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Sample records for 3p 5q 17p

  1. Clonal Ordering of 17p and 5q Allelic Losses in Barrett Dysplasia and Adenocarcinoma

    NASA Astrophysics Data System (ADS)

    Blount, Patricia L.; Meltzer, Stephen J.; Yin, Jing; Huang, Ying; Krasna, Mark J.; Reid, Brian J.

    1993-04-01

    Both 17p and 5q allelic losses appear to be involved in the pathogenesis or progression of many human solid tumors. In colon carcinogenesis, there is strong evidence that the targets of the 17p and 5q allelic losses are TP53, the gene encoding p53, and APC, respectively. It is widely accepted that 5q allelic losses precede 17p allelic losses in the progression to colonic carcinoma. The data, however, supporting this proposed order are largely based on the prevalence of 17p and 5q allelic losses in adenomas and unrelated adenocarcinomas from different patients. We investigated the order in which 17p and 5q allelic losses developed during neoplastic progression in Barrett esophagus by evaluating multiple aneuploid cell populations from the same patient. Using DNA content flow cytometric cell sorting and polymerase chain reaction, 38 aneuploid cell populations from 14 patients with Barrett esophagus who had high grade dysplasia, cancer or both were evaluated for 17p and 5q allelic losses. 17p allelic losses preceded 5q allelic losses in 7 patients, both 17p and 5q allelic losses were present in all aneuploid populations of 4 patients, and only 17p (without 5q) allelic losses were present in the aneuploid populations of 3 patients. In no patient did we find that a 5q allelic loss preceded a 17p allelic loss. Our data suggest that 17p allelic losses typically occur before 5q allelic losses during neoplastic progression in Barrett esophagus.

  2. Partial monosomy 3p (3p26.2 --> pter) and partial trisomy 5q (5q34 --> qter) in a girl with coarctation of the aorta, congenital heart defects, short stature, microcephaly and developmental delay.

    PubMed

    Chen, C P; Lin, S P; Chen, M R; Su, Y N; Chern, S R; Liu, Y P; Su, J W; Lee, M S; Wang, W

    2012-01-01

    A 1-year-and-3-month-old girl presented with psychomotor retardation, developmental delay, clinodactyly of the thumb, coarctation of the aorta, patent ductus arteriosus, peripheral pulmonary stenosis, atrial septal defect, microcephaly, brachycephaly, a small oval face, almond-shaped eyes, a down-turned mouth, a widened nasal bridge, hypertelorism, epicanthic folds, long philtrum, low-set large ears and but no craniosynostosis. Oligonucleotide-based array comparative genomic hybridization revealed a -4.79-Mb deletion of 3p26.2 --> pter encompassing CHL1 and CNTN4, and a -19.56-Mb duplication of 5q34 --> qter encompassing MSX2, NKX2-5 and NSD1. The karyotype of the girl was 46,XX,der(3)t(3;5)(p26.2;q34) pat. The present case adds distal 5q duplication to the list of chromosome aberrations associated with coarctation of the aorta. PMID:23072190

  3. [Mosaic isochromosome Xq and microduplication 17p13.3p13.2 in a patient with Turner syndrome and congenital cataract].

    PubMed

    Rojas Martínez, Jorge A; Acosta Guio, Johanna C

    2015-01-01

    The combination of Turner syndrome with other genetic disorders such as congenital cataract has been reported, but its association with a congenital form with autosomal dominant inheritance and incomplete penetrance has not been previously reported in the literature. There are no reports on its presentations with rearrangements on chromosome 17. We report the exceptional case of a 20 months old girl with a constellation of major and minor anomalies, diagnosed with mosaic Turner syndrome by isochromosome Xq associated with a microduplication 17p13.3p13.2, who also had bilateral congenital nuclear cataract autosomal dominant with incomplete penetrance. We reviewed in the literature the origin and cause of these genetic alterations and we provided an approach to the hypothesis of the pathogenesis of the association of two of these genetic disorders in the same patient.

  4. Gene fusions AHRR-NCOA2, NCOA2-ETV4, ETV4-AHRR, P4HA2-TBCK, and TBCK-P4HA2 resulting from the translocations t(5;8;17)(p15;q13;q21) and t(4;5)(q24;q31) in a soft tissue angiofibroma

    PubMed Central

    Panagopoulos, Ioannis; Gorunova, Ludmila; Viset, Trond; Heim, Sverre

    2016-01-01

    We present an angiofibroma of soft tissue with the karyotype 46,XY,t(4;5)(q24;q31),t(5;8;17)(p15;q13;q21) [8]/46,XY,t(1;14)(p31;q32)[2]/46,XY[3]. RNA-sequencing showed that the t(4;5)(q24;q31) resulted in recombination of the genes TBCK on 4q24 and P4HA2 on 5q31.1 with generation of an in-frame TBCK-P4HA2 and the reciprocal but out-of-frame P4HA2-TBCK fusion transcripts. The putative TBCK-P4HA2 protein would contain the kinase, the rhodanese-like domain, and the Tre-2/Bub2/Cdc16 (TBC) domains of TBCK together with the P4HA2 protein which is a component of the prolyl 4-hydroxylase. The t(5;8;17)(p15;q13;q21) three-way chromosomal translocation targeted AHRR (on 5p15), NCOA2 (on 8q13), and ETV4 (on 17q21) generating the in-frame fusions AHRR-NCOA2 and NCOA2-ETV4 as well as an out-of-frame ETV4-AHRR transcript. In the AHRR-NCOA2 protein, the C-terminal part of AHRR is replaced by the C-terminal part of NCOA2 which contains two activation domains. The NCOA2-ETV4 protein would contain the helix-loop-helix, PAS_9 and PAS_11, CITED domains, the SRC-1 domain of NCOA2 and the ETS DNA-binding domain of ETV4. No fusion gene corresponding to t(1;14)(p31;q32) was found. Our findings indicate that, in spite of the recurrence of AHRR-NCOA2 in angiofibroma of soft tissue, additional genetic events (or fusion genes) might be required for the development of this tumor. PMID:27633981

  5. Recent Advances in the 5q- Syndrome

    PubMed Central

    Pellagatti, Andrea; Boultwood, Jacqueline

    2015-01-01

    The 5q- syndrome is the most distinct of the myelodysplastic syndromes (MDS) and patients with this disorder have a deletion of chromosome 5q [del(5q)] as the sole karyotypic abnormality. Several genes mapping to the commonly deleted region of the 5q- syndrome have been implicated in disease pathogenesis in recent years. Haploinsufficiency of the ribosomal gene RPS14 has been shown to cause the erythroid defect in the 5q- syndrome. Loss of the microRNA genes miR-145 and miR-146a has been associated with the thrombocytosis observed in 5q- syndrome patients. Haploinsufficiency of CSNK1A1 leads to hematopoietic stem cell expansion in mice and may play a role in the initial clonal expansion in patients with 5q- syndrome. Moreover, a subset of patients harbor mutation of the remaining CSNK1A1 allele. Mouse models of the 5q- syndrome, which recapitulate the key features of the human disease, indicate that a p53-dependent mechanism underlies the pathophysiology of this disorder. Importantly, activation of p53 has been demonstrated in the human 5q- syndrome. Recurrent TP53 mutations have been associated with an increased risk of disease evolution and with decreased response to the drug lenalidomide in del(5q) MDS patients. Potential new therapeutic agents for del(5q) MDS include the translation enhancer L-leucine. PMID:26075044

  6. Deletion 5q35.3

    SciTech Connect

    Stratton, R.F.; Tedrowe, N.A.; Tolworthy, J.A.; Patterson, R.M.; Ryan, S.G.; Young, R.S.

    1994-06-01

    The authors report on a 15-month-old boy with a de novo deletion of the terminal band of 5q, macrocephaly, mild retrognathia, anteverted nares with low flat nasal bridge, telecanthus, minor earlobe anomalies, bellshaped chest, diastasis recti, short fingers, and mild developmental delay.

  7. Molecular dissection of the 5q deletion in myelodysplastic syndrome

    PubMed Central

    Ebert, Benjamin L.

    2011-01-01

    The 5q- syndrome is a subtype of myelodysplastic syndrome (MDS) with a defined clinical phenotype associated with heterozygous deletions of Chromosome 5q. While no genes have been identified that undergo recurrent homozygous inactivation, functional studies have revealed individual genes that contribute to the clinical phenotype of MDS through haploinsufficient gene expression. Heterozygous loss of the RPS14 gene on 5q leads to activation of p53 in the erythroid lineage and the macrocytic anemia characteristic of the 5q- syndrome. The megakaryocytic and platelet phenotype of the 5q- syndrome has been attributed to heterozygous deletion of miR145 and miR146a. Murine models have implicated heterozygous loss of APC, EGR1, DIAPH1, and NPM1 in the pathophysiology of del(5q) MDS. These findings indicate that the phenotype of MDS patients with deletions of Chromosome 5q is due to haploinsufficiency of multiple genes. PMID:21943668

  8. Exploding Comet 17P/Holmes

    NASA Astrophysics Data System (ADS)

    Sekanina, Zdenek

    2008-01-01

    The light curve and dust-halo expansion curve of comet 17P are constructed, examined, and compared with those of other comets that experienced outbursts. The 2007 megaburst of 17P is unrivaled as the most powerful event of this kind on record. The proposed scenario for the megaburst involves an exothermic reaction caused by a transition of water ice from low-density amorphous phase to cubic phase in a reservoir spread below a pancake-shaped thick layer of 10^(14) g of terrain on the nucleus' surface. The resulting explosion jettisoned this layer of inert mass into the atmosphere as a major fragment that began to crumble precipitously into a rapidly expanding cloud of microscopic dust immediately upon the lift-off. Fewer than 50 events of this magnitude would consume the entire comet.

  9. Molecular mapping of uncharacteristically small 5q deletions in two patients with the 5q-syndrome: Delineation of the critical region on 5q and identification of a 5q-breakout

    SciTech Connect

    Boultwood, J.; Fidler, C.; Lewis, S.; Littlewood, T.J.; Wainscoat, J.S.; Buckle, V.J. ); Kelly, S. ); Sheridan, H. )

    1994-02-01

    Molecular mapping techniques have defined the region of gene loss in two patients with the 5q-syndrome and uncharacteristically small 5q deletions (5q31-q33). The allelic loss of 10 genes localized to 5q23-qter (centromere-CSF2-EGR1-FGFA-GRL-ADRB2-CSF1R-SPARC-GLUH1-NKSF1-FLT4-telomere) was investigated in peripheral blood cell fractions. Gene dosage experiments demonstrated that CSF2, EGR1, NKSF1, and FLT4 were retained on the 5q-chromosome in both patients and that FGFA was retained in one patient, thus placing these genes outside the critical region. GRL, ADRB2, CSF1R, SPARC, and GLUH1 were shown to be deleted in both patients. The proximal breakpoint is localized between EGR1 and FGFA in one patient and between FGFA and ADRB2 in the other, and the distal breakpoint is localized between GLUH1 and NKSF1 in both patients. Pulsed-field gel electrophoresis was used to map the 5q deletion breakpoints, and breakpoint-specific fragments were detected with FGFA in the granulocyte but not the lymphocyte fraction of one patient. This study has established the critical region of gene loss of the 5q-chromosome in the 5q-syndrome, giving the location for a putative tumor-suppressor gene in the 5.6-Mb region between FGFA and NKSF1. 54 refs., 3 figs., 2 tabs.

  10. 5Q4: Chris Edwards - Child Presence Sensor

    NASA Video Gallery

    Five Questions For (5Q4) Chris Edwards, NASA engineer who was the team lead of a group that invented a child presence sensor designed to alert parents if they've inadvertently left their child in h...

  11. New insights into 5q- syndrome as a ribosomopathy.

    PubMed

    Barlow, Jillian L; Drynan, Lesley F; Trim, Nicola L; Erber, Wendy N; Warren, Alan J; McKenzie, Andrew N J

    2010-11-01

    Myelodysplastic Syndromes (MDS) are a heterogeneous group of acquired clonal bone marrow disorders, characterised by ineffective hematopoiesis. The mechanisms underlying many of these blood disorders have remained elusive due to the difficulty in pinpointing specific gene mutations or haplo-insufficencies, which can occur within large deleted regions. However, there is an increasing interest in the classification of some of these diseases as ribosomopathies. Indeed, studies have implicated Ribosomal Protein (RP) S14 as a strong candidate for haploinsufficiency in 5q- syndrome, a particular form of MDS. Recently, two novel mouse models have provided evidence for the involvement of both RPS14 and the p53 pathway, and specific miRNAs in 5q- syndrome. In this review we will discuss: 5q- syndrome mouse models, the possible mechanisms underlying this blood disorder with respect to the candidate genes and comparisons with other ribosomopathies and the involvement of the p53 pathway in these diseases. PMID:20980806

  12. Cryptorchidism due to chromosome 5q inversion duplication.

    PubMed

    Dutta, M K; Gundgurthi, A; Garg, M K; Pakhetr, R

    2013-12-01

    We present a 15 year old boy who was born out of a non consanguineous marriage, and presented with bilateral cryptorchidism, mental retardation, facial dysmorphism, hypergonadotrophic hypogonadism with failure of anatomical and biochemical localisation of testes. Karyotype analysis showed 46 XY with inverted duplication on chromosome 5q22-31.

  13. I3P Overview

    NASA Video Gallery

    Deborah Diaz, the NASA's Deputy Chief Information Officer, talks about the Information Technology Infrastructure Integration Program (I3P). I3P is NASA's initiative to provide Agency-wide managemen...

  14. A locus regulating bronchial hyperresponsiveness maps to chromosome 5q

    SciTech Connect

    Levitt, R.C.; Meyers, D.A.; Bleecker, E.R.

    1994-09-01

    Bronchial hyperresponsiveness (BHR) is one of the hallmarks of asthma. BHR correlates well with asthmatic symptoms and the response to treatment. Moreover, BHR appears to be closely related to airways inflammation. Numerous studies have demonstrated a familial aggregation; however, this phenotype is not likely inherited as a simple Mendelian trait. BHR is also closely associated with total serum IgE levels, as are allergy and asthma. We studied 92 families from Northern Holland ascertained through a parent with asthma who were originally studied between 1962-1970. Since there are a number of candidate genes on chromosome 5q potentially important in producing BHR, families were genotyped for markers in this region. These genes regulate IgE production and the cellular elements that are likely involved in inflammation associated with BHR, allergy and asthma. They include IL-4, IL-3, IL-5, IL-9, IL-12, IL-13 and GM-CSF. Linkage of BHR with markers on 5q was tested using a model free sib-pair method. The data suggest a locus for BHR maps near the cytokine gene cluster on 5q. This region appears critical in producing susceptibility to BHR and possibly to asthma.

  15. Mutation hot spots in 5q31-linked corneal dystrophies.

    PubMed Central

    Korvatska, E; Munier, F L; Djemaï, A; Wang, M X; Frueh, B; Chiou, A G; Uffer, S; Ballestrazzi, E; Braunstein, R E; Forster, R K; Culbertson, W W; Boman, H; Zografos, L; Schorderet, D F

    1998-01-01

    Mutations in the BIGH3 gene on chromosome 5q31 cause four distinct autosomal dominant diseases of the human cornea: granular (Groenouw type I), Reis-Bücklers, lattice type I, and Avellino corneal dystrophies. All four diseases are characterized by both progressive accumulation of corneal deposits and eventual loss of vision. We have identified a specific recurrent missense mutation for each type of dystrophy, in 10 independently ascertained families. Genotype analysis with microsatellite markers surrounding the BIGH3 locus was performed in these 10 families and in 5 families reported previously. The affected haplotype could be determined in 10 of the 15 families and was different in each family. These data indicate that R555W, R124C, and R124H mutations occurred independently in several ethnic groups and that these mutations do not reflect a putative founder effect. Furthermore, this study confirms the specific importance of the R124 and R555 amino acids in the pathogenesis of autosomal dominant corneal dystrophies linked to 5q. PMID:9463327

  16. Outcome following haematopoietic cell transplantation in patients with myelodysplasia and del (5q) karyotypes.

    PubMed

    Stewart, B; Verdugo, M; Guthrie, K A; Appelbaum, F; Deeg, H J

    2003-12-01

    The deletion (5q) karyotype [del (5q)] in patients with myelodysplastic syndrome (MDS) is considered a good risk feature, while the impact of del (5q) combined with other karyotypic abnormalities [del (5q)+] is less well defined. We analysed the outcome of haematopoietic cell transplants (HCT) in patients with MDS with del (5q) or del (5q)+. Fifty-seven patients, aged 6-72 years, with MDS and del (5q) abnormalities received HCT from related (n = 32) or unrelated (n = 25) donors. By French-American-British (FAB) criteria, 27 patients had refractory anaemia (RA), 10 RA with excess blasts (RAEB), eight RAEB in transformation (RAEB-T) and 12 acute myeloid leukaemia evolving from MDS (tAML). Non-relapse mortality at 1-year post-transplantation was 30% for del (5q) and 38% for del (5q)+ patients. Relapse occurred in one of 20 del (5q) patients and 15 of 37 del (5q)+ patients (P = 0.001). After adjusting for del (5q) status, blast count (<5%) was the only factor significantly associated with relapse-free survival. Patients with del (5q), either as a '5q- syndrome' or with MDS in general, had better outcomes than did patients with del (5q)+. The indication for transplantation in patients with del (5q) was generally severe cytopenias, compared with disease progression to a more advanced FAB stage in patients with del (5q)+. Conceivably, outcome for patients with del (5q)+ would be improved with transplantation earlier in the disease course. PMID:14632779

  17. Familial short stature due to a 5q22.1-q23.2 duplication refines the 5q duplication spectrum.

    PubMed

    Zahnleiter, Diana; Trautmann, Udo; Ekici, Arif B; Goehring, Ina; Reis, André; Dörr, Helmuth-Günther; Rauch, Anita; Thiel, Christian T

    2011-01-01

    We identified a maternally inherited 14.2Mb duplication 5q22.1-q23.2 in two female siblings and their mother by molecular karyotyping. Both siblings were small for gestational age and presented with pronounced postnatal growth retardation, mild motor delay, congenital heart disease in one of the siblings, and distinct facial dysmorphism. As this duplication is one of the smallest reported 5q duplications, short stature and facial dysmorphism can be attributed to duplications of 5q22, whereas severe mental retardation is not part of the phenotypic spectrum of the 5q22.1-q23.2 region. Congenital heart defects, as observed in other 5q duplications, have a variable penetrance. We compared the facial features of patients with 5q duplications and found some consistent features such as high arched eyebrows, bulbous nasal tip and small lips with thin vermilion border. PMID:21777705

  18. A Stellar Appulse by Exploding Comet 17P/Holmes

    NASA Astrophysics Data System (ADS)

    Lacerda, Pedro; Jewitt, D.

    2012-10-01

    Comet 17P/Holmes suffered a massive outburst in October 2007. Its total brightness increased from about 17th to 2nd magnitude over a period of only two days as 17P released about 1-10% of its mass into space in the form of dust. Several theories have been proposed to explain the event but the exact cause for the outburst remains unknown. 17P had suffered a similar outburst more than one century ago, which led to its discovery. These unusual and violent explosions have rendered this otherwise unremarkable Jupiter family comet an interesting target of study, because it may provide clues to the activity in other comets. On 29 October 2007, the optocenter of outbursting 17P passed within 1" of a background star. We used observations taken at the Univ. of Hawaii 2.2m telescope located atop Mauna Kea to measure the brightness of the star as it crossed the coma of 17P in an attempt to estimate the optical depth of the dust. The time sampling was 10-15 min. In addition, we used two-band photometry to look for colour variation as the star crossed the dust cloud. These measurements place the most stringent constraints on the extinction optical depth of any cometary coma.

  19. THE OUTBURST OF COMET 17P/HOLMES

    SciTech Connect

    Lin Zhongyi; Lara, Luisa M.; Lin, C.-S.; Ip, W.-H.

    2009-08-15

    Comet 17P/Holmes had a massive outburst at approximately 2007 October 23.8 and its total brightness reached maximum (from m = 17 to m = 2.5) around 2007 October 25, about 1.7 days (42 hr) after the event. Following the first report of this extraordinary cometary outburst, comprehensive observations were obtained at the Lulin Observatory until early 2008 January by using broadband filters and narrowband cometary filters. The separation velocity, as projected on the plane of the sky, between the nucleus and the coma blob produced by the outburst has been estimated to be 0.132 {+-} 0.004 km s{sup -1} from October 25.8 to November 1.6. The expansion speed, also projected on the plane of the sky of the dust shell has been found to be constant at a rate of approximately 0.554 {+-} 0.005 km s{sup -1} from October 25.8 to November 1.6. The color on December 10 is slightly redder than that of the Sun. Our narrowband observations provide information on the production rates of gas species on October 31: log Q (CN) = 27.103 and log Q (C{sub 2}) = 27.349. The resulting abundance ratios show that the comet 17P can be classified as a 'typical comet' in terms of composition.

  20. EXTINCTION IN THE COMA OF COMET 17P/HOLMES

    SciTech Connect

    Lacerda, Pedro; Jewitt, David

    2012-11-20

    On 2007 October 29, the outbursting comet 17P/Holmes passed within 0.''79 of a background star. We recorded the event using optical, narrowband photometry and detect a 3%-4% dip in stellar brightness bracketing the time of closest approach to the comet nucleus. The detected dimming implies an optical depth {tau} Almost-Equal-To 0.04 at 1.''5 from the nucleus and an optical depth toward the nucleus center {tau}{sub n} < 13.3. At the time of our observations, the coma was optically thick only within {rho} {approx}< 0.''01 from the nucleus. By combining the measured extinction and the scattered light from the coma, we estimate a dust red albedo p{sub d} = 0.006 {+-} 0.002 at {alpha} = 16 Degree-Sign phase angle. Our measurements place the most stringent constraints on the extinction optical depth of any cometary coma.

  1. Mapping of the versican proteoglycan gene (CSPG2) to the long arm of human chromosome 5 (5q12-5q14)

    SciTech Connect

    Iozzo, R.V.; Naso, M.F.; Cannizzaro, L.A. ); Wasmuth, J.J.; McPerson, J.D. )

    1992-12-01

    Versican is a major chondroitin sulfate proteoglycan of vascularized connective tissues whose eponym reflects its functional versatility in macromolecular affinity and interactions. In this report the authors have localized the versican gene (CSPG2) to the long arm of human chromosome 5 by utilizing a combination of somatic cell hybrids, Southern blotting, polymerase chain reaction, and chromosomal in situ hybridization. The proteoglycan gene segregated concordantly with hybrid cell lines containing the long arm of chromosome 5, comprising the 5q12-q14 band regions. To refine this locus further, they screened a chromosome 5-specific library and isolated several genomic clones encoding a portion of the 5[prime] end of versican. One of these genomic clones was used as a probe for in situ hybridization of human chromosome metaphases. The results corroborated the data obtained using somatic cell hybrids and further refined the assignment of the versican gene to the narrow band region of 5q12-5q14, with the primary site likely to be 5q13.2. The availability of novel genomic clones and the mapping data presented here will make possible the identification of any defect genetically linked to this proteoglycan gene. 27 refs., 4 figs.

  2. Lingering Grains of Truth around Comet 17P/Holmes

    NASA Astrophysics Data System (ADS)

    Stevenson, R.; Bauer, J. M.; Kramer, E. A.; Grav, T.; Mainzer, A. K.; Masiero, J. R.

    2014-06-01

    Comet 17P/Holmes underwent a massive outburst in 2007 October, brightening by a factor of almost a million in under 48 hr. We used infrared images taken by the Wide-Field Infrared Survey Explorer mission to characterize the comet as it appeared at a heliocentric distance of 5.1 AU almost 3 yr after the outburst. The comet appeared to be active with a coma and dust trail along the orbital plane. We constrained the diameter, albedo, and beaming parameter of the nucleus to 4.135 ± 0.610 km, 0.03 ± 0.01, and 1.03 ± 0.21, respectively. The properties of the nucleus are consistent with those of other Jupiter family comets. The best-fit temperature of the coma was 134 ± 11 K, slightly higher than the blackbody temperature at that heliocentric distance. Using Finson-Probstein modeling, we found that the morphology of the trail was consistent with ejection during the 2007 outburst and was made up of dust grains between 250 μm and a few cm in radius. The trail mass was ~1.2-5.3 × 1010 kg.

  3. Lingering grains of truth around comet 17P/HOLMES

    SciTech Connect

    Stevenson, R.; Bauer, J. M.; Mainzer, A. K.; Masiero, J. R.; Kramer, E. A.; Grav, T.

    2014-06-01

    Comet 17P/Holmes underwent a massive outburst in 2007 October, brightening by a factor of almost a million in under 48 hr. We used infrared images taken by the Wide-Field Infrared Survey Explorer mission to characterize the comet as it appeared at a heliocentric distance of 5.1 AU almost 3 yr after the outburst. The comet appeared to be active with a coma and dust trail along the orbital plane. We constrained the diameter, albedo, and beaming parameter of the nucleus to 4.135 ± 0.610 km, 0.03 ± 0.01, and 1.03 ± 0.21, respectively. The properties of the nucleus are consistent with those of other Jupiter family comets. The best-fit temperature of the coma was 134 ± 11 K, slightly higher than the blackbody temperature at that heliocentric distance. Using Finson-Probstein modeling, we found that the morphology of the trail was consistent with ejection during the 2007 outburst and was made up of dust grains between 250 μm and a few cm in radius. The trail mass was ∼1.2-5.3 × 10{sup 10} kg.

  4. Water outburst activity in Comet 17P/Holmes

    NASA Astrophysics Data System (ADS)

    de Almeida, Amaury A.; Boice, Daniel C.; Picazzio, Enos; Huebner, Walter F.

    2016-08-01

    Cometary outbursts are sporadic events whose mechanisms are not well known where the activity and consequently the brightness can increase hundreds of thousands of times within a few hours to several days. This indicates a dramatic departure from thermal equilibrium between the comet and interplanetary space and is usually documented by "light curves". In a typical cometary outburst, the brightness can increase by 2-5 magnitudes (Whitney, 1955; Gronkowski and Wesolowski, 2015). In only 42 h, Comet 17P/Holmes was reported to brighten from a magnitude of about 17 to about 2.4 at the height of the burst, representing the largest known outburst by a comet. We present the H2O production rate of Holmes for the megaburst occurring between 23 and 24 October 2007. For this, we selected more than 1900 photometric observations from the International Comet Quarterly Archive of Photometric Data (Green, 2007) and use the Semi-Empirical Method of Visual Magnitudes (SEMVM; de Almeida et al., 2007). We clearly show that the comet achieved an average water production rate of 5 × 1029 molecules s-1, corresponding to a water gas loss rate of 14,960 kg s-1, in very good agreement with Schleicher (2009) who derived the water production rate using OH measurements on 1 Nov 2007 (about 8 days after the outburst). We discuss possible physical processes that might cause cometary outbursts and propose a new qualitative mechanism, the Pressurized Obstructed Pore (POP) model. The key feature of POP is the recrystallization of water in the surface regolith as it cools, plugging pores and blocking the release of subsurface gas flow. As the interior gas pressure increases, an outburst is eventually triggered. POP is consistent with current observations and can be tested in the future with observations (e.g., Rosetta in situ measurements) and detailed simulations.

  5. Non-Diamond Blackfan anemia disorders of ribosome function: Shwachman Diamond syndrome and 5q- syndrome.

    PubMed

    Burwick, Nicholas; Shimamura, Akiko; Liu, Johnson M

    2011-04-01

    A number of human disorders, dubbed ribosomopathies, are linked to impaired ribosome biogenesis or function. These include but are not limited to Diamond Blackfan anemia (DBA), Shwachman Diamond syndrome (SDS), and the 5q- myelodysplastic syndrome (MDS). This review focuses on the latter two non-DBA disorders of ribosome function. Both SDS and 5q- syndrome lead to impaired hematopoiesis and a predisposition to leukemia. SDS, due to bi-allelic mutations of the SBDS gene, is a multi-system disorder that also includes bony abnormalities, and pancreatic and neurocognitive dysfunction. SBDS associates with the 60S subunit in human cells and has a role in subunit joining and translational activation in yeast models. In contrast, 5q- syndrome is associated with acquired haplo-insufficiency of RPS14, a component of the small 40S subunit. RPS14 is critical for 40S assembly in yeast models, and depletion of RPS14 in human CD34(+) cells is sufficient to recapitulate the 5q- erythroid defect. Both SDS and the 5q- syndrome represent important models of ribosome function and may inform future treatment strategies for the ribosomopathies. PMID:21435510

  6. Partial trisomy 5q resulting from chromosome 7 insertion: An expansion of the phenotype

    SciTech Connect

    Fries, M.H.; Reilly, P.A.; Williams, T.C.

    1994-09-01

    Partial trisomy 5q has been categorized into three separate phenotypes; however, a distinctive phenotype has not been described for duplications spanning 5q23-q35. We report a case of partial trisomy 5q for this region as a result of a ins(7,5)(q31.3;q23.2q35.1)mat. The liveborn male infant was delivered by emergency cesarean section at 37 weeks after a pregnancy notable for oligohydramnios, with birth weight 1792 g (<3%). Postnatal course was marked by psychomotor delay, failure to thrive, and biopsy demonstrated neonatal giant cell hepatitis with a paucity of intrahepatic bile ducts. His appearance was remarkable for lack of subcutaneous fat, midline displaced hair whorl, bitemporal narrowing with frontal bossing, wide anterior fontanel, widow`s peak, protuberant eyes with periorbital and lid edema, short flat nasal bridge with broad flattened nasal tip, long smooth philtrum, wide mouth with thin lips, wide gingival ridges, micrognathia, posteriorly rotated low-set ears, hepatomegaly, flexion contractions of elbows, and generalized hypertonicity. Urine organic acids, oligosaccharide/mucopolysaccharide screen, and plasma amino acids were negative. GTG-banding on prometaphase chromosomes showed an unbalanced translocation involving chr. 7. This was identified as an insertion of chr. 5 (q23.2q35.1) into distal 7q after FISH using chr. 5 and chr. 7 painting probes. The infant`s mother carries the balanced insertional rearrangement: 46,XX,dir ins(7,5)(q31.3;q23.2q35.1). This phenotype overlaps that of previously described duplications with the addition of giant cell hepatitis, coarsened facial features, gingival thickening, and flexion contractures, suggestive of a yet undiagnosed storage disorder.

  7. Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS.

    PubMed

    Krönke, Jan; Fink, Emma C; Hollenbach, Paul W; MacBeth, Kyle J; Hurst, Slater N; Udeshi, Namrata D; Chamberlain, Philip P; Mani, D R; Man, Hon Wah; Gandhi, Anita K; Svinkina, Tanya; Schneider, Rebekka K; McConkey, Marie; Järås, Marcus; Griffiths, Elizabeth; Wetzler, Meir; Bullinger, Lars; Cathers, Brian E; Carr, Steven A; Chopra, Rajesh; Ebert, Benjamin L

    2015-07-01

    Lenalidomide is a highly effective treatment for myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)). Here, we demonstrate that lenalidomide induces the ubiquitination of casein kinase 1A1 (CK1α) by the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as CRL4(CRBN)), resulting in CK1α degradation. CK1α is encoded by a gene within the common deleted region for del(5q) MDS and haploinsufficient expression sensitizes cells to lenalidomide therapy, providing a mechanistic basis for the therapeutic window of lenalidomide in del(5q) MDS. We found that mouse cells are resistant to lenalidomide but that changing a single amino acid in mouse Crbn to the corresponding human residue enables lenalidomide-dependent degradation of CK1α. We further demonstrate that minor side chain modifications in thalidomide and a novel analogue, CC-122, can modulate the spectrum of substrates targeted by CRL4(CRBN). These findings have implications for the clinical activity of lenalidomide and related compounds, and demonstrate the therapeutic potential of novel modulators of E3 ubiquitin ligases. PMID:26131937

  8. Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS

    PubMed Central

    Hollenbach, Paul W.; MacBeth, Kyle J.; Hurst, Slater N.; Udeshi, Namrata D.; Chamberlain, Philip P.; Mani, D.R.; Man, Hon Wah; Gandhi, Anita K.; Svinkina, Tanya; Schneider, Rebekka K.; McConkey, Marie; Järås, Marcus; Griffiths, Elizabeth; Wetzler, Meir; Bullinger, Lars; Cathers, Brian E.; Carr, Steven A.; Chopra, Rajesh; Ebert, Benjamin L.

    2015-01-01

    Summary Lenalidomide is a highly effective treatment for myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)). Here, we demonstrate that lenalidomide induces the ubiquitination of casein kinase 1A1 (CK1α) by the CRL4CRBN E3 ubiquitin ligase, resulting in CK1α degradation. CK1α is encoded by a gene within the common deleted region for del(5q) MDS and haploinsufficient expression sensitizes cells to lenalidomide therapy, providing a mechanistic basis for lenalidomide's therapeutic window in del(5q) MDS. We found that mouse cells are resistant to lenalidomide but that changing a single amino acid in mouse Crbn to the corresponding human residue enables lenalidomide-dependent degradation of CK1α. We further demonstrate that minor side chain modifications in thalidomide and a novel analogue, CC-122, can modulate the spectrum of substrates targeted by CRL4CRBN. These findings have implications for the clinical activity of lenalidomide and related compounds and demonstrate the therapeutic potential of novel modulators of E3 ubiquitin ligases. PMID:26131937

  9. Narrowing and genomic annotation of the commonly deleted region of the 5q- syndrome

    SciTech Connect

    Boultwood, Jacqueline; Fidler, Carrie; Strickson, Amanda J.; Watkins, Fiona; Gama, Susana; Kearney, Lyndal; Tosi, Sabrina; Kasprzyk, Arek; Cheng, Jan-Fang; Jaju, Rina J.; Wainscoat, James S.

    2002-01-15

    The 5q syndrome is the most distinct of the myelodysplastic syndromes, and the molecular basis for this disorder remains unknown. We describe the narrowing of the common deleted region (CDR) of the 5q syndrome to the approximately 1.5-megabases interval at 5q32 flanked by D5S413 and the GLRA1 gene. The Ensemblgene prediction program has been used for the complete genomic annotation of the CDR. The CDR is gene rich and contains 24 known genes and 16 novel (predicted) genes. Of 40 genes in the CDR, 33 are expressed in CD34 cells and, therefore, represent candidate genes since they are expressed within the hematopoietic stem/progenitor cell compartment. A number of the genes assigned to the CDR represent good candidates for the 5q syndrome, including MEGF1, G3BP, and several of the novel gene predictions. These data now afford a comprehensive mutational/expression analysis of all candidate genes assigned to the CDR.

