homozygous for risk alleles. However, the risk interval is devoid of protein?coding genes and the mechanism linking the region to CAD risk has remained enigmatic. Here we show that deletion of the orthologous 70kb noncoding interval on mouse chromosome 4 affects cardiac expression of neighboring genes, as well as proliferation properties of vascular cells. Chr4delta70kb/delta70kb mice are viable, but show increased mortality both during development and as adults. Cardiac expression of two genes near the noncoding interval, Cdkn2a and Cdkn2b, is severely reduced in chr4delta70kb/delta70kb mice, indicating that distant-acting gene regulatory functions are located in the noncoding CAD risk interval. Allelespecific expression of Cdkn2b transcripts in heterozygous mice revealed that the deletion affects expression through a cis-acting mechanism. Primary cultures of chr4delta70kb/delta70kb aortic smooth muscle cells exhibited excessive proliferation and diminished senescence, a cellular phenotype consistent with accelerated CAD pathogenesis. Taken together, our results provide direct evidence that the CAD risk interval plays a pivotal role in regulation of cardiac Cdkn2a/b expression and suggest that this region affects CAD progression by altering the dynamics of vascular cell proliferation.

  6. Hubble Space Telescope Observations of the Nucleus of Comet 8P/Tuttle

    NASA Astrophysics Data System (ADS)

    Lamy, Philippe L.; Toth, I.; Jorda, L.; Weaver, H. A.; Groussin, O.; A'Hearn, M. F.

    2008-09-01

    We unambiguously detected the nucleus of comet 8P/Tuttle, a nearly-isotropic comet (NIC) in a 13.5 yr orbital period, during its recent close (0.25 AU) Earth encounter with the Planetary Camera 2 of the Hubble Space Telescope (HST). The observations were performed from December 10.0 to 11.2, 2007, and consisted in 12 visits extending over a 28-hour period. At the mid-point of the observing window, the comet was 1.25 AU from the Sun , 0.48 AU from the Earth and at a phase angle of 46.6 deg. During each visit corresponding to an HST orbit, typically twelve images were obtained through five broadband filters (UBVRI). The light curve exhibits a complex shape best modeled by a bilobate body as evidenced by the radar observations of Harmon et al. (2008). We determined a synodic rotational period of 11.4 hr. Assuming the same albedo of 0.04 for the two lobes, we found respective radii of 1.2 km and 2.8 km. During the HST observations, the nucleus was at an aspect angle (between spin axis and line of sight) of 65 deg.

  7. The 8p23 inversion polymorphism determines local recombination heterogeneity across human populations.

    PubMed

    Alves, Joao M; Chikhi, Lounès; Amorim, António; Lopes, Alexandra M

    2014-04-01

    For decades, chromosomal inversions have been regarded as fascinating evolutionary elements as they are expected to suppress recombination between chromosomes with opposite orientations, leading to the accumulation of genetic differences between the two configurations over time. Here, making use of publicly available population genotype data for the largest polymorphic inversion in the human genome (8p23-inv), we assessed whether this inhibitory effect of inversion rearrangements led to significant differences in the recombination landscape of two homologous DNA segments, with opposite orientation. Our analysis revealed that the accumulation of genetic differentiation is positively correlated with the variation in recombination profiles. The observed recombination dissimilarity between inversion types is consistent across all populations analyzed and surpasses the effects of geographic structure, suggesting that both structures (orientations) have been evolving independently over an extended period of time, despite being subjected to the very same demographic history. Aside this mainly independent evolution, we also identified a short segment (350 kb, <10% of the whole inversion) in the central region of the inversion where the genetic divergence between the two structural haplotypes is diminished. Although it is difficult to demonstrate it, this could be due to gene flow (possibly via double-crossing over events), which is consistent with the higher recombination rates surrounding this segment. This study demonstrates for the first time that chromosomal inversions influence the recombination landscape at a fine-scale and highlights the role of these rearrangements as drivers of genome evolution.

  8. Variation at 3p24.1 and 6q23.3 influences the risk of Hodgkin’s Lymphoma

    PubMed Central

    Frampton, Matthew; da Silva Filho, Miguel Inacio; Broderick, Peter; Thomsen, Hauke; Försti, Asta; Vijayakrishnan, Jayaram; Cooke, Rosie; Enciso-Mora, Victor; Hoffmann, Per; Nöthen, Markus M; Lloyd, Amy; Holroyd, Amy; Eisele, Lewin; Jöckel, Karl-Heinz; Ponader, Sabine; von Strandmann, Elke Pogge; Lightfoot, Tracy; Roman, Eve; Lake, Annette; Montgomery, Dorothy; Jarrett, Ruth F; Swerdlow, Anthony J; Engert, Andreas; Hemminki, Kari; Houlston, Richard S

    2016-01-01

    In addition to HLA, recent genome-wide association studies (GWASs) of Hodgkin’s Lymphoma (HL) have identified susceptibility loci for HL at 2p16.1, 8q24.21 and 10p14. In this study, we perform a GWAS meta-analysis with published GWAS (totaling 1,465 cases and 6,417 controls of European background), and follow up the most significant association signals in 2,024 cases and 1,853 controls. A combined analysis identifies new HL susceptibility loci mapping to 3p24.1 (rs3806624; P=1.14×10-12, odds ratio [OR]=1.26) and 6q23.3 (rs7745098; P=3.42×10-9, OR=1.21). rs3806624 localizes 5’ to the EOMES (eomesodermin) gene within a p53 response element affecting p53 binding. rs7745098 maps intergenic to HBS1L and MYB, a region previously associated with hematopoiesis. These findings provide further insight into the genetic and biological basis of inherited susceptibility to HL. PMID:24149102

  9. Evaluation of a newly discovered breast cancer susceptibility locus at 6q25.1 in Iranian Azari-Turkish women

    PubMed Central

    Garehdaghchi, Ziba; Derakhshan, Siam Mansoori

    2016-01-01

    Aim of the study A recent breast cancer genome-wide association study (GWAS) identified single-nucleotide polymorphism (SNP) rs2046210 on 6q25.1 showing a strong association with breast cancer risk. Numerous association studies have been conducted to investigate the relationship between this polymorphism and breast cancer risk in various populations. There have been conflicting reports about the association of this locus with breast cancer risk in different ethnic groups. For the first time, this study has investigated the association of rs2046210 SNP with breast cancer risk in Iranian Azari-Turkish women in North West Iran. Material and methods In this study 192 breast cancer subjects and 186 healthy controls were genotyped using Taqman SNP genotyping assays for different SNP rs2046210 alleles. Results No significant association between rs2046210 SNP alleles and the risk of breast cancer was detected in Iranian Azari-Turkish women. Conclusions The data suggests that rs2046210SNP does not play a role in the aetiology of breast cancer in the Iranian Azari-Turkish population, and it indicates possible genetic differences for breast cancer between different population ancestries. Our result is an important contribution to the literature about genetic susceptibility for breast cancer in Asian populations. Additional studies are required to confirm our findings. PMID:27688728

  10. Assignment of human elongation factor 1{alpha} genes: EEF1A maps to chromosome 6q14 and EEF1A2 to 20q13.3

    SciTech Connect

    Lund, A.; Clark, B.; Knudsen, S.M.

    1996-09-01

    The human elongation factor 1 {alpha} gene family consists of at least 2 actively transcribed genes, EEF1A and EEF1A2, and more than 18 homologous loci. EEF1A2 is expressed ubiquitously, and both of them can function in translation. An EEF1A cDNA probe has previously been shown to cross-hybridize with several human chromosomes, but the location of the functional gene has not been established. We have mapped the functional EEF1A gene to 6q14 by combined fluorescence in situ hybridization (FISH) and PCR analysis of a somatic cell hybrid panel and mapped EEF1A2 to 20q13.3 by FISH. In addition, the 11 strongest cross-hybridizing loci (EEF1AL2-EEF1AL13) were mapped by FISH to 12p12, 9q34, 7p15-p21, 19q13, 3q26-q27, 7q33-q35, 1p13-p22, 2q12-q14, 5p12-q11, 1q31-q32, and Xq21. 17 refs., 1 fig., 1 tab.

  11. Glucose derepression of gluconeogenic enzymes in Saccharomyces cerevisiae correlates with phosphorylation of the gene activator Cat8p.

    PubMed Central

    Randez-Gil, F; Bojunga, N; Proft, M; Entian, K D

    1997-01-01

    The Cat8p zinc cluster protein is essential for growth of Saccharomyces cerevisiae with nonfermentable carbon sources. Expression of the CAT8 gene is subject to glucose repression mainly caused by Mig1p. Unexpectedly, the deletion of the Mig1p-binding motif within the CAT8 promoter did not increase CAT8 transcription; moreover, it resulted in a loss of CAT8 promoter activation. Insertion experiments with a promoter test plasmid confirmed that this regulatory 20-bp element influences glucose repression and derepression as well. This finding suggests an upstream activating function of this promoter region, which is Mig1p independent, as delta mig1 mutants are still able to derepress the CAT8 promoter. No other putative binding sites such as a Hap2/3/4/5p site and an Abf1p consensus site were functional with respect to glucose-regulated CAT8 expression. Fusions of Cat8p with the Gal4p DNA-binding domain mediated transcriptional activation. This activation capacity was still carbon source regulated and depended on the Cat1p (Snf1p) protein kinase, which indicated that Cat8p needs posttranslational modification to reveal its gene-activating function. Indeed, Western blot analysis on sodium dodecyl sulfate-gels revealed a single band (Cat8pI) with crude extracts from glucose-grown cells, whereas three bands (Cat8pI, -II, and -III) were identified in derepressed cells. Derepression-specific Cat8pII and -III resulted from differential phosphorylation, as shown by phosphatase treatment. Only the most extensively phosphorylated modification (Cat8pIII) depended on the Cat1p (Snf1p) kinase, indicating that another protein kinase is responsible for modification form Cat8pII. The occurrence of Cat8pIII was strongly correlated with the derepression of gluconeogenic enzymes (phosphoenolpyruvate carboxykinase and fructose-1,6-bisphosphatase) and gluconeogenic PCK1 mRNA. Furthermore, glucose triggered the dephosphorylation of Cat8pIII, but this did not depend on the Glc7p (Cid1p

  12. Allelic loss of 9p21.3 is a prognostic factor in 1p/19q codeleted anaplastic gliomas

    PubMed Central

    Alentorn, Agustí; Dehais, Caroline; Ducray, François; Carpentier, Catherine; Mokhtari, Karima; Figarella-Branger, Dominique; Chinot, Olivier; Cohen-Moyal, Elisabeth; Ramirez, Carole; Loiseau, Hugues; Elouahdani-Hamdi, Selma; Beauchesne, Patrick; Langlois, Olivier; Desenclos, Christine; Guillamo, Jean-Sébastien; Dam-Hieu, Phong; Ghiringhelli, François; Colin, Philippe; Godard, Joel; Parker, Fabrice; Dhermain, Frédéric; Carpentier, Antoine F.; Frenel, Jean-Sebastien; Menei, Philippe; Bauchet, Luc; Faillot, Thierry; Fesneau, Mélanie; Fontaine, Denys; Motuo-Fotso, Marie-Jeannette; Vauleon, Elodie; Gaultier, Claude; Le Guerinel, Caroline; Gueye, Edouard-Marcel; Noel, Georges; Desse, Nicolas; Durando, Xavier; Barrascout, Eduardo; Wager, Michel; Ricard, Damien; Carpiuc, Ioana; Delattre, Jean-Yves

    2015-01-01

    Objectives: We aimed to study the potential clinical relevance of 9p allelic loss, with or without copy number variation, in 1p/19q codeleted anaplastic oligodendroglial tumors (AOTs). Methods: This study enrolled 216 patients with 1p/19q codeleted AOT. The prognostic value of 9p allelic loss was investigated using a French nation-wide prospective registry, POLA (prise en charge des tumeurs oligodendrogliales anaplasiques) and high-density single nucleotide polymorphism arrays. We validated our results using the Repository of Molecular Brain Neoplasia Data (REMBRANDT) dataset. Results: The minimal common region of allelic loss in chromosome arm 9p was 9p21.3. Allelic loss of 9p21.3, detected in 41.7% of tumors, was associated with shorter progression-free and overall survival rates in univariate (p = 0.008 and p < 0.001, respectively) and multivariate analyses (p = 0.009 and p = 0.009, respectively). This finding was validated in the REMBRANDT dataset in univariate and multivariate analysis (p = 0.01 and p = 0.01, respectively). Conclusion: Our study highlights a novel potential prognostic biomarker in 1p/19q codeleted AOT. Further prospective studies are warranted to investigate our finding. PMID:26385879

  13. The GPI Transamidase Complex of Saccharomyces cerevisiae Contains Gaa1p, Gpi8p, and Gpi16p

    PubMed Central

    Fraering, Patrick; Imhof, Isabella; Meyer, Urs; Strub, Jean-Marc; van Dorsselaer, Alain; Vionnet, Christine; Conzelmann, Andreas

    2001-01-01

    Gpi8p and Gaa1p are essential components of the GPI transamidase that adds glycosylphosphatidylinositols (GPIs) to newly synthesized proteins. After solubilization in 1.5% digitonin and separation by blue native PAGE, Gpi8p is found in 430–650-kDa protein complexes. These complexes can be affinity purified and are shown to consist of Gaa1p, Gpi8p, and Gpi16p (YHR188c). Gpi16p is an essential N-glycosylated transmembrane glycoprotein. Its bulk resides on the lumenal side of the ER, and it has a single C-terminal transmembrane domain and a small C-terminal, cytosolic extension with an ER retrieval motif. Depletion of Gpi16p results in the accumulation of the complete GPI lipid CP2 and of unprocessed GPI precursor proteins. Gpi8p and Gpi16p are unstable if either of them is removed by depletion. Similarly, when Gpi8p is overexpressed, it largely remains outside the 430–650-kDa transamidase complex and is unstable. Overexpression of Gpi8p cannot compensate for the lack of Gpi16p. Homologues of Gpi16p are found in all eucaryotes. The transamidase complex is not associated with the Sec61p complex and oligosaccharyltransferase complex required for ER insertion and N-glycosylation of GPI proteins, respectively. When GPI precursor proteins or GPI lipids are depleted, the transamidase complex remains intact. PMID:11598210

  14. Monovalent rotavirus vaccine provides protection against an emerging fully heterotypic G9P[4] rotavirus strain in Mexico.

    PubMed

    Yen, Catherine; Figueroa, Jesùs Reyna; Uribe, Edgar Sánchez; Carmen-Hernández, Luz Del; Tate, Jacqueline E; Parashar, Umesh D; Patel, Manish M; Richardson López-Collado, Vesta

    2011-09-01

    After the introduction of monovalent rotavirus vaccine (RV1) in Mexico in 2006-2007, diarrhea mortality and morbidity declined substantially among Mexican children under 5 years of age. In January 2010, surveillance identified the emergence of a novel G9P[4] rotavirus strain nationwide. We conducted a case-control study to assess the field effectiveness of RV1 against severe rotavirus gastroenteritis caused by this unusual strain and to determine whether the G9P[4] emergence was related to vaccine failure or failure to vaccinate. RV1 was 94% effective (95% confidence interval, 16%-100%) against G9P[4] rotavirus-related hospitalization, indicating that its emergence was likely unrelated to vaccine pressure.

  15. CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

    SciTech Connect

    Svensson, Per-Arne; Wahlstrand, Björn; Olsson, Maja; Froguel, Philippe; Falchi, Mario; Bergman, Richard N.; McTernan, Philip G.; Hedner, Thomas; Carlsson, Lena M.S.; Jacobson, Peter

    2014-04-18

    Highlights: • The tumor suppressor gene CDKN2B is highly expressed in human adipose tissue. • Risk alleles at the 9p21 locus modify CDKN2B expression in a BMI-dependent fashion. • There is an inverse relationship between expression of CDKN2B and adipogenic genes. • CDKN2B expression influences to postprandial triacylglycerol clearance. • CDKN2B expression in adipose tissue is linked to markers of hepatic steatosis. - Abstract: Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.

  16. Mapping of a macular drusen susceptibility locus in rhesus macaques to the homologue of human chromosome 6q14-15.

    PubMed

    Singh, Krishna K; Ristau, Steven; Dawson, William W; Krawczak, Michael; Schmidtke, Jörg

    2005-10-01

    Rhesus macaques (Macaca mulatta) are a natural model for retinal drusen formation. The present study aimed at clarifying whether chromosomal regions homologous to candidate genes for drusen formation and progression in humans are also associated with a drusen phenotype in rhesus macaques. Some 42 genetic markers from seven chromosomal regions implicated in macular degeneration syndromes in humans were tested for whether they identified homologous, polymorphic sequences in rhesus DNA. This was found to be the case for seven markers, all of which were subsequently screened for the presence of potentially disease-predisposing alleles in 52 randomly chosen adult animals from the Cayo Santiago population of rhesus macaques (Caribbean Primate Research Center, PR, USA). The high drusen prevalence expected in the Cayo Santiago colony was confirmed in our sample in that 38 animals were found to have drusen (73%). Logistic regression analysis revealed that some alleles of the rhesus homologue of anonymous human marker D6S1036 were consistently over-represented among affected animals. Of two candidate genes located in the respective region, allelic variation in one (IMPG1) showed strong association with drusen formation. We conclude that one or more genes located at the rhesus homologue of human 6q14-15 are likely to play a role in retinal drusen formation, a finding that represents a first step towards the identification of genetic factors implicated in macular drusen formation in rhesus macaques. This is an important tool for the separation of genetic and environmental factors which must occur before satisfactory management methods can be developed.

  17. Fusion of the TBL1XR1 and HMGA1 genes in splenic hemangioma with t(3;6)(q26;p21).

    PubMed

    Panagopoulos, Ioannis; Gorunova, Ludmila; Bjerkehagen, Bodil; Lobmaier, Ingvild; Heim, Sverre

    2016-03-01

    RNA-sequencing of a splenic hemangioma with the karyotype 45~47,XX,t(3;6)(q26;p21) showed that this translocation generated a chimeric TBL1XR1-HMGA1 gene. This is the first time that this tumor has been subjected to genetic analysis, but the finding of an acquired clonal chromosome abnormality in cells cultured from the lesion and the presence of the TBL1XR1-HMGA1 fusion in them strongly favor the conclusion that splenic hemangiomas are of a neoplastic nature. Genomic PCR confirmed the presence of the TBL1XR1-HMGA1 fusion gene, and RT-PCR together with Sanger sequencing verified the presence of the fusion transcripts. The molecular consequences of the t(3;6) would be substantial. The cells carrying the translocation would retain only one functional copy of the wild-type TBL1XR1 gene while the other, rearranged allele could produce a putative truncated form of TBL1XR1 protein containing the LiSH and F-box-like domains. In the TBL1XR1-HMGA1 fusion transcript, furthermore, untranslated exons of HMGA1 are replaced by the first 5 exons of the TBL1XR1 gene. The result is that the entire coding region of HMGA1 comes under the control of the TBL1XR1 promoter, bringing about dysregulation of HMGA1. This is reminiscent of similar pathogenetic mechanisms involving high mobility genes in benign connective tissue tumors such as lipomas and leiomyomas.

  18. Responses of the Q6/Q6s ATD Positioned in Booster Seats in the Far-Side Seat Location of Side Impact Passenger Car and Sled Tests.

    PubMed

    Tylko, Suzanne; Bohman, Katarina; Bussières, Alain

    2015-11-01

    Passenger car side impact crash tests and sled tests were conducted to investigate the influence of booster seats, near-side occupant characteristics and vehicle interiors on the responses of the Q6/Q6s child ATD positioned in the rear, far-side seating location. Data from nine side impact sled tests simulating a EuroNCAP AEMD barrier test were analyzed with data obtained from 44 side impact crash tests. The crash tests included: FMVSS 214 and IIHS MDB, moving car-to-stationary car and moving car-to-moving car. A Q6 or prototype Q6s ATD was seated on the far-side, using a variety of low and high back booster seats. Head and chest responses were recorded and ATD motions were tracked with high-speed videos. The vehicle lateral accelerations resulting from MDB tests were characterized by a much earlier and more rapid rise to peak than in tests where the bullet was another car. The near-side seating position was occupied by a Hybrid III 10-year-old ATD in the sled tests, and a rear or front facing child restraint or a 5th percentile side impact ATD in the crash tests. Head impacts occurred more frequently in vehicles where a forward facing child restraint was present behind the driver seat for both the low and high back booster seats. Pretensioners were found to reduce lateral head displacements in all sled test configurations but the greatest reduction in lateral excursion was obtained with a high back booster seat secured with LATCH and tested in combination with pretensioners.

  19. Responses of the Q6/Q6s ATD Positioned in Booster Seats in the Far-Side Seat Location of Side Impact Passenger Car and Sled Tests.

    PubMed

    Tylko, Suzanne; Bohman, Katarina; Bussières, Alain

    2015-11-01

    Passenger car side impact crash tests and sled tests were conducted to investigate the influence of booster seats, near-side occupant characteristics and vehicle interiors on the responses of the Q6/Q6s child ATD positioned in the rear, far-side seating location. Data from nine side impact sled tests simulating a EuroNCAP AEMD barrier test were analyzed with data obtained from 44 side impact crash tests. The crash tests included: FMVSS 214 and IIHS MDB, moving car-to-stationary car and moving car-to-moving car. A Q6 or prototype Q6s ATD was seated on the far-side, using a variety of low and high back booster seats. Head and chest responses were recorded and ATD motions were tracked with high-speed videos. The vehicle lateral accelerations resulting from MDB tests were characterized by a much earlier and more rapid rise to peak than in tests where the bullet was another car. The near-side seating position was occupied by a Hybrid III 10-year-old ATD in the sled tests, and a rear or front facing child restraint or a 5th percentile side impact ATD in the crash tests. Head impacts occurred more frequently in vehicles where a forward facing child restraint was present behind the driver seat for both the low and high back booster seats. Pretensioners were found to reduce lateral head displacements in all sled test configurations but the greatest reduction in lateral excursion was obtained with a high back booster seat secured with LATCH and tested in combination with pretensioners. PMID:26660749

  20. Intravascular large B-cell lymphoma manifesting as cholecystitis: report of an Asian variant showing gain of chromosome 18 with concurrent deletion of chromosome 6q.

    PubMed

    Tajima, Shogo; Waki, Michihiko; Yamazaki, Hiroyuki; Nagata, Yasuyuki; Fukano, Hana; Hossen, Md Amir; Hoshi, Shoji; Takeuchi, Takahiro

    2014-01-01

    Intravascular large B-cell lymphoma (IVLBCL), which involves the lumen of small vessels, is a rare variant of extranodal diffuse large B-cell lymphomas. Herein, we present a case of IVLBCL manifesting as cholecystitis in a 77-year-old Japanese man. He presented with fever, fatigue, and weight loss. Physical examination revealed tenderness of the right upper quadrant. The white blood cell count and C-reactive protein levels were elevated. Computed tomography revealed gallbladder thickening and pericholecystic fluid collection; these observations were consistent with the diagnosis of cholecystitis. Serum soluble interleukin-2 receptor levels were highly elevated, and gallium scintigraphy revealed an abnormal accumulation in the spleen, implying lymphoma. Consequently, G-banding analysis of the patient's bone marrow aspirates revealed the presence of different abnormal clones, including those with gain of chromosome 18 and deletion of chromosome 6q. As cholecystectomy was necessary, a concurrent splenectomy was performed to diagnose the disease definitively. Histopathologically, atypical large lymphoid cells were observed to be localized in the vasculature in both the spleen and gallbladder; the atypical cells expressed high levels of CD20, CD5, and CD10, immunohistochemically. These findings were consistent with IVLBCL. The patient underwent post-operative treatment with rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone. However, a pancreatic fistula developed during chemotherapy, causing left pleural effusion and peritoneal effusion; the patient developed sepsis from multidrug-resistant microorganisms, and subsequently died of multi-organ failure 6 months after the diagnosis. No obvious recurrence of the tumor was found during autopsy. We discuss the characteristic karyotype and immunohistochemical status observed in this case. PMID:25550870

  1. Fusion of the TBL1XR1 and HMGA1 genes in splenic hemangioma with t(3;6)(q26;p21)

    PubMed Central

    PANAGOPOULOS, IOANNIS; GORUNOVA, LUDMILA; BJERKEHAGEN, BODIL; LOBMAIER, INGVILD; HEIM, SVERRE

    2016-01-01

    RNA-sequencing of a splenic hemangioma with the karyotype 45~47,XX,t(3;6)(q26;p21) showed that this translocation generated a chimeric TBL1XR1-HMGA1 gene. This is the first time that this tumor has been subjected to genetic analysis, but the finding of an acquired clonal chromosome abnormality in cells cultured from the lesion and the presence of the TBL1XR1-HMGA1 fusion in them strongly favor the conclusion that splenic hemangiomas are of a neoplastic nature. Genomic PCR confirmed the presence of the TBL1XR1-HMGA1 fusion gene, and RT-PCR together with Sanger sequencing verified the presence of the fusion transcripts. The molecular consequences of the t(3;6) would be substantial. The cells carrying the translocation would retain only one functional copy of the wild-type TBL1XR1 gene while the other, rearranged allele could produce a putative truncated form of TBL1XR1 protein containing the LiSH and F-box-like domains. In the TBL1XR1-HMGA1 fusion transcript, furthermore, untranslated exons of HMGA1 are replaced by the first 5 exons of the TBL1XR1 gene. The result is that the entire coding region of HMGA1 comes under the control of the TBL1XR1 promoter, bringing about dysregulation of HMGA1. This is reminiscent of similar pathogenetic mechanisms involving high mobility genes in benign connective tissue tumors such as lipomas and leiomyomas. PMID:26708416

  2. Stardust-NExT, Deep Impact, and the Accelerating Spin of 9P/Tempel 1

    NASA Technical Reports Server (NTRS)

    Belton, Michael J. S.; Meech, Karen J.; Chesley, Steven; Pittichova, Jana; Carcich, Brian; Drahus, Michal; Harris, Alan; Gillam, Stephen; Veverka, Joseph; Mastrodemos, Nicholas; Owen, William; A'Hearn, Michael F.; Bagnulo, S.; Bai, J.; Barrera L.; Bastien, Fabienne; Bauer, James M.; Bedient, J.; Bhatt, B. C.; Boehnhardt, Hermann; Brosch, N.; Buie, Marc; Candia, Pablo; Chen, W.-P.; Chiang, P.

    2011-01-01

    The evolution of the spin rate of Comet 9P/Tempel 1 through two perihelion passages (in 2000 and 2005) is determined from 1922 Earth-based observations taken over a period of 13 year as part of a World-Wide observing campaign and from 2888 observations taken over a period of 50 days from the Deep Impact spacecraft. We determine the following sidereal spin rates (periods): 209.023 +/- 0.025deg/dy (41.335 0.005 h) prior to the 2000 perihelion passage, 210.448 +/- 0.016deg/dy (41.055 +/- 0.003 h) for the interval between the 2000 and 2005 perihelion passages, 211.856 +/- 0.030deg/dy (40.783 +/- 0.006 h) from Deep Impact photometry just prior to the 2005 perihelion passage, and 211.625 +/- 0.012deg/dy (40.827 +/- 0.002 h) in the interval 2006-2010 following the 2005 perihelion passage. The period decreased by 16.8 +/- 0.3 min during the 2000 passage and by 13.7 +/- 0.2 min during the 2005 passage suggesting a secular decrease in the net torque. The change in spin rate is asymmetric with respect to perihelion with the maximum net torque being applied on approach to perihelion. The Deep Impact data alone show that the spin rate was increasing at a rate of 0.024 +/- 0.003deg/dy/dy at JD2453530.60510 (i.e., 25.134 dy before impact), which provides independent confirmation of the change seen in the Earth-based observations. The rotational phase of the nucleus at times before and after each perihelion and at the Deep Impact encounter is estimated based on the Thomas et al. (Thomas et al. [2007]. Icarus 187, 4-15) pole and longitude system. The possibility of a 180deg error in the rotational phase is assessed and found to be significant. Analytical and physical modeling of the behavior of the spin rate through of each perihelion is presented and used as a basis to predict the rotational state of the nucleus at the time of the nominal (i.e., prior to February 2010) Stardust-NExT encounter on 2011 February 14 at 20:42. We find that a net torque in the range of 0.3-2.5 x 10(exp

  3. Stardust-NExT, Deep Impact, and the accelerating spin of 9P/Tempel 1

    NASA Astrophysics Data System (ADS)

    Belton, Michael J. S.; Meech, Karen J.; Chesley, Steven; Pittichová, Jana; Carcich, Brian; Drahus, Michal; Harris, Alan; Gillam, Stephen; Veverka, Joseph; Mastrodemos, Nicholas; Owen, William; A'Hearn, Michael F.; Bagnulo, S.; Bai, J.; Barrera, L.; Bastien, Fabienne; Bauer, James M.; Bedient, J.; Bhatt, B. C.; Boehnhardt, Hermann; Brosch, N.; Buie, Marc; Candia, Pablo; Chen, W.-P.; Chiang, P.; Choi, Young-Jun; Cochran, A.; Crockett, Christopher J.; Duddy, S.; Farnham, Tony; Fernández, Yan R.; Gutiérrez, Pedro; Hainaut, Olivier R.; Hampton, Donald; Herrmann, Kimberly A.; Hsieh, Henry; Kadooka, M. A.; Kaluna, H.; Keane, J.; Kim, M.-J.; Klaasen, Kenneth; Kleyna, J.; Krisciunas, Kevin; Lara, Luisa M.; Lauer, Tod R.; Li, Jian-Yang; Licandro, Javier; Lisse, Carey M.; Lowry, Stephen C.; McFadden, Lucy; Moskovitz, N.; Mueller, Beatrice; Polishook, D.; Raja, N. S.; Riesen, T.; Sahu, D. K.; Samarasinha, Nalin; Sarid, G.; Sekiguchi, Tomohiko; Sonnett, S.; Suntzeff, Nicholas B.; Taylor, Brian W.; Thomas, Peter; Tozzi, Gian Paolo; Vasundhara, R.; Vincent, J.-B.; Wasserman, Lawrence H.; Webster-Schultz, Bryant; Yang, B.; Zenn, T.; Zhao, H.

    2011-05-01

    The evolution of the spin rate of Comet 9P/Tempel 1 through two perihelion passages (in 2000 and 2005) is determined from 1922 Earth-based observations taken over a period of 13 year as part of a World-Wide observing campaign and from 2888 observations taken over a period of 50 days from the Deep Impact spacecraft. We determine the following sidereal spin rates (periods): 209.023 ± 0.025°/dy (41.335 ± 0.005 h) prior to the 2000 perihelion passage, 210.448 ± 0.016°/dy (41.055 ± 0.003 h) for the interval between the 2000 and 2005 perihelion passages, 211.856 ± 0.030°/dy (40.783 ± 0.006 h) from Deep Impact photometry just prior to the 2005 perihelion passage, and 211.625 ± 0.012°/dy (40.827 ± 0.002 h) in the interval 2006-2010 following the 2005 perihelion passage. The period decreased by 16.8 ± 0.3 min during the 2000 passage and by 13.7 ± 0.2 min during the 2005 passage suggesting a secular decrease in the net torque. The change in spin rate is asymmetric with respect to perihelion with the maximum net torque being applied on approach to perihelion. The Deep Impact data alone show that the spin rate was increasing at a rate of 0.024 ± 0.003°/dy/dy at JD2453530.60510 (i.e., 25.134 dy before impact), which provides independent confirmation of the change seen in the Earth-based observations. The rotational phase of the nucleus at times before and after each perihelion and at the Deep Impact encounter is estimated based on the Thomas et al. (Thomas et al. [2007]. Icarus 187, 4-15) pole and longitude system. The possibility of a 180° error in the rotational phase is assessed and found to be significant. Analytical and physical modeling of the behavior of the spin rate through of each perihelion is presented and used as a basis to predict the rotational state of the nucleus at the time of the nominal (i.e., prior to February 2010) Stardust-NExT encounter on 2011 February 14 at 20:42. We find that a net torque in the range of 0.3-2.5 × 10 7 kg m 2 s -2

  4. Stardust-NExT, Deep Impact, and the Accelerating Spin of 9P/Tempel One

    NASA Technical Reports Server (NTRS)

    Belton, Michael J. S.; Meech, Karen J.; Chesley, Steven; Pittichova, Jana; Carcich, Brian; Drahus, Michal; Harris, Alan; Gillam, Stephen; Veverka, Joseph; A'Hearn, Michael F.; Bastien, Fabienne; Crockett, Christopher J.; Mastrodemos, Nicholas; Owen, William; Bauer, Gerbs; Boehnhardt, Hermann; Bhatt, B. C.; Buie, Marc; Farnham, Tony; Fernandez, Yan R.; Gutierrez, Pedro; Hainaut, Olivier; Klaasen, Kenneth; Lara, Luisa M.; McFadden, Lucy

    2011-01-01

    The evolution of the spin rate of comet 9P/Tempel 1 through two perihelion passages (CYs 2000 and 2005) is determined from 1922 Earth-based observations taken over a period of 13y as part of a World-Wide observing campaign and 2888 observations taken over a period of 50d from the Deep Impact spacecraft. We determine the following sidereal spin rates (periods): 209.023 +/- 0.025 degrees /day (41.335 +/- 0.005 h) prior to the 2000 perihelion passage, 210.448 +/- 0.016 degrees/day (41.055 +/- 0.003 h) for the interval between the 2000 and 2005 perihelion passages, 211.856 +/- 0.030 degrees/day (40.783 +/- 0.006 h) from Deep Impact photometry just prior to the 2005 perihelion passage, and 211.625 +/- 0.012 degrees /day (40.827 +/- 0.002 h) in the interval 2006-2010 following the 2005 perihelion passage. The period decreased by 16.8 +/- 0.3 min during the 2000 passage and by 13.7 +/- 0.2 min during the 2005 passage suggesting a secular decrease in the net torque. The change in spin rate is asymmetric with respect to perihelion with the maximum net torque being applied on approach to perihelion. The Deep Impact data alone show that the spin rate was increasing at a rate of 0.024 +/- 0.003 degree/d/d at JD2453530.60510 (i.e., 25.134 d before impact) and provides independent confirmation of the change seen in the Earth-based observations. The rotational phase of the nucleus at times before and after each perihelion and at the Deep Impact encounter is estimated based on the Thomas et al. pole and longitude system. The possibility of a 180 degree error in the rotational phase is assessed and found to be significant. Analytical and physical modeling of the behavior of the spin rate through of each perihelion is presented and used as a basis to predict the rotational state of the nucleus at the time of the nominal (i.e., prior to February 2010) Stardust-NExT encounter on 2011 February 14 20:42. We find that a net torque in the range of 0.3 - 2.5 x 10(exp 7) kg.square m2/square

  5. Analysis of a familial three way translocation involving chromosomes 3q, 6q, and 15q by high resolution banding and fluorescent in situ hybridisation (FISH) shows two different unbalanced karyotypes in sibs.

    PubMed Central

    Wieczorek, D; Engels, H; Viersbach, R; Henke, B; Schwanitz, G; Passarge, E

    1998-01-01

    We report on a familial three way translocation involving chromosomes 3, 6, and 15 identified by prometaphase banding and fluorescence in situ hybridisation (FISH). Two mentally retarded sibs with different phenotypic abnormalities, their phenotypically normal sister and mother, and two fetuses of the phenotypically normal sister were analysed. The terminal regions of chromosomes 3q, 6q, and 15q were involved in a reciprocal translocation, in addition to a paracentric inversion of the derivative chromosome 15. Conventional cytogenetic studies with high resolution GTG banding did not resolve this rearrangement. FISH using whole chromosome paints (WCPs) identified the chromosomal regions involved, except the aberrant region of 3q, which was undetectable with these probes. Investigation of this region with the subtelomeric FISH probe D3S1445/D3S1446 showed a balanced karyotype, 46,XX,t(3;15;6) (q29;q26.1;q26), inv der(15) (q15.1q26.1) in two adult females and one fetus. It was unbalanced in two sibs, showing two different types of unbalanced translocation resulting in partial trisomy 3q in combination with partial monosomy 6q in one patient and partial trisomy 15q with partial monosomy 6q in the other patient and one fetus. These represent apparently new chromosomal phenotypes. Images PMID:9678698

  6. Crater-diameter distribution on Comets 9P and 81P and potential meteoroid streams crossing their orbits

    NASA Astrophysics Data System (ADS)

    Ivanova, O. V.; Neslušan, L.; Svoreň, J.; Seman Krišandová, Z.

    2015-07-01

    We attempt to answer two questions concerning the impacts of stream meteoroids on the nuclei of Comets 9P/Tempel 1 and 81P/Wild 2: firstly, how many streams cross the orbits of both comets and, secondly, what is the index of the differential mass distribution of impactors, s, when we assume that a prevailing number of the craters on the surfaces of cometary nuclei were created by stream meteoroids? We found that 110 and 129 potential streams originating from comets likely cross the orbits of 9P and 81P, respectively (and 103 potential streams cross the orbit of 1P/Halley, for comparison). If we consider the more compact streams originating from asteroids, the 9P and 81P pass through such streams 15 664 and 65 368 times. Neither these large numbers of passages imply, however, enough large impactors to excavate the whole observed variety of craters on studied comets. For all craters on 9P and 81P, s = 2.09 ± 0.01 and s = 2.25 ± 0.03 , respectively. The craters on 81P seem to be, however, excavated by the impactors from four discernible sources. For two numerous enough sources we find s = 5.6 ± 0.2 and s = 5.2 ± 0.5 . The difference between the indices for the set of all craters and the sets of their partial groups obviously implies an unknown cosmogonic consequence.

  7. Behavior of Comet 9P/Tempel 1 around the Deep Impact event

    NASA Astrophysics Data System (ADS)

    Lara, L. M.; Boehnhardt, H.; Gredel, R.; Gutiérrez, P. J.; Rodrigo, R.; Vidal-Nuñez, M. J.

    2007-04-01

    Context: Comet 9P/Tempel 1, the target of the Deep Impact (DI) Mission, has been monitored from June 18 until July 12, 2005, as a follow up to the long-term campaign started in Jan. 2005. Aims: The goal of this campaign is to characterize the comet before the DI event and to detect changes in activity and coma morphology produced by the DI experiment on July 04.226 UT 2005. Methods: Optical broadband images and long-slit spectroscopic measurements have been acquired with the instrument CAFOS mounted at the 2.2 m telescope at Calar Alto Observatory (CSIC-MPG) from July 1 to 11, whereas only imaging has been performed with Versarray at the 1.5 m telescope of the Sierra Nevada Observatory (IAA-CSIC) on June 26 and 29, 2005. Results: Fifteen hours after the impact, the ejecta cloud extends over ~240° in position angle (PA) with a symmetry axis at PA ~ 235°. The effect of the solar radiation pressure is already visible as a slight deviation from a fully symmetric plume and the ejecta dust is already feeding the tail. The exhaustive analysis of the broadband images has revealed that no new long-lasting coma structure is produced by the impact. The structures existing in the coma before the event are recovered after the ejecta plume has moved out. The maximum projected expansion velocity of the ejecta dust results in ~230 and ~150 m/s 15 and 40 h after impact, respectively. Surface brightness profiles of the continuum, either azimuthally averaged profiles from the broadband images or in the north-south direction from the long-slit spectra can generally be well fit with a slope m of -0.94 ≤ m ≤ -1.49 in log B - log ρ representation. A few exceptions occur on July 2 and 8-10 when much flatter continuum profiles are detected that are possibly related to fragmentation processes and to the reported outbursts occurring around those dates. Normalized color S' of the dust inside the coma does not show spatial variations excluding July 04.875 UT, our first observation after

  8. Partial trisomy 1p (1p36.22-->pter) and partial monosomy 9p (9p22.2-->pter) associated with achalasia, flexion deformity of the fingers and epilepsy in a girl.

    PubMed

    Chen, C P; Lin, S P; Lee, C C; Town, D D; Wang, W

    2006-01-01

    We report on a 12-year-old girl presenting with mental retardation, trigonocephaly, midface hypoplasia, upward-slanting palpebral fissures, arched eyebrows, bilateral epicanthal folds, hypertelorism, a flattened nasal bridge, a short nose, anteverted nares, a long philtrum, a small mouth, micrognathia, low-set ears, a short neck, long digits, flexion deformity of the fingers of the hands, hypoplasia of the labia majora, hyperplasia of the labia minora, flat feet, dysphagia, frequent regurgitation, prominent esophageal dilation, and achalasia. Seizures were noted since 5 years of age. Cytogenetic analysis of her peripheral blood revealed a karyotype of 46,XX, der(9)t(1;9)(p36.22;p22.2)pat. Achalasia, an uncommon esophageal motor disorder, has not been previously described in association with either a deletion of 9p or a duplication of 1p.

  9. Loss of chromosome 9p21 and decreased p16 expression correlate with malignant gastrointestinal stromal tumor

    PubMed Central

    Zhang, Yun; Cao, Hui; Wang, Ming; Zhao, Wen-Yi; Shen, Zhi-Yong; Shen, Dan-Ping; Ni, Xing-Zhi; Wu, Zhi-Yong; Shen, Yan-Ying; Song, Yan-Yan

    2010-01-01

    AIM: To investigate loss of heterozygosity (LOH) of chromosome 9p21 and the prognostic relevance of p16 expression in gastrointestinal stromal tumor (GIST). METHODS: Fifty-one GIST patients (30 men and 21 women; median age 59 years; range 29-80 years) treated surgically within a 10-year period were grouped by aggressive behavior risk (17 with very low and low, 14 intermediate, and 20 high risk). GISTs were characterized immunohistochemically and evaluated for LOH of 9p21 by microsatellite analysis at D9S1751, D9S1846, D9S942, and D9S1748. LOH of 9p21 and immunohistochemical expression of p16 protein encoded at 9p21 were correlated with clinicopathological parameters, and the prognostic significance of p16 alterations was evaluated. RESULTS: Thirty-one (63.3%) cases showed LOH with at least one microsatellite marker. LOH frequency was 37.0% at D9S1751, 37.5% at D9S1846, 42.1% at D9S942, and 24.2% at D9S1748. There was a higher LOH frequency of D9S942 in high-risk than in non-high-risk tumors (P < 0.05, χ2 = 4.47). Gender, age, tumor size and site were not correlated with allelic loss. Ninety percent (18/20) of the GIST patients in the high risk group showed LOH with at least one of the 9p21 markers, while 57.1% (8/14) in the intermediate risk group and 33.3% (5/15) in the very low and low risk groups, respectively (P < 0.05, χ2 = 12.16). Eight (28.5%) of 31 patients with LOH and 1 (5.6%) of 18 patients without LOH died of the disease during the follow-up period. Loss of p16 protein expression occurred in 41.2%, but in 60% of the high risk group and 23.5% of the very low and low risk groups (P < 0.05, χ2 = 4.98). p16 loss was associated with poor prognosis (P < 0.05, χ2 = 4.18): the 3- and 5-year overall survival rates were 84.8% and 70.8% for p16-negative and 100% and 92.0% for p16-positive patients, respectively. CONCLUSION: LOH at 9p21 appears to play an important role in GIST progression; decreased p16 expression in GIST is highly predictive of poor outcome

  10. Delineation of the critical deletion region for congenital heart defects, on chromosome 8p23.1.

    PubMed Central

    Devriendt, K; Matthijs, G; Van Dael, R; Gewillig, M; Eyskens, B; Hjalgrim, H; Dolmer, B; McGaughran, J; Bröndum-Nielsen, K; Marynen, P; Fryns, J P; Vermeesch, J R

    1999-01-01

    Deletions in the distal region of chromosome 8p (del8p) are associated with congenital heart malformations. Other major manifestations include microcephaly, intrauterine growth retardation, mental retardation, and a characteristic hyperactive, impulsive behavior. We studied genotype-phenotype correlations in nine unrelated patients with a de novo del8p, by using the combination of classic cytogenetics, FISH, and the analysis of polymorphic DNA markers. With the exception of one large terminal deletion, all deletions were interstitial. In five patients, a commonly deleted region of approximately 6 Mb was present, with breakpoints clustering in the same regions. One patient without a heart defect or microcephaly but with mild mental retardation and characteristic behavior had a smaller deletion within this commonly deleted region. Two patients without a heart defect had a more proximal interstitial deletion that did not overlap with the commonly deleted region. Taken together, these data allowed us to define the critical deletion regions for the major features of a del8p. PMID:10090897

  11. Sonographic findings in a case of tetrasomy 9p associated with increased nuchal translucency and Dandy-Walker malformation.

    PubMed

    Nakamura-Pereira, Marcos; Cima, Luciana Carneiro do; Llerena, Juan Clinton; Guerra, Fernando Antonio Ramos; Peixoto-Filho, Fernando Maia

    2009-10-01

    We report a case of a 23-year-old pregnant woman, who underwent amniocentesis after ultrasound (US) examination in the first trimester which revealed a nuchal translucency thickness of 2.9 mm. Cytogenetic analysis revealed complete tetrasomy of the short arm of chromosome 9. Further US evaluation in the second trimester revealed Dandy-Walker malformation, ventriculomegaly, bilateral clubfoot, lip and palate clefts, arthrogryposis and hyperechoic kidneys with bilateral pelvic dilatation. At 30 weeks of gestation, a placental abruption was noted and a Cesarean section was performed. The infant died shortly after birth. A review of previous cases of tetrasomy 9p shows that the remarkable sonographic findings are ventriculomegaly, intrauterine growth restriction, genitourinary anomaly, Dandy-Walker malformation, cleft lip/palate and limb malformation, but the association of tetrasomy 9p and increased nuchal translucency had not been reported. PMID:19655321

  12. Casp8p41: The Protean Mediator of Death in CD4 T-cells that Replicate HIV

    PubMed Central

    Sampath, Rahul; Cummins, Nathan W.; Badley, Andrew D.

    2016-01-01

    HIV cure is now the focus of intense research after Timothy Ray Brown (the Berlin patient) set the precedent of being the first and only person cured. A major barrier to achieving this goal on a meaningful scale is an elimination of the latent reservoir, which is thought to comprise CD4-positive cells that harbor integrated, replication-competent HIV provirus. These cells do not express viral proteins, are indistinguishable from uninfected CD4 cells, and are thought to be responsible for HIV viral rebound—that occurs within weeks of combination anti retroviral therapy (cART) interruption. Modalities to engineer transcriptional stimulation (reactivation) of this dormant integrated HIV provirus, leading to expression of cytotoxic viral proteins, are thought to be a specific way to eradicate the latently infected CD4 pool and are becoming increasingly relevant in the era of HIV cure. HIV protease is one such protein produced after HIV reactivation that cleaves procaspase-8 to generate a novel protein Casp8p41. Casp8p41 then binds to the BH3 domain of BAK, leading to BAK oligomerization, mitochondrial depolarization, and apoptosis. In central memory T cells (TCMs) from HIV-infected patients, an elevated Bcl-2/procaspase-8 ratio was observed, and Casp8p41 binding to Bcl-2 was associated with a lack of reactivation-induced cell death. This was reversed by priming cells with a specific Bcl-2 antagonist prior to reactivation, resulting in increased cell death and decreased HIV DNA in a Casp8p41-dependent pathway. This review describes the biology, clinical relevance, and implications of Casp8p41 for a potential cure. PMID:27721655

  13. The Catalytic and Conformational Cycle of Aquifex aeolicus KDO8P Synthase: Role of the L7 Loop†,‡

    PubMed Central

    Xu, Xingjue; Kona, Fathima; Wang, Jian; Lu, Jinshuang; Stemmler, Timothy; Gatti, Domenico L.

    2015-01-01

    KDO8P synthase catalyzes the condensation of arabinose 5-phosphate (A5P) and phosphoenolpyruvate (PEP) to form the 8-carbon sugar KDO8P and inorganic phosphate (Pi). The X-ray structure of the wild-type enzyme shows that when both PEP and A5P bind, the active site becomes isolated from the environment due to a conformational change of the L7 loop. The structures of the R106G mutant, without substrates, and with PEP and PEP plus A5P bound, were determined and reveal that in R106G closure of the L7 loop is impaired. The structural perturbations originating from the loss of the Arg106 side chain point to a role of the L2 loop in stabilizing the closed conformation of the L7 loop. Despite the increased exposure of the R106G active site, no abnormal reaction of PEP with water was observed, ruling out the hypothesis that the primary function of the L7 loop is to shield the active site from bulk solvent during the condensation reaction. However, the R106G enzyme displays several kinetic abnormalities on both the substrate side (smaller KmPEP, larger KiA5P and KmA5P) and the product side (smaller KiPi and KiKDO8P) of the reaction. As a consequence, the mutant enzyme is less severely inhibited by A5P and more severely inhibited by Pi and KDO8P. Simulations of the flux of KDO8P synthesis under metabolic steady-state conditions (constant concentration of reactants and products over time) suggest that in vivo R106G is expected to perform optimally in a narrower range of substrate and product concentrations than the wild-type enzyme. PMID:16156656

  14. Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD

    PubMed Central

    Momeni, Parastoo; Schymick, Jennifer; Jain, Shushant; Cookson, Mark R; Cairns, Nigel J; Greggio, Elisa; Greenway, Matthew J; Berger, Stephen; Pickering-Brown, Stuart; Chiò, Adriano; Fung, Hon Chung; Holtzman, David M; Huey, Edward D; Wassermann, Eric M; Adamson, Jennifer; Hutton, Michael L; Rogaeva, Ekaterina; St George-Hyslop, Peter; Rothstein, Jeffrey D; Hardiman, Orla; Grafman, Jordan; Singleton, Andrew; Hardy, John; Traynor, Bryan J

    2006-01-01

    Background A new locus for amyotrophic lateral sclerosis – frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p. Methods We identified chromosome 9p segregating haplotypes within two families with ALS-FTD (F476 and F2) and undertook mutational screening of candidate genes within this locus. Results Candidate gene sequencing at this locus revealed the presence of a disease segregating stop mutation (Q342X) in the intraflagellar transport 74 (IFT74) gene in family 476 (F476), but no mutation was detected within IFT74 in family 2 (F2). While neither family was sufficiently informative to definitively implicate or exclude IFT74 mutations as a cause of chromosome 9-linked ALS-FTD, the nature of the mutation observed within F476 (predicted to truncate the protein by 258 amino acids) led us to sequence the open reading frame of this gene in a large number of ALS and FTD cases (n = 420). An additional sequence variant (G58D) was found in a case of sporadic semantic dementia. I55L sequence variants were found in three other unrelated affected individuals, but this was also found in a single individual among 800 Human Diversity Gene Panel samples. Conclusion Confirmation of the pathogenicity of IFT74 sequence variants will require screening of other chromosome 9p-linked families. PMID:17166276

  15. A 6q14.1-q15 microdeletion in a male patient with severe autistic disorder, lack of oral language, and dysmorphic features with concomitant presence of a maternally inherited Xp22.31 copy number gain.

    PubMed

    Quintela, Ines; Fernandez-Prieto, Montse; Gomez-Guerrero, Lorena; Resches, Mariela; Eiris, Jesus; Barros, Francisco; Carracedo, Angel

    2015-06-01

    We report on a male patient with severe autistic disorder, lack of oral language, and dysmorphic features who carries a rare interstitial microdeletion of 4.96 Mb at chromosome 6q14.1-q15. The patient also harbors a maternally inherited copy number gain of 1.69 Mb at chromosome Xp22.31, whose pathogenicity is under debate. PMID:26185640

  16. A de novo 0.63 Mb 6q25.1 deletion associated with growth failure, congenital heart defect, underdeveloped cerebellar vermis, abnormal cutaneous elasticity and joint laxity.

    PubMed

    Salpietro, Vincenzo; Ruggieri, Martino; Mankad, Kshitij; Di Rosa, Gabriella; Granata, Francesca; Loddo, Italia; Moschella, Emanuela; Calabro, Maria Pia; Capalbo, Anna; Bernardini, Laura; Novelli, Antonio; Polizzi, Agata; Seidler, Daniela G; Arrigo, Teresa; Briuglia, Silvana

    2015-09-01

    Deletions of the long arm of chromosome 6 are rare and are characterized by great clinical variability according to the deletion breakpoint. We report a on 6-year-old girl with a de novo 0.63 Mb deletion on chromosome 6q25.1 who demonstrated multiple congenital anomalies including a ventricular septal defect and an underdeveloped cerebellar vermis. She presented with severe pre- and post-natal growth failure, hyperextensible small joints (Beighton scores = 8/9; with normal parental scores), and an abnormally elastic, redundant skin. Abnormally high upper/lower segment ratio (i.e., 1.34 = > 3SD), mild dysmorphic facial features and developmental delay were also present. The girl's phenotype was compared with: (i) two girls, each previously reported by Bisgaard et al. and Caselli et al. with similar albeit larger (2.6-7.21 Mb) deletions; (ii) seven additional individuals (6 M; 1 F) harboring deletions within the 6q25.1 region reported in the literature; and (iii) ten further patients (5 M; 4 F; 1 unrecorded sex) recorded in the DECIPHER 6.0 database. We reported on the present girl as her findings could contribute to advance the phenotype of 6q deletions. In addition, the present deletion is the smallest so far recorded in the 6q25 region encompassing eight known genes [vs. 41 of Bisgaard et al., and 23 of Caselli et al.,], including the TAB2 (likely responsible for the girl's congenital heart defect), LATS1 gene, and the UST gene (a regulator of the homeostasis of proteoglycans, which could have played a role in the abnormal dermal and cartilage elasticity).

  17. A 6q14.1-q15 microdeletion in a male patient with severe autistic disorder, lack of oral language, and dysmorphic features with concomitant presence of a maternally inherited Xp22.31 copy number gain

    PubMed Central

    Quintela, Ines; Fernandez-Prieto, Montse; Gomez-Guerrero, Lorena; Resches, Mariela; Eiris, Jesus; Barros, Francisco; Carracedo, Angel

    2015-01-01

    Key Clinical Message We report on a male patient with severe autistic disorder, lack of oral language, and dysmorphic features who carries a rare interstitial microdeletion of 4.96 Mb at chromosome 6q14.1-q15. The patient also harbors a maternally inherited copy number gain of 1.69 Mb at chromosome Xp22.31, whose pathogenicity is under debate. PMID:26185640

  18. A de novo 0.63 Mb 6q25.1 deletion associated with growth failure, congenital heart defect, underdeveloped cerebellar vermis, abnormal cutaneous elasticity and joint laxity.

    PubMed

    Salpietro, Vincenzo; Ruggieri, Martino; Mankad, Kshitij; Di Rosa, Gabriella; Granata, Francesca; Loddo, Italia; Moschella, Emanuela; Calabro, Maria Pia; Capalbo, Anna; Bernardini, Laura; Novelli, Antonio; Polizzi, Agata; Seidler, Daniela G; Arrigo, Teresa; Briuglia, Silvana

    2015-09-01

    Deletions of the long arm of chromosome 6 are rare and are characterized by great clinical variability according to the deletion breakpoint. We report a on 6-year-old girl with a de novo 0.63 Mb deletion on chromosome 6q25.1 who demonstrated multiple congenital anomalies including a ventricular septal defect and an underdeveloped cerebellar vermis. She presented with severe pre- and post-natal growth failure, hyperextensible small joints (Beighton scores = 8/9; with normal parental scores), and an abnormally elastic, redundant skin. Abnormally high upper/lower segment ratio (i.e., 1.34 = > 3SD), mild dysmorphic facial features and developmental delay were also present. The girl's phenotype was compared with: (i) two girls, each previously reported by Bisgaard et al. and Caselli et al. with similar albeit larger (2.6-7.21 Mb) deletions; (ii) seven additional individuals (6 M; 1 F) harboring deletions within the 6q25.1 region reported in the literature; and (iii) ten further patients (5 M; 4 F; 1 unrecorded sex) recorded in the DECIPHER 6.0 database. We reported on the present girl as her findings could contribute to advance the phenotype of 6q deletions. In addition, the present deletion is the smallest so far recorded in the 6q25 region encompassing eight known genes [vs. 41 of Bisgaard et al., and 23 of Caselli et al.,], including the TAB2 (likely responsible for the girl's congenital heart defect), LATS1 gene, and the UST gene (a regulator of the homeostasis of proteoglycans, which could have played a role in the abnormal dermal and cartilage elasticity). PMID:25940952

  19. Inhibition of atopic dermatitis-like skin lesions by topical application of a novel ceramide derivative, K6PC-9p, in NC/Nga mice.

    PubMed

    Kang, Jong Soon; Yoon, Won Kee; Youm, Jong-Kyung; Jeong, Se Kyoo; Park, Byeong Deog; Han, Mi Hwa; Lee, Hyunju; Moon, Eun-Yi; Han, Sang-Bae; Lee, Chang Woo; Lee, Kiho; Park, Song-Kyu; Yang, Kyu-Hwan; Kim, Hwan Mook

    2008-11-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease that commonly begins in childhood. K6PC-9p (N-(Ethyl dihydrogenphosphate)-2-hexyl-3-oxo-decanamide) is a synthetic ceramide derivative of PC-9S (N-Ethanol-2-mirystyl-3-oxo-staramide), which was known to be effective in atopic patients. In this study, we examined the effect of topical application of K6PC-9p on skin inflammation and AD-like skin lesions in mouse models. K6PC-9p dose-dependently inhibited phorbol ester-induced increase in ear thickness in BALB/c mice. Moreover, topical application of K6PC-9p suppressed dust mite extract-induced AD-like skin lesions in NC/Nga mice. Histopathological analysis revealed that both ear swelling and leucocyte infiltration were suppressed by K6PC-9p treatment. K6PC-9p also suppressed IL-4 and TNF-alpha expression in the ears and mast cell infiltration into the ears in NC/Nga mice. Further study demonstrated that K6PC-9p inhibited ConA-induced IL-4 secretion and LPS-induced macrophage activation. Taken together, our results showed that topical application of K6PC-9p exerts beneficial effects in animal model of skin inflammation and AD, suggesting that K6PC-9p might be a promising topical agent for the treatment of inflammatory skin diseases.

  20. Molecular characterization of two rare human G8P[14] rotavirus strains, detected in Italy in 2012.

    PubMed

    Delogu, Roberto; Ianiro, Giovanni; Morea, Anna; Chironna, Maria; Fiore, Lucia; Ruggeri, Franco M

    2016-10-01

    Since 2007, the Italian Rotavirus Surveillance Program (RotaNet-Italy) has monitored the diversity and distribution of genotypes identified in children hospitalized with rotavirus acute gastroenteritis. We report the genomic characterization of two rare human G8P[14] rotavirus strains, identified in two children hospitalized with acute gastroenteritis in the southern Italian region of Apulia during rotavirus strain surveillance in 2012. Both strains showed a G8-P[14]-I2-R2-C2-M2-A11-N2-T6-E2-H3 genomic constellation (DS-1-like genomic background). Phylogenetic analysis of each genome segment revealed a mixed configuration of genes of animal and zoonotic human origin, indicating that genetic reassortment events generated these unusual human strains. Eight out of 11 genes (VP1, VP2, VP3, VP6, VP7, NSP3, NSP4 and NSP5) of the Italian G8P[14] strains exhibited close identity with a Spanish sheep strain, whereas the remaining genes (VP4, NSP1 and NSP2) were more closely related to human strains. The amino acid sequences of the antigenic regions of outer capsid proteins VP4 and VP7 were compared with vaccine and field strains, showing high conservation between the amino acid sequences of Apulia G8P[14] strains and human and animal strains bearing G8 and/or P[14] proteins, and revealing many substitutions with respect to the RotaTeq™ and Rotarix™ vaccine strains. Conversely, the amino acid analysis of the four antigenic sites of VP6 revealed a high degree of conservation between the two Apulia strains and the human and animal strains analyzed. These results reinforce the potential role of interspecies transmission and reassortment in generating novel rotavirus strains that might not be fully contrasted by current vaccines. PMID:27449953

  1. Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese

    PubMed Central

    Li, Yuanfeng; Si, Lanlan; Zhai, Yun; Hu, Yanling; Hu, Zhibin; Bei, Jin-Xin; Xie, Bobo; Ren, Qian; Cao, Pengbo; Yang, Fei; Song, Qingfeng; Bao, Zhiyu; Zhang, Haitao; Han, Yuqing; Wang, Zhifu; Chen, Xi; Xia, Xia; Yan, Hongbo; Wang, Rui; Zhang, Ying; Gao, Chengming; Meng, Jinfeng; Tu, Xinyi; Liang, Xinqiang; Cui, Ying; Liu, Ying; Wu, Xiaopan; Li, Zhuo; Wang, Huifen; Li, Zhaoxia; Hu, Bo; He, Minghui; Gao, Zhibo; Xu, Xiaobing; Ji, Hongzan; Yu, Chaohui; Sun, Yi; Xing, Baocai; Yang, Xiaobo; Zhang, Haiying; Tan, Aihua; Wu, Chunlei; Jia, Weihua; Li, Shengping; Zeng, Yi-Xin; Shen, Hongbing; He, Fuchu; Mo, Zengnan; Zhang, Hongxing; Zhou, Gangqiao

    2016-01-01

    Hepatitis B virus (HBV) infection is a common infectious disease. Here we perform a genome-wide association study (GWAS) among Chinese populations to identify novel genetic loci involved in persistent HBV infection. GWAS scan is performed in 1,251 persistently HBV infected subjects (PIs, cases) and 1,057 spontaneously recovered subjects (SRs, controls), followed by replications in four independent populations totally consisting of 3,905 PIs and 3,356 SRs. We identify a novel locus at 8p21.3 (index rs7000921, odds ratio=0.78, P=3.2 × 10−12). Furthermore, we identify significant expression quantitative trait locus associations for INTS10 gene at 8p21.3. We demonstrate that INST10 suppresses HBV replication via IRF3 in liver cells. In clinical plasma samples, we confirm that INST10 levels are significantly decreased in PIs compared with SRs, and negatively correlated with the HBV load. These findings highlight a novel antiviral gene INTS10 at 8p21.3 in the clearance of HBV infection. PMID:27244555

  2. Association of rs10757274 and rs2383206 Polymorphisms on 9p21 locus with Coronary Artery Disease in Turkish Population

    PubMed Central

    Okyay, Kaan; Yılmaz, Akın; Şahinarslan, Asife; Yar Sağlam, Atiye Seda; Eyiol, Azmi; Bolayır, Hasan Ata; Sezenöz, Burak; Menevşe, Sevda; Çengel, Atiye

    2016-01-01

    Background and Objectives Genetic predisposition is an important risk factor for coronary artery disease (CAD). In this study, we aimed to evaluate the impact of rs10757274 and rs2383206 polymorphisms in chromosome 9p21 on presence and severity of CAD in a Turkish population. Subjects and Methods A total of 646 patients who underwent coronary angiography were included in this study. Coronary vessel score and Gensini score were calculated to assess the angiographic severity of CAD. Alleles of AA, AG, and GG were determined for rs10757274 (polymorphism-1) and rs2383206 (polymorphism-2) polymorphisms located in chromosome 9p21 from the blood samples. Results There was a significant difference between the alleles in polymorphism-1 in the presence of coronary artery disease (38.9% in AA, 48.0% in GG and 56.4% in AG, p=0.017). However, there was no difference between the alleles in polymorphism-2. According to vessel scores, there was a significant difference between the alleles in polymorphism-1 (AA 0.71±1.04, GG 0.88±1.07, AG 1.06±1.12, p=0.018). In polymorphism-2, vessel scores did not show a difference between the alleles. In polymorphism-1, there was a significant difference in Gensini score (p=0.041). Gensini scores did not differ between the alleles in polymorphism-2 (p>0.05 for all). In multivariate analyses, none of the alleles was an independent factor for presence of CAD. Conclusion The presence of rs10757274 polymorphism including AG allele in chromosome 9p21 was related to CAD. However, this relationship was not independent of other cardiovascular risk factors. PMID:27721851

  3. Ebstein anomaly: Genetic heterogeneity and association with microdeletions 1p36 and 8p23.1.

    PubMed

    Digilio, Maria Cristina; Bernardini, Laura; Lepri, Francesca; Giuffrida, Maria Grazia; Guida, Valentina; Baban, Anwar; Versacci, Paolo; Capolino, Rossella; Torres, Barbara; De Luca, Alessandro; Novelli, Antonio; Marino, Bruno; Dallapiccola, Bruno

    2011-09-01

    Ebstein anomaly is an uncommon congenital heart defect (CHD), characterized by downward displacement of the tricuspid valve into the right ventricle. To uncover the genetic associations with Ebstein anomaly, we have searched chromosomal imbalances using standard cytogenetic and array-CGH analysis, and single gene conditions associated with syndromic Ebstein anomaly (with extracardiac anomalies), and screened GATA4 and NKX2.5 mutations in nonsyndromic patients (without extracardiac anomalies). Between January 1997 and September 2009, 44 consecutive patients with Ebstein anomaly were evaluated in two centers of Pediatric Cardiology. Ebstein anomaly was syndromic in 12 (27%) patients, and nonsyndromic in 32 (73%). A recognizable syndrome or complex was diagnosed by clinical criteria in seven patients. In one syndromic patient an 18q deletion was diagnosed by standard cytogenetic analysis. Array-CGH analysis performed in 10 of the 12 syndromic patients detected an interstitial deletion of about 4 Mb at 8p23.1 in one patient, and a deletion 1pter > 1p36.32/dup Xpter- > Xp22.32 in another patient. In the 28 of 32 nonsyndromic patients who underwent molecular testing, no mutation in GATA4 and NKX2.5 genes were detected. We conclude that Ebstein anomaly is a genetically heterogeneous defect, and that deletion 1p36 and deletion 8p23.1 are the most frequent chromosomal imbalances associated with Ebstein anomaly. Candidate genes include the GATA4 gene (in patients with del 8p23.1), NKX2.5 (based on published patients with isolated Ebstein anomaly) and a hypothetical gene in patients with del 1p36).