  10. Cancer of the ampulla of Vater: chromosome 17p allelic loss is associated with poor prognosis

    PubMed Central

    Scarpa, A; Di, P; Talamini, G; Falconi, M; Lemoine, N; Iacono, C; Achille, A; Baron, A; Zamboni, G

    2000-01-01

    BACKGROUND—Cancer of the ampulla of Vater kills 60% of affected patients. Local spread of the tumour (T stage) is the only reliable prognostic factor. Nevertheless, any cancer stage includes long term survivors and patients dying from the disease. The molecular anomalies involved in this process have the potential to serve as additional prognostic markers.
AIM—To evaluate if allelic losses (LOH) of chromosomes 17p and 18q may be of prognostic value in multivariate survival analysis.
METHODS—We examined 53 ampullary cancers for chromosome 17p and 18q LOH using microsatellite markers and DNA from paraffin embedded tumours. All patients were treated by surgery alone (pancreaticoduodenectomy). Multivariate survival analysis included age, sex, tumour size, macroscopic appearance, grade of differentiation, T stage, lymph node metastasis, and chromosome 17p and 18q status.
RESULTS—Chromosome 17p and 18q LOH were detected in 28 (53%) and 18 (34%) cancers, respectively. Multivariate survival analysis indicated chromosome 17p status as an independent prognostic factor together with T stage. The five year survival for chromosome 17p retention and 17p loss was 80% and 7%, respectively. The risk of death from cancer within the five year follow up period for patients with cancers harbouring chromosome 17p LOH was 11 times higher than that of patients with cancers retaining chromosome 17p (p<0.0001), regardless of the tumour stage at diagnosis.
CONCLUSIONS—Chromosome 17p status is an independent prognostic factor among ampullary cancers at the same stage. The combined use of T stage and chromosome 17p status may help in deciding whether ampullary cancer patients require additional therapy other than surgery alone.


Keywords: ampulla of Vater; cancer; loss of heterozygosity; microsatellites; allelotyping; microsatellite instability PMID:10807898

  11. Molecular analysis of deletion (17)(p11.2p11.2) in a family segregating a 17p paracentric inversion: implications for carriers of paracentric inversions.

    PubMed Central

    Yang, S P; Bidichandani, S I; Figuera, L E; Juyal, R C; Saxon, P J; Baldini, A; Patel, P I

    1997-01-01

    A male child with multiple congenital anomalies initially was clinically diagnosed as having Smith-Lemli-Opitz syndrome (SLOS). Subsequent cytogenetic studies revealed an interstitial deletion of 17p11.2, which is associated with Smith-Magenis syndrome (SMS). Biochemical studies were not supportive of a diagnosis of SLOS, and the child did not display the typical SMS phenotype. The father's karyotype showed a paracentric inversion of 17p, with breakpoints in p11.2 and p13.3, and the same inversion was also found in two of the father's sisters. FISH analyses of the deleted and inverted 17p chromosomes indicated that the deletion was similar to that typically seen in SMS patients and was found to bracket the proximal inversion breakpoint. Available family members were genotyped at 33 polymorphic DNA loci in 17p. These studies determined that the deletion was of paternal origin and that the inversion was of grandpaternal origin. Haplotype analysis demonstrated that the 17p11.2 deletion arose following a recombination event involving the father's normal and inverted chromosome 17 homologues. A mechanism is proposed to explain the simultaneous deletion and apparent "reinversion" of the recombinant paternal chromosome. These findings have implications for prenatal counseling of carriers of paracentric inversions, who typically are considered to bear minimal reproductive risk. Images Figure 1 Figure 2 Figure 3 PMID:9150166

  12. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Proficiency examinations (sections 4p and 17(p) of the Act). 170.10 Section 170.10 Commodity and Securities Exchanges COMMODITY... examinations (sections 4p and 17(p) of the Act). A futures association may prescribe different...

  13. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 2 2014-04-01 2014-04-01 false Proficiency examinations (sections 4p and 17(p) of the Act). 170.10 Section 170.10 Commodity and Securities Exchanges COMMODITY... Proficiency examinations (sections 4p and 17(p) of the Act). A futures association may prescribe...

  14. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Proficiency examinations (sections 4p and 17(p) of the Act). 170.10 Section 170.10 Commodity and Securities Exchanges COMMODITY... examinations (sections 4p and 17(p) of the Act). A futures association may prescribe different...

  15. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 1 2011-04-01 2011-04-01 false Proficiency examinations (sections 4p and 17(p) of the Act). 170.10 Section 170.10 Commodity and Securities Exchanges COMMODITY... examinations (sections 4p and 17(p) of the Act). A futures association may prescribe different...

  16. Duplication of 5q21 in a mildly retarded male and his non-retarded mother

    SciTech Connect

    Stallard, R.; Zurcher, V.; Schwartz, S.

    1994-09-01

    Euchromatic autosomal additions to chromosomal complements are typically associated with global effects including mental retardation (MR) and dysmorphism. We report a familial duplication that does not appear to cause consistent, significant effects. A hyperactive male with mild MR was referred for fra(X) testing at 8 yrs. His karyotype was fra(X) negative and normal except for an addition in one 5q. The abnormal 5 was also in the maternal karyotype, but all other parental chromosomes were normal. The addition (=8.5% the length of a 5) was interpreted as a duplication of band 5q21. FISH with Coatasome 5 (Oncor) showed the addition was from 5. The proband`s karyotype was designated 46,XY,dup(5)(q15q22.1)mat; his mother`s, 46,XX,dup(5)(q15q22.1). Single copy probes are being used to test the cytogenetic interpretation. At 39 yrs, the non-retarded, somewhat inattentive mother, who has a high school diploma and subsequent secretarial courses, cares for the proband and his chromosomally normal, but learning disabled sister at home. The family situation is chaotic with reported paternal psychiatric illness and abuse of the proband and his sister. The mother`s father is dead, but her four younger siblings and mother are reportedly normal. Their chromosomes have not been available. The proband was born at 40 weeks following an uneventful pregnancy, with length and weight at the 5-10th centiles. He walked and talked at about one year. At 9 yrs, his ht/wt ratio was 10th centile. Foot length as <3rd centile; soft masses were present on the anterior ankles. He was otherwise physically normal. His estimated I.Q. was 75 and he was severely hyperactive despite Ritalin. This is the first report of a familial duplication in 5q; no identical, isolated case is known. Although additional family members need evaluation, the presence of the dup(5q) in the non-retarded mother suggests that it may not be associated with the proband`s MR.

  17. The 5q deletion size in myeloid malignancies is correlated to additional chromosomal aberrations and to TP53 mutations.

    PubMed

    Stengel, Anna; Kern, Wolfgang; Haferlach, Torsten; Meggendorfer, Manja; Haferlach, Claudia

    2016-10-01

    Deletions in the long arm of chromosome 5 (del(5q)) are recurrent abnormalities in myeloid malignancies. We analyzed del(5q) and accompanying molecular mutations in MDS, MPN and MDS/MPN cases. A high del(5q) frequency was revealed in MDS (1869/11398 cases; 16%), followed by MDS/MPN (37/1107; 3%) and MPN (97/6373; 2%). To investigate potential associations of the del(5q) size with the respective phenotypes, we applied array CGH analyses in selected cohorts of 61 MDS, 22 MDS/MPN and 23 MPN cases. The size varied between 16 and 119 Mb with no differences between the entities. However, MPN and MDS/MPN cases with del(5q) sole showed a significantly smaller del(5q) than cases with additional aberrations. Sequence analysis of 27 genes revealed ≥1 mutation in 91% of patients. The highest mutation frequencies in the total cohort were observed for TP53 (31%), JAK2 (23%) and DNMT3A (18%). The molecular mutation patterns in the del(5q) cohorts were different between the entities but resembled known patterns of cohorts not selected for del(5q). Further, TP53 mutations were significantly more frequent in cases with a larger deletion size (P = 0.003). The results suggest a correlation of large del(5q) with TP53 mutations and with additional chromosomal aberrations possibly contributing to more severe courses of these cases. © 2016 Wiley Periodicals, Inc. PMID:27218649

  18. Localization of the gene encoding peptidylglycine [alpha]-amidating monooxygenase (PAM) to human chromosome 5q14-5q21

    SciTech Connect

    Ouafik, L.H.; Giraud, P.; Oliver, C. ); Mattei, M.G. ); Eipper, B.A.; Mains, R.E. )

    1993-11-01

    Peptidylglycine [alpha]-amidating monooxygenase (PAM; EC 1.14.17.3) is a multifunctional protein containing two enzymes that act sequentially to catalyze the [alpha]-amidation of neuroendocrine peptides. Southern blot analysis of human placental DNA demonstrated that PAM is encoded by a single gene. The chromosomal localization of the PAM gene was established using in situ hybridization. A 2.2-kb human PAM cDNA hybridized to human metaphase chromosomes revealed a significant clustering of silver grains over chromosome 5 bands q14-q21. The gene encoding another enzyme important in the post-translational processing of neuroendocrine precursors, prohormone convertase 1 (PC1), is localized in the same region (5q15-q21). 14 refs., 2 figs.

  19. A locus regulating total serum IgE maps to chromosome 5q

    SciTech Connect

    Amelung, P.J.; Panhuysen, C.I.M.; Postma, D.S. |

    1994-09-01

    Familial aggregation of allergy has been demonstrated in numerous past studies. However, allergy is a complex disorder which is not inherited as a simple Mendelian trait. Total serum IgE levels correlate with the clinical expression of allergy and asthma and can be utilized as a quantitative measure of the allergic phenotype. We studied 92 families from Northern Holland ascertained through a parent with asthma who were originally studied between 1962-1970. Since there is a large number of candidate genes on chromosome 5q, families were genotyped for markers in this region. These genes either directly or indirectly regulate IgE production and the activation and proliferation of cellular elements that are involved in inflammation associated with allergy and asthma. They include IL-4, IL-3, IL-5, IL-9, IL-12, IL-13 and GM-CSF. Segregation analyses revealed recessive inheritance of `high` levels with a mean for the `low` phenotype of 1.51 (32 IU) and 2.52 (331 IU) for the `high` phenotype. Linkage of log IgE with markers on 5q was tested using the sib-pair and the LOD score methods with the genetic model obtained from the segregation analyses. These results provide evidence for a locus controlling IgE levels near the cytokine gene cluster on 5q. This region appears critical in susceptibility to allergy and asthma.

  20. Localization of a Susceptibility Gene for Common Forms of Stroke to 5q12

    PubMed Central

    Gretarsdottir, Solveig; Sveinbjörnsdottir, Sigurlaug; Jonsson, Hjörtur H.; Jakobsson, Finnbogi; Einarsdottir, Elisabet; Agnarsson, Uggi; Shkolny, Dana; Einarsson, Gisli; Gudjonsdottir, Herdis M.; Valdimarsson, Einar M.; Einarsson, Olafur B.; Thorgeirsson, Gudmundur; Hadzic, Radinka; Jonsdottir, Sif; Reynisdottir, Sigridur Th.; Bjarnadottir, Sigrun M.; Gudmundsdottir, Thorunn; Gudlaugsdottir, Gudrun J.; Gill, Ramanjit; Lindpaintner, Klaus; Sainz, Jesus; Hannesson, Helgi H.; Sigurdsson, Gunnar Th.; Frigge, Michael L.; Kong, Augustine; Gudnason, Vilmundur; Stefansson, Kari; Gulcher, Jeffrey R.

    2002-01-01

    Stroke is one of the most complex diseases, with several subtypes, as well as secondary risk factors, such as hypertension, hyperlipidemia, and diabetes, which, in turn, have genetic and environmental risk factors of their own. Here, we report the results of a genomewide search for susceptibility genes for the common forms of stroke. We cross-matched a population-based list of patients with stroke in Iceland with an extensive computerized genealogy database clustering 476 patients with stroke within 179 extended pedigrees. Linkage to 5q12 was detected, and the LOD score at this locus meets the criteria for genomewide significance (multipoint allele-sharing LOD score of 4.40, P=3.9×10-6). A 20-cM region on 5q was physically and genetically mapped to obtain accurate marker order and intermarker distances. This locus on 5q12, which we have designated as “STRK1,” does not correspond to known susceptibility loci for stroke or for its risk factors and represents the first mapping of a locus for common stroke. PMID:11833004

  1. Lenalidomide for myelodysplastic syndromes with del(5q): how long should it last?

    PubMed

    Vozella, Federico; Latagliata, Roberto; Carmosino, Ida; Volpicelli, Paola; Montagna, Chiara; Romano, Angela; Roberto, Amanda; Finsinger, Paola; Mancini, Marco; Breccia, Massimo; Oliva, Esther; Oliva, Esther

    2015-03-01

    Lenalidomide induces in patients with myelodysplastic syndrome (MDS) and del(5q) erythroid and cytogenetic response rates as high as 75% and 50%, respectively. It is still unclear, however, how long lenalidomide treatment should be continued and whether or not the drug could be interrupted. To assess the feasibility of lenalidomide discontinuation, we revised a cohort of 16 low-risk MDS patients with del(5q) treated at our institute in a phase II multicentric Italian study. Among the 12 responding patients, four discontinued lenalidomide while in complete response. All four patients needed during treatment a permanent lenalidomide reduction from 10 to 5 mg/day because of haematological toxicity (three patients) or grade 3 muscular and bone pain (one patient). At lenalidomide discontinuation after 16, 20, 27 and 20 months from the start, respectively, all four patients were in complete hematologic response and three forth in complete cytogenetic response. Three patients are still in response after 36, 30 and 20 months from lenalidomide discontinuation, respectively: The remaining patient relapsed after 20 months, and she is now receiving a new course of lenalidomide. In conclusion, long-lasting remissions are achievable in MDS patients with del(5q) in complete response after lenalidomide discontinuation. PMID:25950027

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

    SciTech Connect

    Segal, A.L.; McPherson, J.D.; Wasmuth, J.J.

    1994-09-01

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

  3. Chronic lymphocytic leukaemia with 17p deletion: a retrospective analysis of prognostic factors and therapy results.

    PubMed

    Delgado, Julio; Espinet, Blanca; Oliveira, Ana C; Abrisqueta, Pau; de la Serna, Javier; Collado, Rosa; Loscertales, Javier; Lopez, Montserrat; Hernandez-Rivas, Jose A; Ferra, Christelle; Ramirez, Angel; Roncero, Josep M; Lopez, Cristina; Aventin, Anna; Puiggros, Anna; Abella, Eugenia; Carbonell, Felix; Costa, Dolors; Carrio, Anna; Gonzalez, Marcos

    2012-04-01

    Patients with chronic lymphocytic leukaemia (CLL) whose tumour cells harbour a 17p deletion (17p-) are universally considered to have a poor prognosis. The deletion can be detected at diagnosis or during the evolution of the disease, particularly in patients who have received chemotherapy. We sought to evaluate the natural history of patients with 17p- CLL, identify predictive factors within this prognostic subgroup, and evaluate the results of different therapeutic approaches. Data from 294 patients with 17p- CLL followed up at 20 different institutions was retrospectively collected and analysed. Median age was 68 (range 27-98) years at the time of fluorescence in situ hybridization analysis. After 17p- documentation, 52% received treatment, achieving an overall response rate of 50%. Median overall survival was 41 months, and was significantly shorter in patients with elevated beta(2)-microglobulin concentration (P < 0·001), B symptoms (P = 0·016), higher percentage of cells with deletion (P < 0·001), and acquired deletions (P = 0·012). These findings suggest that patients with 17p- CLL have a variable prognosis that can be refined using simple clinical and laboratory features, including 17p- clone size, beta2-microglobulin concentration, presence of B symptoms and type of deletion (de novo versus acquired).

  4. Chronic lymphocytic leukaemia with 17p deletion: a retrospective analysis of prognostic factors and therapy results.

    PubMed

    Delgado, Julio; Espinet, Blanca; Oliveira, Ana C; Abrisqueta, Pau; de la Serna, Javier; Collado, Rosa; Loscertales, Javier; Lopez, Montserrat; Hernandez-Rivas, Jose A; Ferra, Christelle; Ramirez, Angel; Roncero, Josep M; Lopez, Cristina; Aventin, Anna; Puiggros, Anna; Abella, Eugenia; Carbonell, Felix; Costa, Dolors; Carrio, Anna; Gonzalez, Marcos

    2012-04-01

    Patients with chronic lymphocytic leukaemia (CLL) whose tumour cells harbour a 17p deletion (17p-) are universally considered to have a poor prognosis. The deletion can be detected at diagnosis or during the evolution of the disease, particularly in patients who have received chemotherapy. We sought to evaluate the natural history of patients with 17p- CLL, identify predictive factors within this prognostic subgroup, and evaluate the results of different therapeutic approaches. Data from 294 patients with 17p- CLL followed up at 20 different institutions was retrospectively collected and analysed. Median age was 68 (range 27-98) years at the time of fluorescence in situ hybridization analysis. After 17p- documentation, 52% received treatment, achieving an overall response rate of 50%. Median overall survival was 41 months, and was significantly shorter in patients with elevated beta(2)-microglobulin concentration (P < 0·001), B symptoms (P = 0·016), higher percentage of cells with deletion (P < 0·001), and acquired deletions (P = 0·012). These findings suggest that patients with 17p- CLL have a variable prognosis that can be refined using simple clinical and laboratory features, including 17p- clone size, beta2-microglobulin concentration, presence of B symptoms and type of deletion (de novo versus acquired). PMID:22224845

  5. Distal 5q trisomy resulting from an X;5 translocation detected by chromosome painting.

    PubMed

    Abuelo, D N; Ahsanuddin, A N; Mark, H F

    2000-10-23

    We describe the case of a 13-year-old girl with an apparently de novo unbalanced translocation resulting in the presence of additional chromosomal material on the short arm of one X chromosome, which was detected by conventional G-banding studies. Fluorescence in situ hybridization (FISH) using the Chromoprobe Multiprobe-M protocol confirmed that the additional chromosomal material originated from chromosome 5. The karyotype of this patient is now established to be 46,X,der(X) t(X;5)(p22.3;q33), with a deletion of Xp22.3-pter and partial trisomy of 5q33-qter. The distal 5q trisomy genotype has been associated with clinical signs that include growth and mental retardation, eczema, craniofacial anomalies, and malformations of heart, lungs, abdomen, limbs, and genitalia. Our patient also has short stature, a prominent nasal bridge, a flat philtrum, a thin upper lip, dental caries, and limb and cardiac malformations, but she appears to be mildly affected compared with previously reported cases. This is the first case of distal 5q trisomy arising from a translocation with the X chromosome. Replication studies on this patient show that the derivative t(X;5) chromosome is late replicating in almost all cells examined, which indicates that this chromosome is preferentially inactivated. However, the translocated segment of chromosome 5 appears to be early replicating, which implies that the trisomic 5q segment is transcriptionally active. We cannot determine from these studies whether all or only some genes in this segment are expressed, but this patient's relatively mild clinical signs suggest that the critical region(s) that contribute to the distal 5q trisomy phenotype are at least partly suppressed. A review of other patients with X-chromosome translocations indicates that many but not all of them also have attenuated phenotypes. The mechanism of inactivation of autosomal material attached to the X chromosome is complex, with varying effects on the phenotype of the

  6. High-temperature order-disorder transitions in the skutterudites CoGe{sub 1.5}Q{sub 1.5} (Q=S, Te)

    SciTech Connect

    Kaltzoglou, Andreas; Powell, Anthony V.; Knight, Kevin S.; Vaqueiro, Paz

    2013-02-15

    The temperature dependence of anion ordering in the skutterudites CoGe{sub 1.5}Q{sub 1.5} (Q=S, Te) has been investigated by powder neutron diffraction. Both materials adopt a rhombohedral structure at room temperature (space group R3{sup Macron} ) in which the anions are ordered trans to each other within Ge{sub 2}Q{sub 2} rings. In CoGe{sub 1.5}S{sub 1.5}, anion ordering is preserved up to the melting point of 950 Degree-Sign C. However, rhombohedral CoGe{sub 1.5}Te{sub 1.5} undergoes a phase transition at 610 Degree-Sign C involving a change to cubic symmetry (space group Im3{sup Macron }). In the high-temperature modification, there is a statistical distribution of anions over the available sites within the Ge{sub 2}Te{sub 2} rings. The structural transition involves a reduction in the degree of distortion of the Ge{sub 2}Te{sub 2} rings which progressively transform from a rhombus to a rectangular shape. The effect of this transition on the thermoelectric properties has been investigated. - Graphical abstract: Powder neutron diffraction reveals that the skutterudite CoGe{sub 1.5}Te{sub 1.5} undergoes a phase transition at 610 Degree-Sign C, involving the disordering of the anions within the Ge{sub 2}Te{sub 2} rings. Highlights: Black-Right-Pointing-Pointer CoGe{sub 1.5}S{sub 1.5} retains an ordered skutterudite structure up to 950 Degree-Sign C. Black-Right-Pointing-Pointer CoGe{sub 1.5}Te{sub 1.5} undergoes an order-disorder phase transition at 610 Degree-Sign C. Black-Right-Pointing-Pointer Below 610 Degree-Sign C, anions are arranged trans to each other within Ge{sub 2}Te{sub 2} rings. Black-Right-Pointing-Pointer Above 610 Degree-Sign C, anions are statistically distributed within the Ge{sub 2}Te{sub 2} rings. Black-Right-Pointing-Pointer The effect of the phase transition on the thermal conductivity is discussed.

  7. A case of duplication 17p13.1p13.3 confirmed by FISH

    SciTech Connect

    Stephenson, C.F.; Berger, C.S.; Bull, R.M.

    1994-09-01

    There are many reports in the literature of deletions of the p arm of chromosome 17 in the region of p13.3 due to the association with Miller-Dieker Syndrome. However, very little is known about duplications of 17p. We report a duplication of part of 17p in an 8-year-old girl with attention deficit disorder and mild mental retardation. Cytogenetically, the duplicated region appears to include 17p13.1 to p13.3. FISH with a cosmid probe to the Miller-Dieker region at 17p13.3 shows a double hybridization signal, confirming that the duplicated material does indeed include 17q13.3.

  8. Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations.

    PubMed

    Mallo, Mar; Del Rey, Mónica; Ibáñez, Mariam; Calasanz, M José; Arenillas, Leonor; Larráyoz, M José; Pedro, Carmen; Jerez, Andrés; Maciejewski, Jaroslaw; Costa, Dolors; Nomdedeu, Meritxell; Diez-Campelo, María; Lumbreras, Eva; González-Martínez, Teresa; Marugán, Isabel; Such, Esperanza; Cervera, José; Cigudosa, Juan C; Alvarez, Sara; Florensa, Lourdes; Hernández, Jesús M; Solé, Francesc

    2013-07-01

    Lenalidomide is an effective drug in low-risk myelodysplastic syndromes (MDS) with isolated del(5q), although not all patients respond. Studies have suggested a role for TP53 mutations and karyotype complexity in disease progression and outcome. In order to assess the impact of complex karyotypes on treatment response and disease progression in 52 lenalidomide-treated patients with del(5q) MDS, conventional G-banding cytogenetics (CC), single nucleotide polymorphism array (SNP-A), and genomic sequencing methods were used. SNP-A analysis (with control sample, lymphocytes CD3+, in 30 cases) revealed 5q losses in all cases. Other recurrent abnormalities were infrequent and were not associated with lenalidomide responsiveness. Low karyotype complexity (by CC) and a high baseline platelet count (>280 × 10(9) /l) were associated with the achievement of haematological response (P = 0·020, P = 0·013 respectively). Unmutated TP53 status showed a tendency for haematological response (P = 0·061). Complete cytogenetic response was not observed in any of the mutated TP53 cases. By multivariate analysis, the most important predictor for lenalidomide treatment failure was a platelet count <280 × 10(9) /l (Odds Ratio = 6·17, P = 0·040). This study reveals the importance of a low baseline platelet count, karyotypic complexity and TP53 mutational status for response to lenalidomide treatment. It supports the molecular study of TP53 in MDS patients treated with lenalidomide.

  9. Genetic variations in GRIA1 on chromosome 5q33 related to asparaginase hypersensitivity

    PubMed Central

    Chen, Shih-Hsiang; Pei, Deqing; Yang, Wenjian; Cheng, Cheng; Jeha, Sima; Cox, Nancy J.; Evans, William E.; Pui, Ching-Hon; Relling, Mary V.

    2010-01-01

    The genetic variations that lead to asparaginase allergy are unknown. We interrogated over 500,000 single nucleotide polymorphisms (SNPs) in 485 children with acute lymphoblastic leukemia (ALL): 322 in a discovery and 163 in a validation cohort. From the top 100 SNPs associated with allergy in the discovery cohort, chromosome 5 was overrepresented compared to other chromosomes (p = 0.00032), hosting 10 SNPs annotated to genes. Among these 10 SNPs, one SNP (rs4958381), in GRIA1 on chromosome 5q33, replicated in the validation cohort (p = 1.8 × 10−5, 2.9 × 10−3, and 3.5 × 10−7 in the discovery, validation, and combined cohorts, respectively). Four additional SNPs annotated to GRIA1 were also significantly associated with allergy (p < 0.05) in both cohorts. Chromosome 5q33 has previously been associated with asthma and atopy. These data contribute to the growing body of evidence that there is an inherited component to predisposition to drug allergy. PMID:20592726

  10. Clinical phenotype and candidate genes for the 5q31.3 microdeletion syndrome.

    PubMed

    Hosoki, Kana; Ohta, Tohru; Natsume, Jun; Imai, Sumiko; Okumura, Akihisa; Matsui, Takeshi; Harada, Naoki; Bacino, Carlos A; Scaglia, Fernando; Jones, Jeremy Y; Niikawa, Norio; Saitoh, Shinji

    2012-08-01

    Array-based technologies have led to the identification of many novel microdeletion and microduplication syndromes demonstrating multiple congenital anomalies and intellectual disability (MCA/ID). We have used chromosomal microarray analysis for the evaluation of patients with MCA/ID and/or neonatal hypotonia. Three overlapping de novo microdeletions at 5q31.3 with the shortest region of overlap (SRO) of 370 kb were detected in three unrelated patients. These patients showed similar clinical features including severe neonatal hypotonia, neonatal feeding difficulties, respiratory distress, characteristic facial features, and severe developmental delay. These features are consistent with the 5q31.3 microdeletion syndrome originally proposed by Shimojima et al., providing further evidence that this syndrome is clinically discernible. The 370 kb SRO encompasses only four RefSeq genes including neuregulin 2 (NRG2) and purine-rich element binding protein A (PURA). NRG2 is one of the members of the neuregulin family related to neuronal and glial cell growth and differentiation, thus making NRG2 a good candidate for the observed phenotype. Moreover, PURA is also a good candidate because Pura-deficient mice demonstrate postnatal neurological manifestations.

  11. Genome-wide association study identifies two new susceptibility loci for colorectal cancer at 5q23.3 and 17q12 in Han Chinese.

    PubMed

    Jiang, Kewei; Sun, Yimin; Wang, Cheng; Ji, Jiafu; Li, Yaoping; Ye, Yingjiang; Lv, Liang; Guo, Yong; Guo, Sutang; Li, Hai; Zhang, Lianhai; Zhou, Yanbing; Jiang, Bo; Ren, Yonghong; Xu, Youchun; Yang, Xiongfei; Liu, Hongxia; Wang, Yirui; Shen, Zhanlong; Qin, Wenyan; Guo, Peng; Jiang, Yuyang; Hu, Zhibin; Shen, Hongbing; Cheng, Jing; Yang, Yinxue; Wang, Shan

    2015-11-24

    Genome-wide association studies (GWAS) have reported a number of loci harboring common variants that influence risk of colorectal cancer (CRC) in European descent. But all the SNPs identified explained a small fraction of total heritability. To identify more genetic factors that modify the risk of CRC, especially Chinese Han specific, we conducted a three-stage GWAS including a screening stage (932 CRC cases and 966 controls) and two independent validations (Stage 2: 1,759 CRC cases and 1,875 controls; Stage 3: 943 CRC cases and 1,838 controls). In the combined analyses, we discovered two novel loci associated with CRC: rs12522693 at 5q23.3 (CDC42SE2-CHSY3, OR = 1.31, P = 2.08 × 10-8) and rs17836917 at 17q12 (ASIC2-CCL2, OR = 0.75, P = 4.55 × 10-8). Additionally, we confirmed two previously reported risk loci, rs6983267 at 8q24.21 (OR = 1.17, P = 7.17 × 10-7) and rs10795668 at 10p14 (OR = 0.86, P = 2.96 × 10-6) in our cohorts. These results bring further insights into the CRC susceptibility and advance our understanding on etiology of CRC.

  12. De novo and inherited deletions of the 5q13 region in spinal muscular atrophies

    SciTech Connect

    Melki, J.; Lefebvre, S.; Burglen, L.; Burlet, P.; Clermont, O.; Reboullet, S.; Benichou, B.; Zeviani, M. ); Millasseau, P. ); Le Paslier, D. )

    1994-06-03

    Spinal muscular atrophies (SMAs) represent the second most common fatal autosomal recessive disorder after cystic fibrosis. Childhood spinal muscular atrophies are divided into severe (type I) and mild forms (types II and III). By a combination of genetic and physical mapping, a yeast artificial chromosome contig of the 5q13 region spanning the disease locus was constructed that showed the presence of low copy repeats in this region. Allele segregation was analyzed at the closest genetic loci detected by markers C212 and C272 in 201 SMA families. Inherited and de novo deletions were observed in nine unrelated SMA patients. Moreover, deletions were strongly suggested in at least 18 percent of SMA type I patients by the observation of marked heterozygosity deficiency for the loci studied. These results indicate that deletion events are statistically associated with the severe form of spinal muscular atrophy. 25 refs., 5 figs.

  13. The gene for human glutaredoxin (GLRX) is localized to human chromosome 5q14

    SciTech Connect

    Padilla, C.A.; Holmgren, A.; Bajalica, S.; Lagercrantz, J.

    1996-03-05

    Glutaredoxin is a small protein (12 kDa) catalyzing glutathione-dependent disulfide oxidoreduction reactions in a coupled system with NADPH, GSH, and glutathione reductase. A cDNA encoding the human glutaredoxin gene (HGMW-approved symbol GLRX) has recently been isolated and cloned from a human fetal spleen cDNA library. The screening of a human fetal spleen cDNA library. The screening of a human genomic library in Charon 4A led to the identification of three genomic clones. Using fluorescence in situ hybridization to metaphase chromosomes with one genomic clone as a probe, the human glutaredoxin gene was localized to chromosomal region 5q14. This localization at chromosome 5 was in agreement with the somatic cell hybrid analysis, using DNA from a human-hamster and a human-mouse hybrid panel and using a human glutaredoxin cDNA as a probe. 13 refs., 2 figs.

  14. Variation in conserved non-coding sequences on chromosome 5q andsusceptibility to asthma and atopy

    SciTech Connect

    Donfack, Joseph; Schneider, Daniel H.; Tan, Zheng; Kurz,Thorsten; Dubchak, Inna; Frazer, Kelly A.; Ober, Carole

    2005-09-10

    Background: Evolutionarily conserved sequences likely havebiological function. Methods: To determine whether variation in conservedsequences in non-coding DNA contributes to risk for human disease, westudied six conserved non-coding elements in the Th2 cytokine cluster onhuman chromosome 5q31 in a large Hutterite pedigree and in samples ofoutbred European American and African American asthma cases and controls.Results: Among six conserved non-coding elements (>100 bp,>70percent identity; human-mouse comparison), we identified one singlenucleotide polymorphism (SNP) in each of two conserved elements and sixSNPs in the flanking regions of three conserved elements. We genotypedour samples for four of these SNPs and an additional three SNPs each inthe IL13 and IL4 genes. While there was only modest evidence forassociation with single SNPs in the Hutterite and European Americansamples (P<0.05), there were highly significant associations inEuropean Americans between asthma and haplotypes comprised of SNPs in theIL4 gene (P<0.001), including a SNP in a conserved non-codingelement. Furthermore, variation in the IL13 gene was strongly associatedwith total IgE (P = 0.00022) and allergic sensitization to mold allergens(P = 0.00076) in the Hutterites, and more modestly associated withsensitization to molds in the European Americans and African Americans (P<0.01). Conclusion: These results indicate that there is overalllittle variation in the conserved non-coding elements on 5q31, butvariation in IL4 and IL13, including possibly one SNP in a conservedelement, influence asthma and atopic phenotypes in diversepopulations.

  15. Effect of lenalidomide treatment on clonal architecture of myelodysplastic syndromes without 5q deletion.

    PubMed

    Chesnais, Virginie; Renneville, Aline; Toma, Andrea; Lambert, Jérôme; Passet, Marie; Dumont, Florent; Chevret, Sylvie; Lejeune, Julie; Raimbault, Anna; Stamatoullas, Aspasia; Rose, Christian; Beyne-Rauzy, Odile; Delaunay, Jacques; Solary, Eric; Fenaux, Pierre; Dreyfus, François; Preudhomme, Claude; Kosmider, Olivier; Fontenay, Michaela

    2016-02-11

    Non-del(5q) transfusion-dependent low/intermediate-1 myelodysplastic syndrome (MDS) patients achieve an erythroid response with lenalidomide in 25% of cases. Addition of an erythropoiesis-stimulating agent could improve response rate. The impact of recurrent somatic mutations identified in the diseased clone in response to lenalidomide and the drug's effects on clonal evolution remain unknown. We investigated recurrent mutations by next-generation sequencing in 94 non-del(5q) MDS patients randomized in the GFM-Len-Epo-08 clinical trial to lenalidomide or lenalidomide plus epoetin β. Clonal evolution was analyzed after 4 cycles of treatment in 42 cases and reanalyzed at later time points in 18 cases. The fate of clonal architecture of single CD34(+)CD38(-) hematopoietic stem cells was also determined in 5 cases. Mutation frequency was >10%: SF3B1 (74.5%), TET2 (45.7%), DNMT3A (20.2%), and ASXL1 (19.1%). Analysis of variant allele frequencies indicated a decrease of major mutations in 15 of 20 responders compared with 10 of 22 nonresponders after 4 cycles. The decrease in the variant allele frequency of major mutations was more significant in responders than in nonresponders (P < .001). Genotyping of single CD34(+)CD38(-) cell-derived colonies showed that the decrease in the size of dominant subclones could be associated with the rise of founding clones or of hematopoietic stem cells devoid of recurrent mutations. These effects remained transient, and disease escape was associated with the re-emergence of the dominant subclones. In conclusion, we show that, although the drug initially modulates the distribution of subclones, loss of treatment efficacy coincides with the re-expansion of the dominant subclone. This trial was registered at www.clinicaltrials.gov as #NCT01718379.