  4. Identification of Multiple DNA Copy Number Alterations Including Frequent 8p11.22 Amplification in Conjunctival Squamous Cell Carcinoma

    PubMed Central

    Asnaghi, Laura; Alkatan, Hind; Mahale, Alka; Othman, Maha; Alwadani, Saeed; Al-Hussain, Hailah; Jastaneiah, Sabah; Yu, Wayne; Maktabi, Azza; Edward, Deepak P.; Eberhart, Charles G.

    2014-01-01

    Purpose. Little is known about the molecular alterations that drive formation and growth of conjunctival squamous cell carcinoma (cSCC). We therefore sought to identify genetic changes that could be used as diagnostic markers or therapeutic targets. Methods. The DNA extracted from 10 snap-frozen cSCC tumor specimens and 2 in situ carcinomas was analyzed using array-based comparative genomic hybridization (aCGH), and further examined with NanoString and quantitative PCR. Results. The number of regions of DNA loss ranged from 1 to 23 per tumor, whereas gains and amplifications ranged from 1 to 15 per tumor. Most large regions of chromosomal gain and loss were confirmed by NanoString karyotype analysis. The commonest alteration was amplification of 8p11.22 in 9 tumors (75%), and quantitative PCR analysis revealed 100-fold or greater overexpression of ADAM3A mRNA from 8p11.22 locus. In addition, recurring losses were observed at 14q13.2 and 22q11.23, both lost in 5 (42%) of the 12 tumors, and at 12p13.31, lost in 4 (33%) of the 12 samples. Of the eight loci associated with the DNA damage repair syndrome xeroderma pigmentosum, three showed loss of at least one allele in our aCGH analysis, including XPA (9q22.33, one tumor), XPE/DDB2 (11p11.2, one tumor) and XPG/ERCC5 (13q33.1, three tumors). Conclusions. Conjunctival SCC contains a range of chromosomal alterations potentially important in tumor formation and growth. Amplification of 8p11.22 and overexpression of ADAM3A suggests a potential role for this protease. Our findings also suggest that defects in DNA repair loci are important in sporadic cSCC. PMID:25491297

  5. Submicroscopic deletions of 3p sequences in pleomorphic adenomas with t(3;8)(p21;q12).

    PubMed

    Sahlin, P; Mark, J; Stenman, G

    1994-08-01

    A subgroup of benign pleomorphic adenomas of the salivary glands is characterized by translocations, or on rare occasions deletions, with breakpoints at 3p21. We have applied restriction fragment length polymorphism (RFLP) analysis to assess the frequency of allelic losses at four different loci located within 3p21-->p25 in 35 pleomorphic adenomas, 18 of which were also karyotyped. Parallel analysis of constitutional and tumor DNAs in informative tumors revealed that all patients retained heterozygosity in their tumor DNA at the D3S2 and RAF1 loci. Among the 29 tumors informative for THRB three showed loss of heterozygosity (LOH). All three tumors had a t(3;8)(p21;q12). Of the 23 tumors informative for D3F15S2, one showed LOH. This tumor also had a t(3;8)(p21;q12). To further map the deletions in relation to the 3p21 translocation breakpoint, we also sublocalized the THRB locus. Using in situ hybridization we assigned the gene to 3p24.1-3. The fact that none of the tumors with loss of 3p alleles showed cytogenetic evidence of deletions indicates that the losses are submicroscopic, probably interstitial, and in most cases distal to the 3p21 breakpoint. This was confirmed in one case with loss of a THRB allele where both proximal (D3F15S2) and distal (RAF1) markers retained heterozygosity. Our results suggest that deletion of 3p sequences might be of progressional importance in a subset of pleomorphic adenomas with t(3;8)(p21;q12).

  6. A family of octahedral rhenium cluster complexes [Re6Q8(H2O)n(OH)6-n]n-4 (Q=S, Se; n=0-6): structural and pH-dependent spectroscopic studies.

    PubMed

    Brylev, Konstantin A; Mironov, Yuri V; Yarovoi, Spartak S; Naumov, Nikolai G; Fedorov, Vladimir E; Kim, Sung-Jin; Kitamura, Noboru; Kuwahara, Yusuke; Yamada, Konatsu; Ishizaka, Shoji; Sasaki, Yoichi

    2007-09-01

    The conversions of hexahydroxo rhenium cluster complexes [Re6Q8(OH)6]4- (Q=S, Se) in aqueous solutions in a wide pH range were investigated by chemical methods and spectroscopic measurements. Dependences of the spectroscopic and excited-state properties of the solutions on pH have been studied in detail. It has been found that a pH decrease of aqueous solutions of the potassium salts K4[Re6Q8(OH)6].8H2O (Q=S, Se) results in the formation of aquahydroxo and hexaaqua cluster complexes with the general formula [Re6Q8(H2O)n(OH)6-n]n-4 that could be considered as a result of the protonation of the terminal OH- ligands in the hexahydroxo complexes. The compounds K2[Re6S8(H2O)2(OH)4].2H2O (1), [Re6S8(H2O)4(OH)2].12H2O (2), [Re6S8(H2O)6][Re6S6Br8].10H2O (3), and [Re6Se8(H2O)4(OH)2] (4) have been isolated and characterized by X-ray single-crystal diffraction and elemental analyses and infrared (IR) spectroscopy. In crystal structures of the aquahydroxo complexes, the cluster units are connected to each other by an extensive system of very strong hydrogen bonds between terminal ligands. PMID:17676730

  7. Paracentric inversion of chromosome 14 plus rare 9p variant in a couple with habitual spontaneous abortion.

    PubMed

    Turczynowicz, S; Sharma, P; Smith, A; Davidson, A A

    1992-01-01

    A couple presenting with habitual spontaneous abortion both showed a chromosome rearrangement. The male had an apparently balanced paracentric inversion of chromosome 14 - 46,XY,inv(14) (q11q32). The female had a karyotype with a rare large short arm variant of chromosome 9 - 46,XX,var(9) (p11p21). Testing of a living normal child showed that he had inherited both rearrangements. Family testing showed the chromosome 9 variant in three generations, with all carriers being of normal phenotype and intelligence. This study confirms that the presence of more than one chromosomal rearrangement can be compatible with normal development. This is useful for genetic counselling. Nevertheless when such cases arise, each must be individually assessed.

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

    SciTech Connect

    Amati, F.; Mari, A.; Mingarelli, R.

    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.

  9. Evaluation of the 5 and 8 pH point titration methods for monitoring anaerobic digesters treating solid waste.

    PubMed

    Vannecke, T P W; Lampens, D R A; Ekama, G A; Volcke, E I P

    2015-01-01

    Simple titration methods certainly deserve consideration for on-site routine monitoring of volatile fatty acid (VFA) concentration and alkalinity during anaerobic digestion (AD), because of their simplicity, speed and cost-effectiveness. In this study, the 5 and 8 pH point titration methods for measuring the VFA concentration and carbonate system alkalinity (H2CO3*-alkalinity) were assessed and compared. For this purpose, synthetic solutions with known H2CO3*-alkalinity and VFA concentration as well as samples from anaerobic digesters treating three different kind of solid wastes were analysed. The results of these two related titration methods were verified with photometric and high-pressure liquid chromatography measurements. It was shown that photometric measurements lead to overestimations of the VFA concentration in the case of coloured samples. In contrast, the 5 pH point titration method provides an accurate estimation of the VFA concentration, clearly corresponding with the true value. Concerning the H2CO3*-alkalinity, the most accurate and precise estimations, showing very similar results for repeated measurements, were obtained using the 8 pH point titration. Overall, it was concluded that the 5 pH point titration method is the preferred method for the practical monitoring of AD of solid wastes due to its robustness, cost efficiency and user-friendliness.

  10. Genetic Variation at 9p22.2 and Ovarian Cancer Risk for BRCA1 and BRCA2 Mutation Carriers

    PubMed Central

    Kartsonaki, Christiana; Gayther, Simon A.; Pharoah, Paul D. P.; Sinilnikova, Olga M.; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Healey, Sue; Couch, Fergus J.; Wang, Xianshu; Fredericksen, Zachary; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Roversi, Gaia; Barile, Monica; Viel, Alessandra; Allavena, Anna; Ottini, Laura; Papi, Laura; Gismondi, Viviana; Capra, Fabio; Radice, Paolo; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A.; Cruger, Dorthe; Jensen, Uffe Birk; Caligo, Maria Adelaide; Olsson, Håkan; Kristoffersson, Ulf; Lindblom, Annika; Arver, Brita; Karlsson, Per; Stenmark Askmalm, Marie; Borg, Ake; Neuhausen, Susan L.; Ding, Yuan Chun; Nathanson, Katherine L.; Domchek, Susan M.; Jakubowska, Anna; Lubiński, Jan; Huzarski, Tomasz; Byrski, Tomasz; Gronwald, Jacek; Górski, Bohdan; Cybulski, Cezary; Dębniak, Tadeusz; Osorio, Ana; Durán, Mercedes; Tejada, Maria-Isabel; Benítez, Javier; Hamann, Ute; Rookus, Matti A.; Verhoef, Senno; Tilanus-Linthorst, Madeleine A.; Vreeswijk, Maaike P.; Bodmer, Danielle; Ausems, Margreet G. E. M.; van Os, Theo A.; Asperen, Christi J.; Blok, Marinus J.; Meijers-Heijboer, Hanne E. J.; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Dunning, Alison M.; Evans, D. Gareth; Eeles, Ros; Pichert, Gabriella; Cole, Trevor; Hodgson, Shirley; Brewer, Carole; Morrison, Patrick J.; Porteous, Mary; Kennedy, M. John; Rogers, Mark T.; Side, Lucy E.; Donaldson, Alan; Gregory, Helen; Godwin, Andrew; Stoppa-Lyonnet, Dominique; Moncoutier, Virginie; Castera, Laurent; Mazoyer, Sylvie; Barjhoux, Laure; Bonadona, Valérie; Leroux, Dominique; Faivre, Laurence; Lidereau, Rosette; Nogues, Catherine; Bignon, Yves-Jean; Prieur, Fabienne; Collonge-Rame, Marie-Agnès; Venat-Bouvet, Laurence; Fert-Ferrer, Sandra; Miron, Alex; Buys, Saundra S.; Hopper, John L.; Daly, Mary B.; John, Esther M.; Terry, Mary Beth; Goldgar, David; Hansen, Thomas v. O.; Jønson, Lars; Ejlertsen, Bent; Agnarsson, Bjarni A.; Offit, Kenneth; Kirchhoff, Tomas; Vijai, Joseph; Dutra-Clarke, Ana V. C.; Przybylo, Jennifer A.; Montagna, Marco; Casella, Cinzia; Imyanitov, Evgeny N.; Janavicius, Ramunas; Blanco, Ignacio; Lázaro, Conxi; Moysich, Kirsten B.; Karlan, Beth Y.; Gross, Jenny; Beattie, Mary S.; Schmutzler, Rita; Wappenschmidt, Barbara; Meindl, Alfons; Ruehl, Ina; Fiebig, Britta; Sutter, Christian; Arnold, Norbert; Deissler, Helmut; Varon-Mateeva, Raymonda; Kast, Karin; Niederacher, Dieter; Gadzicki, Dorothea; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Simard, Jacques; Soucy, Penny; Spurdle, Amanda B.; Holland, Helene; Chenevix-Trench, Georgia; Easton, Douglas F.; Antoniou, Antonis C.

    2011-01-01

    Background Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2 and decreased risk of ovarian cancer for women in the general population. We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2. Methods We genotyped rs3814113 in 10 029 BRCA1 mutation carriers and 5837 BRCA2 mutation carriers. Associations with ovarian and breast cancer were assessed with a retrospective likelihood approach. All statistical tests were two-sided. Results The minor allele of rs3814113 was associated with a reduced risk of ovarian cancer among BRCA1 mutation carriers (per-allele hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.72 to 0.85; P = 4.8 × 10-9) and BRCA2 mutation carriers (hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.67 to 0.90; P = 5.5 × 10-4). This SNP was not associated with breast cancer risk among either BRCA1 or BRCA2 mutation carriers. BRCA1 mutation carriers with the TT genotype at SNP rs3814113 were predicted to have an ovarian cancer risk to age 80 years of 48%, and those with the CC genotype were predicted to have a risk of 33%. Conclusion Common genetic variation at the 9p22.2 locus was associated with decreased risk of ovarian cancer for carriers of a BRCA1 or BRCA2 mutation. PMID:21169536

  11. Clinical and cytogenetic findings in seven cases of inverted duplication of 8p with evidence of a telomeric deletion using fluorescence in situ hybridization

    SciTech Connect

    Guo, Wen-Jun; Callif-Daley, F.; Zapata, M.C.; Miller, M.E.

    1995-09-11

    We report on the clinical and cytogenetic findings in 7 cases of inverted duplication of region 8p11.2-p23. The phenotype of inv dup (8p) compiled from this series and the literature (N = 29) consists of severe mental retardation (100%), minor facial alterations (97%), agenesis of the corpus callosum (80%), hypotonia (66%), orthopedic abnormalities (58%), scoliosis/kyphosis (40%), and congenital heart defect (26%). A telomeric deletion of region 8p23.3-pter was confirmed in 3 of our cases studied using fluorescent in situ hybridization with a telomeric probe for 8p. Thus, these karyotypes are inv dup del(8) (qter{r_arrow} p23.1::p23.1{r_arrow}p11.2:). Our findings suggest that most cases of inv dup(8p) probably have a telomeric deletion. 20 refs., 4 figs., 2 tabs.

  12. Fluorescence reaction of 5-(p-methoxyphenylazo)-8-(p-tolylsulfonamido)quinoline with cobalt(II) and its analytical application

    SciTech Connect

    Zeng Zuotao ) Xu Qiheng )

    1992-08-01

    5-(p-Methoxyphenylazo)-8-(p-tolylsulfonamido)quinoline(MTAQ) has been synthesized. The product was checked by IR, thermogravimetry, NMR and elemental analysis. A highly sensitive spectrofluorimetric method has been developed for the determination of cobalt(II) based on the formation of a complex with MTAQ in slightly basic medium aqueous solution and in the presence of nonionic surfactant, tween-80. The complex shows two excitation maxima at 304 nm and 338 nm, its emission maximum is centered at 402nm. The fluorescence intensity is proportional to cobalt(II) concentration in the range of 0-85 ppb. The method has good selectivity and has been applied to the direct fluorimetric determination of trace cobalt(II) in pig's liver, Dianchi shrimp and celery.

  13. Schizophrenia: A genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes

    SciTech Connect

    Pulver, A.E.; Lasseter, V.K.; Kasch, L.

    1995-06-19

    Using a systematically ascertained sample of 57 families, each having 2 or more members with a consensus diagnosis of schizophrenia (DSM-III-R criteria), we have carried out linkage studies of 520 loci, covering approximately 70% of the genome for susceptibility loci for schizophrenia. A two-stage strategy based on lod score thresholds from simulation studies of our sample identified regions for further exploration. In each region, a dense map of highly informative dinucleotide repeat polymorphisms (heterozygosity greater than .70) was analyzed using dominant, recessive, and {open_quotes}affected only{close_quotes} models and nonparametric sib pair identity-by-descent methods. For one region, 8p22-p21, affected sib-pair analyses gave a P value = .0001, corresponding to a lod score approximately equal to 3.00. For 8p22-p21, the maximum two-point lod score occurred using the {open_quotes}affected only{close_quotes} recessive model (Z{sub max} = 2.35; {theta}{sub M} = {theta}{sub F}); allowing for a constant sex difference in recombination fractions found in reference pedigrees, Z{sub max} = 2.78 ({theta}{sub M}/{theta}{sub F} = 3). For a second region, 3p26-p24, the maximum two-point lod score was 2.34 ({open_quotes}affected only{close_quotes} dominant model), and the affected sib-pair P value was .01. These two regions are worthy of further exploration as potential sites of susceptibility genes for schizophrenia. 59 refs., 2 figs., 4 tabs.

  14. ORF9p phosphorylation by ORF47p is crucial for the formation and egress of varicella-zoster virus viral particles.

    PubMed

    Riva, Laura; Thiry, Marc; Bontems, Sebastien; Joris, Aline; Piette, Jacques; Lebrun, Marielle; Sadzot-Delvaux, Catherine

    2013-03-01

    The role of the tegument during the herpesvirus lytic cycle is still not clearly established, particularly at the late phase of infection, when the newly produced viral particles need to be fully assembled before being released from the infected cell. The varicella-zoster virus (VZV) protein coded by open reading frame (ORF) 9 (ORF9p) is an essential tegument protein, and, even though its mRNA is the most expressed during the productive infection, little is known about its functions. Using a GalK positive/negative selection technique, we modified a bacterial artificial chromosome (BAC) containing the complete VZV genome to create viruses expressing mutant versions of ORF9p. We showed that ORF9p is hyperphosphorylated during the infection, especially through its interaction with the viral Ser/Thr kinase ORF47p; we identified a consensus site within ORF9p recognized by ORF47p and demonstrated its importance for ORF9p phosphorylation. Strikingly, an ultrastructural analysis revealed that the mutation of this consensus site (glutamate 85 to arginine) strongly affects viral assembly and release, reproducing the ORF47 kinase-dead VZV phenotype. It also slightly diminishes the infectivity toward immature dendritic cells. Taken together, our results identify ORF9p as a new viral substrate of ORF47p and suggest a determinant role of this phosphorylation for viral infectivity, especially during the process of viral particle formation and egress.

  15. Palomar and Table Mountain Observations of 9P/Tempel 1 during the Deep Impact Encounter: First Results

    NASA Technical Reports Server (NTRS)

    Bauer, James M.; Weissman, Paul R.; Choi, Young-Jun; Troy, Mitchell; Young, James W.; Lisse, Carey M.; Dekany, Richard; Hanner, Martha S.; Buratti, Bonnie J.

    2007-01-01

    We present the first results of the Palomar Adaptive Optics observations taken during the Deep Impact encounter with 9P/Tempel 1 in July 2005. We have combined the Palomar near-IR imaging data with our visual wavelength images obtained simultaneously at JPL's Table Mountain Observatory to cover the total wavelength range from 0.4 to 2.3 micrometers in the B, V, R, I, J, H, and K filter bands, spanning the dates from 2005 July 03-07.We also include in our overall analysis images taken on the pre-encounter dates of June 1 and June 15, 2005. The broad wavelength range of our observations, along with high temporal resolution, near-IR sensitivity, and spatial resolution of our imaging, have enabled us to place constraints on the temperature of the impact flash and incandescent plume of greater than 700 K, and to provide mean dust velocities of order 197 +/- 16 m/s approximately 1.25 h after impact derived from our 1.64 micro observations. Our ejected dust mass estimates, as derived from our near-IR observations, are an order of magnitude less than those previously reported for visual wavelength observations.

  16. The MUT9p kinase phosphorylates histone H3 threonine 3 and is necessary for heritable epigenetic silencing in Chlamydomonas.

    PubMed

    Casas-Mollano, J Armando; Jeong, Byeong-Ryool; Xu, Jianping; Moriyama, Hideaki; Cerutti, Heriberto

    2008-04-29

    Changes in chromatin organization are emerging as key regulators in nearly every aspect of DNA-templated metabolism in eukaryotes. Histones undergo many, largely reversible, posttranslational modifications that affect chromatin structure. Some modifications, such as trimethylation of histone H3 on Lys 4 (H3K4me3), correlate with transcriptional activation, whereas others, such as methylation of histone H3 on Lys 27 (H3K27me), are associated with silent chromatin. Posttranslational histone modifications may also be involved in the inheritance of chromatin states. Histone phosphorylation has been implicated in a variety of cellular processes but, because of the dynamic nature of this modification, its potential role in long-term gene silencing has remained relatively unexplored. We report here that a Chlamydomonas reinhardtii mutant defective in a Ser/Thr protein kinase (MUT9p), which phosphorylates histones H3 and H2A, shows deficiencies in the heritable repression of transgenes and transposons. Moreover, based on chromatin immunoprecipitation analyses, phosphorylated H3T3 (H3T3ph) and monomethylated H3K4 (H3K4me1) are inversely correlated with di/trimethylated H3K4 and associate preferentially with silenced transcription units. Conversely, the loss of those marks in mutant strains correlates with the transcriptional reactivation of transgenes and transposons. Our results suggest that H3T3ph and H3K4me1 function as reinforcing epigenetic marks for the silencing of euchromatic loci in Chlamydomonas. PMID:18420823

  17. Search for Ammonia Radio Emission in Comet 9P/Tempel~1 after the Deep Impact Event

    NASA Astrophysics Data System (ADS)

    Tozzi, G. P.; Palagi, F.; Codella, C.; Poppi, S.; Crovisier, J.

    About 30 hours after the DI impact event, comet 9P/Tempel 1 has been observed with the 32 m dish of Medicina observatory (Bologna, Italy) to search for the NH_3 inversion transitions in the region around 24 GHz. The results show the presence of a line with S/N of about 6 and a FWHM equal to 1.35 km/s close to the NH_3(1,1) frequency. The cometary origin of the line seems sure, because the search for possible background sources of such a emission, performed a few days later along the same comet path, did not show any line at that frequency. Its identification is however dubious because of its too high outflow projected velocity and the too high ammonia production necessary to fit the line intensity. The frequency of the line is also close to a transition of methyl formate, a species already observed in comet Hale-Bopp and in hot cores. The outflow projected velocity would be smaller than in the case of the ammonia, but its abundance would be too high as well.

  18. BT2 reveals new 'distributed source' water lines in comet 9P, not observed in 73P

    NASA Astrophysics Data System (ADS)

    Barber, R.; Miller, S.; Stallard, T.; Tennyson, J.

    The recently puplished Barber-Tennyson (BT2) synthetic H2 O water line list is the most complete and accurate line list in existence. It is finding application in a wide range of astrophysical environments. BT2 has been used to identify non-resonant fluorescent transitions in comets and determine rotational and spin temperatures of cometary comas from the intensities of these lines. UKIRT spectra of comet 9P/Tempel 1 reveal H2 O lines not previosly recorded in any other cometary spectra. BT2 has identified these lines as originating from rovibrational states that are not able to be populated by the normal pumping mechanism, and are assumed to be due a first stage of radiative de-excitation by molecules that have sublimed from icy grains produced by the Deep Impact event. These lines were not observed in our follow-up observations on 73P/Schwassmann-Wachmann 3, C fragment. References: Barber R.J., Tennyson J., Harris G., Tolchenov R., 2006, MNRAS, 368, 1087 Dello Russo N., DiSanti M.A., Magee-Sauer K. et al., 2004, Icarus, 168, 186 Dello Russo N., Bonev B.P., DiSanti M.A, et al., 2005, ApJ 621, 537 Barber R.J., Miller S., Stallard T., Tennyson J., et al., Icarus (submitted)

  19. Deletion of Chromosomal Region 8p21 Confers Resistance to Bortezomib and Is Associated with Upregulated Decoy TRAIL Receptor Expression in Patients with Multiple Myeloma.

    PubMed

    Duru, Adil Doganay; Sutlu, Tolga; Wallblom, Ann; Uttervall, Katarina; Lund, Johan; Stellan, Birgitta; Gahrton, Gösta; Nahi, Hareth; Alici, Evren

    2015-01-01

    Loss of the chromosomal region 8p21 negatively effects survival in patients with multiple myeloma (MM) that undergo autologous stem cell transplantation (ASCT). In this study, we aimed to identify the immunological and molecular consequences of del(8)(p21) with regards to treatment response and bortezomib resistance. In patients receiving bortezomib as a single first line agent without any high-dose therapy, we have observed that patients with del(8)(p21) responded poorly to bortezomib with 50% showing no response while patients without the deletion had a response rate of 90%. In vitro analysis revealed a higher resistance to bortezomib possibly due to an altered gene expression profile caused by del(8)(p21) including genes such as TRAIL-R4, CCDC25, RHOBTB2, PTK2B, SCARA3, MYC, BCL2 and TP53. Furthermore, while bortezomib sensitized MM cells without del(8)(p21) to TRAIL/APO2L mediated apoptosis, in cells with del(8)(p21) bortezomib failed to upregulate the pro-apoptotic death receptors TRAIL-R1 and TRAIL-R2 which are located on the 8p21 region. Also expressing higher levels of the decoy death receptor TRAIL-R4, these cells were largely resistant to TRAIL/APO2L mediated apoptosis. Corroborating the clinical outcome of the patients, our data provides a potential explanation regarding the poor response of MM patients with del(8)(p21) to bortezomib treatment. Furthermore, our clinical analysis suggests that including immunomodulatory agents such as Lenalidomide in the treatment regimen may help to overcome this negative effect, providing an alternative consideration in treatment planning of MM patients with del(8)(p21). PMID:26378933

  20. Structural modeling identified the tRNA-binding domain of Utp8p, an essential nucleolar component of the nuclear tRNA export machinery of Saccharomyces cerevisiae.

    PubMed

    McGuire, Andrew T; Keates, Robert A B; Cook, Stephanie; Mangroo, Dev

    2009-04-01

    Utp8p is an essential 80 kDa intranuclear tRNA chaperone that transports tRNAs from the nucleolus to the nuclear tRNA export receptors in Saccharomyces cerevisiae. To help understand the mechanism of Utp8p function, predictive tools were used to derive a partial model of the tertiary structure of Utp8p. Secondary structure prediction, supported by circular dichroism measurements, indicated that Utp8p is divided into 2 domains: the N-terminal beta sheet and the C-terminal alpha helical domain. Tertiary structure prediction was more challenging, because the amino acid sequence of Utp8p is not directly homologous to any known protein structure. The tertiary structures predicted by threading and fold recognition had generally modest scores, but for the C-terminal domain, threading and fold recognition consistently pointed to an alpha-alpha superhelix. Because of the sequence diversity of this fold type, no single structural template was an ideal fit to the Utp8p sequence. Instead, a composite template was constructed from 3 different alpha-alpha superhelix structures that gave the best matches to different portions of the C-terminal domain sequence. In the resulting model, the most conserved sequences grouped in a tight cluster of positive charges on a protein that is otherwise predominantly negative, suggesting that the positive-charge cleft may be the tRNA-binding site. Mutations of conserved positive residues in the proposed binding site resulted in a reduction in the affinity of Utp8p for tRNA both in vivo and in vitro. Models were also derived for the 10 fungal homologues of Utp8p, and the localization of the positive charges on the conserved surface was found in all cases. Taken together, these data suggest that the positive-charge cleft of the C-terminal domain of Utp8p is involved in tRNA-binding.

  1. Deletion of Chromosomal Region 8p21 Confers Resistance to Bortezomib and Is Associated with Upregulated Decoy TRAIL Receptor Expression in Patients with Multiple Myeloma.

    PubMed

    Duru, Adil Doganay; Sutlu, Tolga; Wallblom, Ann; Uttervall, Katarina; Lund, Johan; Stellan, Birgitta; Gahrton, Gösta; Nahi, Hareth; Alici, Evren

    2015-01-01

    Loss of the chromosomal region 8p21 negatively effects survival in patients with multiple myeloma (MM) that undergo autologous stem cell transplantation (ASCT). In this study, we aimed to identify the immunological and molecular consequences of del(8)(p21) with regards to treatment response and bortezomib resistance. In patients receiving bortezomib as a single first line agent without any high-dose therapy, we have observed that patients with del(8)(p21) responded poorly to bortezomib with 50% showing no response while patients without the deletion had a response rate of 90%. In vitro analysis revealed a higher resistance to bortezomib possibly due to an altered gene expression profile caused by del(8)(p21) including genes such as TRAIL-R4, CCDC25, RHOBTB2, PTK2B, SCARA3, MYC, BCL2 and TP53. Furthermore, while bortezomib sensitized MM cells without del(8)(p21) to TRAIL/APO2L mediated apoptosis, in cells with del(8)(p21) bortezomib failed to upregulate the pro-apoptotic death receptors TRAIL-R1 and TRAIL-R2 which are located on the 8p21 region. Also expressing higher levels of the decoy death receptor TRAIL-R4, these cells were largely resistant to TRAIL/APO2L mediated apoptosis. Corroborating the clinical outcome of the patients, our data provides a potential explanation regarding the poor response of MM patients with del(8)(p21) to bortezomib treatment. Furthermore, our clinical analysis suggests that including immunomodulatory agents such as Lenalidomide in the treatment regimen may help to overcome this negative effect, providing an alternative consideration in treatment planning of MM patients with del(8)(p21).

  2. GALAXY EVOLUTION EXPLORER OBSERVATIONS OF CS AND OH EMISSION IN COMET 9P/TEMPEL 1 DURING DEEP IMPACT

    SciTech Connect

    Feldman, Paul D.; McCandliss, Stephan R.; Morgenthaler, Jeffrey P.; Lisse, Carey M.; Weaver, Harold A.; A'Hearn, Michael F.

    2010-03-10

    Galaxy Evolution Explorer (GALEX) observations of comet 9P/Tempel 1 using the near-ultraviolet (NUV) objective grism were made before, during and after the Deep Impact event that occurred on 2005 July 4 at 05:52:03 UT when a 370 kg NASA spacecraft was maneuvered into the path of the comet. The NUV channel provides usable spectral information in a bandpass covering 2000-3400 A with a point source spectral resolving power of R {approx} 100. The primary spectral features in this range include solar continuum scattered from cometary dust and emissions from OH and CS molecular bands centered near 3085 and 2575 A, respectively. In particular, we report the only cometary CS emission detected during this event. The observations allow the evolution of these spectral features to be tracked over the period of the encounter. In general, the NUV emissions observed from Tempel 1 are much fainter than those that have been observed by GALEX from other comets. However, it is possible to derive production rates for the parent molecules of the species detected by GALEX in Tempel 1 and to determine the number of these molecules liberated by the impact. The derived quiescent production rates are Q(H{sub 2}O) = 6.4 x 10{sup 27} molecules s{sup -1} and Q(CS{sub 2}) = 6.7 x 10{sup 24} molecules s{sup -1}, while the impact produced an additional 1.6 x 10{sup 32} H{sub 2}O molecules and 1.3 x 10{sup 29} CS{sub 2} molecules, a similar ratio as in quiescent outgassing.

  3. On the pre-perihelion temporal activity of comet 9P/Tempel 1 during the favorable apparition of 2005

    NASA Astrophysics Data System (ADS)

    de Almeida, A.; Serrano, G.; Sanzovo, G.; Trevisan Sanzovo, D.

    2014-07-01

    The short-period (5.5 years) comet 9P/Tempel 1 was revisited by NASA's Stardust-NExT probe in 2011 February 15, in a flyby at a distance of only about 181 km. This is the first time a comet is visited twice by two different probes (the first visit in 2005 July 4, by NASA's Deep Impact probe). Tempel 1 is not a bright or very active comet. The brightest apparent magnitude in 25 appearances, since the discovery (1867), has been m=9.5, well below the limit of visibility to the naked eye. Here, we study the temporal activity, based on 495 apparent visual magnitude estimates (ICQ), obtained during the very favorable apparition of 2005 (the comet passed at 0.71 au from the Earth in 2005 May 3) by the Semi-Empirical Method of Visual Magnitudes (SEMVM, de Almeida, Singh&Huebner, 1997). We determine a model dependent activity at the time immediately before the Deep Impact (4 July 2005 at 5:52 UTC) in fairly good agreement with Schleicher et al. (2006), Feaga et al. (2007) and Gicquel et al. (2012) from the Spitzer spacecraft observations, and a day later, at the time of the perihelion passage (5 July 2005 at 5:31 UTC), also in good agreement with Biver et al. (2007) and Farnham et al. (2010), most likely powered by water-ice sublimation. Our results are consistent, for an active area of 10% and a minimum nuclear radius of 2.5 km , with the radio OH observations in 18-cm (Howell et al., 2007; Biver et al., 2007), and the H_2O observations by satellites SWAN (Mäkinen et al., 2007; Bensch et al., 2007) and Odin (Biver et al., 2007), in the pre-perihelion phase.

  4. The genes for the {alpha}-type HC3 (PMSA2) and {beta}-type HC5 (PMSB1) subunits of human proteasomes map to chromosomes 6q27 and 7p12-p13 by fluorescence in situ hybridization

    SciTech Connect

    Okumura, Katsuzumi; Nogami, Masahiro; Taguchi, Hiroshi

    1995-05-20

    The authors have determined the locations of the genes for the two subunits, HC3 and HC5, by fluorescence in situ hybridization (FISH). Chromosome spreads were obtained from phytohemagglutinin-stimulated blood lymphocytes of a healthy donor after thymidine synchronization and bromodeoxyuridine incorporation by the method of Takahashi et al. Genomic DNA fragments of HC3 (4.3 kb, including exons 3, 4, and 5) and HC5 (7.5 kb including exons 1 and 2) (11) were labeled with biotin-16-dUTP by nick-translation. In situ hybridization was performed according to Lichter et al. in the presence of COT-1 DNA as a competitor. Hybridized probe was detected with FITC-conjugated avidin without further signal amplification. Comparison of the fluorescence signals and the banding patterns of the chromosomes indicated that the HC3 and HC5 genes were located on chromosome band 6q27 and 7p12-p13, respectively.

  5. Fryns syndrome phenotype caused by chromosome microdeletions at 15q26.2 and 8p23.1

    PubMed Central

    Slavotinek, A; Lee, S; Davis, R; Shrit, A; Leppig, K; Rhim, J; Jasnosz, K; Albertson, D; Pinkel, D

    2005-01-01

    Background: Fryns syndrome (FS) is the commonest autosomal recessive syndrome in which congenital diaphragmatic hernia (CDH) is a cardinal feature. It has been estimated that 10% of patients with CDH have FS. The autosomal recessive inheritance in FS contrasts with the sporadic inheritance for the majority of patients with CDH and renders the correct diagnosis critical for accurate genetic counselling. The cause of FS is unknown. Methods: We have used array comparative genomic hybridisation (array CGH) to screen patients who have CDH and additional phenotypic anomalies consistent with FS for cryptic chromosome aberrations. Results: We present three probands who were previously diagnosed with FS who had submicroscopic chromosome deletions detected by array CGH after normal karyotyping with G-banded chromosome analysis. Two female infants were found to have microdeletions involving chromosome band 15q26.2 and one male had a deletion of chromosome band 8p23.1. Conclusions: We conclude that phenotypes similar to FS can be caused by submicroscopic chromosome deletions and that high resolution karyotyping, including array CGH if possible, should be performed prior to the diagnosis of FS to provide an accurate recurrence risk in patients with CDH and physical anomalies consistent with FS. PMID:16141010

  6. Identification of a novel partner gene, TPR, fused to FGFR1 in 8p11 myeloproliferative syndrome.

    PubMed

    Li, Feng; Zhai, Yong-Ping; Tang, Yu-Mei; Wang, Li-Ping; Wan, Pin-Jun

    2012-09-01

    The 8p11 myeloproliferative syndrome (EMS) is an aggressive neoplasm caused by the fusion of various partner genes to fibroblast growth factor receptor 1 (FGFR1). Various FGFR1 fusions are associated with subtly distinct disease phenotypes. Here, we report a new translocation at the FGFR1 locus in a patient who carried t(1;8)(q25;p11.2) and presented with myeloproliferative neoplasm-like symptoms. The patient was characterized by myeloid hyperplasia of bone marrow, markedly elevated numbers of monocytes, and normal to mildly elevated eosinophils. Initial fluorescent in situ hybridization analysis confirmed that FGFR1 in this patient was disrupted. Subsequent analysis led to the identification of a novel translocation, in which exon 23 of the translocated promoter region (TPR) gene at chromosome band 1q25 was fused to exon 13 of FGFR1 (RefSeq NM_0231102.2). The TPR portion of the fusion protein contains putative functional motifs including an N-terminal TprMet domain, nuclear pore complexes associating domain, and multiple coiled-coil domains. It is likely that one or more of the motifs from TPR contribute to dimerization, resulting in constitutive activation of the FGFR1 kinase domain. Our results further support a critical role of FGFR1 in the pathogenesis of EMS and may lead to more accurate diagnosis and potential targeted therapy.

  7. Linkage disequilibrium and haplotype studies of chromosome 8p 11. 1-21. 1 markers and Werner syndrome

    SciTech Connect

    Yu, Chang-En; Schellenberg, G.D.; Oshima, Junko; Martin, G.M.; Goddard, K.A.B.; Wijsman, E.M. ); Miki, Tetsuro; Nakura, Jun; Ogihara, Toshio ); Poot, M.; Hoehn, H. )

    1994-08-01

    Werner syndrome (WS) is an autosomal recessive disorder, characterized as a progeroid syndrome, previously mapped to the 8p 11.2-21.1 region. Because WS is so rare, and because many patients are from consanguineous marriages, fine localization of the gene by traditional meiotic mapping methods is unlikely to succeed. Here the authors present the results of a search for a region that exhibits linkage disequilibrium with the disorder, under the assumption that identification of such a region may provide an alternative method of narrowing down the location of WRN, the gene responsible for WS. They present allele frequencies in Japanese and Caucasian cases and controls for D8S137, D8S131, D8S87, D8S278, D8S259, D8S283, fibroblast growth factor receptor 1, ankyrin 1, D8S339, and two polymorphisms in glutathione reductase (GSR), covering [approximately] 16.5 cM in total. They show that three of the markers examined - D8S339 and both polymorphisms in the GSR locus - show strong statistically significant evidence of disequilibrium with WRN in the Japanese population but not in the Caucasian population. In addition, they show that a limited number of haplotypes are associated with the disease in both populations and that these haplotypes define clusters of apparently related haplotypes that may identify as many as eight or nine independent WRN mutations in these two populations. 36 refs., 1 fig., 4 tabs.

  8. A Multi-Wavelength Simultaneous Study of the Composition of the Halley Family Comet 8P/Tuttle

    NASA Astrophysics Data System (ADS)

    Jehin, E.; Bockelée-Morvan, D.; Dello Russo, N.; Manfroid, J.; Hutsemékers, D.; Kawakita, H.; Kobayashi, H.; Schulz, R.; Smette, A.; Stüwe, J.; Weiler, M.; Arpigny, C.; Biver, N.; Cochran, A.; Crovisier, J.; Magain, P.; Rauer, H.; Sana, H.; Vervack, R. J.; Weaver, H.; Zucconi, J.-M.

    2009-09-01

    We report on simultaneous optical and infrared observations of the Halley Family comet 8P/Tuttle performed with the ESO Very Large Telescope. Such multi-wavelength and coordinated observations are a good example of what can be done to support space missions. From high resolution optical spectroscopy of the CN (0,0) 388 nm and NH2 (0,9,0) 610 nm bands using UVES at UT2 we determined 12C/13C = 90 ± 10 and 14N/15N = 150 ± 20 in CN and we derived a nuclear spin temperature of NH3 of 29 ± 1 K. These values are similar to those found in Oort-Cloud and Jupiter Family comets. From low resolution long slit spectroscopy with FORS1 at UT2 we determined the CN, C3 and C2 production rates and the parent and daughter scale lengths up to 5.2 105 km tailward. From high resolution IR spectroscopy with CRIRES at UT1 we measured simultaneously the production rates and mixing ratios of H2O, HCN, C2H2, CH4, C2H6, and CH3OH.

  9. Full genomic characterization and phylogenetic analysis of a zoonotic human G8P[14] rotavirus strain detected in a sample from Guatemala.

    PubMed

    Gautam, Rashi; Mijatovic-Rustempasic, Slavica; Roy, Sunando; Esona, Mathew D; Lopez, Beatriz; Mencos, Yolanda; Rey-Benito, Gloria; Bowen, Michael D

    2015-07-01

    We report the genomic characterization of a rare human G8P[14] rotavirus strain, identified in a stool sample from Guatemala (GTM) during routine rotavirus surveillance. This strain was designated as RVA/Human-wt/GTM/2009726790/2009/G8P[14], with a genomic constellation of G8-P[14]-I2-R2-C2-M2-A13-N2-T6-E2-H3. The VP4 gene occupied lineage VII within the P[14] genotype. Phylogenetic analysis of each genome segment revealed close relatedness to several zoonotic simian, guanaco and bovine strains. Our findings suggest that strain RVA/Human-wt/GTM/2009726790/2009/G8P[14] is an example of a direct zoonotic transmission event. The results of this study reinforce the potential role of interspecies transmission and reassortment in generating novel and rare rotavirus strains which infect humans.

  10. Full genomic characterization and phylogenetic analysis of a zoonotic human G8P[14] rotavirus strain detected in a sample from Guatemala.

    PubMed

    Gautam, Rashi; Mijatovic-Rustempasic, Slavica; Roy, Sunando; Esona, Mathew D; Lopez, Beatriz; Mencos, Yolanda; Rey-Benito, Gloria; Bowen, Michael D

    2015-07-01

    We report the genomic characterization of a rare human G8P[14] rotavirus strain, identified in a stool sample from Guatemala (GTM) during routine rotavirus surveillance. This strain was designated as RVA/Human-wt/GTM/2009726790/2009/G8P[14], with a genomic constellation of G8-P[14]-I2-R2-C2-M2-A13-N2-T6-E2-H3. The VP4 gene occupied lineage VII within the P[14] genotype. Phylogenetic analysis of each genome segment revealed close relatedness to several zoonotic simian, guanaco and bovine strains. Our findings suggest that strain RVA/Human-wt/GTM/2009726790/2009/G8P[14] is an example of a direct zoonotic transmission event. The results of this study reinforce the potential role of interspecies transmission and reassortment in generating novel and rare rotavirus strains which infect humans. PMID:25952569

  11. Deep Impact, Stardust-NExT and the Behavior of Comet 9P/Tempel 1 from 1997 to 2010

    NASA Technical Reports Server (NTRS)

    Meech, K. J.; Pittichova, J.; Yang, B.; Zenn, A.; Belton, M. J. S.; A'Hearn, M. F.; Bagnulo, S.; Bai, J.; Barrera, L.; Bauer, J. M.; Bedient, J.; Bhatt, B. C.; Boehnhardt H.; Brosch, N.; Buie, M.; Candia, P.; Chen, W. P.; Chesley, S.; Choi, Y.-J.; Cochran, A.; Duddy, S.; Farnham, T. L.; Fernandez, Y.; Gutierrez, P.

    2011-01-01

    We present observational data for Comet 9P/Tempel 1 taken from 1997 through 2010 in an international collaboration in support of the Deep Impact and Stardust-NExT missions. The data were obtained to characterize the nucleus prior to the Deep Impact 2005 encounter, and to enable us to understand the rotation state in order to make a time of arrival adjustment in February 2010 that would allow us to image at least 25% of the nucleus seen by the Deep Impact spacecraft to better than 80 m/pixel, and to image the crater made during the encounter, if possible. In total, approx.500 whole or partial nights were allocated to this project at 14 observatories worldwide, utilizing 25 telescopes. Seventy percent of these nights yielded useful data. The data were used to determine the linear phase coefficient for the comet in the R-band to be 0.045 +/- 0.001 mag/deg from 1deg to 16deg. Cometary activity was observed to begin inbound near r approx. 4.0 AU and the activity ended near r approx. 4.6 AU as seen from the heliocentric secular light curves, water-sublimation models and from dust dynamical modeling. The light curve exhibits a significant pre- and post-perihelion brightness and activity asymmetry. There was a secular decrease in activity between the 2000 and 2005 perihelion passages of approx. 20%. The post-perihelion light curve cannot be easily explained by a simple decrease in solar insolation or observing geometry. CN emission was detected in the comet at 2.43 AU pre-perihelion, and by r = 2.24 AU emission from C2 and C3 were evident. In December 2004 the production rate of CN increased from 1.8 x 10(exp 23) mol/s to Q(sub CN) = 2.75 x 10(exp 23) mol/s in early January 2005 and 9.3 x 10(exp 24) mol/s on June 6, 2005 at r = 1.53 AU.

  12. A gene defect causing a novel progressive epilepsy with mental retardation, EPMR, maps to chromosome 8p

    SciTech Connect

    Ranta, S.; Tahvanainen, E.; Karila, E.

    1994-09-01

    EPMR (progressive epilepsy with mental retardation) is a newly discovered autosomal recessively inherited disorder which occurs with high frequency in an isolated rural population in Finland. So far 25 patients have been identified, 21 of whom are alive. Twenty-three patients share a common ancestor from the 18th century. The main features of EPMR are: normal early development, tonic-clonic seizures with onset between ages 5 and 10, and mental retardation which begins approximately 2 years after the onset of epilepsy and soon leads to deepening mental retardation. Adult patients do not manage their daily life without help. The EEG is normal at the onset of epilepsy but later progressive slowing of the background activity occurs. The etiology and pathogenesis of EPMR remain known. As this is a novel disease entity without any definitive diagnostic marker we wished to begin its elucidation by first defining its gene locus. A random search for linkage in four multiplex families (only 20 individuals tested) resulted in the finding of linkage to marker D8S264 with a lod score of 4.45 at zero recombination. The EPMR gene resides in a 7 centimorgan interval between marker loci AFM185xb2 and D8S262 with a maximum multipoint lod score of 7.03 at 1.8 centimorgans proximal to D8S264. Physically this region is very distal on 8p. Of the sixteen EPMR chromosomes haplotyped 15 were identical or almost identical. One chromosome, however, had a distinctly different haplotype raising the possibility of there being two different mutations or one very old mutation. These findings are a starting point toward isolating and characterizing the gene and its protein product. Physical mapping has been initiated by isolating nine YACs from the region.

  13. TSQ (6-methoxy-8-p-toluenesulfonamido-quinoline), a common fluorescent sensor for cellular zinc, images zinc proteins.

    PubMed

    Meeusen, Jeffrey W; Tomasiewicz, Henry; Nowakowski, Andrew; Petering, David H

    2011-08-15

    Zn(2+) is a necessary cofactor for thousands of mammalian proteins. Research has suggested that transient fluxes of cellular Zn(2+) are also involved in processes such as apoptosis. Observations of Zn(2+) trafficking have been collected using Zn(2+) responsive fluorescent dyes. A commonly used Zn(2+) fluorophore is 6-methoxy-8-p-toluenesulfonamido-quinoline (TSQ). The chemical species responsible for TSQ's observed fluorescence in resting or activated cells have not been characterized. Parallel fluorescence microscopy and spectrofluorometry of LLC-PK(1) cells incubated with TSQ demonstrated punctate staining that concentrated around the nucleus and was characterized by an emission maximum near 470 nm. Addition of cell permeable Zn-pyrithione resulted in greatly increased, diffuse fluorescence that shifted the emission peak to 490 nm, indicative of the formation of Zn(TSQ)(2). TPEN (N,N,N'N'-tetrakis(-)[2-pyridylmethyl]-ethylenediamine), a cell permeant Zn(2+) chelator, largely quenched TSQ fluorescence returning the residual fluorescence to the 470 nm emission maximum. Gel filtration chromatography of cell supernatant from LLC-PK(1) cells treated with TSQ revealed that TSQ fluorescence (470 nm emission) eluted with the proteome fractions. Similarly, addition of TSQ to proteome prior to chromatography resulted in 470 nm fluorescence emission that was not observed in smaller molecular weight fractions. It is hypothesized that Zn-TSQ fluorescence, blue-shifted from the 490 nm emission maximum of Zn(TSQ)(2), results from ternary complex, TSQ-Zn-protein formation. As an example, Zn-carbonic anhydrase formed a ternary adduct with TSQ characterized by a fluorescence emission maximum of 470 nm and a dissociation constant of 1.55 × 10(-7) M. Quantification of TSQ-Zn-proteome fluorescence indicated that approximately 8% of cellular Zn(2+) was imaged by TSQ. These results were generalized to other cell types and model Zn-proteins. PMID:21774459

  14. Localization of the gene for hyperostosis cranialis interna to chromosome 8p21 with analysis of three candidate genes.

    PubMed

    Borra, V M; Waterval, J J; Stokroos, R J; Manni, J J; Van Hul, W

    2013-07-01

    Hyperostosis cranialis interna (HCI) is a rare autosomal dominant disorder characterized by intracranial hyperostosis and osteosclerosis, which is confined to the skull, especially the calvarium and the skull base. The rest of the skeleton is not affected. Progressive bone overgrowth causes nerve entrapment that leads to recurrent facial nerve palsy, disturbance of the sense of smell, hearing and vision impairments, impairment of facial sensibility, and disturbance of balance due to vestibular areflexia. The treatment is symptomatic. Histomorphological investigations showed increased bone formation with a normal tissue structure. Biochemical parameters were normal. Until today the disease has been described in only three related Dutch families with common progenitors and which consist of 32 individuals over five generations. HCI was observed in 12 family members over four generations. Patients are mildly to severely affected. Besides HCI, several bone dysplasias with hyperostosis and sclerosis of the craniofacial bones are known. Examples are Van Buchem disease, sclerosteosis, craniometaphyseal dysplasia, and Camurati-Engelmann disease. However, in these cases the long bones are affected as well. Linkage analysis in a family with HCI resulted in the localization of the disease-causing gene to a region on chromosome 8p21 delineated by markers D8S282 and D8S382. Interesting candidate genes in this region are BMP1, LOXL2, and ADAM28. Sequence analysis of these genes did not reveal any putative mutations. This suggests that a gene not previously involved in a sclerosing bone dysplasia is responsible for the abnormal growth in the skull of these patients.

  15. Functional characterization, localization, and inhibitor sensitivity of the TPR-FGFR1 fusion in 8p11 myeloproliferative syndrome.

    PubMed

    Malli, Theodora; Buxhofer-Ausch, Veronika; Rammer, Melanie; Erdel, Martin; Kranewitter, Wolfgang; Rumpold, Holger; Marschon, Renate; Deutschbauer, Sabine; Simonitsch-Klupp, Ingrid; Valent, Peter; Muellner-Ammer, Kirsten; Sebesta, Christian; Birkner, Thomas; Webersinke, Gerald

    2016-01-01

    Myeloid and lymphoid neoplasms with fibroblast growth factor receptor 1 (FGFR1) abnormalities, also known as 8p11 myeloproliferative syndrome (EMS), represent rare and aggressive disorders, associated with chromosomal aberrations that lead to the fusion of FGFR1 to different partner genes. We report on a third patient with a fusion of the translocated promoter region (TPR) gene, a component of the nuclear pore complex, to FGFR1 due to a novel ins(1;8)(q25;p11p23). The fact that this fusion is a rare but recurrent event in EMS prompted us to examine the localization and transforming potential of the chimeric protein. TPR-FGFR1 localizes in the cytoplasm, although the nuclear pore localization signal of TPR is retained in the fusion protein. Furthermore, TPR-FGFR1 enables cytokine-independent survival, proliferation, and granulocytic differentiation of the interleukin-3 dependent myeloid progenitor cell line 32Dcl3, reflecting the chronic phase of EMS characterized by myeloid hyperplasia. 32Dcl3 cells transformed with the TPR-FGFR1 fusion and treated with increasing concentrations of the tyrosine kinase inhibitors ponatinib (AP24534) and infigratinib (NVP-BGJ398) displayed reduced survival and proliferation with IC50 values of 49.8 and 7.7 nM, respectively. Ponatinib, a multitargeted tyrosine kinase inhibitor, is already shown to be effective against several FGFR1-fusion kinases. Infigratinib, tested only against FGFR1OP2-FGFR1 to date, is also efficient against TPR-FGFR1. Taking its high specificity for FGFRs into account, infigratinib could be beneficial for EMS patients and should be further investigated for the treatment of myeloproliferative neoplasms with FGFR1 abnormalities.

  16. Cd2+, Mn2+, Ni2+ and Se2+ toxicity to Saccharomyces cerevisiae lacking YPK9p the orthologue of human ATP13A2

    PubMed Central

    Schmidt, Karyn; Wolfe, Devin M; Stiller, Barbara; Pearce, David A

    2014-01-01

    The Saccharomyces cerevisiae gene YPK9 encodes a putative integral membrane protein which is 58% similar and 38% identical in amino acid sequence to the human lysosomal P5B ATPase ATP13A2. Mutations in ATP13A2 have been found in patients with Kufor-Rakeb syndrome, a form of juvenile Parkinsonism. We report that Ypk9p localizes to the yeast vacuole and that deletion of YPK9 confers sensitivity for growth for cadmium, manganese, nickel or selenium. These results suggest that Ypk9p may play a role in sequestration of divalent heavy metal ions. Further studies on the function of Ypk9p/ATP13A2 may help to define the molecular basis of Kufor-Rakeb syndrome and provide a potential link to environmental factors such as heavy metals contributing to some forms of Parkinsonism. PMID:19345671

  17. The relationship between diastolic blood pressure and coronary artery calcification is dependent on single nucleotide polymorphisms on chromosome 9p21.3

    PubMed Central

    2014-01-01

    Background Single nucleotide polymorphisms (SNPs) within the 9p21.3 genomic region have been consistently associated with coronary heart disease (CHD), myocardial infarction, and quantity of coronary artery calcification (CAC), a marker of subclinical atherosclerosis. Prior studies have established an association between blood pressure measures and CAC. To examine mechanisms by which the 9p21.3 genomic region may influence CHD risk, we investigated whether SNPs in 9p21.3 modified associations between blood pressure and CAC quantity. Methods As part of the Genetic Epidemiology Network of Arteriopathy (GENOA) Study, 974 participants underwent non-invasive computed tomography (CT) to measure CAC quantity. Linear mixed effects models were used to investigate whether seven SNPs in the 9p21.3 region modified the association between blood pressure levels and CAC quantity. Four SNPs of at least marginal significance in GENOA for a SNP-by-diastolic blood pressure (DBP) interaction were then tested for replication in the Framingham Heart Study’s Offspring Cohort (N = 1,140). Results We found replicated evidence that one SNP, rs2069416, in CDKN2B-AS1, significantly modified the association between DBP and CAC quantity (combined P = 0.0065; Bonferroni-corrected combined P = 0.0455). Conclusions Our results represent a novel finding that the relationship between DBP and CAC is dependent on genetic variation in the 9p21.3 region. Thus, variation in 9p21.3 may not only be an independent genetic risk factor for CHD, but also may modify the association between DBP levels and the extent of subclinical coronary atherosclerosis. PMID:25185447

  18. Dextrocardia, atrial septal defect, severe developmental delay, facial anomalies, and supernumerary ribs in a child with a complex unbalanced 8;22 translocation including partial 8p duplication.

    PubMed

    Pope, Kathleen; Samanich, Joy; Ramesh, K H; Cannizzaro, Linda; Pan, Qiulu; Babcock, Melanie

    2012-03-01

    We report on a child with dextrocardia, atrial septal defect (ASD), severe developmental delay, hypotonia, 13 pairs of ribs, left preauricular choristoma, hirsutism, and craniofacial abnormalities. Prenatal cytogenetic evaluation showed karyotype 46,XY,?dup(8p)ish del(8)pter. Postnatal array CGH demonstrated a 6.8 Mb terminal deletion at 8p23.3-p23, an interstitial 31.1 Mb duplication within 8p23.1-p11, and a terminal duplication of 0.24 Mb at 22q13.33, refining the karyotype to 46,XY,der(8)dup(8)(p23.1p11.1)t(8;22)(p23.1;q13.1).ish der(8)dup(8)(p23.1p11.1)t(8;22)(p23.1;q13.1) (D8S504-,MS607 + ,ARSA + ,D8Z1 + , RP115713 + +). Previous reports of distal 8p deletion, 8p duplication, and distal 22q duplication have shown similar manifestations, including congenital heart disease, intellectual impairment, and multiple minor anomalies. We correlate the patient's clinical findings with these particular areas of copy number. This case study supports the use of aCGH to identify subtle chromosomal rearrangement in infants with cardiac malformation as their most significant or only apparent birth defect. Additionally, it illustrates why aCGH is essential in the description of chromosome rearrangements, even those seemingly visible via routine karyotype. This method shows that there is often greater complexity submicroscopically, essential to an adequate understanding of a patient's genotype and phenotype.

  19. The OD/OH Isotope Ratio in Comets 8P/Tuttle and C/2012 F6 (Lemmon)

    NASA Astrophysics Data System (ADS)

    Rousselot, Philippe; Jehin, Emmanuel; Hutsemekers, Damien; Manfroid, Jean; Decock, Alice; Bockelee-Morvan, Dominique

    2016-10-01

    The determination of isotopic ratios in solar system objects is an important source of information about their origin, especially for comets. Among these ratios the D/H is of particular importance because of its sensitivity to fractionation processes and physical environment, and the abundance of hydrogen in the solar system. The main molecule used to derive this ratio in comets is water. So far, apart water, only HCN has permitted to derive D/H ratio and not only upper limits.Most of the existing determinations of D/H in water molecules have been obtained by spectroscopic observations of water lines in the sub-mm or near infrared range [1,2]. So far only one measurement has been based on OD/OH emission lines radicals in the near-UV [3] and another one on the Lyman-alpha D emission [4]. In situ measurements have also been obtained in comets 1P/Halley and 67P/Churyumov-Gerasimenko using mass spectrometer [5,6,7,8].In this work we have used the OH and OD ultraviolet bands at 310 nm observed with the ESO 8-m Very Large Telescope feeding the Ultraviolet-Visual Echelle Spectrograph (UVES) for measuring the D/H ratio in comets 8P/Tuttle and C/2012 F6 (Lemmon). The OH and OD being the photodissociation products of H2O and HDO such observations allow to derive D/H ratio for water molecules. This work constitutes an independant determination of the D/H ratios already published for these comets and based on observations performed in the sub-mm and near infrared range of H2O and HDO lines. We present our modeling, data analysis and numerical values obtained for this ratio.[1] D. Bockelée-Morvan et al., 2015, SSR 197, 47-83 [2] N. Biver et al., 2016, A&A 589, id A78, 11p [3] D. Hutsemékers et al., 2008, A&A 490, L31 [4] H.A. Weaver et al., 2008, LPI Contributions 1405, 8216 [5] H. Balsiger, K. Altwegg, J. Geiss, 1995, JGR 100, 5827 [6] P. Eberhardt et al., 1995, A&A 302, 301 [7] R.H. Brown et al., 2012, PSS 60, 166 [8] K. Alwegg et al., 2015, Science 347, article id. 1261952

  20. Gaa1p and Gpi8p Are Components of a Glycosylphosphatidylinositol (GPI) Transamidase That Mediates Attachment of GPI to Proteins

    PubMed Central

    Ohishi, Kazuhito; Inoue, Norimitsu; Maeda, Yusuke; Takeda, Junji; Riezman, Howard; Kinoshita, Taroh

    2000-01-01

    Many eukaryotic cell surface proteins are anchored to the membrane via glycosylphosphatidylinositol (GPI). The GPI is attached to proteins that have a GPI attachment signal peptide at the carboxyl terminus. The GPI attachment signal peptide is replaced by a preassembled GPI in the endoplasmic reticulum by a transamidation reaction through the formation of a carbonyl intermediate. GPI transamidase is a key enzyme of this posttranslational modification. Here we report that Gaa1p and Gpi8p are components of a GPI transamidase. To determine a role of Gaa1p we disrupted a GAA1/GPAA1 gene in mouse F9 cells by homologous recombination. GAA1 knockout cells were defective in the formation of carbonyl intermediates between precursor proteins and transamidase as determined by an in vitro GPI-anchoring assay. We also show that cysteine and histidine residues of Gpi8p, which are conserved in members of a cysteine protease family, are essential for generation of a carbonyl intermediate. This result suggests that Gpi8p is a catalytic component that cleaves the GPI attachment signal peptide. Moreover, Gaa1p and Gpi8p are associated with each other. Therefore, Gaa1p and Gpi8p constitute a GPI transamidase and cooperate in generating a carbonyl intermediate, a prerequisite for GPI attachment. PMID:10793132

  1. Definition of the role of chromosome 9p21 in sporadic melanoma through genetic analysis of primary tumours and their metastases

    PubMed Central

    Palmieri, G; Cossu, A; Ascierto, P A; Botti, G; Strazzullo, M; Lissia, A; Colombino, M; Casula, M; Floris, C; Tanda, F; Pirastu, M; Castello, G

    2000-01-01

    Malignant melanoma (MM) is thought to arise by sequential accumulation of genetic alterations in normal melanocytes. Previous cytogenetic and molecular studies indicated the 9p21 as the chromosomal region involved in MM pathogenesis. In addition to the CDKN genes (p16/CDKN2A, p15/CDKN2B and p19ARF, frequently inactivated in familial MM), widely reported data suggested the presence within this region of other melanoma susceptibility gene(s). To clearly assess the role of the 9p21 region in sporadic melanoma, we evaluated the presence of microsatellite instability (MSI) and loss of heterozygosity (LOH) in primary tumours as well as in synchronous or asynchronous metastases obtained from the same MM patients, using 9 polymorphic markers from a 17-cM region at 9p21. LOH and MSI were found in 27 (41%) and 11 (17%), respectively, out of 66 primary tumours analysed. In corresponding 58 metastases, MSI was found at higher rate (22; 38%), whereas a quite identical pattern of allelic deletions with 27 (47%) LOH+ cases were observed. Although the CDKN locus was mostly affected by LOH, an additional region of common allelic deletion corresponding to marker D9S171 was also identified. No significant statistical correlation between any 9p21 genetic alteration (LOH, MSI or both) and clinicopathological parameters was observed. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11104570

  2. Potential Signals of Natural Selection in the Top Risk Loci for Coronary Artery Disease: 9p21 and 10q11

    PubMed Central

    Zanetti, Daniela; Carreras-Torres, Robert; Esteban, Esther

    2015-01-01

    Background Coronary artery disease (CAD) is a complex disease and the leading cause of death in the world. Populations of different ancestry do not always share the same risk markers. Natural selective processes may be the cause of some of the population differences detected for specific risk mutations. Objective In this study, 384 single nucleotide polymorphisms (SNPs) located in four genomic regions associated with CAD (1p13, 1q41, 9p21 and 10q11) are analysed in a set of 19 populations from Europe, Middle East and North Africa and also in Asian and African samples from the 1000 Genomes Project. The aim of this survey is to explore for the first time whether the genetic variability in these genomic regions is better explained by demography or by natural selection. Results The results indicate significant differences in the structure of genetic variation and in the LD patterns among populations that probably explain the population disparities found in markers of susceptibility to CAD. Conclusions The results are consistent with potential signature of positive selection in the 9p21 region and of balancing selection in the 9p21 and 10q11. Specifically, in Europe three CAD risk markers in the 9p21 region (rs9632884, rs1537371 and rs1333042) show consistent signals of positive selection. The results of this study are consistent with a potential selective role of CAD in the configuration of genetic diversity in current human populations. PMID:26252781

  3. Ring Chromosome 9 and Chromosome 9p Deletion Syndrome in a Patient Associated with Developmental Delay: A Case Report and Review of the Literature.

    PubMed

    Sivasankaran, Aswini; Kanakavalli, Murthy K; Anuradha, Deenadayalu; Samuel, Chandra R; Kandukuri, Lakshmi R

    2016-01-01

    Ring chromosomes have been described for all human chromosomes and are typically associated with physical and/or mental abnormalities resulting from a deletion of the terminal ends of both chromosome arms. This report describes the presence of a ring chromosome 9 in a 2-year-old male child associated with developmental delay. The proband manifested a severe phenotype comprising facial dysmorphism, congenital heart defects, and seizures. The child also exhibited multiple cell lines with mosaic patterns of double rings, a dicentric ring and loss of the ring associated with mitotic instability and dynamic tissue-specific mosaicism. His karyotype was 46,XY,r(9)(p22q34)[89]/46,XY,dic r(9; 9)(p22q34;p22q34)[6]/45, XY,-9[4]/47,XY,r(9),+r(9)[1]. However, the karyotypes of his parents and elder brother were normal. FISH using mBAND probe and subtelomeric probes specific for p and q arms for chromosome 9 showed no deletion in any of the regions. Chromosomal microarray analysis led to the identification of a heterozygous deletion of 15.7 Mb from 9p22.3 to 9p24.3. The probable role of the deleted genes in the manifestation of the phenotype of the proband is discussed.

  4. Ring Chromosome 9 and Chromosome 9p Deletion Syndrome in a Patient Associated with Developmental Delay: A Case Report and Review of the Literature.

    PubMed

    Sivasankaran, Aswini; Kanakavalli, Murthy K; Anuradha, Deenadayalu; Samuel, Chandra R; Kandukuri, Lakshmi R

    2016-01-01

    Ring chromosomes have been described for all human chromosomes and are typically associated with physical and/or mental abnormalities resulting from a deletion of the terminal ends of both chromosome arms. This report describes the presence of a ring chromosome 9 in a 2-year-old male child associated with developmental delay. The proband manifested a severe phenotype comprising facial dysmorphism, congenital heart defects, and seizures. The child also exhibited multiple cell lines with mosaic patterns of double rings, a dicentric ring and loss of the ring associated with mitotic instability and dynamic tissue-specific mosaicism. His karyotype was 46,XY,r(9)(p22q34)[89]/46,XY,dic r(9; 9)(p22q34;p22q34)[6]/45, XY,-9[4]/47,XY,r(9),+r(9)[1]. However, the karyotypes of his parents and elder brother were normal. FISH using mBAND probe and subtelomeric probes specific for p and q arms for chromosome 9 showed no deletion in any of the regions. Chromosomal microarray analysis led to the identification of a heterozygous deletion of 15.7 Mb from 9p22.3 to 9p24.3. The probable role of the deleted genes in the manifestation of the phenotype of the proband is discussed. PMID:27222354

  5. High-resolution comprehensive radiation hybrid maps of the porcine chromosomes 2p and 9p compared with the human chromosome 11.