  16. Effect of lenalidomide treatment on clonal architecture of myelodysplastic syndromes without 5q deletion

    PubMed Central

    Chesnais, Virginie; Renneville, Aline; Toma, Andrea; Lambert, Jérôme; Passet, Marie; Dumont, Florent; Chevret, Sylvie; Lejeune, Julie; Raimbault, Anna; Stamatoullas, Aspasia; Rose, Christian; Beyne-Rauzy, Odile; Delaunay, Jacques; Solary, Eric; Fenaux, Pierre; Dreyfus, François; Preudhomme, Claude; Kosmider, Olivier

    2016-01-01

    Non-del(5q) transfusion-dependent low/intermediate-1 myelodysplastic syndrome (MDS) patients achieve an erythroid response with lenalidomide in 25% of cases. Addition of an erythropoiesis-stimulating agent could improve response rate. The impact of recurrent somatic mutations identified in the diseased clone in response to lenalidomide and the drug’s effects on clonal evolution remain unknown. We investigated recurrent mutations by next-generation sequencing in 94 non-del(5q) MDS patients randomized in the GFM-Len-Epo-08 clinical trial to lenalidomide or lenalidomide plus epoetin β. Clonal evolution was analyzed after 4 cycles of treatment in 42 cases and reanalyzed at later time points in 18 cases. The fate of clonal architecture of single CD34+CD38− hematopoietic stem cells was also determined in 5 cases. Mutation frequency was >10%: SF3B1 (74.5%), TET2 (45.7%), DNMT3A (20.2%), and ASXL1 (19.1%). Analysis of variant allele frequencies indicated a decrease of major mutations in 15 of 20 responders compared with 10 of 22 nonresponders after 4 cycles. The decrease in the variant allele frequency of major mutations was more significant in responders than in nonresponders (P < .001). Genotyping of single CD34+CD38− cell–derived colonies showed that the decrease in the size of dominant subclones could be associated with the rise of founding clones or of hematopoietic stem cells devoid of recurrent mutations. These effects remained transient, and disease escape was associated with the re-emergence of the dominant subclones. In conclusion, we show that, although the drug initially modulates the distribution of subclones, loss of treatment efficacy coincides with the re-expansion of the dominant subclone. This trial was registered at www.clinicaltrials.gov as #NCT01718379. PMID:26626993

  17. A YAC contig of approximately 3 Mb from human chromosome 5q31 [yields] q33

    SciTech Connect

    Li, Xiang; Wang Jabs, E.; Hawkins, A.L.; Griffin, C.A. ); Wise, C.A.; Lovett, M. ); Le Paslier, D. ); Pittler, S.J. )

    1994-02-01

    The human chromosome 5q31-q33 region contains an interesting cluster of growth factor and receptor genes. In addition, several genetic disease loci have been localized within this region, but have not as yet been isolated as molecular clones. These include those loci involved in autosomal dominant limb-girdle muscular dystrophy, diastrophic dysplasia, Treacher Collins syndrome, and myeloid disorders associated with the 5q-syndrome. A yeast artificial chromosome (YAC) contig of this region would assist in the further localization and isolation of these genes. The authors have used YACs isolated from the Washington University and Centre d'Etude du Polymorphisme Humain YAC libraries, including YACs from the large insert (mega) YAC library to build a contig greater than 3 Mb in size. An STS content strategy coupled with limited walking from YAC ends was used to isolate 22 overlapping YACs with as much as sixfold coverage. A total of 20 STSs, derived from genes, anonymous sequences, and vector Alu-PCR or inverse PCR products, were used to compile this contig. The order of loci, centromere-GRL-D5S207-D5S70-D5S545-D5S546-D5S547-D5S68-D5S548-D5S210-D5S549-D5S686- ADRB2-D5S559-CSF1R-D5S551-RPS14-D5S519-SPARC-telomere, was derived from the overlapping clones. This contig and clones derived from it will be useful substrates in selecting candidate cDNAs for the disease loci in this interval. 45 refs., 1 fig., 2 tabs.

  18. Targeted re-sequencing analysis of 25 genes commonly mutated in myeloid disorders in del(5q) myelodysplastic syndromes

    PubMed Central

    Fernandez-Mercado, Marta; Burns, Adam; Pellagatti, Andrea; Giagounidis, Aristoteles; Germing, Ulrich; Agirre, Xabier; Prosper, Felipe; Aul, Carlo; Killick, Sally; Wainscoat, James S.; Schuh, Anna; Boultwood, Jacqueline

    2013-01-01

    Interstitial deletion of chromosome 5q is the most common chromosomal abnormality in myelodysplastic syndromes. The catalogue of genes involved in the molecular pathogenesis of myelodysplastic syndromes is rapidly expanding and next-generation sequencing technology allows detection of these mutations at great depth. Here we describe the design, validation and application of a targeted next-generation sequencing approach to simultaneously screen 25 genes mutated in myeloid malignancies. We used this method alongside single nucleotide polymorphism-array technology to characterize the mutational and cytogenetic profile of 43 cases of early or advanced del(5q) myelodysplastic syndromes. A total of 29 mutations were detected in our cohort. Overall, 45% of early and 66.7% of advanced cases had at least one mutation. Genes with the highest mutation frequency among advanced cases were TP53 and ASXL1 (25% of patients each). These showed a lower mutation frequency in cases of 5q- syndrome (4.5% and 13.6%, respectively), suggesting a role in disease progression in del(5q) myelodysplastic syndromes. Fifty-two percent of mutations identified were in genes involved in epigenetic regulation (ASXL1, TET2, DNMT3A and JAK2). Six mutations had allele frequencies <20%, likely below the detection limit of traditional sequencing methods. Genomic array data showed that cases of advanced del(5q) myelodysplastic syndrome had a complex background of cytogenetic aberrations, often encompassing genes involved in myeloid disorders. Our study is the first to investigate the molecular pathogenesis of early and advanced del(5q) myelodysplastic syndromes using next-generation sequencing technology on a large panel of genes frequently mutated in myeloid malignancies, further illuminating the molecular landscape of del(5q) myelodysplastic syndromes. PMID:23831921

  19. 40 CFR 401.17 - pH Effluent limitations under continuous monitoring.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true pH Effluent limitations under continuous monitoring. 401.17 Section 401.17 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GENERAL PROVISIONS § 401.17 pH Effluent limitations...

  20. 40 CFR 401.17 - pH Effluent limitations under continuous monitoring.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false pH Effluent limitations under continuous monitoring. 401.17 Section 401.17 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GENERAL PROVISIONS § 401.17 pH Effluent limitations...

  1. 17 CFR 170.10 - Proficiency examinations (sections 4p and 17(p) of the Act).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Proficiency examinations (sections 4p and 17(p) of the Act). 170.10 Section 170.10 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION REGISTERED FUTURES ASSOCIATIONS Standards Governing Commission Review of Applications for Registration as a...

  2. 40 CFR 401.17 - pH Effluent limitations under continuous monitoring.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true pH Effluent limitations under continuous monitoring. 401.17 Section 401.17 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GENERAL PROVISIONS § 401.17 pH Effluent limitations under continuous monitoring. (a) Where a...

  3. 40 CFR 401.17 - pH Effluent limitations under continuous monitoring.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 30 2013-07-01 2012-07-01 true pH Effluent limitations under... (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GENERAL PROVISIONS § 401.17 pH Effluent limitations under continuous monitoring. (a) Where a permittee continuously measures the pH of wastewater pursuant to...

  4. RAI1 variations in Smith–Magenis syndrome patients without 17p11.2 deletions

    PubMed Central

    Girirajan, S; Elsas, L; Devriendt, K; Elsea, S

    2005-01-01

    Background: Smith–Magenis syndrome (SMS) (OMIM No 182290) is a mental retardation syndrome characterised by behavioural abnormalities, including self injurious behaviours, sleep disturbance, and distinct craniofacial and skeletal anomalies. It is usually associated with deletion involving 17p11.2 and is estimated to occur in 1/25 000 births. Heterozygous frameshift mutations leading to protein truncation in retinoic acid induced 1 gene (RAI1) have been identified in individuals with phenotypic features consistent with SMS. RAI1 lies within the 17p11.2 locus, but these patients did not have 17p11.2 deletions. Objective: Analysis of four individuals with features consistent with SMS for variations in RAI1, using a polymerase chain reaction and sequencing strategy. None of these patients carry 17p11.2 deletions. Results: Two patients had small deletions in RAI1 resulting in frameshift and premature truncation of the protein. Missense mutations were identified in the other two. Orthologs across other genomes showed that these missense mutations occurred in identically conserved regions of the gene. The mutations were de novo, as all parental samples were normal. Several polymorphisms were also observed, including new and reported SNPs. The patients' clinical features differed from those found in 17p11.2 deletion by general absence of short stature and lack of visceral anomalies. All four patients had developmental delay, reduced motor and cognitive skills, craniofacial and behavioural anomalies, and sleep disturbance. Seizures, not previously thought to be associated with RAI1 mutations, were observed in one patient of the cohort. Conclusions: Haploinsufficiency of the RAI1 gene is associated with most features of SMS, including craniofacial, behavioural, and neurological signs and symptoms. PMID:15788730

  5. Faithful expression of the human 5q31 cytokine cluster intransgenic mice

    SciTech Connect

    Lacy, Dee A.; Wang, Zhi-En; Symula, Derek J.; McArthur, CliffordJ.; Rubin, Edward M.; Frazer, Kelly A.; Locksley, Richard M.

    1999-12-03

    ILs 4,5, and 13, cardinal cytokines produced by Th2 cells,are coordinately expressed and clustered in the 150-kb syntenic regions on mouse chromosome 11 and human chromosome 5q31. We analyzed two sets of human yeast artificial chromosome transgenic mice that contained the5931cytokines to assess whether conserved sequences required for their coordinate and cell-specific regulation are contained within the cytokine cluster itself. Human Il-4, IL-13, and Il-5 were expressed under Th2, but not Th1, conditions in vitro. Each of these cytokines was produced during infection with Nippostrongylus brasiliensis, a Th2 inducing stimulus, and human Il-4 was generated after activation of NK T cells in vivo.Consistently fewer cells produced the endogenous mouse cytokines in transgenic than in control mice, suggesting competition for stable expression between the mouse and human genes. These data imply the existence of both conserved trans-activating factors and cis-regulatory elements that underlie the coordinate expression and lineage specificity of the type 2 ctyokine genes in lymphocytes.

  6. The MEF2C-Related and 5q14.3q15 Microdeletion Syndrome

    PubMed Central

    Zweier, M.; Rauch, A.

    2012-01-01

    Disorders related to the autosomal transcription factor MEF2C located in 5q14.3 were first described in 2009 and have since evolved to one of the more common microdeletion syndromes. Mutational screening in a larger cohort revealed heterozygous de novo mutations of MEF2C in about 1% of patients with moderate to severe intellectual disability, and the phenotype is similar in patients with intragenic deletions and multigenic microdeletions. Clinically, MEF2C-related disorders are characterized by severe intellectual disability with absent speech and limited walking abilities, hypotonia, seizures, and a variety of minor brain anomalies. The majority of patients show a similar facial gestalt with broad forehead, flat nasal bridge, hypotonic mouth, and small chin, as well as strabismus, but this phenotype is clinically not well recognized. The course of the disease is generally quite uniform, but patients with point mutations and smaller deletions seem to have a higher chance of walking skills and a lower risk of refractory seizures. Patients in whom the microdeletion also includes the RASA1 gene show features of the respective capillary and arterio-venous malformations and fistula syndrome. The phenotypic overlap with Rett syndrome is explained by a shared pathway and, accordingly, diminished MECP2 and CDKL5 expression is measureable in patients with MEF2C defects. Further research of this pathway may therefore eventually lead to a common therapeutic target. PMID:22670137

  7. Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure

    PubMed Central

    Smith, J. Gustav; Felix, Janine F.; Morrison, Alanna C.; Trompet, Stella; Wilk, Jemma B.; Gidlöf, Olof; Morley, Michael; Joehanes, Roby; Ligthart, Symen; Shan, Xiaoyin; Bis, Joshua C.; Sjögren, Marketa; Ngwa, Julius; Stott, David J.; Aguilar, David; Rice, Kenneth M.; Sesso, Howard D.; Demissie, Serkalem; Buckley, Brendan M.; Taylor, Kent D.; Ford, Ian; Yao, Chen; Liu, Chunyu; Sotoodehnia, Nona; van der Harst, Pim; Stricker, Bruno H. Ch.; Kritchevsky, Stephen B.; Liu, Yongmei; Gaziano, J. Michael; Hofman, Albert; Moravec, Christine S.; Uitterlinden, André G.; Kellis, Manolis; van Meurs, Joyce B.; Margulies, Kenneth B.; Dehghan, Abbas; Levy, Daniel; Olde, Björn; Psaty, Bruce M.; Cupples, L. Adrienne; Jukema, J. Wouter; Djousse, Luc; Franco, Oscar H.; Boerwinkle, Eric; Boyer, Laurie A.; Newton-Cheh, Christopher; Butler, Javed; Vasan, Ramachandran S.; Cappola, Thomas P.; Smith, Nicholas L.

    2016-01-01

    Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure. PMID:27149122

  8. [Chromosome arm 17p13.3: could HIC1 be the one ?].

    PubMed

    Chopin, Valérie; Leprince, Dominique

    2006-01-01

    Loss of heterozygosity (LOH) of the short arm of chromosome 17 (17p) is one of the most frequent genetic alterations in human cancers. Most often, allelic losses coincide with p53 mutations at 17p13.1. However, in many types of solid tumors including sporadic breast cancers, ovarian cancers, medulloblastomas and small cell lung carcinomas, frequent LOH or DNA methylation changes occur in a more telomeric region at 17p13.3, in absence of any p53 genetic alterations. These results suggest that one or more tumor suppressor genes located at 17p13.3 could be involved in tumorigenesis. In addition, the 17p13.3 region has also been implicated in the Miller-Dieker syndrome (MDS), a severe form of lissencephaly accompanied by developmental anomalies caused by heterozygous gene deletions. Analyses of deletion mapping and CpG island methylation patterns have resulted in the identification of two tumor suppressor genes at 17p13.3, HIC1 (hypermethylated in cancer 1) and OVCA1 (ovarian cancer gene 1). HIC1 is a tumor suppressor gene that encodes a transcriptional repressor with five Krüppel-like C2H2 zinc finger motifs and a N-terminal BTB/POZ domain. Clues to the tumor suppressor function of HIC1 have come from the study of heterozygous Hic1+/- mice, which develop spontaneous malignant tumors of different types. Generation of double heterozygous knockout mice Hic1+/- p53+/- provides strong evidence that epigenetically silenced genes such as HIC1 can significantly influence tumorigenesis driven by mutations of classic tumor suppressor genes. This functional cooperation between HIC1 and p53 is interesting and recently, its has been demonstrated that HIC1 was involved in a certain feedback regulation for p53 in tumor suppression through the histone deacetylase SIRT1. However, despite the fact that epigenetic oncogenesis is one of the most vibrant areas of biologic research, the determinants between genetic versus epigenetic routes of tumor suppressor gene inactivation remain

  9. The gene for creatine kinase, mitochondrial 2 (sarcomeric; CKMT2), maps to chromosome 5q13. 3

    SciTech Connect

    Richard, I.; Devaud, C. ); Cherif, D.; Cohen, D.; Beckmann, J.S. )

    1993-10-01

    YAC clones for the creatine kinase, mitochrondial 2 (sarcomeric; CKMT2), gene were isolated. One of these YACs was localized on chromosome 5q13.3 by fluorescence in situ hybridization. A polymorphic dinucleotide repeat (heterozygosity 0.77) was identified within the seventh intron of the CKMT2 gene. Genotyping of CEPH families allowed positioning of CKMT2 on the multipoint map of chromosome 5 between D5S424 and D5S428, distal to spinal muscular atrophy (SMA) (5q12-q14). 8 refs., 1 fig., 2 tabs.

  10. Microdeletions of chromosome 17p13 as a cause of isolated lissencephaly

    SciTech Connect

    Ledbetter, S.A.; Kuwano, Akira; Ledbetter, D.H. ); Dobyns, W.B. )

    1992-01-01

    Lissencephaly (agyria-pachygyria) is a brain malformation manifested by a smooth cerebral surface, resulting from arrest of neuronal migration at 10-14 wk gestation. Type I, or classical, lissencephaly can occur either in association with the Miller-Dieker syndrome (MDS) or as an isolated finding, termed isolated lissencephaly sequence (ILS). About 90% of MDS patients have visible or submicroscopic deletions of 17p13.3. The authors therefore investigated the possibility that some ILS patients have smaller deletions in this chromosomal region. Forty-five ILS patients with gyral abnormalities ranging from complete agyria to mixed agyria/pachygyria and complete pachygyria were studied. RFLP analysis with five polymorphic loci in 17p13.3 was performed on all patients and their parents. Somatic cell hybrids were constructed on three patients, to confirm a deletion or to determine the boundaries of a deletion. These data demonstrate that a locus on 17p13 represents a major genetic etiology for patients with lissencephaly, ranging from complete agyria to pachygyria. In situ hybridization allows rapid and sensitive deletion detection and is the preferred method for diagnostic evaluation of MDA and ILS patients.

  11. A Locus at 5q33.3 Confers Resistance to Tuberculosis in Highly Susceptible Individuals

    PubMed Central

    Sobota, Rafal S.; Stein, Catherine M.; Kodaman, Nuri; Scheinfeldt, Laura B.; Maro, Isaac; Wieland-Alter, Wendy; Igo, Robert P.; Magohe, Albert; Malone, LaShaunda L.; Chervenak, Keith; Hall, Noemi B.; Modongo, Chawangwa; Zetola, Nicola; Matee, Mecky; Joloba, Moses; Froment, Alain; Nyambo, Thomas B.; Moore, Jason H.; Scott, William K.; Lahey, Timothy; Boom, W. Henry; von Reyn, C. Fordham; Tishkoff, Sarah A.; Sirugo, Giorgio; Williams, Scott M.

    2016-01-01

    Immunosuppression resulting from HIV infection increases the risk of progression to active tuberculosis (TB) both in individuals newly exposed to Mycobacterium tuberculosis (MTB) and in those with latent infections. We hypothesized that HIV-positive individuals who do not develop TB, despite living in areas where it is hyperendemic, provide a model of natural resistance. We performed a genome-wide association study of TB resistance by using 581 HIV-positive Ugandans and Tanzanians enrolled in prospective cohort studies of TB; 267 of these individuals developed active TB, and 314 did not. A common variant, rs4921437 at 5q33.3, was significantly associated with TB (odds ratio = 0.37, p = 2.11 × 10−8). This variant lies within a genomic region that includes IL12B and is embedded in an H3K27Ac histone mark. The locus also displays consistent patterns of linkage disequilibrium across African populations and has signals of strong selection in populations from equatorial Africa. Along with prior studies demonstrating that therapy with IL-12 (the cytokine encoded in part by IL12B, associated with longer survival following MTB infection in mice deficient in CD4 T cells), our results suggest that this pathway might be an excellent target for the development of new modalities for treating TB, especially for HIV-positive individuals. Our results also indicate that studying extreme disease resistance in the face of extensive exposure can increase the power to detect associations in complex infectious disease. PMID:26942285

  12. 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

  13. Multiphysics Applications of ACE3P

    SciTech Connect

    K.H. Lee, C. Ko, Z. Li, C.-K. Ng, L. Xiao, G. Cheng, H. Wang

    2012-07-01

    The TEM3P module of ACE3P, a parallel finite-element electromagnetic code suite from SLAC, focuses on the multiphysics simulation capabilities, including thermal and mechanical analysis for accelerator applications. In this pa- per, thermal analysis of coupler feedthroughs to supercon- ducting rf (SRF) cavities will be presented. For the realistic simulation, internal boundary condition is implemented to capture RF heating effects on the surface shared by a di- electric and a conductor. The multiphysics simulation with TEM3P matched the measurement within 0.4%.

  14. COMET 17P/HOLMES IN OUTBURST: THE NEAR INFRARED SPECTRUM

    SciTech Connect

    Yang Bin; Jewitt, David; Bus, Schelte J. E-mail: jewitt@ifa.hawaii.edu

    2009-05-15

    Jupiter family comet 17P/Holmes underwent a remarkable outburst on UT 2007 October 24, in which the integrated brightness abruptly increased by about a factor of a million. We obtained near infrared (0.8-4.2 {mu}m) spectra of 17P/Holmes on UT 2007 October 27, 28, and 31, using the 3.0 m NASA Infrared Telescope Facility atop Mauna Kea. Two broad absorption bands were found in the reflectance spectra with centers (at 2 {mu}m and 3 {mu}m, respectively) and overall shapes consistent with the presence of water ice grains in the coma. Synthetic mixing models of these bands suggest an origin in cold ice grains of micron size. Curiously, though, the expected 1.5 {mu}m band of water ice was not detected in our data, an observation for which we have no explanation. Simultaneously, excess thermal emission in the spectra at wavelengths beyond 3.2 {mu}m has a color temperature of 360 {+-} 40 K (corresponding to a superheat factor of {approx}2.0 {+-} 0.2 at 2.45 AU). This is too hot for these grains to be icy. The detection of both water ice spectral features and short-wavelength thermal emission suggests that the coma of 17P/Holmes has two components (hot, refractory dust and cold ice grains) which are not in thermal contact. A similarity to grains ejected into the coma of 9P/Tempel 1 by the Deep Impact spacecraft is noted.

  15. Molecular analyses of 17p11.2 deletions in 62 Smith-Magenis syndrome patients.

    PubMed Central

    Juyal, R. C.; Figuera, L. E.; Hauge, X.; Elsea, S. H.; Lupski, J. R.; Greenberg, F.; Baldini, A.; Patel, P. I.

    1996-01-01

    Smith-Magenis syndrome (SMS) is a clinically recognizable, multiple congenital anomalies/mental retardation syndrome caused by an interstitial deletion involving band p11.2 of chromosome 17. Toward the molecular definition of the interval defining this microdeletion syndrome, 62 unrelated SMS patients in conjunction with 70 available unaffected parents were molecularly analyzed with respect to the presence or absence of 14 loci in the proximal region of the short arm of chromosome 17. A multifaceted approach was used to determine deletion status at the various loci that combined (i) FISH analysis, (ii)PCR and Southern analysis of somatic cell hybrids retaining the deleted chromosome 17 from selected patients, and (iii) genotype determination of patients for whom a parent(s) was available at four microsatellite marker loci and at four loci with associated RFLPs. The relative order of two novel anonymous markers and a new microsatellite marker was determined in 17p11.2. The results confirmed that the proximal deletion breakpoint in the majority of SMS patients is located between markers D17S58 (EW301) and D17S446 (FG1) within the 17p11.1-17p11.2 region. The common distal breakpoint was mapped between markers cCI17-638, which lies distal to D17S71, and cCI17-498, which lies proximal to the Charcot Marie-Tooth disease type 1A locus. The locus D17S258 was found to be deleted in all 62 patients, and probes from this region can be used for diagnosis of the SMS deletion by FISH. Ten patients demonstrated molecularly distinct deletions; of these, two patients had smaller deletions and will enable the definition of the critical interval for SMS. Images Figure 2 PMID:8651284

  16. The Synodic Rotation Period of Comet 17P/Holmes %C ALPO

    NASA Astrophysics Data System (ADS)

    Betzler, Alberto Silva; Ferreira, Diego Henrique; Ribeiro Dos Snatos, Tárcio Henrique; Novaes, Alberto Brum; Celedon, Julian Hermógenes Quezada

    2008-06-01

    Comet 17P/Holmes was observed in October and November 2007, after the brightness outburst of 24 October. Approximately 11.5 hours of data were collected. A time series analysis reveals a periodicity of 6.29±0.01 hour in the brightness of the inner coma with a single-peak light curve. The object probably has an extremely active area in the nucleus. Therefore, the synodic rotation period is probably equal to the 6.29-hour periodicity that we found.

  17. [Biosynthesis of cellulolytic enzymes and xylanase during submerged cultivation of the fungus Aspergillus terreus 17P].

    PubMed

    Loginova, L G; Guzhova, E P; Ismanlova, D Iu; Burdenko, L G

    1978-01-01

    The fungus Aspergillus terreus 17P--producer of cellulolytic enzymes--was cultivated in the Biotec 10 l fermenter on the medium containing minced and heated (at 200 degrees) wheat straw aerated with a different rate. At the mixing rate of 350 rpm and aeration rate of 0.7 r/rpm on the fourth day the culture liquid was obtained whose filtrate contained an active complex of cellulolytic enzymes and xylanase: CI--3.4; APB--1.1, Cx--35.7, cellobiase--0.23, xylanase--73.8 units/ml. The fractionation of the culture liquid filtrate with ammonium sulphate showed that the fraction precipitated at an interval of saturation of 0.3--0.7 contained the largest portion of cellulolytic enzymes and xylanase. The isolated enzymic preparations had a cellulolytic and xylanase activity and contained lipase, pectinase, laminarinase. They also contained low quantities of amylase, protease, beta-1,4- and beta-1,6-glucanase. Enzymic hylrolysis by the Asp. terreus 17P preparation of straw yielded glucose and xylose, of cotton, Na-KMC, cellobiose--glucose, Xylane hydrolyzate contained xylose and arabinose.

  18. Precise localisation of 3p25 breakpoints in four patients with the 3p-syndrome.

    PubMed Central

    Drumheller, T; McGillivray, B C; Behrner, D; MacLeod, P; McFadden, D E; Roberson, J; Venditti, C; Chorney, K; Chorney, M; Smith, D I

    1996-01-01

    In patients with the 3p-syndrome, hemizygous deletion of 3p25-pter is associated with profound growth failure, characteristic facial features, and mental retardation. We performed a molecular genetic analysis of 3p25 breakpoints in four patients with the 3p- syndrome, and a fifth patient with a more complex abnormality, 46,XY,der(3)t(3;?)(p25.3;?). EBV transformed lymphoblasts from each of the patients were initially characterised using fluorescent in situ hybridisation (FISH) and polymorphic microsatellite analyses. The 3p-chromosome from each patient was isolated from the normal chromosome 3 in somatic cell hybrid lines and subsequently analysed with polymorphic and monomorphic PCR amplifiable markers from 3p25. The analysis clearly shows that all five breakpoints are distinct. Furthermore, we have identified yeast artificial chromosomes that cross the 3p25 breakpoints of all four 3p-patients. Two of the patients were deleted for the von Hippel-Lindau (VHL) tumour suppressor gene, although neither has yet developed evidence of VHL disease. The patient with the most centromeric breakpoint, between D3S1585 and D3S1263, had the most severe clinical phenotype including an endocardial cushion defect that was not observed in any of the four patients who had more telomeric breakpoints. This study should provide useful insights into critical regions within 3p25 that are involved in normal human growth and development. Images PMID:8933338

  19. Familial 5q11.2 → q13.3 Segmental Duplication Cosegregating With Multiple Anomalies, Including Schizophrenia

    PubMed Central

    McGillivray, Barbara C.; Bassett, Anne S.; Langlois, Sylvie; Pantzar, Tapio; Wood, Stephen

    2011-01-01

    We report on 2 relatives with a segmental duplication of 5q11.2 → 13.3. The phenotype is surprisingly limited for the degree of chromosome imbalance, the propositus presenting with schizophrenia. Using RFLP markers, we have shown that the gene for HEXB lies within the duplicated region. We suggest this region as a candidate region for the location of a single major gene which predisposes to schizophrenia and which may be assessed by linkage analysis. PMID:1967903

  20. A novel 5q11.2 microdeletion in a child with mild developmental delay and dysmorphic features.

    PubMed

    Fontana, Paolo; Tortora, Cristina; Petillo, Roberta; Falco, Mariateresa; Miniero, Martina; De Brasi, Davide; Pisanti, Maria Antonietta

    2016-09-01

    5q11.2 Deletion is a very rare genomic disorder, and its clinical phenotype has not yet been characterized. This report describes a patient with an 8.6 Mb deletion, showing hypotonia, mild developmental delay, short stature, and distinctive dysmorphic features (frontal bossing, square face, deep-set eyes, prominent columella, long philtrum, thin lips). © 2016 Wiley Periodicals, Inc.

  1. A syndromic form of Pierre Robin sequence is caused by 5q23 deletions encompassing FBN2 and PHAX.

    PubMed

    Ansari, Morad; Rainger, Jacqueline K; Murray, Jennie E; Hanson, Isabel; Firth, Helen V; Mehendale, Felicity; Amiel, Jeanne; Gordon, Christopher T; Percesepe, Antonio; Mazzanti, Laura; Fryer, Alan; Ferrari, Paola; Devriendt, Koenraad; Temple, I Karen; FitzPatrick, David R

    2014-10-01

    Pierre Robin sequence (PRS) is an aetiologically distinct subgroup of cleft palate. We aimed to define the critical genomic interval from five different 5q22-5q31 deletions associated with PRS or PRS-associated features and assess each gene within the region as a candidate for the PRS component of the phenotype. Clinical array-based comparative genome hybridisation (aCGH) data were used to define a 2.08 Mb minimum region of overlap among four de novo deletions and one mother-son inherited deletion associated with at least one component of PRS. Commonly associated anomalies were talipes equinovarus (TEV), finger contractures and crumpled ear helices. Expression analysis of the orthologous genes within the PRS critical region in embryonic mice showed that the strongest candidate genes were FBN2 and PHAX. Targeted aCGH of the critical region and sequencing of these genes in a cohort of 25 PRS patients revealed no plausible disease-causing mutations. In conclusion, deletion of ∼2 Mb on 5q23 region causes a clinically recognisable subtype of PRS. Haploinsufficiency for FBN2 accounts for the digital and auricular features. A possible critical region for TEV is distinct and telomeric to the PRS region. The molecular basis of PRS in these cases remains undetermined but haploinsufficiency for PHAX is a plausible mechanism.

  2. Selective expansion of regulatory T cells during lenalidomide treatment of myelodysplastic syndrome with isolated deletion 5q.

    PubMed

    Balaian, Ekaterina; Schuster, Claudia; Schönefeldt, Claudia; Germing, Ulrich; Haase, Detlef; Tuve, Sebastian; Ordemann, Rainer; Ehninger, Gerhard; Bornhäuser, Martin; Oelschlaegel, Uta; Mohr, Brigitte; von Bonin, Malte; Platzbecker, Uwe; Wermke, Martin

    2016-10-01

    Lenalidomide (LEN) leads to erythroid improvement in the majority of patients with myelodysplastic syndrome and isolated deletion of the long arm of chromosome 5 (MDS-del(5q)). This effect is believed to be exerted via its immunomodulatory properties, although the precise nature is still incompletely understood. We prospectively performed immune profiling in the bone marrow and blood of MDS-del(5q) patients undergoing LEN therapy for a median of 6 cycles. Therapy with LEN led to a significant increase in the median absolute lymphocyte count (1.3-fold, p = 0.013) without changes in the distribution of the T helper cells within the entire compartment. In parallel, the frequency of Treg increased significantly during treatment both in the peripheral blood (5.0 vs. 9.6 %, p = 0.001) and bone marrow (3.4 vs. 8.1 %, p = 0.001). Surprisingly, LEN treatment led to a decrease in TGFbeta levels, both in the peripheral blood (4.9 vs. 2.3 ng/ml, p = 0.039) and bone marrow (4.5 vs. 0.8 ng/ml, p = 0.023). These changes were not associated with an increase in pro-inflammatory Th17 cells. Taken together, our results demonstrate that LEN induces a shift in lymphocytic populations towards immunosuppression in MDS-del(5q) patients.

  3. The F17(p,γ)Ne18 resonant cross section

    NASA Astrophysics Data System (ADS)

    Chipps, K. A.; Bardayan, D. W.; Nesaraja, C. D.; Smith, M. S.; Blackmon, J. C.; Chae, K. Y.; Moazen, B. H.; Pittman, S. T.; Greife, U.; Hatarik, R.; Peters, W. A.; Kozub, R. L.; Shriner, J. F., Jr.; Matei, C.; Pain, S. D.

    2009-12-01

    We directly measure the F17(p,γ)Ne18 resonant reaction using a mixed beam of F17 and O17 at the Holifield Radioactive Ion Beam Facility at Oak Ridge National Laboratory (ORNL). The astrophysically important 3+ resonance at ~600 keV above the proton threshold in Ne18 is found to have a partial width Γγ=56±24(stat)±30(sys) meV, in reasonable agreement with the theoretically predicted width. A 2σ upper limit on the direct capture of S(E)⩽65 keV b is determined at an energy of 800 keV. Experimental techniques and astrophysical implications are discussed.

  4. Comet 17P/Holmes: contrast in activity between before and after the 2007 outburst

    SciTech Connect

    Ishiguro, Masateru; Kim, Yoonyoung; Warjurkar, Dhanraj S.; Ham, Ji-Beom; Kim, Junhan; Usui, Fumihiko; Vaubaillon, Jeremie J.; Ishihara, Daisuke; Hanayama, Hidekazu; Sarugaku, Yuki; Hasegawa, Sunao; Kasuga, Toshihiro; Watanabe, Jun-ichi; Pyo, Jeonghyun; Kuroda, Daisuke; Ootsubo, Takafumi; Sakamoto, Makoto; Narusawa, Shin-ya; Takahashi, Jun; Akisawa, Hiroki

    2013-11-20

    A Jupiter-family comet, 17P/Holmes, underwent outbursts in 1892 and 2007. In particular, the 2007 outburst is known as the greatest outburst over the past century. However, little is known about the activity before the outburst because it was unpredicted. In addition, the time evolution of the nuclear physical status has not been systematically studied. Here, we study the activity of 17P/Holmes before and after the 2007 outburst through optical and mid-infrared observations. We found that the nucleus was highly depleted in its near-surface icy component before the outburst but that it became activated after the 2007 outburst. Assuming a conventional 1 μm sized grain model, we derived a surface fractional active area of 0.58% ± 0.14% before the outburst whereas the area was enlarged by a factor of ∼50 after the 2007 outburst. We also found that large (≥1 mm) particles could be dominant in the dust tail observed around aphelion. Based on the size of the particles, the dust production rate was ≳170 kg s{sup –1} at a heliocentric distance of r{sub h} = 4.1 AU, suggesting that the nucleus was still active around the aphelion passage. The nucleus color was similar to that of the dust particles and average for a Jupiter-family comet but different from that of most Kuiper Belt objects, implying that color may be inherent to icy bodies in the solar system. On the basis of these results, we concluded that more than 76 m of surface material was blown off by the 2007 outburst.

  5. p53 protein expression independently predicts outcome in patients with lower-risk myelodysplastic syndromes with del(5q).