    PubMed

    Liu, W-S; Yasue, H; Eyer, K; Hiraiwa, H; Shimogiri, T; Roelofs, B; Landrito, E; Ekstrand, J; Treat, M; Paes, N; Lemos, M; Griffith, A C; Davis, M L; Meyers, S N; Yerle, M; Milan, D; Beever, J E; Schook, L B; Beattie, C W

    2008-01-01

    We are constructing high-resolution, chromosomal 'test' maps for the entire pig genome using a 12,000-rad WG-RH panel (IMNpRH2(12,000-rad))to provide a scaffold for the rapid assembly of the porcine genome sequence. Here we present an initial, comparative map of human chromosome (HSA) 11 with pig chromosomes (SSC) 2p and 9p. Two sets of RH mapping vectors were used to construct the RH framework (FW) maps for SSC2p and SSC9p. One set of 590 markers, including 131 microsatellites (MSs), 364 genes/ESTs, and 95 BAC end sequences (BESs) was typed on the IMNpRH2(12,000-rad) panel. A second set of 271 markers (28 MSs, 138 genes/ESTs, and 105 BESs) was typed on the IMpRH(7,000-rad) panel. The two data sets were merged into a single data-set of 655 markers of which 206 markers were typed on both panels. Two large linkage groups of 72 and 194 markers were assigned to SSC2p, and two linkage groups of 84 and 168 markers to SSC9p at a two-point LOD score of 10. A total of 126 and 114 FW markers were ordered with a likelihood ratio of 1000:1 to the SSC2p and SSC9p RH(12,000-rad) FW maps, respectively, with an accumulated map distance of 4046.5 cR(12,000 )and 1355.2 cR(7,000 )for SSC2p, and 4244.1 cR(12,000) and 1802.5 cR(7,000) for SSC9p. The kb/cR ratio in the IMNpRH2(12,000-rad) FW maps was 15.8 for SSC2p, and 15.4 for SSC9p, while the ratio in the IMpRH(7,000-rad) FW maps was 47.1 and 36.3, respectively, or an approximately 3.0-fold increase in map resolution in the IMNpRH(12,000-rad) panel over the IMpRH(7,000-rad) panel. The integrated IMNpRH(12,000-rad) andIMpRH(7,000-rad) maps as well as the genetic and BAC FPC maps provide an inclusive comparative map between SSC2p, SSC9p and HSA11 to close potential gaps between contigs prior to sequencing, and to identify regions where potential problems may arise in sequence assembly. PMID:18467842

  6. A familial "balanced" 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings.

    PubMed Central

    Wagstaff, J; Hemann, M

    1995-01-01

    A child with phenotypic features of the 9p- syndrome, including metopic craniosynostosis, small ears, abdominal wall defect, and mental retardation, as well as hypopigmentation, was found to have a cytogenetically balanced 3;9 translocation, with breakpoints at 3p11 and 9p23, inherited from his phenotypically normal father. Molecular analysis showed heterozygous deletion of the TYRP (tyrosinase-related protein) locus, as well as loci D9S157, D9S274, D9S268, and D9S267, in the child but in neither parent. FISH analysis of the proband's father indicated that loci deleted in his son, including TYRP, were present on neither the der(3) nor the der(9) translocation products but had been inserted into the long arm of chromosome 8. Therefore, the apparent deletion of these loci in the proband was the result of meiotic segregation of the father's 3;9 translocation chromosomes together with his normal chromosome 8 (not bearing the insertion from 9p23). Neither the deletion of these 9p23 loci from the translocation chromosomes nor their insertion into 8q was detectable by standard chromosome banding techniques. The proband's sister exhibited speech delay, mild facial dysmorphism, and renal malformation, and her karyotype was 46,XX. Molecular analysis showed that she had inherited normal chromosomes 3 and 9, as well as the chromosome 8 with the insertion of 9p23 material, from her father.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 Figure 8 PMID:7825591

  7. 8p23.1 Interstitial Deletion in a Patient with Congenital Cardiopathy, Neurobehavioral Disorders, and Minor Signs Suggesting 22q11.2 Deletion Syndrome.

    PubMed

    Molck, Miriam C; Monteiro, Fabíola P; Simioni, Milena; Gil-da-Silva-Lopes, Vera L

    2015-09-01

    Copy number variation studies of known disorders have the potential to improve the characterization of clinical phenotypes and may help identifying candidate genes and their pathways. The authors described a child with congenital heart disease, microcephaly, facial dysmorphisms, developmental delay, learning difficulties, and behavioral problems. There was initially a clinical suspicion of 22q11.2 deletion syndrome (22q11.2 DS), but molecular cytogenetic analysis (array genomic hybridization [aGH]) showed the presence of a de novo 3.6-Mb interstitial microdeletion in 8p23.1. The main features of 8p23.1 DS include congenital heart disease and behavioral problems, in addition to minor dysmorphisms and mental delay. Therefore, this article highlights the application of aGH to investigate 8p23.1 deletion in nonconfirmed 22q11.2 DS patients presenting neurobehavioral disorders, congenital cardiopathy, and minor dysmorphisms.

  8. Genomic characterization of a rotavirus G8P[1] detected in a child with diarrhea reveal direct animal-to-human transmission.

    PubMed

    Martinez, Magaly; Phan, Tung Gia; Galeano, Maria Eugenia; Russomando, Graciela; Parreno, Viviana; Delwart, Eric; Parra, Gabriel I

    2014-10-01

    Group A rotavirus is a major cause of severe gastroenteritis in children and young animals. During a retrospective analysis of samples collected from Paraguayan children under 5 years old with diarrhea, and previously negative for rotavirus and norovirus, we detected the presence of bovine rotavirus sequences by viral metagenomics. Nucleic acid was extracted direct from stool sample and determined to be G8P[1]. The genomic analyzes revealed that the strain presents an Artiodactyl-like genome (G8-P[1]-I2-R2-C2-M1-Ax-N2-T6-E12-H3) suggesting a direct animal-to-human transmission.

  9. Deletion mapping indicates that MTS1 is the target of frequent deletions at chromosome 9p21 in paediatric acute lymphoblastic leukaemias.

    PubMed

    Guidal-Giroux, C; Gérard, B; Cavé, H; Duval, M; Rohrlich, P; Elion, J; Vilmer, E; Grandchamp, B

    1996-02-01

    Recent reports have indicated a high frequency of deletions of MTS1 (CDKN2, p16ink4, CDKI4) in acute lymphoblastic leukaemias (ALLs). This gene is located at chromosome 9p21 and encodes an inhibitor of cyclin D-dependent kinases. In contrast with the observations in some other malignancies, no inactivation of MTS1 by intragenic mutation was demonstrated in leukaemias. A contribution of MTS1 alterations to leukaemogenesis therefore remains questionable. In order to test for the implication of MTS1 as a tumour suppressor gene in paediatric ALLs we have explored the 9p21 chromosomal region of 46 children with this disease. The copy number of the MTS1 gene in blasts from the patients was determined using a quantitative PCR assay enabling us to precisely detect mono- and bi-allelic deletions. Rearrangements of the gene were sought by Southern blot analysis. The extent of the deletions was studied using microsatellite markers spanning the 9p21 chromosomal region. Point mutations were sought in exon 1 and exon 2 of the MTS1 gene in patients with a mono-allelic deletion in addition, exon 2 of MTS1, which contains two-thirds of the coding region, was sequenced in all patients who had no deletion of the gene. Altogether, our data are consistent with the view that MTS1 is the target of 9p21 deletions. Either one or two alleles of the gene were deleted in 36% of non-selected children with B-lineage ALL and both alleles were deleted in all seven patients we studied with T-lineage ALL. The absence of any point mutation implies that the major mechanism of inactivation of MTS1 in ALLs is deletional.

  10. A New Case of a Complex Small Supernumerary Marker Chromosome: A Der(9)t(7;9)(p22;q22) due to a Maternal Balanced Rearrangement.

    PubMed

    Manvelyan, Marine; Simonyan, Izabella; Hovhannisyan, Galina; Aroutiounian, Rouben; Hamid, Ahmed B; Liehr, Thomas

    2015-12-01

    Complex small supernumerary marker chromosomes (sSMCs) constitute one of the smallest subsets within the patients with an sSMC. Complex sSMCs consist of chromosomal material derived from more than one chromosome, for example, the derivative der(22)t(11;22)(q23;q11.2) in Emanuel syndrome. Here, a yet unreported case of a complex sSMC formed due to a t(7;9)(p22;q22)mat is presented. PMID:27617132

  11. Large-scale whole genome sequencing identifies country-wide spread of an emerging G9P[8] rotavirus strain in Hungary, 2012.

    PubMed

    Dóró, Renáta; Mihalov-Kovács, Eszter; Marton, Szilvia; László, Brigitta; Deák, Judit; Jakab, Ferenc; Juhász, Ágnes; Kisfali, Péter; Martella, Vito; Melegh, Béla; Molnár, Péter; Sántha, Ildikó; Schneider, Ferenc; Bányai, Krisztián

    2014-12-01

    With the availability of rotavirus vaccines routine strain surveillance has been launched or continued in many countries worldwide. In this study relevant information is provided from Hungary in order to extend knowledge about circulating rotavirus strains. Direct sequencing of the RT-PCR products obtained by VP7 and VP4 genes specific primer sets was utilized as routine laboratory method. In addition we explored the advantage of random primed RT-PCR and semiconductor sequencing of the whole genome of selected strains. During the study year, 2012, we identified an increase in the prevalence of G9P[8] strains across the country. This genotype combination predominated in seven out of nine study sites (detection rates, 45-83%). In addition to G9P[8]s, epidemiologically major strains included genotypes G1P[8] (34.2%), G2P[4] (13.5%), and G4P[8] (7.4%), whereas unusual and rare strains were G3P[8] (1%), G2P[8] (0.5%), G1P[4] (0.2%), G3P[4] (0.2%), and G3P[9] (0.2%). Whole genome analysis of 125 Hungarian human rotaviruses identified nine major genotype constellations and uncovered both intra- and intergenogroup reassortment events in circulating strains. Intergenogroup reassortment resulted in several unusual genotype constellations, including mono-reassortant G1P[8] and G9P[8] strains whose genotype 1 (Wa-like) backbone gene constellations contained DS1-like NSP2 and VP3 genes, respectively, as well as, a putative bovine-feline G3P[9] reassortant strain. The conserved genomic constellations of epidemiologically major genotypes suggested the clonal spread of the re-emerging G9P[8] genotype and several co-circulating strains (e.g., G1P[8] and G2P[4]) in many study sites during 2012. Of interest, medically important G2P[4] strains carried bovine-like VP1 and VP6 genes in their genotype constellation. No evidence for vaccine associated selection, or, interaction between wild-type and vaccine strains was obtained. In conclusion, this study reports the reemergence of G9P[8

  12. Comparative In Vitro and In Vivo Studies of Porcine Rotavirus G9P[13] and Human Rotavirus Wa G1P[8

    PubMed Central

    Shao, Lulu; Fischer, David D.; Kandasamy, Sukumar; Rauf, Abdul; Langel, Stephanie N.; Wentworth, David E.; Stucker, Karla M.; Halpin, Rebecca A.; Lam, Ham Ching; Marthaler, Douglas

    2015-01-01

    ABSTRACT The changing epidemiology of group A rotavirus (RV) strains in humans and swine, including emerging G9 strains, poses new challenges to current vaccines. In this study, we comparatively assessed the pathogenesis of porcine RV (PRV) G9P[13] and evaluated the short-term cross-protection between this strain and human RV (HRV) Wa G1P[8] in gnotobiotic pigs. Complete genome sequencing demonstrated that PRV G9P[13] possessed a human-like G9 VP7 genotype but shared higher overall nucleotide identity with historic PRV strains. PRV G9P[13] induced longer rectal virus shedding and RV RNAemia in pigs than HRV Wa G1P[8] and generated complete short-term cross-protection in pigs challenged with HRV or PRV, whereas HRV Wa G1P[8] induced only partial protection against PRV challenge. Moreover, PRV G9P[13] replicated more extensively in porcine monocyte-derived dendritic cells (MoDCs) than did HRV Wa G1P[8]. Cross-protection was likely not dependent on serum virus-neutralizing (VN) antibodies, as the heterologous VN antibody titers in the sera of G9P[13]-inoculated pigs were low. Thus, our results suggest that heterologous protection by the current monovalent G1P[8] HRV vaccine against emerging G9 strains should be evaluated in clinical and experimental studies to prevent further dissemination of G9 strains. Differences in the pathogenesis of these two strains may be partially attributable to their variable abilities to replicate and persist in porcine immune cells, including dendritic cells (DCs). Additional studies are needed to evaluate the emerging G9 strains as potential vaccine candidates and to test the susceptibility of various immune cells to infection by G9 and other common HRV/PRV genotypes. IMPORTANCE The changing epidemiology of porcine and human group A rotaviruses (RVs), including emerging G9 strains, may compromise the efficacy of current vaccines. An understanding of the pathogenesis and genetic, immunological, and biological features of the new emerging

  13. A case of 8p11 myeloproliferative syndrome with BCR-FGFR1 gene fusion presenting with trilineage acute leukemia/lymphoma, successfully treated by cord blood transplantation.

    PubMed

    Morishige, Satoshi; Oku, Eijiro; Takata, Yuka; Kimura, Yoshizo; Arakawa, Fumiko; Seki, Ritsuko; Imamura, Rie; Osaki, Koichi; Hashiguchi, Michitoshi; Yakushiji, Kazuaki; Mizuno, Shinichi; Yoshimoto, Koji; Nagafuji, Koji; Ohshima, Koichi; Okamura, Takashi

    2013-01-01

    The 8p11 myeloproliferative syndrome is a rare neoplasm associated with chromosomal translocations involving the fibroblast growth factor receptor 1 (FGFR1) gene located at chromosome 8p11-12. FGFR1 encodes a transmembrane receptor tyrosine kinase. The resultant fusion proteins are constitutively active tyrosine kinases that drive the proliferation of hematopoietic cells, whose uncontrolled growth can present as a myeloproliferative neoplasm. We report here the case of a 50-year-old man harboring the t(8;22)(p12;q11) chromosomal translocation in cells from both bone marrow and lymph nodes. He presented with acute leukemia and lymphoma with trilineage features. A novel mRNA in-frame fusion between exon 4 of the breakpoint cluster region (BCR) gene at chromosome 22q11 and exon 9 of FGFR1 gene on chromosome 8p11-12 was identified by reverse transcription polymerase chain reaction analysis and was confirmed by DNA sequencing. Because the patient was refractory to chemotherapy, cord blood transplantation was performed in progressive disease. It resulted in a successful outcome in which cytogenetic complete remission has been maintained for 2 years till date. PMID:23171834

  14. Promoter swapping between the genes for a novel zinc finger protein and beta-catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations.

    PubMed

    Kas, K; Voz, M L; Röijer, E; Aström, A K; Meyen, E; Stenman, G; Van de Ven, W J

    1997-02-01

    Pleiomorphic adenoma of the salivary glands is a benign epithelial tumour occurring primarily in the major and minor salivary glands. It is by far the most common type of salivary gland tumour. Microscopically, pleiomorphic adenomas show a marked histological diversity with epithelial, myoepithelial and mesenchymal components in a variety of patterns. In addition to a cytogenetic subgroup with normal karyotypes, pleiomorphic adenomas are characterized by recurrent chromosome rearrangements, particularly reciprocal translocations, with breakpoints at 8q12, 3p21, and 12q13-15, in that order of frequency. The most common abnormality is a reciprocal t(3;8)(p21;q12). We here demonstrate that the t(3;8)(p21;q12) results in promoter swapping between PLAG1, a novel, developmentally regulated zinc finger gene at 8q12, and the constitutively expressed gene for beta-catenin (CTNNB1), a protein interface functioning in the WG/WNT signalling pathway and specification of cell fate during embryogenesis. Fusions occur in the 5'-non-coding regions of both genes, exchanging regulatory control elements while preserving the coding sequences. Due to the t(3;8)(p21;q12), PLAG1 is activated and expression levels of CTNNB1 are reduced. Activation of PLAG1 was also observed in an adenoma with a variant translocation t(8;15)(q12;q14). Our results indicate that PLAG1 activation due to promoter swapping is a crucial event in salivary gland tumourigenesis.

  15. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

    PubMed

    Vigorito, Elena; Kuchenbaecker, Karoline B; Beesley, Jonathan; Adlard, Julian; Agnarsson, Bjarni A; Andrulis, Irene L; Arun, Banu K; Barjhoux, Laure; Belotti, Muriel; Benitez, Javier; Berger, Andreas; Bojesen, Anders; Bonanni, Bernardo; Brewer, Carole; Caldes, Trinidad; Caligo, Maria A; Campbell, Ian; Chan, Salina B; Claes, Kathleen B M; Cohn, David E; Cook, Jackie; Daly, Mary B; Damiola, Francesca; Davidson, Rosemarie; Pauw, Antoine de; Delnatte, Capucine; Diez, Orland; Domchek, Susan M; Dumont, Martine; Durda, Katarzyna; Dworniczak, Bernd; Easton, Douglas F; Eccles, Diana; Edwinsdotter Ardnor, Christina; Eeles, Ros; Ejlertsen, Bent; Ellis, Steve; Evans, D Gareth; Feliubadalo, Lidia; Fostira, Florentia; Foulkes, William D; Friedman, Eitan; Frost, Debra; Gaddam, Pragna; Ganz, Patricia A; Garber, Judy; Garcia-Barberan, Vanesa; Gauthier-Villars, Marion; Gehrig, Andrea; Gerdes, Anne-Marie; Giraud, Sophie; Godwin, Andrew K; Goldgar, David E; Hake, Christopher R; Hansen, Thomas V O; Healey, Sue; Hodgson, Shirley; Hogervorst, Frans B L; Houdayer, Claude; Hulick, Peter J; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jacobs, Lauren; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M; Vijai, Joseph; Karlan, Beth Y; Kast, Karin; Investigators, KConFab; Khan, Sofia; Kwong, Ava; Laitman, Yael; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Lubinski, Jan; Mai, Phuong L; Manoukian, Siranoush; Mazoyer, Sylvie; Meindl, Alfons; Mensenkamp, Arjen R; Montagna, Marco; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Niederacher, Dieter; Olah, Edith; Olopade, Olufunmilayo I; Ong, Kai-Ren; Osorio, Ana; Park, Sue Kyung; Paulsson-Karlsson, Ylva; Pedersen, Inge Sokilde; Peissel, Bernard; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M; Piedmonte, Marion; Poppe, Bruce; Pujana, Miquel Angel; Radice, Paolo; Rennert, Gad; Rodriguez, Gustavo C; Rookus, Matti A; Ross, Eric A; Schmutzler, Rita Katharina; Simard, Jacques; Singer, Christian F; Slavin, Thomas P; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Szabo, Csilla I; Tea, Muy-Kheng; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; van Rensburg, Elizabeth J; Varesco, Liliana; Varon-Mateeva, Raymonda; Vratimos, Athanassios; Weitzel, Jeffrey N; McGuffog, Lesley; Kirk, Judy; Toland, Amanda Ewart; Hamann, Ute; Lindor, Noralane; Ramus, Susan J; Greene, Mark H; Couch, Fergus J; Offit, Kenneth; Pharoah, Paul D P; Chenevix-Trench, Georgia; Antoniou, Antonis C

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.

  16. Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence.

    PubMed

    Balko, Justin M; Schwarz, Luis J; Luo, Na; Estrada, Mónica V; Giltnane, Jennifer M; Dávila-González, Daniel; Wang, Kai; Sánchez, Violeta; Dean, Phillip T; Combs, Susan E; Hicks, Donna; Pinto, Joseph A; Landis, Melissa D; Doimi, Franco D; Yelensky, Roman; Miller, Vincent A; Stephens, Phillip J; Rimm, David L; Gómez, Henry; Chang, Jenny C; Sanders, Melinda E; Cook, Rebecca S; Arteaga, Carlos L

    2016-04-13

    Amplifications at 9p24 have been identified in breast cancer and other malignancies, but the genes within this locus causally associated with oncogenicity or tumor progression remain unclear. Targeted next-generation sequencing of postchemotherapy triple-negative breast cancers (TNBCs) identified a group of 9p24-amplified tumors, which contained focal amplification of the Janus kinase 2 (JAK2) gene. These patients had markedly inferior recurrence-free and overall survival compared to patients with TNBC without JAK2 amplification. Detection of JAK2/9p24 amplifications was more common in chemotherapy-treated TNBCs than in untreated TNBCs or basal-like cancers, or in other breast cancer subtypes. Similar rates of JAK2 amplification were confirmed in patient-derived TNBC xenografts. In patients for whom longitudinal specimens were available, JAK2 amplification was selected for during neoadjuvant chemotherapy and eventual metastatic spread, suggesting a role in tumorigenicity and chemoresistance, phenotypes often attributed to a cancer stem cell-like cell population. In TNBC cell lines with JAK2 copy gains or amplification, specific inhibition of JAK2 signaling reduced mammosphere formation and cooperated with chemotherapy in reducing tumor growth in vivo. In these cells, inhibition of JAK1-signal transducer and activator of transcription 3 (STAT3) signaling had little effect or, in some cases, counteracted JAK2-specific inhibition. Collectively, these results suggest that JAK2-specific inhibitors are more efficacious than dual JAK1/2 inhibitors against JAK2-amplified TNBCs. Furthermore, JAK2 amplification is a potential biomarker for JAK2 dependence, which, in turn, can be used to select patients for clinical trials with JAK2 inhibitors. PMID:27075627

  17. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

    PubMed

    Vigorito, Elena; Kuchenbaecker, Karoline B; Beesley, Jonathan; Adlard, Julian; Agnarsson, Bjarni A; Andrulis, Irene L; Arun, Banu K; Barjhoux, Laure; Belotti, Muriel; Benitez, Javier; Berger, Andreas; Bojesen, Anders; Bonanni, Bernardo; Brewer, Carole; Caldes, Trinidad; Caligo, Maria A; Campbell, Ian; Chan, Salina B; Claes, Kathleen B M; Cohn, David E; Cook, Jackie; Daly, Mary B; Damiola, Francesca; Davidson, Rosemarie; Pauw, Antoine de; Delnatte, Capucine; Diez, Orland; Domchek, Susan M; Dumont, Martine; Durda, Katarzyna; Dworniczak, Bernd; Easton, Douglas F; Eccles, Diana; Edwinsdotter Ardnor, Christina; Eeles, Ros; Ejlertsen, Bent; Ellis, Steve; Evans, D Gareth; Feliubadalo, Lidia; Fostira, Florentia; Foulkes, William D; Friedman, Eitan; Frost, Debra; Gaddam, Pragna; Ganz, Patricia A; Garber, Judy; Garcia-Barberan, Vanesa; Gauthier-Villars, Marion; Gehrig, Andrea; Gerdes, Anne-Marie; Giraud, Sophie; Godwin, Andrew K; Goldgar, David E; Hake, Christopher R; Hansen, Thomas V O; Healey, Sue; Hodgson, Shirley; Hogervorst, Frans B L; Houdayer, Claude; Hulick, Peter J; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jacobs, Lauren; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M; Vijai, Joseph; Karlan, Beth Y; Kast, Karin; Investigators, KConFab; Khan, Sofia; Kwong, Ava; Laitman, Yael; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Lubinski, Jan; Mai, Phuong L; Manoukian, Siranoush; Mazoyer, Sylvie; Meindl, Alfons; Mensenkamp, Arjen R; Montagna, Marco; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Niederacher, Dieter; Olah, Edith; Olopade, Olufunmilayo I; Ong, Kai-Ren; Osorio, Ana; Park, Sue Kyung; Paulsson-Karlsson, Ylva; Pedersen, Inge Sokilde; Peissel, Bernard; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M; Piedmonte, Marion; Poppe, Bruce; Pujana, Miquel Angel; Radice, Paolo; Rennert, Gad; Rodriguez, Gustavo C; Rookus, Matti A; Ross, Eric A; Schmutzler, Rita Katharina; Simard, Jacques; Singer, Christian F; Slavin, Thomas P; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Szabo, Csilla I; Tea, Muy-Kheng; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; van Rensburg, Elizabeth J; Varesco, Liliana; Varon-Mateeva, Raymonda; Vratimos, Athanassios; Weitzel, Jeffrey N; McGuffog, Lesley; Kirk, Judy; Toland, Amanda Ewart; Hamann, Ute; Lindor, Noralane; Ramus, Susan J; Greene, Mark H; Couch, Fergus J; Offit, Kenneth; Pharoah, Paul D P; Chenevix-Trench, Georgia; Antoniou, Antonis C

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population. PMID:27463617

  18. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    PubMed Central

    Vigorito, Elena; Kuchenbaecker, Karoline B.; Beesley, Jonathan; Adlard, Julian; Agnarsson, Bjarni A.; Andrulis, Irene L.; Arun, Banu K.; Barjhoux, Laure; Belotti, Muriel; Benitez, Javier; Berger, Andreas; Bojesen, Anders; Bonanni, Bernardo; Brewer, Carole; Caldes, Trinidad; Caligo, Maria A.; Campbell, Ian; Chan, Salina B.; Claes, Kathleen B. M.; Cohn, David E.; Cook, Jackie; Daly, Mary B.; Damiola, Francesca; Davidson, Rosemarie; de Pauw, Antoine; Delnatte, Capucine; Diez, Orland; Domchek, Susan M.; Dumont, Martine; Durda, Katarzyna; Dworniczak, Bernd; Easton, Douglas F.; Eccles, Diana; Edwinsdotter Ardnor, Christina; Eeles, Ros; Ejlertsen, Bent; Ellis, Steve; Evans, D. Gareth; Feliubadalo, Lidia; Fostira, Florentia; Foulkes, William D.; Friedman, Eitan; Frost, Debra; Gaddam, Pragna; Ganz, Patricia A.; Garber, Judy; Garcia-Barberan, Vanesa; Gauthier-Villars, Marion; Gehrig, Andrea; Gerdes, Anne-Marie; Giraud, Sophie; Godwin, Andrew K.; Goldgar, David E.; Hake, Christopher R.; Hansen, Thomas V. O.; Healey, Sue; Hodgson, Shirley; Hogervorst, Frans B. L.; Houdayer, Claude; Hulick, Peter J.; Imyanitov, Evgeny N.; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jacobs, Lauren; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M.; Vijai, Joseph; Karlan, Beth Y.; Kast, Karin; Investigators, KConFab; Khan, Sofia; Kwong, Ava; Laitman, Yael; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Lubinski, Jan; Mai, Phuong L.; Manoukian, Siranoush; Mazoyer, Sylvie; Meindl, Alfons; Mensenkamp, Arjen R.; Montagna, Marco; Nathanson, Katherine L.; Neuhausen, Susan L.; Nevanlinna, Heli; Niederacher, Dieter; Olah, Edith; Olopade, Olufunmilayo I.; Ong, Kai-ren; Osorio, Ana; Park, Sue Kyung; Paulsson-Karlsson, Ylva; Pedersen, Inge Sokilde; Peissel, Bernard; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M.; Piedmonte, Marion; Poppe, Bruce; Pujana, Miquel Angel; Radice, Paolo; Rennert, Gad; Rodriguez, Gustavo C.; Rookus, Matti A.; Ross, Eric A.; Schmutzler, Rita Katharina; Simard, Jacques; Singer, Christian F.; Slavin, Thomas P.; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Szabo, Csilla I.; Tea, Muy-Kheng; Teixeira, Manuel R.; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; van Rensburg, Elizabeth J.; Varesco, Liliana; Varon-Mateeva, Raymonda; Vratimos, Athanassios; Weitzel, Jeffrey N.; McGuffog, Lesley; Kirk, Judy; Toland, Amanda Ewart; Hamann, Ute; Lindor, Noralane; Ramus, Susan J.; Greene, Mark H.; Couch, Fergus J.; Offit, Kenneth; Pharoah, Paul D. P.; Chenevix-Trench, Georgia; Antoniou, Antonis C.

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10−16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10−6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population. PMID:27463617

  19. Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence.

    PubMed

    Balko, Justin M; Schwarz, Luis J; Luo, Na; Estrada, Mónica V; Giltnane, Jennifer M; Dávila-González, Daniel; Wang, Kai; Sánchez, Violeta; Dean, Phillip T; Combs, Susan E; Hicks, Donna; Pinto, Joseph A; Landis, Melissa D; Doimi, Franco D; Yelensky, Roman; Miller, Vincent A; Stephens, Phillip J; Rimm, David L; Gómez, Henry; Chang, Jenny C; Sanders, Melinda E; Cook, Rebecca S; Arteaga, Carlos L

    2016-04-13

    Amplifications at 9p24 have been identified in breast cancer and other malignancies, but the genes within this locus causally associated with oncogenicity or tumor progression remain unclear. Targeted next-generation sequencing of postchemotherapy triple-negative breast cancers (TNBCs) identified a group of 9p24-amplified tumors, which contained focal amplification of the Janus kinase 2 (JAK2) gene. These patients had markedly inferior recurrence-free and overall survival compared to patients with TNBC without JAK2 amplification. Detection of JAK2/9p24 amplifications was more common in chemotherapy-treated TNBCs than in untreated TNBCs or basal-like cancers, or in other breast cancer subtypes. Similar rates of JAK2 amplification were confirmed in patient-derived TNBC xenografts. In patients for whom longitudinal specimens were available, JAK2 amplification was selected for during neoadjuvant chemotherapy and eventual metastatic spread, suggesting a role in tumorigenicity and chemoresistance, phenotypes often attributed to a cancer stem cell-like cell population. In TNBC cell lines with JAK2 copy gains or amplification, specific inhibition of JAK2 signaling reduced mammosphere formation and cooperated with chemotherapy in reducing tumor growth in vivo. In these cells, inhibition of JAK1-signal transducer and activator of transcription 3 (STAT3) signaling had little effect or, in some cases, counteracted JAK2-specific inhibition. Collectively, these results suggest that JAK2-specific inhibitors are more efficacious than dual JAK1/2 inhibitors against JAK2-amplified TNBCs. Furthermore, JAK2 amplification is a potential biomarker for JAK2 dependence, which, in turn, can be used to select patients for clinical trials with JAK2 inhibitors.

  20. Association between 9p21 genetic variants and mortality risk in a prospective cohort of patients with type 2 diabetes (ZODIAC-15).

    PubMed

    Landman, Gijs W D; van Vliet-Ostaptchouk, Jana V; Kleefstra, Nanne; van Hateren, Kornelis J J; Drion, Iefke; Groenier, Klaas H; Gans, Rijk O B; Snieder, Harold; Hofker, Marten H; Bilo, Henk J G

    2012-11-07

    The genomic region at 9p21 chromosome near the CDKN2A/CDKN2B genes is associated with type 2 diabetes(T2D) and cardiovascular disease(CVD). The effect of the 9p21 locus on long-term mortality in patients with T2D has yet to be determined.We examined three single nucleotide polymorphisms (SNPs) on 9p21, consistently and independently associated with T2D (rs10811661) or CVD (rs10757278, rs2383206), in relation to the risk of total and cardiovascular mortality in diabetic patients. We also aimed to replicate the previously observed interaction between rs2383206 and glycemic control on mortality.Genotypes for three SNPs were determined in 914 individuals from a prospective cohort of T2D patients of Dutch origin. Associations with mortality were assessed using Cox proportional hazard analyses.After a median follow-up of 9.5 years, 358 out of 914 patients had died. The hazard ratio (HR) for total mortality among individuals homozygous for the T2D-risk allele of rs10811661 compared to non-homozygous individuals was 0.74(95%CI 0.59-0.93). For the carriers of both CVD-risk alleles of rs10757278, the HR for total mortality was 1.31(95%CI 1.01-1.70). We found a significant interaction between rs2383206 and HbA1c on mortality, which was higher among patients with two CVD-risk alleles in the two lowest HbA1c tertiles (HR 1.68(95%CI 1.08-2.63); HR 1.48(95%CI 1.01-2.18).In conclusion, common variants on 9p21 were associated with mortality in patients with T2D in a Dutch population. The T2D SNP was inversely associated with mortality, while the CVD SNP increased the risk for mortality. We confirmed a possible, although different, synergistic relationship between HbA1c and rs2383206 on total mortality.

  1. Association between 9p21 genetic variants and mortality risk in a prospective cohort of patients with type 2 diabetes (ZODIAC-15).

    PubMed

    Landman, Gijs W D; van Vliet-Ostaptchouk, Jana V; Kleefstra, Nanne; van Hateren, Kornelis J J; Drion, Iefke; Groenier, Klaas H; Gans, Rijk O B; Snieder, Harold; Hofker, Marten H; Bilo, Henk J G

    2012-01-01

    The genomic region at 9p21 chromosome near the CDKN2A/CDKN2B genes is associated with type 2 diabetes(T2D) and cardiovascular disease(CVD). The effect of the 9p21 locus on long-term mortality in patients with T2D has yet to be determined.We examined three single nucleotide polymorphisms (SNPs) on 9p21, consistently and independently associated with T2D (rs10811661) or CVD (rs10757278, rs2383206), in relation to the risk of total and cardiovascular mortality in diabetic patients. We also aimed to replicate the previously observed interaction between rs2383206 and glycemic control on mortality.Genotypes for three SNPs were determined in 914 individuals from a prospective cohort of T2D patients of Dutch origin. Associations with mortality were assessed using Cox proportional hazard analyses.After a median follow-up of 9.5 years, 358 out of 914 patients had died. The hazard ratio (HR) for total mortality among individuals homozygous for the T2D-risk allele of rs10811661 compared to non-homozygous individuals was 0.74(95%CI 0.59-0.93). For the carriers of both CVD-risk alleles of rs10757278, the HR for total mortality was 1.31(95%CI 1.01-1.70). We found a significant interaction between rs2383206 and HbA1c on mortality, which was higher among patients with two CVD-risk alleles in the two lowest HbA1c tertiles (HR 1.68(95%CI 1.08-2.63); HR 1.48(95%CI 1.01-2.18).In conclusion, common variants on 9p21 were associated with mortality in patients with T2D in a Dutch population. The T2D SNP was inversely associated with mortality, while the CVD SNP increased the risk for mortality. We confirmed a possible, although different, synergistic relationship between HbA1c and rs2383206 on total mortality. PMID:23134948

  2. From a single whole exome read to notions of clinical screening: primary ciliary dyskinesia and RSPH9 p.Lys268del in the Arabian Peninsula.

    PubMed

    Alsaadi, Muslim M; Gaunt, Tom R; Boustred, Christopher R; Guthrie, Philip A I; Liu, Xuan; Lenzi, Luca; Rainbow, Lucille; Hall, Neil; Alharbi, Khalid K; Day, Ian N M

    2012-05-01

    Primary ciliary dyskinesia (PCD) is a genetic disorder, usually autosomal recessive, causing early respiratory disease and later subfertility. Whole exome sequencing may enable efficient analysis for locus heterogeneous disorders such as PCD. We whole-exome-sequenced one consanguineous Saudi Arabian with clinically diagnosed PCD and normal laterality, to attempt ab initio molecular diagnosis. We reviewed 13 known PCD genes and potentially autozygous regions (extended homozygosity) for homozygous exon deletions, non-dbSNP codon, splice-site base variants or small indels. Homozygous non-dbSNP changes were also reviewed exome-wide. One single molecular read representing RSPH9 p.Lys268del was observed, with no wild-type reads, and a notable deficiency of mapped reads at this location. Among all observations, RSPH9 was the strongest candidate for causality. Searching unmapped reads revealed seven more mutant reads. Direct assay for p.Lys268del (MboII digest) confirmed homozygosity in the affected individual, then confirmed homozygosity in three siblings with bronchiectasis. Our finding in southwest Saudi Arabia indicates that p.Lys268del, previously observed in two Bedouin families (Israel, UAE), is geographically widespread in the Arabian Peninsula. Analogous with cystic fibrosis CFTR p.Phe508del, screening for RSPH9 p.Lys268del (which lacks sentinel dextrocardia) in those at risk would help in early diagnosis, tailored clinical management, genetic counselling and primary prevention.

  3. Fine-mapping chromosomal loss at 9p21: correlation with prognosis in primary cutaneous diffuse large B-cell lymphoma, leg type.

    PubMed

    Senff, Nancy J; Zoutman, Willem H; Vermeer, Maarten H; Assaf, Chalid; Berti, Emilio; Cerroni, Lorenzo; Espinet, Blanca; de Misa Cabrera, Ricardo Fernandez; Geerts, Marie-Louise; Kempf, Werner; Mitchell, Tracey J; Paulli, Marco; Petrella, Tony; Pimpinelli, Nicola; Santucci, Marco; Whittaker, Sean J; Willemze, Rein; Tensen, Cornelis P

    2009-05-01

    Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT) is the most aggressive type of primary cutaneous B-cell lymphoma. In a recent study on 12 patients it was found that inactivation of CDKN2A by either deletion of 9p21.3 or promoter hypermethylation is correlated with a worse prognosis. In the present EORTC multicenter study, skin biopsies of 64 PCLBCL, LT patients were analyzed by multiplex ligation-dependent probe amplification to validate these previous results and to fine-map the losses in this region. Although no minimal common region of loss could be identified, most homozygous loss was observed in the CDKN2A gene (43 of 64; 67%) encoding p16 and p14ARF. Promoter hypermethylation of p16 and p14ARF was found in six and zero cases, respectively. Survival was markedly different between patients with versus without aberrations in the CDKN2A gene (5-year disease-specific survival 43 versus 70%; P=0.06). In conclusion, our results confirm that deletion of chromosome 9p21.3 is found in a considerable proportion of PCLBCL, LT patients and that inactivation of the CDKN2A gene is associated with an unfavorable prognosis. In most patients the deletion involves a large area of at least several kilobase pairs instead of a small minimal common region.

  4. Post-zygotic breakage of a dicentric chromosome results in mosaicism for a telocentric 9p marker chromosome in a boy with developmental delay.

    PubMed

    Pedurupillay, C R J; Misceo, D; Gamage, T H; Dissanayake, V H W; Frengen, E

    2014-01-01

    Chromosomal rearrangements resulting in an inverted duplication and a terminal deletion (inv dup del) can occur due to three known mechanisms, two of them resulting in a normal copy region between the duplicated regions. These mechanisms involve the formation of a dicentric chromosome, which undergo breakage during cell division resulting in cells with either an inverted duplication and deletion or a terminal deletion. We describe a mosaic 3 year old patient with two cell lines carrying a chromosome 9p deletion where one of the cell lines contains an additional telocentric marker chromosome. Our patient is mosaic for the product of a double breakage of a dicentric chromosome including a centric fission. Mosaicism involving different rearrangements of the same chromosome is rare and suggests an early mitotic breakage event. Chr9p terminal deletions associated with duplications have previously been reported in 11 patients. We compare the clinical features of all 12 patients including the patient that we report here. To the best to our knowledge this is a first case reported where the double breakage occurred in the dicentric derivative chromosome 9.

  5. Molecular screening for microdeletions at 9p22-p24 and 11q23-q24 in a large cohort of patients with trigonocephaly.

    PubMed

    Jehee, F S; Johnson, D; Alonso, L G; Cavalcanti, D P; de Sá Moreira, E; Alberto, F L; Kok, F; Kim, C; Wall, S A; Jabs, E W; Boyadjiev, S A; Wilkie, A O M; Passos-Bueno, M R

    2005-06-01

    Trigonocephaly is a rare form of craniosynostosis characterized by the premature closure of the metopic suture. To contribute to a better understanding of the genetic basis of metopic synostosis and in an attempt to restrict the candidate regions related to metopic suture fusion, we studied 76 unrelated patients with syndromic and non-syndromic trigonocephaly. We found a larger proportion of syndromic cases in our population and the ratio of affected male to female was 1.8 : 1 and 5 : 1 in the non-syndromic and syndromic groups, respectively. A microdeletion screening at 9p22-p24 and 11q23-q24 was carried out for all patients and deletions in seven of them were detected, corresponding to 19.4% of all syndromic cases. Deletions were not found in non-syndromic patients. We suggest that a molecular screening for microdeletions at 9p22-p24 and 11q23-q24 should be offered to all syndromic cases with an apparently normal karyotype because it can potentially elucidate the cause of trigonocephaly in this subset of patients. We also suggest that genes on the X-chromosome play a major role in syndromic trigonocephaly.

  6. The rs10757278 Polymorphism of the 9p21.3 Locus Is Associated with Premature Coronary Artery Disease in Polish Patients

    PubMed Central

    Gorczynska-Kosiorz, Sylwia; Iwanicki, Tomasz; Krauze, Jolanta; Trautsolt, Wanda; Grzeszczak, Wladyslaw; Bochenek, Andrzej; Zak, Iwona

    2012-01-01

    Recently, genome-wide association studies have revealed a locus associated with coronary artery disease (CAD) and myocardial infarction, namely, 9p21.3. Its participation in the conditioning of the disease has been proven in many populations of European descent, but not yet in Slavs. Allelic variants of the rs10757278 polymorphism functionally affect the activity of the 9p21.3 locus; therefore, we conducted a study to determine whether the rs10757278 is associated with premature CAD in Polish patients. We studied 320 subjects aged 25–55 years, divided into two groups matched by sex and age: (1) patients with angiographically proven premature CAD (n=160), and (2) blood donors as a control group (n=160). The rs10757278 was genotyped using the method of fluorescently labeled allele-specific oligonucleotides. The frequency of the G allele was significantly higher in patients than in controls (58.2% vs. 42.8%, respectively, p=0.011) and was similar to the frequency of the GG homozygotes (30.6% vs. 17.5%, respectively, p=0.006). Both the GG homozygosity (odds ratio [OR]=2.08, 95% confidence interval [CI]: 1.19–3.66) as well as the G allele (OR=1.49, 95% CI: 1.08–2.07) have been associated with CAD in the analyzed population. These variants may be considered as risk factors, also in the Polish population. PMID:22946666

  7. The 9p21.3 risk of childhood acute lymphoblastic leukaemia is explained by a rare high-impact variant in CDKN2A

    PubMed Central

    Vijayakrishnan, Jayaram; Henrion, Marc; Moorman, Anthony V.; Fiege, Bettina; Kumar, Rajiv; Inacio da Silva Filho, Miguel; Holroyd, Amy; Koehler, Rolf; Thomsen, Hauke; Irving, Julie A.; Allan, James M.; Lightfoot, Tracy; Roman, Eve; Kinsey, Sally E.; Sheridan, Eamonn; Thompson, Pamela D.; Hoffmann, Per; Nöthen, Markus M.; Mühleisen, Thomas W.; Eisele, Lewin; Bartram, Claus R.; Schrappe, Martin; Greaves, Mel; Hemminki, Kari; Harrison, Christine J.; Stanulla, Martin; Houlston, Richard S.

    2015-01-01

    Genome-wide association studies (GWAS) have provided strong evidence for inherited predisposition to childhood acute lymphoblastic leukaemia (ALL) identifying a number of risk loci. We have previously shown common SNPs at 9p21.3 influence ALL risk. These SNP associations are generally not themselves candidates for causality, but simply act as markers for functional variants. By means of imputation of GWAS data and subsequent validation SNP genotyping totalling 2,177 ALL cases and 8,240 controls, we have shown that the 9p21.3 association can be ascribed to the rare high-impact CDKN2A p.Ala148Thr variant (rs3731249; Odds ratio = 2.42, P = 3.45 × 10−19). The association between rs3731249 genotype and risk was not specific to particular subtype of B-cell ALL. The rs3731249 variant is associated with predominant nuclear localisation of the CDKN2A transcript suggesting the functional effect of p.Ala148Thr on ALL risk may be through compromised ability to inhibit cyclin D within the cytoplasm. PMID:26463672

  8. Structures of Aquifex aeolicus KDO8P synthase in complex with R5P and PEP, and with a bisubstrate inhibitor: role of active site water in catalysis.

    PubMed

    Wang, J; Duewel, H S; Woodard, R W; Gatti, D L

    2001-12-25

    We have determined the crystal structures of the metalloenzyme 3-deoxy-D-manno-octulosonate 8-phosphate (KDO8P) synthase from Aquifex aeolicus in complex with phosphoenolpyruvate (PEP) and ribose 5-phosphate (R5P), and with a bisubstrate inhibitor that mimics the postulated linear reaction intermediate. R5P, which is not a substrate for KDO8P synthase, binds in a manner similar to that of arabinose 5-phosphate (A5P), which is the natural substrate. The lack of reactivity of R5P appears to be primarily a consequence of the loss of a water molecule coordinated to Cd(2+) and located on the si side of PEP. This water molecule is no longer present because it cannot form a hydrogen bond with C2-OH(R5P), which is oriented in a different direction from C2-OH(A5P). The bisubstrate inhibitor binds with its phosphate and phosphonate moieties occupying the positions of the phosphate groups of A5P and PEP, respectively. One of the inhibitor hydroxyls replaces water as a ligand of Cd(2+). The current work supports a mechanism for the synthesis of KDO8P, in which a hydroxide ion on the si side of PEP attacks C2(PEP), forming a tetrahedral-like intermediate with a buildup of negative charge at C3(PEP). The ensuing condensation of C3(PEP) with C1(A5P) would be favored by a proton transfer from the phosphate moiety of PEP to the aldehyde carbonyl of A5P to generate the hydroxyl. Overall, the process can be described as a syn addition of water and A5P to the si side of PEP.

  9. Association Study between Coronary Artery Disease and rs1333049 and rs10757274 Polymorphisms at 9p21 Locus in South-West Iran

    PubMed Central

    Foroughmand, Ali Mohammad; Nikkhah, Emad; Galehdari, Hamid; Jadbabaee, Mohammad Hossin

    2015-01-01

    Objective Coronary artery disease (CAD) is a multi-factorial and heterogenic disease with atherosclerosis plaques formation in internal wall of coronary artery. Plaque formation results to limitation of the blood reaching to myocardium leading to appearance of some problems, such as ischemia, sudden thrombosis veins and myocardial infarction (MI). Several environmental and genetic factors are involved in prevalence and incident of CAD as follows: hypertension, high low density lipoprotein-cholesterol (LDL-C), age, diabetes mellitus, family history of early-onset heart disease and smoking. According to genome wide association studies (GWAS), five polymorphisms in the 9p21 locus seem to be associated with the CAD. We aimed to evaluate the remarkable association of two polymorphisms at 9p21 locus, rs1333049 and rs10757274, with CAD. Materials and Methods This experimental study was conducted in Golestan, Aria Hospitals and Genetics Lab of Shahid Chamran University in the city of Ahvaz, Iran, in 2010- 2011. The collected blood samples belonging to 170 CAD patients (case group) and 100 healthy individuals (control group) were analyzed by tetra-primer amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) technique. The results were analyzed using software package used for statistical analysis (SPSS; SPSS Inc., USA) version 16. A value of p<0.05 and an odd ratio (OR) with 95% confidence intervals (CI) were considered significant. Results The frequencies of CC, CG and GG genotypes for rs1333049 polymorphism in patients were 18.2, 65.3 and 16.5%, while in controls, the related values were 25, 67 and 8%, respectively. GG genotypes of rs1333049 polymorphism in CAD patients were more than control cases (OR: 0.354, 95%CI: 0.138-0.912, p=0.032). The frequencies of AA, AG and GG genotypes for rs10757274 in CAD patients were 8.2, 58.3 and 33.5%, while in controls, the related values were 35, 63 and 2%, respectively. GG Genotype in rs10757274 polymorphism

  10. Linkage of Type 2 Diabetes on Chromosome 9p24 in Mexican Americans: Additional Evidence from the Veterans Administration Genetic Epidemiology Study (VAGES)

    PubMed Central

    Farook, Vidya S.; Coletta, Dawn K.; Puppala, Sobha; Schneider, Jennifer; Chittoor, Geetha; Hu, Shirley L.; Winnier, Deidre A.; Norton, Luke; Dyer, Thomas D.; Arya, Rector; Cole, Shelley A.; Carless, Melanie; Göring, Harald H.; Almasy, Laura; Mahaney, Michael C.; Comuzzie, Anthony G.; Curran, Joanne E.; Blangero, John; Duggirala, Ravindranath; Lehman, Donna M.; Jenkinson, Christopher P.; DeFronzo, Ralph A.

    2014-01-01

    Objective Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage analysis to localize T2DM susceptibility loci in Mexican Americans. Methods We used the phenotypic and genotypic data from 1,122 Mexican American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). Genome-wide linkage analysis was performed, using the variance components approach. Data from two additional Mexican American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence. Results After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h2 = 0.62, P = 2.7 × 10−6). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 (LOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region in SAFDGS also, we found the significant and increased linkage evidence (LOD = 4.3, empirical P = 1.0 × 10−5, genome-wide P = 1.6 × 10−3) for T2DM at the same chromosomal region when we performed genome-wide linkage analysis of the VAGES data combined with SAFHS and SAFDGS data. Conclusion Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies (GWASs) involving T2DM related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes. PMID:24060607

  11. Pre- and Postnatal Analysis of Chromosome 15q26.1 and 8p23.1 Deletions in Congenital Diaphragmatic Hernia

    PubMed Central

    Shetty, Mitesh; Kadandale, Jayarama; Hegde, Sridevi

    2016-01-01

    Congenital diaphragmatic hernia (CDH) is defined as a protrusion of abdominal content into the thoracic cavity through an abnormal opening in the diaphragm present at birth. It is a common birth defect with high mortality and morbidity. Submicroscopic deletions of 15q26.1 and 8p23.1 have been reported in several cases of CDH. We studied a total of 17 cases with CDH in pre- and postnatal samples using FISH probes. Deletion 15q26.1 was seen in 1/17 prenatal samples. There was no deletion for 8p23.1 in all the samples analyzed. CDH has a genetic etiology, and deletion 15q26.1 increases the risk of CDH. Deletion 15q26.1 in a fetus with CDH is a predictor of poor prognosis. This deletion is also seen in a phenotype similar to Fryns syndrome. CDH identified pre- or postnatally should be investigated further to exclude a 15q26.1 deletion and enable appropriate parental counseling. PMID:26997946

  12. Influence of microstructure on soft magnetic properties of low coreloss and high Bs Fe85Si2B8P4Cu1 nanocrystalline alloy

    NASA Astrophysics Data System (ADS)

    Sharma, Parmanand; Zhang, Xin; Zhang, Yan; Makino, Akihiro

    2014-05-01

    Microstructure and magnetic properties of high Bs Fe85Si2B8P4Cu1 nano-crystalline alloy were tailored. The Bs ˜ 1.85 T and low coercivity Hc ˜ 6 A/m were obtained by conventional annealing (i.e., one step) at a heating rate of ˜400 °C/min. While one step annealing process produces a fairly stable nanostructure, for short times at temperatures <425 °C, the nanostructure and concomitant magnetic properties of this alloy are shown to be tunable by two step annealing process. Nanocrystalline ribbons with grain size (D) ranging from ˜15 to 32 nm, Hc ˜ 6 to 140 A/m and core-loss at 1.5 T, 50 Hz ˜ 0.39 ˜ 5.0 W/kg were obtained. The Hc of Fe85Si2B8P4Cu1 alloy is shown to vary as D6, but a small deviation was noticed, which may be due to weak anisotropy.

  13. Construction of 110 cosmid markers and a 4.5-Mb YAC contig on human chromosome 8p12-q11

    SciTech Connect

    Kurimasa, Akihiro; Suzuki, Noriyuki; Kumano, Satoshi; Oshimura, Mitsuo

    1995-07-20

    Microcell hybrids containing various regions of human chromosome 8 were formed by microcell-mediated transfer of neo-tagged chromosome 8 into the cells derived from severe combined immunodeficiency (SCID) mouse. Thus, 110 cosmid markers were isolated from SV40-transformed SCID fibroblast cell line (SCVA) containing a p12-q11.1 region of human chromosome 8 and were assigned to eight regions in 8p12-q11.1, using a microcell-hybrid panel. For positional cloning of a human gene that restores the DNA-repair defect in a mouse with SCID on 8p11.1-q11.1 (SCID region), we constructed a yeast artificial chromosome (YAC) contig of about 4.5 Mb. Overlapping YACs were further aligned by restriction mapping, using rare-cutting restriction endonucleases. The cosmids and YAC contig should facilitate isolation of the SCID gene and other genes, such as the Werner syndrome-responsible gene in or near this region. 29 refs., 5 figs.

  14. Monosomy 9p24{r_arrow}pter and trisomy 5q31{r_arrow}qter: Case report and review of two cases

    SciTech Connect

    Schimmenti, L.A.; Steinberger, J.; Mammel, M.C.

    1995-05-22

    Partial deletion of the short arm of chromosome 9 (p24{r_arrow}pter) and partial duplication of the long arm of chromosome 5 (q32{r_arrow}qter) were observed in an abnormal boy who died at age 8 weeks of a complex cyanotic cardiac defect. He also had minor anomalies, sagittal craniosynostosis, triphalangeal thumbs, hypospadias, and a bifid scrotum. Two other infants with similar cytogenetic abnormalities were described previously. These patients had severe congenital heart defect, genitourinary anomalies, broad nasal bridge, low hairline, apparently low-set ears, short neck, and triphalangeal thumbs, in common with our patient. We suggest that combined monosomy 9q23,24{r_arrow}pter and trisomy 5q31,32{r_arrow}qter may constitute a clinically recognizable syndrome. 13 refs., 2 figs., 2 tabs.

  15. Alterations of p16-pRb pathway and chromosome locus 9p21-22 in sporadic invasive breast carcinomas.

    PubMed Central

    Gorgoulis, V. G.; Koutroumbi, E. N.; Kotsinas, A.; Zacharatos, P.; Markopoulos, C.; Giannikos, L.; Kyriakou, V.; Voulgaris, Z.; Gogas, I.; Kittas, C.

    1998-01-01

    The p16-pRb pathway represents a vital cell-cycle checkpoint. In the present study we investigated the alterations of this G1-phase protein pathway using immunohistochemical and molecular methods in a series of 55 breast carcinomas and correlated the findings with clinicopathological features of the patients. Furthermore, we examined its relationship with the status of the chromosomal region 9p21-22 performing a deletion map analysis because there are indications that, in addition to CDKN2 and MTS2/p15(INK4B) tumor suppressor genes (TSGs), this area harbors other TSG(s). Aberrant expression (Ab) of p16 and pRb was observed in 26 (47%) and 16 (29%) of the carcinomas, respectively. A statistical trend pointing out an inverse relationship between p16 and pRb expression was found (p = 0.079). Analysis of the region that encodes for p16 by deletion mapping, a PCR-based methylation assay and PCR-SSCP, revealed that deletions and transcriptional silencing by methylation might represent the main mechanisms of CDKN2/p16(INK4A) inactivation in breast carcinomas. The results of deletion mapping also suggest that another TSG(s) may reside at the 9p21-22 area particularly at the D9S162 loci and that co-deletion of this putative gene with CDKN2/p16(INK4A) may play a role in breast carcinogenesis. In addition, microsatellite instability (MI), a marker of replication error phenotype (RER+), was observed with a frequency of 16% in the area examined and was inversely related with loss of heterozygosity (LOH). Interestingly, most cases with MI at the region encoding for p16 were aggregated in a subgroup of breast carcinomas with no other obvious genetic and/or epigenetic CDKN2/p16(INK4A) alterations. We speculate that there is an additional mechanism of CDKN2/p16(INK4A) inactivation. The relationship of p16 protein level pRb, status, the p16-pRb combined immunoprofiles, and the microsatellite alterations detected at the 9p21-22 locus with the patients' clinicopathological parameters

  16. Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss, genomic instability, and angiogenic gene expression

    PubMed Central

    Reyes-Botero, German; Dehais, Caroline; Idbaih, Ahmed; Martin-Duverneuil, Nadine; Lahutte, Marion; Carpentier, Catherine; Letouzé, Eric; Chinot, Olivier; Loiseau, Hugues; Honnorat, Jerome; Ramirez, Carole; Moyal, Elisabeth; Figarella-Branger, Dominique; Ducray, François; Desenclos, Christine; Sevestre, Henri; Menei, Philippe; Michalak, Sophie; Al Nader, Edmond; Godard, Joel; Viennet, Gabriel; Carpentier, Antoine; Eimer, Sandrine; Dam-Hieu, Phong; Quintin-Roué, Isabelle; Guillamo, Jean-Sebastien; Lechapt-Zalcman, Emmanuelle; Kemeny, Jean-Louis; Verrelle, Pierre; Faillot, Thierry; Gaultier, Claude; Tortel, Marie Christine; Christov, Christo; Le Guerinel, Caroline; Aubriot-Lorton, Marie-Hélène; Ghiringhelli, Francois; Berger, François; Lacroix, Catherine; Parker, Fabrice; Dubois, François; Maurage, Claude-Alain; Gueye, Edouard-Marcel; Labrousse, Francois; Jouvet, Anne; Bauchet, Luc; Rigau, Valérie; Beauchesne, Patrick; Vignaud, Jean-Michel; Campone, Mario; Loussouarn, Delphine; Fontaine, Denys; Vandenbos, Fanny; Campello, Chantal; Roger, Pascal; Fesneau, Melanie; Heitzmann, Anne; Delattre, Jean-Yves; Elouadhani, Selma; Mokhtari, Karima; Polivka, Marc; Ricard, Damien; Levillain, Pierre-Marie; Wager, Michel; Colin, Philippe; Diebold, Marie-Danièle; Chiforeanu, Dan; Vauleon, Elodie; Langlois, Olivier; Laquerriere, Annie; Motsuo Fotso, Marie Janette; Peoc'h, Michel; Andraud, Marie; Mouton, Servane; Chenard, Marie-Pierre; Noel, Georges; Desse, Nicolas; Soulard, Raoulin; Amiel-Benouaich, Alexandra; Uro-Coste, Emmanuelle; Dhermain, Frederic

    2014-01-01

    Background The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs). Methods The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays. Results Most of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2. Conclusion In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume. PMID:24353325

  17. Extension of chronological life span by reduced TOR signaling requires down-regulation of Sch9p and involves increased mitochondrial OXPHOS complex density

    PubMed Central

    Pan, Yong; Shadel, Gerald S.

    2009-01-01

    The nutrient-sensing target of rapamycin (TOR) pathway appears to have a conserved role in regulating life span. This signaling network is complex, with many downstream physiological outputs, and thus the mechanisms underlying its age-related effects have not been elucidated fully. We demonstrated previously that reduced TOR signaling (intor1Δ strains) extends yeast chronological life span (CLS) by increasing mitochondrial oxygen consumption, in part, by up-regulating translation of mtDNA-encoded oxidative phosphorylation (OXPHOS) subunits. Here, we have examined in greater detail how TOR signaling influences mitochondrial function and CLS and the role of the Sch9p kinase in the TOR-mitochondria pathway. As is the case for oxygen consumption, mitochondrial translation is elevated in tor1Δ strains only during active growth and early stationary phase growth points. This is accompanied by a corresponding increase in the abundance of both mtDNA-encoded and nucleus-encoded OXPHOS subunits per mitochondrial mass. However, this increased OXPHOS complex density is not associated with more mitochondria/cell or cellular ATP and leads to an overall decrease in membrane potential, suggesting that TOR signaling may influence respiration uncoupling. Finally, we document that the Sch9p kinase is a key downstream effector of OXPHOS, ROS and CLS in the TOR-mitochondria pathway. Altogether, our results demonstrate that TOR signaling has a global role in regulating mitochondrial proteome dynamics and function that is important for its role in aging and provide compelling evidence for involvement of a "mitochondrial pre-conditioning" effect in CLS determination. PMID:20157595

  18. KAT6A, a chromatin modifier from the 8p11-p12 amplicon is a candidate oncogene in luminal breast cancer.

    PubMed

    Turner-Ivey, Brittany; Guest, Stephen T; Irish, Jonathan C; Kappler, Christiana S; Garrett-Mayer, Elizabeth; Wilson, Robert C; Ethier, Stephen P

    2014-08-01

    The chromosome 8p11-p12 amplicon is present in 12% to 15% of breast cancers, resulting in an increase in copy number and expression of several chromatin modifiers in these tumors, including KAT6A. Previous analyses in SUM-52 breast cancer cells showed amplification and overexpression of KAT6A, and subsequent RNAi screening identified KAT6A as a potential driving oncogene. KAT6A is a histone acetyltransferase previously identified as a fusion partner with CREB binding protein in acute myeloid leukemia. Knockdown of KAT6A in SUM-52 cells, a luminal breast cancer cell line harboring the amplicon, resulted in reduced growth rate compared to non-silencing controls and profound loss of clonogenic capacity both in mono-layer and in soft agar. The normal cell line MCF10A, however, did not exhibit slower growth with knockdown of KAT6A. SUM-52 cells with KAT6A knockdown formed fewer mammospheres in culture compared to controls, suggesting a possible role for KAT6A in self-renewal. Previous data from our laboratory identified FGFR2 as a driving oncogene in SUM-52 cells. The colony forming efficiency of SUM-52 KAT6A knockdown cells in the presence of FGFR inhibition was significantly reduced compared to cells with KAT6A knockdown only. These data suggest that KAT6A may be a novel oncogene in breast cancers bearing the 8p11-p12 amplicon. While there are other putative oncogenes in the amplicon, the identification of KAT6A as a driving oncogene suggests that chromatin-modifying enzymes are a key class of oncogenes in these cancers, and play an important role in the selection of this amplicon in luminal B breast cancers. PMID:25220592

  19. KAT6A, a Chromatin Modifier from the 8p11-p12 Amplicon is a Candidate Oncogene in Luminal Breast Cancer

    PubMed Central

    Turner-Ivey, Brittany; Guest, Stephen T.; Irish, Jonathan C.; Kappler, Christiana S.; Garrett-Mayer, Elizabeth; Wilson, Robert C.; Ethier, Stephen P.

    2014-01-01

    The chromosome 8p11-p12 amplicon is present in 12% to 15% of breast cancers, resulting in an increase in copy number and expression of several chromatin modifiers in these tumors, including KAT6A. Previous analyses in SUM-52 breast cancer cells showed amplification and overexpression of KAT6A, and subsequent RNAi screening identified KAT6A as a potential driving oncogene. KAT6A is a histone acetyltransferase previously identified as a fusion partner with CREB binding protein in acute myeloid leukemia. Knockdown of KAT6A in SUM-52 cells, a luminal breast cancer cell line harboring the amplicon, resulted in reduced growth rate compared to non-silencing controls and profound loss of clonogenic capacity both in mono-layer and in soft agar. The normal cell line MCF10A, however, did not exhibit slower growth with knockdown of KAT6A. SUM-52 cells with KAT6A knockdown formed fewer mammospheres in culture compared to controls, suggesting a possible role for KAT6A in self-renewal. Previous data from our laboratory identified FGFR2 as a driving oncogene in SUM-52 cells. The colony forming efficiency of SUM-52 KAT6A knockdown cells in the presence of FGFR inhibition was significantly reduced compared to cells with KAT6A knockdown only. These data suggest that KAT6A may be a novel oncogene in breast cancers bearing the 8p11-p12 amplicon. While there are other putative oncogenes in the amplicon, the identification of KAT6A as a driving oncogene suggests that chromatin-modifying enzymes are a key class of oncogenes in these cancers, and play an important role in the selection of this amplicon in luminal B breast cancers. PMID:25220592

  20. Methylation-associated silencing of SFRP1 with an 8p11-12 amplification inhibits canonical and non-canonical WNT pathways in breast cancers

    PubMed Central

    Yang, Zeng-Quan; Liu, Gang; Bollig-Fischer, Aliccia; Haddad, Ramsi; Tarca, Adi L; Ethier, Stephen P.

    2009-01-01

    Recently we analyzed the 8p11-12 genomic region for copy number and gene expression changes in a panel of human breast cancer cell lines and primary specimens. We found that SFRP1 (Secreted frizzled related protein 1) is frequently under expressed even in breast tumors with copy number increases in this genomic region. SFRP1 encodes a WNT signaling antagonist, and plays a role in the development of multiple solid tumor types. In this study, we analyzed methylation-associated silencing of the SFRP1 gene in breast cancer cells with the 8p11-12 amplicon, and investigated the tumor suppressor properties of SFRP1 in breast cancer cells. SFRP1 expression was markedly reduced in both the breast cancer cell lines and primary tumor specimens relative to normal primary human mammary epithelial cells even when SFRP1 is amplified. Suppression of SFRP1 expression in breast cancer cells with an SFRP1 gene amplification is associated with SFRP1 promoter methylation. Furthermore, restoration of SFRP1 expression suppressed the growth of breast cancer cells in monolayer, and inhibited anchorage independent growth. We also examined the releationship between the silencing of SFRP1 gene and WNT signaling in breast cancer. Ectopic SFRP1 expression in breast cancer cells suppressed both canonical and non-canonical WNT signaling pathways, and SFRP1 expression was negatively associated with the expression of a subset of WNT responsive genes including RET and MSX2. Thus, down-regulation of SFRP1 can be triggered by epigenetic and/or genetic events and may contribute to the tumorigenesis of human breast cancer through both canonical and non-canonical WNT signaling pathways. PMID:19569235

  1. Common Variants at 9p21 and 8q22 Are Associated with Increased Susceptibility to Optic Nerve Degeneration in Glaucoma

    PubMed Central

    Hauser, Michael A.; Kang, Jae H.; Allingham, R. Rand; Olson, Lana M.; Abdrabou, Wael; Fan, Bao J.; Wang, Dan Y.; Brodeur, Wendy; Budenz, Donald L.; Caprioli, Joseph; Crenshaw, Andrew; Crooks, Kristy; DelBono, Elizabeth; Doheny, Kimberly F.; Friedman, David S.; Gaasterland, Douglas; Gaasterland, Terry; Laurie, Cathy; Lee, Richard K.; Lichter, Paul R.; Loomis, Stephanie; Liu, Yutao; Medeiros, Felipe A.; McCarty, Cathy; Mirel, Daniel; Moroi, Sayoko E.; Musch, David C.; Realini, Anthony; Rozsa, Frank W.; Schuman, Joel S.; Scott, Kathleen; Singh, Kuldev; Stein, Joshua D.; Trager, Edward H.; VanVeldhuisen, Paul; Vollrath, Douglas; Wollstein, Gadi; Yoneyama, Sachiko; Zhang, Kang; Weinreb, Robert N.; Ernst, Jason; Kellis, Manolis; Masuda, Tomohiro; Zack, Don; Richards, Julia E.; Pericak-Vance, Margaret; Pasquale, Louis R.; Haines, Jonathan L.