    PubMed

    Saft, Leonie; Karimi, Mohsen; Ghaderi, Mehran; Matolcsy, András; Mufti, Ghulam J; Kulasekararaj, Austin; Göhring, Gudrun; Giagounidis, Aristoteles; Selleslag, Dominik; Muus, Petra; Sanz, Guillermo; Mittelman, Moshe; Bowen, David; Porwit, Anna; Fu, Tommy; Backstrom, Jay; Fenaux, Pierre; MacBeth, Kyle J; Hellström-Lindberg, Eva

    2014-06-01

    Del(5q) myelodysplastic syndromes defined by the International Prognostic Scoring System as low- or intermediate-1-risk (lower-risk) are considered to have an indolent course; however, recent data have identified a subgroup of these patients with more aggressive disease and poorer outcomes. Using deep sequencing technology, we previously demonstrated that 18% of patients with lower-risk del(5q) myelodysplastic syndromes carry TP53 mutated subclones rendering them at higher risk of progression. In this study, bone marrow biopsies from 85 patients treated with lenalidomide in the MDS-004 clinical trial were retrospectively assessed for p53 expression by immunohistochemistry in association with outcome. Strong p53 expression in ≥ 1% of bone marrow progenitor cells, observed in 35% (30 of 85) of patients, was significantly associated with higher acute myeloid leukemia risk (P=0.0006), shorter overall survival (P=0.0175), and a lower cytogenetic response rate (P=0.009), but not with achievement or duration of 26-week transfusion independence response. In a multivariate analysis, p53-positive immunohistochemistry was the strongest independent predictor of transformation to acute myeloid leukemia (P=0.0035). Pyrosequencing analysis of laser-microdissected cells with strong p53 expression confirmed the TP53 mutation, whereas cells with moderate expression predominantly had wild-type p53. This study validates p53 immunohistochemistry as a strong and clinically useful predictive tool in patients with lower-risk del(5q) myelodysplastic syndromes. This study was based on data from the MDS 004 trial (clinicaltrials.gov identifier: NCT00179621). PMID:24682512

  6. p53 protein expression independently predicts outcome in patients with lower-risk myelodysplastic syndromes with del(5q)

    PubMed Central

    Saft, Leonie; Karimi, Mohsen; Ghaderi, Mehran; Matolcsy, András; Mufti, Ghulam J.; Kulasekararaj, Austin; Göhring, Gudrun; Giagounidis, Aristoteles; Selleslag, Dominik; Muus, Petra; Sanz, Guillermo; Mittelman, Moshe; Bowen, David; Porwit, Anna; Fu, Tommy; Backstrom, Jay; Fenaux, Pierre; MacBeth, Kyle J.; Hellström-Lindberg, Eva

    2014-01-01

    Del(5q) myelodysplastic syndromes defined by the International Prognostic Scoring System as low- or intermediate-1-risk (lower-risk) are considered to have an indolent course; however, recent data have identified a subgroup of these patients with more aggressive disease and poorer outcomes. Using deep sequencing technology, we previously demonstrated that 18% of patients with lower-risk del(5q) myelodysplastic syndromes carry TP53 mutated subclones rendering them at higher risk of progression. In this study, bone marrow biopsies from 85 patients treated with lenalidomide in the MDS-004 clinical trial were retrospectively assessed for p53 expression by immunohistochemistry in association with outcome. Strong p53 expression in ≥1% of bone marrow progenitor cells, observed in 35% (30 of 85) of patients, was significantly associated with higher acute myeloid leukemia risk (P=0.0006), shorter overall survival (P=0.0175), and a lower cytogenetic response rate (P=0.009), but not with achievement or duration of 26-week transfusion independence response. In a multivariate analysis, p53-positive immunohistochemistry was the strongest independent predictor of transformation to acute myeloid leukemia (P=0.0035). Pyrosequencing analysis of laser-microdissected cells with strong p53 expression confirmed the TP53 mutation, whereas cells with moderate expression predominantly had wild-type p53. This study validates p53 immunohistochemistry as a strong and clinically useful predictive tool in patients with lower-risk del(5q) myelodysplastic syndromes. This study was based on data from the MDS 004 trial (clinicaltrials.gov identifier: NCT00179621). PMID:24682512

  7. A novel microdeletion syndrome involving 5q14.3-q15: clinical and molecular cytogenetic characterization of three patients

    PubMed Central

    Engels, Hartmut; Wohlleber, Eva; Zink, Alexander; Hoyer, Juliane; Ludwig, Kerstin U; Brockschmidt, Felix F; Wieczorek, Dagmar; Moog, Ute; Hellmann-Mersch, Birgit; Weber, Ruthild G; Willatt, Lionel; Kreiß-Nachtsheim, Martina; Firth, Helen V; Rauch, Anita

    2009-01-01

    Molecular karyotyping is being increasingly applied to delineate novel disease causing microaberrations and related syndromes in patients with mental retardation of unknown aetiology. We report on three unrelated patients with overlapping de novo interstitial microdeletions involving 5q14.3-q15. All three patients presented with severe psychomotor retardation, epilepsy or febrile seizures, muscular hypotonia and variable brain and minor anomalies. Molecular karyotyping revealed three overlapping microdeletions measuring 5.7, 3.9 and 3.6 Mb, respectively. The microdeletions were identified using single nucleotide polymorphism (SNP) arrays (Affymetrix 100K and Illumina 550K) and array comparative genomic hybridization (1 Mb Sanger array-CGH). Confirmation and segregation studies were performed using fluorescence in situ hybridization (FISH) and quantitative PCR. All three aberrations were confirmed and proven to have occurred de novo. The boundaries and sizes of the deletions in the three patients were different, but an overlapping region of around 1.6 Mb in 5q14.3 was defined. It included five genes: CETN3, AC093510.2, POLR3G, LYSMD3 and the proximal part of GPR98/MASS1, a known epilepsy gene. Haploinsufficiency of GPR98/MASS1 is probably responsible for the seizure phenotype in our patients. At least one other gene contained in the commonly deleted region, LYSMD3, shows a high level of central nervous expression during embryogenesis and is also, therefore, a good candidate gene for other central nervous system (CNS) symptoms, such as psychomotor retardation, brain anomalies and muscular hypotonia of the 5q14.3 microdeletion syndrome. PMID:19471318

  8. Linkage disequilibrium between a 5q13 microsatellite null allele and SMA indicates complex but stable deletions/duplications

    SciTech Connect

    Surhk, L.C.; Aubry, H.L.; MacKenzie, A.E.

    1994-09-01

    SMA is a recessively inherited degeneration of alpha motor neurons presenting in three distinct types with diverse onsets ranging from infancy (type I) to childhood (types II and III). All forms have been mapped to chromosome 5q13.1. We have developed PCR primers for two distinct microsatellite repeats (MSR), CATT-40G1 and CATT-192F7. These subloci are constituents of a previously reported 5q13.1 complex CA dinucleotide MSR, CATT-1, with four or more copies per chromosome. Type 1 SMA families (n=35) were examined because stricter clinical criteria permitted greater diagnostic accuracy and, possibly, greater mutational homogeneity. One allele per chromosome is amplified with the 40G1 and 192F7 subloci-specific primers out of a total of 3 and 7 possible alleles, respectively. Significant linkage disequilibrium was observed between the disease phenotype and the 40G1 null allele ({chi}{sup 2}=38.23) and 192F7 allele with 19 CA repeats ({chi}{sup 2}=6.62) in contrast to two markers D5S435 ({chi}{sup 2}=.42) and D5S351 ({chi}{sup 2}=.16), which have been shown to flank the SMA locus at less than 1% recombination. The null alleles present in both subloci appeared to be due to stable deletions rather than isolated DNA sequence polymorphisms. In contrast to recent reports, no evidence of de novo rearrangements were observed. Furthermore, duplications of these subloci have been observed in three normal chromosomes. Our data are consistent with unequal cross-overs generating deletions/duplications which not only account for the complexity being observed in the genomic walk within the critical SMA region, but could also be causally related SMA mutations. Results of similar linkage disequilibrium analyses employing 3 additional 5q13.1 microsatellites will also be presented.

  9. Cytogenetic follow-up by karyotyping and fluorescence in situ hybridization: implications for monitoring patients with myelodysplastic syndrome and deletion 5q treated with lenalidomide

    PubMed Central

    Göhring, Gudrun; Giagounidis, Aristoteles; Büsche, Guntram; Hofmann, Winfried; Kreipe, Hans Heinrich; Fenaux, Pierre; Hellström-Lindberg, Eva; Schlegelberger, Brigitte

    2011-01-01

    In patients with low and intermediate risk myelodysplastic syndrome and deletion 5q (del(5q)) treated with lenalidomide, monitoring of cytogenetic response is mandatory, since patients without cytogenetic response have a significantly increased risk of progression. Therefore, we have reviewed cytogenetic data of 302 patients. Patients were analyzed by karyotyping and fluorescence in situ hybridization. In 85 patients, del(5q) was only detected by karyotyping. In 8 patients undergoing karyotypic evolution, the del(5q) and additional chromosomal aberrations were only detected by karyotyping. In 3 patients, del(5q) was only detected by fluorescence in situ hybridization, but not by karyotyping due to a low number of metaphases. Karyotyping was significantly more sensitive than fluorescence in situ hybridization in detecting the del(5q) clone. In conclusion, to optimize therapy control of myelodysplastic syndrome patients with del(5q) treated with lenalidomide and to identify cytogenetic non-response or progression as early as possible, fluorescence in situ hybridization alone is inadequate for evaluation. Karyotyping must be performed to optimally evaluate response. (clinicaltrials.gov identifier: NCT01099267 and NCT00179621) PMID:21109690

  10. Fine localization of the locus for autosomal dominant retinitis pigmentosa on chromosome 17p

    SciTech Connect

    Goliath, R.; Janssens, P.; Beighton, P.

    1995-10-01

    The term {open_quotes}retintis pigmentosa{close_quotes} (RP) refers to a group of inherited retinal degenerative disorders. Clinical manifestations include night-blindness, with variable age of onset, followed by constriction of the visual field that may progress to total loss of sight in later life. Previous studies have shown that RP is caused by mutations within different genes and may be inherited as an X-linked recessive (XLRRP), autosomal recessive (ARRP), or autosomal dominant (ADRP) trait. The AD form of this group of conditions has been found to be caused by mutations within the rhodopsin gene in some families and the peripherin/RDS gene in others. In addition, some ADRP families have been found to be linked to anonymous markers on 8cen, 7p, 7q,19q, and, more recently, 17p. The ADRP gene locus on the short arm of chromosome 17 was identified in a large South African family (ADRP-SA) of British origin. The phenotypic expression of the disorder, which has been described elsewhere is consistent in the pedigree with an early onset of disease symptoms. In all affected subjects in the family, onset of symptoms commenced before the age of 10 years. 16 refs., 3 figs., 1 tab.

  11. Identification of a functional variant for colorectal cancer risk mapping to chromosome 5q31.1

    PubMed Central

    Chen, Xueqin; Li, Jiaoyuan; Liu, Cheng; Gong, Yajie; Yang, Yang; Zhu, Ying; Zhang, Yi; Tian, Jianbo; Chang, Jiang; Zhong, Rong; Gong, Jing; Miao, Xiaoping

    2016-01-01

    Genome-wide association studies (GWASs) have established chromosome 5q31.1 as a risk locus for colorectal cancer (CRC). We previously identified a potentially regulatory single nucleotide polymorphism (SNP) rs17716310 within 5q31.1. Now, we extended our study with another independent Chinese population, functional assays and analyses of TCGA (The Cancer Genome Atlas) data. Significant associations between rs17716310 and CRC risk were found in Present Study including 1075 CRC cases and 1999 controls (additive model: OR = 1.149, 95% CI = 1.027–1.286, P = 0.016), and in Combined Study including 1766 cases and 2708 controls (additive model: OR = 1.145, 95% CI = 1.045–1.254, P = 0.004). Dual luciferase reporter gene assays indicated that the variant C allele obviously increased transcriptional activity. Using TCGA datasets, we indicated rs17716310 as a cis expression quantitative trait locus (eQTL) for the gene SMAD5, whose expression was significantly higher in CRC tissues. These findings suggested that the functional polymorphism rs17716310 A > C might be a genetic modifier for CRC, promoting the expression of SMAD5 that belonged to the transforming growth factor beta (TGF-β) signaling pathway. PMID:27177089

  12. Novel microsatellite repeats (MSRs) and linkage disequilibrium analysis in the SMA region of 5q13.1

    SciTech Connect

    Yaraghi, Z.; Roy, N.; MacKenzie, A.E.

    1994-09-01

    The spinal muscular atrophies (SMA) are characterized by degeneration of the anterior horn cells of the spinal cord, leading to muscular atrophy associated with progressive paralysis. The gene involved in SMA has been mapped by linkage analysis to a region of 5q13.1 flanked centromerically by D5S435 and telomerically by D5S557. We are in the process of identifying new microsatellite repeats to further define the genetic map of the SMA region. A contiguous array of YAC clones covering the SMA containing D5S435-D56S112 interval of 5q13.1 was established. From this contig, a 700 kb clone 76C1, which contains the 200 kb CMS-1/CATT-1 critical region, was used to generate a partial Sau3A1 phage library. We have previously shown that 2 CATT-1 subloci are in linkage disequilibrium with type I SMA. The 76C1 subloci are in linkage disequilibrium with type I SMA. The 76C1 phage library has been screened for human MSRs. To date we have identified two novel polymorphic microsatellites and four further candidates are being characterized. Results of linkage disequilibrium studies currently underway will be presented. The identification of a linkage disequilibrium maximum will be helpful in the further narrowing of the SMA region.

  13. Fine-Mapping of 5q12.1–13.3 Unveils New Genetic Contributors to Caries

    PubMed Central

    Shimizu, T.; Deeley, K.; Briseño-Ruiz, J.; Faraco, I.M.; Poletta, F.A.; Brancher, J.A.; Pecharki, G.D.; Küchler, E.C.; Tannure, P.N.; Lips, A.; Vieira, T.C.S.; Patir, A.; Yildirim, M.; Mereb, J.C.; Resick, J.M.; Brandon, C.A.; Cooper, M.E.; Seymen, F.; Costa, M.C.; Granjeiro, J.M.; Trevilatto, P.C.; Orioli, I.M.; Castilla, E.E.; Marazita, M.L.; Vieira, A.R.

    2013-01-01

    Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. Our previous genome-wide linkage scan has identified the interval 5q12.1–5q13.3 as linked to low caries susceptibility in Filipino families. Here we fine-mapped this region in order to identify genetic contributors to caries susceptibility. Four hundred and seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. DMFT scores and genotype data of 75 single-nucleotide polymorphisms were evaluated in the Filipino families with the Family-Based Association Test. For replication purposes, a total 1,467 independent subjects from five different populations were analyzed in a case-control format. In the Filipino cohort, statistically significant and borderline associations were found between low caries experience and four genes spanning 13 million base pairs (PART1, ZSWIM6, CCNB1, and BTF3). We were able to replicate these results in some of the populations studied. We detected PART1 and BTF3 expression in whole saliva, and the expression of BTF3 was associated with caries experience. Our results suggest BTF3 may have a functional role in protecting against caries. PMID:23363935

  14. TP53 and MDM2 single nucleotide polymorphisms influence survival in non-del(5q) myelodysplastic syndromes

    PubMed Central

    Sallman, David A.; Basiorka, Ashley A.; Irvine, Brittany A.; Zhang, Ling; Epling-Burnette, P.K.; Rollison, Dana E.; Mallo, Mar; Sokol, Lubomir; Solé, Francesc; Maciejewski, Jaroslaw; List, Alan F.

    2015-01-01

    P53 is a key regulator of many cellular processes and is negatively regulated by the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are linked to cancer susceptibility, disease progression, and therapy response. We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was performed on DNA isolated from 208 MDS cases. Utilizing a novel functional SNP scoring system ranging from +2 to −2 based on predicted p53 activity, we found statistically significant differences in overall survival (OS) (p = 0.02) and progression-free survival (PFS) (p = 0.02) in non-del(5q) MDS patients with low functional scores. In univariate analysis, only IPSS and the functional SNP score predicted OS and PFS in non-del(5q) patients. In multivariate analysis, the functional SNP score was independent of IPSS for OS and PFS. These data underscore the importance of TP53 R72P and MDM2 SNP309 SNPs in MDS, and provide a novel scoring system independent of IPSS that is predictive for disease outcome. PMID:26416416

  15. TP53 and MDM2 single nucleotide polymorphisms influence survival in non-del(5q) myelodysplastic syndromes.

    PubMed

    McGraw, Kathy L; Cluzeau, Thomas; Sallman, David A; Basiorka, Ashley A; Irvine, Brittany A; Zhang, Ling; Epling-Burnette, P K; Rollison, Dana E; Mallo, Mar; Sokol, Lubomir; Solé, Francesc; Maciejewski, Jaroslaw; List, Alan F

    2015-10-27

    P53 is a key regulator of many cellular processes and is negatively regulated by the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are linked to cancer susceptibility, disease progression, and therapy response. We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was performed on DNA isolated from 208 MDS cases. Utilizing a novel functional SNP scoring system ranging from +2 to -2 based on predicted p53 activity, we found statistically significant differences in overall survival (OS) (p = 0.02) and progression-free survival (PFS) (p = 0.02) in non-del(5q) MDS patients with low functional scores. In univariate analysis, only IPSS and the functional SNP score predicted OS and PFS in non-del(5q) patients. In multivariate analysis, the functional SNP score was independent of IPSS for OS and PFS. These data underscore the importance of TP53 R72P and MDM2 SNP309 SNPs in MDS, and provide a novel scoring system independent of IPSS that is predictive for disease outcome. PMID:26416416

  16. High levels of loss at the 17p telomere suggest the close proximity of a tumour suppressor.

    PubMed Central

    White, G. R.; Stack, M.; Santibáñez-Koref, M.; Liscia, D. S.; Venesio, T.; Wang, J. C.; Helms, C.; Donis-Keller, H.; Betticher, D. C.; Altermatt, H. J.; Hoban, P. R.; Heighway, J.

    1996-01-01

    High levels of loss of distal markers on 17p13.3 in breast cancer suggested the presence within the region of at least one tumour-suppressor gene. Here we describe the derivation of two biallelic polymorphisms from the 17p telomeric yeast artificial chromosome (YAC) TYAC98. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex PCR analysis demonstrated that the high level of allelic imbalance observed in breast tumours represented loss of constitutional heterozygosity (LOH) and that this LOH extended to the telomere. Lung carcinoma (but not Wilms' tumour)-derived DNA again revealed a high level of loss of subtelomeric 17p sequences. Telomeric microsatellite polymorphisms from other chromosome arms did not show such elevated loss in either tumour type. This suggested that the 17p loss observed did not reflect a general telomeric instability and provided further evidence for the presence of a breast cancer tumour-suppressor gene in the distal region of 17p13.3. Images Figure 1 Figure 2 Figure 3 PMID:8826850

  17. Miller-Dieker syndrome associated with duplication of 17p13.3 confirmed by fluorescence in situ hybridization (FISH)

    SciTech Connect

    Li, S.; Tuck-Muller, C.M.; Martinez, J.E.

    1994-09-01

    Miller-Dieker syndrome is characterized by profound mental retardation, craniofacial abnormalities, and lissencephaly (smooth brain). Microscopic or submicroscopic deletions of the 17p13.3 region have been reported in Miller-Dieker patients. We report a patient with this syndrome in whom a duplication of the 17p13.3 region was detected by FISH. The 9-year-old female proband was referred because of features of Miller-Dieker syndrome: microcephaly, profound psychomotor retardation, seizures, characteristic facies, and lissencephaly shown by MRI studies. High-resolution G-banding failed to demonstrate an abnormality in chromosome 17. However, FISH analysis with the DNA probe (Oncor No. 5101) specific for Miller-Dieker region of chromosome 17p13.3 demonstrated duplication of this segment instead of the classic deletion. We know of no other report of Miller-Dieker syndrome associated with duplication of 17p13.3. The family study revealed normal chromosomes in both parents by cytogenetic and FISH analysis. Our investigation suggests that duplications, as well as deletions, of the 17p13.3 region are associated with the Miller-Dieker syndrome. The presence of deletions or duplications of the same chromosomal region in patients with features of Miller-Dieker syndrome suggests that its pathogenesis may be due to gene dosage effects.

  18. 17p13.3 microduplication including CRK leads to overgrowth and elevated growth factors: A case report.

    PubMed

    Henry, Rohan K; Astbury, Caroline; Stratakis, Constantine A; Hickey, Scott E

    2016-10-01

    17p13.3 microduplications classified as class I duplications involving YWHAE but not PAFAH1B1 (formerly LIS1) and class II duplications which extend to involve PAFAH1B1, are associated with diverse phenotypes including intellectual disability and structural brain malformations. We report a girl with an approximately 1.58 Mb apparently terminal gain of 17p13.3, which contains more than 20 genes including the YWHAE and CRK genes (OMIM: 164762). She had increased growth factors accompanied by pathologic tall stature. In addition to these, she developed central precocious puberty at 7 years old. In individuals with class I 17p13.3 microduplications including CRK, we recommend biochemical evaluation of the growth hormone axis. Providers caring for these patients should be aware of their possible risk for the development of central precocious puberty. PMID:27633569

  19. Neurologic and developmental features of the Smith-Magenis syndrome (del 17p11.2).

    PubMed

    Gropman, Andrea L; Duncan, Wallace C; Smith, Ann C M

    2006-05-01

    The Smith-Magenis syndrome is a rare, complex multisystemic disorder featuring, mental retardation and multiple congenital anomalies caused by a heterozygous interstitial deletion of chromosome 17p11.2. The phenotype of Smith-Magenis syndrome is characterized by a distinct pattern of features including infantile hypotonia, generalized complacency and lethargy in infancy, minor skeletal (brachycephaly, brachydactyly) and craniofacial features, ocular abnormalities, middle ear and laryngeal abnormalities including hoarse voice, as well as marked early expressive speech and language delays, psychomotor and growth retardation, and a 24-hour sleep disturbance. A striking neurobehavioral pattern of stereotypies, hyperactivity, polyembolokoilamania, onychotillomania, maladaptive and self-injurious and aggressive behavior is observed with increasing age. The diagnosis of Smith-Magenis syndrome is based upon the clinical recognition of a constellation of physical, developmental, and behavioral features in combination with a sleep disorder characterized by inverted circadian rhythm of melatonin secretion. Many of the features of Smith-Magenis syndrome are subtle in infancy and early childhood, and become more recognizable with advancing age. Infants are described as looking "cherubic" with a Down syndrome-like appearance, whereas with age the facial appearance is that of relative prognathism. Early diagnosis requires awareness of the often subtle clinical and neurobehavioral phenotype of the infant period. Speech delay with or without hearing loss is common. Most children are diagnosed in mid-childhood when the features of the disorder are most recognizable and striking. While improvements in cytogenetic analysis help to bring cases to clinical recognition at an earlier age, this review seeks to increase clinical awareness about Smith-Magenis syndrome by presenting the salient features observed at different ages including descriptions of the neurologic and behavioral

  20. Detection of Remnant Dust Cloud Associated with the 2007 Outburst of 17P/Holmes

    NASA Astrophysics Data System (ADS)

    Ishiguro, Masateru; Sarugaku, Yuki; Kuroda, Daisuke; Hanayama, Hidekazu; Kim, Yoonyoung; Kwon, Yuna G.; Maehara, Hiroyuki; Takahashi, Jun; Terai, Tsuyoshi; Usui, Fumihiko; Vaubaillon, Jeremie J.; Morokuma, Tomoki; Kobayashi, Naoto; Watanabe, Jun-ichi

    2016-01-01

    This article reports a new optical observation of 17P/Holmes one orbital period after the historical outburst event in 2007. We detected not only a common dust tail near the nucleus but also a long narrow structure that extended along the position angle 274.°6 ± 0.°1 beyond the field of view (FOV) of the Kiso Wide Field Camera, i.e., >0.°2 eastward and >2.°0 westward from the nuclear position. The width of the structure decreased westward with increasing distance from the nucleus. We obtained the total cross section of the long extended structure in the FOV, CFOV = (2.3 ± 0.5) × 1010 m2. From the position angle, morphology, and mass, we concluded that the long narrow structure consists of materials ejected during the 2007 outburst. On the basis of the dynamical behavior of dust grains in the solar radiation field, we estimated that the long narrow structure would be composed of 1 mm-1 cm grains having an ejection velocity of >50 m s-1. The velocity was more than one order of magnitude faster than that of millimeter-centimeter grains from typical comets around a heliocentric distance rh of 2.5 AU. We considered that sudden sublimation of a large amount of water-ice (≈1030 mol s-1) would be responsible for the high ejection velocity. We finally estimated a total mass of MTOT = (4-8) × 1011 kg and a total kinetic energy of ETOT = (1-6) × 1015 J for the 2007 outburst ejecta, which are consistent with those of previous studies that were conducted soon after the outburst.

  1. The carboxy terminal WD domain of the pre-mRNA splicing factor Prp17p is critical for function.

    PubMed Central

    Lindsey-Boltz, L A; Chawla, G; Srinivasan, N; Vijayraghavan, U; Garcia-Blanco, M A

    2000-01-01

    In Saccharomyces cerevisiae, Prp17p is required for the efficient completion of the second step of pre-mRNA splicing. The function and interacting factors for this protein have not been elucidated. We have performed a mutational analysis of yPrp17p to identify protein domains critical for function. A series of deletions were made throughout the region spanning the N-terminal 158 amino acids of the protein, which do not contain any identified structural motifs. The C-terminal portion (amino acids 160-455) contains a WD domain containing seven WD repeats. We determined that a minimal functional Prp17p consists of the WD domain and 40 amino acids N-terminal to it. We generated a three-dimensional model of the WD repeats in Prp17p based on the crystal structure of the beta-transducin WD domain. This model was used to identify potentially important amino acids for in vivo functional characterization. Through analysis of mutations in four different loops of Prp17p that lie between beta strands in the WD repeats, we have identified four amino acids, 235TETG238, that are critical for function. These amino acids are predicted to be surface exposed and may be involved in interactions that are important for splicing. Temperature-sensitive prp17 alleles with mutations of these four amino acids are defective for the second step of splicing and are synthetically lethal with a U5 snRNA loop I mutation, which is also required for the second step of splicing. These data reinforce the functional significance of this region within the WD domain of Prp17p in the second step of splicing. PMID:10999606

  2. Susceptibility gene for familial acute myeloid leukemia associated with loss of 5q and/or 7q is not localized on the commonly deleted portion of 5q.

    PubMed

    Gao, Q; Horwitz, M; Roulston, D; Hagos, F; Zhao, N; Freireich, E J; Golomb, H M; Olopade, O I

    2000-06-01

    The molecular mechanism for the occurrence of leukemia in multiple members of a family has not been fully elucidated but data support the contribution of highly penetrant mutations in leukemia susceptibility genes. We have investigated the genetic etiology of an unusual three-generation family with apparent autosomal dominant transmission of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) accompanied by somatic loss of the long arm of chromosome 5 and/or loss of heterozygosity (LOH) analysis and fluorescence in situ hybridization (FISH) of leukemia cells have been performed, confirming acquired hemi- and homozygous deletion of the long arm of chromosome 5. However, the chromosome lost in the observed LOH event is from the affected parent, in contradiction to the expectation for a two-hit hypothesis involving a tumor suppressor gene. Furthermore, genetic linkage has been performed at 5q31-33 as well as other loci (21q22 and 16q21-23.2) previously implicated in familial leukemia. In this family, linkage analysis excludes loci at 5q31-33 and 21q22, but localization to 16q21-23.2 cannot be excluded. We observed a maximum multipoint LOD score of 1.19 between marker D16S265 and D16S503 at 16q22 (P = 0.03), suggesting possible linkage to this locus. Considering this family and the previous 16q-linked family together, the linkage of a leukemia susceptibility gene to 16q22 achieved an LOD score of 3.63 at D16S265 with theta = 0. Thus, somatic deletion of the long arm of chromosome 5 appears as a necessary but surprisingly noncausative event for onset of AML and MDS in this family, thereby confirming a multistep etiology in which chromosome 5 plays an important secondary role.

  3. Interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q

    SciTech Connect

    Le Beau, M.M.; Epstein, N.D.; O'Brien, S.J.; Nienhuis, A.W.; Yang, Y.C.; Clark, S.C.; Rowley, J.D.

    1987-08-01

    The gene IL-3 encodes interleukin 3, a hematopoietic colony-stimulating factor (CSF) that is capable of supporting the proliferation of a broad range of hematopoietic cell types. By using somatic cell hybrids and in situ chromosomal hybridization, the authors localized this gene to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted (del(5q)) in patients with myeloid disorders. By in situ hybridization, IL-3 was found to be deleted in the 5q-chromosome of one patient with refractory anemia who had a del(5)(q15q33.3), of three patients with refractory anemia (two patients) or acute nonlymphocytic leukemia (ANLL) de novo who had a similar distal breakpoint (del(5)(q13q33.3)), and of a fifth patient, with therapy-related ANLL, who had a similar distal breakpoint in band q33(del(5)(q14q33.3)). Southern blot analysis of somatic cell hybrids retaining the normal or the deleted chromosome 5 from two patients with the refractory anemia 5q- syndrome indicated that IL-3 sequences were absent from the hybrids retaining the deleted chromosome 5 but not from hybrids that had a cytologically normal chromosome 5. Thus, a small segment of chromosome 5 contains IL-3, GM-CSF, CSF-1, and FMS. The findings and earlier results indicating that GM-CSF, CSF-1, and FMS were deleted in the 5q- chromosome, suggest that loss of IL-3 or of other CSF genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q).

  4. The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q.

    PubMed Central

    Le Beau, M M; Epstein, N D; O'Brien, S J; Nienhuis, A W; Yang, Y C; Clark, S C; Rowley, J D

    1987-01-01

    The gene IL-3 encodes interleukin 3, a hematopoietic colony-stimulating factor (CSF) that is capable of supporting the proliferation of a broad range of hematopoietic cell types. By using somatic cell hybrids and in situ chromosomal hybridization, we localized this gene to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, IL-3 was found to be deleted in the 5q-chromosome of one patient with refractory anemia who had a del(5)(q15q33.3), of three patients with refractory anemia (two patients) or acute nonlymphocytic leukemia (ANLL) de novo who had a similar distal breakpoint [del(5)(q13q33.3)], and of a fifth patient, with therapy-related ANLL, who had a similar distal breakpoint in band q33 [del(5)(q14q33.3)]. Southern blot analysis of somatic cell hybrids retaining the normal or the deleted chromosome 5 from two patients with the refractory anemia 5q- syndrome indicated that IL-3 sequences were absent form the hybrids retaining the deleted chromosome 5 but not from hybrids that had a cytologically normal chromosome 5. Thus, a small segment of chromosome 5 contains IL-3, GM-CSF (the gene encoding granulocyte-macrophage-CSF), CSF-1 (the gene encoding macrophage-CSF), and FMS (the human c-fms protooncogene, which encodes the CSF-1 receptor). Our findings and earlier results indicating that GM-CSF, CSF-1, and FMS were deleted in the 5q-chromosome, suggest that loss of IL-3 or of other CSF genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q). Images PMID:3497400

  5. Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level.

    PubMed

    Nilsson, L; Astrand-Grundström, I; Arvidsson, I; Jacobsson, B; Hellström-Lindberg, E; Hast, R; Jacobsen, S E

    2000-09-15

    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis and frequent progression to acute myeloid leukemia. Within MDS, 5q- syndrome constitutes a distinct clinical entity characterized by an isolated deletion of the long arm of chromosome 5 (5q-), a relatively good prognosis, and infrequent transformation to acute leukemia. The cell of origin in 5q- syndrome as well as in other 5q-deleted MDS patients has not been established, but evidence for involvement of multiple myeloid (but not lymphoid) lineages has suggested that a myeloid-restricted progenitor rather than a pluripotent (lympho-myeloid) stem cell might be the primary target in most patients. Although in 9 patients no evidence of peripheral blood T-cell and only 1 case of B-cell involvement was found, the data herein support that 5q deletions occur in hematopoietic stem cells (HSCs) with a combined lympho-myeloid potential. First, in all investigated patients a minimum of 94% of cells in the minor CD34(+)CD38(-) HSC compartment were 5q deleted as determined by fluorescence in situ hybridization. Second, in 3 of 5 patients 5q aberrations were detected in a large fraction (25% to 90%) of purified CD34(+)CD19(+) pro-B cells. Furthermore, extensive functional characterization with regard to responsiveness to early-acting cytokines, long-term culture-initiating cells, and nonobese diabetic/severe combined immunodeficiency repopulating cells supported that MDS HSCs in 5q-deleted patients are CD34(+)CD38(-), but inefficient at reconstituting hematopoiesis.

  6. Complex repetitive arrangements of gene sequence in the candidate region of the spinal muscular atrophy gene in 5q13

    SciTech Connect

    Theodosiou, A.M.; Nesbit, A.M.; Daniels, R.J.; Campbell, L.; Francis, M.J.; Christodoulou, Z.; Morrison, K.E.; Davies, K.E. |

    1994-12-01

    Childhood-onset proximal spinal muscular atrophy (SMA) is a heritable neurological disorder, which has been mapped by genetic linkage analysis to chromosome 5q13, in the interval between markers D5S435 and D5S557. Here, we present gene sequences that have been isolated from this interval, several of which show sequence homologies to exons of {beta}-glucuronidase. These gene sequences are repeated several times across the candidate region and are also present on chromosome 5p. The arrangement of these repetitive gene motifs is polymorphic between individuals. The high degree of variability observed may have some influence on the expression of the genes in the region. Since SMA is not inherited as a classical autosomal recessive disease, novel genomic rearrangements arising from aberrant recombination events between the complex repeats may be associated with the phenotype observed.

  7. PECULIAR NEAR-NUCLEUS OUTGASSING OF COMET 17P/HOLMES DURING ITS 2007 OUTBURST

    SciTech Connect

    Qi, Chunhua; Gurwell, Mark A.; Wilner, David J.; Hogerheijde, Michiel R.; Jewitt, David

    2015-01-20

    We present high angular resolution Submillimeter Array observations of the outbursting Jupiter family comet 17P/Holmes on 2007 October 26-29, achieving a spatial resolution of 2.''5, or ∼3000 km at the comet distance. The observations resulted in detections of the rotational lines CO 3-2, HCN 4-3, H{sup 13}CN 4-3, CS 7-6, H{sub 2}CO 3{sub 1,} {sub 2}-2{sub 1,} {sub 1}, H{sub 2}S 2{sub 2,} {sub 0}-2{sub 1,} {sub 1}, and multiple CH{sub 3}OH lines, along with the associated dust continuum at 221 and 349 GHz. The continuum has a spectral index of 2.7 ± 0.3, slightly steeper than blackbody emission from large dust particles. From the imaging data, we identify two components in the molecular emission. One component is characterized by a relatively broad line width (∼1 km s{sup –1} FWHM) exhibiting a symmetric outgassing pattern with respect to the nucleus position. The second component has a narrower line width (<0.5 km s{sup –1} FWHM) with the line center redshifted by 0.1-0.2 km s{sup –1} (cometocentric frame), and shows a velocity shift across the nucleus position with the position angle gradually changing from 66° to 30° within the four days of observations. We determine distinctly different CO/HCN ratios for each of the components. For the broad-line component we find CO/HCN < 7, while in the narrow-line component, CO/HCN = 40 ± 5. We hypothesize that the narrow-line component originates from the ice grain halo found in near-nucleus photometry, believed to be created by sublimating recently released ice grains around the nucleus during the outburst. In this interpretation, the high CO/HCN ratio of this component reflects the more pristine volatile composition of nucleus material released in the outburst.

  8. Activation of the mTOR pathway by the amino acid (L)-leucine in the 5q- syndrome and other ribosomopathies.

    PubMed

    Boultwood, Jacqueline; Yip, Bon Ham; Vuppusetty, Chaitanya; Pellagatti, Andrea; Wainscoat, James S

    2013-01-01

    Patients with the 5q- syndrome and Diamond-Blackfan anemia (DBA) suffer from a severe macrocytic anemia. The 5q- syndrome and DBA are disorders of aberrant ribosome biogenesis (ribosomopathies) and haploinsufficiency of the ribosomal protein genes RPS14 and RPS19, respectively, underlies the anemia found in these disorders. Erythroblasts obtained from patients with the 5q- syndrome and DBA show impaired mRNA translation and this defect in translation may represent a potential therapeutic target in these ribosomopathies. There are some indications that the amino acid l-leucine, a translation enhancer, may have some efficacy in this group of disorders. Recent studies have shown that l-leucine treatment of zebrafish and murine models of the 5q- syndrome and DBA results in a marked improvement in the anemia. l-leucine treatment of RPS14-deficient and RPS19-deficient erythroblasts and erythroblasts from patients with the 5q- syndrome has been shown to result in an increase in cell proliferation, erythroid differentiation and mRNA translation in culture. l-leucine has been shown to improve hemoglobin levels and transfusion independence in a patient with DBA. l-leucine activates the mTOR (mammalian target of rapamycin) signaling pathway that controls cell growth and mRNA translation. There is evidence to suggest that the promotion of translation via the mTOR pathway by l-leucine is the mechanism that underlies the enhanced erythroid progenitor cell growth and differentiation observed in animal and cellular models of the 5q- syndrome and DBA treated with this amino acid. These data support the rationale for clinical trials of l-leucine as a therapeutic agent for the 5q- syndrome and DBA. PMID:23031788

  9. Explosion of Comet 17P/Holmes as revealed by the Spitzer Space Telescope

    NASA Astrophysics Data System (ADS)

    Reach, William T.; Vaubaillon, Jeremie; Lisse, Carey M.; Holloway, Mikel; Rho, Jeonghee

    2010-07-01

    An explosion on Comet 17P/Holmes occurred on 2007 October 23, projecting particulate debris of a wide range of sizes into the interplanetary medium. We observed the comet using the mid-Infrared Spectrograph (5-40 μm), on 2007 November 10 and 2008 February 27, and the imaging photometer (24 and 70 μm), on 2008 March 13, on board the Spitzer Space Telescope. The 2007 November 10 spectral mapping revealed spatially diffuse emission with detailed mineralogical features, primarily from small crystalline olivine grains. The 2008 February 27 spectra, and the central core of the 2007 November 10 spectral map, reveal nearly featureless spectra, due to much larger grains that were ejected from the nucleus more slowly. Optical images were obtained on multiple dates spanning 2007 October 27-2008 March 10 at the Holloway Comet Observatory and 1.5-m telescope at Palomar Observatory. The images and spectra can be segmented into three components: (1) a hemispherical shell fully 28' on the sky in 2008 March, due to the fastest (262 m s -1), smallest (2 μm) debris, with a mass 1.7×1012g; (2) a 'blob' or 'pseudonucleus' offset from the true nucleus and subtending some 10' on the sky, due to intermediate speed (93 m s -1) and size (8 μm) particles, with a total mass 2.7×1012g; and (3) a 'core' centered on the nucleus due to slower (9 m s -1), larger (200 μm) ejecta, with a total mass 3.9×1012g. This decomposition of the mid-infrared observations can also explain the temporal evolution of the millimeter-wave flux. The orientation of the leading edge of the ejecta shell and the ejecta 'blob,' relative to the nucleus, do not change as the orientation of the Sun changes; instead, the configuration was imprinted by the orientation of the initial explosion. The distribution and speed of ejecta implies an explosion in a conical pattern directed approximately in the solar direction on the date of explosion. The kinetic energy of the ejecta >10 21 erg is greater than the gravitational

  10. Genomic Copy Number Variations in the Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients with del(5q) and/or -7/del(7q).

    PubMed

    Zhang, Rui; Kim, Young-Mi; Wang, Xianfu; Li, Yan; Lu, Xianglan; Sternenberger, Andrea R; Li, Shibo; Lee, Ji-Yun

    2015-01-01

    The most common chromosomal abnormalities in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are -5/del(5q) and -7/del(7q). When -5/del(5q) and -7/del(7q) coexist in patients, a poor prognosis is typically associated. Given that -5/del(5q) and/or -7/del(7q) often are accompanied with additional recurrent chromosomal alterations, genetic change(s) on the accompanying chromosome(s) other than chromosomes 5 and 7 may be important factor(s) affecting leukemogenesis and disease prognosis. Using an integrated analysis of karyotype, FISH and array CGH results in this study, we evaluated the smallest region of overlap (SRO) of chromosomes 5 and 7 as well as copy number alterations (CNAs) on the other chromosomes. Moreover, the relationship between the CNAs and del(5q) and -7/del(7q) was investigated by categorizing the cases into three groups based on the abnormalities of chromosomes 5 and 7 [group I: cases only with del(5q), group II: cases only with -7/del(7q) and group III: concurrent del(5q) and del(7q) cases]. The overlapping SRO of chromosome 5 from groups I and III was 5q31.1-33.1 and of chromosome 7 from groups II and III was 7q31.31-q36.1. A total of 318 CNAs were observed; ~ 78.3% of them were identified on chromosomes other than chromosomes 5 and 7, which were defined as 'other CNAs'. Group III was a distinctive group carrying the most high number (HN) CNAs, cryptic CNAs and 'other CNAs'. The loss of TP53 was highly associated with del(5q). The loss of ETV6 was specifically associated with group III. These CNAs or genes may play a secondary role in disease progression and should be further evaluated for their clinical significance and influence on therapeutic approaches in patients with MDS/AML carrying del(5q) and/or -7/del(7q) in large-scale, patient population study. PMID:26392809

  11. Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes.

    PubMed

    Giagounidis, Aristoteles; Mufti, Ghulam J; Fenaux, Pierre; Germing, Ulrich; List, Alan; MacBeth, Kyle J

    2014-01-01

    Deletion of the long arm of chromosome 5, del(5q), is the most prevalent cytogenetic abnormality in patients with myelodysplastic syndromes (MDS). In isolation, it is traditionally associated with favorable prognosis compared with other subtypes of MDS. However, owing to the inherent heterogeneity of the disease, prognosis for patients with del(5q) MDS is highly variable depending on the presence of factors such as additional chromosomal abnormalities, >5 % blasts in the bone marrow (BM), or transfusion dependence. Over recent years, the immunomodulatory drug lenalidomide has demonstrated remarkable efficacy in patients with del(5q) MDS. Advances in the understanding of the pathogenesis of the disease have suggested that lenalidomide targets aberrant signaling pathways caused by haplosufficiency of specific genes in a commonly deleted region on chromosome 5 (e.g., SPARC, RPS14, Cdc25C, and PP2A). As a result, the agent specifically targets del(5q) clones while also promoting erythropoiesis and repopulation of the bone marrow in normal cells. This review discusses recent developments in the understanding of the mechanism of action of lenalidomide, and how this underlies favorable outcomes in patients with del(5q) MDS. In addition, we discuss how improved understanding of the mechanism of disease will facilitate clinicians' ability to predict/monitor response and identify patients at risk of relapse. PMID:24018623

  12. Important Genes in the Pathogenesis of 5q- Syndrome and Their Connection with Ribosomal Stress and the Innate Immune System Pathway

    PubMed Central

    Fuchs, Ota

    2012-01-01

    Myelodysplastic syndrome (MDS) with interstitial deletion of a segment of the long arm of chromosome 5q [del(5q)] is characterized by bone marrow erythroid hyperplasia, atypical megakaryocytes, thrombocythemia, refractory anemia, and low risk of progression to acute myeloid leukemia (AML) compared with other types of MDS. The long arm of chromosome 5 contains two distinct commonly deleted regions (CDRs). The more distal CDR lies in 5q33.1 and contains 40 protein-coding genes and genes coding microRNAs (miR-143, miR-145). In 5q-syndrome one allele is deleted that accounts for haploinsufficiency of these genes. The mechanism of erythroid failure appears to involve the decreased expression of the ribosomal protein S14 (RPS14) gene and the upregulation of the p53 pathway by ribosomal stress. Friend leukemia virus integration 1 (Fli1) is one of the target genes of miR145. Increased Fli1 expression enables effective megakaryopoiesis in 5q-syndrome. PMID:23213547

  13. Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes.

    PubMed

    Giagounidis, Aristoteles; Mufti, Ghulam J; Fenaux, Pierre; Germing, Ulrich; List, Alan; MacBeth, Kyle J

    2014-01-01

    Deletion of the long arm of chromosome 5, del(5q), is the most prevalent cytogenetic abnormality in patients with myelodysplastic syndromes (MDS). In isolation, it is traditionally associated with favorable prognosis compared with other subtypes of MDS. However, owing to the inherent heterogeneity of the disease, prognosis for patients with del(5q) MDS is highly variable depending on the presence of factors such as additional chromosomal abnormalities, >5 % blasts in the bone marrow (BM), or transfusion dependence. Over recent years, the immunomodulatory drug lenalidomide has demonstrated remarkable efficacy in patients with del(5q) MDS. Advances in the understanding of the pathogenesis of the disease have suggested that lenalidomide targets aberrant signaling pathways caused by haplosufficiency of specific genes in a commonly deleted region on chromosome 5 (e.g., SPARC, RPS14, Cdc25C, and PP2A). As a result, the agent specifically targets del(5q) clones while also promoting erythropoiesis and repopulation of the bone marrow in normal cells. This review discusses recent developments in the understanding of the mechanism of action of lenalidomide, and how this underlies favorable outcomes in patients with del(5q) MDS. In addition, we discuss how improved understanding of the mechanism of disease will facilitate clinicians' ability to predict/monitor response and identify patients at risk of relapse.

  14. Transcription factors Fli1 and EKLF in the differentiation of megakaryocytic and erythroid progenitor in 5q- syndrome and in Diamond-Blackfan anemia.

    PubMed

    Neuwirtova, Radana; Fuchs, Ota; Holicka, Monika; Vostry, Martin; Kostecka, Arnost; Hajkova, Hana; Jonasova, Anna; Cermak, Jaroslav; Cmejla, Radek; Pospisilova, Dagmar; Belickova, Monika; Siskova, Magda; Hochova, Ivana; Vondrakova, Jana; Sponerova, Dana; Kadlckova, Eva; Novakova, Ludmila; Brezinova, Jana; Michalova, Kyra

    2013-01-01

    Friend leukemia virus integration 1 (Fli1) and erythroid Krüppel-like factor (EKLF) participate under experimental conditions in the differentiation of megakaryocytic and erythroid progenitor in cooperation with other transcription factors, cytokines, cytokine receptors, and microRNAs. Defective erythropoiesis with refractory anemia and effective megakaryopoiesis with normal or increased platelet count is typical for 5q- syndrome. We decided to evaluate the roles of EKLF and Fli1 in the pathogenesis of this syndrome and of another ribosomopathy, Diamond-Blackfan anemia (DBA). Fli1 and EKLF mRNA levels were examined in mononuclear blood and bone marrow cells from patients with 5q- syndrome, low-risk MDS patients with normal chromosome 5, DBA patients, and healthy controls. In 5q- syndrome, high Fli1 mRNA levels in the blood and bone marrow mononuclear cells were found. In DBA, Fli1 expression did not differ from the controls. EKLF mRNA level was significantly decreased in the blood and bone marrow of 5q- syndrome and in all DBA patients. We propose that the elevated Fli1 in 5q- syndrome protects megakaryocytic cells from ribosomal stress contrary to erythroid cells and contributes to effective though dysplastic megakaryopoiesis.

  15. Follow-up observations of Comet 17P/Holmes after its extreme outburst in brightness end of October 2007

    NASA Astrophysics Data System (ADS)

    Mugrauer, M.; Hohle, M. M.; Ginski, C.; Vanko, M.; Freistetter, F.

    2009-05-01

    We present follow-up observations of comet 17/P Holmes after its extreme outburst in brightness, which occurred end of October 2007. We obtained 58 V-band images of the comet between October 2007 and February 2008, using the Cassegrain-Teleskop-Kamera (CTK) at the University Observatory Jena. We present precise astrometry of the comet, which yields its most recent Keplerian orbital elements. Furthermore, we show that the comet's coma expands quite linearly with a velocity of about 1650 km/s between October and December 2007. The photometric monitoring of comet 17/P Holmes shows that its photometric activity level decreased by about 5.9 mag within 105 days after its outburst. Based on observations obtained with telescopes of the University Observatory Jena, which is operated by the Astrophysical Institute of the Friedrich-Schiller-University.

  16. Development profile in a patient with monosomy 10q and Dup(17p) associated with a peripheral neuropathy

    SciTech Connect

    Pellegrino, J.E.; Spinner, N.B.; Zackai, E.H.

    1996-02-02

    We report on a patient with dup(17p) and monosomy (10q) resulting from a familial translocation. Manifestations typical of both syndromes were present. The overall development of this patient was better by comparison with similar reported cases of either anomaly. Our evaluation detected severe gross motor delay and signs of a demyelinating peripheral neuropathy. This patient is trisomic for the region of 17p which includes the peripheral myelin protein-22 (PMP-22) gene, known to be duplicated in Charcot-Marie-Tooth neuropathy type 1A (CMT1A). Our analysis in this patient suggests that trisomy for the PMP-22 gene led to the demyelinating neuropathy and contributed to his severe motor development delay. 33 refs., 3 figs., 1 tab.

  17. p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma.

    PubMed

    von Deimling, A; Eibl, R H; Ohgaki, H; Louis, D N; von Ammon, K; Petersen, I; Kleihues, P; Chung, R Y; Wiestler, O D; Seizinger, B R

    1992-05-15

    Loss of genetic material on the short arm of chromosome 17 is observed in approximately 40% of human astrocytomas (WHO grades II and III) and in approximately 30% of cases of glioblastoma multiforme (WHO grade IV). Previous studies of glioblastoma multiforme have shown that the p53 gene, located on the short arm of chromosome 17, is frequently mutated in these glioblastomas. To explore whether lower-grade astrocytomas are also associated with corresponding mutations of the p53 gene, we have investigated a series of 22 human astrocytomas of WHO grades II and III both for loss of heterozygosity on chromosome 17p and for p53 mutations. Mutations in the conserved regions of the p53 gene were identified by single strand conformation polymorphism analysis of exons 5, 6, 7, and 8 and were verified by direct DNA sequencing of the polymerase chain reaction products. p53 mutations were observed in 3 of 8 grade II astrocytomas and 4 of 14 grade II astrocytomas. In all 22 tumors, allelic loss of the short arm of chromosome 17 was investigated by restriction fragment length polymorphism analysis. One-half of the grade II astrocytomas (4 of 8) and grade III astrocytomas (7 of 14) exhibited allelic loss on chromosome 17p. Mutations in the p53 gene were exclusively observed in tumors with allelic loss on 17p. Our results show that p53 mutations are not restricted to glioblastoma multiforme and may be important in the tumorigenesis of lower-grade astrocytomas and that p53 mutations in lower-grade astrocytomas are associated with loss of chromosome 17p. These findings are consistent with a recessive mechanism of action of p53 in WHO grade II and III astrocytoma tumorigenesis.

  18. Myelodysplastic Syndrome with concomitant t(5;21)(q15;q22) and del(5)(q13q33): case report and review of literature.

    PubMed

    Kasi Loknath Kumar, Anup; Weckbaugh, Brandon; Sirridge, Christopher; Woodroof, Janet; Persons, Diane; Kambhampati, Suman

    2016-01-01

    Chromosomal abnormalities lead to the development of hematologic malignancies such as Myelodysplastic Syndrome (MDS). Known chromosomal changes causing MDS include deletion of the long arm of chromosome 5, runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1), and very rarely fusion genes involving RUNX1 at t(5;21)(q15;q22). We present a case of a 71-year-old female with MDS, refractory anemia with excess blasts, type 1, with a combination of two cytogenetic abnormalities, specifically a concomitant translocation between chromosomes 5q15 and 21q22 and deletion of chromosome 5q13q33. Fluorescence in-situ hybridization (FISH) using a probe for RUNX1 (AML1), localized to 21q22, showed three FISH signals for RUNX1, consistent with rearrangement of RUNX1. Therapy was started with Lenalidomide leading to normal blood counts. Most significantly, repeat cytogenetics revealed normal karyotype and resolution of deletion on the long arm of chromosome 5 and a t(5;21). FISH negative for deletion 5q. The results altogether meet criteria for a complete cytogenetic remission (CR). We report a new case of t(5;21)(q15;q22) involving the RUNX1 gene and del(5)(q13q33) in a MDS patient, a combination of chromosomal abnormalities heretofore not reported in the literature. RUNX1 rearrangement is usually associated with an adverse prognosis in AML and MDS. Deletions of 5q are typically associated with poor prognosis in AML, however it is usually associated with a favorable prognosis in MDS. Our patient responded very well to Lenalidomide therapy with achievement of CR. Lenalidomide is approved for treatment of anemia in low and intermediate risk MDS with del (5q), however based on a search of literature it seems that RUNX1 mutations are also more prominent in patients who have responded to Lenalidomide therapy. MDS is a genomically unstable disease. Hence, it is conceivable that our patient started with a 5q minus syndrome and then acquired the

  19. Molecular cloning of the human leukotriene C4 synthase gene and assignment to chromosome 5q35.

    PubMed Central

    Bigby, T. D.; Hodulik, C. R.; Arden, K. C.; Fu, L.

    1996-01-01

    BACKGROUND: Cysteinyl leukotrienes (LT) are mediators involved in inflammatory and allergic disorders LTC4 synthase catalyzes the first committed step in the synthesis of these inflammatory mediators, and its cellular distribution appears to be unique. MATERIALS AND METHODS: A human genomic library was screened by polymerase chain reaction (PCR) with primers that were designed based on the reported cDNA sequence for the LTC4 synthase gene. The gene was identified in one clone by Southern blotting of restriction enzyme digests, subcloning of fragments containing regions of interest, and DNA sequencing of these subclones. The transcription initiation site was determined by primer extension analysis. Chromosome location was determined by fluorescent in situ hybridization and screening of somatic cell hybrids by PCR. RESULTS: The LTC4 synthase gene is approximately 2.5 kb in length, consisting of five exons (136, 100, 71, 82, and 257 bp, respectively) and four introns (1,447, 102, 84, and 230 bp, respectively). Transcription initiation occurs at a single site 78 bp upstream of the coding region. The 5'-flanking region contains neither a TATA nor a CAAT box. The first 1 kb of the 5'-flanking region, however, contains putative DNA binding motifs for SP-1, AP-1, AP-2, ets factors, and CREB/ATF. A STAT binding motif is present in the first intron. The LTC4 synthase gene is located in the distal region of the long arm of chromosome 5 in 5q35. CONCLUSIONS: The LTC4 synthase gene does not contain elements of a typical regulated gene and may therefore contain novel regulatory elements. This gene is also located in a region on chromosome 5 that appears to play a role in allergic and inflammatory disorders, such as asthma. Images FIG. 1 FIG. 5 FIG. 4 FIG. 6 PMID:8898379

  20. Association of chromosome 5q21.3 polymorphisms with the exploratory eye movement dysfunction in schizophrenia.

    PubMed

    Ma, Yuanlin; Li, Jun; Yu, Hao; Wang, Lifang; Lu, Tianlan; Pan, Chao; Han, Yonghua; Zhang, Dai; Yue, Weihua

    2015-08-05

    Schizophrenia patients show abnormalities in many eye movement tasks. Among them, exploratory eye movements (EEM) dysfunction seems to be specific to schizophrenia. However the mechanism of EEM disturbances in schizophrenia patients remains elusive. We investigate the relationship between EEM and single nucleotide polymorphisms (SNPs) or genes to identify susceptibility loci for EEM in schizophrenia. We firstly performed EEM test, then performed a genome-wide association study (GWAS) and gene-based association study of EEM in 128 individuals with schizophrenia and 143 healthy control subjects. Comparing to healthy controls, schizophrenia patients show significant decrease in NEF (22.99 ± 3.96 vs. 26.02 ± 5.72, P <0.001), TESL (368.78 ± 123.57 vs. 603.12 ± 178.63, P <0.001), MESL (16.86 ± 5.27 vs. 24.42 ± 6.46, P <0.001), RSS (8.22 ± 1.56 vs. 10.92 ± 1.09, P <0.001), and CSS (5.06 ± 0.97 vs. 6.64 ± 0.87, P <0.001). Five SNPs of the MAN2A1, at 5q21.3, were associated with EEM abnormalities (deceased CSS) and satisfied the criteria of GWAS significance threshold. One is localized near 5'-UTR (rs17450784) and four are in intron (rs1438663, rs17162094, rs6877440 and rs10067856) of the gene. Our findings suggest that the identified loci may control the schizophrenia-related quantitative EEM trait. And the identified gene, associated with the EEM phenotype, may lead to new insights into the etiology of schizophrenia.

  1. Delayed globin synthesis leads to excess heme and the macrocytic anemia of Diamond Blackfan anemia and del(5q) myelodysplastic syndrome.

    PubMed

    Yang, Zhantao; Keel, Siobán B; Shimamura, Akiko; Liu, Li; Gerds, Aaron T; Li, Henry Y; Wood, Brent L; Scott, Bart L; Abkowitz, Janis L

    2016-05-11

    Diamond Blackfan anemia (DBA) and myelodysplastic syndrome (MDS) with isolated del(5q) are severe macrocytic anemias; although both are associated with impaired ribosome assembly, why the anemia occurs is not known. We cultured marrow cells from DBA (n = 3) and del(5q) MDS (n = 6) patients and determined how heme (a toxic chemical) and globin (a protein) are coordinated. We show that globin translation initiates slowly, whereas heme synthesis proceeds normally. This results in insufficient globin protein, excess heme and excess reactive oxygen species in early erythroid precursors, and CFU-E (colony-forming unit-erythroid)/proerythroblast cell death. The cells that can more rapidly and effectively export heme or can slow heme synthesis preferentially survive and appropriately mature. Consistent with these observations, treatment with 10 μM succinylacetone, a specific inhibitor of heme synthesis, improved the erythroid cell output of DBA and del(5q) MDS marrow cultures by 68 to 95% (P = 0.03 to 0.05), whereas the erythroid cell output of concurrent control marrow cultures decreased by 4 to 13%. Our studies demonstrate that erythropoiesis fails when heme exceeds globin. Our data further suggest that therapies that decrease heme synthesis (or facilitate heme export) could improve the red blood cell production of persons with DBA, del(5q) MDS, and perhaps other macrocytic anemias.

  2. De novo apparently balanced reciprocal translocation between 5q11.2 and 17q23 associated with Klippel-Feil anomaly and type A1 brachydactyly

    SciTech Connect

    Fukushima, Yoshimitsu; Ohashi, Hirofumi; Wakui, Keiko

    1995-07-03

    We report on a girl with Klippel-Feil anomaly, type A1 brachydactyly, and minor facial anomalies. She has an apparently balanced de novo reciprocal translocation between 5q11.2 and 17q23. The possible significance of this chromosomal abnormality is discussed. 7 refs., 3 figs.

  3. Delayed globin synthesis leads to excess heme and the macrocytic anemia of Diamond Blackfan anemia and del(5q) myelodysplastic syndrome.

    PubMed

    Yang, Zhantao; Keel, Siobán B; Shimamura, Akiko; Liu, Li; Gerds, Aaron T; Li, Henry Y; Wood, Brent L; Scott, Bart L; Abkowitz, Janis L

    2016-05-11

    Diamond Blackfan anemia (DBA) and myelodysplastic syndrome (MDS) with isolated del(5q) are severe macrocytic anemias; although both are associated with impaired ribosome assembly, why the anemia occurs is not known. We cultured marrow cells from DBA (n = 3) and del(5q) MDS (n = 6) patients and determined how heme (a toxic chemical) and globin (a protein) are coordinated. We show that globin translation initiates slowly, whereas heme synthesis proceeds normally. This results in insufficient globin protein, excess heme and excess reactive oxygen species in early erythroid precursors, and CFU-E (colony-forming unit-erythroid)/proerythroblast cell death. The cells that can more rapidly and effectively export heme or can slow heme synthesis preferentially survive and appropriately mature. Consistent with these observations, treatment with 10 μM succinylacetone, a specific inhibitor of heme synthesis, improved the erythroid cell output of DBA and del(5q) MDS marrow cultures by 68 to 95% (P = 0.03 to 0.05), whereas the erythroid cell output of concurrent control marrow cultures decreased by 4 to 13%. Our studies demonstrate that erythropoiesis fails when heme exceeds globin. Our data further suggest that therapies that decrease heme synthesis (or facilitate heme export) could improve the red blood cell production of persons with DBA, del(5q) MDS, and perhaps other macrocytic anemias. PMID:27169803

  4. L-Leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway.

    PubMed

    Payne, Elspeth M; Virgilio, Maria; Narla, Anupama; Sun, Hong; Levine, Michelle; Paw, Barry H; Berliner, Nancy; Look, A Thomas; Ebert, Benjamin L; Khanna-Gupta, Arati

    2012-09-13

    Haploinsufficiency of ribosomal proteins (RPs) has been proposed to be the common basis for the anemia observed in Diamond-Blackfan anemia (DBA) and myelodysplastic syndrome with loss of chromosome 5q [del(5q) MDS]. We have modeled DBA and del(5q) MDS in zebrafish using antisense morpholinos to rps19 and rps14, respectively, and have demonstrated that, as in humans, haploinsufficient levels of these proteins lead to a profound anemia. To address the hypothesis that RP loss results in impaired mRNA translation, we treated Rps19 and Rps14-deficient embryos with the amino acid L-leucine, a known activator of mRNA translation. This resulted in a striking improvement of the anemia associated with RP loss. We confirmed our findings in primary human CD34⁺ cells, after shRNA knockdown of RPS19 and RPS14. Furthermore, we showed that loss of Rps19 or Rps14 activates the mTOR pathway, and this is accentuated by L-leucine in both Rps19 and Rps14 morphants. This effect could be abrogated by rapamycin suggesting that mTOR signaling may be responsible for the improvement in anemia associated with L-leucine. Our studies support the rationale for ongoing clinical trials of L-leucine as a therapeutic agent for DBA, and potentially for patients with del(5q) MDS.

  5. Delayed globin synthesis leads to excess heme and the macrocytic anemia of Diamond Blackfan anemia and del(5q) myelodysplastic syndrome

    PubMed Central

    Yang, Zhantao; Keel, Siobán B.; Shimamura, Akiko; Liu, Li; Gerds, Aaron T.; Li, Henry Y.; Wood, Brent L.; Scott, Bart L.; Abkowitz, Janis L.

    2016-01-01

    Diamond Blackfan anemia (DBA) and myelodysplastic syndrome (MDS) with isolated del(5q) are severe macrocytic anemias; although both are associated with impaired ribosome assembly, why the anemia occurs is not known. We cultured marrow cells from DBA (n = 3) and del(5q) MDS (n = 6) patients and determined how heme (a toxic chemical) and globin (a protein) are coordinated. We show that globin translation initiates slowly, whereas heme synthesis proceeds normally. This results in insufficient globin protein, excess heme and excess reactive oxygen species in early erythroid precursors, and CFU-E (colony-forming unit–erythroid)/proerythroblast cell death. The cells that can more rapidly and effectively export heme or can slow heme synthesis preferentially survive and appropriately mature. Consistent with these observations, treatment with 10 mM succinylacetone, a specific inhibitor of heme synthesis, improved the erythroid cell output of DBA and del(5q) MDS marrow cultures by 68 to 95% (P = 0.03 to 0.05), whereas the erythroid cell output of concurrent control marrow cultures decreased by 4 to 13%. Our studies demonstrate that erythropoiesis fails when heme exceeds globin. Our data further suggest that therapies that decrease heme synthesis (or facilitate heme export) could improve the red blood cell production of persons with DBA, del(5q) MDS, and perhaps other macrocytic anemias. PMID:27169803

  6. A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1-17p13.3.

    PubMed

    Lezirovitz, Karina; Maestrelli, Sylvia Regina Pedrosa; Cotrim, Nelson Henderson; Otto, Paulo A; Pearson, Peter L; Mingroni-Netto, Regina Celia

    2008-07-01

    Split-hand/foot malformation (SHFM) associated with aplasia of long bones, SHFLD syndrome or Tibial hemimelia-ectrodactyly syndrome is a rare condition with autosomal dominant inheritance, reduced penetrance and an incidence estimated to be about 1 in 1,000,000 liveborns. To date, three chromosomal regions have been reported as strong candidates for harboring SHFLD syndrome genes: 1q42.2-q43, 6q14.1 and 2q14.2. We characterized the phenotype of nine affected individuals from a large family with the aim of mapping the causative gene. Among the nine affected patients, four had only SHFM of the hands and no tibial defects, three had both defects and two had only unilateral tibial hemimelia. In keeping with previous publications of this and other families, there was clear evidence of both variable expression and incomplete penetrance, the latter bearing hallmarks of anticipation. Segregation analysis and multipoint Lod scores calculations (maximum Lod score of 5.03 using the LINKMAP software) using all potentially informative family members, both affected and unaffected, identified the chromosomal region 17p13.1-17p13.3 as the best and only candidate for harboring a novel mutated gene responsible for the syndrome in this family. The candidate gene CRK located within this region was sequenced but no pathogenic mutation was detected.

  7. Structural analysis of a hepatitis B virus genome integrated into chromosome 17p of a human hepatocellular carcinoma.

    PubMed Central

    Zhou, Y Z; Slagle, B L; Donehower, L A; vanTuinen, P; Ledbetter, D H; Butel, J S

    1988-01-01

    Hepatitis B virus (HBV) is clearly a factor in the development of hepatocellular carcinoma, but its mechanism of action remains obscure. One possibility is that the HBV integration event alters the expression of a nearby growth-regulatory cellular gene. A 9-kilobase (kb) DNA fragment containing an HBV insert plus flanking cellular sequences was cloned from a hepatoma specimen from Shanghai, People's Republic of China. Restriction mapping of the insert revealed a large inverted repeat structure consisting of both viral sequences (encompassing all of the core and pre-S regions and portions of the X and S genes) and at least 3 kb of unique cellular sequences. The virus-cell junction mapped 11 nucleotides from the DR1 region, in a position within the HBV X gene and included in the cohesive overlap region. A probe generated from 1.0 kb of the flanking cellular DNA mapped the viral insert to chromosome 17 in the region designated 17p11.2-17p12, which is near the human proto-oncogene p53. Sequence data from a portion of the flanking cellular DNA revealed a stretch of approximately 70 base pairs that showed highly significant homology with a conserved region of a number of functional mammalian DNAs, including the human autonomously replicating sequence 1 (ARS1). Images PMID:2845134

  8. Structural analysis of a hepatitis B virus genome integrated into chromosome 17p of a human hepatocellular carcinoma

    SciTech Connect

    Zhou, Y.Z.; Slagle, B.L.; Donehower, L.A.; van Tuinen, P.; Ledbetter, D.H.; Butel, J.S.

    1988-11-01

    Hepatitis B virus (HBV) is clearly a factor in the development of hepatocellular carcinoma, but its mechanism of action remains obscure. One possibility is that the HBV integration event alters the expression of a nearby growth-regulatory cellular gene. A 9-kilobase (kb) DNA fragment containing an HBV insert plus flanking cellular sequences was cloned from a hepatoma specimen from Shanghai, People's Republic of China. Restriction mapping of the insert revealed a large inverted repeat structure consisting of both viral sequences (encompassing all of the core and pre-S regions and portions of the X and S genes) and at least 3 kb of unique cellular sequences. The virus-cell junction mapped 11 nucleotides from the DRI region, in a position within the HBV X gene and included in the cohesive overlap region. A probe generated from 1.0 kb of the flanking cellular DNA mapped the viral insert to chromosome 17 in the region designated 17p11.2-17p12, which is near the human proto-oncogene p53. Sequence data from a portion of the flanking cellular DNA revealed a stretch of approximately 70 base pairs that showed highly significant homology with a conserved region of a number of functional mammalian DNA, including the human autonomously replicating sequence 1 (ASRI).

  9. Homotypic vacuole fusion requires Sec17p (yeast alpha-SNAP) and Sec18p (yeast NSF).

    PubMed Central

    Haas, A; Wickner, W

    1996-01-01

    In Saccharomyces cerevisiae, vacuoles are inherited by the formation of tubular and vesicular structures from the mother vacuole, the directed projection of these structures into the bud and the homotypic fusion of these vesicles. We have previously exploited a cell-free inheritance assay to show that the fusion step of vacuole inheritance requires cytosol, ATP and the GTPase Ypt7p. Here we demonstrate, using affinity-purified antibodies and purified recombinant proteins, a requirement for Sec17p (yeast alpha-SNAP) and Sec18p (yeast NSF) in homotypic vacuole fusion in vitro. Thus, Sec17p and Sec18p, which are typically involved in heterotypic transport steps, can also be involved in homotypic organelle fusion. We further show that vacuole-to-vacuole fusion is stimulated by certain fatty acyl-coenzyme A compounds in a Sec18p-dependent fashion. Finally, our data suggest the presence of a cytosolic factor which activates vacuole membrane-bound Sec18p. Images PMID:8670830

  10. A gene for autosomal dominant progressive cone dystrophy (CORD5) maps to chromosome 17p12-p13

    SciTech Connect

    Balciuniene, J.; Holmgren, G.; Forsman, K.

    1995-11-20

    Inherited retinal dystrophy is a common cause of visual impairment. Cone dystrophy affects the cone function and is manifested as progressive loss of the central vision, defective color vision, and photophobia. Linkage was demonstrated between progressive cone dystrophy (CORD5) and genetic markers on chromosome 17p12-p13 in a five-generation family. Multipoint analysis gave a maximum lod score of 7.72 at the marker D17S938. Recombinant haplotypes in the family suggest that the cone dystrophy locus is located in a 25-cM interval between the markers D17S926/D17S849 and D17S804/D17S945. Furthermore, one recombination was detected between the disease locus and a microsatellite marker in the candidate gene RCV1, encoding the retinal protein recoverin. Two additional candidate genes encoding retinal guanylate cyclase (GUC2D) and pigment epithelium-derived factor (PEDF) are located at 17p13.1. Moreover, loci for retinitis pigmentosa and Leber congenital amaurosis have been mapped to the same region. Identification of the cone dystrophy locus may be of importance not only for identifying functional genes in the cone system, but also for identifying genes for other retinal disorders. 34 refs., 3 figs., 2 tabs.

  11. 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.

  12. 5q14.3 deletion neurocutaneous syndrome: Contiguous gene syndrome caused by simultaneous deletion of RASA1 and MEF2C: A progressive disease.

    PubMed

    Ilari, Rita; Agosta, Guillermo; Bacino, Carlos

    2016-03-01

    We report the case of a young girl who was presented with complex clinical symptoms caused by the deletion of contiguous genes: RASA1 and MEF2C, located on chromosome 5q14.3. Specifically, the diagnosis of her skin disorder and vascular malformations involving central nervous system is consistent with a RASopathy. The child's neurological manifestations are observed in most patients suffering from 5q14.3 by deletion or mutation of the MEF2C gene. A review of the literature allowed us to conclude that the contiguous deletion of genes RASA1 and MEF2C fulfills the criteria for the diagnosis of a Neurocutaneous syndrome as proposed by Carr et al. [2011]. We also assessed the penetrance of RASA1 and clinical manifestations of MEF2C according to the type of deletion. This child described presents the complete symptomatology of both deleted genes. We would also like to highlight the progression of the disorder.