    2012-01-01

    Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95%CI 0.63–0.75], p = 1.86×10−18), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95%CI 1.21–1.43], p = 3.87×10−11). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95% CI 0.50–0.67], p = 1.17×10−12) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95% CI 0.53–0.72], p = 8.88×10−10). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95% CI 0.41–0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95% CI 0.54–1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple

  2. Chromosome 9p21 and ABCA1 Genetic Variants and Their Interactions on Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population

    PubMed Central

    Cao, Xiao-Li; Yin, Rui-Xing; Huang, Feng; Wu, Jin-Zhen; Chen, Wu-Xian

    2016-01-01

    The single nucleotide polymorphisms (SNPs) related to both coronary heart disease (CHD) and ischemic stroke (IS) in Chinese individuals have not been identified definitely. This study was developed to evaluate the genetic susceptibility to CHD and IS on the chromosome 9p21 and the adenosine triphosphate (ATP)-binding cassette transporter A1 genes (ABCA1) in a Chinese Han population. Genotypes of the rs1333040, rs1333042, rs4977574, rs2066715 and rs2740483 SNPs were determined in 1134 unrelated patients (CHD, 565 and IS, 569) and 541 controls. The frequencies of the rs4977574 genotypes and alleles between CHD and control groups, and the rs2740483 genotypes and alleles between IS and control groups were different (p = 0.006–0.001). The subjects with rs1333042GG genotype and the carriers of the rs4977574G allele were associated with increased risk of CHD. The carriers of the rs4977574G allele were associated with increased risk of IS. However, the carriers of the rs2740483C allele had lower risk of IS than the non-carriers of the rs2740483C allele after controlling for potential confounders. The rs4977574GG-age (>60 year) interaction increased the risk of CHD (p = 0.022), whereas the rs2740483CG/CC-body mass index (>24 kg/m2) interaction decreased the risk of IS (p = 0.035). The interactions of rs1333040-rs1333042 on the risk of CHD and IS were relatively strong, whereas the interactions of rs1333040-rs1333042-rs2066715 and rs1333040-rs1333042-rs2066715-rs2740483 on the risk of CHD, and rs1333040-rs1333042-rs4977574 and rs1333040-rs1333042-rs4977574-rs2740483 on the risk of IS were relatively weak. These findings suggest that some common variants on the chromosome 9p21 and ABCA1 and their interactions may significantly modify the risk of CHD and IS independent of effects on serum lipid levels. PMID:27096864

  3. The spatial distribution of water in the inner coma of Comet 9P/Tempel 1: Comparison between models and observations

    NASA Astrophysics Data System (ADS)

    Finklenburg, S.; Thomas, N.; Su, C. C.; Wu, J.-S.

    2014-07-01

    The near nucleus coma of Comet 9P/Tempel 1 has been simulated with the 3D Direct Simulation Monte Carlo (DSMC) code PDSC++ (Su, C.-C. [2013]. Parallel Direct Simulation Monte Carlo (DSMC) Methods for Modeling Rarefied Gas Dynamics. PhD Thesis, National Chiao Tung University, Taiwan) and the derived column densities have been compared to observations of the water vapour distribution found by using infrared imaging spectrometer on the Deep Impact spacecraft (Feaga, L.M., A’Hearn, M.F., Sunshine, J.M., Groussin, O., Farnham, T.L. [2007]. Icarus 191(2), 134-145. http://dx.doi.org/10.1016/j.icarus.2007.04.038). Modelled total production rates are also compared to various observations made at the time of the Deep Impact encounter. Three different models were tested. For all models, the shape model constructed from the Deep Impact observations by Thomas et al. (Thomas, P.C., Veverka, J., Belton, M.J.S., Hidy, A., A’Hearn, M.F., Farnham, T.L., et al. [2007]. Icarus, 187(1), 4-15. http://dx.doi.org/10.1016/j.icarus.2006.12.013) was used. Outgassing depending only on the cosine of the solar insolation angle on each shape model facet is shown to provide an unsatisfactory model. Models constructed on the basis of active areas suggested by Kossacki and Szutowicz (Kossacki, K., Szutowicz, S. [2008]. Icarus, 195(2), 705-724. http://dx.doi.org/10.1016/j.icarus.2007.12.014) are shown to be superior. The Kossacki and Szutowicz model, however, also shows deficits which we have sought to improve upon. For the best model we investigate the properties of the outflow.

  4. The Light Curve Of The Dust Cloud Ejected By The Collision Between The Deep Impact Projectile And The Nucleus Of Comet 9P/Tempel 1

    NASA Astrophysics Data System (ADS)

    Kueppers, Michael; Rengel, M.; Keller, H. U.; Gutiérrez, P. J.; Hviid, S. F.

    2007-10-01

    When Deep Impact fired its projectile into the nucleus of comet 9P/Tempel 1, a cloud made of dust and icy grains was ejected from the impact crater. The dust was subsequently accelerated by gas drag. About a week after the impact event, the dust cloud had dispersed due to its expansion and the force exerted by solar radiation pressure. The light curve of the dust cloud contains information about its formation and evolution: The time scale of production of impact created material can be derived from the time scale of the brightness increase. The velocity distribution of the cloud is indicative of acceleration processes in the inner coma of the comet. Finally, the abundance of large dust particles created by the impact can be estimated from the brightness of the cloud several days after the impact when small particles have been pushed away by radiation pressure. Here we analyze data obtained by the Narrow Angle Camera (NAC) of OSIRIS onboard the ESA spacecraft Rosetta to derive the velocity distribution of the dust cloud from an inversion of its light curve. OSIRIS observed comet Tempel 1 near-continuously for more than two weeks around the impact. A model of the expansion of the ejecta is compared to the light curve seen by the NAC. We derive a broad velocity distribution of the dust particles, which peaks at around 225 m/s, in good agreement with published estimates. The velocities suggest that the impact ejecta were quickly accelerated by gas in the cometary coma. We will discuss implications of our results for the evolution of the dust cloud during the first hours after the impact and provide estimates of the released dust mass. OSIRIS is funded by the agencies ASI, CNES, DLR, the Spanish Space Program (Ministerio de Educación y Ciencia), SNSB, and ESA.

  5. Experimental and DFT studies on the vibrational and electronic spectra of 9-p-tolyl-9H-carbazole-3-carbaldehyde.

    PubMed

    Wang, Yiwei; Zhang, Yu; Ni, Haiwei; Meng, Nana; Ma, Kuirong; Zhao, Jianying; Zhu, Dunru

    2015-01-25

    The compound 9-p-tolyl-9H-carbazole-3-carbaldehyde (HCCD) was synthesized and characterized by X-ray diffraction, FT-IR, FT-Raman and UV-Vis spectra. The X-ray diffraction study showed that HCCD has a Z-configuration. The benzene ring including methyl is twisted from the mean plane of the carbazole group by 59.7(3)°, which is comparable with the calculated result 65° for B3LYP/6-311++G(d, p) method. Vibrational spectra and electronic spectra measurements were made for the compound. Optimized geometrical structure and harmonic vibrational frequencies were computed with B-based DFT (BLYP, B3LYP and cam-B3LYP) methods, and WB-based DFT (WB97, WB97X and WB97XD) methods and ab initio RHF method using 6-311++G(d, p) basis set. Assignments of the observed spectra were proposed. The equilibrium geometries computed by all of the methods were compared with X-ray diffraction results. The absorption spectra of the title compound were computed both in gas phase and in DMF solution using TD-(cam)B3LYP/6-311++G(d, p) and PCM-(cam)B3LYP/6-311++G(d, p) approaches, respectively. The calculated results provide good descriptions of the bands maxima in the observed electronic spectrum. Temperature dependence of thermodynamic parameters in the range of 100-1000 K was determined. The natural atomic hybrids were calculated and discussed.

  6. Assignment of the gene coding for the human high-affinity glutamate transporter EAAC1 to 9p24: Potential role in dicarboxylic aminoaciduria and neurodegenerative disorders

    SciTech Connect

    Smith, C.P.; Kanai, Y.; Stelzner, M.; Hediger, M.A.; Weremowicz, S.; Morton, C.C. )

    1994-03-15

    Functional defects of high-affinity glutamate transporters have been implicated in the pathophysiology of neurodegenerative diseases such as amyotrophic lateral sclerosis. In small intestine and kidney, in which the high-affinity glutamate transporter mediates net absorption of glutamate and aspartate across epithelial cells, an inborn error of glutamate transport is thought to cause dicarboxylic aminoaciduria. This disorder is characterized by increased urinary excretion of glutamate and aspartate and is, in general, associated with neurologic and developmental abnormalities. Recently, the authors isolated a cDNA encoding a high-affinity glutamate transporter (EAAC1) that also transports aspartate but not other amino acids. EAAC1 is ubiquitously expressed throughout the body, particularly in brain (neurons), intestine, and kidney. Here, the authors present mapping of the chromosome location of EAAC1 using Southern analysis of a panel of human/rodent somatic cell hybrids and fluorescence in situ hybridization (FISH). Southern analysis of EcoRI-digested DNA gave bands at 6.5, 5.6, 5.1, and 1.2 kb for human genomic DNA; 7.5 kb for mouse genomic DNA; and 7.3, 3.2, and 1 kb for hamster genomic DNA. All four human EAAC1-specific bands were observed in the lane corresponding to the human/Chinese hamster hybrid containing chromosome 9 but not in lanes corresponding to any other hybrid. Because the human/Chinese hamster hybrid is the only one retaining chromosome 9, this result unambiguously assigns human EAAC1 to chromosome 9. For precise chromosome assignment of the human EAAC1 gene, they employed FISH. Map position of the EAAC1 probe was assigned by visual inspection of the fluorescent signal on the DAPI-stained metaphase chromosomes. The human EAAC1 gene was assigned to 9p24.

  7. Nanoparticle formulation enhanced protective immunity provoked by PYGPI8p-transamidase related protein (PyTAM) DNA vaccine in Plasmodium yoelii malaria model.

    PubMed

    Cherif, Mahamoud Sama; Shuaibu, Mohammed Nasir; Kodama, Yukinobu; Kurosaki, Tomoaki; Helegbe, Gideon Kofi; Kikuchi, Mihoko; Ichinose, Akitoyo; Yanagi, Tetsuo; Sasaki, Hitoshi; Yui, Katsuyuki; Tien, Nguyen Huy; Karbwang, Juntra; Hirayama, Kenji

    2014-04-01

    We have previously reported the new formulation of polyethylimine (PEI) with gamma polyglutamic acid (γ-PGA) nanoparticle (NP) to have provided Plasmodium yoelii merozoite surface protein-1 (PyMSP-1) plasmid DNA vaccine with enhanced protective cellular and humoral immunity in the lethal mouse malaria model. PyGPI8p-transamidase-related protein (PyTAM) was selected as a possible candidate vaccine antigen by using DNA vaccination screening from 29 GPI anchor and signal sequence motif positive genes picked up using web-based bioinformatics tools; though the observed protection was not complete. Here, we observed augmented protective effect of PyTAM DNA vaccine by using PEI and γ-PGA complex as delivery system. NP-coated PyTAM plasmid DNA immunized mice showed a significant survival rate from lethal P. yoelii challenge infection compared with naked PyTAM plasmid or with NP-coated empty plasmid DNA group. Antigen-specific IgG1 and IgG2b subclass antibody levels, proportion of CD4 and CD8T cells producing IFN-γ in the splenocytes and IL-4, IFN-γ, IL-12 and TNF-α levels in the sera and in the supernatants from ex vivo splenocytes culture were all enhanced by the NP-coated PyTAM DNA vaccine. These data indicates that NP augments PyTAM protective immune response, and this enhancement was associated with increased DC activation and concomitant IL-12 production.

  8. Differential Flo8p-dependent regulation of FLO1 and FLO11 for cell-cell and cell-substrate adherence of S. cerevisiae S288c.

    PubMed

    Fichtner, Lars; Schulze, Florian; Braus, Gerhard H

    2007-12-01

    Cell-cell and cell-surface adherence represents initial steps in forming multicellular aggregates or in establishing cell-surface interactions. The commonly used Saccharomyces cerevisiae laboratory strain S288c carries a flo8 mutation, and is only able to express the flocculin-encoding genes FLO1 and FLO11, when FLO8 is restored. We show here that the two flocculin genes exhibit differences in regulation to execute distinct functions under various environmental conditions. In contrast to the laboratory strain Sigma1278b, haploids of the S288c genetic background require FLO1 for cell-cell and cell-substrate adhesion, whereas FLO11 is required for pseudohyphae formation of diploids. In contrast to FLO11, FLO1 repression requires the Sin4p mediator tail component, but is independent of the repressor Sfl1p. FLO1 regulation also differs from FLO11, because it requires neither the KSS1 MAP kinase cascade nor the pathways which lead to the transcription factors Gcn4p or Msn1p. The protein kinase A pathway and the transcription factors Flo8p and Mss11p are the major regulators for FLO1 expression. Therefore, S. cerevisiae is prepared to simultaneously express two genes of its otherwise silenced FLO reservoir resulting in an appropriate cellular surface for different environments. PMID:18001350

  9. Cloning and characterization of Rep-8 (D8S2298E) in the human chromosome 8p11.2-p12

    SciTech Connect

    Yamabe, Yukako; Ichikawa, Koji; Sugawara, Kahori

    1997-01-15

    A novel human gene referred to as the Rep-8 gene (D8S2298E) was cloned by a combination of exon trapping, thermal asymmetric interlaced-PCR, and screening of a cDNA library. It is located in human chromosome 8p.11.2-p12. The gene consists of eight exons and spans about 20 kb between the glutathione S-reductase and the protein phosphatase 2A beta subunit genes. The full-length Rep-8 gene contains 1483 nucleotides and codes for a protein of 270 amino acids. Southern blot experiments showed that the Rep-8 gene exists as a single copy per haploid. With a zoo blot analysis, human Rep-8 DNA hybridized strongly with the monkey DNA, but only weakly with the DNAs of species other than Homo sapiens. Northern blot analysis showed that it is expressed abundantly in the testis and ovary, suggesting that the Rep-8 gene product may play a role in reproduction. 16 refs., 5 figs., 1 tab.

  10. Toward localization of the Werner syndrome gene by linkage disequilibrium and ancestral haplotyping: Lessons learned from analysis of 35 chromosome 8p11.1-21.1 markers

    SciTech Connect

    Goddard, K.A.B.; Wijsman, E.M.; Martin, G.M.

    1996-06-01

    Werner syndrome (WS) is an autosomal recessive disorder characterized by premature onset of a number of age-related diseases. The gene for WS, WRN, has been mapped to the 8p11.1-21.1 region with further localization through linkage disequilibrium mapping. Here we present the results of linkage disequilibrium and ancestral haplotype analyses of 35 markers to further refine the location of WRN. We identified an interval in this region in which 14 of 18 markers tested show significant evidence of linkage disequilibrium in at least one of the two populations tested. Analysis of extended and partial haplotypes covering 21 of the markers studied supports the existence of both obligate and probable ancestral recombinant events which localize WRN almost certainly to the interval between DSS2196 and D8S2186, and most likely to the narrower interval between D8S2168 and D8S2186. These haplotype analyses also suggest that there are multiple WRN mutations in each of the two populations under study. We also present a comparison of approaches to performing disequilibrium tests with multiallelic markers, and show that some commonly used approximations for such tests perform poorly in comparison to exact probability tests. Finally, we discuss some of the difficulties introduced by the high mutation rate at microsatellite markers which influence our ability to use ancestral haplotype analysis to localize disease genes. 51 refs., 6 figs., 7 tabs.

  11. 8-p-Hdroxybenzoyl Tovarol Induces Paraptosis Like Cell Death and Protective Autophagy in Human Cervical Cancer HeLa Cells.

    PubMed

    Zhang, Cui; Jiang, Yingnan; Zhang, Jin; Huang, Jian; Wang, Jinhui

    2015-01-01

    8-p-Hdroxybenzoyl tovarol (TAW) is a germacrane-type sesquiterpenoid that can be isolated from the roots of Ferula dissecta (Ledeb.) Ledeb. In this study, the growth inhibitory effects induced by TAW were screened on some types of tumor cells, and the mechanism was investigated on TAW-induced growth inhibition, including paraptosis and autophagy in human cervical cancer HeLa cells. TAW-induced paraptosis involved extensive cytoplasmic vacuolization in the absence of caspase activation. Additionally, TAW evoked cell paraptotic death mediated by endoplasmic reticulum (ER) stress and unfolded protein response (UPR). Autophagy induced by TAW was found to antagonize paraptosis in HeLa cells. This effect was enhanced by rapamycin and suppressed by the autophagy inhibitor, 3-methyladenine (3MA). Loss of beclin 1 (an autophagic regulator) function led to promote ER stress. Taken together, these results suggest that TAW induces paraptosis like cell death and protective autophagy in HeLa cells, which would provide a new clue for exploiting TAW as a promising agent for the treatment of cervical cancer.

  12. Pressure-induced interband optical transitions in an InAs0.8P0.2/InP quantum wire

    NASA Astrophysics Data System (ADS)

    Saravanan, S.; Peter, A. John; Lee, Chang Woo

    2015-12-01

    Hydrostatic pressure-induced exciton binding energy in an InAs0.8P0.2/InP quantum well wire is investigated taking into account the geometrical confinement effect. Numerical calculations are carried out using variational approach within the single-band effective-mass approximation. The compressive strain contribution to the confinement potential is included throughout the calculations. The energy difference of the ground and the first excited state is found with the consideration of spatial confinement effect in the influence of pressure. The second-order susceptibility of harmonic generation is carried out using the compact density method. The optical gain as a function of incident photon energy is computed in the presence of the hydrostatic pressure. The result shows that the range of wavelength for the potential applications of telecommunications (1.3-1.55 μm) can be obtained by the application of the hydrostatic pressure. We believe that the obtained results can be applied for tuning the ranges of fibre optical wavelength in telecommunications.

  13. Cobalt oxide nanoparticles induced oxidative stress linked to activation of TNF-α/caspase-8/p38-MAPK signaling in human leukemia cells.

    PubMed

    Chattopadhyay, Sourav; Dash, Sandeep Kumar; Tripathy, Satyajit; Das, Balaram; Kar Mahapatra, Santanu; Pramanik, Panchanan; Roy, Somenath

    2015-06-01

    The purpose of this study was to determine the intracellular signaling transduction pathways involved in oxidative stress induced by nanoparticles in cancer cells. Activation of reactive oxygen species (ROS) has some therapeutic benefits in arresting the growth of cancer cells. Cobalt oxide nanoparticles (CoO NPs) are an interesting compound for oxidative cancer therapy. Our results showed that CoO NPs elicited a significant (P <0.05) amount of ROS in cancer cells. Co-treatment with N-aceyltine cystine (an inhibitor of ROS) had a protective role in cancer cell death induced by CoO NPs. In cultured cells, the elevated level of tumor necrosis factor-alpha (TNF-α) was noted after CoO NPs treatment. This TNF-α persuaded activation of caspase-8 followed by phosphorylation of p38 mitogen-activated protein kinase and induced cell death. This study showed that CoO NPs induced oxidative stress and activated the signaling pathway of TNF-α-Caspase-8-p38-Caspase-3 to cancer cells.

  14. Localization of the gene causing keratolytic winter erythema to chromosome 8p22-p23, and evidence for a founder effect in South African Afrikaans-speakers.

    PubMed Central

    Starfield, M; Hennies, H C; Jung, M; Jenkins, T; Wienker, T; Hull, P; Spurdle, A; Küster, W; Ramsay, M; Reis, A

    1997-01-01

    Keratolytic winter erythema (KWE), also known as "Oudtshoorn skin disease," or "erythrokeratolysis hiemalis," is an autosomal dominant skin disorder of unknown etiology characterized by a cyclical erythema, hyperkeratosis, and recurrent and intermittent peeling of the palms and soles, particularly during winter. Initially KWE was believed to be unique to South Africa, but recently a large pedigree of German origin has been identified. The disorder occurs with a prevalence of 1/7,000 in the South African Afrikaans-speaking Caucasoid population, and this high frequency has been attributed to founder effect. After a number of candidate regions were excluded from linkage to KWE in both the German family and several South African families, a genomewide analysis was embarked on. Linkage to the microsatellite marker D8S550 on chromosome 8p22-p23 was initially observed, with a maximum LOD score (Z(max)) of 9.2 at a maximum recombination fraction (theta(max)) of .0 in the German family. Linkage was also demonstrated in five of the larger South African families, with Z(max) = 7.4 at theta(max) = .02. When haplotypes were constructed, 11 of 14 South African KWE families had the complete "ancestral" haplotype, and 3 demonstrated conservation of parts of this haplotype, supporting the hypothesis of founder effect. The chromosome segregating with the disease in the German family demonstrated a different haplotype, suggesting that these chromosomes do not have a common origin. Recombination events place the KWE gene in a 6-cM interval between D8S550 and D8S552. If it is assumed that there was a single South African founder, a proposed ancestral recombinant suggests that the gene is most likely in a 1-cM interval between D8S550 and D8S265. PMID:9311742

  15. A genome‐wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain

    PubMed Central

    Deshmukh, H.A.; van Zuydam, N.R.; Liu, Y.; Donnelly, L.A.; Zhou, K.; Morris, A.D.; Colhoun, H.M.; Palmer, C.N.A.; Smith, B.H.

    2015-01-01

    Abstract Background Neuropathic pain, caused by a lesion or a disease affecting the somatosensory system, is one of the most common complications in diabetic patients. The purpose of this study is to identify genetic factors contributing to this type of pain in a general diabetic population. Method We accessed the Genetics of Diabetes Audit and Research Tayside (GoDARTS) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by Affymetrix SNP6.0 or Illumina OmniExpress chips. Cases of neuropathic pain were defined as diabetic patients with a prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain and in whom monofilament test result was positive for sensory neuropathy in at least one foot. Controls were individuals who did not have a record of receiving any opioid analgesics. Imputation of non‐genotyped SNPs was performed by IMPUTE2, with reference files from 1000 Genomes Phase I datasets. Results After data cleaning and relevant exclusions, imputed genotypes of 572 diabetic neuropathic pain cases and 2491 diabetic controls were used in the Fisher's exact test. We identified a cluster in the Chr8p21.3, next to GFRA2 with a lowest p‐value of 1.77 × 10−7 at rs17428041. The narrow‐sense heritability of this phenotype was 11.00%. Conclusion This genome‐wide association study on diabetic neuropathic pain suggests new evidence for the involvement of variants near GFRA2 with the disorder, which needs to be verified in an independent cohort and at the molecular level. PMID:24974787

  16. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

    PubMed Central

    Murabito, Joanne M.; White, Charles C.; Kavousi, Maryam; Sun, Yan V.; Feitosa, Mary F.; Nambi, Vijay; Lamina, Claudia; Schillert, Arne; Coassin, Stefan; Bis, Joshua C.; Broer, Linda; Crawford, Dana C.; Franceschini, Nora; Frikke-Schmidt, Ruth; Haun, Margot; Holewijn, Suzanne; Huffman, Jennifer E.; Hwang, Shih-Jen; Kiechl, Stefan; Kollerits, Barbara; Montasser, May E.; Nolte, Ilja M.; Rudock, Megan E.; Senft, Andrea; Teumer, Alexander; van der Harst, Pim; Vitart, Veronique; Waite, Lindsay L.; Wood, Andrew R.; Wassel, Christina L.; Absher, Devin M.; Allison, Matthew A.; Amin, Najaf; Arnold, Alice; Asselbergs, Folkert W.; Aulchenko, Yurii; Bandinelli, Stefania; Barbalic, Maja; Boban, Mladen; Brown-Gentry, Kristin; Couper, David J.; Criqui, Michael H.; Dehghan, Abbas; Heijer, Martin den; Dieplinger, Benjamin; Ding, Jingzhong; Dörr, Marcus; Espinola-Klein, Christine; Felix, Stephan B.; Ferrucci, Luigi; Folsom, Aaron R.; Fraedrich, Gustav; Gibson, Quince; Goodloe, Robert; Gunjaca, Grgo; Haltmayer, Meinhard; Heiss, Gerardo; Hofman, Albert; Kieback, Arne; Kiemeney, Lambertus A.; Kolcic, Ivana; Kullo, Iftikhar J.; Kritchevsky, Stephen B.; Lackner, Karl J.; Li, Xiaohui; Lieb, Wolfgang; Lohman, Kurt; Meisinger, Christa; Melzer, David; Mohler, Emile R; Mudnic, Ivana; Mueller, Thomas; Navis, Gerjan; Oberhollenzer, Friedrich; Olin, Jeffrey W.; O’Connell, Jeff; O’Donnell, Christopher J.; Palmas, Walter; Penninx, Brenda W.; Petersmann, Astrid; Polasek, Ozren; Psaty, Bruce M.; Rantner, Barbara; Rice, Ken; Rivadeneira, Fernando; Rotter, Jerome I.; Seldenrijk, Adrie; Stadler, Marietta; Summerer, Monika; Tanaka, Toshiko; Tybjaerg-Hansen, Anne; Uitterlinden, Andre G.; van Gilst, Wiek H.; Vermeulen, Sita H.; Wild, Sarah H.; Wild, Philipp S.; Willeit, Johann; Zeller, Tanja; Zemunik, Tatijana; Zgaga, Lina; Assimes, Themistocles L.; Blankenberg, Stefan; Boerwinkle, Eric; Campbell, Harry; Cooke, John P.; de Graaf, Jacqueline; Herrington, David; Kardia, Sharon L. R.; Mitchell, Braxton D.; Murray, Anna; Münzel, Thomas; Newman, Anne; Oostra, Ben A.; Rudan, Igor; Shuldiner, Alan R.; Snieder, Harold; van Duijn, Cornelia M.; Völker, Uwe; Wright, Alan F.; Wichmann, H.-Erich; Wilson, James F.; Witteman, Jacqueline C.M.; Liu, Yongmei; Hayward, Caroline; Borecki, Ingrid B.; Ziegler, Andreas; North, Kari E.; Cupples, L. Adrienne; Kronenberg, Florian

    2012-01-01

    Background Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. Methods and Results Continuous ABI and PAD (ABI≤0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ~2.5 million SNPs in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed-effects inverse variance weighted meta-analyses. There were a total of 41,692 participants of European ancestry (~60% women, mean ABI 1.02 to 1.19), including 3,409 participants with PAD and with GWAS data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (β= −0.006, p=2.46x10−8). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16,717). The association for rs10757269 strengthened in the combined discovery and replication analysis (p=2.65x10−9). No other SNP associations for ABI or PAD achieved genome-wide significance. However, two previously reported candidate genes for PAD and one SNP associated with coronary artery disease (CAD) were associated with ABI : DAB21P (rs13290547, p=3.6x10−5); CYBA (rs3794624, p=6.3x10−5); and rs1122608 (LDLR, p=0.0026). Conclusions GWAS in more than 40,000 individuals identified one genome-wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for CAD are associated with ABI. PMID:22199011

  17. Broad- and narrowband visible imaging of comet 9P/Tempel 1 at ESO around the time of the Deep Impact event

    NASA Astrophysics Data System (ADS)

    Boehnhardt, H.; Pompei, E.; Tozzi, G. P.; Hainaut, O.; Ageorges, N.; Bagnulo, S.; Barrera, L.; Bonev, T.; Käufl, H. U.; Kerber, F.; Locurto, G.; Marco, O.; Pantin, E.; Rauer, H.; Saviane, I.; Selman, F.; Sterken, C.; Weiler, M.

    2007-08-01

    Context: On 4 July 2005 at 05:52UT the impactor of NASA's DeepImpact (DI) mission exploded at comet 9P/Tempel 1. The ejecta material of the impact expanded into the coma that is produced by normal cometary activity. The La Silla and Paranal sites of the European Southern Observatory ESO in Chile participated in the world-wide campaign to observe this event. Aims: The gas and dust content of the cometary coma is observed around the time of the DI event to identify signatures of the impact, like changes in the gas production (CN, C{3}, C{2}, NH{2} and Na) and in the dust properties. The study also describes the normal activity pattern in the coma and the expanding ejecta cloud. Methods: The gas production rates and the dust reddening slope are measured in images obtained through narrowband cometary filters. The ejecta cloud and the features of normal cometary activity, as imaged in narrow- and broadband filter images, are studied with respect to geometry, intensity, and persistence. Results: The production of CN, C{3}, and C{2} gas by the nucleus is at similar level on 3 July and 9+10 July 2005. The mixing ratios of these gases are in the range of those for “typical” comets. NH{2} and Na gas are not detected above the dust continuum flux in the coma. The reddening slope of the dust continuum changes from a value of 9%/100 nm, constant throughout 20 000 km distance around the nucleus, on 3 July to about 19-20%/100 nm on 9+10 July 2005. An increase of the slope with radial distance is found. Both changes might be due to the presence of dust from the ejecta cloud. The dust coma of the comet showed a porcupine pattern of 9 coma jets before impact which remained intact after impact. It can be interpreted as being due to embedded fan structures produced by at least 4 active regions on the rotating nucleus. The ejecta cloud contains dust grains of likely absorbing material and possibly dielectric admixtures with solar radiation pressure factors β of 0.2-1.9 and

  18. Cd{sup 2+}, Mn{sup 2+}, Ni{sup 2+} and Se{sup 2+} toxicity to Saccharomyces cerevisiae lacking YPK9p the orthologue of human ATP13A2

    SciTech Connect

    Schmidt, Karyn; Wolfe, Devin M.; Stiller, Barbara; Pearce, David A.

    2009-05-29

    The Saccharomyces cerevisiae gene YPK9 encodes a putative integral membrane protein which is 58% similar and 38% identical in amino acid sequence to the human lysosomal P{sub 5B} ATPase ATP13A2. Mutations in ATP13A2 have been found in patients with Kufor-Rakeb syndrome, a form of juvenile Parkinsonism. We report that Ypk9p localizes to the yeast vacuole and that deletion of YPK9 confers sensitivity for growth for cadmium, manganese, nickel or selenium. These results suggest that Ypk9p may play a role in sequestration of divalent heavy metal ions. Further studies on the function of Ypk9p/ATP13A2 may help to define the molecular basis of Kufor-Rakeb syndrome and provide a potential link to environmental factors such as heavy metals contributing to some forms of Parkinsonism.

  19. Utp22p acts in concert with Utp8p to channel aminoacyl-tRNA from the nucleolus to the nuclear tRNA export receptor Los1p but not Msn5p.

    PubMed

    Eswara, Manoja B K; Clayton, Ashley; Mangroo, Dev

    2012-12-01

    Utp8p is an essential nucleolar protein that channels aminoacyl-tRNAs from aminoacyl-tRNA synthetases in the nucleolus to the nuclear tRNA export receptors located in the nucleoplasm and nuclear pore complex in Saccharomyces cerevisiae. Utp8p is also part of the U3 snoRNA-associated protein complex involved in 18S rRNA biogenesis in the nucleolus. We report that Utp22p, which is another member of the U3 snoRNA-associated protein complex, is also an intranuclear component of the nuclear tRNA export machinery. Depletion of Utp22p results in nuclear retention of mature tRNAs derived from intron-containing and intronless precursors. Moreover, Utp22p copurifies with the nuclear tRNA export receptor Los1p, the aminoacyl-tRNA synthetase Tys1p and Utp8p, but not with the RanGTPase Gsp1p and the nuclear tRNA export receptor Msn5p. Utp22p interacts directly with Utp8p and Los1p in a tRNA-independent manner in vitro. Utp22p also interacts directly with Tys1p, but this binding is stimulated when Tys1p is bound to tRNA. However, Utp22p, unlike Utp8p, does not bind tRNA saturably. These data suggest that Utp22p recruits Utp8p to aminoacyl-tRNA synthetases in the nucleolus to collect aminoacyl-tRNA and then accompanies the Utp8p-tRNA complex to deliver the aminoacyl-tRNAs to Los1p but not Msn5p. It is possible that Nrap/Nol6, the mammalian orthologue of Utp22p, plays a role in channelling aminoacyl-tRNA to the nuclear tRNA export receptor exportin-t.

  20. Haplotyping and copy number estimation of the highly polymorphic human beta-defensin locus on 8p23 by 454 amplicon sequencing

    PubMed Central

    2010-01-01

    Background The beta-defensin gene cluster (DEFB) at chromosome 8p23.1 is one of the most copy number (CN) variable regions of the human genome. Whereas individual DEFB CNs have been suggested as independent genetic risk factors for several diseases (e.g. psoriasis and Crohn's disease), the role of multisite sequence variations (MSV) is less well understood and to date has only been reported for prostate cancer. Simultaneous assessment of MSVs and CNs can be achieved by PCR, cloning and Sanger sequencing, however, these methods are labour and cost intensive as well as prone to methodological bias introduced by bacterial cloning. Here, we demonstrate that amplicon sequencing of pooled individual PCR products by the 454 technology allows in-depth determination of MSV haplotypes and estimation of DEFB CNs in parallel. Results Six PCR products spread over ~87 kb of DEFB and harbouring 24 known MSVs were amplified from 11 DNA samples, pooled and sequenced on a Roche 454 GS FLX sequencer. From ~142,000 reads, ~120,000 haplotype calls (HC) were inferred that identified 22 haplotypes ranging from 2 to 7 per amplicon. In addition to the 24 known MSVs, two additional sequence variations were detected. Minimal CNs were estimated from the ratio of HCs and compared to absolute CNs determined by alternative methods. Concordance in CNs was found for 7 samples, the CNs differed by one in 2 samples and the estimated minimal CN was half of the absolute in one sample. For 7 samples and 2 amplicons, the 454 haplotyping results were compared to those by cloning/Sanger sequencing. Intrinsic problems related to chimera formation during PCR and differences between haplotyping by 454 and cloning/Sanger sequencing are discussed. Conclusion Deep amplicon sequencing using the 454 technology yield thousands of HCs per amplicon for an affordable price and may represent an effective method for parallel haplotyping and CN estimation in small to medium-sized cohorts. The obtained haplotypes

  1. A novel isoform of the 8p22 tumor suppressor gene DLC1 suppresses tumor growth and is frequently silenced in multiple common tumors.

    PubMed

    Low, J S W; Tao, Q; Ng, K M; Goh, H K; Shu, X-S; Woo, W L; Ambinder, R F; Srivastava, G; Shamay, M; Chan, A T C; Popescu, N C; Hsieh, W-S

    2011-04-21

    The critical 8p22 tumor suppressor deleted in liver cancer 1 (DLC1) is frequently inactivated by aberrant CpG methylation and/or genetic deletion and implicated in tumorigeneses of multiple tumor types. Here, we report the identification and characterization of its new isoform, DLC1 isoform 4 (DLC1-i4). This novel isoform encodes an 1125-aa (amino acid) protein with distinct N-terminus as compared with other known DLC1 isoforms. Similar to other isoforms, DLC1-i4 is expressed ubiquitously in normal tissues and immortalized normal epithelial cells, suggesting a role as a major DLC1 transcript. However, differential expression of the four DLC1 isoforms is found in tumor cell lines: Isoform 1 (longest) and 3 (short thus probably nonfunctional) share a promoter and are silenced in almost all cancer and immortalized cell lines, whereas isoform 2 and 4 utilize different promoters and are frequently downregulated. DLC1-i4 is significantly downregulated in multiple carcinoma cell lines, including 2/4 nasopharyngeal, 8/16 (50%) esophageal, 4/16 (25%) gastric, 6/9 (67%) breast, 3/4 colorectal, 4/4 cervical and 2/8(25%) lung carcinoma cell lines. The functional DLC1-i4 promoter is within a CpG island and is activated by wild-type p53. CpG methylation of the DLC1-i4 promoter is associated with its silencing in tumor cells and was detected in 38-100% of multiple primary tumors. Treatment with 5-aza-2'-deoxycytidine or genetic double knockout of DNMT1 and DNMT3B led to demethylation of the promoter and reactivation of its expression, indicating a predominantly epigenetic mechanism of silencing. Ectopic expression of DLC1-i4 in silenced tumor cells strongly inhibited their growth and colony formation. Thus, we identified a new isoform of DLC1 with tumor suppressive function. The differential expression of various DLC1 isoforms suggests interplay in modulating the complex activities of DLC1 during carcinogenesis. PMID:21217778

  2. Specific labeling and permanent activation of the retinal rod cGMP-activated channel by the photoaffinity analog 8-p-azidophenacylthio-cGMP.

    PubMed Central

    Brown, R L; Gerber, W V; Karpen, J W

    1993-01-01

    Cyclic nucleotide-gated ion channels play a key role in visual excitation and a variety of other signaling pathways. The photoaffinity probe 8-p-azidophenacylthio-cGMP (APT-cGMP) has been developed for structural and functional studies of the cGMP-activated channel of retinal rod outer segments. Using this analog, we have demonstrated both specific labeling of the channel in a partially purified biochemical preparation from bovine rod outer segments and permanent activation of the channel current in excised membrane patches from salamander outer segments. After UV illumination, a 32P-labeled version of APT-cGMP was shown by SDS/PAGE and autoradiography to be covalently attached to the 63-kDa channel subunit. This incorporation was significantly reduced by 8-Br-cGMP but was not reduced by 5'-GMP. In patch-clamp experiments APT-cGMP was a potent activator of the channel; APT-cGMP typically opened half of the channels in a patch at a 10-fold lower concentration than cGMP. Exposure of membrane patches to UV light in the presence of APT-cGMP resulted in a persistent current observed in the absence of bath-applied nucleotide. This current increased with repeated exposure of the patch to both UV light and fresh APT-cGMP, approaching the maximum current originally evoked by saturating (500 microM) cGMP. At this point, addition of 500 microM cGMP caused a negligible increase in current. The persistent current had several other properties expected of current through cGMP-activated channels: it was outwardly rectifying; outward current was blocked > 90% by 2 mM internal Mg2+, whereas inward current was blocked much less efficiently; a low concentration of cGMP caused a larger increase in current atop a half-maximal persistent current than it did originally. We conclude that the persistent current was caused by the covalent tethering of cGMP moieties to channel binding sites, resulting in irreversible channel activation. APT-cGMP should prove useful for further studies of

  3. A familial {open_quotes}balanced{close_quotes} 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings

    SciTech Connect

    Wagstaff, J.; Hemann, M.

    1995-01-01

    A child with phenotypic features of the 9p{sup {minus}} syndrome, including metopic craniosynostosis, small ears, abdominal wall defect, and mental retardation, as well as hypopigmentation, was found to have a cytogenetically balanced 3;9 translocation, with breakpoints at 3p11 and 9p23, inherited from his phenotypically normal father. Molecular analysis showed heterozygous deletion of the TYRP (tyrosinase-related protein) locus, as well as loci D9S157, D9S274, D9S268, and D9S267, in the child but in neither parent. FISH analysis of the proband`s father indicated that loci deleted in his son, including TYRP, were present on neither the der(3) nor the der(9) translocation products but had been inserted into the long arm of chromosome 8. Therefore, the apparent deletion of these loci in the proband was the result of meiotic segregation of the father`s 3;9 translocation chromosomes together with his normal chromosome 8 (not bearing the insertion from 9p23). Neither the deletion of these 9p23 loci from the translocation chromosomes nor their insertion into 8q was detectable by standard chromosome banding techniques. The proband`s sister exhibited speech delay, mild facial dysmorphism, and renal malformation, and her karyotype was 46,XX. Molecular analysis showed that she had inherited normal chromosomes 3 and 9, as well as the chromosome 8 with the insertion of 9p23 material, from her father. This analysis illustrates a new mechanism to explain cases in which an apparently balanced translocation has been transmitted from a normal parent to a child with a phenotypic abnormality: submicroscopic deletion of material from the translocation breakpoint and insertion into a third chromosome in the balanced parent, with meiotic segregation leading to loss of the inserted material in the child. 36 refs., 9 figs., 1 tab.

  4. A familial {open_quotes}balanced{close_quotes} 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings

    SciTech Connect

    Wagstaff, J.; Hemann, M.

    1994-09-01

    Families in which a balanced translocation has been transmitted from a normal parent to a child with a phenotypic abnormality have been a longstanding puzzle for human geneticists. A child with phenotypic features of the 9p- syndrome, including metopic craniosynostosis, small ears, abdominal wall defect, and mental retardation, was found to have a cytogenetically balanced 3;9 translocation, with breakpoints at 3p11 and 9p23, inherited from his normal father. He also exhibited marked hypopigmentation of hair and skin. Analysis with a cDNA probe from the TYRP1 (tyrosinase-related protein 1) gene in 9p23 showed heterozygous deletion in the child but in neither parent. This submicroscopic deletion also included loci D9S157, D9S274, D9S268, and D9S267. FISH analysis of the proband`s father indicated the 9p23 loci deleted in his son were present on neither the der(3) nor the der(9) translocation product, but had been inserted into the long arm of chromosome 8. Therefore, the apparent deletion of these loci in the proband was the result of meiotic segregation of the father`s 3;9 translocation chromosomes together with his normal chromosome 8. Neither the deletion from the translocation chromosomes nor the insertion into 8q was detectable by standard chromosome banding techniques. The proband`s sister exhibited speech delay, mild facial dysmorphism, and renal malformation, and her karyotype was 46,XX. Molecular analysis of this sister showed 3 copies of 9p23 sequences, indicating that she had inherited normal chromosomes 3 and 9 from her father as well as the chromosome 8 with the insertion from 9p23. This analysis illustrates a new mechanism to explain cases of phenotypic discordance in familial balanced translocations: submicroscopic deletion of material from the translocation breakpoint and insertion into a third chromosome in the balanced parent, with meiotic segregation leading to loss of the inserted material in the child.

  5. Optical rectification in a strained GaAs{sub 0.9}P{sub 0.1}/GaAs{sub 0.6}P{sub 0.4} quantum dot: Simultaneous effects of electric and magnetic fields

    SciTech Connect

    Vinolin, Ada; Peter, A. John

    2014-04-24

    Simultaneous effects of electric field and magnetic field on exciton binding energy as a function of dot radius in a cylindrical GaAs{sub 0.9}P{sub 0.1}/GaAs{sub 0.6}P{sub 0.4} strained quantum dot are investigated. The strain contribution includes the strong built-in electric field induced by the spontaneous and piezoelectric polarizations. Numerical calculations are performed using variational procedure within the single band effective mass approximation. Optical rectification in the GaAs{sub 0.9}P{sub 0.1}/GaAs{sub 0.6}P{sub 0.4} quantum dot is computed in the presence of electric and magnetic fields.

  6. Duplication 5q and deletion 9p due to a t(5;9)(q34;p23) in 2 cousins with features of Hunter-McAlpine syndrome and hypothyroidism.

    PubMed

    Vásquez-Velásquez, A I; García-Castillo, H A; González-Mercado, M G; Dávalos, I P; Raca, G; Xu, X; Dwyer, E; Rivera, H

    2011-01-01

    We report on 2 similarly affected cousins with a compound imbalance resulting from a familial t(5;9)(q34;p23) and entailing both an ∼17-Mb 5q terminal duplication and an ∼12-Mb 9p terminal deletion as determined by G-banding, subtelomere FISH, and aCGH. The proband's karyotype was 46,XX,der(9)t(5;9)(q34;p23)mat.ish der(9)t(5;9)(q34;p23)(9pter-,5qter+).arr 5q34q35(163,328,000-180,629,000)×3, 9p24p23(194,000-12,664,000)×1. Her cousin had the same unbalanced karyotype inherited from his father. The clinical phenotype mainly consists of a distinct craniofacial dysmorphism featuring microcephaly, flat facies, down slanting palpebral fissures, small flat nose, long philtrum, and small mouth with thin upper lip. Additional remarkable findings were craniosynostosis of several sutures, craniolacunia and preaxial polydactyly in the proband and hypothyroidism in both subjects. The observed clinical constellation generally fits the phenotypic spectrum of the 5q distal duplication syndrome (known also as Hunter-McAlpine syndrome), except for the thyroid insufficiency which can likely be ascribed to the concurrent 9p deletion, as at least 4 other 9pter monosomic patients without chromosome 5 involvement had this hormonal disorder. The present observation further confirms the etiology of the HMS phenotype from gain of the 5q35→qter region, expands the clinical pictures of partial trisomy 5q and monosomy 9p, and provides a comprehensive list of 160 patients with 5q distal duplication. PMID:21063078

  7. Thermodynamic analysis of binary Fe85B15 to quinary Fe85Si2B8P4Cu1 alloys for primary crystallizations of α-Fe in nanocrystalline soft magnetic alloys

    NASA Astrophysics Data System (ADS)

    Takeuchi, A.; Zhang, Y.; Takenaka, K.; Makino, A.

    2015-05-01

    Fe-based Fe85B15, Fe84B15Cu1, Fe82Si2B15Cu1, Fe85Si2B12Cu1, and Fe85Si2B8P4Cu1 (NANOMET®) alloys were experimental and computational analyzed to clarify the features of NANOMET that exhibits high saturation magnetic flux density (Bs) nearly 1.9 T and low core loss than conventional nanocrystalline soft magnetic alloys. The X-ray diffraction analysis for ribbon specimens produced experimentally by melt spinning from melts revealed that the samples were almost formed into an amorphous single phase. Then, the as-quenched samples were analyzed with differential scanning calorimeter (DSC) experimentally for exothermic enthalpies of the primary and secondary crystallizations (ΔHx1 and ΔHx2) and their crystallization temperatures (Tx1 and Tx2), respectively. The ratio ΔHx1/ΔHx2 measured by DSC experimentally tended to be extremely high for the Fe85Si2B8P4Cu1 alloy, and this tendency was reproduced by the analysis with commercial software, Thermo-Calc, with database for Fe-based alloys, TCFE7 for Gibbs free energy (G) assessments. The calculations exhibit that a volume fraction (Vf) of α-Fe tends to increase from 0.56 for the Fe85B15 to 0.75 for the Fe85Si2B8P4Cu1 alloy. The computational analysis of the alloys for G of α-Fe and amorphous phases (Gα-Fe and Gamor) shows that a relationship Gα-Fe ˜ Gamor holds for the Fe85Si2B12Cu1, whereas Gα-Fe < Gamor for the Fe85Si2B8P4Cu1 alloy at Tx1 and that an extremely high Vf = 0.75 was achieved for the Fe85Si2B8P4Cu1 alloy by including 2.8 at. % Si and 4.5 at. % P into α-Fe. These computational results indicate that the Fe85Si2B8P4Cu1 alloy barely forms amorphous phase, which, in turn, leads to high Vf and resultant high Bs.

  8. Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes.

    PubMed

    Rubio-Moscardo, Fanny; Blesa, David; Mestre, Cinta; Siebert, Reiner; Balasas, Theo; Benito, Adalberto; Rosenwald, Andreas; Climent, Joan; Martinez, Jose I; Schilhabel, Markus; Karran, E Lorraine; Gesk, Stefan; Esteller, Manel; deLeeuw, Ronald; Staudt, Louis M; Fernandez-Luna, Jose Luis; Pinkel, Daniel; Dyer, Martin J S; Martinez-Climent, Jose A

    2005-11-01

    Deletions of chromosome 8p are a recurrent event in B-cell non-Hodgkin lymphoma (B-NHL), suggesting the presence of a tumor suppressor gene. We have characterized these deletions using comparative genomic hybridization to microarrays, fluorescence in situ hybridization (FISH) mapping, DNA sequencing, and functional studies. A minimal deleted region (MDR) of 600 kb was defined in chromosome 8p21.3, with one mantle cell lymphoma cell line (Z138) exhibiting monoallelic deletion of 650 kb. The MDR extended from bacterial artificial chromosome (BAC) clones RP11-382J24 and RP11-109B10 and included the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene loci. Sequence analysis of the individual expressed genes within the MDR and DNA sequencing of the entire MDR in Z138 did not reveal any mutation. Gene expression analysis and quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) showed down-regulation of TRAIL-R1 and TRAIL-R2 receptor genes as a consistent event in B-NHL with 8p21.3 loss. Epigenetic inactivation was excluded via promoter methylation analysis. In vitro studies showed that TRAIL-induced apoptosis was dependent on TRAIL-R1 and/or -R2 dosage in most tumors. Resistance to apoptosis of cell lines with 8p21.3 deletion was reversed by restoration of TRAIL-R1 or TRAIL-R2 expression by gene transfection. Our data suggest that TRAIL-R1 and TRAIL-R2 act as dosage-dependent tumor suppressor genes whose monoallelic deletion can impair TRAIL-induced apoptosis in B-cell lymphoma. PMID:16051735

  9. Direct imaging of structural heterogeneity of the melt-spun Fe{sub 85.2}Si{sub 2}B{sub 8}P{sub 4}Cu{sub 0.8} alloy

    SciTech Connect

    Sato, Kazuhisa Takenaka, Kana; Makino, Akihiro; Hirotsu, Yoshihiko

    2015-06-15

    A structural heterogeneity of the melt-spun Fe{sub 85.2}Si{sub 2}B{sub 8}P{sub 4}Cu{sub 0.8} alloy has been studied by spherical aberration (C{sub s}) corrected high-resolution transmission electron microscopy. Hollow-cone illumination imaging revealed that the density of coherent scattering regions in the as-quenched Fe{sub 85.2}Si{sub 2}B{sub 8}P{sub 4}Cu{sub 0.8} alloy is much higher than that in the Fe{sub 76}Si{sub 9}B{sub 10}P{sub 5} bulk metallic glass. According to the C{sub s}-corrected TEM, crystalline atomic clusters, typically of ∼1 nm in diameter, are densely distributed in an amorphous matrix of Fe{sub 85.2}Si{sub 2}B{sub 8}P{sub 4}Cu{sub 0.8} alloy. Observation of four-fold and six-fold atomic arrangements of these clusters implies existence of Fe clusters with the body centered cubic structure. These Fe clusters must be responsible for the formation of ultrahigh-density α-Fe nanocrystals produced by post-annealing.

  10. Time-resolved UV-IR pump-stimulated emission pump spectroscopy to probe collisional relaxation of the 8p2P3/2 state of Cs I

    NASA Astrophysics Data System (ADS)

    Salahuddin, Mohammed; Arndt, Phill; McFarland, Jacob; Bayram, S. Burçin

    2015-12-01

    We describe and use a time-resolved pump-stimulated emission pump spectroscopic technique to measure collisional relaxation in a high-lying energy level of atomic cesium. Aligned 8p2P3/2 cesium atoms were produced by a pump laser. A second laser, the stimulated emission pump, promoted the population exclusively to the 5d2D5/2 level. The intensity of the 5 d 5/2 2 D → 6 s 1/2 2S cascade fluorescence at 852.12 nm was monitored. The linear polarization dependence of the 6 s 1/2 2S → 8 p 3/2 2P → 5 d 5/2 2S transition was measured in the presence of argon gas at various pressures. From the measurement, we obtained the disalignment cross sectional value for the 8p2P3/2 level due to collisions with ground-level argon atoms.

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

    PubMed Central

    Ballana, Ester; Mercader, Josep Maria; Fischel-Ghodsian, Nathan; Estivill, Xavier

    2007-01-01

    Background Mitochondrial DNA (mtDNA) mutations account for at least 5% of cases of postlingual, nonsyndromic hearing impairment. Among them, mutation A1555G is frequently found associated with aminoglycoside-induced and/or nonsyndromic hearing loss in families presenting with extremely variable clinical phenotypes. Biochemical and genetic data have suggested that nuclear background is the main factor involved in modulating the phenotypic expression of mutation A1555G. However, although a major nuclear modifying locus was located on chromosome 8p23.1 and regardless intensive screening of the region, the gene involved has not been identified. Methods With the aim to gain insights into the factors that determine the phenotypic expression of A1555G mutation, we have analysed in detail different genetic and genomic elements on 8p23.1 region (DEFA3 gene absence, CLDN23 gene and MRPS18CP2 pseudogene) in a group of 213 A1555G carriers. Results Family based association studies identified a positive association for a polymorphism on MRPS18CP2 and an overrepresentation of DEFA3 gene absence in the deaf group of A1555G carriers. Conclusion Although none of the factors analysed seem to have a major contribution to the phenotype, our findings provide further evidences of the involvement of 8p23.1 region as a modifying locus for A1555G 12S rRNA gene mutation. PMID:18154640

  12. A genome-wide scan shows significant linkage between bipolar disorder and chromosome 12q24.3 and suggestive linkage to chromosomes 1p22-21, 4p16, 6q14-22, 10q26 and 16p13.3.

    PubMed

    Ewald, H; Flint, T; Kruse, T A; Mors, O

    2002-01-01

    The present study reports a genomewide scan using linkage analysis for risk genes involved in bipolar disorder with 613 microsatellite markers including additional testing of promising regions. As previously published significant linkage was obtained at chromosome 12q24.3 with a two-point parametric lod score of 3.42 at D12S1639 including all members in both families (empirical P-value 0.00004, genome-wide P-value 0.0417). The multipoint parametric lod score at D12S1639 was 3.63 (genome-wide P-value 0.0265). At chromosome 1p22-p21 a parametric, affecteds-only two-point lod score of 2.75 at marker D1S216 was found (empirical P-value 0.0002, genome-wide P-value 0.1622). A three-point lod score of 2.98 (genome-wide P-value 0.1022) at D1S216, and a multipoint non-parametric analysis with a maximum NPL-all score of 17.60 (P-value 0.00079) at D1S216 further supported this finding. A number of additional loci on chromosomes 4p16, 6q14-q22, 10q26 and 16p13.3 yielded parametric lod scores around or above 2.

  13. Optical transition energy of magneto-polaron in a GaAs{sub 0.9}P{sub 0.1}/GaAs{sub 0.6}P{sub 0.4} quantum dot

    SciTech Connect

    Vinolin, Ada; Peter, A. John

    2015-06-24

    Magneto-LO-polaron in a cylindrical GaAs{sub 0.9} P{sub 0.1} / GaAs{sub 0.6} P{sub 0.4} quantum dot is investigated taking into consideration of geometrical confinement effect. The effects of phonon on the exciton binding energy and the interband emission energy as a function of dot radius are found. The calculations are performed within the single band effective mass approximation using the variational method based on the Lee-Low-Pine LLP transformation.

  14. The magnetic phase transition in Mn{sub 1.1}Fe{sub 0.9}P{sub 1−x}Ge{sub x} magnetocaloric alloys

    SciTech Connect

    Chen, X.; Ramanujan, R. V.

    2015-02-14

    Mn-Fe-P-Ge alloys are promising, low cost, high performance candidates for magnetic cooling applications based on the magnetocaloric effect. These alloys undergo a magnetic phase transition which induces a large entropy change (ΔS). Experimental and modeling studies were conducted to study this transition for varying Ge content. Landau theory and the Bean-Rodbell model were applied to Mn{sub 1.1}Fe{sub 0.9}P{sub 1−x}Ge{sub x} (x = 0.26, 0.3, and 0.32) melt spun ribbons to model the phase transition and the associated entropy change. The critical behavior of these alloys was studied. The critical composition range at which the cross over from first order to second order magnetic transition occurs was determined. The calculated thermodynamic values and critical temperatures were in good agreement with our experimental results. A high maximum entropy change (ΔS) of ∼44.9 J kg{sup −1} K{sup −1} was observed in Mn{sub 1.1}Fe{sub 0.9}P{sub 0.74}Ge{sub 0.26} in a 5 T applied magnetic field. The results suggest that Mn-Fe-P-Ge alloys are very attractive materials for near room temperature magnetic cooling.

  15. Translation initiation in Saccharomyces cerevisiae mitochondria: functional interactions among mitochondrial ribosomal protein Rsm28p, initiation factor 2, methionyl-tRNA-formyltransferase and novel protein Rmd9p.

    PubMed

    Williams, Elizabeth H; Butler, Christine A; Bonnefoy, Nathalie; Fox, Thomas D

    2007-03-01

    Rsm28p is a dispensable component of the mitochondrial ribosomal small subunit in Saccharomyces cerevisiae that is not related to known proteins found in bacteria. It was identified as a dominant suppressor of certain mitochondrial mutations that reduced translation of the COX2 mRNA. To explore further the function of Rsm28p, we isolated mutations in other genes that caused a synthetic respiratory defective phenotype together with rsm28Delta. These mutations identified three nuclear genes: IFM1, which encodes the mitochondrial translation initiation factor 2 (IF2); FMT1, which encodes the methionyl-tRNA-formyltransferase; and RMD9, a gene of unknown function. The observed genetic interactions strongly suggest that the ribosomal protein Rsm28p and Ifm1p (IF2) have similar and partially overlapping functions in yeast mitochondrial translation initiation. Rmd9p, bearing a TAP-tag, was localized to mitochondria and exhibited roughly equal distribution in soluble and membrane-bound fractions. A small fraction of the Rmd9-TAP sedimented together with presumed monosomes, but not with either individual ribosomal subunit. Thus, Rmd9 is not a ribosomal protein, but may be a novel factor associated with initiating monosomes. The poorly respiring rsm28Delta, rmd9-V363I double mutant did not have a strong translation-defective phenotype, suggesting that Rmd9p may function upstream of translation initiation, perhaps at the level of localization of mitochondrially coded mRNAs.

  16. Pericentric inversion of chromosome 7 (inv(7) (p22q11.2)) and ring chromosome 8 (r(8) (p23q24.3)) in a girl with minor anomalies.

    PubMed Central

    Verma, R S; Conte, R A; Pitter, J H; Luke, S

    1992-01-01

    A 13 year old girl was referred with congenital microcephaly, developmental delay, a prominent nose, highly arched palate, and an apparently low set left ear. She was found to have a pericentric inversion of one chromosome 7 and a ring chromosome 8, 46,XX,inv(7) (pter----p22::q11.23----p22::q11.23----qter), r(8) (p23q24.3). The concurrence of these two abnormalities is a rare event and has not been reported previously. Images PMID:1552550

  17. Atomic packing and diffusion in Fe{sub 85}Si{sub 2}B{sub 9}P{sub 4} amorphous alloy analyzed by ab initio molecular dynamics simulation

    SciTech Connect

    Wang, Yaocen; Takeuchi, Akira; Makino, Akihiro; Liang, Yunye; Kawazoe, Yoshiyuki

    2015-05-07

    In the work reported in this paper, ab initio molecular dynamics simulation was performed on Fe{sub 85}Si{sub 2}B{sub 9}P{sub 4} amorphous alloy. Preferred atomic environment of the elements was analyzed with Voronoi polyhedrons. It showed that B and P atoms prefer less neighbors compared with Fe and Si, making them structurally incompatible with Fe rich structure and repulsive to the formation of α-Fe. However, due to the low bonding energy of B and P caused by low coordination number, the diffusion rates of them were considerably large, resulting in the requirement of fast annealing for achieving optimum nano-crystallization for its soft magnetic property. The simulation work also indicates that diffusion rate in amorphous alloy is largely determined by bonding energy rather than atomic size.

  18. A Comparative Study of the Dust Environment near the Nuclei of Comets 1P/Halley, 19P/Borrelly, 81P/Wild 2 & 9P/Tempel1

    NASA Astrophysics Data System (ADS)

    Ho, Tra-Mi; Knollenberg, Joerg; Hoekzema, N.; Boice, Daniel; Kuehrt, Ekkehard; Schulz, Rita; Stuewe, J.; Thomas, Nicolas

    There have been four comets imaged by spacecrafts: 19P/Halley (HMC on Giotto); 19P/Borrelly (MICAS on DS1); 81P/Wild 2 (NavCam on Stardust); and 9P/Tempel 1 (MIR & HIR on Deep Impact). This paper presents a comparative studies of the dust emission within the first 30 - 40 km of the nuclei of these four comets. On March 14, 1986, Giotto encountered comet 1P/Halley's nucleus at a distance of 596km carrying the Halley Multicolour Camera (HMC) [1]. Five years later, Deep Space 1 obtained images of the nucleus of comet 19P/Borrelly with the Miniature Integrated Camera and Spectrometer (MICAS) at a closest distance of 2174km [2]. The next cometary flyby occurred when Stardust approached comet 81P/Wild 2 at 236km on January 2, 2004, tracking its nucleus with its optical navigation camera (NavCam) [3]. The latest close encounter occurred in July 4, 2005, when Deep Impact flew by 9P/Tempel 1 at 500km [4] carrying the Medium Resolution Instrument (MIR). Since the nuclei of 1P/Halley, 19P/Borrelly, 81P/Wild 2 and 9P/Tempel 1 have been observed under similar phase angles (108° , 88° , 73° , and 63° , respectively), we can do a comparative analysis of the inner dust environment of these data sets. The inner dust coma morphology, particularly dust jets and broader fans, of these four comets has been investigated by several authors [5]-[8]. We concentrate on the comparative study of their dust emission. The outflow of dust particles is force-free at large radial distance from the comet nucleus. Thus, integrating the intensity Ids [9] around a comet results in constant Ids. However, the integrated intensities of comets 1P/Halley and 19P/Borrelly indicate deviation from the expected behavior within the first 50 km from their nuclei [10]. 1P/Halley's Ids decreases near the nucleus surface whereas comet 19P/Borrelly's Ids increases. But at large distances, they both converge to constant values. These opposite effects in the first 50km indicate that different mechanisms dominate

  19. A t(17;19)(q22;p13.3) Involving TCF3, a t(1;9)(p13;p13), and a 5' IGH Deletion in a Case of Adult B-cell Acute Lymphoblastic Leukemia.

    PubMed

    Chow, R; Shabsovich, D; Schiller, G; Kallen, M; Tirado, Carlos A

    2016-01-01

    TCF3 (19p13.3) abnormalities are relatively common in B-cell acute lymphoblastic leukemia (B-ALL). The t(1;19)(q23;p13) involving PBX1 is the most common of these rearrangements. The t(17;19)(q22;p13.3), resulting in the TCF3-HLF fusion gene, is also seen in B-ALL and is associated with an extremely poor prognosis. Herein, we present the case of a 25-year-old male diagnosed with B-ALL whose initial karyotype showed a t(17;19)(q22p13.3). FISH confirmed TCF3 involvement and also revealed a 5' IGH deletion. After treatment, the patient relapsed, at which point conventional cytogenetic studies showed a t(17;19), loss of the 5' IGH region, and a t(3;10) not seen in initial studies. After hematopoietic stem cell transplantation, the patient relapsed again, at which point conventional cytogenetic studies showed a complex karyotype with t(17;19), t(1;9)(p13;p13), and structural anomalies involving chromosomes 5, 7, and 14, but no IGH abnormalities by FISH. The t(1;9) has been shown to involve PAX5, which plays numerous regulatory roles in B-cell differentiation. Other PAX5 rearrangements have been detected in B-ALL cases of young adults and adolescents, but with unclear clinical significance. To the best of our knowledge, this is the first reported case of t(17;19)-ALL with concomitant 5' IGH deletion and t(1;9)(p13;p13) potentially involving PAX5, albeit at different time points in disease progression. This case provides insight into the clonal evolution of t(17;19)-ALL and the potential involvement of PAX5 and IGH aberrations in the evolution of this malignancy. PMID:27183380

  20. A Genome-wide Association Study Provides Evidence of Sex-specific Involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) With Diabetic Neuropathic Pain.

    PubMed

    Meng, Weihua; Deshmukh, Harshal A; Donnelly, Louise A; Torrance, Nicola; Colhoun, Helen M; Palmer, Colin N A; Smith, Blair H

    2015-10-01

    Neuropathic pain is defined as pain arising as a direct consequence of a lesion or a disease affecting the somatosensory system and it affects around 1 in 4 diabetic patients in the UK. The purpose of this genome-wide association study (GWAS) was to identify genetic contributors to this disorder. Cases of neuropathic pain were defined as diabetic patients with a multiple prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain. Controls were diabetic individuals who were not prescribed any of these drugs, nor amitriptyline, carbamazepine, or nortriptyline. Overall, 961 diabetic neuropathic pain cases and 3260 diabetic controls in the Genetics of Diabetes Audit and Research Tayside (GoDARTS) cohort were identified. We found a cluster in the Chr1p35.1 (ZSCAN20-TLR12P) with a lowest P value of 2.74 × 10(- 7) at rs71647933 in females and a cluster in the Chr8p23.1, next to HMGB1P46 with a lowest P value of 8.02 × 10(- 7) at rs6986153 in males. Sex-specific narrow sense heritability was higher in males (30.0%) than in females (14.7%). This GWAS on diabetic neuropathic pain provides evidence for the sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P) and Chr8p23.1 (HMGB1P46) with the disorder, indicating the need for further research. PMID:26629533

  1. Synthesis of a novel chromium-phosphate built up with unprecedented [CR{sub 9}P{sub 12}O{sub 58}H{sub 12}]{sup 17-} clusters under hydrothermal conditions

    SciTech Connect

    Liu Wei; Xiong Dingbang; Yang Xinxin; Zhao Jingtai

    2007-07-15

    A new chromium-phosphate has been prepared under hydrothermal conditions for the first time. It crystallizes in the Monoclinic system, space group C2/c, a=17.002(3) A, b=26.333(5) A, c=16.017(4) A, {beta}=96.63 (3){sup o}, V=7123.07(2) A{sup 3} and Z=4. The crystal structure displays a centrosymmetric complex aggregate [Cr{sub 9}P{sub 12}O{sub 58}H{sub 12}]{sup 17-}, constructed from the unprecedented enneanucleus chromic core Cr{sub 9}O{sub 10} with peripheral ligations provided by 12 phosphate groups. The sodium ions and water as guests fill in the cavities among the clusters to satisfy the charge balance and keep the structural stability. The magnetic measurement indicates the existence of antiferromagnetic interactions. - Graphical abstract: Polyhedral representation of the oxo-chromium core in compound 1, showing the bridging function of phosphate groups around the octahedral chromium core (CrO{sub 6} octahedron, grey and transparent; Cr, green sphere; P, pink sphere; O, red sphere; H, small black sphere)

  2. Pre- and postnatal findings in a patient with a novel rec(8)dup(8q)inv(8)(p23.2q22.3) associated with San Luis Valley syndrome.

    PubMed

    Vera-Carbonell, Ascensión; López-González, Vanesa; Bafalliu, Juan Antonio; Piñero-Fernández, Juan; Susmozas, Joaquín; Sorli, Moisés; López-Pérez, Rocío; Fernández, Asunción; Guillén-Navarro, Encarna; López-Expósito, Isabel

    2013-09-01

    San Luis Valley syndrome, which is due to a recombinant chromosome 8 (SLV Rec8) found in Hispanic individuals from Southwestern United States, is a well-established syndrome associated with intellectual disabilities and, frequently, severe cardiac anomalies. We report for the first time on a Moroccan girl with a recombinant chromosome 8 prenatally diagnosed as SLV Rec8 by conventional cytogenetic studies. At birth, an oligo array-CGH (105 K) defined the breakpoints and the size of the imbalanced segments, with a deletion of ≈ 2.27 Mb (8p23.2-pter) and a duplication of ≈ 41.93 Mb (8q22.3-qter); thus this recombinant chromosome 8 differed from that previously reported in SLV Rec8 syndrome. The phenotypic characteristics associated with this SLV Rec8 genotype overlap those commonly found in patients with 8q duplication reported in the literature. We review SLV Rec8 and other chromosome 8 aberrations and suggest that the overexpression of cardiogenic genes located at 8q may be the cause of the cardiac defects in this patient.