  13. Spontaneous isolated superior mesenteric artery dissection: genetic heterogeneity of chromosome locus 5q13-14 in 2 male familial cases.

    PubMed

    Jia, Zhongzhi; Zhang, Xiaoping; Wang, Weiping; Tian, Feng; Jiang, Guomin; Li, Maoquan

    2015-07-01

    Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare disease that occurs sporadically. In this report, we describe 2 cases of SISMAD involving an uncle and his nephew. Genetic studies revealed the presence of heterogeneity of a chromosome locus at 5q13-14 in 3 family members (the 2 patients and the nephew's mother), an area previously found to be linked to familial ascending aortic aneurysms and dissections.

  14. Neuroendocrine phenotypes in a boy with 5q14 deletion syndrome implicate the regulatory roles of myocyte-specific enhancer factor 2C in the postnatal hypothalamus.

    PubMed

    Sakai, Yasunari; Ohkubo, Kazuhiro; Matsushita, Yuki; Akamine, Satoshi; Ishizaki, Yoshito; Torisu, Hiroyuki; Ihara, Kenji; Sanefuji, Masafumi; Kim, Min-Seon; Lee, Ki-Up; Shaw, Chad A; Lim, Janghoo; Nakabeppu, Yusaku; Hara, Toshiro

    2013-09-01

    The 5q14.3 deletion syndrome is a rare chromosomal disorder characterized by moderate to severe intellectual disability, seizures and dysmorphic features. We report a 14-year-old boy with 5q14.3 deletion syndrome who carried a heterozygous deletion of the myocyte-specific enhancer factor 2c (MEF2C) gene. In addition to the typical neurodevelopmental features of 5q14.3 deletion syndrome, he showed recurrent hypoglycemia, appetite loss and hypothermia. Hormonal loading tests using insulin, arginine and growth hormone-releasing factor revealed that growth hormone was insufficiently released into serum in response to these stimuli, thus disclosing the hypothalamic dysfunction in the present case. To uncover the biological roles of MEF2C in the hypothalamus, we studied its expression in the postnatal mouse brain. Notably, neuropeptide Y (NPY)-positive interneurons in the hypothalamic arcuate nuclei highly expressed MEF2C. In contrast, the Rett syndrome-associated protein, Methyl-CpG binding Protein 2 (MECP2) was barely expressed in these neurons. MEF2C knockdown or overexpression experiments using Neuro2a cells revealed that MEF2C activated the endogenous transcription of NPY. Conversely, siRNA-mediated knockdown of MECP2 led to derepression of the Npy gene. These data support the concept that MEF2C and MECP2 share common molecular pathways regulating the homeostatic expression of NPY in the adult hypothalamus. We propose that individuals with 5q14.3 deletion syndrome may exhibit neuroendocrine phenotypes through the functional loss of MEF2C in the postnatal hypothalamus.

  15. Immune complex-mediated autoimmunity in a patient With Smith-Magenis syndrome (del 17p11.2).

    PubMed

    Yang, Jianying; Chandrasekharappa, Settara C; Vilboux, Thierry; Smith, Ann C M; Peterson, Erik J

    2014-08-01

    Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721-20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell-activating factor) receptor TACI as a contributing factor to human autoimmune phenomena.

  16. Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS

    PubMed Central

    List, A F; Bennett, J M; Sekeres, M A; Skikne, B; Fu, T; Shammo, J M; Nimer, S D; Knight, R D; Giagounidis, A

    2014-01-01

    Lenalidomide is the approved treatment for patients with red blood cell (RBC) transfusion-dependent lower-risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)). We report the long-term outcomes (median follow-up 3.2 years) in patients treated with lenalidomide in the MDS-003 trial. RBC transfusion independence (TI) ⩾8 weeks was achieved in 97 of 148 treated patients (65.5%), with a median response duration of 2.2 years. Partial or complete cytogenetic response was achieved by 63 of 88 evaluable patients (71.6%). Median overall survival (OS) was longer in patients achieving RBC-TI ⩾8 weeks (4.3 vs 2.0 years in non-responders; P<0.0001) or cytogenetic response (4.9 vs 3.1 years in non-responders; P=0.010). Time to acute myeloid leukemia (AML) progression was longer in patients achieving RBC-TI ⩾8 weeks or any cytogenetic response versus non-responders (P=0.001 and P=0.0002, respectively). In a landmark multivariate analysis, RBC-TI ⩾8 weeks was associated with prolonged OS (P<0.001) and a trend toward reduced relative risk of AML progression (P=0.080). Among these lower-risk MDS patients with del(5q), lenalidomide was associated with prolonged RBC-TI and cytogenetic responses, which were linked to improved OS and reduced risk of AML progression. PMID:24150217

  17. The human and mouse receptors of hyaluronan-mediated motility, RHAMM, genes (HMMR) map to human chromosome 5q33.2-qter and mouse chromosome 11

    SciTech Connect

    Spicer, A.P.; McDonald, J.A.; Roller, M.L.; Camper, S.A.

    1995-11-01

    The gene for the receptor for hyaluronan-mediated motility, RHAAM (designated hyaluronan-mediated motility receptor, HMMR (human) and Hmmr (mouse), for mapping purposes), was localized to human chromosome 5q33.2-qter by somatic cell and radiation hybrid analyses. Investigation of two interspecific back-crosses localized the mouse RHAMM (Hmmr) locus 18 cM from the centromere of mouse chromosome 11 within a region of synteny homology with human chromosome 5q23-q35 genes. The map position of the human RHAMM gene places it in a region comparatively rich in disease-associated genes, including those for low-frequency hearing loss, dominant limb-girdle muscular dystrophy, diastrophic dysplasia, Treacher Collins syndrome, and myeloid disorders associated with the 5q-syndrome. The RHAMM gene location and its ability to transform cells when overexpressed implicate RHAMM as a possible candidate gene in the pathogenesis of the recently described t(5;14)(q33-q34;q11) acute lymphoblastic leukemias. 18 refs., 1 fig.

  18. Definition of 5q11.2 microdeletion syndrome reveals overlap with CHARGE syndrome and 22q11 deletion syndrome phenotypes.

    PubMed

    Snijders Blok, Charlotte; Corsten-Janssen, Nicole; FitzPatrick, David R; Romano, Corrado; Fichera, Marco; Vitello, Girolamo Aurelio; Willemsen, Marjolein H; Schoots, Jeroen; Pfundt, Rolph; van Ravenswaaij-Arts, Conny M A; Hoefsloot, Lies; Kleefstra, Tjitske

    2014-11-01

    Microdeletions of the 5q11.2 region are rare; in literature only two patients with a deletion in this region have been reported so far. In this study, we describe four additional patients and further define this new 5q11.2 microdeletion syndrome. A comparison of the features observed in all six patients with overlapping 5q11.2 deletions showed a phenotypic spectrum that overlaps with CHARGE syndrome and 22q11.2 deletion syndrome including choanal atresia, developmental delay, heart defects, external ear abnormalities, and short stature. No colobomas or abnormalities of semicircular canals and olfactory nerves were reported. Two male patients had genital abnormalities. We estimated a 2.0 Mb (53.0-55.0 Mb) Shortest Region of Overlap (SRO) for the main clinical characteristics of the syndrome. This region contains nine genes and two non-coding microRNAs. In this region DHX29 serves as the candidate gene as it encodes an ATP-dependent RNA-helicase that is involved in the initiation of RNA translation. Screening a small cohort of 14 patients who presented the main features, however, did not reveal any pathogenic abnormalities of DHX29.

  19. Clinical utility of a DNA probe to 17p11.2 in screening of patients with a peripheral neuropathy

    SciTech Connect

    Blancato, J.; Precht, K.; Meck, J.

    1994-09-01

    We assessed the usefulness of in situ hybridization with a DNA probe to the area of chromosome 17 at p11.2 as a diagnostic tool for screening for Charcot Marte Tooth 1A (CMT 1A). In situ hybridization with a probe to 17p11.2 was performed on fixed lymphocytes from the following groups of individuals: (1) normal controls; (2) patients evoking a strong clinical suspicion of CMT 1A; and (3) 3 families with an apparent autosomal dominant peripheral neuropathy of unknown diagnoses. Group 2 patients had evidence of demyelination as defined by nerve conduction of less that 50% of the normal mean or terminal latency greater than 50% of the normal mean in conduction studies. Analysis of interphase cells hybridized with a cosmid DNA probe to 17p11.2 requires inclusion of a normal control with each trial and masked observer. Due to the size of the target DNA and the nature of the centromeric heterochromatin, the scoring of this probe is more subjective than centromere probes. For example, if the two 17 chromosomes are decondensed as in interphase, two tandem signals may be visualized as one. Results from duplication positive patients demonstrate a large proportion of cells with two closely aligned, but separate, signals with an additional single signal. Normal results demonstrate a majority of cells with two separate signals representing both normal homologues. None of the 3 families with questionable diagnosis revealed a duplication at the region, reinforcing our belief that a clinical diagnosis is the most discriminating tool available for diagnosis of CMT 1A. We concur with Boylan that molecular analysis for CMT 1A is useful for establishing a diagnosis of CMT 1A, but is not a primary differential diagnostic test. The yield in screening patients without physiologic evidence of demyelination is likely to be low. We further find that the use of in situ hybridization is a simple method of performing the duplication analysis.

  20. Deletion 17p11.2 (Smith-Magenis syndrome) is relatively common among patients having mental retardation and myopia

    SciTech Connect

    Finucane, B.; Jaeger, E.R.; Freitag, S.K.

    1994-09-01

    We recently reported the finding of moderate to severe myopia in 6 of 10 patients with Smith-Magenis syndrome (SMS). To investigate the prevalence of SMS among mentally retarded people having myopia, we surveyed a cohort of patients residing at a facility for individuals with mental retardation (MR). Of 547 institutionalized individuals with MR, 72 (13.2%) had moderate to high myopia defined as a visual acuity of minus 3 diopters or more. It should be noted that our institution does not specifically select for people with visual impairment; rather, the facility serves people with a primary diagnosis of MR. Sixty-five of 72 (90.3%) myopic individuals identified were available for cytogenetic analysis. Seventeen (26.2%) of these patients had trisomy 21. Down syndrome (DS) is well known to be associated with eye abnormalities, including myopia. Of 48 individuals with moderate to high myopia not having DS, 5 (10.4%) were shown to have deletions of 17p11.2. This is a high prevalence considering the relative rarity of SMS. By contrast, in a randomized sample of 48 patients without significant myopia at the same facility, we found no individuals with deletion 17p11.2. We conclude that the diagnosis of SMS should be considered in any non-Down syndrome individual having MR and myopia, and that ophthalmologists serving people with MR should be made aware of this deletion syndrome. Furthermore, our results suggest that significant numbers of people having SMS could be identified through selective institutional screening of patients having a combination of MR and moderate to severe myopia.

  1. On Ramsey (P3, P6)-minimal graphs

    NASA Astrophysics Data System (ADS)

    Rahmadani, Desi; Baskoro, Edy Tri; Assiyatun, Hilda

    2016-02-01

    Finding all Ramsey (G, H)-minimal graphs for a certain pair of graphs G and H is an interesting and difficult problem. Even though, it is just for small graphs G and H. In this paper, we determine some Ramsey (P3, P6)-minimal graphs of small order. We also characterize all such Ramsey minimal graphs of order 6 by using their degree sequences. We prove that Ramsey (P3, P6)-minimal graphs have diameter at least two. We construct an infinite class of trees [6] which provides Ramsey (P3, P6)-minimal graphs.

  2. Obtaining P3P privacy policies for composite services.

    PubMed

    Sun, Yi; Huang, Zhiqiu; Ke, Changbo

    2014-01-01

    With the development of web services technology, web services have changed from single to composite services. Privacy protection in composite services is becoming an important issue. P3P (platform for privacy preferences) is a privacy policy language which was designed for single web services. It enables service providers to express how they will deal with the privacy information of service consumers. In order to solve the problem that P3P cannot be applied to composite services directly, we propose a method to obtain P3P privacy policies for composite services. In this method, we present the definitions of Purpose, Recipient, and Retention elements as well as Optional and Required attributes for P3P policies of composite services. We also provide an instantiation to illustrate the feasibility of the method.

  3. Obtaining P3P privacy policies for composite services.

    PubMed

    Sun, Yi; Huang, Zhiqiu; Ke, Changbo

    2014-01-01

    With the development of web services technology, web services have changed from single to composite services. Privacy protection in composite services is becoming an important issue. P3P (platform for privacy preferences) is a privacy policy language which was designed for single web services. It enables service providers to express how they will deal with the privacy information of service consumers. In order to solve the problem that P3P cannot be applied to composite services directly, we propose a method to obtain P3P privacy policies for composite services. In this method, we present the definitions of Purpose, Recipient, and Retention elements as well as Optional and Required attributes for P3P policies of composite services. We also provide an instantiation to illustrate the feasibility of the method. PMID:25126609

  4. Auger decay of 3p-ionized krypton

    SciTech Connect

    Jonauskas, V.; Kucas, S.; Karazija, R.

    2011-11-15

    A theoretical study of Auger cascades during the decay of 3p{sub 1/2} and 3p{sub 3/2} vacancies in krypton has been performed by level-by-level calculations using a wide configuration interaction basis. Auger spectra for all steps of the cascades are presented and are compared with the existing experimental data. Good agreement of our results with the branching ratios of ions measured by a coincidence technique is obtained.

  5. The Cox3p assembly module of yeast cytochrome oxidase

    PubMed Central

    Su, Chen-Hsien; McStay, Gavin P.; Tzagoloff, Alexander

    2014-01-01

    Yeast cytochrome oxidase (COX) was previously inferred to assemble from three modules, each containing one of the three mitochondrially encoded subunits and a different subset of the eight nuclear gene products that make up this respiratory complex. Pull-down assays of pulse-labeled mitochondria enabled us to characterize Cox3p subassemblies that behave as COX precursors and contain Cox4p, Cox7p, and Cox13p. Surprisingly, Cox4p is a constituent of two other complexes, one of which was previously proposed to be an intermediate of Cox1p biogenesis. This suggests that Cox4p, which contacts Cox1p and Cox3p in the holoenzyme, can be incorporated into COX by two alternative pathways. In addition to subunits of COX, some Cox3p intermediates contain Rcf1p, a protein associated with the supercomplex that stabilizes the interaction of COX with the bc1 (ubiquinol-cytochrome c reductase) complex. Finally, our results indicate that although assembly of the Cox1p module is not contingent on the presence of Cox3p, the converse is not true, as none of the Cox3p subassemblies were detected in a mutant blocked in translation of Cox1p. These studies support our proposal that Cox3p and Cox1p are separate assembly modules with unique compositions of ancillary factors and subunits derived from the nuclear genome. PMID:24478450

  6. Nephropathic cystinosis (CTNS-LSB): construction of a YAC contig comprising the refined critical region on chromosome 17p13.

    PubMed

    Peters, U; Senger, G; Rählmann, M; Du Chesne, I; Stec, I; Köhler, M R; Weissenbach, J; Leal, S M; Koch, H G; Deufel, T; Harms, E

    1997-01-01

    A yeast artificial chromosome (YAC) contig was constructed encompassing the entire region on chromosome 17p13 where the autosomal recessive disorder infantile nephropathic cystinosis (MIM 21980, CTNS-LSB) has been genetically mapped. It comprises seven clones ordered by their content of a series of six sequence-tagged sites (STSs). Fluorescence in situ hybridisation (FISH) revealed two chimaeric clones. The order of four polymorphic STSs mapped with the contig was consistent with that of the known genetic map with the exception of markers D17S1583 (AFMb307zg5) and D17S1798 (AFMa202xf5) where a telomeric location of D17S1583 was inferred from the contig; two non-polymorphic STSs were localised within the marker frame-work. From the analysis of recombination events in an unaffected individual as defined by leucocyte cystine levels we support the high-resolution mapping of this region to a small genetic interval and show that it is entirely represented on a single, non-chimaeric YAC clone in the contig.

  7. Allogeneic stem cell transplantation in chronic lymphocytic leukemia patients with 17p deletion: consult-transplant v consult-no-transplant analysis

    PubMed Central

    Poon, Michelle L.; Fox, Patricia S.; Samuels, Barry I.; O’Brien, Susan; Jabbour, Elias; Hsu, Yvonne; Gulbis, Alison; Korbling, Martin; Champlin, Richard; Abruzzo, Lynne V.; Bassett, Roland L.; Khouri, Issa F.

    2015-01-01

    Allogeneic stem cell transplantation (alloSCT) can overcome the adverse prognosis of chronic lymphocytic leukemia with 17p deletion (17p- CLL). However, its applicability remains unclear. Since 2007, our leukemia service has referred 17p- CLL patients for alloSCT at presentation. In this study, the outcomes of these patients were reviewed retrospectively to determine whether they underwent alloSCT and why patients did not undergo alloSCT. Fifty-two patients with 17p- CLL, who were referred to the transplant service from 2007 to 2010, were identified. Of these patients, 32 (62%) patients did not undergo alloSCT, mainly because of treatment- or disease-related complications (n=15). The 2-year post-referral overall survival rates of the alloSCT and non-SCT groups were 64% and 25%, respectively (p = 0.001). These findings suggest that while alloSCT is an effective therapy in 17p- CLL patients, pre-SCT complications may preclude a significant proportion of patients from undergoing the procedure. PMID:24913509

  8. Allele loss on chromosomes 10 and 17p and epidermal growth factor receptor gene amplification in human malignant astrocytoma related to prognosis.

    PubMed Central

    Leenstra, S.; Bijlsma, E. K.; Troost, D.; Oosting, J.; Westerveld, A.; Bosch, D. A.; Hulsebos, T. J.

    1994-01-01

    Patients with high-grade astrocytomas have a poor prognosis. However, considerable variation exists within this group of patients with respect to post-operative survival. In order to determine whether genetic alterations might be of help in subdividing this group, we used allele loss on chromosomes 10 and 17p and epidermal growth factor receptor (EGFR) gene amplification in the tumours as genetic parameters and determined their prognostic value. A series of 47 malignant (grade III and grade IV) tumours were genetically characterised, and four types of tumours were found. Type 1 tumours had loss of heterozygosity on chromosome arm 17p (LOH 17p) as the sole genetic alteration. Patients with this type of tumour were relatively young (mean age 39 years) and had a median survival period of 17 months. Type 2 tumours displayed only allele loss on chromosome 10 (LOH 10), type 3 tumours had LOH 10 + LOH 17p and type 4 tumours contained LOH 10 + EGFR gene amplification. Patients with types 2, 3 and 4 tumours were older (mean ages 59, 65 and 54 years respectively) and had a shorter survival (median duration 6, 3 and 2 months respectively) than type 1 patients. Multivariate analysis indicated that the genetic subdivision was a significant prognostic variable. In this study, age proved to be of minor importance with regard to survival. Our study revealed a predominance of frontally located tumours in patients with type 1 tumours, i.e. with LOH 17p only. Images Figure 2 PMID:7917918

  9. [17p13.3 duplication as a cause of psychomotor developmental delay in an infant - a further case of a new syndrome].

    PubMed

    Przybylska-Kruszewska, Amanda; Kutkowska-Kaźmierczak, Anna; Krzywdzińska, Amanda; Smyk, Marta; Nowakowska, Beata; Gryglicka, Halina; Obersztyn, Ewa; Hozyasz, Kamil K

    2016-04-01

    17p13.3 duplication is a rare and heterogeneous genetic syndrome. Microdeletions of this region are responsible for the symptoms of Miller-Dieker syndrome. We present a case of 17p13.3 duplication consisting of about 730kb in a patient with psychomotor developmental delay, concerning eye-hand coordination, posture, locomotion and speech. Among other symptoms, we found excessive physical development in relation to age, hypotonia, dysmorphic facial features (high and prominent forehead, low-set ears, hypertelorism, short nose, small upturned nose, narrow lips and pointed chin) and discrete changes in the CNS - enhanced frontal horns of the lateral ventricles and quite narrow corpus callosum. These symptoms overlap with phenotype of previously described patients with 17p13.3 duplication. The aberration has been identified by array comparative genomic hybridization (aCGH) and confirmed by fluorescence in situ hybridization (FISH). This publication presents a detailed, comparative characteristic of clinical fetures expression in discussed patient with 17p13.3 duplication and patients previously described in medical literature. Further cases with different variants of 17p13.3 duplication may contribute to characterise the specific genotypephenotype correlation. PMID:27137828

  10. Miller-Dieker syndrome due to maternal cryptic translocation t(10;17)(q26.3;p13.3)

    SciTech Connect

    Masuno, Mitsuo; Imaizumi, Kiyoshi; Nakamura, Mihoko; Kuroki, Yoshikazu

    1995-12-04

    We report on a 3-month-old girl with Miller-Dieker syndrome resulting from a maternal full-cryptic translocation t(10;17)(q26.3;p13.3) detectable only by using fluorescence in situ hybridization (FISH). Parental studies using FISH are crucial for genetic counselling in cases of Miller-Dieker syndrome with submicroscopic deletion at 17p13.3. In a family with a parental cryptic translocation and high recurrence risk, prenatal diagnosis using FISH is feasible. 15 refs., 3 figs.

  11. Microdeletions of chromosome 17p13.3 markers in an unselected survey of probands with type I lissencephaly

    SciTech Connect

    Giannakoudis, J.; Wrisch, A.; Farber, C.

    1994-09-01

    Type I lissencephaly (MIM No.247200, McKusick, 1992), a brain malformation characterized by a smooth cerebral surface, exhibits a four-layered cortex and leads to mental retardation and other neurological anomalies. Lissencephaly, type I occurs either isolated (ILS) or in association with dysmorphic facial features (Miller-Dieker syndrome, MDS). Microdeletions were detected within a 350 kb critical segment in 17p13.3 in about 13% of patients with ILS and about 90% with MDS. Most of these patients were selected for molecular analysis, however, by an already known abnormal karyotype. Therefore, the diagnostic value of microsatellite and VNTR markers to identify deletions in unselected ILS/MDS patients is still unknown. We have tested the respective significance of a novel (CA)17 VNDR element (D17S379) and of the VNTR marker YNZ22 (D17S5) to identify deletions in an unselected survey of 28 ILS/MDS patients. For D17S379, 50% of our patients were heterozygous, while 46% were uninformative with respect to segregation of alleles within their family. One patient (3.6%) was shown to be deleted for a paternal allele. PCR for D17S5, which maps proximal to the ILS region, disclosed a deletion in 3 patients (10.7%), including the one seen also by D17S379. Altogether, 75% were heterozygous and only 14% uninformative for this locus. Our results suggest that the combined PCR analysis for two of the most significant markers within the ILS/MDS region disclose a deletion in about 10% of unselected patients with features of type I lissencephaly. The low frequency of deletions detected may reflect different mutation mechanisms, genetic heterogeneity, the need for more densely spaced markers around the critical region, and/or more strict clinical criteria for defining the study group.

  12. Narrowing the position of the Treacher Collins syndrome locus to a small interval between three new microsatellite markers at 5q32-33. 1

    SciTech Connect

    Dixon, M.J.; Dixon, J. ); Houseal, T.; Klinger, K.; Landes, G.M. ); Bhatt, M.; Ward, D.C. )

    1993-05-01

    Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. The TCOF1 locus has been localized to chromosome 5q32-33.2. In the present study the authors have used the combined techniques of genetic linkage analysis and fluorescence in situ hybridization (FISH) to more accurately define the TCOF1 critical region. Cosmids IG90 and SPARC, which map to distal 5q, encompass two and one hypervariable microsatellite markers, respectively. The heterozygosity values of these three markers range from .72 to .81. Twenty-two unrelated TCOF1 families have been analyzed for linkage to these markers. There is strong evidence demonstrating linkage to all three markers, the strongest support for positive linkage being provided by haplotyping those markers at the locus encompassed by the cosmid IG90 (Z[sub max]= 19.65; 0 = .010). FISH to metaphase chromosomes and interphase nuclei established that IG90 lies centromeric to SPARC. This information combined with the data generated by genetic linkage analysis demonstrated that the TCOF1 locus is closely flanked proximally by IG90 and distally by SPARC. 30 refs., 2 figs., 4 tabs.

  13. A 26-Year-Old Female with Systemic Mastocytosis with Associated Myeloid Neoplasm with Eosinophilia and Abnormalities of PDGFRB, t(4;5)(q21;q33).

    PubMed

    Brown, Laura E; Zhang, Da; Persons, Diane L; Yacoub, Abdulraheem; Ponnala, Shivani; Cui, Wei

    2016-01-01

    Various translocations involving the PDGFRB gene are identified in myeloid neoplasms. However, the PRKG2/PDGFRB fusion gene associated with t(4;5)(q21;q33) has previously been reported in only 3 patients. We present the case of a 26-year-old woman with microcytic anemia, basophilia, thrombocytosis, and massive splenomegaly, who was found to have systemic mastocytosis and associated clonal hematological non-mast cell lineage disease (SM-AHNMD), with myeloid neoplasm with PRKG2/PDGFRB rearrangement. Initial findings included basophilia (37%, 4.1 k/μL), hypercellular marrow with eosinophilia, and increased and atypical megakaryocytes, suggestive of myeloproliferative neoplasm. Additional studies revealed large clusters of CD25 positive mast cells, fulfilling the criteria for the diagnosis of systemic mastocytosis. Consistent with prior reports of this translocation, our patient has responded well to imatinib. This case, in conjunction with others in the literature, suggests a possible connection between t(4;5)(q21;q33) PRKG2/PDGFRB and systemic mastocytosis and highlights their favorable response to imatinib. PMID:27648315

  14. A 26-Year-Old Female with Systemic Mastocytosis with Associated Myeloid Neoplasm with Eosinophilia and Abnormalities of PDGFRB, t(4;5)(q21;q33)

    PubMed Central

    Persons, Diane L.; Ponnala, Shivani

    2016-01-01

    Various translocations involving the PDGFRB gene are identified in myeloid neoplasms. However, the PRKG2/PDGFRB fusion gene associated with t(4;5)(q21;q33) has previously been reported in only 3 patients. We present the case of a 26-year-old woman with microcytic anemia, basophilia, thrombocytosis, and massive splenomegaly, who was found to have systemic mastocytosis and associated clonal hematological non-mast cell lineage disease (SM-AHNMD), with myeloid neoplasm with PRKG2/PDGFRB rearrangement. Initial findings included basophilia (37%, 4.1 k/μL), hypercellular marrow with eosinophilia, and increased and atypical megakaryocytes, suggestive of myeloproliferative neoplasm. Additional studies revealed large clusters of CD25 positive mast cells, fulfilling the criteria for the diagnosis of systemic mastocytosis. Consistent with prior reports of this translocation, our patient has responded well to imatinib. This case, in conjunction with others in the literature, suggests a possible connection between t(4;5)(q21;q33) PRKG2/PDGFRB and systemic mastocytosis and highlights their favorable response to imatinib. PMID:27648315

  15. Identification of a Potential Regulatory Variant for Colorectal Cancer Risk Mapping to Chromosome 5q31.1: A Post-GWAS Study

    PubMed Central

    Ke, Juntao; Lou, Jiao; Chen, Xueqin; Li, Jiaoyuan; Liu, Cheng; Gong, Yajie; Yang, Yang; Zhu, Ying; Zhang, Yi; Gong, Jing

    2015-01-01

    Large-scale genome-wide association studies (GWAS) have established chromosome 5q31.1 as a susceptibility locus for colorectal cancer (CRC), which was still lack of causal genetic variants. We searched potentially regulatory single nucleotide polymorphisms (SNPs) in the overlap region between linkage disequilibrium (LD) block of 5q31.1 and regulatory elements predicted by histone modifications, then tested their association with CRC via a case-control study. Among three candidate common variants, we found rs17716310 conferred significantly (heterozygous model: OR = 1.273, 95% confidence interval (95%CI) = 1.016–1.595, P = 0.036) and marginally (dominant model: OR = 1.238, 95%CI = 1.000–1.532, P = 0.050) increase risk for CRC in a Chinese population including 695 cases and 709 controls. This variation was suggested to be regulatory altering the activity of enhancer that control PITX1 expression. Using epigenetic information such as chromatin immunoprecipitation-sequencing (ChIP-seq) data might help researchers to interpret the results of GWAS and locate causal variants for diseases in post-GWAS era. PMID:26381143

  16. A physical map of 15 loci on human chromosome 5q23-q33 by two-color fluorescence in situ hybridization

    SciTech Connect

    Saltman, D.L.; Dolganov, G.M. ); Warrington, J.A.; Wasmuth, J.J. ); Lovett, M. )

    1993-06-01

    The q23-q33 region of human chromosome 5 encodes a large number of growth factors, growth factor receptors, and hormone/neurotransmitter receptors. This is also the general region into which several disease genes have been mapped, including diastrophic dysplasia, Treacher Collins syndrome, hereditary startle disease, the myeloid disorders that are associated with the 5q-syndrome, autosomal-dominant forms of hereditary deafness, and limb girdle muscular dystrophy. The authors have developed a framework physical map of this region using cosmid clones isolated from the Los Alamos arrayed chromosome 5-specific library. Entry points into this library included 14 probes to genes within this interval and one anonymous polymorphic marker locus. A physical map has been constructed using fluorescence in situ hybridization of these cosmids on metaphase and interphase chromosomes, and this is in good agreement with the radiation hybrid map of the region. The derived order of loci across the region is cen-IL4-IL5-IRF1-IL3-IL9-EGR1-CD14-FGFA-GRL-D5S207-ADRB2-SPARC-RPS14-CSF1R-ADRA1, and the total distance spanned by these loci is approximately 15 Mb. The framework map, genomic clones, and contig expansion within 5q23-q33 should provide valuable resources for the eventual isolation of the clinically relevant loci that reside in this region. 31 refs., 3 figs., 2 tabs.

  17. Reactions Of Atomic Oxygen {O(3P)} With Polybutadienes

    NASA Technical Reports Server (NTRS)

    Golub, Morton A.; Lerner, Narcinda R.; Wydeven, Theodore

    1991-01-01

    Report describes experimental study of chemical reactions of atomic oxygen in ground state {O(3P)} with polybutadienes and related polymers. Attention focused on such reactions because of adverse effects of environmental atomic oxygen on polymeric materials in low orbits around Earth.

  18. THE LONG-TERM DECAY IN PRODUCTION RATES FOLLOWING THE EXTREME OUTBURST OF COMET 17P/HOLMES

    SciTech Connect

    Schleicher, David G.

    2009-10-15

    Numerous sets of narrowband filter photometry were obtained of Comet 17P/Holmes from Lowell Observatory during the interval of 2007 November 1 to 2008 March 5. Observations began 8 days following its extreme outburst, at which time the derived water production rate, based on OH measurements, was 5 x 10{sup 29} molecule s{sup -1} and the derived proxy of dust production, A({theta})f{rho}, was about 5 x 10{sup 5} cm. Relative production rates for the other gas species, CN, C{sub 2}, C{sub 3}, and NH, are consistent with 'typical' composition (based on our update to the classifications by A'Hearn et al.). An exponential decay in the logarithm of measured production rates as a function of time was observed for all species, with each species dropping by factors of about 200-500 after 125 days. All gas species exhibited clear trends with aperture size, and these trends are consistent with larger apertures having a greater proportion of older material that was released when production rates were higher. Much larger aperture trends were measured for the dust, most likely because the dust grains have smaller outflow velocities and longer lifetimes than the gas species; therefore, a greater proportion of older, i.e., higher production dust is contained within a given aperture. By extrapolating to a sufficiently small aperture size, we derive near-instantaneous water and dust production rates throughout the interval of observation, and also estimate values immediately following the outburst. The finite lifetime of the gas species requires that much higher ice vaporization rates were taking place throughout the observation interval than occurred prior to the outburst, likely due to the continued release of icy grains from the nucleus. The relatively small aperture trends for the gas species also imply that the bulk of fresh, excess volatiles are confined to the nucleus and near-nucleus regime, rather than being associated with the outburst ejecta cloud. A minimum of about 0

  19. Assignment of CSF-1 to 5q33.1: evidence for clustering of genes regulating hematopoiesis and for their involvement in the deletion of the long arm of chromosome 5 in myeloid disorders.

    PubMed Central

    Pettenati, M J; Le Beau, M M; Lemons, R S; Shima, E A; Kawasaki, E S; Larson, R A; Sherr, C J; Diaz, M O; Rowley, J D

    1987-01-01

    The CSF-1 gene encodes a hematopoietic colony-stimulating factor (CSF) that promotes growth, differentiation, and survival of mononuclear phagocytes. By using somatic cell hybrids and in situ hybridization, we localized this gene to human chromosome 5 at bands q31 to q35, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the CSF-1 gene was found to be deleted in the 5q- chromosome of a patient with refractory anemia who had a del(5)(q15q33.3) and in that of a second patient with acute nonlymphocytic leukemia de novo who had a similar distal breakpoint [del(5)(q13q33.3)]. The gene was present in the deleted chromosome of a third patient, with therapy-related acute nonlymphocytic leukemia, who had a more proximal breakpoint in band q33 [del(5)(q22q33.1)]. Hybridization of the CSF-1 probe to metaphase cells of a fourth patient, with acute nonlymphocytic leukemia de novo, who had a rearrangement of chromosomes 5 and 21 [ins(21;5)(q22;q31.3q33.1)] resulted in labeling of the breakpoint junctions of both rearranged chromosomes; this suggested that CSF-1 is located at 5q33.1. Thus, a small segment of chromosome 5 contains GM-CSF (the gene encoding the granulocyte-macrophage CSF), CSF-1, and FMS, which encodes the CSF-1 receptor, in that order from the centromere; this cluster of genes may be involved in the altered hematopoiesis associated with a deletion of 5q. Images PMID:3495006

  20. Identification of Nine New RAI1-Truncating Mutations in Smith-Magenis Syndrome Patients without 17p11.2 Deletions

    PubMed Central

    Dubourg, C.; Bonnet-Brilhault, F.; Toutain, A.; Mignot, C.; Jacquette, A.; Dieux, A.; Gérard, M.; Beaumont-Epinette, M.-P.; Julia, S.; Isidor, B.; Rossi, M.; Odent, S.; Bendavid, C.; Barthélémy, C.; Verloes, A.; David, V.

    2014-01-01

    Smith-Magenis syndrome (SMS) is an intellectual disability syndrome with sleep disturbance, self-injurious behaviors and dysmorphic features. It is estimated to occur in 1/25,000 births, and in 90% of cases it is associated with interstitial deletions of chromosome 17p11.2. RAI1 (retinoic acid induced 1; OMIM 607642) mutations are the second most frequent molecular etiology, with this gene being located in the SMS locus at 17p11.2. Here, we report 9 new RAI1-truncating mutations in nonrelated individuals referred for molecular analysis due to a possible SMS diagnosis. None of these patients carried a 17p11.2 deletion. The 9 mutations include 2 nonsense mutations and 7 heterozygous frameshift mutations leading to protein truncation. All mutations map in exon 3 of RAI1 which codes for more than 98% of the protein. RAI1 regulates gene transcription, and its targets are themselves involved in transcriptional regulation, cell growth and cell cycle regulation, bone and skeletal development, lipid and glucide metabolisms, neurological development, behavioral functions, and circadian activity. We report the clinical features of the patients carrying these deleterious mutations in comparison with those of patients carrying 17p11.2 deletions. PMID:24715852

  1. Microarray delineation of familial chromosomal imbalance with deletion 5q35 and duplication 10q25 in a child showing multiple anomalies and dysmorphism.