  3. Sperm FISH analysis of a 46,XY,t(3;6)(p24;p21.2),inv (8)(p11;2q21.2) double chromosomal rearrangement.

    PubMed

    Ferfouri, Fatma; Boitrelle, Florence; Tapia, Sylvie; Molina Gomes, Denise; Selva, Jacqueline; Vialard, François

    2012-02-01

    A complex chromosome rearrangement (CCR) can be defined as a structural chromosomal aberration that involves at least three breakpoints located on two or more chromosomes. Highly unbalanced gametes may lead to infertility or congenital malformations. Here is reported a double rearrangement considered as the simplest possible CCR and, in a sense, not a true CCR, meiotic segregation for a 46,XY,t(3;6)(p24;p21.2),inv(8)(p11;2q21.2) male patient referred after his partner had undergone three early miscarriages. Sperm fluorescence in-situ hybridization was used to screen for translocation and inversion segregation and an interchromosomal effect (ICE) for 13 chromosomes not involved in CCR. The malsegregation rates for the reciprocal translocation and pericentric inversion were 61.2% and 1.7%, respectively. ICE analysis revealed that the observed chromosome aneuploidy rates of between 0.1% and 0.8% did not differ significantly from control values. A slight increase in cumulative ICE (P=0.049) was observed in the patient, relative to control spermatozoa (with rates of 4.6% and 3.1%). The sperm DNA fragmentation rate differed significantly from control values (5.0%; P=0.001). Reciprocal translocation had no impact on meiotic segregation of the pericentric inversion in this double rearrangement. No conclusion could be drawn regarding the impact of pericentric inversion on translocation.

  4. Experimental and DFT studies on the vibrational and electronic spectra and NBO analysis of 2-amino-3-((E)-(9-p-tolyl-9H-carbazol-3-yl) methyleneamino) maleonitrile.

    PubMed

    Meng, Nana; Zhang, Yu; Wang, Yiwei; Ma, Kuirong; Zhao, Jianying; Tang, Guodong

    2014-01-01

    2-Amino-3-((E)-(9-p-tolyl-9H-carbazol-3-yl) methyleneamino) maleonitrile (ACMM) was synthesized and characterized by X-ray diffraction, FT-IR, FT-Raman and UV-Vis spectra. The X-ray diffraction study showed that ACMM has a Z-configuration, due to the intramolecular C18H18A⋯N2, N3H3A⋯N2 and C20H20A⋯N4 hydrogen bonds and intermolecular C10H10A⋯N4, N3H3B⋯N9 (2-x, 2-y, 2-z) and N3H8C⋯N4 (2-x, 1-y, 2-z) hydrogen bonds. The benzene ring including methyl is twisted from the mean plane of the carbazole group by 59.7(3)°. Vibrational spectra and electronic spectra measurements were made for the compound. Optimized geometrical structure and harmonic vibrational frequencies were computed with DFT (B3-based B3P86, B3LYP, B3PW91 and B-based BP86, BLYP, BPW91) methods and ab initio RHF method using 6-311++G(d, p) basis set. Assignments of the observed spectra were proposed. The equilibrium geometries computed by all of the methods were compared with X-ray diffraction results. The absorption spectra of the title compound were computed both in gas phase and in DMF solution using TD-B3LYP/6-311++G(d, p) and PCM-B3LYP/6-311++G(d, p) approaches, respectively. The calculated results provide a good description of positions of the bands maxima in the observed electronic spectrum. Temperature dependence of thermodynamic parameters in the range of 100-1000K were determined. The bond orbital occupancies, contribution from parent natural bond orbital (NBO), the natural atomic hybrids was calculated and discussed.

  5. Low core losses and magnetic properties of Fe85-86Si1-2B8P4Cu1 nanocrystalline alloys with high B for power applications (invited)

    NASA Astrophysics Data System (ADS)

    Makino, Akihiro; Kubota, Takeshi; Yubuta, Kunio; Inoue, Akihisa; Urata, Akiri; Matsumoto, Hiroyuki; Yoshida, Shigeyoshi

    2011-04-01

    Recently, the energy crisis and the continued growth in electrical power generation strongly demand minimization of wasteful energy dissipation. Magnetic core loss (W) is the main source of energy dissipation in motors and transformers. This requires the development of soft magnetic materials with low coercivity (Hc) and high magnetic flux density (B). Fe-rich Fe85-86Si1-2B8P4Cu1 (at. %) alloy ribbons made from industrial raw materials (containing some impurities) with 6 mm in width have a heteroamorphous structure containing a large number of extremely small Fe grains (less than 3 nm), resulting from the unique effects of P and Cu addition in proper amounts. Crystallization of these alloys by annealing shows a uniform precipitation of α-Fe, leading to a uniform nanocrystallized structure of α-Fe grains, 16-19 nm in size, accompanied by an intergranular amorphous layer about 1 nm in width. The wide ribbons exhibit high B of 1.82-1.85 T (at 800 A/m), almost comparable to commercial oriented Fe-3 mass% Si alloys. Excellent magnetic softness (low Hc of 2.6-5.8 A/m, high permeability of 2.4-2.7 × 104 at 1 kHz and small saturation magnetostriction of 2.3-2.4 × 10-6) along with high electrical resistivity (0.67-0.74 μΩ m) of these alloys result in superior frequency characteristics of core losses and a much lower W at 50 Hz up to the maximum induction of 1.75 T, in comparison to the silicon steels now in practical use for power applications.

  6. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

    PubMed Central

    2012-01-01

    Introduction Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). Methods To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Results Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). Conclusions The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers. PMID:22348646

  7. Electronic Structure of the Metal Center in the Cd[superscript 2+], Zn[superscript 2+], and Cu[superscript 2+] Substituted Forms of KDO8P Synthase: Implications for Catalysis

    SciTech Connect

    Kona, Fathima; Tao, Peng; Martin, Philip; Xu, Xingjue; Gatti, Domenico L.

    2009-07-31

    Aquifex aeolicus 3-deoxy-D-manno-octulosonate 8-phosphate synthase (KDO8PS) is active with a variety of different divalent metal ions bound in the active site. The Cd{sup 2+}, Zn{sup 2+}, and Cu{sup 2+} substituted enzymes display similar values of k{sub cat} and similar dependence of K{sub m}{sup PEP} and K{sub m}{sup A5P} on both substrate and product concentrations. However, the flux-control coefficients for some of the catalytically relevant reaction steps are different in the presence of Zn{sup 2+} or Cu{sup 2+}, suggesting that the type of metal bound in the active site affects the behavior of the enzyme in vivo. The type of metal also affects the rate of product release in the crystal environment. For example, the crystal structure of the Cu{sup 2+} enzyme incubated with phosphoenolpyruvate (PEP) and arabinose 5-phosphate (A5P) shows the formed product, 3-deoxy-D-manno-octulosonate 8-phosphate (KDO8P), still bound in the active site in its linear conformation. This observation completes our structural studies of the condensation reaction, which altogether have provided high-resolution structures for the reactants, the intermediate, and the product bound forms of KDO8PS. The crystal structures of the Cd{sup 2+}, Zn{sup 2+}, and Cu{sup 2+} substituted enzymes show four residues (Cys-11, His-185, Glu-222, and Asp-233) and a water molecule as possible metal ligands. Combined quantum mechanics/molecular mechanics (QM/MM) geometry optimizations reveal that the metal centers have a delocalized electronic structure, and that their true geometry is square pyramidal for Cd{sup 2+} and Zn{sup 2+} and distorted octahedral or distorted tetrahedral for Cu{sup 2+}. These geometries are different from those obtained by QM optimization in the gas phase (tetrahedral for Cd{sup 2+} and Zn{sup 2+}, distorted tetrahedral for Cu{sup 2+}) and may represent conformations of the metal center that minimize the reorganization energy between the substrate-bound and product-bound states

  8. New case of trichorinophalangeal syndrome-like phenotype with a de novo t(2;8)(p16.1;q23.3) translocation which does not disrupt the TRPS1 gene

    PubMed Central

    2014-01-01

    Background Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterised by distinctive craniofacial and skeletal abnormalities. TRPS is generally associated with mutations in the TRPS1 gene at 8q23.3 or microdeletions of the 8q23.3-q24.11 region. However, three deletions affecting the same chromosome region and a familial translocation t(8;13) co-segregating with TRPS, which do not encompass or disrupt the TRPS1 gene, have been reported. A deregulated expression of TRPS1 has been hypothesised as cause of the TRPS phenotype of these patients. Case presentation We report the clinical and molecular characterisation of a 57-year-old Caucasian woman carrying the t(2;8)(p16.1;q23.3) de novo balanced translocation. The proband presented with peculiar clinical features (severe craniofacial dysmorphism, alopecia universalis, severe scoliosis, mitral valve prolapse, mild mental impairment and normal growth parameters) that partially overlap with TRPS I. Mutational and array CGH analyses ruled out any genetic defect affecting TRPS1 or genomic alteration at the translocation breakpoint or elsewhere in the genome. Breakpoint mapping excluded disruption of TRPS1, and revealed that the chromosome 8q23.3 breakpoint was located within the IVS10 of the long intergenic non-coding RNA LINC00536, at approximately 300 kb from the TRPS1 5’ end. Conversely, the 2p16.1 breakpoint mapped within a LINE sequence, in a region that lacks transcriptional regulatory elements. As a result of the translocation, nucleotide base pair additions and deletions were detected at both breakpoint junction fragments, and an evolutionarily conserved VISTA enhancer element from 2p16.1 was relocated at approximately 325 kb from the TRPS1 promoter. Conclusions We suggest that the disruption of the genomic architecture of cis regulatory elements downstream the TRPS1 5′ region, combined with the translocation of a novel enhancer element nearby TRPS1, might be the

  9. 75 FR 21623 - Commission Information Collection Activities (FERC Form Nos. 6 and 6-Q); Comment Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ...''), ``Annual Report of Oil Pipeline Companies,'' implemented in 18 CFR Sections 357.1, 357.2, and 385.2011; OMB... of Oil Pipeline Companies,'' implemented in 18 CFR Section 357.4; OMB Control No. 1902-0206. The... Value Put-In Place (VPIP) for oil pipeline utilities. Census VPIP serves as a major source data input...

  10. Thermodynamic analysis of binary Fe{sub 85}B{sub 15} to quinary Fe{sub 85}Si{sub 2}B{sub 8}P{sub 4}Cu{sub 1} alloys for primary crystallizations of α-Fe in nanocrystalline soft magnetic alloys

    SciTech Connect

    Takeuchi, A. Zhang, Y.; Takenaka, K.; Makino, A.

    2015-05-07

    Fe-based Fe{sub 85}B{sub 15}, Fe{sub 84}B{sub 15}Cu{sub 1}, Fe{sub 82}Si{sub 2}B{sub 15}Cu{sub 1}, Fe{sub 85}Si{sub 2}B{sub 12}Cu{sub 1}, and Fe{sub 85}Si{sub 2}B{sub 8}P{sub 4}Cu{sub 1} (NANOMET{sup ®}) alloys were experimental and computational analyzed to clarify the features of NANOMET that exhibits high saturation magnetic flux density (B{sub s}) nearly 1.9 T and low core loss than conventional nanocrystalline soft magnetic alloys. The X-ray diffraction analysis for ribbon specimens produced experimentally by melt spinning from melts revealed that the samples were almost formed into an amorphous single phase. Then, the as-quenched samples were analyzed with differential scanning calorimeter (DSC) experimentally for exothermic enthalpies of the primary and secondary crystallizations (ΔH{sub x1} and ΔH{sub x2}) and their crystallization temperatures (T{sub x1} and T{sub x2}), respectively. The ratio ΔH{sub x1}/ΔH{sub x2} measured by DSC experimentally tended to be extremely high for the Fe{sub 85}Si{sub 2}B{sub 8}P{sub 4}Cu{sub 1} alloy, and this tendency was reproduced by the analysis with commercial software, Thermo-Calc, with database for Fe-based alloys, TCFE7 for Gibbs free energy (G) assessments. The calculations exhibit that a volume fraction (V{sub f}) of α-Fe tends to increase from 0.56 for the Fe{sub 85}B{sub 15} to 0.75 for the Fe{sub 85}Si{sub 2}B{sub 8}P{sub 4}Cu{sub 1} alloy. The computational analysis of the alloys for G of α-Fe and amorphous phases (G{sub α-Fe} and G{sub amor}) shows that a relationship G{sub α-Fe} ∼ G{sub amor} holds for the Fe{sub 85}Si{sub 2}B{sub 12}Cu{sub 1}, whereas G{sub α-Fe} < G{sub amor} for the Fe{sub 85}Si{sub 2}B{sub 8}P{sub 4}Cu{sub 1} alloy at T{sub x1} and that an extremely high V{sub f} = 0.75 was achieved for the Fe{sub 85}Si{sub 2}B{sub 8}P{sub 4}Cu{sub 1} alloy by including 2.8 at. % Si and 4.5 at. % P into α-Fe. These computational results indicate that the Fe{sub 85}Si{sub 2}B

  11. A Novel Cryptic Three-Way Translocation t(2;9;18)(p23.2;p21.3;q21.33) with Deletion of Tumor Suppressor Genes in 9p21.3 and 13q14 in a T-Cell Acute Lymphoblastic Leukemia.

    PubMed

    Othman, Moneeb A K; Rincic, Martina; Melo, Joana B; Carreira, Isabel M; Alhourani, Eyad; Hunstig, Friederike; Glaser, Anita; Liehr, Thomas

    2014-01-01

    Acute leukemia often presents with pure chromosomal resolution; thus, aberrations may not be detected by banding cytogenetics. Here, a case of 26-year-old male diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) and a normal karyotype after standard GTG-banding was studied retrospectively in detail by molecular cytogenetic and molecular approaches. Besides fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and high resolution array-comparative genomic hybridization (aCGH) were applied. Thus, cryptic chromosomal aberrations not observed before were detected: three chromosomes were involved in a cytogenetically balanced occurring translocation t(2;9;18)(p23.2;p21.3;q21.33). Besides a translocation t(10;14)(q24;q11) was identified, an aberration known to be common in T-ALL. Due to the three-way translocation deletion of tumor suppressor genes CDKN2A/INK4A/p16, CDKN2B/INK4B/p15, and MTAP/ARF/p14 in 9p21.3 took place. Additionally RB1 in 13q14 was deleted. This patient, considered to have a normal karyotype after low resolution banding cytogenetics, was treated according to general protocol of anticancer therapy (ALL-BFM 95).

  12. Phase transition from fcc to bcc structure of the Cu-clusters during nanocrystallization of Fe{sub 85.2}Si{sub 1}B{sub 9}P{sub 4}Cu{sub 0.8} soft magnetic alloy

    SciTech Connect

    Nishijima, Masahiko; Matsuura, Makoto; Takenaka, Kana; Takeuchi, Akira; Makino, Akihiro; Ofuchi, Hironori

    2014-05-15

    A role of Cu on the nanocrystallization of an Fe{sub 85.2}Si{sub 1}B{sub 9}P{sub 4}Cu{sub 0.8} alloy was investigated by X-ray absorption fine structure (XAFS) and transmission electron microscopy (TEM). The Cu K-edge XAFS results show that local structure around Cu is disordered for the as-quenched sample whereas it changes to fcc-like structure at 613 K. The fcc Cu-clusters are, however, thermodynamically unstable and begin to transform into bcc structure at 638 K. An explicit bcc structure is observed for the sample annealed at 693 K for 600 s in which TEM observation shows that precipitated bcc-Fe crystallites with ∼12 nm are homogeneously distributed. The bcc structure of the Cu-clusters transforms into the fcc-type again at 973 K, which can be explained by the TEM observations; Cu segregates at grain boundaries between bcc-Fe crystallites and Fe{sub 3}(B,P) compounds. Combining the XAFS results with the TEM observations, the structure transition of the Cu-clusters from fcc to bcc is highly correlated with the preliminary precipitation of the bcc-Fe which takes place prior to the onset of the first crystallization temperature, T{sub x1} = 707 K. Thermodynamic analysis suggests that an interfacial energy density γ between an fcc-Cu cluster and bcc-Fe matrix dominates at a certain case over the structural energy between fcc and bcc Cu, ΔG{sub fcc} {sub −} {sub bcc}, which causes phase transition of the Cu clusters from fcc to bcc structure.

  13. A study of loss of heterozygosity at 70 loci in anaplastic astrocytoma and glioblastoma multiforme with implications for tumor evolution.

    PubMed Central

    Wooten, E. C.; Fults, D.; Duggirala, R.; Williams, K.; Kyritsis, A. P.; Bondy, M. L.; Levin, V. A.; O'Connell, P.

    1999-01-01

    Cancers that arise from astrocytes in the adult CNS present as either anaplastic astrocytomas (AAs) or as more aggressive glioblastomas multiforme (GBMs). GBMs either form de novo or progress from AAs. We proposed to examine the molecular genetic relationship between these CNS tumors by conducting a genome-wide allelic imbalance analysis that included 70 loci on examples of AA and GBM. We found significant loss of heterozygosity (LOH) at 13 discrete chromosomal loci in both AAs and GBMs. Loss was significant in both AAs and GBMs at 9 of these loci. AAs show the highest rates of LOH at chromosomes 1p, 4q, 6p, 9p, 11p, 11q, 13q, 14q, 15p, 17p, 17q, and 19q. GBMs showed the greatest losses at 1p, 6q, 8p, 9p, 10p, 10q, 11p, 13q, 17p, 17q, 18p, 18q, and 19q. GBMs also demonstrated significant amplification at the epidermal growth factor receptor locus (7p12). These data suggest that there are three classes of loci involved in glioma evolution. First are loci that are likely involved in early events in the evolution of both AAs and GBMs. The second class consists of AA-specific loci, typified by higher LOH frequency than observed in GBMs (4q, 6p, 17p, 17q, 19q). The third class consists of GBM-specific loci (6q, 8p, 10, 18q). Damage at these loci may either lead to de novo GBMs or permit existing AAs to progress to GBMs. Glioma-related LOH profiles may have prognostic implications that could lead to better diagnosis and treatment of brain cancer patients. PMID:11550311

  14. Non-mosaic tetrasomy 9p in a liveborn infant with multiple congenital anomalies: Case report and comparison with trisomy 9p

    SciTech Connect

    Leichtman, L.G.; Zackowski, J.L.; Storto, P.D.; Newlin, A.

    1996-06-14

    Tetrasomy of the short(p) arm of chromosome 9 has been reported in few cases. Most of these children present with microbrachycephaly, wide forehead, hypertelorism, lowset, malformed ears, beaked noses, and micrognathia. Additional anomalies include short neck, congenital heart disease, genital abnormalities, multiple limb defects, hypotonia, and early death.

  15. Fluorescence in situ hybridization evaluation of chromosome deletion patterns in prostate cancer.

    PubMed Central

    Huang, S. F.; Xiao, S.; Renshaw, A. A.; Loughlin, K. R.; Hudson, T. J.; Fletcher, J. A.

    1996-01-01

    Various nonrandom chromosomal aberrations have been identified in prostate carcinoma. These aberrations include deletions of several chromosome regions, particularly the chromosome 8 short arm. Large-scale numerical aberrations, reflected in aberrant DNA ploidy, are also found in a minority of cases. However, it is unclear whether prostate carcinomas contain aberrations of certain chromosome regions that are deleted frequently in other common types of cancer. In this study, we performed dual-color fluorescence in situ hybridization on intact nuclei from touch preparations of 16 prostate cancers. Chromosome copy number was determined using pericentromeric probes, whereas potential chromosome arm deletions were evaluated using yeast artificial chromosome (YAC) and P1 probes. Two YAC probes targeted chromosome 8 short arm regions known to be deleted frequently in prostate cancer. Other YACs and P1s were for chromosome regions, including 1p22, 3p14, 6q21, 9p21, and 22q12, that are deletion targets in a variety of cancers although not extensively studied in prostate cancer. Hybridization efficiencies and signal intensities were excellent for both repeat sequence (alpha-satellite) and single, copy (YAC and P1) fluorescence in situ hybridization probes. Of 16 prostate cancers, 11 had clonal aberrations of 1 or more of the 13 chromosome regions evaluated, and 10 cases (62.5%) had 8p deletions, including 4 cases with 8p deletion in virtually all cells and aneuploidy in only a subset of those deleted cells. Deletions at 3p14, 6q21, and 22q12 were identified in 2, 1, and 1 case, respectively, and each of those cases had a similarly sized cell population with 8p deletion. These studies confirm 8p deletion in the majority of prostate carcinomas. 8p deletions appear to be early events in prostate tumorigenesis, often antedating aneuploidy. Fluorescence in situ hybridization strategies incorporating pericentromeric and single-copy regional chromosome probes offer a powerful and

  16. Parent volatiles in comet 9P/Tempel 1: before and after impact.

    PubMed

    Mumma, Michael J; DiSanti, Michael A; Magee-Sauer, Karen; Bonev, Boncho P; Villanueva, Geronimo L; Kawakita, Hideyo; Dello Russo, Neil; Gibb, Erika L; Blake, Geoffrey A; Lyke, James E; Campbell, Randall D; Aycock, Joel; Conrad, Al; Hill, Grant M

    2005-10-14

    We quantified eight parent volatiles (H2O, C2H6, HCN, CO, CH3OH, H2CO, C2H2, and CH4) in the Jupiter-family comet Tempel 1 using high-dispersion infrared spectroscopy in the wavelength range 2.8 to 5.0 micrometers. The abundance ratio for ethane was significantly higher after impact, whereas those for methanol and hydrogen cyanide were unchanged. The abundance ratios in the ejecta are similar to those for most Oort cloud comets, but methanol and acetylene are lower in Tempel 1 by a factor of about 2. These results suggest that the volatile ices in Tempel 1 and in most Oort cloud comets originated in a common region of the protoplanetary disk.

  17. Parent volatiles in comet 9P/Tempel 1: before and after impact

    NASA Technical Reports Server (NTRS)

    Mumma, Michael J.; DiSanti, Michael A.; Magee-Sauer, Karen; Bonev, Boncho P.; Villanueva, Geronimo L.; Kawakita, Hideyo; Dello Russo, Neil; Gibb, Erika L.; Blake, Geoffrey A.; Lyke, James E.; Campbell, Randall D.; Aycock, Joel; Conrad, Al; Hill, Grant M.

    2005-01-01

    We quantified eight parent volatiles (H2O, C2H6, HCN, CO, CH3OH, H2CO, C2H2, and CH4) in the Jupiter-family comet Tempel 1 using high-dispersion infrared spectroscopy in the wavelength range 2.8 to 5.0 micrometers. The abundance ratio for ethane was significantly higher after impact, whereas those for methanol and hydrogen cyanide were unchanged. The abundance ratios in the ejecta are similar to those for most Oort cloud comets, but methanol and acetylene are lower in Tempel 1 by a factor of about 2. These results suggest that the volatile ices in Tempel 1 and in most Oort cloud comets originated in a common region of the protoplanetary disk.

  18. Parent volatiles in comet 9P/Tempel 1: before and after impact.

    PubMed

    Mumma, Michael J; DiSanti, Michael A; Magee-Sauer, Karen; Bonev, Boncho P; Villanueva, Geronimo L; Kawakita, Hideyo; Dello Russo, Neil; Gibb, Erika L; Blake, Geoffrey A; Lyke, James E; Campbell, Randall D; Aycock, Joel; Conrad, Al; Hill, Grant M

    2005-10-14

    We quantified eight parent volatiles (H2O, C2H6, HCN, CO, CH3OH, H2CO, C2H2, and CH4) in the Jupiter-family comet Tempel 1 using high-dispersion infrared spectroscopy in the wavelength range 2.8 to 5.0 micrometers. The abundance ratio for ethane was significantly higher after impact, whereas those for methanol and hydrogen cyanide were unchanged. The abundance ratios in the ejecta are similar to those for most Oort cloud comets, but methanol and acetylene are lower in Tempel 1 by a factor of about 2. These results suggest that the volatile ices in Tempel 1 and in most Oort cloud comets originated in a common region of the protoplanetary disk. PMID:16166477

  19. The Nucleus of Comet 9P-Tempel 1: Shape and Geology from Two Flybys

    NASA Technical Reports Server (NTRS)

    Thomas, P.; A'Hearn, M.; Belton, M. J. S.; Brownlee, D.; Carcich, B.; Hermalyn, B.; Klaasen, K.; Sackett, S.; Schultz, P. H.; Veverka, J.; Bhaskaran, S.; Bodewits, D.; Chesley, S.; Clark, B.; Farnham, T.; Groussin, O.; Harris, J.; Kissel, J.; Li, J.-Y; Meech, K.; Melosh, J.; Quick, A.; Richardson, J.; Sunshine, J.; Wellnitz, D.

    2012-01-01

    The nucleus of comet Tempel 1 has been investigated at close range during two spacecraft missions separated by one comet orbit of the Sun, 5 1/2 years. The combined imaging covers 70% of the surface of this object which has a mean radius of 2.83 +/- 0.1 km. The surface can be divided into two terrain types: rough, pitted terrain and smoother regions of varying local topography. The rough surface has round depressions from resolution limits (10 m/pixel) up to 1 km across, spanning forms from crisp steep-walled pits, to subtle albedo rings, to topographic rings, with all ranges of morphologic gradation. Three gravitationally low regions of the comet have smoother terrain, parts of which appear to be deposits from minimally modified flows, with other parts likely to be heavily eroded portions of multiple layer piles. Changes observed between the two missions are primarily due to backwasting of scarps bounding one of these probable flow deposits. This style of erosion is also suggested by remnant mesa forms in other areas of smoother terrain. The two distinct terrains suggest either an evolutionary change in processes, topographically- controlled processes, or a continuing interaction of erosion and deposition.

  20. Deep Impact 9P/TEMPEL Cruise - Raw its Nav Images V1.1

    NASA Astrophysics Data System (ADS)

    Carcich, B.; Shaw, A. S.; Desnoyer, M.; McLaughlin, S. A.; Mastrodemos, N.; Klaasen, K. P.

    2010-01-01

    This data set contains raw calibration and test images acquired by the Deep Impact Impactor Targeting Sensor Visible CCD during the cruise phase of the mission. These observations were used for optical and autonomous navigation (NAV) of the impactor spacecraft. These data were collected from 7 April to 30 April 2005. The comet was not imaged during cruise. In this version 1.1 of the data set, the values for the INTEGRATION_DURATION keyword in the PDS data labels were corrected. This revised data set supersedes version 1.0.

  1. Ground Optical Navigation for the Stardust-Next Mission to Comet 9P/TEMPEL1

    NASA Technical Reports Server (NTRS)

    Gillam, Stephen D.; Riedel, J. Ed.; Owen, William M., Jr.; Wang, Tseng-Chan Mike; Werner, Robert A.; Bhaskaran, Shyam; Chesley, Steven R.; Thompson, Paul F.; Wolf, Aron A.

    2011-01-01

    Ground-based optical navigation (OpNav) using pictures taken by the Naviga-tion camera on the Stardust spacecraft provided the target-relative information needed to design maneuvers during its approach to comet Tempel 1. Hardware problems, limited downlink bandwidth, and changes in the flight profile affected the OpNav picture schedule, sometimes in near-real time. The Stardust naviga-tion camera and attitude control presented challenges. Picture-processing techniques were developed during approach that included background estimation, co-addition, and co-registration. These techniques, along with adaptive picture scheduling, successfully addressed the challenges.

  2. Localisation of the gene for cylindromatosis (turban tumor syndrome) to chromosome 9p12-13

    SciTech Connect

    Wooster, R.; Mangion, J.; Quirk, Y.

    1994-09-01

    Cylindromatosis (multiple cylindromas, tomato syndrome syndrome, turban tumor syndrome) is a rare autosomal dominant disease characterized by the development of multiple, slow growing neoplasms of the skin appendages. The tumors, known as dermal cylindromas, exhibit histological features of eccrine or apocrine sweat glands and occur most commonly in the scalp area. Genetic linkage analysis of two families yielded a maximum two point LOD score of 3.2 at D9S169. Critical recombinants place the gene between D9S161 and IFN, a distance of approximately 9 cM. This region of chromosome 9 harbors a gene that encodes a 16 kD protein which is an inhibitor of cyclin dependent kinase 4 (CDK-4) and which is somatically mutated in many classes of cancer. However, the observation of recombinants between the disease and a polymorphic microsatellite repeat CT29 close to this gene, suggests that the CDK-4 inhibitor gene is unlikely to be responsible for cylindromatosis.

  3. A Girl with Pervasive Developmental Disorder and Complex Chromosome Rearrangement Involving 8p and 10p

    ERIC Educational Resources Information Center

    Zwaigenbaum, L; Sonnenberg, L. K.; Heshka, T.; Eastwood, S.; Xu, J.

    2005-01-01

    We report a 4-year-old girl with a "de novo", apparently balanced complex chromosome rearrangement. She initially presented for assessment of velopharyngeal insufficiency due to hypernasal speech. She has distinctive facial features (long face, broad nasal bridge, and protuberant ears with simplified helices), bifid uvula, strabismus, and joint…

  4. Materials Data on Bi8(P2O9)3 (SG:1) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-07-09

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  5. Candidate Luminal B Breast Cancer Genes Identified by Genome, Gene Expression and DNA Methylation Profiling

    PubMed Central

    Addou-Klouche, Lynda; Finetti, Pascal; Saade, Marie-Rose; Manai, Marwa; Carbuccia, Nadine; Bekhouche, Ismahane; Letessier, Anne; Charafe-Jauffret, Emmanuelle; Jacquemier, Jocelyne; Spicuglia, Salvatore; de The, Hugues; Viens, Patrice; Bertucci, François; Birnbaum, Daniel; Chaffanet, Max

    2014-01-01

    Breast cancers (BCs) of the luminal B subtype are estrogen receptor-positive (ER+), highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this subtype we compared DNA copy number aberrations (CNAs), DNA promoter methylation, gene expression profiles, and somatic mutations in nine selected genes, in 32 luminal B tumors with those observed in 156 BCs of the other molecular subtypes. Frequent CNAs included 8p11-p12 and 11q13.1-q13.2 amplifications, 7q11.22-q34, 8q21.12-q24.23, 12p12.3-p13.1, 12q13.11-q24.11, 14q21.1-q23.1, 17q11.1-q25.1, 20q11.23-q13.33 gains and 6q14.1-q24.2, 9p21.3-p24,3, 9q21.2, 18p11.31-p11.32 losses. A total of 237 and 101 luminal B-specific candidate oncogenes and tumor suppressor genes (TSGs) presented a deregulated expression in relation with their CNAs, including 11 genes previously reported associated with endocrine resistance. Interestingly, 88% of the potential TSGs are located within chromosome arm 6q, and seven candidate oncogenes are potential therapeutic targets. A total of 100 candidate oncogenes were validated in a public series of 5,765 BCs and the overexpression of 67 of these was associated with poor survival in luminal tumors. Twenty-four genes presented a deregulated expression in relation with a high DNA methylation level. FOXO3, PIK3CA and TP53 were the most frequent mutated genes among the nine tested. In a meta-analysis of next-generation sequencing data in 875 BCs, KCNB2 mutations were associated with luminal B cases while candidate TSGs MDN1 (6q15) and UTRN (6q24), were mutated in this subtype. In conclusion, we have reported luminal B candidate genes that may play a role in the development and/or hormone resistance of this aggressive subtype. PMID:24416132

  6. Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling.

    PubMed

    Cornen, Stéphanie; Guille, Arnaud; Adélaïde, José; Addou-Klouche, Lynda; Finetti, Pascal; Saade, Marie-Rose; Manai, Marwa; Carbuccia, Nadine; Bekhouche, Ismahane; Letessier, Anne; Raynaud, Stéphane; Charafe-Jauffret, Emmanuelle; Jacquemier, Jocelyne; Spicuglia, Salvatore; de The, Hugues; Viens, Patrice; Bertucci, François; Birnbaum, Daniel; Chaffanet, Max

    2014-01-01

    Breast cancers (BCs) of the luminal B subtype are estrogen receptor-positive (ER+), highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this subtype we compared DNA copy number aberrations (CNAs), DNA promoter methylation, gene expression profiles, and somatic mutations in nine selected genes, in 32 luminal B tumors with those observed in 156 BCs of the other molecular subtypes. Frequent CNAs included 8p11-p12 and 11q13.1-q13.2 amplifications, 7q11.22-q34, 8q21.12-q24.23, 12p12.3-p13.1, 12q13.11-q24.11, 14q21.1-q23.1, 17q11.1-q25.1, 20q11.23-q13.33 gains and 6q14.1-q24.2, 9p21.3-p24,3, 9q21.2, 18p11.31-p11.32 losses. A total of 237 and 101 luminal B-specific candidate oncogenes and tumor suppressor genes (TSGs) presented a deregulated expression in relation with their CNAs, including 11 genes previously reported associated with endocrine resistance. Interestingly, 88% of the potential TSGs are located within chromosome arm 6q, and seven candidate oncogenes are potential therapeutic targets. A total of 100 candidate oncogenes were validated in a public series of 5,765 BCs and the overexpression of 67 of these was associated with poor survival in luminal tumors. Twenty-four genes presented a deregulated expression in relation with a high DNA methylation level. FOXO3, PIK3CA and TP53 were the most frequent mutated genes among the nine tested. In a meta-analysis of next-generation sequencing data in 875 BCs, KCNB2 mutations were associated with luminal B cases while candidate TSGs MDN1 (6q15) and UTRN (6q24), were mutated in this subtype. In conclusion, we have reported luminal B candidate genes that may play a role in the development and/or hormone resistance of this aggressive subtype.

  7. Comprehensive high-resolution genomic profiling and cytogenetics of two pediatric and one adult medulloblastoma.

    PubMed

    Holland, Heidrun; Xu, Li-Xin; Ahnert, Peter; Kirsten, Holger; Koschny, Ronald; Bauer, Manfred; Schober, Ralf; Meixensberger, Jürgen; Krupp, Wolfgang

    2013-09-01

    Medulloblastoma (WHO grade IV) is a rare, malignant, invasive, embryonal tumor which mainly occurs in children and represents less than 1% of all adult brain tumors. Systematic comprehensive genetic analyses on medulloblastomas are rare but necessary to provide more detailed information. Therefore, we performed comprehensive cytogenetic analyses (blood and tissue) of two pediatric and one adult medulloblastoma, using trypsin-Giemsa staining, spectral karyotyping (tissues only), SNP-arrays, and gene expression analyses. We confirmed frequently detected chromosomal aberrations in medulloblastoma, such as +7q, -8p/q, -9q, -11q, -12q, and +17q and identified novel genetic events. Applying SNP-array, we identified constitutional de novo losses 5q21.1, 15q11.2, 17q21.31, 19p12 (pediatric medulloblastoma), 9p21.1, 19p12, 19q13.3, 21q11.2 (adult medulloblastoma) and gains 16p11.1-16p11.2, 18p11.32, Yq11.223-Yq11.23 (pediatric medulloblastoma), Xp22.31 (adult medulloblastoma) possibly representing inherited causal events for medulloblastoma formation. We show evidence for somatic segmental uniparental disomy in regions 1p36, 6q16.3, 6q24.1, 14q21.2, 17p13.3, and 17q22 not previously described for primary medulloblastoma. Gene expression analysis supported classification of the adult medulloblastoma to the WNT-subgroup and classification of pediatric medulloblastomas to group 3 tumors. Analyses of tumors and matched normal tissues (blood) with a combination of complementary techniques will help to further elucidate potentially causal genetic events for medulloblastomas.

  8. Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

    PubMed

    Dunning, Alison M; Michailidou, Kyriaki; Kuchenbaecker, Karoline B; Thompson, Deborah; French, Juliet D; Beesley, Jonathan; Healey, Catherine S; Kar, Siddhartha; Pooley, Karen A; Lopez-Knowles, Elena; Dicks, Ed; Barrowdale, Daniel; Sinnott-Armstrong, Nicholas A; Sallari, Richard C; Hillman, Kristine M; Kaufmann, Susanne; Sivakumaran, Haran; Moradi Marjaneh, Mahdi; Lee, Jason S; Hills, Margaret; Jarosz, Monika; Drury, Suzie; Canisius, Sander; Bolla, Manjeet K; Dennis, Joe; Wang, Qin; Hopper, John L; Southey, Melissa C; Broeks, Annegien; Schmidt, Marjanka K; Lophatananon, Artitaya; Muir, Kenneth; Beckmann, Matthias W; Fasching, Peter A; Dos-Santos-Silva, Isabel; Peto, Julian; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; González-Neira, Anna; Perez, Jose I A; Anton-Culver, Hoda; Eunjung, Lee; Arndt, Volker; Brenner, Hermann; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Aittomäki, Kristiina; Blomqvist, Carl; Ito, Hidemi; Matsuo, Keitaro; Bogdanova, Natasha; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Kosma, Veli-Matti; Mannermaa, Arto; Tseng, Chiu-Chen; Wu, Anna H; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Rudolph, Anja; Peterlongo, Paolo; Radice, Paolo; Olson, Janet E; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Henderson, Brian E; Goldberg, Mark S; Teo, Soo H; Yip, Cheng Har; Nord, Silje; Borresen-Dale, Anne-Lise; Kristensen, Vessela; Long, Jirong; Zheng, Wei; Pylkäs, Katri; Winqvist, Robert; Andrulis, Irene L; Knight, Julia A; Devilee, Peter; Seynaeve, Caroline; Figueroa, Jonine; Sherman, Mark E; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; van den Ouweland, Ans M W; Humphreys, Keith; Gao, Yu-Tang; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S; Blot, William; Cai, Qiuyin; Ghoussaini, Maya; Perkins, Barbara J; Shah, Mitul; Choi, Ji-Yeob; Kang, Daehee; Lee, Soo Chin; Hartman, Mikael; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Brennan, Paul; Sangrajrang, Suleeporn; Ambrosone, Christine B; Toland, Amanda E; Shen, Chen-Yang; Wu, Pei-Ei; Orr, Nick; Swerdlow, Anthony; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Kapuscinski, Miroslav; John, Esther M; Terry, Mary Beth; Daly, Mary B; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ejlertsen, Bent; Hansen, Thomas V O; Osorio, Ana; Benitez, Javier; Rando, Rachel; Weitzel, Jeffrey N; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Papi, Laura; Ottini, Laura; Konstantopoulou, Irene; Apostolou, Paraskevi; Garber, Judy; Rashid, Muhammad Usman; Frost, Debra; Izatt, Louise; Ellis, Steve; Godwin, Andrew K; Arnold, Norbert; Niederacher, Dieter; Rhiem, Kerstin; Bogdanova-Markov, Nadja; Sagne, Charlotte; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Sinilnikova, Olga M; Mazoyer, Sylvie; Isaacs, Claudine; Claes, Kathleen B M; De Leeneer, Kim; de la Hoya, Miguel; Caldes, Trinidad; Nevanlinna, Heli; Khan, Sofia; Mensenkamp, Arjen R; Hooning, Maartje J; Rookus, Matti A; Kwong, Ava; Olah, Edith; Diez, Orland; Brunet, Joan; Pujana, Miquel Angel; Gronwald, Jacek; Huzarski, Tomasz; Barkardottir, Rosa B; Laframboise, Rachel; Soucy, Penny; Montagna, Marco; Agata, Simona; Teixeira, Manuel R; Park, Sue Kyung; Lindor, Noralane; Couch, Fergus J; Tischkowitz, Marc; Foretova, Lenka; Vijai, Joseph; Offit, Kenneth; Singer, Christian F; Rappaport, Christine; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Imyanitov, Evgeny N; Hulick, Peter J; Phillips, Kelly-Anne; Piedmonte, Marion; Mulligan, Anna Marie; Glendon, Gord; Bojesen, Anders; Thomassen, Mads; Caligo, Maria A; Yoon, Sook-Yee; Friedman, Eitan; Laitman, Yael; Borg, Ake; von Wachenfeldt, Anna; Ehrencrona, Hans; Rantala, Johanna; Olopade, Olufunmilayo I; Ganz, Patricia A; Nussbaum, Robert L; Gayther, Simon A; Nathanson, Katherine L; Domchek, Susan M; Arun, Banu K; Mitchell, Gillian; Karlan, Beth Y; Lester, Jenny; Maskarinec, Gertraud; Woolcott, Christy; Scott, Christopher; Stone, Jennifer; Apicella, Carmel; Tamimi, Rulla; Luben, Robert; Khaw, Kay-Tee; Helland, Åslaug; Haakensen, Vilde; Dowsett, Mitch; Pharoah, Paul D P; Simard, Jacques; Hall, Per; García-Closas, Montserrat; Vachon, Celine; Chenevix-Trench, Georgia; Antoniou, Antonis C; Easton, Douglas F; Edwards, Stacey L

    2016-04-01

    We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.

  9. 31 CFR 30.6 - Q-6: How does a TARP recipient comply with the requirement under § 30.4 (Q-4) of this part that...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... manipulation of reported earnings of the TARP recipient to enhance the compensation of any of the TARP... manipulation of reported earnings of the TARP recipient to enhance the compensation of any of the TARP... plans that could encourage the manipulation of reported earnings of the TARP recipient to enhance...

  10. Assignment of the gene encoding the 5-HT{sub 1E} serotonin receptor (S31) (locus HTR1E) to human chromosome 6q14-q15

    SciTech Connect

    Levy, F.O.; Tasken, K.; Solberg, R.

    1994-08-01

    The human gene for the 5-HT{sub 1E} serotonin receptor was recently cloned, but no chromosomal assignment has yet been given to this gene (locus HTR1E). In this work, we demonstrate by two independent polymerase chain reactions on a panel of human-hamster somatic cell hybrid genomic DNA that the 5-HT{sub 1E} serotonin receptor gene is localized on human chromosome 6. Furthermore, by means of in situ hybridization to human metaphase chromosomes, using the cloned 5-HT{sub 1E} receptor gene (phage clone {lambda}-S31) as a probe, we demonstrate that this gene is localized to the q14-q15 region on chromosome 6. Screening of genomic DNA from 15 unrelated Caucasian individuals, using as a probe the open reading frame of the cloned 5-HT{sub 1E} receptor gene, did not reveal any restriction fragment length polymorphisms with the enzymes BamHI, BanII, BglII, EcoRI, HincII, HindIII, HinfI, MspI, PstI, and PvuII. Since the 5-HT{sub 1E} receptor is found mainly in the cerebral cortex and abnormal function of the serotonergic system has been implicated in a variety of neurologic and psychiatric diseases, the precise chromosomal assignment of the 5-HT{sub 1E} receptor gene is the crucial first step toward the evaluation of this locus as a candidate for mutations in such syndromes. 28 refs., 2 figs., 2 tabs.

  11. Transmission-ratio distortion and allele sharing in affected sib pairs: a new linkage statistic with reduced bias, with application to chromosome 6q25.3.

    PubMed

    Lemire, Mathieu; Roslin, Nicole M; Laprise, Catherine; Hudson, Thomas J; Morgan, Kenneth

    2004-10-01

    We studied the effect of transmission-ratio distortion (TRD) on tests of linkage based on allele sharing in affected sib pairs. We developed and implemented a discrete-trait allele-sharing test statistic, Sad, analogous to the Spairs test statistic of Whittemore and Halpern, that evaluates an excess sharing of alleles at autosomal loci in pairs of affected siblings, as well as a lack of sharing in phenotypically discordant relative pairs, where available. Under the null hypothesis of no linkage, nuclear families with at least two affected siblings and one unaffected sibling have a contribution to Sad that is unbiased, with respect to the effects of TRD independent of the disease under study. If more distantly related unaffected individuals are studied, the bias of Sad is generally reduced compared with that of Spairs, but not completely. Moreover, Sad has higher power, in some circumstances, because of the availability of unaffected relatives, who are ignored in affected-only analyses. We discuss situations in which it may be an efficient use of resources to genotype unaffected relatives, which would give insights for promising study designs. The method is applied to a sample of pedigrees ascertained for asthma in a chromosomal region in which TRD has been reported. Results are consistent with the presence of transmission distortion in that region. PMID:15322985

  12. Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

    PubMed

    Dunning, Alison M; Michailidou, Kyriaki; Kuchenbaecker, Karoline B; Thompson, Deborah; French, Juliet D; Beesley, Jonathan; Healey, Catherine S; Kar, Siddhartha; Pooley, Karen A; Lopez-Knowles, Elena; Dicks, Ed; Barrowdale, Daniel; Sinnott-Armstrong, Nicholas A; Sallari, Richard C; Hillman, Kristine M; Kaufmann, Susanne; Sivakumaran, Haran; Moradi Marjaneh, Mahdi; Lee, Jason S; Hills, Margaret; Jarosz, Monika; Drury, Suzie; Canisius, Sander; Bolla, Manjeet K; Dennis, Joe; Wang, Qin; Hopper, John L; Southey, Melissa C; Broeks, Annegien; Schmidt, Marjanka K; Lophatananon, Artitaya; Muir, Kenneth; Beckmann, Matthias W; Fasching, Peter A; Dos-Santos-Silva, Isabel; Peto, Julian; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; González-Neira, Anna; Perez, Jose I A; Anton-Culver, Hoda; Eunjung, Lee; Arndt, Volker; Brenner, Hermann; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Aittomäki, Kristiina; Blomqvist, Carl; Ito, Hidemi; Matsuo, Keitaro; Bogdanova, Natasha; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Kosma, Veli-Matti; Mannermaa, Arto; Tseng, Chiu-Chen; Wu, Anna H; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Rudolph, Anja; Peterlongo, Paolo; Radice, Paolo; Olson, Janet E; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Henderson, Brian E; Goldberg, Mark S; Teo, Soo H; Yip, Cheng Har; Nord, Silje; Borresen-Dale, Anne-Lise; Kristensen, Vessela; Long, Jirong; Zheng, Wei; Pylkäs, Katri; Winqvist, Robert; Andrulis, Irene L; Knight, Julia A; Devilee, Peter; Seynaeve, Caroline; Figueroa, Jonine; Sherman, Mark E; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; van den Ouweland, Ans M W; Humphreys, Keith; Gao, Yu-Tang; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S; Blot, William; Cai, Qiuyin; Ghoussaini, Maya; Perkins, Barbara J; Shah, Mitul; Choi, Ji-Yeob; Kang, Daehee; Lee, Soo Chin; Hartman, Mikael; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Brennan, Paul; Sangrajrang, Suleeporn; Ambrosone, Christine B; Toland, Amanda E; Shen, Chen-Yang; Wu, Pei-Ei; Orr, Nick; Swerdlow, Anthony; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Kapuscinski, Miroslav; John, Esther M; Terry, Mary Beth; Daly, Mary B; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ejlertsen, Bent; Hansen, Thomas V O; Osorio, Ana; Benitez, Javier; Rando, Rachel; Weitzel, Jeffrey N; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Papi, Laura; Ottini, Laura; Konstantopoulou, Irene; Apostolou, Paraskevi; Garber, Judy; Rashid, Muhammad Usman; Frost, Debra; Izatt, Louise; Ellis, Steve; Godwin, Andrew K; Arnold, Norbert; Niederacher, Dieter; Rhiem, Kerstin; Bogdanova-Markov, Nadja; Sagne, Charlotte; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Sinilnikova, Olga M; Mazoyer, Sylvie; Isaacs, Claudine; Claes, Kathleen B M; De Leeneer, Kim; de la Hoya, Miguel; Caldes, Trinidad; Nevanlinna, Heli; Khan, Sofia; Mensenkamp, Arjen R; Hooning, Maartje J; Rookus, Matti A; Kwong, Ava; Olah, Edith; Diez, Orland; Brunet, Joan; Pujana, Miquel Angel; Gronwald, Jacek; Huzarski, Tomasz; Barkardottir, Rosa B; Laframboise, Rachel; Soucy, Penny; Montagna, Marco; Agata, Simona; Teixeira, Manuel R; Park, Sue Kyung; Lindor, Noralane; Couch, Fergus J; Tischkowitz, Marc; Foretova, Lenka; Vijai, Joseph; Offit, Kenneth; Singer, Christian F; Rappaport, Christine; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Imyanitov, Evgeny N; Hulick, Peter J; Phillips, Kelly-Anne; Piedmonte, Marion; Mulligan, Anna Marie; Glendon, Gord; Bojesen, Anders; Thomassen, Mads; Caligo, Maria A; Yoon, Sook-Yee; Friedman, Eitan; Laitman, Yael; Borg, Ake; von Wachenfeldt, Anna; Ehrencrona, Hans; Rantala, Johanna; Olopade, Olufunmilayo I; Ganz, Patricia A; Nussbaum, Robert L; Gayther, Simon A; Nathanson, Katherine L; Domchek, Susan M; Arun, Banu K; Mitchell, Gillian; Karlan, Beth Y; Lester, Jenny; Maskarinec, Gertraud; Woolcott, Christy; Scott, Christopher; Stone, Jennifer; Apicella, Carmel; Tamimi, Rulla; Luben, Robert; Khaw, Kay-Tee; Helland, Åslaug; Haakensen, Vilde; Dowsett, Mitch; Pharoah, Paul D P; Simard, Jacques; Hall, Per; García-Closas, Montserrat; Vachon, Celine; Chenevix-Trench, Georgia; Antoniou, Antonis C; Easton, Douglas F; Edwards, Stacey L

    2016-04-01

    We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression. PMID:26928228

  13. Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

    PubMed Central

    Dunning, Alison M; Michailidou, Kyriaki; Kuchenbaecker, Karoline B; Thompson, Deborah; French, Juliet D; Beesley, Jonathan; Healey, Catherine S; Kar, Siddhartha; Pooley, Karen A; Lopez-Knowles, Elena; Dicks, Ed; Barrowdale, Daniel; Sinnott-Armstrong, Nicholas A; Sallari, Richard C; Hillman, Kristine M; Kaufmann, Susanne; Sivakumaran, Haran; Marjaneh, Mahdi Moradi; Lee, Jason S; Hills, Margaret; Jarosz, Monika; Drury, Suzie; Canisius, Sander; Bolla, Manjeet K; Dennis, Joe; Wang, Qin; Hopper, John L; Southey, Melissa C; Broeks, Annegien; Schmidt, Marjanka K; Lophatananon, Artitaya; Muir, Kenneth; Beckmann, Matthias W; Fasching, Peter A; dos-Santos-Silva, Isabel; Peto, Julian; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; González-Neira, Anna; Perez, Jose I A; Anton-Culver, Hoda; Eunjung, Lee; Arndt, Volker; Brenner, Hermann; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Aittomäki, Kristiina; Blomqvist, Carl; Ito, Hidemi; Matsuo, Keitaro; Bogdanova, Natasha; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Kosma, Veli-Matti; Mannermaa, Arto; Tseng, Chiu-chen; Wu, Anna H; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Rudolph, Anja; Peterlongo, Paolo; Radice, Paolo; Olson, Janet E; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Henderson, Brian E; Goldberg, Mark S; Teo, Soo H; Yip, Cheng Har; Nord, Silje; Borresen-Dale, Anne-Lise; Kristensen, Vessela; Long, Jirong; Zheng, Wei; Pylkäs, Katri; Winqvist, Robert; Andrulis, Irene L; Knight, Julia A; Devilee, Peter; Seynaeve, Caroline; Figueroa, Jonine; Sherman, Mark E; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; van den Ouweland, Ans M W; Humphreys, Keith; Gao, Yu-Tang; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S; Blot, William; Cai, Qiuyin; Ghoussaini, Maya; Perkins, Barbara J; Shah, Mitul; Choi, Ji-Yeob; Kang, Daehee; Lee, Soo Chin; Hartman, Mikael; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Brennan, Paul; Sangrajrang, Suleeporn; Ambrosone, Christine B; Toland, Amanda E; Shen, Chen-Yang; Wu, Pei-Ei; Orr, Nick; Swerdlow, Anthony; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Kapuscinski, Miroslav; John, Esther M; Terry, Mary Beth; Daly, Mary B; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ejlertsen, Bent; Hansen, Thomas V O; Osorio, Ana; Benitez, Javier; Rando, Rachel; Weitzel, Jeffrey N; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Papi, Laura; Ottini, Laura; Konstantopoulou, Irene; Apostolou, Paraskevi; Garber, Judy; Rashid, Muhammad Usman; Frost, Debra; Izatt, Louise; Ellis, Steve; Godwin, Andrew K; Arnold, Norbert; Niederacher, Dieter; Rhiem, Kerstin; Bogdanova-Markov, Nadja; Sagne, Charlotte; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Sinilnikova, Olga M; Mazoyer, Sylvie; Isaacs, Claudine; Claes, Kathleen B M; De Leeneer, Kim; de la Hoya, Miguel; Caldes, Trinidad; Nevanlinna, Heli; Khan, Sofia; Mensenkamp, Arjen R; Hooning, Maartje J; Rookus, Matti A; Kwong, Ava; Olah, Edith; Diez, Orland; Brunet, Joan; Pujana, Miquel Angel; Gronwald, Jacek; Huzarski, Tomasz; Barkardottir, Rosa B; Laframboise, Rachel; Soucy, Penny; Montagna, Marco; Agata, Simona; Teixeira, Manuel R; Park, Sue Kyung; Lindor, Noralane; Couch, Fergus J; Tischkowitz, Marc; Foretova, Lenka; Vijai, Joseph; Offit, Kenneth; Singer, Christian F; Rappaport, Christine; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Imyanitov, Evgeny N; Hulick, Peter J; Phillips, Kelly-Anne; Piedmonte, Marion; Mulligan, Anna Marie; Glendon, Gord; Bojesen, Anders; Thomassen, Mads; Caligo, Maria A; Yoon, Sook-Yee; Friedman, Eitan; Laitman, Yael; Borg, Ake; von Wachenfeldt, Anna; Ehrencrona, Hans; Rantala, Johanna; Olopade, Olufunmilayo I; Ganz, Patricia A; Nussbaum, Robert L; Gayther, Simon A; Nathanson, Katherine L; Domchek, Susan M; Arun, Banu K; Mitchell, Gillian; Karlan, Beth Y; Lester, Jenny; Maskarinec, Gertraud; Woolcott, Christy; Scott, Christopher; Stone, Jennifer; Apicella, Carmel; Tamimi, Rulla; Luben, Robert; Khaw, Kay-Tee; Helland, Åslaug; Haakensen, Vilde; Dowsett, Mitch; Pharoah, Paul D P; Simard, Jacques; Hall, Per; García-Closas, Montserrat; Vachon, Celine; Chenevix-Trench, Georgia; Antoniou, Antonis C; Easton, Douglas F; Edwards, Stacey L

    2016-01-01

    We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER+ or ER−) and human ERBB2 (HER2+ or HER2−) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER− tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression. PMID:26928228

  14. 31 CFR 30.6 - Q-6: How does a TARP recipient comply with the requirement under § 30.4 (Q-4) of this part that...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... manipulation of reported earnings of the TARP recipient to enhance the compensation of any of the TARP... manipulation of reported earnings of the TARP recipient to enhance the compensation of any of the TARP... plans that could encourage the manipulation of reported earnings of the TARP recipient to enhance...

  15. Chromosomal alterations in the clonal evolution to the metastatic stage of squamous cell carcinomas of the lung.

    PubMed

    Petersen, S; Aninat-Meyer, M; Schlüns, K; Gellert, K; Dietel, M; Petersen, I

    2000-01-01

    Comparative genomic hybridization (CGH) was applied to squamous cell carcinomas (SCC) of the lung to define chromosomal imbalances that are associated with the metastatic phenotype. In total, 64 lung SCC from 50 patients were investigated, 25 each with or without evidence of metastasis formation. The chromosomal imbalances summarized by a CGH histogram of the 50 cases revealed deletions most frequently on chromosomes 1p21-p31, 2q34-q36, 3p, 4p, 4q, 5q, 6q14-q24, 8p, 9p, 10q, 11p12-p14, 13q13-qter, 18q12-qter and 21q21. DNA over-representations were most pronounced for chromosomes 1q11-q25, 1q32-q41, 3q, 5p, 8q22-qter, 11q13, 12p, 17q21-q22, 17q24-q25, 19, 20q and 22q. In ten cases, paired samples of primaries and at least one metastasis were analysed. The comparison revealed a considerable chromosomal instability and genetic heterogeneity; however, the CGH pattern indicated a clonal relationship in each case. The difference in histograms from the metastatic and non-metastatic tumour groups was most useful in pinpointing chromosomal imbalances associated with the metastatic phenotype, indicating that the deletions at 3p12-p14, 3p21, 4p15-p16, 6q24-qter, 8p22-p23, 10q21-qter and 21q22, as well as the over-representations at 1q21-q25, 8q, 9q34, 14q12 and 15q12-q15, occurred significantly more often in the metastatic tumour group. The comparison of the paired samples confirmed these findings in individual cases and suggested distinct genetic changes, in particular the extension of small interstitial deletions, during tumour progression. Importantly, metastasis-associated lesions were frequently detectable in the primary tumour providing a method of identifying patients at risk for tumour dissemination. Individual profiles and histograms are accessible at our web site http://amba.charite.de/cgh.

  16. Materials Data on Li14Co9(P2O7)8 (SG:2) by Materials Project

    SciTech Connect

    Kristin Persson

    2014-10-02

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  17. 77 FR 51698 - Authorization To Seize Property Involved in Drug Offenses for Administrative Forfeiture (2012R-9P)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-27

    ....130(b). ATF investigations focusing on violent crime frequently involve complex criminal organizations.... 107-296). One of the primary missions of the ATF is to combat firearm-related violent crime. The nexus... effectiveness of ATF in the investigation of violent crimes involving firearms. Consequently, by this final...

  18. Materials Data on Na4Nb9(P2O13)3 (SG:18) by Materials Project

    DOE Data Explorer

    Kristin Persson

    2014-07-09

    Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

  19. A Novel 6.14 Mb Duplication of Chromosome 8p21 in a Patient with Autism and Self Mutilation

    ERIC Educational Resources Information Center

    Ozgen, Heval M.; Staal, Wouter G.; Barber, John C.; de Jonge, Maretha V.; Eleveld, Marc J.; Beemer, Frits A.; Hochstenbach, Ron; Poot, Martin

    2009-01-01

    Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with a strong genetic etiology. Cytogenetic abnormalities have been detected in 5-10% of the patients with autism. In this study, we present the clinical, cytogenetic and array-comparative genomic hybridization (array-CGH) evaluation of a 13-year-old male with severe…

  20. 75 FR 20007 - Proposal Review Panel for Chemistry; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-16

    ... Proposal Review Panel for Chemistry; Notice of Meeting In accordance with the Federal Advisory Committee... by NSF Division of Chemistry (1191). Dates & Times: May 9, 2010; 8 p.m.-9 p.m., May 10, 2010; 8 a.m.- 9 p.m., May 11, 2010; 8 a.m.-1 p.m. Place: Department of Chemistry, California Institute...

  1. Large-scale polymorphism near the ends of several human chromosomes analyzed by using fluorescence in situ hybridization (FISH)

    SciTech Connect

    Trask, B.J.; Friedman, C.; Giorgi, D.

    1994-09-01

    We have discovered a large DNA segment that is polymorphically present at the ends of several human chromosomes. The segment, f7501, was originally derived form a human chromosome 19-specific cosmid library. FISH was used to determine the cosmid`s chromosomal distribution on 44 unrelated humans and several closely related primates. The human subjects represent a diversity of reproductively isolated ethnic populations. FISH analysis revealed that sequences highly homologous to the cosmid`s insert are present on both homologs at 3q, 15q,. and 19p in almost all individuals (88, 85, and 87 of 88 homologs, respectively). Other chromosomes sites were labeled much more rarely in the sampled individuals. For example, 56 of the 88 analyzed chromosomes 11 were labeled (18+/+, 6-/-, and 20+/- individuals). In contrast, 2q was labeled on only 1/88 sampled chromosomes. The termini of 2q, 5q, 6p, 6q, 7p, 8p, 9p, 9q, 11p, 12q, 16p, 19q, and 20q and an interstitial site at 2q13-14 were labeled in at least one individual of the set. EcoR1-fragments derived from the cosmid showed the same hybridization pattern as the entire cosmid, indicating that at least 40 kbp is shared by these chromosome ends. Ethnic differences in the allele frequency of these polymorphic variants was observed. For example, signals were observed on 8/10 and 7/10 of the chromosomes 7p and 16q, respectively, derived form Biakan Pygmies, but these sites were infrequently labeled in non-Pygmy human populations (2/68, respectively). This region has undergone significant changes in chromosome location during human evolution. Strong signal was seen on chimpanzee and gorilla chromosome 3, which is homologous to human chromosome 4, a chromosome unlabeled in any of the humans we have analyzed.

  2. Frequent deletion of CDKN2A and recurrent coamplification of KIT, PDGFRA, and KDR in fibrosarcoma of bone--an array comparative genomic hybridization study.

    PubMed

    Niini, Tarja; López-Guerrero, José Antonio; Ninomiya, Shinsuke; Guled, Mohamed; Hattinger, Claudia Maria; Michelacci, Francesca; Böhling, Tom; Llombart-Bosch, Antonio; Picci, Piero; Serra, Massimo; Knuutila, Sakari

    2010-02-01

    Very little is known about the genetics of fibrosarcoma (FS) of bone. We applied array comparative genomic hybridization (CGH) to identify genes and genomic regions with potential role in the pathogenesis of this tumor. Seventeen patients with FS of bone were included in the study. Array CGH analysis was carried out in 13 fresh frozen tissue specimens from 11 of these patients (nine primary tumors and four local recurrences). DNA was extracted and hybridizations were performed on Agilent 244K CGH oligoarrays. The data were analyzed using Agilent DNA Analytics Software. The number of changes per patient ranged from 0 to 132 (average = 43). Losses were most commonly detected at 6q, 8p, 9p, 10, 13q, and 20p. CDKN2A was homozygously deleted in 7/11 patients. Hypermethylation of both p16(INK4a) and p14(ARF) was found in 1/14 patients. An internal deletion of STARD13 was found in a region with common losses at 13q13.1. The most frequent gains were seen at 1q, 4q, 5p, 8q, 12p, 15q, 16q, 17q, 20q, 22q, and Xp. Single recurrent high level amplification was detected at 4q12, including KIT, PDGFRA, and KDR. No activating mutations were found in any of them. Immunohistochemistry revealed expression of PDGFRA and/or PDGFRB in 12/17 samples. Moreover, small regions of gains pinpointed genes of particular interest, such as IGF1R at 15q26.3 and CHD1L at 1q21.1. In conclusion, our analysis provided novel findings that can be exploited when searching for markers for diagnosis and prognosis, and targets of therapy in this tumor type.

  3. Acinar cell carcinomas of the pancreas: a molecular analysis in a series of 57 cases.

    PubMed

    Bergmann, Frank; Aulmann, Sebastian; Sipos, Bence; Kloor, Matthias; von Heydebreck, Anja; Schweipert, Johannes; Harjung, Andreas; Mayer, Philipp; Hartwig, Werner; Moldenhauer, Gerhard; Capper, David; Dyckhoff, Gerhard; Freier, Kolja; Herpel, Esther; Schleider, Anja; Schirmacher, Peter; Mechtersheimer, Gunhild; Klöppel, Günter; Bläker, Hendrik

    2014-12-01

    Pancreatic acinar cell carcinomas (PACs) are rare but are distinct aggressive neoplasms that phenotypically differ from pancreatic ductal adenocarcinomas (PDACs) and pancreatic neuroendocrine neoplasms (PNENs). Despite recent work on the genetic changes of PACs, their molecular pathogenesis is still poorly understood. In this study, we focus on a comparative genomic hybridization analysis. Based on frequent chromosomal imbalances, the involvement of DCC and c-MYC in the pathogenesis of PACs is further investigated. Moreover, we examine markers harboring potential therapeutic relevance (K-RAS, BRAF, EGFR, MGMT, HSP90, L1CAM, Her2). PACs revealed a microsatellite stable, chromosomal unstable genotype, defined by recurrent chromosomal losses of 1p, 3p, 4q, 5q, 6q, 8p, 9p, 11q, 13q, 16q, and 18, as well as gains of 1q, 7, 8q, 12, 17q, and 20q. Subsets of PAC displayed reduction/loss of DCC (79 %) and c-MYC-amplification (17 %). Significant EGFR expression occurred in 42 %, HSP90 expression in 98 %, L1CAM expression in 72 %, and loss of MGMT in 26 %. Two cases carried a K-RAS mutation. Mutations of EGFR or BRAF were not detected. All cases were Her2/neu-negative. PACs display characteristic chromosomal imbalances which are distinctly different from those in pancreatic ductal adenocarcinomas and pancreatic neuroendocrine neoplasms. Our findings suggest that DCC and c-MYC alterations may play an important role in the pathogenesis of PACs. Furthermore, EGFR, MGMT, HSP90, and L1CAM may be useful as therapeutic markers and predictors of response to therapy in a subset of PACs. PMID:25298229

  4. Genomic imbalances in esophageal squamous cell carcinoma identified by molecular cytogenetic techniques

    PubMed Central

    2010-01-01

    This review summarizes the chromosomal changes detected by molecular cytogenetic approaches in esophageal squamous cell carcinoma (ESCC), the ninth most common malignancy in the world. Whole genome analyses of ESCC cell lines and tumors indicated that the most frequent genomic gains occurred at 1, 2q, 3q, 5p, 6p, 7, 8q, 9q, 11q, 12p, 14q, 15q, 16, 17, 18p, 19q, 20q, 22q and X, with focal amplifications at 1q32, 2p16-22, 3q25-28, 5p13-15.3, 7p12-22, 7q21-22, 8q23-24.2, 9q34, 10q21, 11p11.2, 11q13, 13q32, 14q13-14, 14q21, 14q31-32, 15q22-26, 17p11.2, 18p11.2-11.3 and 20p11.2. Recurrent losses involved 3p, 4, 5q, 6q, 7q, 8p, 9, 10p, 12p, 13, 14p, 15p, 18, 19p, 20, 22, Xp and Y. Gains at 5p and 7q, and deletions at 4p, 9p, and 11q were significant prognostic factors for patients with ESCC. Gains at 6p and 20p, and losses at 10p and 10q were the most significant imbalances, both in primary carcinoma and in metastases, which suggested that these regions may harbor oncogenes and tumor suppressor genes. Gains at 12p and losses at 3p may be associated with poor relapse-free survival. The clinical applicability of these changes as markers for the diagnosis and prognosis of ESCC, or as molecular targets for personalized therapy should be evaluated. PMID:21637470

  5. Tandem duplication/deletion in a maternally derived chromosome 9 supernumerary derivative resulting in 9p trisomy and partial 9q tetrasomy.

    PubMed

    Wyandt, H E; Lebo, R V; Fenerci, E Y; Sadhu, D N; Milunsky, J M

    2000-08-14

    A 19-week stillborn female fetus with bilateral cleft palate, horseshoe kidney, bicornuate uterus, low-set ears, and intrauterine growth retardation (IUGR) was found to have a supernumerary derivative chromosome 9 (der(9)) with an apparent tandem duplication in the long arm. PCR analysis at five polymorphic loci confirmed the duplication and showed an adjacent deletion, while whole chromosome FISH demonstrated only chromosome 9 to be involved. Further FISH studies of der(9) found the 9qh region to be duplicated, telomeric sequences to be intact, and subtelomeric sequences to be absent. Thus, the fetus was determined to be trisomic for 9pter-->9q12 and 9q34.3-->9qter, tetrasomic for 9q12--> 9q33, and disomic for 9q33-->9q34.3. These results are consistent with a tandem duplication of 9q12-->9q33 and adjacent distal deletion as designated by the karyotype, 47,XX,+der(9)dup(9) (q12q33)del(9) (q33q34.3).ish der(9)(WCP9+,D9Z1x2,STP9q-, AHT+) de novo. In addition to characterizing der(9), the combined PCR and cytogenetic studies refined the Genome Database Map of three loci (D9S907, D9S155, and D9S302) approximately to the distal 9q33 region. Without the attempt to refine breakpoints by PCR analysis, the deletion in distal 9q would not have been detected. Tandem direct duplication/deletion chromosomes have been reported in fewer cases than inverted duplication/deletions. We propose mechanisms of origin, consistent with those for recurrent inter stitial microdeletion and microduplication syndromes, shown to arise by recombination at homologous, flanking DNA sequences. PMID:10946358

  6. Assignment of ALDH3 to human chromosome 17p11.2 and ALDH5 to human chromosome 9p13

    SciTech Connect

    Hiraoka, L.R.; Hsu, L.; Hsieh, C.L.

    1995-01-01

    Aldehyde dehydrogenases are a group of enzymes responsible for catalyzing the conversion of numerous aldehydes to their corresponding acids. These enzymes play a major role in the detoxification of alcohol-derived acetaldehydes and in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. ALDH activities are found in most tissues, with the highest activity in the liver. Five human liver ALDH isozymes, ALDH1, 2, 3, 4, and {gamma}-butyrylaldehyde dehydrogenase ({gamma}-ABDH), have been purified and characterized, and one isozyme, ALDH5, has been identified by using a 29-nucleotide probe that is conserved in ALDH1 and ALDH2 for cDNA library screening. Several other isozymes from other tissues have also been reported. Genes for ALDH3 and ALDH5 have been previously localized to chromosomes 17 and 9, respectively. Here we report the regional assignment of these two loci. 17 refs., 1 fig.

  7. Carbonate in Comets: A Comparison of Comets 1P/Halley, 9P/Temple 1, and 81P/Wild 2

    NASA Technical Reports Server (NTRS)

    Flynn, G. J.; Leroux, H.; Tomeoka, K.; Tomioka, N.; Ohnishi, I.; Mikouchi, T.; Wirick, S.; Keller, L. P.; Jacobsen, C.; Sanford, S. A.

    2008-01-01

    Comets are generally believed to have formed in a cold region, trapping in the cometary ices the original low-temperature condensate grains of our Solar System. These grains would have been preserved in cold-storage, at a temperature below the freezing point of CO2, for the last 4.5+ billion years. Carbonates are common in hydrous meteorites and hydrous interplanetary dust particles (IDPs), where they are believed to have formed by parent-body aqueous processing. Since simple models of cometary evolution involve no aqueous processing, carbonates were generally presumed not to occur in comets. However, Toppani et al. [1] have performed experiments that indicate carbonate can be formed by non-equilibrium condensation in circumstellar environments where water is present as a vapor, not as a liquid. This suggests carbonate might have condensed in cold regions of the Solar Nebula, and might be present in comets.

  8. Measurement of Anomalously Strong Emission from the 1s-9p Transition in the Spectrum of H-like Phosphorus Following Charge Exchange with Molecular Hydrogen

    NASA Technical Reports Server (NTRS)

    Leutenegger, M. A.; Beiersdorfer, P.; Brown, G. V.; Kelley, R. L.; Porter, F. S.

    2010-01-01

    We have measured K-shell x-ray spectra of highly ionized argon and phosphorus following charge exchange with molecular hydrogen at low collision energy in an electron beam ion trap using an x-ray calorimeter array with approx.6 eV resolution. We find that the emission at the high-end of the Lyman series is greater by a factor of two for phosphorus than for argon, even though the measurement was performed concurrently and the atomic numbers are similar. This does not agree with current theoretical models and deviates from the trend observed in previous measurements.

  9. A case of partial (9p) trisomy in a family with a balanced translocation 46,XX,t(1p+9q-).

    PubMed Central

    Mason, M K; Spencer, D A; Rutter, A

    1975-01-01

    A case of partial trisomy 9 is described, conforming that this will produce a recognizable syndrome of a characteristic facies with deep-set eyes and an unusual shape of the nose. Failure of secondary sexual characteristics to develop appears to be a feature in adults. In this case the mother had a balanced translocation between chromosomes 1 and 9 and must have, in addition, had a non-disjunction of her normal and her deleted No. 9 in order to produce the unbalanced state in her daughter. Images PMID:1177287

  10. Cloning of the breakpoints of a de novo inversion of chromosome 8, inv (8)(p11.2q23.1) in a patient with Ambras syndrome.

    PubMed

    Tadin-Strapps, M; Warburton, D; Baumeister, F A M; Fischer, S G; Yonan, J; Gilliam, T C; Christiano, A M

    2004-01-01

    Ambras syndrome (AMS) is a unique form of universal congenital hypertrichosis. In patients with this syndrome, the whole body is covered with fine long hair, except for areas where normally no hair grows. There is accompanying facial dysmorphism and teeth abnormalities, including retarded first and second dentition and absence of teeth. In 1993, Baumeister et al. reported an isolated case of Ambras syndrome in association with a pericentric inversion of chromosome 8. Subsequently, another patient with congenital hypertrichosis and rearrangement of chromosome 8 was reported by Balducci et al. (1998). Both of these patients have a breakpoint in 8q22 in common suggesting that this region of chromosome 8 contains a gene involved in regulation of hair growth. In order to precisely determine the nature of the rearrangement in the case of Ambras syndrome, we have used fluorescent in situ hybridization (FISH) analysis. We have cloned the inversion breakpoints in this patient and generated a detailed physical map of the inversion breakpoint interval. Analysis of the transcripts that map in the vicinity of the breakpoints revealed that the inversion does not disrupt a gene, and suggests that the phenotype is caused by a position effect.

  11. A genetic model of melanoma tumorigenesis based on allelic losses

    SciTech Connect

    Hayward, N.K.; Palmer, J.M.; Walters, M.K.

    1994-09-01

    Previous karyotypic studies have indicated a possible series of non-random chromosomal events involved in the progression of melanoma. We sought to define a model of melanocyte tumorigenesis by studying allelic deletions of polymorphic simple tandem repeat markers mapping to chromosome 1, 6q, 7, 9p, 10, 11, 17, and 21 in thirty matched pairs of melanoma and constitutional DNAs. The most frequent and earliest deletions were found on 9p (57%) and 10q (32%) and with the exception of one case, no sample has loss of markers on another chromosome without concomitant loss of markers on 9p and/or 10q. Losses on 6q were also a frequent (32%) event that sometimes occurred in primary melanomas, whereas losses of loci on distal 1p (26%) or 11q (26%) occurred only in metastic melanomas. A background rate (0-17%) of allele loss was seen on chromosomes 7, 17, and 21. Homozygous deletions in a panel of 31 melanoma cell lines were only detected for markers on 9p (4 cases). These data strongly support the previous model of melanoma tumorigenesis based primarily on karyotypic findings in melanocytic lesions. However, we have been able to further augment the model by delimiting the regions of loss on 10q to a region distal to D10S254, and on 1p, to between D1S243 and D1S160.

  12. Nonlinear infrared generation in alkali metal vapors: steady state susceptibilities and dynamic behavior. Effective relaxation rates and preliminary Raman gain predictions for the Cs system. Technical progress report, 1 July-31 December 1986

    SciTech Connect

    Lawandy, N.M.

    1986-12-01

    Effective relaxation rates for atomic cesium pumped by doubled Alexandrite radiation are presented. Laser radiation levels are 8S 1/2 and 9S 1/2; resonance levels 3 = 8P 1/2 and 8P 1/2, respectively. In addition, Raman gain is represented in two graphs which plot chi per atom (10 to the -13 power) at Raman peak versus the infrared wave number per centimeter and the corresponding doubled Alexandrite wave number. One graph covers resonance level 8P, the other 9P; in both cases cesium is pumped with a peak pulse height of 0.5 MW in a 200 micron diameter spot size.

  13. Nonlinear infrared generation in alkali metal vapors: Steady state susceptibilities and dynamic behavior. Effective relaxation rates and preliminary Raman gain predictions for the Cs system

    NASA Technical Reports Server (NTRS)

    Lawandy, N. M.

    1986-01-01

    Effective relaxation rates for atomic cesium pumped by doubled Alexandrite radiation are presented. Laser radiation levels are 8S 1/2 and 9S 1/2; resonance levels 3 = 8P 1/2 and 8P 1/2, respectively. In addition, Raman gain is represented in two graphs which plot chi per atom (10 to the -13 power) at Raman peak versus the infrared wave number per centimeter and the corresponding doubled Alexandrite wave number. One graph covers resonance level 8P, the other 9P; in both cases cesium is pumped with a peak pulse height of 0.5 MW in a 200 micron diameter spot size.

  14. 33 CFR 117.587 - Apponagansett River.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Apponagansett River. 117.587... hour between 5 a.m. and 9 a.m. and between 8 p.m. and 9 p.m. (2) The bridge shall open on signal, once... section 118.160 of this chapter....

  15. 33 CFR 117.587 - Apponagansett River.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Apponagansett River. 117.587... and half hour between 6 a.m. and 9 a.m. and between 8 p.m. and 9 p.m. (2) The bridge shall open on... provisions of section 118.160 of this chapter....

  16. 33 CFR 117.587 - Apponagansett River.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Apponagansett River. 117.587... hour between 5 a.m. and 9 a.m. and between 8 p.m. and 9 p.m. (2) The bridge shall open on signal, once... section 118.160 of this chapter....

  17. Consistent chromosome abnormalities including double minutes (dms) in adenocarcinoma of the pancreas

    SciTech Connect

    Griffin, C.A.; Morsberger, L.; Ellingham, T.

    1994-09-01

    Little is known about the somatic genetic changes which characterize pancreatic adenocarcinoma (PA), and identification of acquired genomic alterations would further our understanding of the biology of this neoplasm. We have studied 62 primary specimens of PA using classical and FISH methods. Clonally abnormal karyotypes were observed in 44 neoplasms. Karyotypes were generally complex (greater than 3 abnormalities) including both numerical and structural chromosome changes. Many tumors contained at least one marker chromosome. The most frequent whole chromosomal gains were chromosomes 20 (7 tumors) and 7 (5 tumors). Losses were much more frequent: chromosome 18 was lost in 22 tumors, followed by chromosomes 13 (15 tumors), 12 (13 tumors), and 6 (12 tumors). Structural abnormalities were common. 200 chromosome breakpoints were identified. Excluding Robertsonian translocations, chromosomal arms most frequently involved were 6q (12 chromosomes), 1p and 3p (10 each), 11p and 17p (9 each), 1q (8), 8p and 19q (7 each). Of particular interest, we found dms in 6 cases. These represent the first PAs with cytogenetic evidence of gene amplification, and are under investigation using chromosome microdissection. To begin to define the smallest region of 6q which is deleted, 5 tumors with 6q deletions were hybridized with a biotin-labeled probe, made by microdissection of 6q24-qter. Loss of one copy of this region was verified in 4/5 tumors; additional probes are being made. Our results are similar to those of 34 other reported PAs, and the combined data suggest that gains of chromosomes 7 and 20 and deletions and rearrangements of 1p and 6q may be particularly important in the biology of adenocarcinoma of the pancreas.

  18. A new locus (SPG46) maps to 9p21.2-q21.12 in a Tunisian family with a complicated autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum.

    PubMed

    Boukhris, Amir; Feki, Imed; Elleuch, Nizar; Miladi, Mohamed Imed; Boland-Augé, Anne; Truchetto, Jérémy; Mundwiller, Emeline; Jezequel, Nadia; Zelenika, Diana; Mhiri, Chokri; Brice, Alexis; Stevanin, Giovanni

    2010-10-01

    Hereditary spastic paraplegia (HSP) with thin corpus callosum (TCC) and mental impairment is a frequent subtype of complicated HSP, often inherited as an autosomal recessive (AR) trait. It is clear from molecular genetic analyses that there are several underlying causes of this syndrome, with at least six genetic loci identified to date. However, SPG11 and SPG15 are the two major genes for this entity. To map the responsible gene in a large AR-HSP-TCC family of Tunisian origin, we investigated a consanguineous family with a diagnosis of AR-HSP-TCC excluded for linkage to the SPG7, SPG11, SPG15, SPG18, SPG21, and SPG32 loci. A genome-wide scan was undertaken using 6,090 SNP markers covering all chromosomes. The phenotypic presentation in five patients was suggestive of a complex HSP that associated an early-onset spastic paraplegia with mild handicap, mental deterioration, congenital cataract, cerebellar signs, and TCC. The genome-wide search identified a single candidate region on chromosome 9, exceeding the LOD score threshold of +3. Fine mapping using additional markers narrowed the candidate region to a 45.1-Mb interval (15.4 cM). Mutations in three candidate genes were excluded. The mapping of a novel AR-HSP-TCC locus further demonstrates the extensive genetic heterogeneity of this condition. We propose that testing for this locus should be performed, after exclusion of mutations in SPG11 and SPG15 genes, in AR-HSP-TCC families, especially when cerebellar ataxia and cataract are present.

  19. Replication of KCNJ11 (p.E23K) and ABCC8 (p.S1369A) Association in Russian Diabetes Mellitus 2 Type Cohort and Meta-Analysis

    PubMed Central

    Sokolova, Ekaterina Alekseevna; Bondar, Irina Arkadievna; Shabelnikova, Olesya Yurievna; Pyankova, Olga Vladimirovna; Filipenko, Maxim Leonidovich

    2015-01-01

    The genes ABCC8 and KCNJ11 have received intense focus in type 2 diabetes mellitus (T2DM) research over the past two decades. It has been hypothesized that the p.E23K (KCNJ11) mutation in the 11p15.1 region may play an important role in the development of T2DM. In 2009, Hamming et al. found that the p.1369A (ABCC8) variant may be a causal factor in the disease; therefore, in this study we performed a meta-analysis to evaluate the association between these single nucleotide polymorphisms (SNPs), including our original data on the Siberian population (1384 T2DM and 414 controls). We found rs5219 and rs757110 were not associated with T2DM in this population, and that there was linkage disequilibrium in Siberians (D’=0.766, r2= 0.5633). In addition, the haplotype rs757110[T]-rs5219[C] (p.23K/p.S1369) was associated with T2DM (OR = 1.52, 95% CI: 1.04-2.24). We included 44 original studies published by June 2014 in a meta-analysis of the p.E23K association with T2DM. The total OR was 1.14 (95% CI: 1.11-1.17) for p.E23K for a total sample size of 137,298. For p.S1369A, a meta-analysis was conducted on a total of 10 studies with a total sample size of 14,136 and pooled OR of 1.14 [95% CI (1.08-1.19); p = 2 x 10-6]. Our calculations identified causal genetic variation within the ABCC8/KCNJ11 region for T2DM with an OR of approximately 1.15 in Caucasians and Asians. Moreover, the OR value was not dependent on the frequency of p.E23K or p.S1369A in the populations. PMID:25955821

  20. Phosphorylation of αS1-casein is regulated by different genes.

    PubMed

    Bijl, E; van Valenberg, H J F; Huppertz, T; van Hooijdonk, A C M; Bovenhuis, H

    2014-11-01

    Casein phosphorylation is a posttranslational modification catalyzed by kinase enzymes that attach phosphate groups to specific AA in the protein sequence. This modification is one of the key factors responsible for the stabilization of calcium phosphate nanoclusters in casein micelles and for the internal structure of the casein micelles. α(S1)-Casein (α(s1)-CN) is of special interest because it constitutes up to 40% of the total casein fraction in milk, and it has 2 common phosphorylation states, with 8 (α(S1)-CN-8P) and 9 (α(S1)-CN-9P) phosphorylated serine residues. Factors affecting this variation in the degree of phosphorylation are not currently known. The objective of this research was to determine the genetic background of α(S1)-CN-8P and α(S1)-CN-9P. The genetic and phenotypic correlation between α(S1)-CN-8P and α(S1)-CN-9P was low (0.18 and 0.19, respectively). This low genetic correlation suggests a different genetic background. These differences were further investigated by means of a genome-wide association study, which showed that both α(S1)-CN-8P and α(S1)-CN-9P were affected by a region on Bos taurus autosome (BTA) 6, but only α(S1)-CN-8P was affected by a region on BTA11 that contains the gene that encodes for β-lactoglobulin (β-LG), and only α(S1)-CN-9P was affected by a region on BTA14 that contains the diacylglycerol acyltransferase 1 (DGAT1) gene. Estimated effects of β-LG protein genotypes showed that only α(S1)-CN-8P was associated with the β-LG A/B polymorphism (g.1772G>A and g.3054C>T); the AA genotype of β-LG was associated with a lower concentration of α(S1)-CN-8P (-0.32% wt/wt) than the BB genotype (+0.41% wt/wt). Estimated effects of DGAT1 K232A genotypes showed that only α(S1)-CN-9P was associated with the DGAT1 gene polymorphism; DGAT1 AA genotype was associated with a higher α(S1)-CN-9P concentration (+0.53% wt/wt) than the DGAT1 KK genotype (-0.44% wt/wt). The results give insight in phosphorylation of α(S1

  1. The Essential Function of the Small Tim Proteins in the TIM22 Import Pathway Does Not Depend on Formation of the Soluble 70-Kilodalton Complex

    PubMed Central

    Murphy, Michael P.; Leuenberger, Danielle; Curran, Sean P.; Oppliger, Wolfgang; Koehler, Carla M.

    2001-01-01

    The TIM22 protein import pathway of the yeast mitochondrion contains several components, including a family of five proteins (Tim8p, -9p, -10p, -12p, and -13p [Tim, for translocase of inner membrane]) that are located in the intermembrane space and are 25% identical. Tim9p and Tim10p have dual roles in mediating the import of inner membrane proteins. Like the Tim8p-Tim13p complex, the Tim9p-Tim10p complex functions as a putative chaperone to guide hydrophobic precursors across the intermembrane space. Like membrane-associated Tim12p, they are members of the Tim18p-Tim22p-Tim54p membrane complex that mediates precursor insertion into the membrane. To understand the role of this family in protein import, we have used a genetic approach to manipulate the complement of the small Tim proteins. A strain has been constructed that lacks the 70-kDa soluble Tim8p-Tim13p and Tim9p-Tim10p complexes in the intermembrane space. Instead, a functional version of Tim9p (Tim9S67Cp), identified as a second-site suppressor of a conditional tim10 mutant, maintains viability. Characterization of this strain revealed that Tim9S67Cp and Tim10p were tightly associated with the inner membrane, the soluble 70-kDa Tim8p-Tim13p and Tim9p-Tim10p complexes were not detectable, and the rate of protein import into isolated mitochondria proceeded at a slower rate. An arrested translocation intermediate bound to Tim9S67Cp was located in the intermembrane space, associated with the inner membrane. We suggest that the 70-kDa complexes facilitate import, similar to the outer membrane receptors of the TOM (hetero-oligomeric translocase of the outer membrane) complex, and the essential role of Tim9p and Tim10p may be to mediate protein insertion in the inner membrane with the TIM22 complex. PMID:11509656

  2. Pseudouridylation at position 32 of mitochondrial and cytoplasmic tRNAs requires two distinct enzymes in Saccharomyces cerevisiae.

    PubMed

    Behm-Ansmant, Isabelle; Grosjean, Henri; Massenet, Séverine; Motorin, Yuri; Branlant, Christiane

    2004-12-17

    Cytoplasmic and mitochondrial tRNAs contain several pseudouridylation sites, and the tRNA:Psi-synthase acting at position 32 had not been identified in Saccharomyces cerevisiae. By combining genetic and biochemical analyses, we demonstrate that two enzymes, Rib2/Pus8p and Pus9p, are required for Psi32 formation in cytoplasmic and mitochondrial tRNAs, respectively. Pus9p acts mostly in mitochondria, and Rib2/Pus8p is strictly cytoplasmic. This is the first case reported so far of two distinct tRNA modification enzymes acting at the same position but present in two different compartments. This peculiarity may be the consequence of a gene fusion that occurred during yeast evolution. Indeed, Rib2/Pus8p displays two distinct catalytic activities involved in completely unrelated metabolism: its C-terminal domain has a DRAP-deaminase activity required for riboflavin biogenesis in the cytoplasm, whereas its N-terminal domain carries the tRNA:Psi32-synthase activity. Pus9p has only a tRNA:Psi32-synthase activity and contains a characteristic mitochondrial targeting sequence at its N terminus. These results are discussed in terms of RNA:Psi-synthase evolution.

  3. Numerical and structural genomic aberrations are reliably detectable in tissue microarrays of formalin-fixed paraffin-embedded tumor samples by fluorescence in-situ hybridization.

    PubMed

    Horn, Heike; Bausinger, Julia; Staiger, Annette M; Sohn, Maximilian; Schmelter, Christopher; Gruber, Kim; Kalla, Claudia; Ott, M Michaela; Rosenwald, Andreas; Ott, German

    2014-01-01

    Few data are available regarding the reliability of fluorescence in-situ hybridization (FISH), especially for chromosomal deletions, in high-throughput settings using tissue microarrays (TMAs). We performed a comprehensive FISH study for the detection of chromosomal translocations and deletions in formalin-fixed and paraffin-embedded (FFPE) tumor specimens arranged in TMA format. We analyzed 46 B-cell lymphoma (B-NHL) specimens with known karyotypes for translocations of IGH-, BCL2-, BCL6- and MYC-genes. Locus-specific DNA probes were used for the detection of deletions in chromosome bands 6q21 and 9p21 in 62 follicular lymphomas (FL) and six malignant mesothelioma (MM) samples, respectively. To test for aberrant signals generated by truncation of nuclei following sectioning of FFPE tissue samples, cell line dilutions with 9p21-deletions were embedded into paraffin blocks. The overall TMA hybridization efficiency was 94%. FISH results regarding translocations matched karyotyping data in 93%. As for chromosomal deletions, sectioning artefacts occurred in 17% to 25% of cells, suggesting that the proportion of cells showing deletions should exceed 25% to be reliably detectable. In conclusion, FISH represents a robust tool for the detection of structural as well as numerical aberrations in FFPE tissue samples in a TMA-based high-throughput setting, when rigorous cut-off values and appropriate controls are maintained, and, of note, was superior to quantitative PCR approaches.

  4. [A comparative cytogenetic analysis in large scale between adult and childhood patients with acute lymphoblastic leukemia].

    PubMed

    Liu, Xu-Ping; Zhu, Xiao-Fan; Wang, Jian-Xiang; Mi, Ying-Chang; Zou, Yao; Chen, Yu-Mei; Li, Cheng-Wen; Dai, Yun; Qin, Shuang; Xiao, Ji-Gang; Xu, Fang-Yun; Gong, Jin-Ying; Wang, Si-Ping; Yu, Cheng-Long; Fan, Jing

    2009-12-01

    This study was purposed to comparatively analyze the cytogenetic characteristics between 566 cases of adult acute lymphoblastic leukemia (aALL) and 586 cases of childhood acute lymphoblastic leukemia (cALL). The cytogenetic analysis of all the patients was performed, and the FISH detection for partial patients was carried out. The result showed that the difference of chromosome abnormality between cALL and aALL was statistically significant. The percentage of abnormal karyotypes in aALL was 62.0%, including mainly t(9;22)(q34;q11), hypodiploidy, hyperdiploidy (47 - 50), abn(6q), abn(9p) and -7, most of which conferring an unfavorable prognosis. The percentage of abnormal karyotypes in cALL was 39.2%, composed mainly of high hyperdiploidy, hypodiploidy, TEL/AML1(+), +8, hyperdiploidy (47 - 50) and +21, etc, most of which conferring a favorable prognosis. The incidences of abnormal karyotypes, total hypodiploidy, total hyperdiploidy (47 - 50), t(9;22)(q34;q11), -7, abn(7q), abn(14q32) and +Ph in aALL were significantly higher than those of cALL (p < 0.05), whereas the incidences of normal karyotype (N), high hyperdiploidy, +8, +21*2 and TEL/AML1(+) in cALL were significantly higher than those of aALL (p < 0.05). 20.5% of aALL were Ph+ aALL, with 63.8% of which being with additional abnormalities, composed mainly of +Ph, -7, i (9q+), 9p-, +8, +21, +X, 6q-, abn(14q32) and +14. In contrast, only 4.4% of cALL were Ph+ aALL, with 42.3% of which being with additional abnormalities, including mainly abn(9p), abn(7p), -7, 17p- and +21. It is concluded that almost every chromosome is involved in the numerical and structural abnormalities and complex karyotypes are common. The significant difference of chromosome abnormality exists between aALL and cALL.

  5. Patient Access to Online Visit Notes: Perceptions of Doctors and Patients at an Urban HIV/AIDS Clinic

    PubMed Central

    Oster, Natalia V.; Jackson, Sara L.; Dhanireddy, Shireesha; Mejilla, Roanne; Ralston, James D.; Leveille, Suzanne; Delbanco, Tom; Walker, Janice D.; Bell, Sigall K.; Elmore, Joann G.

    2014-01-01

    Patients living with HIV/AIDS face large societal and medical challenges. Inviting patients to read their doctors’ visit notes via secure electronic portals may empower patients and improve health. We investigated whether utilization and perceptions about access to doctors’ notes differed among doctors and patients in an HIV/AIDS clinic versus primary care setting. We analyzed pre- and 1-year postintervention data from 99 doctors and 3819 patients. HIV clinic patients did not report differences in perceived risks and benefits compared to primary care clinic patients, however, they were more likely to share notes with friends (33% versus 9%, P = .002), other health professionals (24% versus 8%, P = .03), or another doctor (38% versus 9%, P < .0001). HIV clinic doctors were less likely than primary care doctors to change=the level of candor in visit notes (P < .04). Our findings suggest that HIV clinic patients and doctors are ready to share visit notes online. PMID:24729072

  6. A suggested periodic table up to Z≤ 172, based on Dirac-Fock calculations on atoms and ions.

    PubMed

    Pyykkö, Pekka

    2011-01-01

    Extended Average Level (EAL) Dirac-Fock calculations on atoms and ions agree with earlier work in that a rough shell-filling order for the elements 119-172 is 8s < 5g≤ 8p(1/2) < 6f < 7d < 9s < 9p(1/2) < 8p(3/2). The present Periodic Table develops further that of Fricke, Greiner and Waber [Theor. Chim. Acta 1971, 21, 235] by formally assigning the elements 121-164 to (nlj) slots on the basis of the electron configurations of their ions. Simple estimates are made for likely maximum oxidation states, i, of these elements M in their MX(i) compounds, such as i = 6 for UF(6). Particularly high i are predicted for the 6f elements.

  7. Alteration of chromosome arm 6p is characteristic of primary mediastinal B-cell lymphoma, as identified by genome-wide allelotyping.

    PubMed

    Rigaud, G; Moore, P S; Taruscio, D; Scardoni, M; Montresor, M; Menestrina, F; Scarpa, A

    2001-06-01

    Five cases of primary mediastinal B-cell lymphoma (PMBL) each have been studied with 375 microsatellite markers from all 22 autosomes. Of the 151 genomic alterations among the 1,875 assays, only five were allelic losses. The remainder of the microsatellite alterations consisted of 114 allelic imbalances and 32 instabilities. Microsatellite alterations were found in all cases on chromosomal arms 6p and 9p. These allelic imbalances most likely are indicative of genetic amplification, a finding agreeing well with those of studies using either comparative genomic hybridization or arbitrarily primed polymerase chain reaction, in which amplification of chromosome arm 9p in PMBL has been found. The allelic imbalances on chromosome arm 6p always included marker D6S276 located at 6p21.3-p22.3, where the MHC class I genes reside. These allelic imbalances may be reflective of alterations in the expression of the MHC gene products, characteristic of PMBL. Allelic anomalies close to the MYB gene locus on 6q were detected in two cases and prompted the analysis of MYB rearrangements in a series of 30 lymphomas. One rearrangement was detected in one of 18 cases of PMBL and in none of 10 diffuse, large B-cell lymphomas and two T-cell lymphomas. Our genome-wide microsatellite analysis provides independent confirmation that PMBL is characterized by infrequent chromosomal losses and by frequent genetic alterations involving chromosomal arm 9p. For the first time, chromosomal arm 6p has been identified as a highly frequent target of genetic alterations in this tumor type. Finally, MYB may also be involved occasionally in PMBL pathogenesis.

  8. Oligonucleotide array-CGH identifies genomic subgroups and prognostic markers for tumor stage mycosis fungoides.

    PubMed

    Salgado, Rocío; Servitje, Octavio; Gallardo, Fernando; Vermeer, Maarten H; Ortiz-Romero, Pablo L; Karpova, Maria B; Zipser, Marie C; Muniesa, Cristina; García-Muret, María P; Estrach, Teresa; Salido, Marta; Sánchez-Schmidt, Júlia; Herrera, Marta; Romagosa, Vicenç; Suela, Javier; Ferreira, Bibiana I; Cigudosa, Juan C; Barranco, Carlos; Serrano, Sergio; Dummer, Reinhard; Tensen, Cornelis P; Solé, Francesc; Pujol, Ramon M; Espinet, Blanca

    2010-04-01

    Mycosis fungoide (MF) patients who develop tumors or extracutaneous involvement usually have a poor prognosis with no curative therapy available so far. In the present European Organization for Research and Treatment of Cancer (EORTC) multicenter study, the genomic profile of 41 skin biopsies from tumor stage MF (MFt) was analyzed using a high-resolution oligo-array comparative genomic hybridization platform. Seventy-six percent of cases showed genomic aberrations. The most common imbalances were gains of 7q33.3q35 followed by 17q21.1, 8q24.21, 9q34qter, and 10p14 and losses of 9p21.3 followed by 9q31.2, 17p13.1, 13q14.11, 6q21.3, 10p11.22, 16q23.2, and 16q24.3. Three specific chromosomal regions, 9p21.3, 8q24.21, and 10q26qter, were defined as prognostic markers showing a significant correlation with overall survival (OS) (P=0.042, 0.017, and 0.022, respectively). Moreover, we have established two MFt genomic subgroups distinguishing a stable group (0-5 DNA aberrations) and an unstable group (>5 DNA aberrations), showing that the genomic unstable group had a shorter OS (P=0.05). We therefore conclude that specific chromosomal abnormalities, such as gains of 8q24.21 (MYC) and losses of 9p21.3 (CDKN2A, CDKN2B, and MTAP) and 10q26qter (MGMT and EBF3) may have an important role in prognosis. In addition, we describe the MFt genomic instability profile, which, to our knowledge, has not been reported earlier.

  9. Karyotypic abnormalities in tumours of the pancreas.

    PubMed Central

    Bardi, G.; Johansson, B.; Pandis, N.; Mandahl, N.; Bak-Jensen, E.; Andrén-Sandberg, A.; Mitelman, F.; Heim, S.

    1993-01-01

    Short-term cultures from 20 pancreatic tumours, three endocrine and 17 exocrine, were cytogenetically analysed. All three endocrine tumours had a normal chromosome complement. Clonal chromosome aberrations were detected in 13 of the 17 exocrine tumours: simple karyotypic changes were found in five carcinomas and numerous numerical and/or structural changes in eight. When the present findings and those previously reported by our group were viewed in conjunction, the most common numerical imbalances among the 22 karyotypically abnormal pancreatic carcinomas thus available for evaluation turned out to be, in order of falling frequency, -18, -Y, +20, +7, +11 and -12. Imbalances brought about by structural changes most frequently affected chromosomes 1 (losses in 1p but especially gains of 1q), 8 (in particular 8q gains but also 8p losses), and 17 (mostly 17q gain but also loss of 17p). Chromosomal bands 1p32, 1q10, 6q21, 7p22, 8p21, 8q11, 14p11, 15q10-11, and 17q11 were the most common breakpoint sites affected by the structural rearrangements. Abnormal karyotypes were detected more frequently in poorly differentiated and anaplastic carcinomas than in moderately and well differentiated tumours. Images Figure 1 PMID:8494707

  10. Up-conversion routines of Er{sup 3+}–Yb{sup 3+} doped Y{sub 6}O{sub 5}F{sub 8} and YOF phosphors

    SciTech Connect

    Park, Sangmoon; Yang, Wonseok; Park, Chu-Young; Noh, Minhee; Choi, Seulki; Park, Dahye; Jang, Ho Seong; Cho, So-Hye

    2015-11-15

    Highlights: • Single-phase optical materials of Y{sub 6}O{sub 5}F{sub 8}:Er and YOF:Er were prepared. • Effective spectral converting properties were observed in Y{sub 6}O{sub 5}F{sub 8}:Er,Yb. • 980 nm diode laser was irradiated for up-converting analysis. • A multi-photon process in the phosphors was investigated. - Abstract: Optical materials composed of a Y{sub 6(1−p−q)}Er{sub 6p}Yb{sub 6q}O{sub 5}F{sub 8} (p = 0.001–0.1, q = 0.005–0.1) solid solution with Y{sub 0.99}Er{sub 0.01}OF were prepared via a solid-state reaction using excess NH{sub 4}F flux at 950 °C for 30 min. X-ray diffraction patterns of Y{sub 6(1−p−q)}Er{sub 6p}Yb{sub 6q}O{sub 5}F{sub 8} and Y{sub 0.99}Er{sub 0.01}OF were compared upon altering the synthesis temperature and the molar ratio of the NH{sub 4}F flux to the Y{sup 3+} (Er{sup 3+}, Yb{sup 3+}) ions. The effective spectral-conversion properties of Er{sup 3+} and Er{sup 3+}–Yb{sup 3+} ions in Y{sub 6}O{sub 5}F{sub 8} phosphors were monitored during excitation with a 980 nm wavelength diode-laser. Selection of appropriate Er{sup 3+} and/or Yb{sup 3+} concentrations in the Y{sub 6}O{sub 5}F{sub 8} structure led to achievement of the desired up-conversion emission, from the green to the red regions of the spectra. Furthermore, the mechanism of up-conversion in the phosphors was described by an energy-level schematic. Up-conversion emission spectra and the dependence of the emission intensity on pump power (between 193 and 310 mW) in the Y{sub 6(0.995−q)}Er{sub 0.03}Yb{sub 6q}O{sub 5}F{sub 8} phosphors were also investigated.

  11. Genomic aberration patterns and expression profiles of squamous cell carcinomas of the vulva.

    PubMed

    Micci, Francesca; Panagopoulos, Ioannis; Haugom, Lisbeth; Dahlback, Hanne-Sofie S; Pretorius, Maria E; Davidson, Ben; Abeler, Vera M; Tropé, Claes G; Danielsen, Håvard E; Heim, Sverre

    2013-06-01

    Little is known about the genomic abnormalities of squamous cell carcinomas (SCC) of the vulva and how they correlate with gene expression. We determined the genomic and expression profiles of 15 such SCC using karyotyping, DNA ploidy analysis, arrayCGH, and expression arrays. Four of the five cases with clonal chromosomal aberrations found by G-banding showed highly abnormal karyotypes with multiple rearrangements. The imbalances scored by arrayCGH mapped to different chromosomes with losses being more common than gains. Frequent losses were scored from 3p and 8p whereas gains were frequent from 3q and 8q (loss of 8p with concomitant gain of 8q mostly occurred via 8q isochromosome formation). This is the first study of vulvar tumors using arrayCGH, and some frequent imbalances could be defined precisely. Of particular note were the sometimes large, sometimes small deletions of 3p and 9p which had minute areas in 3p14 and 9p23 as minimal commonly deleted regions. FHIT (3p14) and PTPRD (9p23) are the only genes here. They were both lost in seven cases, including homozygous losses of PTPRD in four tumors. Using qPCR we could demonstrate deregulation of the FHIT gene in tumor cells. Hence, this gene is likely to play a pathogenetic role in vulvar SCC tumorigenesis. Expression array analyses also identified a number of other genes whose expression profile was altered. Notable among the downregulated genes were MAL (in 2q11), KRT4 (in 12q13), and OLFM4 (in 13q14), whereas upregulated genes included SPRR2G (in 1q21.3) and S100A7A (in 1q21.3).

  12. The relationships among bovine αS-casein phosphorylation isoforms suggest different phosphorylation pathways.

    PubMed

    Fang, Z H; Visker, M H P W; Miranda, G; Delacroix-Buchet, A; Bovenhuis, H; Martin, P

    2016-10-01

    Casein (CN) phosphorylation is an important posttranslational modification and is one of the key factors responsible for constructing and stabilizing casein micelles. Variation in phosphorylation degree of αS-CN is of great interest because it is suggested to affect milk technological properties. This study aimed to investigate the variation in phosphorylation degree of αS-CN among milk of individual cows and to explore relationships among different phosphorylation isoforms of αS-CN. For this purpose, we analyzed morning milk samples from 529 French Montbéliarde cows using liquid chromatography coupled with electrospray ionization mass spectrometry. We detected 3 new phosphorylation isoforms: αS2-CN-9P, αS2-CN-14P, and αS2-CN-15P in bovine milk, in addition to the known isoforms αS1-CN-8P, αS1-CN-9P, αS2-CN-10P, αS2-CN-11P, αS2-CN-12P, and αS2-CN-13P. The relative concentrations of each αS-CN phosphorylation isoform varied considerably among individual cows. Furthermore, the phenotypic correlations and hierarchical clustering suggest at least 2 regulatory systems for phosphorylation of αS-CN: one responsible for isoforms with lower levels of phosphorylation (αS1-CN-8P, αS2-CN-10P, and αS2-CN-11P), and another responsible for isoforms with higher levels of phosphorylation (αS1-CN-9P, αS2-CN-12P, αS2-CN-13P, and αS2-CN-14P). Identifying all phosphorylation sites of αS2-CN and investigating the genetic background of different αS2-CN phosphorylation isoforms may provide further insight into the phosphorylation mechanism of caseins.

  13. The relationships among bovine αS-casein phosphorylation isoforms suggest different phosphorylation pathways.

    PubMed

    Fang, Z H; Visker, M H P W; Miranda, G; Delacroix-Buchet, A; Bovenhuis, H; Martin, P

    2016-10-01

    Casein (CN) phosphorylation is an important posttranslational modification and is one of the key factors responsible for constructing and stabilizing casein micelles. Variation in phosphorylation degree of αS-CN is of great interest because it is suggested to affect milk technological properties. This study aimed to investigate the variation in phosphorylation degree of αS-CN among milk of individual cows and to explore relationships among different phosphorylation isoforms of αS-CN. For this purpose, we analyzed morning milk samples from 529 French Montbéliarde cows using liquid chromatography coupled with electrospray ionization mass spectrometry. We detected 3 new phosphorylation isoforms: αS2-CN-9P, αS2-CN-14P, and αS2-CN-15P in bovine milk, in addition to the known isoforms αS1-CN-8P, αS1-CN-9P, αS2-CN-10P, αS2-CN-11P, αS2-CN-12P, and αS2-CN-13P. The relative concentrations of each αS-CN phosphorylation isoform varied considerably among individual cows. Furthermore, the phenotypic correlations and hierarchical clustering suggest at least 2 regulatory systems for phosphorylation of αS-CN: one responsible for isoforms with lower levels of phosphorylation (αS1-CN-8P, αS2-CN-10P, and αS2-CN-11P), and another responsible for isoforms with higher levels of phosphorylation (αS1-CN-9P, αS2-CN-12P, αS2-CN-13P, and αS2-CN-14P). Identifying all phosphorylation sites of αS2-CN and investigating the genetic background of different αS2-CN phosphorylation isoforms may provide further insight into the phosphorylation mechanism of caseins. PMID:27522420

  14. Immobilized pH gradients (IPG) simulator--an additional step in pH gradient engineering: II. Nonlinear pH gradients.

    PubMed

    Righetti, P G; Tonani, C

    1991-12-01

    While in the companion paper (Tonani, C. & Righetti, P. G., Electrophoresis 1991, 12, 1011-1021) we gave the general outline of our new computer program, immobilized pH gradients (IPG) simulator, able to simulate and optimize linear pH gradients for isoelectric focusing in immobilized pH gradients, in the present report we extend the application of such a program to: (i) convex exponential gradients, (ii) logarithmic and (iii) polynomial gradients. Such gradients are meant to give equal space to protein spots in complex protein mixtures (e.g., cell lysates, biological fluids) and follow the statistical distribution of protein pI values along the pH axis. They will prove of fundamental importance in two-dimensional maps, both because they optimize the spreading of spots in the two-dimensional plane and because of the excellent reproducibility of immobilized pH gradients. The following concave exponential recipes are given: pH 3-8, pH 3-9, pH 3-10, pH 3-11, pH 4-7, pH 4-8, pH 4-9, pH 4-10, pH 4-11, pH 5-8, pH 5-9, and pH 5-10, as well as the most extended pH 2.5-11 interval. Two interesting logarithmic gradients are described: pH 3-6 and pH 3-7 and one sigmoidal (derived with a polynomial of 5th degree): pH 3-11.

  15. A skill-based conditioning games approach to metabolic conditioning for elite rugby football players.

    PubMed

    Gamble, Paul

    2004-08-01

    The purpose of this study was to evaluate changes in endurance fitness of elite-level rugby union players (n = 35) undertaking skill-based conditioning games for a 9-week preseason training period. Metabolic conditioning was conducted exclusively in the form of skill-based conditioning games in conjunction with heart rate (HR) telemetry. Two markers of cardiorespiratory fitness were assessed at weekly intervals via the recording of HR responses to an intermittent multistage shuttle test. Significant differences post-training were observed for the percentage of maximal HR (% HRmax) reached during the final test stage and the percentage of HR recovery (% HR recovery) from the end of the final stage to the end of the final 1-minute rest period. Significant improvements were demonstrated for % HR recovery at week 7 (p < 0.05) and week 9 (p < 0.01), and % HRmax in the final test stage was significantly lower at weeks 4, 5, and 7 (p < 0.05) and week 9 (p < 0.01). Further improvements from mid-preseason to the end of the preseason training period were observed for % HR recovery scores in week 8 (p < 0.01) and week 9 (p = 0.012) and for % HRmax reached in the final test stage at week 9 (p < 0.05). These results indicate skill-based conditioning games were successful at improving markers of cardiorespiratory endurance for the duration of a 9-week training period in the elite-level professional rugby union players studied. The HR monitoring was demonstrated to be an effective and practical means of quantifying intensity in the conditioning games format and of tracking changes in cardiorespiratory fitness.

  16. Chromosomal Aberrations in ETV6/RUNX1-positive Childhood Acute Lymphoblastic Leukemia using 244K Oligonucleotide Array Comparative Genomic Hybridization

    PubMed Central

    2012-01-01

    Background Acute lymphoblastic leukemia (ALL) is a heterogeneous form of hematological cancer consisting of various subtypes. We are interested to study the genetic aberration in precursor B-cell ALL with specific t(12;21) translocation in childhood ALL patients. A high resolution 244K array-based Comparative Genomic Hybridization (array-CGH) was used to study eleven ETV6/RUNX1-positive childhood acute lymphoblastic leukemia (ALL) patients. Result 155 chromosomal aberrations (119 losses, 36 gains) were reported in the array findings, corresponding to 76.8% deletions and 23.2% amplifications. The ETV6 gene deletion occurred in 4 of the patients, corresponding to 45% of the sample. The most common alterations above 1 Mb were deletion 6q (13%), 12p (12%) and 9p (8%), and duplication 4q (6%) and Xq (4%). Other genes important in ALL were also identified in this study including RUNX1, CDKN2A, FHIT, and PAX5. The array-CGH technique was able to detect microdeletion as small as 400 bp. Conclusion The results demonstrate the usefulness of high resolution array-CGH as a complementary tool in the investigation of ALL. PMID:23151340

  17. Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

    PubMed Central

    Mitchell, Jonathan S.; Li, Ni; Weinhold, Niels; Försti, Asta; Ali, Mina; van Duin, Mark; Thorleifsson, Gudmar; Johnson, David C.; Chen, Bowang; Halvarsson, Britt-Marie; Gudbjartsson, Daniel F.; Kuiper, Rowan; Stephens, Owen W.; Bertsch, Uta; Broderick, Peter; Campo, Chiara; Einsele, Hermann; Gregory, Walter A.; Gullberg, Urban; Henrion, Marc; Hillengass, Jens; Hoffmann, Per; Jackson, Graham H.; Johnsson, Ellinor; Jöud, Magnus; Kristinsson, Sigurður Y.; Lenhoff, Stig; Lenive, Oleg; Mellqvist, Ulf-Henrik; Migliorini, Gabriele; Nahi, Hareth; Nelander, Sven; Nickel, Jolanta; Nöthen, Markus M.; Rafnar, Thorunn; Ross, Fiona M.; da Silva Filho, Miguel Inacio; Swaminathan, Bhairavi; Thomsen, Hauke; Turesson, Ingemar; Vangsted, Annette; Vogel, Ulla; Waage, Anders; Walker, Brian A.; Wihlborg, Anna-Karin; Broyl, Annemiek; Davies, Faith E.; Thorsteinsdottir, Unnur; Langer, Christian; Hansson, Markus; Kaiser, Martin; Sonneveld, Pieter; Stefansson, Kari; Morgan, Gareth J.; Goldschmidt, Hartmut; Hemminki, Kari; Nilsson, Björn; Houlston, Richard S.

    2016-01-01

    Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10−8), 6q21 (rs9372120, P=9.09 × 10−15), 7q36.1 (rs7781265, P=9.71 × 10−9), 8q24.21 (rs1948915, P=4.20 × 10−11), 9p21.3 (rs2811710, P=1.72 × 10−13), 10p12.1 (rs2790457, P=1.77 × 10−8), 16q23.1 (rs7193541, P=5.00 × 10−12) and 20q13.13 (rs6066835, P=1.36 × 10−13), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development. PMID:27363682

  18. Compositions and methods for detecting gene rearrangements and translocations

    DOEpatents

    Rowley, Janet D.; Diaz, Manuel O.

    2000-01-01

    Disclosed is a series of nucleic acid probes for use in diagnosing and monitoring certain types of leukemia using, e.g., Southern and Northern blot analyses and fluorescence in situ hybridization (FISH). These probes detect rearrangements, such as translocations involving chromosome band 11q23 with other chromosomes bands, including 4q21, 6q27, 9p22, 19p13.3, in both dividing leukemic cells and interphase nuclei. The breakpoints in all such translocations are clustered within an 8.3 kb BamHI genomic region of the MLL gene. A novel 0.7 kb BamH1 cDNA fragment derived from this gene detects rearrangements on Southern blot analysis with a single BamHI restriction digest in all patients with the common 11q23 translocations and in patients with other 11q23 anomalies. Northern blot analyses are presented demonstrating that the MLL gene has multiple transcripts and that transcript size differentiates leukemic cells from normal cells. Also disclosed are MLL fusion proteins, MLL protein domains and anti-MLL antibodies.

  19. Genome-wide association study identifies multiple susceptibility loci for multiple myeloma.

    PubMed

    Mitchell, Jonathan S; Li, Ni; Weinhold, Niels; Försti, Asta; Ali, Mina; van Duin, Mark; Thorleifsson, Gudmar; Johnson, David C; Chen, Bowang; Halvarsson, Britt-Marie; Gudbjartsson, Daniel F; Kuiper, Rowan; Stephens, Owen W; Bertsch, Uta; Broderick, Peter; Campo, Chiara; Einsele, Hermann; Gregory, Walter A; Gullberg, Urban; Henrion, Marc; Hillengass, Jens; Hoffmann, Per; Jackson, Graham H; Johnsson, Ellinor; Jöud, Magnus; Kristinsson, Sigurður Y; Lenhoff, Stig; Lenive, Oleg; Mellqvist, Ulf-Henrik; Migliorini, Gabriele; Nahi, Hareth; Nelander, Sven; Nickel, Jolanta; Nöthen, Markus M; Rafnar, Thorunn; Ross, Fiona M; da Silva Filho, Miguel Inacio; Swaminathan, Bhairavi; Thomsen, Hauke; Turesson, Ingemar; Vangsted, Annette; Vogel, Ulla; Waage, Anders; Walker, Brian A; Wihlborg, Anna-Karin; Broyl, Annemiek; Davies, Faith E; Thorsteinsdottir, Unnur; Langer, Christian; Hansson, Markus; Kaiser, Martin; Sonneveld, Pieter; Stefansson, Kari; Morgan, Gareth J; Goldschmidt, Hartmut; Hemminki, Kari; Nilsson, Björn; Houlston, Richard S

    2016-07-01

    Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10(-8)), 6q21 (rs9372120, P=9.09 × 10(-15)), 7q36.1 (rs7781265, P=9.71 × 10(-9)), 8q24.21 (rs1948915, P=4.20 × 10(-11)), 9p21.3 (rs2811710, P=1.72 × 10(-13)), 10p12.1 (rs2790457, P=1.77 × 10(-8)), 16q23.1 (rs7193541, P=5.00 × 10(-12)) and 20q13.13 (rs6066835, P=1.36 × 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.

  20. Loss of heterozygosity occurs predominantly, but not exclusively, in the epithelial compartment of pleomorphic adenoma.

    PubMed

    Poetsch, Micaela; Zimmermann, Anett; Wolf, Eduard; Kleist, Britta

    2005-07-01

    Pleomorphic adenoma (PA), being the most common benign tumor of the salivary glands, is composed of epithelial and mesenchymal compartments. In this study, we analyzed 19 microsatellite markers from chromosomal arms 6q, 8q, 9p, 12q, and 17p in 31 PAs and 3 carcinoma ex pleomorphic adenomas (CXPAs) as well as 11 other non-PA-related carcinomas of the salivary gland for comparison. In our analysis, we differentiated between epithelial and mesenchymal tissues. Loss of heterozygosity (LOH) in PAs was most often found in 8q (32%) and 12q (29%). Two of the three CXPAs displayed allelic loss at all chromosomal arms investigated, whereas the results of the non-PA-related carcinomas were rather heterogeneous. LOH could not only be detected in the epithelial, but also in the mesenchymal, compartments of a subset of PAs, especially at chromosomal arm 8q. Concerning the CXPAs, we were able to demonstrate allelic losses not only in the malignant epithelial compartment, but also in the residual adenoma parts. Our data give further evidence that alterations in 8q may be an early event in PA tumorigenesis, whereas LOH in 12q may characterize cells with the potential to transform in CXPAs.

  1. Assignment of the group A rotavirus NSP4 gene into genotypes using a hemi-nested multiplex PCR assay: a rapid and reproducible assay for strain surveillance studies.

    PubMed

    Bányai, Krisztián; Bogdán, Agnes; Szücs, György; Arista, Serenella; De Grazia, Simona; Kang, Gagandeep; Banerjee, Indrani; Iturriza-Gómara, Miren; Buonavoglia, Canio; Martella, Vito

    2009-03-01

    The rotavirus non-structural protein NSP4 has been implicated in a number of biological functions during the rotavirus cellular cycle and pathogenesis, and has been addressed as a target for vaccine development. The NSP4 gene has been classified into six genotypes (A-F). A semi-nested triplex PCR was developed for genotyping the major human NSP4 genotypes (A-C), which are common in human rotavirus strains but are also shared among most mammalian rotavirus strains. A total of 192 previously characterized human strains representing numerous G and P type specificities (such as G1P[8], G1P[4], G2P[4], G3P[3], G3P[8], G3P[9], G4P[6], G4P[8], G6P[4], G6P[9], G6P[14], G8P[10], G8P[14], G9P[8], G9P[11], G10P[11], G12P[6] and G12P[8]) were tested for NSP4 specificity by the collaborating laboratories. An additional 35 animal strains, including the reference laboratory strains SA11 (simian, G3P[2]), NCDV (bovine, G6P[1]), K9 and CU-1 (canine, G3P[3]), together with 31 field isolates (canine, G3P[3]; feline, G3P[9]; porcine, G2P[23], G3P[6], G4P[6], G5P[6], G5P[7], G5P[26], G5P[27], G9P[6] and G9P[7]) were also successfully NSP4-typed. Four human G3P[9] strains and one feline G3P[9] strain were found to possess an NSP4 A genotype, instead of NSP4 C, suggesting a reassortment event between heterologous strains. Routine NSP4 genotyping may help to determine the genomic constellation of rotaviruses of man and livestock, and identify interspecies transmission of heterologous strains. PMID:19208878

  2. Chromosome aberrations, spontaneous SCE, and growth kinetics in PHA-stimulated lymphocytes of five cases with Sézary syndrome.

    PubMed

    Limon, J; Nedoszytko, B; Brozek, I; Hellmann, A; Zajaczek, S; Lubiński, J; Mrózek, K

    1995-08-01

    Cytogenetic studies of five patients with Sézary syndrome (SS) revealed clonal chromosome aberrations in all cases. In one patient, a del(8)(p21) was the sole abnormality, whereas the remaining cases had karyotypes with multiple chromosome changes. In three SS cases with hypodiploid chromosome numbers, structural rearrangements affecting regions 10q22-24 and 12p11-13, and aberrations leading to loss of material from 17p were found concurrently. Bands 14q11 and 14q32 were involved in structural rearrangements in one case each. Our results and review of 51 published previously SS cases that were analyzed with banding techniques indicate that the chromosomes most frequently involved in structural changes were chromosomes 1 and 2 (in 43% of cases), 6 (in 38%), 17 (in 34%), 14 (in 27%), 11 (in 25%), 13 (in 21%), and 9 (in 20%). In particular, the breakpoints tended to aggregate at 1p11, 1p36, 2p11-24, 6q, 9q, 11q, 13q11-14, 14q11, 14q32, and in the pericentric region of chromosome 17. The most common numerical change was loss of chromosome 10, detected in 32% of SS cases. In our studies of three SS cases, sister chromatid exchange frequencies were significantly higher in comparison to the normal control. Cell cycle kinetics analysis revealed that the cell cycle time in the malignant cells was significantly longer than in lymphocytes of normal individuals.

  3. A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy.

    PubMed

    Milillo, Annamaria; La Carpia, Francesca; Costanzi, Stefano; D'Urbano, Vanessa; Martini, Maurizio; Lanuti, Paola; Vischini, Gisella; Larocca, Luigi M; Marchisio, Marco; Miscia, Sebastiano; Amoroso, Antonio; Gurrieri, Fiorella; Sangiorgi, Eugenio

    2015-12-01

    IgA nephropathy (IgAN) represents the most common primary glomerulonephritis worldwide with a prevalence of 25-50% among patients with primary glomerulopathies. In ~5-10% of the patients the disease segregates with an autosomal dominant (AD) pattern. Association studies identified loci on chromosomes 1q32, 6p21, 8p23, 17p13, 22q12, whereas classical linkage studies on AD families identified loci on chromosomes 2q36, 4q26-31, 6q22, 17q12-22. We have studied a large Sicilian family where IgAN segregates with an AD transmission. To identify the causal gene, the exomes of two affected and one unaffected individual have been sequenced. From the bioinformatics analysis a p.(Arg119Trp) variant in the SPRY2 gene was identified as the probable disease-causing mutation. Moreover, functional characterization of this variant showed that it is responsible for the inhibition of the MAPK/ERK1/2 pathway. The same effect was observed in two sporadic IgAN patients carriers of wild-type SPRY2, suggesting that downregulation of the MAPK/ERK1/2 pathway represents a common mechanism leading to IgAN.

  4. Copy Number Alterations in Prostate Tumors and Disease Aggressiveness

    PubMed Central

    Cheng, Iona; Levin, Albert M.; Tai, Yu Chuan; Plummer, Sarah; Chen, Gary K.; Neslund-Dudas, Christine; Casey, Graham; Rybicki, Benjamin A.; Witte, John S.

    2011-01-01

    Detecting genomic alterations that result in more aggressive prostate cancer may improve clinical treatment and our understanding of the biology underlying this common but complex disease. To this end, we undertook a genome-wide copy number alterations (CNAs) study of clinicopathological characteristics of 62 prostate tumors using the Illumina 1M SNP array. The highest overall frequencies of CNAs were on chromosomes 8q (gains), 8p (loss and copy-neutral) and 6q (copy-loss). Combined loss and copy-neutral events were associated with increasing disease grade (p=0.03), stage (p=0.01), and diagnostic PSA (p=0.01). Further evaluation of CNAs using gene ontology identified pathways involved with disease aggressiveness. The ‘regulation of apoptosis’ pathway was associated with stage of disease (p=0.004), while the ‘reproductive cellular process’ pathway was associated with diagnostic PSA (p=0.00038). Specific genes within these pathways exhibited strong associations with clinical characteristics; for example, in the apoptosis pathway BNIP3L was associated with increasing prostate tumor stage (p=0.007). These findings confirm known regions of CNAs in prostate cancer, and localize additional regions and possible genes (e.g., BNIP3L, WWOX, and GATM) that may help clarify the genetic basis of prostate cancer aggressiveness. PMID:21965145

  5. Prospects of molybdenum and rhenium octahedral cluster complexes as X-ray contrast agents.

    PubMed

    Krasilnikova, Anna A; Shestopalov, Michael A; Brylev, Konstantin A; Kirilova, Irina A; Khripko, Olga P; Zubareva, Kristina E; Khripko, Yuri I; Podorognaya, Valentina T; Shestopalova, Lidiya V; Fedorov, Vladimir E; Mironov, Yuri V

    2015-03-01

    Investigation of new X-ray contrast media for radiography is an important field of science since discovering of X-rays in 1895. Despite the wide diversity of available X-ray contrast media the toxicity, especially nephrotoxicity, is still a big problem to be solved. The octahedral metal-cluster complexes of the general formula [{M6Q8}L6] can be considered as quite promising candidates for the role of new radiocontrast media due to the high local concentration of heavy elements, high tuning ability of ligand environment and low toxicity. To exemplify this, the X-ray computed tomography experiments for the first time were carried out on some octahedral cluster complexes of molybdenum and rhenium. Based on the obtained data it was proposed to investigate the toxicological proprieties of cluster complex Na2H8[{Re6Se8}(P(CH2CH2CONH2)(CH2CH2COO)2)6]. Observed low cytotoxic and acute toxic effects along with rapid renal excretion of the cluster complex evidence its perspective as an X-ray contrast media for radiography.

  6. Association between Genetic Subgroups of Pancreatic Ductal Adenocarcinoma Defined by High Density 500 K SNP-Arrays and Tumor Histopathology

    PubMed Central

    Gutiérrez, María Laura; Muñoz-Bellvis, Luís; Abad, María del Mar; Bengoechea, Oscar; González-González, María

    2011-01-01

    The specific genes and genetic pathways associated with pancreatic ductal adenocarcinoma are still largely unknown partially due to the low resolution of the techniques applied so far to their study. Here we used high-density 500 K single nucleotide polymorphism (SNP)-arrays to define those chromosomal regions which most commonly harbour copy number (CN) alterations and loss of heterozygozity (LOH) in a series of 20 PDAC tumors and we correlated the corresponding genetic profiles with the most relevant clinical and histopathological features of the disease. Overall our results showed that primary PDAC frequently display (>70%) extensive gains of chromosomes 1q, 7q, 8q and 20q, together with losses of chromosomes 1p, 9p, 12q, 17p and 18q, such chromosomal regions harboring multiple cancer- and PDAC-associated genes. Interestingly, these alterations clustered into two distinct genetic profiles characterized by gains of the 2q14.2, 3q22.1, 5q32, 10q26.13, 10q26.3, 11q13.1, 11q13.3, 11q13.4, 16q24.1, 16q24.3, 22q13.1, 22q13.31 and 22q13.32 chromosomal regions (group 1; n = 9) versus gains at 1q21.1 and losses of the 1p36.11, 6q25.2, 9p22.1, 9p24.3, 17p13.3 and Xp22.33 chromosomal regions (group 2; n = 11). From the clinical and histopathological point of view, group 1 cases were associated with smaller and well/moderately-differentiated grade I/II PDAC tumors, whereas and group 2 PDAC displayed a larger size and they mainly consisted of poorly-differentiated grade III carcinomas. These findings confirm the cytogenetic complexity and heterogenity of PDAC and provide evidence for the association between tumor cytogenetics and its histopathological features. In addition, we also show that the altered regions identified harbor multiple cancer associate genes that deserve further investigation to determine their relevance in the pathogenesis of PDAC. PMID:21811587

  7. Preoperative whole body disinfection--a controlled clinical study.

    PubMed

    Hayek, L J; Emerson, J M

    1988-04-01

    Preoperative whole body washing with chlorhexidine scrub was compared with soap for its effect on prevention of wound infection in clean surgery. Two thousand and fifteen patients were studied using chlorhexidine scrub, placebo or plain soap. The overall infection rate in the control and placebo groups was 12.8% (p less than 0.05) and 11.7% as opposed to 9% (p less than 0.05) in the treated group. Three per cent fewer infections were found in treated 'clean surgery' patients, and the incidence of Staphylococcus aureus infections was reduced from 6% (bar soap) to 3% (chlorhexidine). The saving in bed occupancy from prevention of infection is a significant cost-saving.

  8. Altered cortical microarchitecture in patients with monoclonal gammopathy of undetermined significance

    PubMed Central

    Farr, Joshua N.; Zhang, Wei; Kumar, Shaji K.; Jacques, Richard M.; Ng, Alvin C.; McCready, Louise K.; Rajkumar, S. Vincent

    2014-01-01

    Patients with monoclonal gammopathy of undetermined significance (MGUS) are at increased fracture risk, and we have previously shown that MGUS patients have altered trabecular bone microarchitecture compared with controls. However, there are no data on whether the porosity of cortical bone, which may play a greater role in bone strength and the occurrence of fractures, is increased in MGUS. Thus, we studied cortical porosity and bone strength (apparent modulus) using high-resolution peripheral quantitative computed tomography imaging of the distal radius in 50 MGUS patients and 100 age-, gender-, and body mass index–matched controls. Compared with controls, MGUS patients had both significantly higher cortical porosity (+16.8%; P < .05) and lower apparent modulus (–8.9%; P < .05). Despite their larger radial bone size, MGUS patients have significantly increased cortical bone porosity and reduced bone strength relative to controls. This increased cortical porosity may explain the increased fracture risk seen in MGUS patients. PMID:24227822

  9. DDE at low dietary levels kills captive American kestrels

    USGS Publications Warehouse

    Porter, Ron; Wiemeyer, Stanley N.

    1972-01-01

    Two of 14 male American kestrels died after 14 and 16 months on a diet containing 2.8 p.p.m., wet weight, p, p'-DDE. The brains of the two birds contained DDE residues of 213 and 301 p.p.m. compared with 14.9 p.p.m. (range, 4.47-26.6 p.p.m.) (wet weights) for 11 of the adult males which were sacrificed after 12 to 16 months on dosage. Autopsies of the two birds compared with autopsies of the sacrificed birds, revealed other characteristics typical of DDE poisoning. Neither bird, when autopsied, displayed characteristics which would suggest that they died of causes other than DDE poisoning.

  10. Familial complex autosomal translocations involving chromosomes 7, 8, and 9 exhibiting male and female transmission with segregation and recombination.