    PubMed

    Masri, Amira; Gimelli, Stefania; Hamamy, Hanan; Sloan-Béna, Frédérique

    2014-05-01

    We describe a 6-month-old female with developmental delay, hypotonia, supernumerary nipples, and distinct craniofacial features. Postnatal chromosome analysis revealed an unbalanced karyotype involving a der (5) and array-CGH defined two unbalanced regions with partial 2.3 Mb deletion of 5q35.3 in combination with a large 19.5 Mb duplication of chromosome 10 from q25.3 to q26.3. Parental karyotyping analysis showed that the father was carrier of a balanced t(5;10)(q35;q25). Two cousins of the proband with similar facial features had the same unbalanced karyotype with presence of the der (5) inherited from the malsegregation of the familial translocation. Additionally, three siblings (two deceased and one abortion) manifested a more severe phenotype including congenital heart defect, cleft palate, and agenesis of the corpus callosum and were diagnosed with unbalanced karyotypes inherited from the familial balanced translocation. PMID:24478242

  2. Myelodysplastic disorders carrying both isolated del(5q) and JAK2(V617F) mutation: concise review, with focus on lenalidomide therapy.

    PubMed

    Musto, Pellegrino; Simeon, Vittorio; Guariglia, Roberto; Bianchino, Gabriella; Grieco, Vitina; Nozza, Filomena; La Rocca, Francesco; Marziano, Gioacchino; Lalinga, Anna Vittoria; Fabiani, Emiliano; Voso, Maria Teresa; Scaravaglio, Patrizia; Mecucci, Cristina; D'Arena, Giovanni

    2014-01-01

    The concomitant presence of del(5q) and JAK2(V617F) mutation is an infrequent event which occurs in rare patients with peculiar cytogenetic, molecular, morphological and clinical features, resembling those of both myelodysplastic syndromes and myeloproliferative neoplasms. Lenalidomide may induce rapid, profound, and long-lasting responses in a subset of these patients. However, the mechanism(s) by which the drug acts in these conditions remain not completely elucidated. A new case report and a review of all cases published so far in this setting are provided. Furthermore, the possibility of categorizing - from a clinical, pathological, and biological point of view - for at least some of these patients as a potential distinct entity is discussed.

  3. Myelodysplastic disorders carrying both isolated del(5q) and JAK2V617F mutation: concise review, with focus on lenalidomide therapy

    PubMed Central

    Musto, Pellegrino; Simeon, Vittorio; Guariglia, Roberto; Bianchino, Gabriella; Grieco, Vitina; Nozza, Filomena; La Rocca, Francesco; Marziano, Gioacchino; Lalinga, Anna Vittoria; Fabiani, Emiliano; Voso, Maria Teresa; Scaravaglio, Patrizia; Mecucci, Cristina; D’Arena, Giovanni

    2014-01-01

    The concomitant presence of del(5q) and JAK2V617F mutation is an infrequent event which occurs in rare patients with peculiar cytogenetic, molecular, morphological and clinical features, resembling those of both myelodysplastic syndromes and myeloproliferative neoplasms. Lenalidomide may induce rapid, profound, and long-lasting responses in a subset of these patients. However, the mechanism(s) by which the drug acts in these conditions remain not completely elucidated. A new case report and a review of all cases published so far in this setting are provided. Furthermore, the possibility of categorizing – from a clinical, pathological, and biological point of view – for at least some of these patients as a potential distinct entity is discussed. PMID:24966686

  4. Complex Karyotype is a Stronger Predictor than Del(17p) for Inferior Outcome in Relapsed or Refractory CLL Patients Treated with Ibrutinib-Based Regimens

    PubMed Central

    Thompson, Philip A.; O’Brien, Susan M.; Wierda, William G.; Ferrajoli, Alessandra; Stingo, Francesco; Smith, Susan C.; Burger, Jan A.; Estrov, Zeev; Jain, Nitin; Kantarjian, Hagop M.; Keating, Michael J.

    2016-01-01

    Background Ibrutinib is active in patients with relapsed/refractory (R/R) CLL. In patients treated with ibrutinib for R/R CLL, del(17p) identified by interphase fluorescence in situ hybridization (FISH) is associated with inferior progression-free survival, despite equivalent initial response rates. Del(17p) is frequently associated with complex metaphase karyotype (CKT); the prognostic significance of CKT in ibrutinib-treated patients has not been reported. Methods We reviewed 88 patients treated for R/R CLL at MD Anderson Cancer Center with investigational ibrutinib-based regimens from 2010–2013. Pre-treatment FISH and Lipopolysaccharide-stimulated metaphase cytogenetic analysis were performed on bone marrow. Results Adequate pre-treatment metaphase karyotype was available for 56/88 patients. Karyotype was complex in 21 of 56 cases; 17 of the 21 had del(17p) by FISH. Overall response rate, including partial remission with persistent lymphocytosis, was 94% with 17% complete responses. In multivariable analysis (MVA), only CKT was significantly associated with event-free survival (EFS) [HR 6.6 (1.7–25.6), p=0.006]. Fludarabine-refractory CLL [HR 6.9 (1.8–27.1), p=0.005] and CKT [HR 5.9 (1.6–22.2), p=0.008] were independently associated with inferior overall survival (OS) in MVA. Del(17p) by FISH was not significantly associated with EFS or OS in MVA. Conclusions CKT is a powerful predictor of outcome in ibrutinib-treated patients with R/R CLL and may be a stronger predictor of biological behavior than del(17p) by FISH. Given their relatively poor outcomes, patients with CKT are ideal candidates for studies of consolidative treatment strategies or novel treatment combinations. PMID:26193999

  5. Molecular Analysis of the Retinoic Acid Induced 1 Gene (RAI1) in Patients with Suspected Smith-Magenis Syndrome without the 17p11.2 Deletion

    PubMed Central

    Vilboux, Thierry; Ciccone, Carla; Blancato, Jan K.; Cox, Gerald F.; Deshpande, Charu; Introne, Wendy J.; Gahl, William A.; Smith, Ann C. M.; Huizing, Marjan

    2011-01-01

    Smith-Magenis syndrome (SMS) is a complex neurobehavioral disorder characterized by multiple congenital anomalies. The syndrome is primarily ascribed to a ∼3.7 Mb de novo deletion on chromosome 17p11.2. Haploinsufficiency of multiple genes likely underlies the complex clinical phenotype. RAI1 (Retinoic Acid Induced 1) is recognized as a major gene involved in the SMS phenotype. Extensive genetic and clinical analyses of 36 patients with SMS-like features, but without the 17p11.2 microdeletion, yielded 10 patients with RAI1 variants, including 4 with de novo deleterious mutations, and 6 with novel missense variants, 5 of which were familial. Haplotype analysis showed two major RAI1 haplotypes in our primarily Caucasian cohort; the novel RAI1 variants did not occur in a preferred haplotype. RNA analysis revealed that RAI1 mRNA expression was significantly decreased in cells of patients with the common 17p11.2 deletion, as well as in those with de novo RAI1 variants. Expression levels varied in patients with familial RAI1 variants and in non-17p11.2 deleted patients without identified RAI1 defects. No correlation between SNP haplotype and RAI1 expression was found. Two clinical features, ocular abnormalities and polyembolokoilomania (object insertion), were significantly correlated with decreased RAI1 expression. While not significantly correlated, the presence of hearing loss, seizures, hoarse voice, childhood onset of obesity and specific behavioral aspects and the absence of immunologic abnormalities and cardiovascular or renal structural anomalies, appeared to be specific for the de novo RAI1 subgroup. Recognition of the combination of these features will assist in referral for RAI1 analysis of patients with SMS-like features without detectable microdeletion of 17p11.2. Moreover, RAI1 expression emerged as a genetic target for development of therapeutic interventions for SMS. PMID:21857958

  6. Molecular analysis of the Retinoic Acid Induced 1 gene (RAI1) in patients with suspected Smith-Magenis syndrome without the 17p11.2 deletion.

    PubMed

    Vilboux, Thierry; Ciccone, Carla; Blancato, Jan K; Cox, Gerald F; Deshpande, Charu; Introne, Wendy J; Gahl, William A; Smith, Ann C M; Huizing, Marjan

    2011-01-01

    Smith-Magenis syndrome (SMS) is a complex neurobehavioral disorder characterized by multiple congenital anomalies. The syndrome is primarily ascribed to a ∼3.7 Mb de novo deletion on chromosome 17p11.2. Haploinsufficiency of multiple genes likely underlies the complex clinical phenotype. RAI1 (Retinoic Acid Induced 1) is recognized as a major gene involved in the SMS phenotype. Extensive genetic and clinical analyses of 36 patients with SMS-like features, but without the 17p11.2 microdeletion, yielded 10 patients with RAI1 variants, including 4 with de novo deleterious mutations, and 6 with novel missense variants, 5 of which were familial. Haplotype analysis showed two major RAI1 haplotypes in our primarily Caucasian cohort; the novel RAI1 variants did not occur in a preferred haplotype. RNA analysis revealed that RAI1 mRNA expression was significantly decreased in cells of patients with the common 17p11.2 deletion, as well as in those with de novo RAI1 variants. Expression levels varied in patients with familial RAI1 variants and in non-17p11.2 deleted patients without identified RAI1 defects. No correlation between SNP haplotype and RAI1 expression was found. Two clinical features, ocular abnormalities and polyembolokoilomania (object insertion), were significantly correlated with decreased RAI1 expression. While not significantly correlated, the presence of hearing loss, seizures, hoarse voice, childhood onset of obesity and specific behavioral aspects and the absence of immunologic abnormalities and cardiovascular or renal structural anomalies, appeared to be specific for the de novo RAI1 subgroup. Recognition of the combination of these features will assist in referral for RAI1 analysis of patients with SMS-like features without detectable microdeletion of 17p11.2. Moreover, RAI1 expression emerged as a genetic target for development of therapeutic interventions for SMS.

  7. Genetic and physical mapping of the Treacher Collins syndrome locus with respect to loci in the chromosome 5q3 region

    SciTech Connect

    Jabs, E.W.; Li, Xiang; Coss, C.; Taylor, E. ); Lovett, M. ); Yamaoka, L.H.; Speer, M.C. ); Cadle, R.; Hall, B. ); Brown, K. )

    1993-10-01

    Treacher Collins syndrome is an autosomal dominant, craniofacial developmental disorder, and its locus (TCOF1) has been mapped to chromosome 5q3. To refine the location of the gene within this region, linkage analysis was performed among the TCOF1 locus and 12 loci (IL9, FGFA, GRL, D5S207, D5S210, D5S376, CSF1R, SPARC, D5S119, D5S209, D5S527, FGFR4) in 13 Treacher Collins syndrome families. The highest maximum lod score was obtained between loci TCOF1 and D5S210 (Z = 10.52; [theta] = 0.02 [+-] 0.07). The best order, IL9-GRL-D5S207/D5S210-CSF1R-SPARC-D5S119, and genetic distances among these loci were determined in the 40 CEPH families by multipoint linkage analysis. YAC clones were used to establish the order of loci, centromere-5[prime]GRL3[prime]-D5S207-D5S210-D5S376-CSF1R-SPARC-D5S119-telomere. By combining known physical mapping data with ours, the order of chromosome 5q3 markers is centomere-IL9-FGFA-5[prime]GRL3[prime]-D5s207-D5S210-D5S376-CSF1R-SPARC-D5S119-D5S209-FGFR4-telomere. Based on this order, haplotype analysis suggests that the TCOF1 locus resides distal CSF1R and proximal to SPARC within a region less than 1 Mb in size. 29 refs., 2 figs., 2 tabs.

  8. Hyperfine quenching of the 3s3p 3P0 level in Mg-like ions

    NASA Astrophysics Data System (ADS)

    Kang, Huihui; Li, Jiguang; Dong, Chenzhong; Jönsson, Per; Gaigalas, Gediminas

    2009-10-01

    Hyperfine quenching rates of the 3s3p3P0 level in Mg-like ions were calculated using the GRASP2K package based on the multi-configuration Dirac-Hartree-Fock method. Valence and core-valence correlation effects were accounted for in a systematic way. Breit interactions and QED effects were included in the subsequent relativistic CI calculations. Calculated rates were compared with other theoretical values and with experiment, and a good agreement with the latest experimental value for the ^{27Al^+} ion (Rosenband et al 2007 Phys. Rev. Lett. 98 220801) was found. Furthermore, we showed in detail the contributions from Breit interaction and QED effects to concerned physical properties. Finally, electronic data were presented in terms of a general scaling law in Z that, given isotopic nuclear spin and magnetic moment, allows hyperfine-induced decay rates to be estimated for any isotope along the isoelectronic sequence.

  9. Products of the Benzene + O(3P) Reaction

    SciTech Connect

    Taatjes, Craig A.; Osborn, David L.; Selby, Talitha M.; Meloni, Giovanni; Trevitt, Adam J.; Epifanovsky, Evgeny; Krylov, Anna I.; Sirjean, Baptiste; Dames, Enoch; Wang, Hai

    2009-12-21

    The gas-phase reaction of benzene with O(3P) is of considerable interest for modeling of aromatic oxidation, and also because there exist fundamental questions concerning the prominence of intersystem crossing in the reaction. While its overall rate constant has been studied extensively, there are still significant uncertainties in the product distribution. The reaction proceeds mainly through the addition of the O atom to benzene, forming an initial triplet diradical adduct, which can either dissociate to form the phenoxy radical and H atom, or undergo intersystem crossing onto a singlet surface, followed by a multiplicity of internal isomerizations, leading to several possible reaction products. In this work, we examined the product branching ratios of the reaction between benzene and O(3P) over the temperature range of 300 to 1000 K and pressure range of 1 to 10 Torr. The reactions were initiated by pulsed-laser photolysis of NO2 in the presence of benzene and helium buffer in a slow-flow reactor, and reaction products were identified by using the multiplexed chemical kinetics photoionization mass spectrometer operating at the Advanced Light Source (ALS) of Lawrence Berkeley National Laboratory. Phenol and phenoxy radical were detected and quantified. Cyclopentadiene and cyclopentadienyl radical were directly identified for the first time. Finally, ab initio calculations and master equation/RRKM modeling were used to reproduce the experimental branching ratios, yielding pressure-dependent rate expressions for the reaction channels, including phenoxy + H, phenol, cyclopentadiene + CO, which are proposed for kinetic modeling of benzene oxidation.

  10. The brain finger protein gene (ZNF179), a member of the RING finger family, maps within the Smith-Magenis syndrome region at 17p11.2

    SciTech Connect

    Kimura, Toshiyuki; Arakawa, Yoshiki; Inazawa, Johji

    1997-03-31

    Smith-Magenis syndrome (SAIS) is caused by a microdeletion of 17p11.2 and comprises developmental and growth delay, facial abnormalities, unusual behavior and sleep problems. This phenotype may be due to haploinsufficiency of several contiguous genes. The human brain finger protein gene (ZNF179), a member of the RING finger protein family, has been isolated and mapped to l7p11.2. FISH analyses of metaphase or interphase chromosomes of 6 patients with SMS show that ZNF179 was deleted in one of the 2 homologs (17p11.2), indicating a possible association of the defect of this gene with the pathogenesis of SMS. Furthermore, using a prophase FISH ordering system, we sublocalized ZNF179 proximally to LLGL which lies on the critical region for SMS. 27 refs., 2 figs.

  11. Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1.

    PubMed

    Glubb, Dylan M; Maranian, Mel J; Michailidou, Kyriaki; Pooley, Karen A; Meyer, Kerstin B; Kar, Siddhartha; Carlebur, Saskia; O'Reilly, Martin; Betts, Joshua A; Hillman, Kristine M; Kaufmann, Susanne; Beesley, Jonathan; Canisius, Sander; Hopper, John L; Southey, Melissa C; Tsimiklis, Helen; Apicella, Carmel; Schmidt, Marjanka K; Broeks, Annegien; Hogervorst, Frans B; van der Schoot, C Ellen; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A; Ruebner, Matthias; Ekici, Arif B; Beckmann, Matthias W; Peto, Julian; dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Pharoah, Paul D P; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Burwinkel, Barbara; Marme, Frederik; Yang, Rongxi; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; González-Neira, Anna; Benitez, Javier; Zamora, M Pilar; Arias Perez, Jose Ignacio; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Ko, Yon-Dschun; Brüning, Thomas; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tanaka, Hideo; Dörk, Thilo; Bogdanova, Natalia V; Helbig, Sonja; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Wu, Anna H; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O; Lambrechts, Diether; Zhao, Hui; Weltens, Caroline; van Limbergen, Erik; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Seibold, Petra; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Capra, Fabio; Couch, Fergus J; Olson, Janet E; Hallberg, Emily; Vachon, Celine; Giles, Graham G; Milne, Roger L; McLean, Catriona; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; See, Mee-Hoong; Cornes, Belinda; Cheng, Ching-Yu; Ikram, M Kamran; Kristensen, Vessela; Zheng, Wei; Halverson, Sandra L; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Van Asperen, Christi J; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Czene, Kamila; Klevebring, Daniel; Darabi, Hatef; Eriksson, Mikael; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John W M; Collée, J Margriet; Hall, Per; Li, Jingmei; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Blot, William; Signorello, Lisa B; Cai, Qiuyin; Shah, Mitul; Ghoussaini, Maya; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Tang, Anthony; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Olswold, Curtis; Slager, Susan; Toland, Amanda E; Yannoukakos, Drakoulis; Shen, Chen-Yang; Wu, Pei-Ei; Yu, Jyh-Cherng; Hou, Ming-Feng; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S; Brown, Melissa A; Ponder, Bruce A J; Chenevix-Trench, Georgia; Thompson, Deborah J; Edwards, Stacey L; Easton, Douglas F; Dunning, Alison M; French, Juliet D

    2015-01-01

    Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and control individuals from 52 studies in the Breast Cancer Association Consortium. Multiple logistic regression analyses identified three independent risk signals: the strongest associations were with 15 correlated variants (iCHAV1), where the minor allele of the best candidate, rs62355902, associated with significantly increased risks of both estrogen-receptor-positive (ER(+): odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.21-1.27, ptrend = 5.7 × 10(-44)) and estrogen-receptor-negative (ER(-): OR = 1.10, 95% CI = 1.05-1.15, ptrend = 3.0 × 10(-4)) tumors. After adjustment for rs62355902, we found evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [pcond = 1.61 × 10(-5)]) and five variants composing iCHAV3 (lead rs11949391; ER(+): OR = 0.90, 95% CI = 0.87-0.93, pcond = 1.4 × 10(-4)). Twenty-six percent of the prioritized candidate variants coincided with four putative regulatory elements that interact with the MAP3K1 promoter through chromatin looping and affect MAP3K1 promoter activity. Functional analysis indicated that the cancer risk alleles of four candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3K1 expression in vivo and might promote breast cancer cell survival. PMID:25529635

  12. Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1

    PubMed Central

    Glubb, Dylan M.; Maranian, Mel J.; Michailidou, Kyriaki; Pooley, Karen A.; Meyer, Kerstin B.; Kar, Siddhartha; Carlebur, Saskia; O’Reilly, Martin; Betts, Joshua A.; Hillman, Kristine M.; Kaufmann, Susanne; Beesley, Jonathan; Canisius, Sander; Hopper, John L.; Southey, Melissa C.; Tsimiklis, Helen; Apicella, Carmel; Schmidt, Marjanka K.; Broeks, Annegien; Hogervorst, Frans B.; van der Schoot, C. Ellen; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Ruebner, Matthias; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Pharoah, Paul D.P.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Burwinkel, Barbara; Marme, Frederik; Yang, Rongxi; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; González-Neira, Anna; Benitez, Javier; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Anton-Culver, Hoda; Neuhausen, Susan L.; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Ko, Yon-Dschun; Brüning, Thomas; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tanaka, Hideo; Dörk, Thilo; Bogdanova, Natalia V.; Helbig, Sonja; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Wu, Anna H.; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O.; Lambrechts, Diether; Zhao, Hui; Weltens, Caroline; van Limbergen, Erik; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Seibold, Petra; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Capra, Fabio; Couch, Fergus J.; Olson, Janet E.; Hallberg, Emily; Vachon, Celine; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; See, Mee-Hoong; Cornes, Belinda; Cheng, Ching-Yu; Ikram, M. Kamran; Kristensen, Vessela; Zheng, Wei; Halverson, Sandra L.; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Van Asperen, Christi J.; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J.; Lissowska, Jolanta; Czene, Kamila; Klevebring, Daniel; Darabi, Hatef; Eriksson, Mikael; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W.M.; Collée, J. Margriet; Hall, Per; Li, Jingmei; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S.; Reed, Malcolm W.R.; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Shah, Mitul; Ghoussaini, Maya; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Tang, Anthony; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Olswold, Curtis; Slager, Susan; Toland, Amanda E.; Yannoukakos, Drakoulis; Shen, Chen-Yang; Wu, Pei-Ei; Yu, Jyh-Cherng; Hou, Ming-Feng; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Pita, Guillermo; Alonso, M. Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S.; Brown, Melissa A.; Ponder, Bruce A.J.; Chenevix-Trench, Georgia; Thompson, Deborah J.; Edwards, Stacey L.; Easton, Douglas F.; Dunning, Alison M.; French, Juliet D.

    2015-01-01

    Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and control individuals from 52 studies in the Breast Cancer Association Consortium. Multiple logistic regression analyses identified three independent risk signals: the strongest associations were with 15 correlated variants (iCHAV1), where the minor allele of the best candidate, rs62355902, associated with significantly increased risks of both estrogen-receptor-positive (ER+: odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.21–1.27, ptrend = 5.7 × 10−44) and estrogen-receptor-negative (ER−: OR = 1.10, 95% CI = 1.05–1.15, ptrend = 3.0 × 10−4) tumors. After adjustment for rs62355902, we found evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [pcond = 1.61 × 10−5]) and five variants composing iCHAV3 (lead rs11949391; ER+: OR = 0.90, 95% CI = 0.87–0.93, pcond = 1.4 × 10−4). Twenty-six percent of the prioritized candidate variants coincided with four putative regulatory elements that interact with the MAP3K1 promoter through chromatin looping and affect MAP3K1 promoter activity. Functional analysis indicated that the cancer risk alleles of four candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3K1 expression in vivo and might promote breast cancer cell survival. PMID:25529635

  13. Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1.

    PubMed

    Glubb, Dylan M; Maranian, Mel J; Michailidou, Kyriaki; Pooley, Karen A; Meyer, Kerstin B; Kar, Siddhartha; Carlebur, Saskia; O'Reilly, Martin; Betts, Joshua A; Hillman, Kristine M; Kaufmann, Susanne; Beesley, Jonathan; Canisius, Sander; Hopper, John L; Southey, Melissa C; Tsimiklis, Helen; Apicella, Carmel; Schmidt, Marjanka K; Broeks, Annegien; Hogervorst, Frans B; van der Schoot, C Ellen; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A; Ruebner, Matthias; Ekici, Arif B; Beckmann, Matthias W; Peto, Julian; dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Pharoah, Paul D P; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Burwinkel, Barbara; Marme, Frederik; Yang, Rongxi; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; González-Neira, Anna; Benitez, Javier; Zamora, M Pilar; Arias Perez, Jose Ignacio; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Ko, Yon-Dschun; Brüning, Thomas; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tanaka, Hideo; Dörk, Thilo; Bogdanova, Natalia V; Helbig, Sonja; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Wu, Anna H; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O; Lambrechts, Diether; Zhao, Hui; Weltens, Caroline; van Limbergen, Erik; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Seibold, Petra; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Capra, Fabio; Couch, Fergus J; Olson, Janet E; Hallberg, Emily; Vachon, Celine; Giles, Graham G; Milne, Roger L; McLean, Catriona; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; See, Mee-Hoong; Cornes, Belinda; Cheng, Ching-Yu; Ikram, M Kamran; Kristensen, Vessela; Zheng, Wei; Halverson, Sandra L; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Van Asperen, Christi J; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Czene, Kamila; Klevebring, Daniel; Darabi, Hatef; Eriksson, Mikael; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John W M; Collée, J Margriet; Hall, Per; Li, Jingmei; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Blot, William; Signorello, Lisa B; Cai, Qiuyin; Shah, Mitul; Ghoussaini, Maya; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Tang, Anthony; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Olswold, Curtis; Slager, Susan; Toland, Amanda E; Yannoukakos, Drakoulis; Shen, Chen-Yang; Wu, Pei-Ei; Yu, Jyh-Cherng; Hou, Ming-Feng; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S; Brown, Melissa A; Ponder, Bruce A J; Chenevix-Trench, Georgia; Thompson, Deborah J; Edwards, Stacey L; Easton, Douglas F; Dunning, Alison M; French, Juliet D

    2015-01-01

    Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and control individuals from 52 studies in the Breast Cancer Association Consortium. Multiple logistic regression analyses identified three independent risk signals: the strongest associations were with 15 correlated variants (iCHAV1), where the minor allele of the best candidate, rs62355902, associated with significantly increased risks of both estrogen-receptor-positive (ER(+): odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.21-1.27, ptrend = 5.7 × 10(-44)) and estrogen-receptor-negative (ER(-): OR = 1.10, 95% CI = 1.05-1.15, ptrend = 3.0 × 10(-4)) tumors. After adjustment for rs62355902, we found evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [pcond = 1.61 × 10(-5)]) and five variants composing iCHAV3 (lead rs11949391; ER(+): OR = 0.90, 95% CI = 0.87-0.93, pcond = 1.4 × 10(-4)). Twenty-six percent of the prioritized candidate variants coincided with four putative regulatory elements that interact with the MAP3K1 promoter through chromatin looping and affect MAP3K1 promoter activity. Functional analysis indicated that the cancer risk alleles of four candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3K1 expression in vivo and might promote breast cancer cell survival.

  14. Physical mapping of chromosome 17p13.3 in the region of a putative tumor suppressor gene important in medulloblastoma

    SciTech Connect

    McDonald, J.D.; Daneshvar, L.; Willert, J.R.

    1994-09-01

    Deletion mapping of a medulloblastoma tumor panel revealed loss of distal chromosome 17p13.3 sequences in tumors from 14 of 32 patients (44%). Of the 14 tumors showing loss of heterozygosity by restriction fragment length polymorphism analysis, 14 of 14 (100%) displayed loss of the telomeric marker p144-D6 (D17S34), while a probe for the ABR gene on 17p13.3 was lost in 7 of 8 (88%) informative cases. Using pulsed-field gel electrophoresis, we localized the polymorphic marker (VNTR-A) of the ABR gene locus to within 220 kb of the p144-D6 locus. A cosmid contig constructed in this region was used to demonstrate by fluorescence in situ hybridization that the ABR gene is oriented transcriptionally 5{prime} to 3{prime} toward the telomere. This report provides new physical mapping data for the ABR gene, which has not been previously shown to be deleted in medulloblastoma. These results provide further evidence for the existence of a second tumor suppressor gene distinct from p53 on distal chromosome 17p. 12 refs., 3 figs.

  15. Dosage changes of a segment at 17p13.1 lead to intellectual disability and microcephaly as a result of complex genetic interaction of multiple genes.

    PubMed

    Carvalho, Claudia M B; Vasanth, Shivakumar; Shinawi, Marwan; Russell, Chad; Ramocki, Melissa B; Brown, Chester W; Graakjaer, Jesper; Skytte, Anne-Bine; Vianna-Morgante, Angela M; Krepischi, Ana C V; Patel, Gayle S; Immken, LaDonna; Aleck, Kyrieckos; Lim, Cynthia; Cheung, Sau Wai; Rosenberg, Carla; Katsanis, Nicholas; Lupski, James R

    2014-11-01

    The 17p13.1 microdeletion syndrome is a recently described genomic disorder with a core clinical phenotype of intellectual disability, poor to absent speech, dysmorphic features, and a constellation of more variable clinical features, most prominently microcephaly. We identified five subjects with copy-number variants (CNVs) on 17p13.1 for whom we performed detailed clinical and molecular studies. Breakpoint mapping and retrospective analysis of published cases refined the smallest region of overlap (SRO) for microcephaly to a genomic interval containing nine genes. Dissection of this phenotype in zebrafish embryos revealed a complex genetic architecture: dosage perturbation of four genes (ASGR1, ACADVL, DVL2, and GABARAP) impeded neurodevelopment and decreased dosage of the same loci caused a reduced mitotic index in vitro. Moreover, epistatic analyses in vivo showed that dosage perturbations of discrete gene pairings induce microcephaly. Taken together, these studies support a model in which concomitant dosage perturbation of multiple genes within the CNV drive the microcephaly and possibly other neurodevelopmental phenotypes associated with rearrangements in the 17p13.1 SRO. PMID:25439725

  16. Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes

    PubMed Central

    Carvalho, Claudia M.B.; Vasanth, Shivakumar; Shinawi, Marwan; Russell, Chad; Ramocki, Melissa B.; Brown, Chester W.; Graakjaer, Jesper; Skytte, Anne-Bine; Vianna-Morgante, Angela M.; Krepischi, Ana C.V.; Patel, Gayle S.; Immken, LaDonna; Aleck, Kyrieckos; Lim, Cynthia; Cheung, Sau Wai; Rosenberg, Carla; Katsanis, Nicholas; Lupski, James R.

    2014-01-01

    The 17p13.1 microdeletion syndrome is a recently described genomic disorder with a core clinical phenotype of intellectual disability, poor to absent speech, dysmorphic features, and a constellation of more variable clinical features, most prominently microcephaly. We identified five subjects with copy-number variants (CNVs) on 17p13.1 for whom we performed detailed clinical and molecular studies. Breakpoint mapping and retrospective analysis of published cases refined the smallest region of overlap (SRO) for microcephaly to a genomic interval containing nine genes. Dissection of this phenotype in zebrafish embryos revealed a complex genetic architecture: dosage perturbation of four genes (ASGR1, ACADVL, DVL2, and GABARAP) impeded neurodevelopment and decreased dosage of the same loci caused a reduced mitotic index in vitro. Moreover, epistatic analyses in vivo showed that dosage perturbations of discrete gene pairings induce microcephaly. Taken together, these studies support a model in which concomitant dosage perturbation of multiple genes within the CNV drive the microcephaly and possibly other neurodevelopmental phenotypes associated with rearrangements in the 17p13.1 SRO. PMID:25439725

  17. Detection of classical 17p11.2 deletions, an atypical deletion and RAI1 alterations in patients with features suggestive of Smith–Magenis syndrome

    PubMed Central

    Vieira, Gustavo H; Rodriguez, Jayson D; Carmona-Mora, Paulina; Cao, Lei; Gamba, Bruno F; Carvalho, Daniel R; de Rezende Duarte, Andréa; Santos, Suely R; de Souza, Deise H; DuPont, Barbara R; Walz, Katherina; Moretti-Ferreira, Danilo; Srivastava, Anand K

    2012-01-01

    Smith–Magenis syndrome (SMS) is a complex disorder whose clinical features include mild to severe intellectual disability with speech delay, growth failure, brachycephaly, flat midface, short broad hands, and behavioral problems. SMS is typically caused by a large deletion on 17p11.2 that encompasses multiple genes including the retinoic acid induced 1, RAI1, gene or a mutation in the RAI1 gene. Here we have evaluated 30 patients with suspected SMS and identified SMS-associated classical 17p11.2 deletions in six patients, an atypical deletion of ∼139 kb that partially deletes the RAI1 gene in one patient, and RAI1 gene nonsynonymous alterations of unknown significance in two unrelated patients. The RAI1 mutant proteins showed no significant alterations in molecular weight, subcellular localization and transcriptional activity. Clinical features of patients with or without 17p11.2 deletions and mutations involving the RAI1 gene were compared to identify phenotypes that may be useful in diagnosing patients with SMS. PMID:21897445

  18. A new 17p13.3 microduplication including the PAFAH1B1 and YWHAE genes resulting from an unbalanced X;17 translocation.

    PubMed

    Hyon, Capucine; Marlin, Sandrine; Chantot-Bastaraud, Sandra; Mabboux, Philippe; Beaujard, Marie-Paule; Al Ageeli, Essam; Vazquez, Marie-Paule; Picard, Arnaud; Siffroi, Jean-Pierre; Portnoï, Marie-France

    2011-01-01

    Submicroscopic duplications of the genomic interval deleted in Miller-Dieker syndrome (MDS) were recently identified by array-based comparative genomic hybridization (a-CGH) studies, describing new genomic disorders in the MDS locus. These rearrangements of varying size, from 59-88 kb to 4 Mb, were non-recurrent, and appear to result from diverse molecular mechanisms. Only five patients had overlapping 17p13.3 duplications including the entire MDS critical region. We describe here a 13-year-old girl with a novel microduplication of the MDS critical region, involving the PAFAH1B1 and YWHAE genes. She presented with moderate psychomotor retardation, speech delay, behavioral problems, and bilateral cleft lip and palate, a previously unreported manifestation. Initially diagnosed as having an apparently simple terminal Xq26 deletion on standard cytogenetic analysis, she was found to have an associated terminal 4.2 Mb 17p13.3 submicroscopic duplication, identified by subtelomere FISH analysis, further characterized by high-resolution array CGH, resulting from an unbalanced X;17 translocation. Phenotypic comparison with the 5 other patients previously described, revealed common phenotypic features, such as hypotonia, mild to moderate developmental delay/mental retardation, speech abnormalities, behavioral problems, recurrent infections, relatively increase of body weight, discrete facial dysmorphism including downslanting palpebral fissures, broad midface, pointed chin, contributing to further delineate this new 17p13.3 microduplication syndrome.

  19. Reactions of atomic oxygen /O(3P)/ with polymer films

    NASA Technical Reports Server (NTRS)

    Golub, Morton A.

    1992-01-01

    The reactions of polymer films with oxygen atoms are reviewed focusing on laboratory tests on polybutadienes with different amount of 1,4 or 1,2 double bonds and their polyalkenamer homologues, polyimide (Kapton), and a series of polyolefines with increasing fluorine content. It is found that etch rates increase with decrease in -CH=CH- unsaturation, starting with 1,4 -polybutadiene and reaching the maximum rate with polyethylene or ethylene-propylene rubber. IN polybutadienes with both 1,4 and 1,2 double bonds, the rate of O(3P)-induced etching is lower the higher the 1,2 content. The reactions are confined to the polymer surface.

  20. Refined physical map of the Spinal Muscular Atrophy gene (SMA) region at 5q13 based on YAC and cosmid contiguous arrays

    SciTech Connect

    Roy, N.; Yaraghi, Z.; McLean, M.D.