    PubMed Central

    Walker, S; Howard, P J; Hunter, D

    1985-01-01

    A family showing a complex translocation between chromosomes 7, 8, and 9 with breakpoints at 7q21, 7q33, 8p23, and 9p23 is described. The proband had been referred because of repeated spontaneous abortions. This is only the second family to be ascertained in this way. Twenty-three other cases of complex translocations are briefly reviewed, eight of which were de novo in origin and 15 familial. All but one of the familial cases showed maternal transmission only. The present family shows both maternal and paternal transmission and is thought to be the first exhibiting recombination from a male carrier. The origin and transmission of the complex translocation is followed through three generations. Images PMID:3841161

  11. Malignant and benign ganglioglioma: A pathological and molecular study1

    PubMed Central

    Pandita, Ajay; Balasubramaniam, Anandh; Perrin, Richard; Shannon, Patrick; Guha, Abhijit

    2007-01-01

    Gangliogliomas are generally benign tumors, composed of transformed neuronal and glial elements, with rare malignant progression of the glial component. The current study of a rare case of a woman harboring a ganglioglioma with areas of malignant transformation addresses two fundamental questions: (1) Are the ganglioglioma and its malignant component clonal in origin? (2) What are the genetic alterations associated with the initiation and subsequent malignant progression of ganglioglioma? By using the human androgen receptor gene (HUMARA) assay, we found the ganglioglioma and the malignant component to be clonal in origin, suggestive of initial transformation of a single neuroglial precursor cell with subsequent malignant progression. Conventional and array comparative genomic hybridization (approximately 2.5-Mb resolution) analyses found chromosomal losses to be predominant in the benign areas of the ganglioglioma, with gains more prevalent in the malignant component. Regions of chromosomal loss, postulated to harbor genes involved in the initiation of ganglioglioma, included 1p35-36, 2p16-15, 3q13.1-13.3, 3q24-25.3, 6p21.3-21.2, 6q24-25.2, 9p12, Xp11.3-11.22, and Xq22.1-22.3. Direct analysis demonstrated loss of p19 expression and p53 mutation in the malignant areas, highly suggestive of these alterations being involved in the malignant progression of the ganglioglioma. Additional chromosomal alterations specific to the malignancy involved gains on 1p35-34.2, 2q24.1-32.3, 3q13.1-13.3, 6q13-16.2, 7q11.2-31.3, 8q21.1-23, 11q12-31, and 12q13.2-21.3. This molecular-pathological study has provided insight into the pathogenesis of gangliogliomas and associated rare malignant progression. Deciphering the specific genes residing in these chromosomal regions may further our understanding of not only these rare tumors but also the more common gliomas. PMID:17259542

  12. Benefits of maltodextrin intake 2 hours before cholecystectomy by laparotomy in respiratory function and functional capacity: a prospective randomized clinical trial

    PubMed Central

    Zani, Fabiana Vieira Breijão; Aguilar-Nascimento, José Eduardo; Nascimento, Diana Borges Dock; da Silva, Ageo Mário Cândido; Caporossi, Fernanda Stephan; Caporossi, Cervantes

    2015-01-01

    ABSTRACT Objective: To evaluate the change in respiratory function and functional capacity according to the type of preoperative fasting. Methods: Randomized prospective clinical trial, with 92 female patients undergoing cholecystectomy by laparotomy with conventional or 2 hours shortened fasting. The variables measured were the peak expiratory flow, forced expiratory volume in the first second, forced vital capacity, dominant handgrip strength, and non-dominant handgrip strength. Evaluations were performed 2 hours before induction of anesthesia and 24 hours after the operation. Results: The two groups were similar in preoperative evaluations regarding demographic and clinical characteristics, as well as for all variables. However, postoperatively the group with shortened fasting had higher values than the group with conventional fasting for lung function tests peak expiratory flow (128.7±62.5 versus 115.7±59.9; p=0.040), forced expiratory volume in the first second (1.5±0.6 versus 1.2±0.5; p=0.040), forced vital capacity (2.3±1.1 versus 1.8±0.9; p=0.021), and for muscle function tests dominant handgrip strength (24.9±6.8 versus 18.4±7.7; p=0.001) and non-dominant handgrip strength (22.9±6.3 versus 17.0±7.8; p=0.0002). In the intragroup evaluation, there was a decrease in preoperative compared with postoperative values, except for dominant handgrip strength (25.2±6.7 versus 24.9±6.8; p=0.692), in the shortened fasting group. Conclusion: Abbreviation of preoperative fasting time with ingestion of maltodextrin solution is beneficial to pulmonary function and preserves dominant handgrip strength. PMID:26154547

  13. The Empirical Comparison of Coordinate Transformation Models and Distortion Modeling Methods Based on a Case Study of Croatia

    NASA Astrophysics Data System (ADS)

    Grgic, M.; Varga, M.; Bašić, T.

    2015-12-01

    Several coordinate transformation models enable performing of the coordinate transformations between the historical astro-geodetic datums, which were utilized before the GNSS (Global Navigation Satellite System) technologies were developed, and datums related to the International Terrestrial Reference System (ITRS), which today are most often used to determine the position. The decision on the most appropriate coordinate transformation model is influenced by many factors, such as: required accuracy, available computational resources, possibility of the model application regarding the size and shape of the territory, coordinate distortion that very often exist in historical astro-geodetic datums, etc. This study is based on the geodetic data of the Republic of Croatia in both, historical and ITRS-related datum. It investigates different transformation models, including conformal Molodensky 3 parameters (p) and 5p (standard and abridged) transformation models, 7p transformation models (Bursa-Wolf and Molodensky-Badekas model), Affine transformation models (8p, 9p, 12p), and Multiple Regression Equation approach. Besides, it investigates the 7p, 8p, 9p, and 12p transformation models extended with distortion modeling, and the grid based only transformation model (NTv2 model). Furthermore, several distortion modeling methods were used to produce various models of distortion shifts in different resolutions. Thereafter, their performance and the performance of the transformation models was evaluated using summary statistics derived from the remained positional residuals that were computed for the independent control spatial data set. Lastly, the most appropriate method(s) of distortion modeling and most appropriate coordinate transformation model(s) were defined regarding the required accuracy for the Croatian case.

  14. Abundance and diversity of plasmid-associated genes among clinical isolates of Enterococcus faecalis.

    PubMed

    Wardal, Ewa; Gawryszewska, Iwona; Hryniewicz, Waleria; Sadowy, Ewa

    2013-11-01

    Enterococcus faecalis, a normal compound of the human intestinal microbiome, plays an important role in hospital-acquired infections. Plasmids make a significant contribution to the acquisition of the novel traits such as antimicrobial resistance and virulence by this pathogen. The study investigated the plasmid content and the diversity of plasmid-associated genes in a group of 152 hospital isolates of E. faecalis. The majority of plasmids visualized by pulsed-field gel electrophoresis of S1 nuclease-digested DNA fell into the range of 50-100 kb. PCR-based screening allowed detection of genes of the rep1(pIP501), rep2(pRE25), rep4(pMBB1), rep6(pS86), rep7(pT181), rep8(pAM373), rep9(pAD1/pTEF2/pCF10), rep10(pIM13) and rep13(pC194) families in 29 different combinations. The par and ω-ε-ζ plasmid stabilization systems were ubiquitous (45 isolates, 29.6% and 88 isolates, 57.9%, respectively), while the axe-txe system was not found. The asa1 gene homologues encoding aggregation substance characteristic for the pAD1 and related group of pheromone-responsive plasmids were present in 106 isolates. A variety of sequence variants, including novel ones, of genes associated with pheromone-responsive plasmids, such as rep8(pAM373), rep9(pAD1/pTEF2/pCF10), par, and asa1 were observed. In conclusion, there is a big and only partially characterized pool of diverse plasmids in clinical E. faecalis.

  15. Effect of a two-year national quality improvement program on surgical checklist implementation.

    PubMed

    Mascherek, Anna C; Bezzola, Paula; Gehring, Katrin; Schwappach, David L B

    2016-01-01

    Use of the surgical checklist in Switzerland is still incomplete and unsatisfactory. A national improvement program was developed and conducted in Switzerland to implement and improve the use of the surgical safety checklists. The aims of the implementation program were to implement comprehensive and correct checklist use in participating hospitals in every patient and in every surgical procedure; and to improve safety climate and teamwork as important cultural context variables. 10 hospitals were selected for participation in the implementation program. A questionnaire assessing use, knowledge, and attitudes towards the checklist and the Safety Climate Survey were conducted at two measurement occasions each in October/November 2013 and January/February 2015. Significant increases emerged for frequency of checklist use (F(1,1001)=340.9, p<0.001), satisfaction (F(1,1232)=25.6, p<0.001), and knowledge(F(1,1294)=184.5, p<0.001). While significant differences in norms (F(1,1284)=17.9, p<0.001) and intentions (F(1,1284)=7.8, p<0.01) were observed, this was not the case for attitudes (F(1,1283)=.8, n.s.) and acceptance (F(1,1284)=0.1, n.s.). Significant differences for safety climate and teamwork emerged in the present study (F(1,3555)=11.8, p<0.001 and F(1,3554)=24.6, p<0.001, respectively). However, although statistical significance was reached, effects are very small and practical relevance is thus questionable. The results of the present study suggest that the quality improvement program conducted by the Swiss Patient Safety Foundation in 10 hospitals led to successful checklist implementation. The strongest effects were seen in aspects concerning behaviour and knowledge specifically related to checklist use. Less impact was achieved on general cultural variables safety climate and teamwork. However, as a trend was observable, these variables may simply need more time in order to change substantially. PMID:27566268

  16. A Prospective Study of Quality of Life in Patients Undergoing Pelvic Exenteration: Interim Results

    PubMed Central

    Rezk, Youssef A; Hurley, Karen E; Carter, Jeanne; Dao, Fanny; Bochner, Bernard H; Aubey, Janice J; Caceres, Aileen; Einstein, M. Heather; Abu-Rustum, Nadeem R; Barakat, Richard R; Chi, Dennis S; Maker, Vicky

    2014-01-01

    Purpose Little prospective data exist on quality of life (QOL) after pelvic exenteration (PE). This ongoing study prospectively examines the QOL-changes following this radical procedure using a comprehensive battery of psychological instruments. Methods Since 2005, enrolled patients were interviewed (EORTC QLQ-C30, EORTC QLQ-CR38, EORTC QLQ-BLM30, BFI, BPI-SF, IADL, CES-D, IES-R) preoperatively and at 3, 6, and 12 months after PE for physical/psychological symptoms. Data were examined using repeated measure ANOVA. Results Sixteen women (3 anterior, 1 posterior, and 12 total PE’s), with more than one year of follow up, completed all scheduled interviews. Median age was 58 years (28–76). Overall QOL (F=6.3, p<0.02), ability to perform instrumental daily activities (F=6.8, p<0.02), body image (F=11.9, p<0.00) and sexual function (F=8.0, p<0.01) all declined at 3 months but were near baseline by 12 months after PE. Although, overall, physical function followed a similar trend (F=14.8, p<0.00), it did not return to baseline. At the 12-month interview, patients reported increased gastrointestinal symptoms (F=8.9, p<0.01) but significantly less stress-related ideation (F=6.1, p<0.03) compared to baseline. Pain levels did not change significantly during the study period (F=0.4, p<0.74). Conclusions Although patients report lingering gastrointestinal symptoms and some persistent decline in physical function after PE, most adjust well, returning to almost baseline functioning within a year. Providers can counsel patients that many, though not all, symptoms in the first 3 months following exenteration are likely to improve as they adapt to their changed health status. These preliminary results await confirmation of a larger analysis. PMID:23063761

  17. Specific Secondary Genetic Alterations in Mantle Cell Lymphoma Provide Prognostic Information Independent of the Gene Expression–Based Proliferation Signature

    PubMed Central

    Salaverria, Itziar; Zettl, Andreas; Beà, Sílvia; Moreno, Victor; Valls, Joan; Hartmann, Elena; Ott, German; Wright, George; Lopez-Guillermo, Armando; Chan, Wing C.; Weisenburger, Dennis D.; Gascoyne, Randy D.; Grogan, Thomas M.; Delabie, Jan; Jaffe, Elaine S.; Montserrat, Emili; Muller-Hermelink, Hans-Konrad; Staudt, Louis M.; Rosenwald, Andreas

    2008-01-01

    Purpose To compare the genetic relationship between cyclin D1–positive and cyclin D1–negative mantle cell lymphomas (MCLs) and to determine whether specific genetic alterations may add prognostic information to survival prediction based on the proliferation signature of MCLs. Patients and Methods Seventy-one cyclin D1–positive and six cyclin D1–negative MCLs previously characterized by gene expression profiling were examined by comparative genomic hybridization (CGH). Results Cyclin D1–negative MCLs were genetically characterized by gains of 3q, 8q, and 15q, and losses of 1p, 8p23-pter, 9p21-pter, 11q21–q23, and 13q that were also the most common alterations in conventional MCLs. Parallel analysis of CGH aberrations and locus-specific gene expression profiles in cyclin D1–positive patients showed that chromosomal imbalances had a substantial impact on the expression levels of the genes located in the altered regions. The analysis of prognostic factors revealed that the proliferation signature, the number of chromosomal aberrations, gains of 3q, and losses of 8p, 9p, and 9q predicted survival of MCL patients. A multivariate analysis showed that the gene expression-based proliferation signature was the strongest predictor for shorter survival. However, 3q gains and 9q losses provided prognostic information that was independent of the proliferative activity. Conclusion Cyclin D1–positive and –negative MCLs share the same secondary genetic aberrations, supporting the concept that they correspond to the same genetic entity. The integration of genetic information on chromosome 3q and 9q alterations into a proliferation signature-based model may improve the ability to predict survival in patients with MCL. PMID:17296973

  18. Effects of 1 versus 2 games a week on physical and subjective scores of subelite soccer players.

    PubMed

    Rollo, Ian; Impellizzeri, Franco M; Zago, Matteo; Iaia, F Marcello

    2014-05-01

    The physical-performance profiles of subelite male footballers were monitored during 6 wk of a competitive season. The same squad of players played either 1 (1G, n = 15) or 2 (2G, n = 15) competitive matches per week. On weeks 0, 3, and 6, 48 h postmatch, players completed countermovement jump (CMJ), 10- and 20-m sprints, the Yo-Yo Intermittent Recovery Test (YYIRT), and the Recovery-Stress Questionnaire. Both groups undertook 2 weekly training sessions. The 2G showed after 6 wk lower YYIRT (-11% to 3%, 90% CI -15.8% to -6.8%; P < .001) and CMJ performances (-18.7%, -21.6 to -15.9%; P = .007) and higher 10-m (4.4%, 1.8-6.9%; P = .007) and 20-m sprints values (4.7%, 2.9% to 6.4%; P < .001). No differences were found at 3 wk (.06 < P < .99). No changes over time (.169 < P < .611) and no differences time × group interactions (.370 < P < .550) were found for stress, recovery, and the Stress Recovery Index. In conclusion players' ability to sprint, jump, and perform repeated intense exercise was impaired when playing 2 competitive matches a week over 6 wk.

  19. Homozygous losses detected by array comparative genomic hybridization in multiplex urothelial carcinomas of the bladder.

    PubMed

    Beothe, Tamas; Zubakov, Dmitry; Kovacs, Gyula

    2015-09-01

    Urothelial carcinomas (UCs) may present at first as a solitary or multifocal neoplasm. We applied high resolution array comparative genomic hybridization to 24 solitary and 32 multiplex UCs and used the hidden Markov model algorithm to identify the copy number changes at the probe level. Copy number losses and homozygous deletions at the chromosome 9p region affecting the CDKN2A and MTAP genes were the most frequent alterations in both groups of tumors. We have delineated two new tumor suppressor gene regions at chromosome 9p that harbor the PTPRD and BNC2 genes. Copy number losses at chromosomal regions 2q, 8p, and 18p occurred preferentially in solitary UCs, whereas multiplex UCs displayed loss of large chromosomal regions at 9q, 10q, 11q, 18q, and 21q. Homozygous deletions harboring loci of cell adhesion genes such as claudins, desmocollins, and desmogleins were seen exclusively in multiplex UCs. Amplifications occurred only in invasive G3 UCs irrespective of staging. Our study suggests that solitary and multiplex UCs may have divergent genetic pathways. The biallelic inactivation of cellular adhesion genes by homozygous deletions in multiplex UCs may explain the frequent intravesical spreading of tumor cells. .

  20. Allelic imbalances and microdeletions affecting the PTPRD gene in cutaneous squamous cell carcinomas detected using single nucleotide polymorphism microarray analysis.

    PubMed

    Purdie, Karin J; Lambert, Sally R; Teh, Muy-Teck; Chaplin, Tracy; Molloy, Gael; Raghavan, Manoj; Kelsell, David P; Leigh, Irene M; Harwood, Catherine A; Proby, Charlotte M; Young, Bryan D

    2007-07-01

    Cutaneous squamous cell carcinomas (SCC) are the second most commonly diagnosed cancers in fair-skinned people; yet the genetic mechanisms involved in SCC tumorigenesis remain poorly understood. We have used single nucleotide polymorphism (SNP) microarray analysis to examine genome-wide allelic imbalance in 16 primary and 2 lymph node metastatic SCC using paired non-tumour samples to counteract normal copy number variation. The most common genetic change was loss of heterozygosity (LOH) on 9p, observed in 13 of 16 primary SCC. Other recurrent events included LOH on 3p (9 tumors), 2q, 8p, and 13 (each in 8 SCC) and allelic gain on 3q and 8q (each in 6 tumors). Copy number-neutral LOH was observed in a proportion of samples, implying that somatic recombination had led to acquired uniparental disomy, an event not previously demonstrated in SCC. As well as recurrent patterns of gross chromosomal changes, SNP microarray analysis revealed, in 2 primary SCC, a homozygous microdeletion on 9p23 within the protein tyrosine phosphatase receptor type D (PTPRD) locus, an emerging frequent target of homozygous deletion in lung cancer and neuroblastoma. A third sample was heterozygously deleted within this locus and PTPRD expression was aberrant. Two of the 3 primary SCC with PTPRD deletion had demonstrated metastatic potential. Our data identify PTPRD as a candidate tumor suppressor gene in cutaneous SCC with a possible association with metastasis.

  1. Genomic alterations in Warthin tumors of the parotid gland.

    PubMed

    Wemmert, Silke; Willnecker, Vivienne; Sauter, Birgit; Schuh, Sebastian; Brunner, Christian; Bohle, Rainer Maria; Urbschat, Steffi; Schick, Bernhard

    2014-04-01

    Despite the fact that Warthin tumors are the second most common type of benign salivary gland tumors, information regarding genetic alterations is extremely limited, and the tumorigenesis of these tumors has not been elucidated. The present results of the largest series of 30 tumors analyzed by comparative genomic hybridization (CGH) to date confirmed previous genetic findings and identified significant new candidate regions. The most commonly observed alterations were deletions of the short arm of chromosome 8, followed by deletions on 9p. Further representative changes were deletions on 16p and 22q with the minimal overlapping region at 16p12p13.1 and 22q12.1q12.3. Moreover, we indicated two different patterns of chromosomal aberrations. One group harbors deletions on 8p partly apparent with deletions on 9q, 11q 15q, 16p and 22. The second group shows gains on 22, partly apparent with gains on 1p and 20q and deletions on 9p. This leads to the assumption that Warthin tumors, in particular those with a high number of alterations, can be divided into two different genetic groups based on the pattern of numerical chromosomal aberrations. Further studies should address whether these subgroups also reflect a different clinical presentation.

  2. Outcome of liver transplantation in patients with diabetes mellitus: a case-control study.

    PubMed

    John, P R; Thuluvath, P J

    2001-11-01

    The influence of preexisting diabetes mellitus (DM) on outcome after orthotopic liver transplantation (OLT) has not been well defined. The objective of our study was to compare the morbidity and mortality after OLT in 57 patients with preexisting DM (3 type I, 54 type II) with 114 age-, sex-, and race-matched patients without DM (case controls). The demographics were similar in both groups. Pretransplantation serum creatinine was significantly higher in the diabetic group compared with case controls. The incidence of the following complications was significantly higher in the diabetic group after OLT: cardiovascular (61.4% vs. 21.9%, P <.001), major (54.4% vs. 29.8%, P =.002) and minor infections (29.8% vs. 7.9%, P <.0001), renal (59.7% vs. 20.2%, P <.001), ophthalmologic (10.5% vs. 0.9%, P =.01), respiratory (24.6% vs. 7.0%, P =.001), neurologic (31.6% vs. 7.0%, P <.001), hematologic (19.3% vss 2.6%, P =.001), musculoskeletal (24.6% vs. 5.3%, P =.001), and malignancy (22.8% vs. 10.5%, P =.03). The duration of hospital stay, cost of hospitalization, retransplantation, and overall graft survival were similar. Acute rejection was seen in 50.9% of diabetics compared with 25.4% in controls (P =.0009). One-year (87% vs. 77%) and 2-year (81.6% vs. 70.1%) patient survival was similar, but 5-year survival was lower in the DM group (34.4% vs. 67.7%, P =.002). In conclusion, preexisting diabetes is associated with a significant post-OLT morbidity and mortality, and our observations suggest that patients with DM warrant more rigorous pre- and post-OLT evaluation. PMID:11679959

  3. Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico.

    PubMed

    Cahua-Pablo, José Ángel; Cruz, Miguel; Méndez-Palacios, Abigail; Antúnez-Ortiz, Diana Lizzete; Vences-Velázquez, Amalia; del Carmen Alarcón-Romero, Luz; Parra, Esteban Juan; Tello-Flores, Vianet Argelia; Leyva-Vázquez, Marco Antonio; Valladares-Salgado, Adán; Pérez-Macedonio, Claudia Paola; Flores-Alfaro, Eugenia

    2015-09-08

    Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.

  4. Impact of maternal HIV infection on obstetrical and early neonatal outcome.

    PubMed

    Braddick, M R; Kreiss, J K; Embree, J B; Datta, P; Ndinya-Achola, J O; Pamba, H; Maitha, G; Roberts, P L; Quinn, T C; Holmes, K K

    1990-10-01

    In a case-control study of 177 HIV-seropositive and 326 seronegative women and their newborns in Nairobi, Kenya, maternal HIV infection at term was independently associated with travel to other African countries [odds ratio (OR) 4.9, P less than 0.0001], history of a blood transfusion since 1980 (OR 3.5, P = 0.01), history of more than one sexual partner in the previous 5 years (OR 1.8, P = 0.02) and unmarried status (OR 1.8, P = 0.02). Neonates of HIV-positive and HIV-negative women differed little with respect to occurrence of congenital malformations, stillbirths, in-hospital mortality, sex, APGAR score, or gestational age. However, the mean birth weight of singleton neonates of HIV-positive women was significantly lower than that of controls (3090 versus 3220 g, P = 0.005), and birth weight was less than 2500 g in 9% of cases and 3% of controls (OR 3.0, P = 0.007). Among neonates of HIV-seropositive women, birth weight was less than 2500 g in 17% if mothers were symptomatic and 6% if mothers were asymptomatic (OR 3.4, P = 0.08). PMID:2261113

  5. Effect of thrombin and bradykinin on endothelial cell mechanical properties monitored through membrane deformation.

    PubMed

    Cuerrier, Charles M; Gagner, Andréanne; Lebel, Réjean; Gobeil, Fernand; Grandbois, Michel

    2009-01-01

    The endothelium is closely implicated in the control and maintenance of the vascular homeostasis. The functions of endothelial cells are highly regulated by several agonists of G protein-coupled receptors (GPCR), which can mediate signals involved in morphological remodeling. Here, we evaluated the mechanical properties of human umbilical vein endothelial cells (HUVEC) in responses to two physiological agonists namely thrombin and bradykinin. We used the atomic force microscopy (AFM) technique to study changes in cell membrane stiffness and interaction between the actin cytoskeleton and the cell membrane. HUVEC stimulated with thrombin (10 nM) and bradykinin (1 microM) showed a temporal increase in their membrane stiffness from 5.0 +/- 0.1 kPa (control) to 8.2 +/- 0.4 kPa (thrombin) and 7.3 +/- 0.5 kPa (bradykinin) and in membrane tethers elongation forces from 43.9 +/- 0.9 pN (control) to 49.5 +/- 0.8 pN (thrombin) and 53.1 +/- 0.8 pN (bradykinin). These results were consistent with the reorganization of the actin cytoskeleton observed in fluorescence microscopy. This study demonstrates that these agonists induce important modifications of the cell membrane properties that can be directly linked to the reorganization and the interaction of the actin cytoskeleton near the apical side of the membrane. These changes in the mechanical properties of endothelial cells provide relevant informations in the biological and pathophysiological behaviors of endothelial cells. PMID:19415761

  6. Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico

    PubMed Central

    Cahua-Pablo, José Ángel; Cruz, Miguel; Méndez-Palacios, Abigail; Antúnez-Ortiz, Diana Lizzete; Vences-Velázquez, Amalia; del Carmen Alarcón-Romero, Luz; Parra, Esteban Juan; Tello-Flores, Vianet Argelia; Leyva-Vázquez, Marco Antonio; Valladares-Salgado, Adán; Pérez-Macedonio, Claudia Paola; Flores-Alfaro, Eugenia

    2015-01-01

    Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features. PMID:26370976

  7. Live Birth and Cumulative Live Birth Rates in Expected Poor Ovarian Responders Defined by the Bologna Criteria Following IVF/ICSI Treatment

    PubMed Central

    Chai, Joyce; Lee, Vivian Chi-Yan; Yeung, Tracy Wing-Yee; Li, Raymond Wun-Hang; Ho, Pak-Chung; Ng, Ernest Hung-Yu

    2015-01-01

    Objective To determine the live birth and cumulative live birth rates of expected poor ovarian responders according to the Bologna criteria and to compare their outcomes with those of expected normal responders Design Retrospective analysis Setting University infertility clinic Patients A total of 1,152 subfertile women undergoing their first in vitro fertilization (IVF) cycle Interventions Women were classified into 4 groups according to the Bologna criteria for comparison Main Outcome Measure(s) Live birth and cumulative live birth rates Results Women with expected poor response (POR) had the lowest live birth rate than the other 3 groups (23.8%, p = 0.031). Cumulative live birth rates were significantly lower in those with expected POR than those with expected normal ovarian response (NOR) (35.8% vs 62.8%, p<0.0001). In the subgroup analysis, the cumulative live birth rates in expected PORs were significantly lower in those who had ≤3 oocytes retrieved (18.6% for ≤3 oocytes vs 44.0% for >3 oocytes, p = 0.006) whereas the live birth rates in fresh cycle did not differ (17.8% vs 30.9%, p = 0.108). Conclusion Women who were expected POR according to the Bologna criteria had lower live birth and cumulative live birth than expected NOR but they still can achieve reasonable treatment outcomes and IVF treatment should not be precluded. PMID:25748478

  8. Airway inflammation in Japanese COPD patients compared with smoking and nonsmoking controls

    PubMed Central

    Ishikawa, Nobuhisa; Hattori, Noboru; Kohno, Nobuoki; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Johnson, Malcolm

    2015-01-01

    Purpose To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD) by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups. Patients and methods This was the first study of its type in Japanese COPD patients. It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients. All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures. Results The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies. Increasing levels of neutrophils, interleukin 8 (IL-8), surfactant protein D (SP-D), and Krebs von den Lungen 6 (KL-6) in sputum and clara cell 16 (CC-16), high-sensitivity C-reactive protein (hs-CRP), and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants. In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; P<0.001), neutrophils and MMP-9 (P<0.001), macrophages and KL-6 (P<0.01), total cell count and IL-8 (P<0.05), neutrophils and IL-8 (P<0.05), and macrophages and MMP-9 (P<0.05). Significant correlations were also observed between some inflammatory cells in sputum and biomarkers in serum, with the most significant between serum CC-16 and both total cell count (P<0.005) and neutrophils (P<0.005) in sputum. Conclusion These results provide evidence for the first time that COPD in Japanese patients is a multicomponent disease, involving both airway and systemic inflammation, in addition to airway obstruction. Therefore, intervention with anti-inflammatory therapy may provide additional

  9. Structure-Function Analysis of 2-Keto-3-Deoxy-D-Glycero-D-Galacto-Nononate-9-Phosphate Phosphatase Defines Specificity Elements in Type C0 had Family Members

    SciTech Connect

    Lu, Z.; Wang, L; Dunaway-Mariano, D; Allen, K

    2009-01-01

    The phosphotransferases of the haloalkanoate dehalogenase superfamily (HADSF) act upon a wide range of metabolites in all eukaryotes and prokaryotes and thus constitute a significant force in cell function. The challenge posed for biochemical function assignment of HADSF members is the identification of the structural determinants that target a specific metabolite. The '8KDOP' subfamily of the HADSF is defined by the known structure and catalytic activity of 2-keto-3-deoxy-8-phospho-d-manno-octulosonic acid (KDO-8-P) phosphatase. Homologues of this enzyme have been uniformly annotated as KDO-8-P phosphatase. One such gene, BT1713, from the Bacteroides thetaiotaomicron genome was recently found to encode the enzyme 2-keto-3-deoxy-d-glycero-d-galacto-9-phosphonononic acid (KDN-9-P) phosphatase in the biosynthetic pathway of the 9-carbon ?-keto acid, 2-keto-3-deoxy-d-glycero-d-galactonononic acid (KDN). To find the structural elements that provide substrate-specific interactions and to allow identification of genomic sequence markers, the x-ray crystal structures of BT1713 liganded to the cofactor Mg2+and complexed with tungstate or Formula/Neu5Ac were determined to 1.1, 1.85, and 1.63 A resolution, respectively. The structures define the active site to be at the subunit interface and, as confirmed by steady-state kinetics and site-directed mutagenesis, reveal Arg-64*, Lys-67*, and Glu-56 to be the key residues involved in sugar binding that are essential for BT1713 catalytic function. Bioinformatic analyses of the differentially conserved residues between BT1713 and KDO-8-P phosphatase homologues guided by the knowledge of the structure-based specificity determinants define Glu-56 and Lys-67* to be the key residues that can be used in future annotations.

  10. Cellular mechanisms mediating rat renal microvascular constriction by angiotensin II.

    PubMed Central

    Takenaka, T; Suzuki, H; Fujiwara, K; Kanno, Y; Ohno, Y; Hayashi, K; Nagahama, T; Saruta, T

    1997-01-01

    To assess cellular mechanisms mediating afferent (AA) and efferent arteriolar (EA) constriction by angiotensin II (AngII), experiments were performed using isolated perfused hydronephrotic kidneys. In the first series of studies, AngII (0.3 nM) constricted AAs and EAs by 29+/-3 (n = 8, P < 0.01) and 27+/-3% (n = 8, P < 0.01), respectively. Subsequent addition of nifedipine restored AA but not EA diameter. Manganese (8 mM) reversed EA constriction by 65+/-9% (P < 0.01). In the second group, the addition of N-ethylmaleimide (10 microM), a Gi/Go protein antagonist, abolished AngII- induced EA (n = 6) but not AA constriction (n = 6). In the third series of experiments, treatment with 2-nitro-4-carboxyphenyl-N, N-diphenyl-carbamate (200 microM), a phospholipase C inhibitor, blocked both AA and EA constriction by AngII (n = 6 for each). In the fourth group, thapsigargin (1 microM) prevented AngII-induced AA constriction (n = 8) and attenuated EA constriction (8+/-2% decrease in EA diameter at 0.3 nM AngII, n = 8, P < 0.05). Subsequent addition of manganese (8 mM) reversed EA constriction. Our data provide evidence that in AAs, AngII stimulates phospholipase C with subsequent calcium mobilization that is required to activate voltage-dependent calcium channels. Our results suggest that AngII constricts EAs by activating phospholipase C via the Gi protein family, thereby eliciting both calcium mobilization and calcium entry. PMID:9329977

  11. A new dietary strategy for long-term treatment of the metabolic syndrome is compared with the American Heart Association (AHA) guidelines: the MEtabolic Syndrome REduction in NAvarra (RESMENA) project.

    PubMed

    de la Iglesia, Rocio; Lopez-Legarrea, Patricia; Abete, Itziar; Bondia-Pons, Isabel; Navas-Carretero, Santiago; Forga, Luis; Martinez, J Alfredo; Zulet, M Angeles

    2014-02-01

    The long-term effects of dietary strategies designed to combat the metabolic syndrome (MetS) remain unknown. The present study evaluated the effectiveness of a new dietary strategy based on macronutrient distribution, antioxidant capacity and meal frequency (MEtabolic Syndrome REduction in NAvarra (RESMENA) diet) for the treatment of the MetS when compared with the American Heart Association guidelines, used as Control. Subjects with the MetS (fifty-two men and forty-one women, age 49 (se 1) years, BMI 36·11 (se 0·5) kg/m²) were randomly assigned to one of two dietary groups. After a 2-month nutritional-learning intervention period, during which a nutritional assessment was made for the participants every 15 d, a 4-month self-control period began. No significant differences were found between the groups concerning anthropometry, but only the RESMENA group exhibited a significant decrease in body weight ( - 1·7%; P= 0·018), BMI ( - 1·7%; P= 0·019), waist circumference ( - 1·8%; P= 0·021), waist:hip ratio ( - 1·4%; P= 0·035) and android fat mass ( - 6·9%; P= 0·008). The RESMENA group exhibited a significant decrease in alanine aminotransferase and aspartate aminotransferase (AST) concentrations ( - 26·8%; P= 0·008 and - 14·0%; P= 0·018, respectively), while the Control group exhibited a significant increase in glucose (7·9%; P= 0·011), AST (11·3%; P= 0·045) and uric acid (9·0%; P< 0·001) concentrations. LDL-cholesterol (LDL-C) concentrations were increased (Control group: 34·4%; P< 0·001 and RESMENA group: 33·8%; P< 0·001), but interestingly so were the LDL-C:apoB ratio (Control group: 28·7%; P< 0·001, RESMENA group: 17·1%; P= 0·009) and HDL-cholesterol concentrations (Control group: 21·1%; P< 0·001, RESMENA group: 8·7; P= 0·001). Fibre was the dietary component that most contributed to the improvement of anthropometry, while body-weight loss explained changes in some biochemical markers. In conclusion, the RESMENA diet is a good

  12. Prognostic Implications of Diabetes in Patients With Left-Sided Endocarditis

    PubMed Central

    Olmos, Carmen; Vilacosta, Isidre; Pozo, Eduardo; Fernández, Cristina; Sarriá, Cristina; López, Javier; Ferrera, Carlos; Maroto, Luis; González, Isabel; Vivas, David; Palacios, Julián; San Román, José Alberto

    2014-01-01

    Abstract Patients with diabetes mellitus (DM) have a higher incidence of infections, and those with bacteremia are more prone to develop sepsis and infective endocarditis (IE). Nevertheless, data concerning the impact of DM on the prognosis of patients with IE are limited and sometimes contradictory. We examined the impact of DM on the inhospital outcome of left-sided IE in a large cohort of patients. We studied 594 consecutive episodes of left-sided IE diagnosed at 3 tertiary care centers. They were divided into 2 groups: episodes in patients with DM (n = 114) and episodes in patients without DM (n = 480). We retrospectively analyzed the influence of DM therapy on patient outcome. Compared to patients without DM, patients with DM were older (67 ± 10 vs. 60 ± 15 yr; p < 0.001), less frequently male (53.5% vs. 67.9%; p = 0.004), and more commonly had chronic renal failure (23.9% vs. 6.9%; p < 0.001) and chronic obstructive pulmonary disease (14.6% vs. 7.8%; p = 0.019). Enterococcus (14.9% vs. 7.4%; p = 0.011) and Streptococcus bovis (8.8% vs. 3.8%; p = 0.024) were isolated more frequently. In the univariable analysis, septic shock (29.2% vs. 16.4%; p = 0.005) and mortality (43.5% vs. 30.0%; p = 0.008) were more common among patients with DM than in those without. Considering the different treatments for DM, septic shock (33.3%; p = 0.011) and death (50.8%; p = 0.012) were more frequent in patients receiving oral medication to treat diabetes than in patients with the other treatment modalities. However, multivariable analysis showed that DM had an independent association with development of septic shock (OR 2.282; 95% CI 1.186–4.393), but it was not a predictor of inhospital mortality. Staphylococci were the most frequently involved microorganisms in all patients; however, Enterococcus and Streptococcus bovis were more frequently isolated from individuals with DM and left-sided IE, whereas viridans group streptococci were more commonly isolated from those with

  13. Molecular mechanisms of pancreatic carcinogenesis.

    PubMed

    Furukawa, Toru; Sunamura, Makoto; Horii, Akira

    2006-01-01

    Pancreatic ductal adenocarcinoma is one of the most fatal malignancies. Intensive investigation of molecular pathogenesis might lead to identifying useful molecules for diagnosis and treatment of the disease. Pancreatic ductal adenocarcinoma harbors complicated aberrations of alleles including losses of 1p, 6q, 9p, 12q, 17p, 18q, and 21q, and gains of 8q and 20q. Pancreatic cancer is usually initiated by mutation of KRAS and aberrant expression of SHH. Overexpression of AURKA mapping on 20q13.2 may significantly enhance overt tumorigenesity. Aberrations of tumor suppressor genes synergistically accelerate progression of the carcinogenic pathway through pancreatic intraepithelial neoplasia (PanIN) to invasive ductal adenocarcinoma. Abrogation of CDKN2A occurs in low-grade/early PanIN, whereas aberrations of TP53 and SMAD4 occur in high-grade/late PanIN. SMAD4 may play suppressive roles in tumorigenesis by inhibition of angiogenesis. Loss of 18q precedes SMAD4 inactivation, and restoration of chromosome 18 in pancreatic cancer cells results in tumor suppressive phenotypes regardless of SMAD4 status, indicating the possible existence of a tumor suppressor gene(s) other than SMAD4 on 18q. DUSP6 at 12q21-q22 is frequently abrogated by loss of expression in invasive ductal adenocarcinomas despite fairly preserved expression in PanIN, which suggests that DUSP6 works as a tumor suppressor in pancreatic carcinogenesis. Restoration of chromosome 12 also suppresses growths of pancreatic cancer cells despite the recovery of expression of DUSP6; the existence of yet another tumor suppressor gene on 12q is strongly suggested. Understanding the molecular mechanisms of pancreatic carcinogenesis will likely provide novel clues for preventing, detecting, and ultimately curing this life-threatening disease. PMID:16367914

  14. No prognostic effect of additional chromosomal abnormalities in children with acute lymphoblastic leukemia and 11q23 abnormalities.

    PubMed

    Moorman, A V; Raimondi, S C; Pui, C H; Baruchel, A; Biondi, A; Carroll, A J; Forestier, E; Gaynon, P S; Harbott, J; Harms, D O; Heerema, N; Pieters, R; Schrappe, M; Silverman, L B; Vilmer, E; Harrison, C J

    2005-04-01

    This study characterized the additional chromosomal abnormalities (ACA) associated with 11q23 rearrangements in 450 infants and children with acute lymphoblastic leukemia (ALL) and examined the impact of these ACA on survival. Overall, 213 (47%) cases had ACA but the incidence varied according to patient age and 11q23 subgroup. Infants and patients with t(4;11)(q21;q23) had the lowest incidence of ACA (50/182 (27%) and 57/216 (26%) respectively), whereas patients with del(11)(q23) had the highest incidence (66/93 (71%)). Del(11)(q23) abnormalities were heterogeneous and occasionally secondary to t(9;22)(q34;q11.2). Thus, patients with del(11)(q23) comprised a separate biological entity, which was clearly distinct from those with an 11q23 translocation. The most frequent specific ACA were trisomy X (n = 38), abnormal 12p (n = 32), abnormal 9p (n = 28) and del(6q) (n = 19). The presence of ACA did not change the 5 year event-free survival estimates among children (56% (95% Cl 46-65%) vs 62% (54-69%)) or infants (22% (15-29%) vs 18% (9-29%)), nor when the different 11q23 subgroups were analyzed separately. This study has conclusively demonstrated that there is no prognostic effect of secondary chromosomal changes in association with 11q23 abnormalities in childhood ALL. However, characterization of these ACA is important to determine their potential role in initiation of MLL driven leukemogenesis.

  15. DNA copy number changes in Schistosoma-associated and non-Schistosoma-associated bladder cancer.

    PubMed

    El-Rifai, W; Kamel, D; Larramendy, M L; Shoman, S; Gad, Y; Baithun, S; El-Awady, M; Eissa, S; Khaled, H; Soloneski, S; Sheaff, M; Knuutila, S

    2000-03-01

    DNA copy number changes were investigated in 69 samples of schistosoma-associated (SA) and non-schistosoma-associated (NSA) squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC) of the bladder by comparative genomic hybridization (CGH). DNA copy number changes were detected in 47 tumors. SA tumors had more changes than NSA tumors (mean, 7 vs. 4), whereas the number of changes in SCC and TCC tumors was similar. SA tumors displayed more gains than losses (1.7:1), whereas NSA tumors showed an equal number of gains and losses. Changes that were observed at similar frequencies in SCC and TCC, irrespective of the schistosomal status, included gains and high-level amplifications at 1q, 8q, and 20q and losses in 9p and 13q. These changes may be involved in a common pathway for bladder tumor development and progression independent of schistosomal status or histological subtype. Losses in 3p and gains at 5p were seen only in SCC (P < 0.01) and losses in 5q were more frequent in SA-SCC than in other tumors (P < 0.05). However, changes that were more frequent in TCC than those in SCC included gains at 17q (P < 0.01) and losses in 4q (P < 0.05) and 6q (P < 0.01). Gains and high-level amplifications at 5p were seen only in SA-SCC (P < 0. 01), whereas gains and high-level amplifications with minimal common overlapping regions at 11q13 were more frequently seen both in SA-SCC and SA-TCC tumors (P < 0.01). In addition to the above mentioned alterations, several other changes were also seen at lower frequencies. The variations in the DNA copy number changes observed in TCC, SCC, SA, and NSA bladder carcinomas suggest that these tumors have different genetic pathways. PMID:10702404

  16. Fluorescence In Situ Hybridization for Melanoma Diagnosis: A Review and a Reappraisal.

    PubMed

    Ferrara, Gerardo; De Vanna, Anna Chiara

    2016-04-01

    Although conventional histopathological examination is the undisputable mainstay for the diagnosis of melanocytic skin neoplasms, fluorescence in situ hybridization (FISH) has the potential to provide important information to morphologically challenging cases. The standard melanoma FISH test targeting RREB1 (6p25), MYB (6q23), CCND1 (11q13), and centromere 6 is an effective compromise between cost, technical complexity, and sensitivity. The authors use the standard FISH-positivity as a tie-breaker for challenging melanocytic neoplasms mainly in a non-Spitzoid morphologic context because the currently available test leaves several unresolved issues: namely, a relatively low diagnostic accuracy in morphologically ambiguous melanocytic neoplasms; a relatively low sensitivity and specificity in Spitzoid neoplasms; and the occurrence of false positives due to tetraploidy in Spitz nevi and in nevi with an atypical epithelioid component. Under investigation is currently a new melanoma probe cocktail targeting RREB1 (6p25), C-MYC (8q24), CDKN2A (9p21), and CCND1 (11q13). However, CDKN2A is a significant parameter only if lost in homozygosis, and this complicates the interpretation of the results. Furthermore, the new melanoma probe cocktail has been tested on cases of atypical Spitzoid proliferations with fatal outcomes which at present are too few to allow definite conclusions. The authors propose the implementation of a FISH algorithm (standard 4-probe test followed by either C-MYC or CDKN2A/centromere 9) to assist the histopathological diagnosis and minimize the technical problems. Nevertheless, because the diagnostic accuracy of the FISH technique is far from being absolute, the overall clinicopathological context must always guide the decision-making process about the management of morphobiologically ambiguous melanocytic proliferations. PMID:26999337

  17. Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection

    PubMed Central

    Lambros, Maryou B; Campion-Flora, Adriana; Rodrigues, Daniel Nava; Gauthier, Arnaud; Cabral, Cecilia; Pawar, Vidya; Mackay, Alan; A’Hern, Roger; Marchiò, Caterina; Palacios, Jose; Natrajan, Rachael; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    The mechanisms underlying the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast are yet to be fully elucidated. Several hypotheses have been put forward to explain the progression from DCIS to IDC, including the selection of a subpopulation of cancer cells with specific genetic aberrations, the acquisition of new genetic aberrations or non-genetic mechanisms mediated by the tumour microenvironment. To determine whether synchronously diagnosed ipsilateral DCIS and IDCs have modal populations with distinct repertoires of gene copy number aberrations and mutations in common oncogenes, matched frozen samples of DCIS and IDCs were retrieved from 13 patients and subjected to microarray-based comparative genomic hybridisation (aCGH), and Sequenom MassARRAY (Oncocarta v1.0 panel). Fluorescence in situ hybridisation and Sanger sequencing were employed to validate the aCGH and Sequenom findings, respectively. Although the genomic profiles of matched DCIS and IDCs were similar, in three of 13 matched pairs amplification of distinct loci (i.e. 1q41, 2q24.2, 6q22.31, 7q11.21, 8q21.2 and 9p13.3) was either restricted to, or more prevalent in, the modal population of cancer cells of one of the components. Sequenom MassARRAY identified PIK3CA mutations restricted to the DCIS component in two cases, and in a third case, the frequency of the PIK3CA mutant allele reduced from 49% in the DCIS to 25% in the IDC component. Despite the genomic similarities between synchronous DCIS and IDC, our data provide strong circumstantial evidence to suggest that in some cases the progression from DCIS to IDC is driven by the selection of non-modal clones that harbour a specific repertoire of genetic aberrations. PMID:22252965

  18. Genomic Landscape of Primary Mediastinal B-Cell Lymphoma Cell Lines.

    PubMed

    Dai, Haiping; Ehrentraut, Stefan; Nagel, Stefan; Eberth, Sonja; Pommerenke, Claudia; Dirks, Wilhelm G; Geffers, Robert; Kalavalapalli, Srilaxmi; Kaufmann, Maren; Meyer, Corrina; Faehnrich, Silke; Chen, Suning; Drexler, Hans G; MacLeod, Roderick A F

    2015-01-01

    Primary mediastinal B-Cell lymphoma (PMBL) is a recently defined entity comprising ~2-10% non-Hodgkin lymphomas (NHL). Unlike most NHL subtypes, PMBL lacks recurrent gene rearrangements to serve as biomarkers or betray target genes. While druggable, late chemotherapeutic complications warrant the search for new targets and models. Well characterized tumor cell lines provide unlimited material to serve as preclinical resources for verifiable analyses directed at the discovery of new biomarkers and pathological targets using high throughput microarray technologies. The same cells may then be used to seek intelligent therapies directed at clinically validated targets. Four cell lines have emerged as potential PMBL models: FARAGE, KARPAS-1106P, MEDB-1 and U-2940. Transcriptionally, PMBL cell lines cluster near c(lassical)-HL and B-NHL examples showing they are related but separate entities. Here we document genomic alterations therein, by cytogenetics and high density oligonucleotide/SNP microarrays and parse their impact by integrated global expression profiling. PMBL cell lines were distinguished by moderate chromosome rearrangement levels undercutting cHL, while lacking oncogene translocations seen in B-NHL. In total 61 deletions were shared by two or more cell lines, together with 12 amplifications (≥4x) and 72 homozygous regions. Integrated genomic and transcriptional profiling showed deletions to be the most important class of chromosome rearrangement. Lesions were mapped to several loci associated with PMBL, e.g. 2p15 (REL/COMMD1), 9p24 (JAK2, CD274), 16p13 (SOCS1, LITAF, CIITA); plus new or tenuously associated loci: 2p16 (MSH6), 6q23 (TNFAIP3), 9p22 (CDKN2A/B), 20p12 (PTPN1). Discrete homozygous regions sometimes substituted focal deletions accompanied by gene silencing implying a role for epigenetic or mutational inactivation. Genomic amplifications increasing gene expression or gene-activating rearrangements were respectively rare or absent. Our findings

  19. Genomic Landscape of Primary Mediastinal B-Cell Lymphoma Cell Lines.

    PubMed

    Dai, Haiping; Ehrentraut, Stefan; Nagel, Stefan; Eberth, Sonja; Pommerenke, Claudia; Dirks, Wilhelm G; Geffers, Robert; Kalavalapalli, Srilaxmi; Kaufmann, Maren; Meyer, Corrina; Faehnrich, Silke; Chen, Suning; Drexler, Hans G; MacLeod, Roderick A F

    2015-01-01

    Primary mediastinal B-Cell lymphoma (PMBL) is a recently defined entity comprising ~2-10% non-Hodgkin lymphomas (NHL). Unlike most NHL subtypes, PMBL lacks recurrent gene rearrangements to serve as biomarkers or betray target genes. While druggable, late chemotherapeutic complications warrant the search for new targets and models. Well characterized tumor cell lines provide unlimited material to serve as preclinical resources for verifiable analyses directed at the discovery of new biomarkers and pathological targets using high throughput microarray technologies. The same cells may then be used to seek intelligent therapies directed at clinically validated targets. Four cell lines have emerged as potential PMBL models: FARAGE, KARPAS-1106P, MEDB-1 and U-2940. Transcriptionally, PMBL cell lines cluster near c(lassical)-HL and B-NHL examples showing they are related but separate entities. Here we document genomic alterations therein, by cytogenetics and high density oligonucleotide/SNP microarrays and parse their impact by integrated global expression profiling. PMBL cell lines were distinguished by moderate chromosome rearrangement levels undercutting cHL, while lacking oncogene translocations seen in B-NHL. In total 61 deletions were shared by two or more cell lines, together with 12 amplifications (≥4x) and 72 homozygous regions. Integrated genomic and transcriptional profiling showed deletions to be the most important class of chromosome rearrangement. Lesions were mapped to several loci associated with PMBL, e.g. 2p15 (REL/COMMD1), 9p24 (JAK2, CD274), 16p13 (SOCS1, LITAF, CIITA); plus new or tenuously associated loci: 2p16 (MSH6), 6q23 (TNFAIP3), 9p22 (CDKN2A/B), 20p12 (PTPN1). Discrete homozygous regions sometimes substituted focal deletions accompanied by gene silencing implying a role for epigenetic or mutational inactivation. Genomic amplifications increasing gene expression or gene-activating rearrangements were respectively rare or absent. Our findings

  20. Genomic Landscape of Primary Mediastinal B-Cell Lymphoma Cell Lines

    PubMed Central

    Nagel, Stefan; Eberth, Sonja; Pommerenke, Claudia; Dirks, Wilhelm G.; Geffers, Robert; Kalavalapalli, Srilaxmi; Kaufmann, Maren; Meyer, Corrina; Faehnrich, Silke; Chen, Suning; Drexler, Hans G.; MacLeod, Roderick A. F.

    2015-01-01

    Primary mediastinal B-Cell lymphoma (PMBL) is a recently defined entity comprising ~2–10% non-Hodgkin lymphomas (NHL). Unlike most NHL subtypes, PMBL lacks recurrent gene rearrangements to serve as biomarkers or betray target genes. While druggable, late chemotherapeutic complications warrant the search for new targets and models. Well characterized tumor cell lines provide unlimited material to serve as preclinical resources for verifiable analyses directed at the discovery of new biomarkers and pathological targets using high throughput microarray technologies. The same cells may then be used to seek intelligent therapies directed at clinically validated targets. Four cell lines have emerged as potential PMBL models: FARAGE, KARPAS-1106P, MEDB-1 and U-2940. Transcriptionally, PMBL cell lines cluster near c(lassical)-HL and B-NHL examples showing they are related but separate entities. Here we document genomic alterations therein, by cytogenetics and high density oligonucleotide/SNP microarrays and parse their impact by integrated global expression profiling. PMBL cell lines were distinguished by moderate chromosome rearrangement levels undercutting cHL, while lacking oncogene translocations seen in B-NHL. In total 61 deletions were shared by two or more cell lines, together with 12 amplifications (≥4x) and 72 homozygous regions. Integrated genomic and transcriptional profiling showed deletions to be the most important class of chromosome rearrangement. Lesions were mapped to several loci associated with PMBL, e.g. 2p15 (REL/COMMD1), 9p24 (JAK2, CD274), 16p13 (SOCS1, LITAF, CIITA); plus new or tenuously associated loci: 2p16 (MSH6), 6q23 (TNFAIP3), 9p22 (CDKN2A/B), 20p12 (PTPN1). Discrete homozygous regions sometimes substituted focal deletions accompanied by gene silencing implying a role for epigenetic or mutational inactivation. Genomic amplifications increasing gene expression or gene-activating rearrangements were respectively rare or absent. Our findings

  1. Prenatal and postnatal bisphenol A exposure and asthma development among inner-city children

    PubMed Central

    Donohue, Kathleen M.; Miller, Rachel L.; Perzanowski, Matthew S.; Just, Allan C.; Hoepner, Lori A.; Arunajadai, Srikesh; Canfield, Stephen; Resnick, David; Calafat, Antonia M.; Perera, Frederica P.; Whyatt, Robin M.

    2013-01-01

    Background Bisphenol A (BPA) is used widely to manufacture food container linings. Mouse models suggest exposure to BPA might increase allergic inflammation. Objectives We hypothesized that BPA exposure, as assessed based on urinary BPA concentrations, would be associated with increased odds of wheeze and asthma and increased fraction of exhaled nitric oxide (FENO) values in children. Methods The Columbia Center for Children’s Environmental Health recruited pregnant women for a prospective birth cohort study (n = 568). Mothers during the third trimester and children at ages 3, 5, and 7 years provided spot urine samples. Total urinary BPA concentrations were measured by using online solid-phase extraction, high-performance liquid chromatography, isotope-dilution tandem mass spectrometry. Wheeze in the last 12 months was measured by using questionnaires at ages 5, 6, and 7 years. Asthma was determined by a physician once between ages 5 and 12 years. FENO values were measured at ages 7 to 11 years. Results Prenatal urinary BPA concentrations were associated inversely with wheeze at age 5 years (odds ratio [OR], 0.7; 95% CI, 0.5–0.9; P = .02). Urinary BPA concentrations at age 3 years were associated positively with wheeze at ages 5 years (OR, 1.4; 95% CI, 1.1–1.8; P = .02) and 6 years (OR, 1.4; 95% CI, 1.0–1.9; P = .03). BPA concentrations at age 7 years were associated with wheeze at age 7 years (OR, 1.4; 95% CI, 1.0–1.9; P = .04) and FENO values (β = 0.1; 95% CI, 0.02–0.2; P = .02). BPA concentrations at ages 3, 5, and 7 years were associated with asthma (OR, 1.5 [95% CI, 1.1–2.0], P = .005; OR, 1.4 [95% CI, 1.0–1.9], P = .03; and OR, 1.5 [95% CI, 1.0–2.1], P = .04, respectively). Conclusions This is the first report of an association between postnatal urinary BPA concentrations and asthma in children. PMID:23452902

  2. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia.

    PubMed

    Lewis, Cathryn M; Levinson, Douglas F; Wise, Lesley H; DeLisi, Lynn E; Straub, Richard E; Hovatta, Iiris; Williams, Nigel M; Schwab, Sibylle G; Pulver, Ann E; Faraone, Stephen V; Brzustowicz, Linda M; Kaufmann, Charles A; Garver, David L; Gurling, Hugh M D; Lindholm, Eva; Coon, Hilary; Moises, Hans W; Byerley, William; Shaw, Sarah H; Mesen, Andrea; Sherrington, Robin; O'Neill, F Anthony; Walsh, Dermot; Kendler, Kenneth S; Ekelund, Jesper; Paunio, Tiina; Lönnqvist, Jouko; Peltonen, Leena; O'Donovan, Michael C; Owen, Michael J; Wildenauer, Dieter B; Maier, Wolfgang; Nestadt, Gerald; Blouin, Jean-Louis; Antonarakis, Stylianos E; Mowry, Bryan J; Silverman, Jeremy M; Crowe, Raymond R; Cloninger, C Robert; Tsuang, Ming T; Malaspina, Dolores; Harkavy-Friedman, Jill M; Svrakic, Dragan M; Bassett, Anne S; Holcomb, Jennifer; Kalsi, Gursharan; McQuillin, Andrew; Brynjolfson, Jon; Sigmundsson, Thordur; Petursson, Hannes; Jazin, Elena; Zoëga, Tomas; Helgason, Tomas

    2003-07-01

    Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.

  3. Prenatally diagnosed de novo complex chromosome rearrangements: Two new cases and review of the literature

    SciTech Connect

    Ruiz, C.; Grubs, R.E.; Jewett, T.

    1994-09-01

    Complex chromosome rearrangements (CCR) are rare structural rearrangements involving at least three chromosomes with three or more breakpoints. Although there have been numerous reports of individuals with CCR, most have been ascertained through the presence of multiple congenital anomalies, recurrent pregnancy loss, or infertility. Few cases have been ascertained prenatally. We present two new cases of prenatally ascertained CCR. In the first case, an amniocentesis revealed an apparently balanced de novo rearrangement in which chromosomes 5, 6 and 11 were involved in a three-way translocation: 46,XY,t(6;5)(5;11)(q23;p14.3;q15;p13). The pregnancy was unevenful. Recently, at the age of 9 months, a physical and developmental evaluation were normal but, height, weight, and head circumference were below the 5th percentile. In the second case an amniocentesis revealed an unbalanced de novo rearrangement involving separate translocations and an interstitial deletion: 46,XY,del(6)(q25.3q27),t(3;8)(p13;q21.3),t(6;18)(p11.2;q11.2). A meconium plug was present at birth and at 6 months of age surgery for Hirschsprung`s disease was required. Currently, at 10 months of age, the patient has hypotonia and developmental delay. The paucity of information regarding prenatally diagnosed CCR poses a problem in counseling families. Of the four prenatally diagnosed balanced de novo CCR cases, three had abnormal outcomes. In a review of the literature, approximately 70% of the postnatally ascertained balanced de novo CCR cases were associated with congenital anomalies, growth retardation and/or mental retardation. More information regarding the outcome of prenatally ascertained balanced de novo CCR is required for accurate risk assessment.

  4. Cytogenetic and Molecular Findings in Children with Acute Lymphoblastic Leukemia: Experience of a Single Institution in Argentina

    PubMed Central

    Coccé, Mariela C.; Alonso, Cristina N.; Rossi, Jorge G.; Bernasconi, Andrea R.; Rampazzi, Maria A.; Felice, Maria S.; Rubio, Patricia L.; Eandi Eberle, Silvia; Medina, Adriana; Gallego, Marta S.

    2015-01-01

    The purpose of the current study was to evaluate the cytogenetic findings in 1,057 children with acute lymphoblastic leukemia (ALL) referred to the cytogenetics laboratory at the Hospital de Pediatría Dr. Juan P. Garrahan, between 1991 and 2014. Chromosomal abnormalities were evaluated by G-banding and FISH. Since December 2002, RT-PCR determinations were systematically carried out for BCR-ABL1, KMT2A-AFF1, ETV6-RUNX1, and TCF3-PBX1 rearrangements in children, adding KMT2A-MLLT3 and KMT2A-MLLT1 in infants. The percentage of abnormalities detected by cytogenetics was 70.1%. Four novel abnormalities, t(2;8)(p11.2;p22), inv(4)(p16q25), t(1;7)(q25;q32), and t(5;6)(q21;q21), were found in this cohort. We compared cytogenetic and RT-PCR results for BCR-ABL1, KMT2A-AFF1 and TCF3-PBX1 rearrangements in 497 children evaluated by both methods. The results were highly concordant (p < 0.7), and interestingly, FISH was relevant to confirm G-banding findings that were discordant with RT-PCR studies. This study showed the importance of performing G-banding, FISH and RT-PCR simultaneously to improve the detection of chromosomal abnormalities considering their important value in the diagnosis and prognosis of childhood ALL patients. Finally, to the best of our knowledge, this is the first series of cytogenetic findings in children with ALL reported in Argentina. PMID:26648836

  5. Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: Schizophrenia

    PubMed Central

    Lewis, Cathryn M.; Levinson, Douglas F.; Wise, Lesley H.; DeLisi, Lynn E.; Straub, Richard E.; Hovatta, Iiris; Williams, Nigel M.; Schwab, Sibylle G.; Pulver, Ann E.; Faraone, Stephen V.; Brzustowicz, Linda M.; Kaufmann, Charles A.; Garver, David L.; Gurling, Hugh M. D.; Lindholm, Eva; Coon, Hilary; Moises, Hans W.; Byerley, William; Shaw, Sarah H.; Mesen, Andrea; Sherrington, Robin; O’Neill, F. Anthony; Walsh, Dermot; Kendler, Kenneth S.; Ekelund, Jesper; Paunio, Tiina; Lönnqvist, Jouko; Peltonen, Leena; O’Donovan, Michael C.; Owen, Michael J.; Wildenauer, Dieter B.; Maier, Wolfgang; Nestadt, Gerald; Blouin, Jean-Louis; Antonarakis, Stylianos E.; Mowry, Bryan J.; Silverman, Jeremy M.; Crowe, Raymond R.; Cloninger, C. Robert; Tsuang, Ming T.; Malaspina, Dolores; Harkavy-Friedman, Jill M.; Svrakic, Dragan M.; Bassett, Anne S.; Holcomb, Jennifer; Kalsi, Gursharan; McQuillin, Andrew; Brynjolfson, Jon; Sigmundsson, Thordur; Petursson, Hannes; Jazin, Elena; Zoëga, Tomas; Helgason, Tomas

    2003-01-01

    Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (Ravg) and then weighted for sample size (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}\\sqrt{N[affected cases]}\\end{equation*}\\end{document}). A permutation test was used to compute the probability of observing, by chance, each bin’s average rank (PAvgRnk) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (Pord). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both PAvgRnk and Pord<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with Pord<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations. PMID:12802786

  6. Interstitial deletion of the long arm of chromosome 6 associated with unusual limb anomalies: report of two new patients and review of the literature.

    PubMed

    Pandya, A; Braverman, N; Pyeritz, R E; Ying, K L; Kline, A D; Falk, R E

    1995-10-23

    We report on unusual manifestations in 2 unrelated children with interstitial deletion of 6q, with nearly identical breakpoints of 6q16.2q23.1 and 6q16.3q22.3. Major findings include growth retardation, profound developmental delay, microcephaly, facial anomalies, sparse hair, congenital heart defects, and striking hand malformations. Discordant anomalies were duodenal atresia and hypoplastic genitalia in 1 child. Split-hand defect, polydactyly, gastrointestinal anomalies, and ectodermal dysplasia have not been described previously in children with 6q deletion. The presence of hand malformations in 2 children with similar deletion breakpoints strongly suggests that this is a candidate region for one or more genes involved in limb development. Comparison of the clinical findings of other patients with 6q2 deletion suggests a recognizable phenotype.

  7. Prevalence, correlates and clinical usefulness of antibodies to RNA polymerase III in systemic sclerosis: a cross-sectional analysis of data from an Australian cohort

    PubMed Central

    2011-01-01

    Introduction The prevalence of antibodies to RNA polymerase III (anti-RNAP) differs among systemic sclerosis (SSc) cohorts worldwide. Previously reported associations of anti-RNAP include diffuse cutaneous disease, tendon friction rubs and renal crisis, with recent reports suggesting a close temporal association between malignancy and SSc disease onset among patients with anti-RNAP. Methods Patients with SSc were tested for the presence of anti-RNAP at recruitment into the Australian Scleroderma Cohort Study. We used univariate and multivariable methods to identify and quantify clinical and laboratory correlates of anti-RNAP in SSc. Diagnostic testing procedures were used to determine the usefulness of these antibodies in estimating the likelihood of clinically important outcomes. Results There were 451 patients with mean ± standard deviation age and disease duration at recruitment of 58.1 ± 12.4 and 11.6 ± 10.0 years, respectively; 151 (33.5%) patients were recruited within 5 years of diagnosis of SSc. Overall, 69 (15.3%) patients had anti-RNAP. Univariate associations of anti-RNAP were diffuse disease (75.4% vs. 20.9%, P < 0.0001), joint contractures (73.9% vs. 30.1%, P < 0.0001), greater highest-recorded modified Rodnan skin score (20.6 ± 12.4 vs. 10.1 ± 7.9, P < 0.0001), synovitis (31.9% vs. 19.9%, P = 0.03), myositis (2.9% vs. 0.5%, P = 0.05), systemic hypertension (59.4% vs. 39.7%, P = 0.002), renal crisis (24.6% vs. 1.8%, P < 0.0001) and malignancy diagnosed within 5 years of onset of SSc skin disease (13.3% vs. 3.9%, P = 0.01). In multiple regression analysis, after adjustment for other covariates, anti-RNAP were independently associated with renal crisis (odds ratio (OR) 3.8, 95% confidence interval (CI) 1.2 to 11.5, P = 0.02; positive predictive value (PPV) 24.6%, negative predictive value (NPV) 98.2%), diffuse disease (OR 6.4, 95% CI 2.9 to 13.8, P < 0.0001; PPV 75.4%, NPV 20.9%), joint contractures (OR 2.5, 95% CI 1.2 to 5.3, P = 0.02; PPV 73

  8. [Effects of Short-time Conservation Tillage Managements on Greenhouse Gases Emissions from Soybean-Winter Wheat Rotation System].

    PubMed

    Xie, Yan; Chen, Xi; Hu, Zheng-hua; Chen, Shu-tao; Zhang, Han; Ling, Hui; Shen, Shuang-he

    2016-04-15

    Field experiments including one soybean growing season and one winter-wheat growing season were adopted. The experimental field was divided into four equal-area sub-blocks which differed from each other only in tillage managements, which were conventional tillage (T) , no-tillage with no straw cover ( NT) , conventional tillage with straw cover (TS) , and no-tillage with straw cover (NTS). CO₂ and N₂O emission fluxes from soil-crop system were measured by static chamber-gas chromatograph technique. The results showed that: compared with T, in the soybean growing season, NTS significantly increased the cumulative amount of CO₂ (CAC) from soil-soybean system by 27.9% (P = 0.045) during the flowering-podding stage, while NT significantly declined CAC by 28.9% (P = 0.043) during the grain filling-maturity stage. Compared with T, NT significantly declined the cumulative amount of N₂O (CAN) by 28.3% (P = 0.042) during the grain filling-maturity stage. In the winter-wheat growing season, compared with T, TS and NT significantly declined CAC by 24.3% (P = 0.032) and 36.0% (P = 0.041) during the elongation-booting stage, and also declined CAC by 26.8% (P = 0.027) and 33.1% (P = 0.038) during the maturity stage. During the turning-green stage, compared with T treatment, NT, NTS, and TS treatments had no significant effect on CAN, while NTS significant declined CAN by 42.0% (P = 0.035) compared with NT. Our findings suggested that conservation tillage managements had a more significant impact on CO₂ emission than 20 emission from soil-crop system.

  9. Survival analysis of patients with advanced-stage nasopharyngeal carcinoma according to the Epstein-Barr virus status

    PubMed Central

    Peng, Hao; Chen, Lei; Zhang, Yuan; Guo, Rui; Li, Wen-Fei; Mao, Yan-Ping; Tan, Ling-Long; Sun, Ying; Zhang, Fan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Ma, Jun

    2016-01-01

    Purpose The main aim of this study is to analyze the prognostic differences in nasopharyngeal carcinoma (NPC) patients who are positive and negative for Epstein-Barr virus (EBV). Results Of the 1106 patients, 248 (22.4%) had undetectable pre-treatment plasma EBV DNA levels. The total distant metastasis rate for EBV-negative group vs. EBV-positive group were 3.6% (9/248) vs. 15.0% (128/858) (P < 0.001). The estimated 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) for EBV-negative group vs. EBV-positive group were 88.9% vs. 76.9% (P < 0.001), 93.6% vs. 85.9% (P = 0.001), 96.7% vs. 84.8% (P < 0.001) and 94.1% vs. 90.0% (P = 0.1), respectively. Multivariate analysis revealed that the EBV status was an independent prognostic factor for DFS (HR, 1.813; 95% CI, 1.219-2.695; P = 0.003), OS (HR, 1.828; 95% CI, 1.075-3.107; P = 0.026) and DMFS (HR, 3.678; 95% CI, 1.859-7.277; P <0.001), and overall stage still remained the most important prognostic factor in patients with stage III-IVB NPC. Methods and Materials Data on 1106 patients with non-metastatic, histologically proven advanced-stage (III-IVB) NPC who underwent intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Patient survival between different EBV status groups were compared. Conclusions EBV status was an independent prognostic factor for patients with stage III–IVB NPC. Neoadjuvant chemotherapy (NCT) plus concurrent chemoradiotherapy (CCRT) should be better treatment regimen for EBV-positive patients since distant metastasis was the main failure pattern, and CCRT may be enough for EBV-negative patients. PMID:27008701

  10. Genetic susceptibility to anthracycline-related congestive heart failure in survivors of haematopoietic cell transplantation.

    PubMed

    Armenian, Saro H; Ding, Yan; Mills, George; Sun, Canlan; Venkataraman, Kalyanasundaram; Wong, Florence Lennie; Neuhausen, Susan L; Senitzer, David; Wang, Shirong; Forman, Stephen J; Bhatia, Smita

    2013-10-01

    Haematopoietic cell transplantation (HCT) survivors are at increased risk for developing congestive heart failure (CHF), primarily due to pre-HCT exposure to anthracyclines. We examined the association between the development of CHF after HCT and polymorphisms in 16 candidate genes involved in anthracycline metabolism, iron homeostasis, anti-oxidant defence, and myocardial remodelling. A nested case-control study design was used. Cases (post-HCT CHF) were identified from 2950 patients who underwent HCT between 1988 and 2007 at City of Hope and had survived ≥1 year. This cohort formed the sampling frame for selecting controls (without CHF) matched on: age, race/ethnicity, cumulative anthracycline exposure, stem cell source (allogeneic, autologous), and length of follow-up. Seventy-seven cases with pre-HCT germline DNA and 178 controls were genotyped. Multivariate analysis revealed that the odds of CHF was higher in females [Odds Ratio (OR) = 2·9, P < 0·01], individuals with pre-HCT chest radiation (OR = 4·7, P = 0·05), hypertension (OR = 2·9, P = 0·01), and with variants of genes coding for the NAD(P)H-oxidase subunit RAC2 (rs13058338, 7508T→A; OR = 2·8, P < 0·01), HFE (rs1799945, 63C→G; OR = 2·5, P = 0·05) or the doxorubicin efflux transporter ABCC2 (rs8187710, 1515G→A; OR = 4·3, P < 0·01). A combined (clinical and genetic) CHF predictive model performed better [area under the curve (AUC), 0·79] than the genetic (AUC = 0·67) or the clinical (AUC = 0·69) models alone.

  11. Impact of Childbearing Decisions on Family Size of Korean Women with Systemic Lupus Erythematosus

    PubMed Central

    2016-01-01

    Systemic lupus erythematosus (SLE) predominantly affects women in their reproductive years and has a significant impact on childbearing. We investigated the influence of personal decision on family size among Korean women with SLE and factors that affect the decisions. A case-control study comparing childbearing history and decisions of 112 SLE patients and 135 controls was performed. Women with SLE participating in the Network for Lupus Clinical Research in South Korea and matching controls between ages of 18-45, who are/were married or living with a partner were included. Data regarding socio-demographics, reproductive history, and childbearing decisions were collected through a survey using a standardized questionnaire and medical record review. More women with SLE reported at least one pregnancy (85.7% vs. 71.9%, P = 0.009) or at least one live birth (85.7% vs. 71.9%, P = 0.003) compared with controls. Mean number of pregnancies was significantly higher (2.4 ± 1.6 vs. 1.4 ± 1.3, P < 0.001), and mean number of live births was significantly lower in women with SLE (1.2 ± 0.8 vs. 1.6 ± 0.8, P < 0.001). Significantly more women with SLE made the decision not to have children compared with controls (54.5% vs. 40.7%, P = 0.031), and health-related concerns were the major cause of the decision. Other socio-demographic factors did not influence the decision to limit childbearing in SLE women. The disease-related concerns had significant impact on family size and childbearing decisions among Korean women with SLE. PMID:27134494

  12. Single-photon emission computed tomographic imaging of the early time course of therapy-induced cell death using technetium 99m tricarbonyl His-annexin A5 in a colorectal cancer xenograft model.

    PubMed

    Vangestel, Christel; Van de Wiele, Christophe; Mees, Gilles; Mertens, Koen; Staelens, Steven; Reutelingsperger, Chris; Pauwels, Patrick; Van Damme, Nancy; Peeters, Marc

    2012-04-01

    As apoptosis occurs over an interval of time after administration of apoptosis-inducing therapy in tumors, the changes in technetium 99m ((99m)Tc)-tricarbonyl (CO)₃ His-annexin A5 (His-ann A5) accumulation over time were examined. Colo205-bearing mice were divided into six treatment groups: (1) control, (2) 5-fluorouracil (5-FU; 250 mg/kg), (3) irinotecan (100 mg/kg), (4) oxaliplatin (30 mg/kg), (5) bevacizumab (5 mg/kg), and (6) panitumumab (6 mg/kg). (99m)Tc-(CO)₃ His-ann A5 was injected 4, 8, 12, 24, and 48 hours posttreatment, and micro-single-photon emission computed tomography was performed. Immunostaining of caspase-3 (apoptosis), survivin (antiapoptosis), and LC3-II (autophagy marker) was also performed. Different dynamics of (99m)Tc-(CO)₃ His-ann A5 uptake were observed in this colorectal cancer xenograft model, in response to a single dose of three different chemotherapeutics (5-FU, irinotecan, and oxaliplatin). Bevacizumab-treated mice showed no increased uptake of the radiotracer, and a peak of (99m)Tc-(CO)₃ His-ann A5 uptake in panitumumab-treated mice was observed 24 hours posttreatment, as confirmed by caspase-3 immunostaining. For irinotecan-, oxaliplatin-, and bevacizumab-treated tumors, a significant correlation was established between the radiotracer uptake and caspase-3 immunostaining (r  =  .8, p < .05; r  =  .9, p < .001; r  =  .9, p < .001, respectively). For 5-FU- and panitumumab-treated mice, the correlation coefficients were r  =  .7 (p  =  .18) and r  =  .7 (p  =  .19), respectively. Optimal timing of annexin A5 imaging after the start of different treatments in the Colo205 model was determined.

  13. Stress and Coping Strategies of Students in a Medical Faculty in Malaysia

    PubMed Central

    Al-Dubai, Sami Abdo Radman; Al-Naggar, Redhwan Ahmed; Alshagga, Mustafa Ahmed; Rampal, Krishna Gopal

    2011-01-01

    Background: Stress may affect students’ health and their academic performance. Coping strategies are specific efforts that individuals employ to manage stress. This study aimed to assess the perception of stress among medical students and their coping strategies. Methods: A cross-sectional study was conducted among 376 medical and medical sciences undergraduates in Management and Science University in Malaysia. Stress was assessed by a global rating of stress. Sources of stress were assessed using a 17-item questionnaire. The validated Brief COPE inventory was used to assess coping strategies. Results: The majority of respondents were females (64.4%), aged 21 years or older (63.0%), and were Malays (68.9%). Forty-six percent felt stress. The most common stressor was worries of the future (71.0%), followed by financial difficulties (68.6%). Significant predictors of stress were smoking (OR = 2.9, 95% CI 1.3–6.8, P = 0.009), worries of the future (OR = 2.1, 95% CI 1.3–3.4, P = 0.005), self-blame (OR = 1.3, 95% CI 1.1–1.5, P = 0.001), lack of emotional support (OR = 0.8, 95% CI 0.7–0.9, P = 0.017), and lack of acceptance (OR = 0.8, 95% CI 0.6–0.9, P = 0.010). Students used active coping, religious coping reframing, planning, and acceptance to cope with stress. Conclusion: Stressors reported by the students were mainly financial and academic issues. Students adopted active coping strategies rather than avoidance. Students should receive consultation on how to manage and cope with stress. PMID:22135602

  14. Increases in Entamoeba histolytica Antibody-Positive Rates in Human Immunodeficiency Virus-Infected and Noninfected Patients in Japan: A 10-Year Hospital-Based Study of 3,514 Patients.

    PubMed

    Yanagawa, Yasuaki; Nagata, Naoyoshi; Watanabe, Koji; Tsukada, Kunihisa; Teruya, Katsuji; Kikuchi, Yoshimi; Gatanaga, Hiroyuki; Akiyama, Junichi; Uemura, Naomi; Oka, Shinichi

    2016-09-01

    Serological evidence of the epidemiological trends in Entamoeba histolytica infection is scarce, especially in nonendemic countries. We aimed to determine the antibody-positive rates over a 10-year period, and compare the trends between human immunodeficiency virus (HIV)-infected and -noninfected patients. We reviewed 3,514 patients who underwent antibody testing during the study periods, which were divided into five annual categories: 2004-2005, 2006-2007, 2008-2009, 2010-2011, and 2012-2013. Anti-E. histolytica antibody was assessed by indirect immunofluorescence assay. The antibody-positive rate increased yearly from 2004-2005 to 2012-2013 (P < 0.001), although there was no increase in the annual number of antibody tests. This trend was seen among males (18.6-28.3%; P < 0.01), females (5.4-28.2%; P < 0.01), HIV-infected patients (18.4-26.9%; P < 0.001), and non-HIV-infected patients (14.6-36.8%; P < 0.001), and HIV-infected men who have sex with men (19.4-29.1%; P < 0.001). Among antibody-positive patients, there was a significant increase in the proportion of patients with high (≥ 1,600) titers (0.7-12.9%; P < 0.001), whereas this trend was not seen in patients with low (100) or intermediate (200-800) titers (P = 0.282 and 0.409, respectively). This large hospital-based study demonstrated that positive anti-E. histolytica antibody rates increased over 10 years, even though the annual number of antibody tests remained constant. Moreover, this trend was identified in non-high-risk patients (females and non-HIV-infected patients) as well as in high-risk patients. The proportion of patients with high antibody titers significantly increased among the antibody-positive patients. PMID:27296390

  15. STAAR: improving the reliability of care coordination and reducing hospital readmissions in an academic medical centre

    PubMed Central

    Carter, Jocelyn Alexandria; Carr, Laura S; Collins, Jacqueline; Doyle Petrongolo, Joanne; Hall, Kathryn; Murray, Jane; Smith, Jessica; Tata, Lee Ann

    2015-01-01

    Setting Massachusetts General Hospital embarked on a 4-year project to reduce readmissions in a high volume general medicine unit (November 2009 to September 2013). Objective To reduce 30-day readmissions to 10% through improved care coordination. Design As a before–after study, a total of 7586 patients admitted to the medicine unit during the intervention period included 2620 inpatients meeting high risk for readmission criteria. Of those, 2620 patients received nursing interventions and 539 patients received pharmacy interventions. Intervention The introduction of a Discharge Nurse (D/C RN) for patient/family coaching and a Transitional Care Pharmacist (TC PharmD) for predischarge medication reconciliation and postdischarge patient phone calls. Other interventions included modifications to multidisciplinary care rounds and electronic medication reconciliation. Main outcome measure All-cause 30-day readmission rates. Results Readmission rates decreased by 30% (21% preintervention to 14.5% postintervention) (p<0.05). From July 2010 to December 2011, rates of readmission among high-risk patients who received the D/C RN intervention with or without the TC PharmD medication reconciliation/education intervention decreased to 15.9% (p=0.59). From January to June 2010, rates of readmission among high-risk patients who received the TC PharmD postdischarge calls decreased to 12.9% (p=0.55). From June 2010 to December 2011, readmission rates for patients on the medical unit that did not receive the designated D/C RN or TC PharmD interventions decreased to 15.8% (p=0.61) and 16.2% (0.31), respectively. Conclusions A multidisciplinary approach to improving care coordination reduced avoidable readmissions both among those who received interventions and those who did not. This further demonstrated the importance of multidisciplinary collaboration. PMID:26246901

  16. Particular difficulties faced by GPs with young adults who will attempt suicide: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Suicide is a major public health problem in young people. General Practitioners (GPs) play a central role in suicide prevention. However data about how physicians deal with suicidal youths are lacking. This study aims to compare young adult suicide attempters (from 18 to 39 years old) with older adults in a primary care setting. Methods A cross-sectional study was carried. All suicide attempts (N=270) reported to the French Sentinel surveillance System from 2009 to 2011 were considered. We conducted comparison of data on the last GP’s consultation and GPs’ management in the last three months between young adults and older adults. Results In comparison with older adults, young adults consulted their GP less frequently in the month preceding the suicidal attempt (40.9 vs. 64.6%, p=.01). During the last consultation prior to the suicidal attempt, they expressed suicidal ideas less frequently (11.3 vs. 21.9%, p=.03). In the year preceding the suicidal attempt, GPs identified depression significantly less often (42.0 vs. 63.4%, p=.001). In the preceding three months, GPs realized significantly less interventions: less psychological support (37.5 vs. 53.0%, p=.02), prescribed less antidepressants (28.6 vs. 54.8%, p<.0001) or psychotropic drugs (39.1 vs. 52.9%, p=.03) and made fewer attempts to refer to a mental health specialist (33.3 vs. 45.5%, p=.05). Conclusion With young adults who subsequently attempt suicide, GPs face particular difficulties compared to older adults, as a significant proportion of young adults were not seen in the previous six months, as GPs identified less depressions in the preceding year and were less active in managing in the preceding three months. Medical training and continuing medical education should include better instruction on challenges relative to addressing suicide risk in this particular population. PMID:23706018

  17. [Effects of Short-time Conservation Tillage Managements on Greenhouse Gases Emissions from Soybean-Winter Wheat Rotation System].

    PubMed

    Xie, Yan; Chen, Xi; Hu, Zheng-hua; Chen, Shu-tao; Zhang, Han; Ling, Hui; Shen, Shuang-he

    2016-04-15

    Field experiments including one soybean growing season and one winter-wheat growing season were adopted. The experimental field was divided into four equal-area sub-blocks which differed from each other only in tillage managements, which were conventional tillage (T) , no-tillage with no straw cover ( NT) , conventional tillage with straw cover (TS) , and no-tillage with straw cover (NTS). CO₂ and N₂O emission fluxes from soil-crop system were measured by static chamber-gas chromatograph technique. The results showed that: compared with T, in the soybean growing season, NTS significantly increased the cumulative amount of CO₂ (CAC) from soil-soybean system by 27.9% (P = 0.045) during the flowering-podding stage, while NT significantly declined CAC by 28.9% (P = 0.043) during the grain filling-maturity stage. Compared with T, NT significantly declined the cumulative amount of N₂O (CAN) by 28.3% (P = 0.042) during the grain filling-maturity stage. In the winter-wheat growing season, compared with T, TS and NT significantly declined CAC by 24.3% (P = 0.032) and 36.0% (P = 0.041) during the elongation-booting stage, and also declined CAC by 26.8% (P = 0.027) and 33.1% (P = 0.038) during the maturity stage. During the turning-green stage, compared with T treatment, NT, NTS, and TS treatments had no significant effect on CAN, while NTS significant declined CAN by 42.0% (P = 0.035) compared with NT. Our findings suggested that conservation tillage managements had a more significant impact on CO₂ emission than 20 emission from soil-crop system. PMID:27548975

  18. [Culicidae of Itaipu lake, in the Paraná river, southern Brazil].

    PubMed

    Teodoro, U; Guilherme, A L; Lozovei, A L; La Salvia Filho, V; Fukushigue, Y; Spinosa, R P; Ferreira, M E; Barbosa, O C; de Lima, E M

    1995-02-01

    Mosquito catches were made in Guaíra county, Paraná State, southern Brazil, in the vicinity of Itaipu dam, from January to December 1991. The catches were made with a Shannon light trap and human bait. The Shannon light trap was installed beside the highway that used, formerly, to lead to the Sete Quedas cataracts and the human bait was used in the urban area. Data about the Culicidae fauna were obtained as to predominant species, seasonal variation, time of highest density and affinity with human host. Forty-one species were identified as belonging to the Anopheles, Aedes, Aedomyia, Coquillettidia, Culex, Mansonia, Psorophora and Uranotaenia genera. With the Shannon light trap 21,280 mosquitoes were caught and with human bait 1,010. In the catches made with the Shannon light trap, Coquillettidia shannoni, Mansonia humeralis, Anopheles trianulatus, Aedes scapularis and Anopheles albitarsis accounted for 82.78% of all mosquitoes taken. In the catches made on human bait the highest densities of these mosquitoes occurred between 7 p.m. and 9 p.m. Aedes scapularis, Mansonia humeralis and Anopheles albitarsis represented 91.21% of all mosquitoes caught with human bait. The highest densities of Aedes scapularis, on human bait, were found between 8 p.m. and 9 p.m. and those of Mansonia humeralis and Anopheles albitarsis between 6 p.m. and 7 p.m. Among the genera caught with the Shannon light trap Coquillettidia shannoni, Mansonia humeralis and Anopheles albitarsis were most frequent in April, Anopheles triannulatus in January and Aedes scapularis in February.

  19. Status of radiation damage measurements in room temperature semiconductor radiation detectors

    SciTech Connect

    Franks, L.A.; James, R.B.

    1998-04-01

    The literature of radiation damage measurements on cadmium zinc telluride (CZT), cadmium telluride (CT), and mercuric iodide (HgI{sub 2}) is reviewed for the purpose of determining their applicability to space applications. CZT strip detectors exposed to intermediate energy (1.3 MeV) proton fluences exhibit increased interstrip leakage after 10{sup 10} p/cm{sup 2} and significant bulk leakage after 10{sup 12} p/cm{sup 2}. CZT exposed to 200 MeV protons shows a two-fold loss in energy resolution after a fluence of 5 {times} 10{sup 9} p/cm{sup 2} in thick (3 mm) planar devices but little effect in 2 mm devices. No energy resolution effects were noted from moderated fission spectrum neutrons after fluences up to 10{sup 10} n/cm{sup 2}, although activation was evident. CT detectors show resolution losses after fluences of 3 {times} 10{sup 9} p/cm{sup 2} at 33 MeV for chlorine-doped detectors. Indium doped material may be more resistant. Neutron exposures (8 MeV) caused resolution losses after fluences of 2 {times} 10{sup 10} n/cm{sup 2}. Mercuric iodide has been studied with intermediate energy protons (10 to 33 MeV) at fluences up to 10{sup 12} p/cm{sup 2} and with 1.5 GeV protons at fluences up to 1.2 {times} 10{sup 8} p/cm{sup 2}. Neutron exposures at 8 MeV have been reported at fluences up to 10{sup 15} n/cm{sup 2}. No radiation damage was found under these irradiation conditions.

  20. Effects of cardiovascular lifestyle change on lipoprotein subclass profiles defined by nuclear magnetic resonance spectroscopy

    PubMed Central

    Decewicz, David J; Neatrour, David M; Burke, Amy; Haberkorn, Mary Jane; Patney, Heather L; Vernalis, Marina N; Ellsworth, Darrell L

    2009-01-01

    Background Low-density lipoprotein (LDL) cholesterol lowering is a primary goal in clinical management of patients with cardiovascular disease, but traditional cholesterol levels may not accurately reflect the true atherogenicity of plasma lipid profiles. The size and concentration of lipoprotein particles, which transport cholesterol and triglycerides, may provide additional information for accurately assessing cardiovascular risk. This study evaluated changes in plasma lipoprotein profiles determined by nuclear magnetic resonance (NMR) spectroscopy in patients participating in a prospective, nonrandomized lifestyle modification program designed to reverse or stabilize progression of coronary artery disease (CAD) to improve our understanding of lipoprotein management in cardiac patients. Results The lifestyle intervention was effective in producing significant changes in lipoprotein subclasses that contribute to CAD risk. There was a clear beneficial effect on the total number of LDL particles (-8.3%, p < 0.05 compared to matched controls), small dense LDL particles (-9.5%, p < 0.05), and LDL particle size (+0.8%; p < 0.05). Likewise, participants showed significant improvement in traditional CAD risk factors such as body mass index (-9.9%, p < 0.01 compared to controls), total cholesterol (-5.5%, p < 0.05), physical fitness (+37.2%, p < 0.01), and future risk for CAD (-7.9%, p < 0.01). Men and women responded differently to the program for all clinically-relevant variables, with men deriving greater benefit in terms of lipoprotein atherogenicity. Plasma lipid and lipoprotein responses to the lifestyle change program were not confounded by lipid-lowering medications. Conclusion In at risk patients motivated to participate, an intensive lifestyle change program can effectively alter traditional CAD risk factors and plasma lipoprotein subclasses and may reduce risk for cardiovascular events. Improvements in lipoprotein subclasses are more evident in men compared to

  1. Examining incentive design strategies for worksite wellness program engagement.

    PubMed

    Norman, Gregory J; Heltemes, Kevin J; Drew, Joseph

    2014-12-01

    The objective was to examine employee engagement in worksite wellness activities at 2 large US companies that differed in engagement strategy and incentive plan. Inclusion criteria were US employees aged 18 to 65 who were eligible to receive wellness benefits throughout 2012. Company B's incentive was twice the dollar value of Company A's and produced higher engagement rates for the health assessment (HA; 26.1% vs. 24.4%, P<.001), and biometric screening (32.8% vs. 25.4%, P<.001). Among the subgroup of employees who completed the HA and the biometric screening, 44.6% (N=2,309) at Company A engaged in at least 1 coaching session compared to 8.9% (N=594) at Company B. Fewer employees at Company A with high-risk cholesterol engaged in coaching compared to Company B (44.6% vs. 54.9%, P=.009). However, more Company A employees with high-risk blood pressure engaged in coaching compared to Company B (41.3% vs. 34.8%, P=.053). Company A engaged more obese employees compared to Company B (43.7% vs. 13.9%, P<.001), although obesity was not directly targeted at either company. Predictors of enrolling in coaching included being female, older age, higher education, and those not at high risk for stress, diet, and tobacco for Company A, and older age, and high risk for blood pressure, cholesterol, and obesity for Company B. A population approach to incentive design for program engagement engaged high-risk employees in coaching, and engaged a high proportion of employees not at high risk, but who can still be at risk for chronic diseases.

  2. Maternal determinants of child survival in a rural African community.

    PubMed

    Van den Broeck, J; Eeckels, R; Massa, G

    1996-10-01

    During August 1989-April 1992 in northern Zaire, random cluster sampling was taken of 16 villages in the health zone of Bwamanda. Health workers visited 766 exclusively breastfed infants, 0-3 months old, every 3 months for a total of 6 visits. This prospective study aimed to identify maternal determinants of child survival. The mortality rate was about 7.5%. More than 3% of the mothers suffered from chronic illness. 28.2% had at least 2 children. 86.1% were illiterate. 55% had already experienced at least 1 child death. Four variables were interrelated and, together, increased the risk of mortality: parity, number of surviving children, maternal age, and number of dead children. The multiple logistic regression analysis found the risk factors for mortality to include parity greater than 5 (conditional odds ratio [COR] = 4.9; p 0.01), more than 5 km distance from the health center (COR = 1.9; p = 0.06), at least 2 signs or symptoms of maternal chronic disease (COR = 4.8; p = 0.03), and any education for mothers (COR = 2.2; p = 0.05). Contrary to findings of other studies, mother-child separation and problems with breast feeding, rare in this area of northern Zaire, did not contribute significantly to mortality, but higher levels of maternal education were associated with increased levels of child mortality. These findings show that, in this rural area of subsistence farming, high parity, and illiteracy, chronic maternal stress situations (e.g., previous child deaths, maternal invalidity, high parity, great distance from health care facilities, and high child mortality) hamper child survival. PMID:8921486

  3. Examining incentive design strategies for worksite wellness program engagement.

    PubMed

    Norman, Gregory J; Heltemes, Kevin J; Drew, Joseph

    2014-12-01

    The objective was to examine employee engagement in worksite wellness activities at 2 large US companies that differed in engagement strategy and incentive plan. Inclusion criteria were US employees aged 18 to 65 who were eligible to receive wellness benefits throughout 2012. Company B's incentive was twice the dollar value of Company A's and produced higher engagement rates for the health assessment (HA; 26.1% vs. 24.4%, P<.001), and biometric screening (32.8% vs. 25.4%, P<.001). Among the subgroup of employees who completed the HA and the biometric screening, 44.6% (N=2,309) at Company A engaged in at least 1 coaching session compared to 8.9% (N=594) at Company B. Fewer employees at Company A with high-risk cholesterol engaged in coaching compared to Company B (44.6% vs. 54.9%, P=.009). However, more Company A employees with high-risk blood pressure engaged in coaching compared to Company B (41.3% vs. 34.8%, P=.053). Company A engaged more obese employees compared to Company B (43.7% vs. 13.9%, P<.001), although obesity was not directly targeted at either company. Predictors of enrolling in coaching included being female, older age, higher education, and those not at high risk for stress, diet, and tobacco for Company A, and older age, and high risk for blood pressure, cholesterol, and obesity for Company B. A population approach to incentive design for program engagement engaged high-risk employees in coaching, and engaged a high proportion of employees not at high risk, but who can still be at risk for chronic diseases. PMID:24865388

  4. Selective vitamin D receptor activation as anti-inflammatory target in chronic kidney disease.

    PubMed

    Donate-Correa, J; Domínguez-Pimentel, V; Méndez-Pérez, M L; Muros-de-Fuentes, M; Mora-Fernández, C; Martín-Núñez, E; Cazaña-Pérez, V; Navarro-González, J F

    2014-01-01

    Paricalcitol, a selective vitamin D receptor (VDR) activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD), has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m(2) and an intact parathyroid hormone (PTH) level higher than 110 pg/mL received oral paricalcitol (1  μg/48 hours) as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level <110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%, P < 0.01), TNF-α (11.9%, P = 0.01), and IL-6 (7%, P < 0.05), with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNFα and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% (P = 0.01) and 35.4% (P = 0.01), respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD.

  5. Selective Vitamin D Receptor Activation as Anti-Inflammatory Target in Chronic Kidney Disease

    PubMed Central

    Donate-Correa, J.; Domínguez-Pimentel, V.; Méndez-Pérez, M. L.; Muros-de-Fuentes, M.; Mora-Fernández, C.; Martín-Núñez, E.; Cazaña-Pérez, V.; Navarro-González, J. F.

    2014-01-01

    Paricalcitol, a selective vitamin D receptor (VDR) activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD), has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m2 and an intact parathyroid hormone (PTH) level higher than 110 pg/mL received oral paricalcitol (1 μg/48 hours) as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level <110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%, P < 0.01), TNF-α (11.9%, P = 0.01), and IL-6 (7%, P < 0.05), with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNFα and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% (P = 0.01) and 35.4% (P = 0.01), respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD. PMID:24511210

  6. Impact of previous cyst-enterostomy on patients’ outcome following resection of bile duct cysts

    PubMed Central

    Ouaissi, Mehdi; Kianmanesh, Reza; Ragot, Emilia; Belghiti, Jacques; Majno, Pietro; Nuzzo, Gennaro; Dubois, Remi; Revillon, Yann; Cherqui, Daniel; Azoulay, Daniel; Letoublon, Christian; Pruvot, François-René; Paye, François; Rat, Patrick; Boudjema, Karim; Roux, Adeline; Mabrut, Jean-Yves; Gigot, Jean-François

    2016-01-01

    AIM: To analyze the impact of previous cyst-enterostomy of patients underwent congenital bile duct cysts (BDC) resection. METHODS: A multicenter European retrospective study between 1974 and 2011 were conducted by the French Surgical Association. Only Todani subtypes I and IVb were included. Diagnostic imaging studies and operative and pathology reports underwent central revision. Patients with and without a previous history of cyst-enterostomy (CE) were compared. RESULTS: Among 243 patients with Todani types I and IVb BDC, 16 had undergone previous CE (6.5%). Patients with a prior history of CE experienced a greater incidence of preoperative cholangitis (75% vs 22.9%, P < 0.0001), had more complicated presentations (75% vs 40.5%, P = 0.007), and were more likely to have synchronous biliary cancer (31.3% vs 6.2%, P = 0.004) than patients without a prior CE. Overall morbidity (75% vs 33.5%; P < 0.0008), severe complications (43.8% vs 11.9%; P = 0.0026) and reoperation rates (37.5% vs 8.8%; P = 0.0032) were also significantly greater in patients with previous CE, and their Mayo Risk Score, during a median follow-up of 37.5 mo (range: 4-372 mo) indicated significantly more patients with fair and poor results (46.1% vs 15.6%; P = 0.0136). CONCLUSION: This is the large series to show that previous CE is associated with poorer short- and long-term results after Todani types I and IVb BDC resection. PMID:27358675

  7. GATA3 immunohistochemistry expression in histologic subtypes of primary breast carcinoma and metastatic breast carcinoma cytology.

    PubMed

    Deftereos, Georgios; Sanguino Ramirez, Angela M; Silverman, Jan F; Krishnamurti, Uma

    2015-09-01

    GATA3 plays a role in cell proliferation and differentiation in many tissues, including breast, and it has been suggested that GATA3 expression correlates with ER expression. However, little is known on GATA3 expression in various subtypes of breast carcinoma, its utilization in cytology, and on how GATA3 performs in comparison with GCDFP-15 and mammaglobin. Eighty-four histology cases of breast carcinoma of various subtypes, including 28 triple-negative breast carcinomas, along with 20 cytology cases of metastatic breast carcinoma and 12 cytology cases of ER-positive metastatic gynecologic malignancies, were stained for GATA3, GCDFP-15, and mammaglobin. In non-triple-negative breast carcinomas (n=56), GATA3 showed 100% sensitivity, higher than GCDFP-15 (42.8%; P<0.0001) and mammaglobin (58.9%; P<0.0001), whereas staining patterns were similar for all the histologic subtypes examined. Staining scores were determined by multiplying the percentage of cancer cells staining with an intensity score of 1+, 2+, or 3+ (range, 0 to 300). In non-triple-negative carcinomas, GATA3 showed a mean score of 273.7, higher than GCDFP-15 (107.5; P<0.0001) and mammaglobin (147.7; P<0.0001). In triple-negative breast carcinomas (n=28), GATA3 showed a sensitivity of 60.7%, greater than GCDFP-15 (17.9%; P=0.0022) and mammaglobin (7.1%; P<0.0001). These results were consistent irrespective of the subtype examined. In breast carcinoma cytology cases, 100% stained with GATA3, higher than GCDFP-15 (20%; P<0.0001) and mammaglobin (45%; P<0.0001). None of the metastatic endometrial or ovarian carcinomas were positive for GATA3. Although GATA3 expression correlates with ER expression in breast, no correlation is observed in gynecologic malignancies. Thus, in working up ER-positive metastatic malignancies GATA3 demonstrates specificity for breast.

  8. The influence of challenging objects and horse-rider matching on heart rate, heart rate variability and behavioural score in riding horses.

    PubMed

    Munsters, Carolien C B M; Visser, Kathalijne E K; van den Broek, Jan; Sloet van Oldruitenborgh-Oosterbaan, Marianne M

    2012-04-01

    A good horse-rider 'match' is important in the context of equine welfare. To quantify the influence of repetition and horse-rider matching on the stress of horses encountering challenging objects, 16 Warmblood horses were ridden in a test-setting on three occasions. On each occasion the horse was ridden by a different rider and was challenged by three objects (A-C). Heart rate (HR), heart rate variability (HRV) of horse and rider, and behaviour score (BS) of the horse were obtained for each object and as a total for each test. The horse-rider interaction was evaluated with each combination and assessed as 'matching' or 'mismatching', and the horses were categorised as 'compliant', 'partly-compliant' or 'non-compliant'. Horses exhibited a decreased HR (P=0.015) and a decreased BS (P=0.004) within and across different tests. 'Matching' horse-rider combinations exhibited less stress as indicated by reduced HR ('match' 69±10 vs. 'mismatch' 72±9, P=0.001) and BS ('match' 1.9±1.1 vs. 'mismatch' 3.8±1.4, P=0.017) of the horse. 'Compliant' (68±8, P<0.001) and 'partly-compliant' (71±9, P=0.002) horses had significantly lower HR than 'non-compliant' (75±9) animals. The findings of the study indicate that HR and BS measurements support a subjective 'match' diagnosis and HR measurement may be a valuable tool in assessing horse compliance.

  9. Percentage of Cancer Volume in Biopsy Cores Is Prognostic for Prostate Cancer Death and Overall Survival in Patients Treated With Dose-Escalated External Beam Radiotherapy

    SciTech Connect

    Vance, Sean M.; Stenmark, Matthew H.; Blas, Kevin; Halverson, Schulyer; Hamstra, Daniel A.; Feng, Felix Y.

    2012-07-01

    Purpose: To investigate the prognostic utility of the percentage of cancer volume (PCV) in needle biopsy specimens for prostate cancer patients treated with dose-escalated external beam radiotherapy. Methods and Materials: The outcomes were analyzed for 599 men treated for localized prostate cancer with external beam radiotherapy to a minimal planning target volume dose of 75 Gy (range, 75-79.2). We assessed the effect of PCV and the pretreatment and treatment-related factors on the freedom from biochemical failure, freedom from metastasis, cause-specific survival, and overall survival. Results: The median number of biopsy cores was 7 (interquartile range, 6-12), median PCV was 10% (interquartile range, 2.5-25%), and median follow-up was 62 months. The PCV correlated with the National Comprehensive Cancer Network risk group and individual risk features, including T stage, prostate-specific antigen level, Gleason score, and percentage of positive biopsy cores. On log-rank analysis, the PCV stratified by quartile was prognostic for all endpoints, including overall survival. In addition, the PCV was a stronger prognostic factor than the percentage of positive biopsy cores when the two metrics were analyzed together. On multivariate analysis, the PCV predicted a worse outcome for all endpoints, including freedom from biochemical failure, (hazard ratio, 1.9; p = .0035), freedom from metastasis (hazard ratio, 1.7, p = .09), cause-specific survival (hazard ratio, 3.9, p = .014), and overall survival (hazard ratio, 1.8, p = .02). Conclusions: For patients treated with dose-escalated external beam radiotherapy, the volume of cancer in the biopsy specimen adds prognostic value for clinically relevant endpoints, particularly in intermediate- and high-risk patients. Although the PCV determination is more arduous than the percentage of positive biopsy cores, it provides superior risk stratification.

  10. A novel curvilinear approach for prostate seed implantation

    SciTech Connect

    Podder, Tarun K.; Dicker, Adam P.; Hutapea, Parsaoran; Darvish, Kurosh; Yu Yan

    2012-04-15

    Purpose: A new technique called ''curvilinear approach'' for prostate seed implantation has been proposed. The purpose of this study is to evaluate the dosimetric benefit of curvilinear distribution of seeds for low-dose-rate (LDR) prostate brachytherapy. Methods: Twenty LDR prostate brachytherapy cases planned intraoperatively with VariSeed planning system and I-125 seeds were randomly selected as reference rectilinear cases. All the cases were replanned by using curved-needle approach keeping the same individual source strength and the volume receiving 100% of prescribed dose 145 Gy (V{sub 100}). Parameters such as number of needles, seeds, and the dose coverage of the prostate (D{sub 90}, V{sub 150}, V{sub 200}), urethra (D{sub 30}, D{sub 10}) and rectum (D{sub 5}, V{sub 100}) were compared for the rectilinear and the curvilinear methods. Statistical significance was assessed using two-tailed student's t-test. Results: Reduction of the required number of needles and seeds in curvilinear method were 30.5% (p < 0.001) and 11.8% (p < 0.49), respectively. Dose to the urethra was reduced significantly; D{sub 30} reduced by 10.1% (p < 0.01) and D{sub 10} reduced by 9.9% (p < 0.02). Reduction in rectum dose D{sub 5} was 18.5% (p < 0.03) and V{sub 100} was also reduced from 0.93 cc in rectilinear to 0.21 cc in curvilinear (p < 0.001). Also the V{sub 150} and V{sub 200} coverage of prostate reduced by 18.8% (p < 0.01) and 33.9% (p < 0.001), respectively. Conclusions: Significant improvement in the relevant dosimetric parameters was observed in curvilinear needle approach. Prostate dose homogeneity (V{sub 150}, V{sub 200}) improved while urethral dose was reduced, which might potentially result in better treatment outcome. Reduction in rectal dose could potentially reduce rectal toxicity and complications. Reduction in number of needles would minimize edema and thereby could improve postimplant urinary incontinence. This study indicates that the curvilinear implantation

  11. Transient congenital hypothyroidism caused by compound heterozygous mutations affecting the NADPH-oxidase domain of DUOX2.

    PubMed

    Yoshizawa-Ogasawara, Atsuko; Abe, Kiyomi; Ogikubo, Sayaka; Narumi, Satoshi; Hasegawa, Tomonobu; Satoh, Mari

    2016-03-01

    Here, we describe three cases of loss-of-function mutations in the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase (NOX) domain of dual oxidase 2 (DUOX2) occurring along with concurrent missense mutations in thyroid peroxidase (TPO), leading to transient congenital hypothyroidism (CH). Three Japanese boys with nonconsanguineous parents were diagnosed with CH during their neonatal screenings. All patients presented with moderate-to-severe neonatal hypothyroidism and were diagnosed with transient CH after re-evaluation of thyroid function. Two siblings were compound heterozygous for p.[R1110Q]+[Y1180X] in DUOX2; one of them was also heterozygous for p.[R361L] in TPO. The third patient was compound heterozygous for p.[L1160del]+[R1334W] in DUOX2 and heterozygous for p.[P883S] in TPO. This is the first report of a de novo L1160del mutation affecting the DUOX2 gene and of the novel mutations Y1180X in DUOX2 and R361L in TPO. R1110Q and L1160del were found to reduce H2O2 production (5%-9%, p<0.01), while Y1180X, which introduces a premature stop codon, did not confer detectable H2O2 production (-0.7%±0.6%, p<0.01). Moreover, R1334W, a missense mutation possibly affecting electron transfer, led to reduced H2O2 production (24%±0.9%, p<0.01) in vitro, and R1110Q and R1334W resulted in reduced protein expression. Y1180X was detected in a 120 kDa truncated form, whereas L1160del expression was maintained. Further, R361L, a novel missense mutation in TPO, caused partial reduction in peroxidase activity (20.6%±0.8%, p=0.01), whereas P883S, a missense variant, increased it (133.7%±2.8%, p=0.02). The protein expression levels in the case of R361L and P883S were maintained. In conclusion, we provide clinical and in vitro demonstrations of different functional defects and phenotypic heterogeneity in the same thyroid hormonogenesis pathway.

  12. Effects of Acetaminophen on Left Atrial Contractility

    PubMed Central

    Chang, Jun-Hei; Cheng, Pao-Yun; Hsu, Chih-Hsueng; Chen, Yao-Chang; Hong, Po-Da

    2016-01-01

    Background It has been observed that acetaminophen shows cardioprotective efficacy in mammals. In this study, we investigated the electromechanical effects of acetaminophen on the left atrium (LA). Methods Conventional microelectrodes were used to record the action potentials (AP) in rabbit LA preparations. The action potential duration (APD) at repolarization levels of 90%, 50% and 20% of the AP amplitude (APD90, APD50, and APD20, respectively), resting membrane potential, and contractile force were measured during 2 Hz electrical stimulation before and after sequential acetaminophen administration to the LA. Results Acetaminophen (0.1, 0.3, 1, and 3 mM) reduced APD20 from 9.4 ± 1.2 to 8.0 ± 1.1 (p < 0.05), 7.1 ± 0.8 (p < 0.05), 7.8 ± 1.1, and 6.8 ± 1.2 ms (p < 0.05), respectively, and APD50 from 20.2 ± 1.9 to 17.4 ± 2.0, 15.6 ± 1.8 (p < 0.05), 15.8 ± 2.2 (p < 0.05), and 14.1 ± 2.4 ms (p < 0.05), respectively, in a concentration-dependent manner. APD90 was reduced from 72.0 ± 3.6 to 64.7 ± 4.2, 61.9 ± 4.3, 60.5 ± 3.7, and 53.4 ± 4.4 ms (p < 0.05), respectively. Acetaminophen increased LA contractility from 45 ± 9 to 52 ± 10 (p < 0.05), 55 ± 9 (p < 0.01), 58 ± 9 (p < 0.01), and 60 ± 9 mg (p < 0.01), respectively, in a concentration-dependent manner. In the presence of the NOS inhibitor L-NAME or PKG-I inhibitor DT-2, additional acetaminophen treatment did not significantly increase LA contractility. Conclusions Acetaminophen modulated the electromechanical characteristics of LA by inhibiting the NOS and PKG I pathway, and then contributed to the positive inotropic effect. PMID:27471362

  13. Extensively reared Iberian pigs versus intensively reared white pigs for the manufacture of liver pâté.

    PubMed

    Estévez, M; Morcuende, D; Ramírez, R; Ventanas, J; Cava, R

    2004-07-01

    Physico-chemical characteristics and quality traits of the raw ingredients (muscle cuadriceps femoris, liver and adipose tissue) and the pâtés made from extensively reared Iberian pigs and intensively reared white pigs, were evaluated. The differences found between muscles, livers and adipose tissues from Iberian and white pigs influenced the characteristics of the pâtés. Compared to pâtés from white pigs, pâtés from Iberian pigs had a higher content of heme iron (27.5 μg/g vs 11.5 μg/g; p<0.05) and lower content of non-heme iron (27.5 μg/g vs 33.7 μg/g; p<0.05). Pâtés from Iberian pigs exhibited a darker colour (L (∗):18.6 vs 15.9, p<0.05) with less redness (a (∗) values: 9.1 vs 11.3; p<0.05) and yellowness (b (∗) values: 13.1 vs 14.8, p<0.05). Thus, pâtés from white pigs had higher values of chroma (18.6 vs 15.9, p<0.05) and smaller values of hue (52.5 vs 55.2, p<0.05) that those from Iberian pigs' pâtés. In fatty acid composition, pâtés from white pigs had higher proportions of SFA (37.9% vs 32.8%, p<0.05) and PUFA (14.4% vs 9.6%, p<0.05) than pâtés from Iberian pigs and lower percentages of oleic (53.4% vs 43.6%, p<0.05) and total of MUFA (57.5% vs 47.6%, p<0.05). Pâtés from Iberian pigs had a lower n-6/n-3 values (13.2 vs 17.2; p<0.05).

  14. Effect of ThermaCare HeatWraps and Icy Hot Cream/Patches on Skin and Quadriceps Muscle Temperature and Blood Flow

    PubMed Central

    Petrofsky, Jerrold Scott; Laymon, Michael; Berk, Lee; Bains, Gurinder

    2016-01-01

    Objectives The purpose of this study was to compare the effects of over-the-counter treatments—ThermaCare HeatWraps (chemical reaction to produce heat above the skin), Icy Hot Patch, and Icy Hot Cream (topically applied menthol)—on skin and deep tissue temperature. Methods This was a longitudinal crossover study. On each of 3 days, a ThermaCare HeatWrap, Icy Hot Cream, or Icy Hot Patch was applied randomly over the quadriceps muscle in 15 healthy volunteers with normal body mass. Skin and muscle temperature and blood flow were measured by laser flowmetry every 15 minutes for 2 hours. Results After 2 hours, mean temperature decreased by 2.1°C (7.0%; P = .02) in skin and 1.0°C (2.9%; P = .01) in muscle with Icy Hot Cream. Icy Hot Patch decreased skin and muscle temperature by 1.7°C (5.4%; P = .03) and 1.3°C (3.8%; P = .01), respectively. In contrast, ThermaCare raised skin and muscle temperature by 7.8°C (25.8%; P = .001) and 2.7°C (7.7%; P = .002), respectively; both were significantly warmer with ThermaCare vs either Icy Hot product (all P < .007). Icy Hot products produced a net decrease in skin blood flow (Cream: 56.7 flux [39.3%; P = .003]; Patch: 19.1 flux [16.7%; P = .045]). Muscle blood flow decreased with the Patch (6.7 flux [7.0%; P = .02]). After a period of fluctuations, Icy Hot Cream produced a net increase vs baseline of 7.0 flux (16.9%; P = .02). ThermaCare more than doubled blood flow in skin (83.3 flux [109.7%; P = .0003]) and muscle (25.1 flux [148.5%; P = .004]). Conclusions In this group of 15 healthy volunteers, ThermaCare HeatWraps provided the greatest degree of tissue warming and increase in tissue blood flow. PMID:27069427

  15. Changes in maximal and explosive strength, electromyography, and muscle thickness of lower and upper extremities induced by combined strength and endurance training in soldiers.

    PubMed

    Santtila, Matti; Kyröläinen, Heikki; Häkkinen, Keijo

    2009-07-01

    The purpose of present study was to examine to what extent an 8-week endurance-based military training period interferes with muscle strength development in the conscripts (n = 72) compared with that caused by sport-related military training with added strength training (ST) or endurance training (ET). More specifically, we examined the effects of these 3 training modes on maximal isometric force, maximal rate of force development (RFD), electromyography (EMG), and muscle thickness of the lower and upper extremities. The measurements included isometric force-time parameters of leg and arm extensors and EMG activity from the vastus lateralis, vastus medialis, rectus femoris, and triceps brachii muscles. The 8-week basic training period combined with added ST and ET significantly improved maximal bilateral isometric force of the arm extensors in ST by 11.8% (p < 0.001), ET by 13.9% (p < 0.001), and normal training (NT) by 7.8% (p < 0.05). Strength training and ET showed significant increases in maximal EMG activity of the trained arm muscles. A significant increase was observed in maximal RFD of the upper extremities only in ST by 28.1% (p < 0.05). Both ST and ET increased their maximal leg extension strength by 12.9% (p < 0.01) and 9.1% (p < 0.05), respectively, whereas no significant change occurred in NT (5.2%, p = 0.45). No significant changes were observed in the shape of the force-time curves of leg extensors. No increases occurred in muscle thickness either in the lower or upper extremities. The present BT training with a large amount of endurance-based military training interfered with strength development, and especially, explosive power development of the lower extremities in the ST group. The optimal improvements in neuromuscular characteristics may not be possible without some decreases in the amount of the endurance-based military training and/or some increases in the amount of the maximal/explosive strength training during the BT.

  16. Sleep Environment Risks for Younger and Older Infants

    PubMed Central

    Collie-Akers, Vicki; Schunn, Christy; Moon, Rachel Y.

    2014-01-01

    OBJECTIVE: Sudden infant death syndrome and other sleep-related causes of infant mortality have several known risk factors. Less is known about the association of those risk factors at different times during infancy. Our objective was to determine any associations between risk factors for sleep-related deaths at different ages. METHODS: A cross-sectional study of sleep-related infant deaths from 24 states during 2004–2012 contained in the National Center for the Review and Prevention of Child Deaths Case Reporting System, a database of death reports from state child death review teams. The main exposure was age, divided into younger (0–3 months) and older (4 months to 364 days) infants. The primary outcomes were bed-sharing, objects in the sleep environment, location (eg, adult bed), and position (eg, prone). RESULTS: A total of 8207 deaths were analyzed. Younger victims were more likely bed-sharing (73.8% vs 58.9%, P < .001) and sleeping in an adult bed/on a person (51.6% vs 43.8%, P < .001). A higher percentage of older victims had an object in the sleep environment (39.4% vs 33.5%, P < .001) and changed position from side/back to prone (18.4% vs 13.8%, P < .001). Multivariable regression confirmed these associations. CONCLUSIONS: Risk factors for sleep-related infant deaths may be different for different age groups. The predominant risk factor for younger infants is bed-sharing, whereas rolling into objects in the sleep area is the predominant risk factor for older infants. Parents should be warned about the dangers of these specific risk factors appropriate to their infant’s age. PMID:25022735

  17. The Cyclooctadepsipeptide Anthelmintic Emodepside Differentially Modulates Nematode, Insect and Human Calcium-Activated Potassium (SLO) Channel Alpha Subunits

    PubMed Central

    Schoenhense, Eva; Harder, Achim; Raming, Klaus; O’Kelly, Ita; Ndukwe, Kelechi; O’Connor, Vincent; Walker, Robert J.; Holden-Dye, Lindy

    2015-01-01

    The anthelmintic emodepside paralyses adult filarial worms, via a mode of action distinct from previous anthelmintics and has recently garnered interest as a new treatment for onchocerciasis. Whole organism data suggest its anthelmintic action is underpinned by a selective activation of the nematode isoform of an evolutionary conserved Ca2+-activated K+ channel, SLO-1. To test this at the molecular level we compared the actions of emodepside at heterologously expressed SLO-1 alpha subunit orthologues from nematode (Caenorhabditis elegans), Drosophila melanogaster and human using whole cell voltage clamp. Intriguingly we found that emodepside modulated nematode (Ce slo-1), insect (Drosophila, Dm slo) and human (hum kcnma1)SLO channels but that there are discrete differences in the features of the modulation that are consistent with its anthelmintic efficacy. Nematode SLO-1 currents required 100 μM intracellular Ca2+ and were strongly facilitated by emodepside (100 nM; +73.0 ± 17.4%; n = 9; p<0.001). Drosophila Slo currents on the other hand were activated by emodepside (10 μM) in the presence of 52 nM Ca2+ but were inhibited in the presence of 290 nM Ca2+ and exhibited a characteristic loss of rectification. Human Slo required 300nM Ca2+ and emodepside transiently facilitated currents (100nM; +33.5 ± 9%; n = 8; p<0.05) followed by a sustained inhibition (-52.6 ± 9.8%; n = 8; p<0.001). This first cross phyla comparison of the actions of emodepside at nematode, insect and human channels provides new mechanistic insight into the compound’s complex modulation of SLO channels. Consistent with whole organism behavioural studies on C. elegans, it indicates its anthelmintic action derives from a strong activation of SLO current, not observed in the human channel. These data provide an important benchmark for the wider deployment of emodepside as an anthelmintic treatment. PMID:26437177

  18. Influence of abusive vocal habits, hydration, mastication, and sleep in the occurrence of vocal symptoms in teachers.

    PubMed

    Ferreira, Leslie Piccolotto; de Oliveira Latorre, Maria do Rosario Dias; Pinto Giannini, Susana Pimentel; de Assis Moura Ghirardi, Ana Carolina; de Fraga e Karmann, Delmira; Silva, Eliana Egerland; Figueira, Silmara

    2010-01-01

    Some vocal disorders in teachers are associated with occupational factors, but there are few studies that analyze the influence of vocal habits, fluid intake, mastication, and sleep on these disorders. The objective was to analyze the occurrence of vocal fatigue, hoarseness, and dry throat in elementary and high school teachers and their association with vocal habits, fluid intake, mastication, and sleep. A sample of 422 elementary and secondary school teachers was studied using a specific questionnaire. The multiple regression analysis showed that hoarseness was associated with absence of water intake (odds ratio (OR)=1.7; P=0.047), yelling/speaking loudly (OR=1.6; P=0.058), jaw-opening limitations (OR=3.8; P=0.003), average of 6 hours of sleep/night (OR=1.7; P=0.039), and waking-up feeling replenished (OR=2.0; P=0.020). The presence of vocal fatigue was significantly associated with yelling/speaking loudly (OR=2.2; P=0.013), speaking excessively (OR=2.4; P=0.023), difficulty to open the mouth to masticate (OR=6.6; P=0.003), less than 6 hours of sleep (OR=4.0; P=0.008), and waking-up feeling replenished (sometimes OR=2.8; P=0.003; or never OR=3.3; P=0.002). The presence of dry throat was associated with being a former smoker (OR=3.3; P=0.011) and having jaw-opening limitations (OR=3.9; P=0.021). In recent years, speech and hearing interventions with teachers have focused on health-care promotion actions and prevention of vocal disorders, prioritizing issues related with hydration and healthy vocal use habits. However, the findings in the present study show the need to further focus on lifestyle habits related to sleep and eating habits.

  19. A Protocolised Once a Day Modified Early Warning Score (MEWS) Measurement Is an Appropriate Screening Tool for Major Adverse Events in a General Hospital Population

    PubMed Central

    Ludikhuize, Jeroen; Kramer, Mark H. H.

    2016-01-01

    Background The Modified Early Warning Score (MEWS) was developed to timely recognise clinically deteriorating hospitalised patients. However, the ability of the MEWS in predicting serious adverse events (SAEs) in a general hospital population has not been examined prospectively. The aims were to (1) analyse protocol adherence to a MEWS protocol in a real-life setting and (2) to determine the predictive value of protocolised daily MEWS measurement on SAEs: death, cardiac arrests, ICU-admissions and readmissions. Methods All adult patients admitted to 6 hospital wards in October and November 2015 were included. MEWS were checked each morning by the research team. For each critical score (MEWS ≥ 3), the clinical staff was inquired about the actions performed. 30-day follow-up for SAEs was performed to compare between patients with and without a critical score. Results 1053 patients with 3673 vital parameter measurements were included, 200 (19.0%) had a critical score. The protocol adherence was 89.0%. 18.2% of MEWS were calculated wrongly. Patients with critical scores had significant higher rates of unplanned ICU admissions [7.0% vs 1.3%, p < 0.001], in-hospital mortality [6.0% vs 0.8%, p < 0.001], 30-day readmission rates [18.6% vs 10.8%, p < 0.05], and a longer length of stay [15.65 (SD: 15.7 days) vs 6.09 (SD: 6.9), p < 0.001]. Specificity of MEWS related to composite adverse events was 83% with a negative predicting value of 98.1%. Conclusions Protocol adherence was high, even though one-third of the critical scores were calculated wrongly. Patients with a MEWS ≥ 3 experienced significantly more adverse events. The negative predictive value of early morning MEWS < 3 was 98.1%, indicating the reliability of this score as a screening tool. PMID:27494719

  20. Long-Term Weight Change after Initiating Second-Generation Antidepressants.

    PubMed

    Arterburn, David; Sofer, Tamar; Boudreau, Denise M; Bogart, Andy; Westbrook, Emily O; Theis, Mary Kay; Simon, Greg; Haneuse, Sebastien

    2016-01-01

    (1) OBJECTIVE: To examine the relationship between the choice of second-generation antidepressant drug treatment and long-term weight change; (2) METHODS: We conducted a retrospective cohort study to investigate the relationship between choice of antidepressant medication and weight change at two years among adult patients with a new antidepressant treatment episode between January, 2006 and October, 2009 in a large health system in Washington State. Medication use, encounters, diagnoses, height, and weight were collected from electronic databases. We modeled change in weight and BMI at two years after initiation of treatment using inverse probability weighted linear regression models that adjusted for potential confounders. Fluoxetine was the reference treatment; (3) RESULTS: In intent-to-treat analyses, non-smokers who initiated bupropion treatment on average lost 7.1 lbs compared to fluoxetine users who were non-smokers (95% CI: -11.3, -2.8; p-value < 0.01); smokers who initiated bupropion treatment gained on average 2.2 lbs compared to fluoxetine users who were smokers (95% CI: -2.3, 6.8; p-value = 0.33). Changes in weight associated with all other antidepressant medications were not significantly different than fluoxetine, except for sertraline users, who gained an average of 5.9 lbs compared to fluoxetine users (95% CI: 0.8, 10.9; p-value = 0.02); (4) CONCLUSION: Antidepressant drug therapy is significantly associated with long-term weight change at two years. Bupropion may be considered as the first-line drug of choice for overweight and obese patients unless there are other existing contraindications. PMID:27089374

  1. Hypospadias and variants in genes related to sex hormone biosynthesis and metabolism.

    PubMed

    Carmichael, S L; Witte, J S; Ma, C; Lammer, E J; Shaw, G M

    2014-01-01

    We examined whether variants in genes related to sex hormone biosynthesis and metabolism were associated with hypospadias in humans. We examined 332 relatively common tag single-nucleotide polymorphisms (tagSNPs) in 20 genes. Analyses included 633 cases (84 mild, 322 moderate, 212 severe and 15 undetermined severity) and 855 population-based non-malformed male controls born in California from 1990 to 2003. We used logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for each SNP. Several of the 332 studied SNPs had p < 0.01: one in CYP3A4, four in HSD17B3, one in HSD3B1, two in STARD3, 10 in SRD5A2 and seven in STS. In addition, haplotype analyses gave several associations with p < 0.01. For HSD17B3, 14-SNP and 5-SNP blocks had ORs of 1.5 (95% CI 1.1, 2.0, p < 0.001) and 2.8 (95% CI 1.6, 4.8, p < 0.001) respectively. For SRD5A2, 9-SNP, 3-SNP and 8-SNP blocks had ORs of 1.7 (95% CI 1.3, 2.2, p < 0.001), 1.4 (95% CI 1.1, 1.8, p = 0.008) and 1.5 (95% CI 1.2, 1.9, p = 0.002) respectively. Our study indicates that several genes that contribute to sex hormone biosynthesis and metabolism are associated with hypospadias risk.

  2. Residential radon exposure and lung cancer in Sweden

    SciTech Connect

    Pershagen, G.; Akerblom, G.; Axelson, O.; Clavensjoe, B.D.; Damber, L.; Desai, G.; Enflo, A.; Lagarde, F.; Mellander, H.; Svartengren, M. )

    1994-01-20

    BACKGROUND. Residential radon is the principal source of exposure to ionizing radiation in most countries. To determine the implications for the risk of lung cancer, we performed a nationwide case-control study in Sweden. METHODS. The study included 586 women and 774 men 35 to 74 years of age with lung cancer that was diagnosed between 1980 and 1984. For comparison, 1380 female and 1467 male controls were studied. Radon was measured in 8992 dwellings occupied by the study subjects at some time since 1947. Information on smoking habits and other risk factors for lung cancer was obtained from questionnaires. RESULTS. Radon levels followed a log-normal distribution, with geometric and arithmetic means of 1.6 and 2.9 pCi per liter (60.5 and 106.5 Bq per cubic meter), respectively. The risk of lung cancer increased in relation to both estimated cumulative and time-weighted exposure to radon. In comparison with time-weighted average radon concentrations up to 1.4 pCi per liter (50 Bq per cubic meter), the relative risk was 1.3 (95 percent confidence interval, 1.1 to 1.6) for average radon concentrations of 3.8 to 10.8 pCi per liter (140 to 400 Bq per cubic meter), and it was 1.8 (95 percent confidence interval, 1.1 to 2.9) at concentrations exceeding 10.8 pCi per liter. The estimates of risk were in the same range as those projected from data in miners. The interaction between radon exposure and smoking with regard to lung cancer exceeded additivity and was closer to a multiplicative effect. CONCLUSIONS. Residential exposure to radon is an important cause of lung cancer in the general population. The risks appear consistent with earlier estimates based on data in miners.

  3. Orthodontic treatment outcomes obtained by application of a finishing protocol

    PubMed Central

    Carvajal-Flórez, Alvaro; Barbosa-Lis, Diana María; Zapata-Noreña, Oscar Arturo; Marín-Velásquez, Julissa Andrea; Afanador-Bayona, Sergio Andrés

    2016-01-01

    ABSTRACT Objective: To evaluate the results of a finishing protocol implemented in patients treated in the Orthodontics graduate program at Universidad de Antioquia. Evaluation was carried out by means of the criteria set by the Objective Grading System (OGS) of the American Board of Orthodontics (ABO). Methods: Cast models and panoramic radiographs of 34 patients were evaluated. The intervention group (IG) consisted of 17 patients (19.88 ± 4.4 years old) treated under a finishing protocol. This protocol included training in finishing, application of a finishing guide, brackets repositioning and patient's follow-up. Results of the IG were compared to a control group of 17 patients (21.88 ± 7.0 years old) selected by stratified randomization without finishing intervention (CG). Results: The scores for both CG and IG were 38.00 ± 9.0 and 31.41 ± 9.6 (p = 0.048), respectively. The score improved significantly in the IG group, mainly regarding marginal ridges (CG: 5.59 ± 2.2; IG: 3.65 ± 1.8) (p = 0.009) and root angulation (CG: 7.59 ± 2.8; IG: 4.88 ± 2.6) (p = 0.007). Criteria that did not improve, but had the highest scores were: alignment (CG: 6.35 ± 2.7; IG: 6.82 ± 2.8) (p = 0.62) and buccolingual inclination (CG: 3.6 ± 5.88; IG: 5.29 ± 3.9) (p = 0.65). Conclusions: Standardization and implementation of a finishing protocol contributed to improve clinical performance in the Orthodontics graduate program, as expressed by occlusal outcomes. Greater emphasis should be given on the finishing phase to achieve lower scores in the ABO grading system. PMID:27275620

  4. Long-Term Weight Change after Initiating Second-Generation Antidepressants

    PubMed Central

    Arterburn, David; Sofer, Tamar; Boudreau, Denise M.; Bogart, Andy; Westbrook, Emily O.; Theis, Mary Kay; Simon, Greg; Haneuse, Sebastien

    2016-01-01

    (1) Objective: To examine the relationship between the choice of second-generation antidepressant drug treatment and long-term weight change; (2) Methods: We conducted a retrospective cohort study to investigate the relationship between choice of antidepressant medication and weight change at two years among adult patients with a new antidepressant treatment episode between January, 2006 and October, 2009 in a large health system in Washington State. Medication use, encounters, diagnoses, height, and weight were collected from electronic databases. We modeled change in weight and BMI at two years after initiation of treatment using inverse probability weighted linear regression models that adjusted for potential confounders. Fluoxetine was the reference treatment; (3) Results: In intent-to-treat analyses, non-smokers who initiated bupropion treatment on average lost 7.1 lbs compared to fluoxetine users who were non-smokers (95% CI: −11.3, −2.8; p-value < 0.01); smokers who initiated bupropion treatment gained on average 2.2 lbs compared to fluoxetine users who were smokers (95% CI: −2.3, 6.8; p-value = 0.33). Changes in weight associated with all other antidepressant medications were not significantly different than fluoxetine, except for sertraline users, who gained an average of 5.9 lbs compared to fluoxetine users (95% CI: 0.8, 10.9; p-value = 0.02); (4) Conclusion: Antidepressant drug therapy is significantly associated with long-term weight change at two years. Bupropion may be considered as the first-line drug of choice for overweight and obese patients unless there are other existing contraindications. PMID:27089374

  5. Improving Access to Online Health Information With Conversational Agents: A Randomized Controlled Experiment

    PubMed Central

    2016-01-01

    Background Conventional Web-based search engines may be unusable by individuals with low health literacy for finding health-related information, thus precluding their use by this population. Objective We describe a conversational search engine interface designed to allow individuals with low health and computer literacy identify and learn about clinical trials on the Internet. Methods A randomized trial involving 89 participants compared the conversational search engine interface (n=43) to the existing conventional keyword- and facet-based search engine interface (n=46) for the National Cancer Institute Clinical Trials database. Each participant performed 2 tasks: finding a clinical trial for themselves and finding a trial that met prespecified criteria. Results Results indicated that all participants were more satisfied with the conversational interface based on 7-point self-reported satisfaction ratings (task 1: mean 4.9, SD 1.8 vs mean 3.2, SD 1.8, P<.001; task 2: mean 4.8, SD 1.9 vs mean 3.2, SD 1.7, P<.001) compared to the conventional Web form-based interface. All participants also rated the trials they found as better meeting their search criteria, based on 7-point self-reported scales (task 1: mean 3.7, SD 1.6 vs mean 2.7, SD 1.8, P=.01; task 2: mean 4.8, SD 1.7 vs mean 3.4, SD 1.9, P<.01). Participants with low health literacy failed to find any trials that satisfied the prespecified criteria for task 2 using the conventional search engine interface, whereas 36% (5/14) were successful at this task using the conversational interface (P=.05). Conclusions Conversational agents can be used to improve accessibility to Web-based searches in general and clinical trials in particular, and can help decrease recruitment bias against disadvantaged populations. PMID:26728964

  6. Cardiorenal Involvement in Metabolic Syndrome Induced by Cola Drinking in Rats: Proinflammatory Cytokines and Impaired Antioxidative Protection.

    PubMed

    Otero-Losada, Matilde; Gómez Llambí, Hernán; Ottaviano, Graciela; Cao, Gabriel; Müller, Angélica; Azzato, Francisco; Ambrosio, Giuseppe; Milei, José

    2016-01-01

    We report experimental evidence confirming renal histopathology, proinflammatory mediators, and oxidative metabolism induced by cola drinking. Male Wistar rats drank ad libitum regular cola (C, n = 12) or tap water (W, n = 12). Measures. Body weight, nutritional data, plasma glucose, cholesterol fractions, TG, urea, creatinine, coenzyme Q10, SBP, and echocardiograms (0 mo and 6 mo). At 6 months euthanasia was performed. Kidneys were processed for histopathology and immunohistochemistry (semiquantitative). Compared with W, C rats showed (I) overweight (+8%, p < 0.05), hyperglycemia (+11%, p < 0.05), hypertriglyceridemia (2-fold, p < 0.001), higher AIP (2-fold, p < 0.01), and lower Q10 level (-55%, p < 0.05); (II) increased LV diastolic diameter (+9%, p < 0.05) and volume (systolic +24%, p < 0.05), posterior wall thinning (-8%, p < 0.05), and larger cardiac output (+24%, p < 0.05); (III) glomerulosclerosis (+21%, p < 0.05), histopathology (+13%, p < 0.05), higher tubular expression of IL-6 (7-fold, p < 0.001), and TNFα (4-fold, p < 0.001). (IV) Correlations were found for LV dimensions with IL-6 (74%, p < 0.001) and TNFα (52%, p < 0.001) and ful