    1995-04-10

    The gene for the autosomal recessive neurodegenerative disorder spinal muscular atrophy has been mapped to a region of 5q13 flanked proximally by CMS-1 and distally by D5S557. We present a 2-Mb yeast artificial chromosome (YAC) contig constructed from three libraries encompassing the D5S435/D5S629/CMS-1-SMA-D5S557/D5S112 interval. The D5S629/CMS-1-SMA-D5S557 interval is unusual insofar as chromosome 5-specific repetitive sequences are present and many of the simple tandem repeats (STR) are located at multiple loci that are unstable in our YAC clones. A long-range restriction map that demonstrates the SMA-containing interval to be 550 kb is presented. Moreover, a 210-kb cosmid array from both a YAC-specific and a chromosome 5-specific cosmid library encompassing the multilocus STRs CATT-1, CMS-1, D5F149, D5F150, and D5F153 has been assembled. We have recently reported strong linkage disequilibrium with Type I SMA for two of these STRs, indicating that the gene is located in close proximity to or within our cosmid clone array. 39 refs., 5 figs., 2 tabs.

  1. 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

  2. Coinage metal complexes supported by a "PN(3)P" scaffold.

    PubMed

    Rao, Gyandshwar Kumar; Gorelsky, Serge I; Korobkov, Ilia; Richeson, Darrin

    2015-11-28

    A series of monovalent group 11 complexes, [2,6-{Ph2PNMe}2(NC5H3)]CuBr 1, [2,6-{Ph2PNMe}2(NC5H3)]CuOTf 2, [2,6-{Ph2PNMe}2(NC5H3)]AgOTf 3, and [2,6-{Ph2PNMe}2(NC5H3)](AuCl)24, supported by a neutral PN(3)P ligand have been synthesized and characterized by multinuclear NMR and single crystal X-ray diffraction studies. The variation of the coordination properties were analyzed and electronic structure calculations have been carried out to provide insight on the bonding details in these complexes. The Cu(I) complexes displayed an unusual coordination geometry with a tridentate pincer ligand and an overall four coordinate trigonal pyramidal geometry. In contrast the Ag(I) analogue displayed a bidentate κ(2)-P,P' ligation leaving the pyridyl-N atom uncoordinated and yielding a pyramidalized trigonal planar geometry around Ag. The bimetallic Au(I) complex completed the series and displayed a monodentate P-bonded ligand and a linear coordination geometry.

  3. Lenalidomide for the Treatment of Low- or Intermediate-1-Risk Myelodysplastic Syndromes Associated with Deletion 5q Cytogenetic Abnormality: An Evidence Review of the NICE Submission from Celgene.

    PubMed

    Blommestein, Hedwig M; Armstrong, Nigel; Ryder, Steve; Deshpande, Sohan; Worthy, Gill; Noake, Caro; Riemsma, Rob; Kleijnen, Jos; Severens, Johan L; Al, Maiwenn J

    2016-01-01

    The National Institute for Health and Care Excellence (NICE) invited the manufacturer of lenalidomide (Celgene) to submit evidence of the clinical and cost effectiveness of the drug for treating adults with myelodysplastic syndromes (MDS) associated with deletion 5q cytogenetic abnormality, as part of the Institute's single technology appraisal (STA) process. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company's submission, the ERG review, and the NICE's subsequent decisions. The ERG reviewed the evidence for clinical and cost effectiveness of the technology, as submitted by the manufacturer to the NICE. The ERG searched for relevant additional evidence and validated the manufacturer's decision analytic model to examine the robustness of the cost-effectiveness results. Clinical effectiveness was obtained from a three-arm, European, randomized, phase III trial among red blood cell (RBC) transfusion-dependent patients with low-/intermediate-1-risk del5q31 MDS. The primary endpoint was RBC independence for ≥26 weeks, and was reached by a higher proportion of patients in the lenalidomide 10 and 5 mg groups compared with placebo (56.1 and 42.6 vs 5.9 %, respectively; both p < 0.001). The option of dose adjustments after 16 weeks due to dose-limiting toxicities or lack of response made long-term effectiveness estimates unreliable, e.g. overall survival (OS). The de novo model of the manufacturer included a Markov state-transition cost-utility model implemented in Microsoft Excel. The base-case incremental cost-effectiveness ratio (ICER) of the manufacturer was £56,965. The ERG assessment indicated that the modeling structure represented the course of the disease; however, a few errors were identified and some of the input parameters were challenged. In response to the appraisal documentation, the company revised the economic model

  4. Identification of a gene disrupted by inv(11)(q13.5;q25) in a patient with left-right axis malformation.

    PubMed

    Iida, A; Emi, M; Matsuoka, R; Hiratsuka, E; Okui, K; Ohashi, H; Inazawa, J; Fukushima, Y; Imai, T; Nakamura, Y

    2000-03-01

    An inv(11)(q13.5;q25) inversion was previously identified in a 9-month-old male patient with complex cyanotic heart defects, altered lung lobation, symmetric liver, and abnormally lobulated spleen (polysplenia). This chromosomal rearrangement was inherited from the phenotypically normal father. We termed these regions DHTX-A (disrupted in heterotaxy)-- A at 11q13.5 and DHTX-B at 11q25. Here, we report the isolation and characterization of the inversion breakpoints and the gene that is disrupted by the DHTX-A breakpoint. The putative DHTX is identical to the UVRAG gene, which was originally identified as a gene that complements the UV sensitivity of xeroderma pigmentosum complementation group C. The 4-kb mRNA was found to be encoded by a large gene, at least 300 kb long, composed of 15 exons. The function of the gene product remains largely unknown. However, the near central portion of the UVRAG protein is predicted to contain a coiled-coil domain, which has been implicated in mediating protein-protein interactions. Southern analyses and fluorescence in situ hybridization (FISH) revealed that the DHTX-A breakpoint in the patient and his father lies within the intron between exons 6 and 7 of UVRAG. Northern blot analysis indicated strong expression in human fetal and adult tissues and in mouse embryonic day-7 and adult tissues, respectively. Whole mount in situ hybridization also showed that the Uvrag gene is expressed in the presomite-stage embryo. Several hypotheses are discussed to explain the relationship between the chromosomal inversion and the accompanying phenotypes. PMID:10798355

  5. A novel sodium bicarbonate cotransporter-like gene in an ancient duplicated region: SLC4A9 at 5q31

    PubMed Central

    Lipovich, Leonard; Lynch, Eric D; Lee, Ming K; King, Mary-Claire

    2001-01-01

    Background: Sodium bicarbonate cotransporter (NBC) genes encode proteins that execute coupled Na+ and HCO3- transport across epithelial cell membranes. We report the discovery, characterization, and genomic context of a novel human NBC-like gene, SLC4A9, on chromosome 5q31. Results: SLC4A9 was initially discovered by genomic sequence annotation and further characterized by sequencing of long-insert cDNA library clones. The predicted protein of 990 amino acids has 12 transmembrane domains and high sequence similarity to other NBCs. The 23-exon gene has 14 known mRNA isoforms. In three regions, mRNA sequence variation is generated by the inclusion or exclusion of portions of an exon. Noncoding SLC4A9 cDNAs were recovered multiple times from different libraries. The 3' untranslated region is fragmented into six alternatively spliced exons and contains expressed Alu, LINE and MER repeats. SLC4A9 has two alternative stop codons and six polyadenylation sites. Its expression is largely restricted to the kidney. In silico approaches were used to characterize two additional novel SLC4A genes and to place SLC4A9 within the context of multiple paralogous gene clusters containing members of the epidermal growth factor (EGF), ankyrin (ANK) and fibroblast growth factor (FGF) families. Seven human EGF-SLC4A-ANK-FGF clusters were found. Conclusion: The novel sodium bicarbonate cotransporter-like gene SLC4A9 demonstrates abundant alternative mRNA processing. It belongs to a growing class of functionally diverse genes characterized by inefficient highly variable splicing. The evolutionary history of the EGF-SLC4A-ANK-FGF gene clusters involves multiple rounds of duplication, apparently followed by large insertions and deletions at paralogous loci and genome-wide gene shuffling. PMID:11305939

  6. A Narrow and Highly Significant Linkage Signal for Severe Bipolar Disorder in the Chromosome 5q33 Region in Latin American Pedigrees

    PubMed Central

    Jasinska, A.J.; Service, S.; Jawaheer, D.; DeYoung, J.; Levinson, M.; Zhang, Z.; Kremeyer, B.; Muller, H.; Aldana, I.; Garcia, J.; Restrepo, G.; Lopez, C.; Palacio, C.; Duque, C.; Parra, M.; Vega, J.; Ortiz, D.; Bedoya, G.; Mathews, C.; Davanzo, P.; Fournier, E.; Bejarano, J.; Ramirez, M.; Ortiz, C. Araya; Araya, X.; Molina, J.; Sabatti, C.; Reus, V.; Ospina, J.; Macaya, G.; Ruiz-Linares, A.; Freimer, N.B.

    2016-01-01

    We previously reported linkage of bipolar disorder to 5q33-q34 in families from two closely related population isolates, the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (CO). Here we present follow up results from fine-scale mapping in large CVCR and CO families segregating severe bipolar disorder, BP-I, and in 343 population trios/duos from CVCR and CO. Employing densely spaced SNPs to fine map the prior linkage peak region increases linkage evidence and clarifies the position of the putative BP-I locus. We performed two-point linkage analysis with 1134 SNPs in an approximately 9 Mb region between markers D5S410 and D5S422. Combining pedigrees from CVCR and CO yields a LOD score of 4.9 at SNP rs10035961. Two other SNPs (rs7721142 and rs1422795) within the same 94 kb region also displayed LOD scores greater than 4. This linkage peak coincides with our prior microsatellite results and suggests a narrowed BP-I susceptibility regions in these families. To investigate if the locus implicated in the familial form of BP-I also contributes to disease risk in the population, we followed up the family results with association analysis in duo and trio samples, obtaining signals within 2 Mb of the peak linkage signal in the pedigrees; rs12523547 and rs267015 (P = 0.00004 and 0.00016, respectively) in the CO sample and rs244960 in the CVCR sample and the combined sample, with P = 0.00032 and 0.00016, respectively. It remains unclear whether these association results reflect the same locus contributing to BP susceptibility within the extended pedigrees. PMID:19319892

  7. A transcription map of the regions surrounding the CSF1R locus on human chromosome 5q31: Candidate genes for diastrophic dysplasia

    SciTech Connect

    Clines, G.; Lovett, M.

    1994-09-01

    Diastrophic dysplasia (DTD) is an autosomal recessive disorder of unknown pathogenesis that is characterized by abnormal skeletal and cartilage growth. Phenotypic characteristics of the disorder include short stature, scoliosis, and deformation of the first metacarpal. The diastrophic dysplasia gene has been localized to chromosome 5q31-33, within {approximately}60 kb of the colony stimulating factor 1 receptor gene (CSF1R). We have used direct cDNA selection to build a transcription map across {approximately}250 kb surrounding and including the CSF1R locus. cDNA pools from human placenta, activated T cells, cerebellum, Hela cells, fetal brain, chondrocytes, chondrosarcomas and osteosarcomas were multiplexed in these selections. After two rounds of selection, an analysis revealed that {approximately}70% of the selected cDNAs were contained within the contig. DNA sequencing and cosmid mapping data from a collection of 310 clones revealed the presence of three new genes in this region that show no appreciable homologies on sequence database searches, as well as cDNA clones from the CSF1R and the PDGFRB loci (another of the known genes in the region). An additional cDNA was found with 100% homology to the gene encoding human ribosomal protein L7 (RPL7). This cDNA comprised {approximately}25% of all selected clones. However, further analysis of the genomic contig revealed the presence of an RPL7 processed pseudogene in very close proximity to the CSF1R and PDGFRB genes. The selection of processed pseudogenes is one previously anticipated artifact of selection metholodolgies, but has not been previously observed. Mutational analysis of the three new genes is underway in diastrophic dysplasia families, as is derivation of full length cDNA clones and the expansion of this detailed transcription map into a larger genomic contig.

  8. Physical map, marker order, and YAC contig of an 11 cM region of 5q31 involved in myeloid leukemia and limb girdle muscular dystrophy

    SciTech Connect

    Horrigan, S.K.; Ramesar, R.S.; Yamaoka, L.H.

    1994-09-01

    Chromosome band 5q31 contains a large number of disease genes including those for limb girdle muscular dystrophy 1 (LGM1), an autosomal dominant form of hereditary deafness, corneal dystrophies, as well as a putative tumor suppressor gene involved in myelodysplastic syndrome/acute myeloid leukemia. To facilitate the identification of these genes, we prepared a YAC contig spanning the region from IL9 to D5S434. This was done with reference to a composite map consisting of markers which had been ordered physically by FISH, which was integrated with CEPH and CHLC markers that had been ordered genetically. These markers were used to screen the CEPH megaYAC library, and also to extract YACs from the CEPH-genethon physical map data base. YAC overlaps were used to confirm marker order and localize additional markers to the region. This YAC contig spans approximately 11 cM and contains 24 polymorphic microsatellite markers, 12 non-polymorphic STS markers and 6 known genes (including IL9, CDC25, EGR1, CD14, FGF1, GRL). A total of 51 YACs were isolated using these markers. YAC overlaps were identified by STS content and Alu-PCR hybridization. Thirty nine YACs fall within the minimum deleted region involved in acute myeloid leukemia (IL9 to D5S166 interval); these YACs were further used to order 10 microsatellite and 8 STS markers that had been regionally localized. This map and the new markers will be used to facilitate the search for candidate genes for the myeloid leukemia tumor suppressor and for LGM1.

  9. The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1.

    PubMed

    Yoneda-Kato, N; Look, A T; Kirstein, M N; Valentine, M B; Raimondi, S C; Cohen, K J; Carroll, A J; Morris, S W

    1996-01-18

    A t(3;5)(q25.1;q34) chromosomal translocation associated with myelodysplastic syndrome and acute myeloid leukemia (AML) was found to rearrange part of the nucleophosmin (NPM) gene on chromosome 5 with sequences from a novel gene on chromosome 3. Chimeric transcripts expressed by these cells contain 5' NPM coding sequences fused in-frame to those of the new gene, which we named myelodysplasia/myeloid leukemia factor 1 (MLF1). RNA-based polymerase chain reaction analysis revealed identical NPM-MLF1 mRNA fusions in each of the three t(3;5)-positive cases of AML examined. The predicted MLF1 amino acid sequence lacked homology to previously characterized proteins and did not contain known functional motifs. Normal MLF1 transcripts were expressed in a variety of tissues, most abundantly in testis, ovary, skeletal muscle, heart, kidney and colon. Anti-MLF1 antibodies detected the wild-type 31 kDa protein in K562 and HEL erythroleukemia cell lines, but not in HL-60, U937 or KG-1 myeloid leukemia lines. By contrast, t(3;5)-positive leukemia cells expressed a 54 kDa NPM-MLF1 protein, but not normal MLF1. Immunostaining experiments indicated that MLF1 is normally located in the cytoplasm, whereas NPM-MLF1 is targeted to the nucleus, with highest levels in the nucleolus. The nuclear/nucleolar localization of NPM-MLF1 mirrors that of NPM, indicating that NPM trafficking signals direct MLF1 to an inappropriate cellular compartment in myeloid leukemia cells.

  10. 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

  11. 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.

  12. Crystallization of Gas-Laden Amorphous Water Ice, Activated by Heat Transport to its Subsurface Reservoirs, as Trigger of Huge Explosions of Comet 17P/Holmes

    NASA Astrophysics Data System (ADS)

    Sekanina, Zdenek

    2009-10-01

    Thick terrain layers, of the type recognized on the Deep Impact mission's close-up images of the nucleus of comet 9P/Tempel, and each 10^(13) to 10^(14) grams in mass, are suggested to be attractive candidate carriers of solid material released into the atmosphere during super-massive explosions (megabursts) and/or major fragmentation events. The properties of the 2007 megaburst of comet 17P/Holmes are shown to be consistent with the triggering mechanism being a transformation of gas-laden water ice from low-density amorphous phase to cubic phase (crystallization) in a reservoir located beneath a layer tens of meters thick. Molecules of highly volatile gases, carbon monoxide in particular, trapped in amorphous water ice and released during the phase transition (at 130 K to 150 K), are superheated, generating -- almost instantly in a runaway process -- a momentum needed to lift off, from the comet's nucleus, the mass of the layer and, after its collapse, to accelerate the pile of mostly microscopic dust debris to subkilometer-per-second velocities. Strongly temperature dependent, the crystallization rate increases progressively between about 100 K at aphelion and nearly 120 K (with about 10 percent of the ice in cubic phase) some 10 days before the megaburst and explosively afterwards, due to the release of the trapped volatiles and completion of the phase transition. The proposed model is in agreement with a wide range of relevant observations of the 2007 megaburst of comet 17P, including the event's post-perihelion timing, the water production rate, the CO-to-H_2O production rate ratio, the dust halo's expansion rate, and the energy involved. The observed recurrence rate of super-massive explosions of comet 17P is explained by heat transport through the terrain layers whose effective thermal conductivity is about 0.2 W m^(-1) K^(-1).

  13. Ge0.83Sn0.17 p-channel metal-oxide-semiconductor field-effect transistors: Impact of sulfur passivation on gate stack quality

    NASA Astrophysics Data System (ADS)

    Lei, Dian; Wang, Wei; Zhang, Zheng; Pan, Jisheng; Gong, Xiao; Liang, Gengchiau; Tok, Eng-Soon; Yeo, Yee-Chia

    2016-01-01

    The effect of room temperature sulfur passivation of the surface of Ge0.83Sn0.17 prior to high-k dielectric (HfO2) deposition is investigated. X-ray photoelectron spectroscopy (XPS) was used to examine the chemical bonding at the interface of HfO2 and Ge0.83Sn0.17. Sulfur passivation is found to be effective in suppressing the formation of both Ge oxides and Sn oxides. A comparison of XPS results for sulfur-passivated and non-passivated Ge0.83Sn0.17 samples shows that sulfur passivation of the GeSn surface could also suppress the surface segregation of Sn atoms. In addition, sulfur passivation reduces the interface trap density Dit at the high-k dielectric/Ge0.83Sn0.17 interface from the valence band edge to the midgap of Ge0.83Sn0.17, as compared with a non-passivated control. The impact of the improved Dit is demonstrated in Ge0.83Sn0.17 p-channel metal-oxide-semiconductor field-effect transistors (p-MOSFETs). Ge0.83Sn0.17 p-MOSFETs with sulfur passivation show improved subthreshold swing S, intrinsic transconductance Gm,int, and effective hole mobility μeff as compared with the non-passivated control. At a high inversion carrier density Ninv of 1 × 1013 cm-2, sulfur passivation increases μeff by 25% in Ge0.83Sn0.17 p-MOSFETs.

  14. The Putative Exchange Factor Gef3p Interacts with Rho3p GTPase and the Septin Ring during Cytokinesis in Fission Yeast*

    PubMed Central

    Muñoz, Sofía; Manjón, Elvira; Sánchez, Yolanda

    2014-01-01

    The small GTP-binding proteins of the Rho family and its regulatory proteins play a central role in cytokinetic actomyosin ring assembly and cytokinesis. Here we show that the fission yeast guanine nucleotide exchange factor Gef3p interacts with Rho3p at the division site. Gef3p contains a putative DH homology domain and a BAR/IMD-like domain. The protein localized to the division site late in mitosis, where it formed a ring that did not constrict with actomyosin ring (cytokinetic actomyosin ring) invagination; instead, it split into a double ring that resembled the septin ring. Gef3p co-localized with septins and Mid2p and required septins and Mid2p for its localization. Gef3p interacts physically with the GTP-bound form of Rho3p. Although Gef3p is not essential for cell separation, the simultaneous disruption of gef3+ and Rho3p-interacting proteins, such as Sec8p, an exocyst component, Apm1p, a subunit of the clathrin adaptor complex or For3p, an actin-polymerizing protein, yielded cells with strong defects in septation and polarity respectively. Our results suggest that interactions between septins and Rho-GEFs provide a new targeting mechanism for GTPases in cytokinesis, in this case probably contributing to Rho3p function in vesicle tethering and vesicle trafficking in the later steps of cell separation. PMID:24947517

  15. Apparent mosaicism for del(17)(p11.2) ruled out by fluorescence in situ hybridization in a Smith-Magenis syndrome patient

    SciTech Connect

    Juyal, R.C.; Shaffer, L.G.; Lupski, J.R.; Greenberg, F.; Baldini, A.; Patel, P.I.

    1995-11-20

    Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome typically associated with a deletion of band p11.2 of human chromosome 17. Finucane et al. reported a 14-year-old boy with mild physical and behavior manifestations of SMS. No evidence for deletion was initially evident in 20 peripheral blood lymphocytes examined at 850 band level of resolution. Examination of metaphase chromosomes of skin fibroblasts showed a deletion of 17p11.2 in 25/25 cells examined which was consistent with the patient`s clinical manifestations of SMS. Subsequent examination of 25 cells from peripheral blood cultures indicated that 11% of cells harbored a deletion at 17p11.2, thus suggesting a mosaicism for the deletion. A third study of 20 peripheral blood lymphocytes examined at 550-850 band length resolution in a different laboratory, indicated that 13 cells had no apparent deletion, 4 cells had an apparent deletion and 3 cells were questionable. 7 refs.

  16. Genetic homogeneity in Sjoegren-Larsson syndrome: Linkage to chromosome 17p in families of different non-Swedish ethnic origins

    SciTech Connect

    Rogers, G.R.; Lee, M.; Compton, J.G.

    1995-11-01

    Sjoegren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder that is characterized by congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia. Three United States families, three Egyptian families, and one Israeli Arab family were investigated for linkage of the SLS gene to a region of chromosome 17. Pairwise and multipoint linkage analysis with nine markers mapped the SLS gene to the same region of the genome as that reported in Swedish SLS pedigrees. Examination of recombinants by haplotype analysis showed that the gene lies in the region containing the markers D17S953, D17S805, D17S689, and D17S842. D17S805 is pericentromeric on 17p. Patients in two consanguineous Egyptian families were homozygous at the nine marker loci tested, and another patient from a third family was homozygous for eight of the nine, suggesting that within each of these families the region of chromosome 17 carrying the SLS gene is identical by descent. Linkage of the SLS gene to chromosome 17p in families of Arabic, mixed European, Native American, and Swedish descent provides evidence for a single SLS locus and should prove useful for diagnosis and carrier detection in worldwide cases. 25 refs., 4 figs., 1 tab.

  17. BCOR as a novel fusion partner of retinoic acid receptor alpha in a t(X;17)(p11;q12) variant of acute promyelocytic leukemia.

    PubMed

    Yamamoto, Yukiya; Tsuzuki, Sachiko; Tsuzuki, Motohiro; Handa, Kousuke; Inaguma, Yoko; Emi, Nobuhiko

    2010-11-18

    The majority of acute promyelocytic leukemia (APL) cases are characterized by the presence of a promyelocytic leukemia-retinoic acid receptor alpha(RARA) fusion gene. In a small subset, RARA is fused to a different partner, usually involved in regulating cell growth and differentiation. Here, we identified a novel RARA fusion transcript, BCOR-RARA, in a t(X;17)(p11;q12) variant of APL with unique morphologic features, including rectangular and round cytoplasmic inclusion bodies. Although the patient was clinically responsive to all-trans retinoic acid, several relapses occurred with standard chemotherapy and all-trans retinoic acid. BCOR is a transcriptional corepressor through the proto-oncoprotein, BCL6, recruiting histone deacetylases and polycomb repressive complex 1 components. BCOR-RARA was found to possess common features with other RARA fusion proteins. These included: (1) the same break point in RARA cDNA; (2) self-association; (3) retinoid X receptor alpha is necessary for BCOR-RARA to associate with the RARA responsive element; (4) action in a dominant-negative manner on RARA transcriptional activation; and (5) aberrant subcellular relocalization. It should be noted that there was no intact BCOR found in the 45,-Y,t(X;17)(p11;q12) APL cells because they featured only a rearranged X chromosome. These results highlight essential features of pathogenesis in APL in more detail. BCOR appears to be involved not only in human congenital diseases, but also in a human cancer. PMID:20807888

  18. Association between rs2431697 T allele on 5q33.3 and systemic lupus erythematosus: case-control study and meta-analysis.

    PubMed

    Tang, Zhao-Ming; Wang, Ping; Chang, Pan-Pan; Hasahya, Tony; Xing, Hui; Wang, Jin-Ping; Hu, Li-Hua

    2015-11-01

    rs2431697 is located on 5q33.3, between pituitary tumor-transforming gene 1 and miR-146a. Several studies have estimated the association between rs2431697 and systemic lupus erythematosus risk. However, the results were inconsistent. A case-control study was carried out to explore the association between rs2431697 and systemic lupus erythematosus risk in a central Chinese population. Meta-analyses combining present with previous studies were conducted to further explore the association. Our case-control study included 322 cases and 353 controls. rs2431697 T allele was associated with increased risk of systemic lupus erythematosus (odds ratios (ORs) = 1.461, 95% confidence intervals (CI) 1.091-1.957, P = 0.011). The association was stronger between T allele and the risk of anti-double-stranded DNA (dsDNA)-positive systemic lupus erythematosus (OR = 2.510, 95% CI 1.545-4.077, P < 0.001). The meta-analyses included 8648 systemic lupus erythematosus patients and 10947 controls. rs2431697 T allele had an overall OR of 1.262 (95% CI 1.205-1.323, P < 0.001) under fixed-effects model. After stratified by ethnicity, I (2) reduced from 24.3 to 0 %. T allele had an OR of 1.213 (95% CI 1.145-1.284, P < 0.001) in European descendant and 1.365 (95% CI 1.259-1.480, P < 0.001) in Asian under fixed-effects model. Data on women were also extracted, and T allele had an OR of 1.337 (95% CI 1.162-1.539, P < 0.001) under random-effects model. The pooled ORs were not influenced by each study in sensitivity analyses. There were no publication biases observed in these analyses. The results from our case-control study and the meta-analyses indicate that rs2431697 T allele significantly associates with the increased risk of systemic lupus erythematosus.

  19. Reciprocal Crossovers and a Positional Preference for Strand Exchange in Recombination Events Resulting in Deletion or Duplication of Chromosome 17p11.2

    PubMed Central

    Bi, Weimin; Park, Sung-Sup; Shaw, Christine J.; Withers, Marjorie A.; Patel, Pragna I.; Lupski, James R.

    2003-01-01

    Smith-Magenis syndrome (SMS) is caused by an ∼4-Mb heterozygous interstitial deletion on chromosome 17p11.2 in ∼80%–90% of affected patients. Three large (∼200 kb), complex, and highly homologous (∼98%) low-copy repeats (LCRs) are located inside or flanking the SMS common deletion. These repeats, also known as “SMS-REPs,” are termed “distal,” “middle,” and “proximal.” The directly oriented distal and proximal copies act as substrates for nonallelic homologous recombination resulting in both the deletion associated with SMS and the reciprocal duplication: dup(17)(p11.2p11.2). Using restriction enzyme cis-morphism analyses and direct sequencing, we mapped the regions of strand exchange in 16 somatic-cell hybrids that harbor only the recombinant SMS-REP. Our studies showed that the sites of crossovers were distributed throughout the region of homology between the distal and proximal SMS-REPs. However, despite ∼170 kb of high homology, 50% of the recombinant junctions occurred in a 12.0-kb region within the KER gene clusters. DNA sequencing of this hotspot (positional preference for strand exchange) in seven recombinant SMS-REPs narrowed the crossovers to an ∼8-kb interval. Four of them occurred in a 1,655-bp region rich in polymorphic nucleotides that could potentially reflect frequent gene conversion. For further evaluation of the strand exchange frequency in patients with SMS, novel junction fragments from the recombinant SMS-REPs were identified. As predicted by the reciprocal-recombination model, junction fragments were also identified from this hotspot region in patients with dup(17)(p11.2p11.2), documenting reciprocity of the positional preference for strand exchange. Several potential cis-acting recombination-promoting sequences were identified within the hotspot. It is interesting that we found 2.1-kb AT-rich inverted repeats flanking the proximal and middle KER gene clusters but not the distal one. The role of any or all of these

  20. LETTER TO THE EDITOR: Observation and interpretation of the metastable 3p63d Ca+ ion spectrum in the 3p excitation region

    NASA Astrophysics Data System (ADS)

    Kjeldsen, H.; Folkmann, F.; Innocenti, F.; Zuin, L.; Hansen, J. E.

    2002-08-01

    A measurement of the 3p absolute photoionization cross section of Ca+ ions is reported. The experiments were performed by means of the merged-beam technique and utilizing a target ion beam containing both 3p64s ground-state ions and 3p63d metastable ions. By combining measurements performed with different fractions of metastable ions, it was possible to obtain separate cross-section data for the two species, and we present here for the first time the photoionization spectrum of the metastable 3p63d state of the Ca+ ion. Comparison with theoretical predictions allows an interpretation of the strongest features in terms of 3p → 3d transitions.

  1. Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk

    PubMed Central

    Broderick, Peter; Chen, Bowang; Johnson, David C; Försti, Asta; Vijayakrishnan, Jayaram; Migliorini, Gabriele; Dobbins, Sara E; Holroyd, Amy; Hose, Dirk; Walker, Brian A; Davies, Faith E; Gregory, Walter A; Jackson, Graham H; Irving, Julie A; Pratt, Guy; Fegan, Chris; Fenton, James AL; Neben, Kai; Hoffmann, Per; Nöthen, Markus M; Mühleisen, Thomas W; Eisele, Lewin; Ross, Fiona M; Straka, Christian; Einsele, Hermann; Langer, Christian; Dörner, Elisabeth; Allan, James M; Jauch, Anna; Morgan, Gareth J; Hemminki, Kari; Houlston, Richard S; Goldschmidt, Hartmut

    2016-01-01

    To identify variants for multiple myeloma risk, we conducted a genome-wide association study with validation in additional series totaling 4,692 cases and 10,990 controls. We identified four risk loci at 3q26.2 (rs10936599, P=8.70x10-14), 6p21.33 (rs2285803, PSORS1C2; P= 9.67x10-11), 17p11.2 (rs4273077, TNFRSF13B; P=7.67x10-9) and 22q13.1 (rs877529, CBX7; P=7.63x10-16). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy and insight into the biological basis of predisposition. PMID:23955597

  2. A Case of Concurrent Miller-Dieker Syndrome (17p13.3 Deletion) and 22q11.2 Deletion Syndrome.

    PubMed

    Atwal, Paldeep S; Macmurdo, C

    2015-12-01

    Features of Miller-Dieker syndrome (MDS, 17p13.3 deletion syndrome, LIS1-associated lissencephaly) include classic lissencephaly, microcephaly, cardiac malformations, growth restriction, and characteristic facial changes. Individuals with 22q11.2 deletion syndrome (DiGeorge syndrome or velocardiofacial syndrome) are known to have congenital cardiac malformations (in particular conotruncal defects), palatal abnormalities (especially velopharyngeal insufficiency), hypocalcemia, immune deficiency, learning disabilities, and characteristic facial features. This case report describes phenotypic characteristics of a patient with extremely rare instance of having both MDS and 22q11.2 deletion syndrome that is unique in the medical literature. Prognosis in this concurrent phenotype is poor with our patient suffering from several malformations seen in both conditions and expiring in the neonatal period.

  3. Microdeletion on 17p11.2 in a Smith-Magenis syndrome patient with mental retardation and congenital heart defect: first report from China.

    PubMed

    Huang, C; Yang, Y-F; Zhang, H; Xie, L; Chen, J-L; Wang, J; Tan, Z-P; Luo, H

    2012-01-01

    Smith-Magenis syndrome (SMS) is a rare syndrome with multiple congenital malformations, including development and mental retardation, behavioral problems and a distinct facial appearance. SMS is caused by haploinsufficiency of RAI1 (deletion or mutation of RAI1). We describe an eight-year-old female Chinese patient with multiple malformations, congenital heart defect, mental retardation, and behavioral problems (self hugging, sleeping disturbance). High-resolution genome wide single nucleotide polymorphism array revealed a 3.7-Mb deletion in chromosome region 17p11.2. This chromosome region contains RAI1, a critical gene involved in SMS. To the best of our knowledge, this is the first report of an SMS patient in mainland China. PMID:22911601

  4. Superior verbal ability and nonverbal learning disability in a child with a novel 17p12p13.1 deletion.

    PubMed

    Steele, D L; Chisholm, A K; McGhie, J D R; Gardner, R J M; Scheffer, I E; Slater, H R; Dawson, G

    2005-04-01

    We report the case of a 10-year-old girl with the karyotype 46,XX,del(17)(p12p13.1) who presented a remarkable incongruence in higher cerebral functioning. Certain language skills were very superior, with reading and spelling at a 17-19 year-old level of proficiency. Nonverbal skills, however, were mostly below average, executive functioning and socialization were impaired, and a diagnosis of "nonverbal learning disability" is applied. We speculate that the genes deleted include one or some which code for certain specific categories of neural substrate that subserve aspects of visual processing and higher functioning, but that no "language loci" have been deleted. The particular neuropsychological profile that we describe may assist diagnosis of this chromosomal deletion. PMID:15717294

  5. A Case of Concurrent Miller-Dieker Syndrome (17p13.3 Deletion) and 22q11.2 Deletion Syndrome.

    PubMed

    Atwal, Paldeep S; Macmurdo, C

    2015-12-01

    Features of Miller-Dieker syndrome (MDS, 17p13.3 deletion syndrome, LIS1-associated lissencephaly) include classic lissencephaly, microcephaly, cardiac malformations, growth restriction, and characteristic facial changes. Individuals with 22q11.2 deletion syndrome (DiGeorge syndrome or velocardiofacial syndrome) are known to have congenital cardiac malformations (in particular conotruncal defects), palatal abnormalities (especially velopharyngeal insufficiency), hypocalcemia, immune deficiency, learning disabilities, and characteristic facial features. This case report describes phenotypic characteristics of a patient with extremely rare instance of having both MDS and 22q11.2 deletion syndrome that is unique in the medical literature. Prognosis in this concurrent phenotype is poor with our patient suffering from several malformations seen in both conditions and expiring in the neonatal period. PMID:27617133

  6. ICL-induced miR139-3p and miR199a-3p have opposite roles in hematopoietic cell expansion and leukemic transformation.

    PubMed

    Alemdehy, Mir Farshid; Haanstra, Jurgen R; de Looper, Hans W J; van Strien, Paulina M H; Verhagen-Oldenampsen, Judith; Caljouw, Yvette; Sanders, Mathijs A; Hoogenboezem, Remco; de Ru, Arnoud H; Janssen, George M C; Smetsers, Stephanie E; Bierings, Marc B; van Veelen, Peter A; von Lindern, Marieke; Touw, Ivo P; Erkeland, Stefan J

    2015-06-18

    Interstrand crosslinks (ICLs) are toxic DNA lesions that cause severe genomic damage during replication, especially in Fanconi anemia pathway-deficient cells. This results in progressive bone marrow failure and predisposes to acute myeloid leukemia (AML). The molecular mechanisms responsible for these defects are largely unknown. Using Ercc1-deficient mice, we show that Trp53 is responsible for ICL-induced bone marrow failure and that loss of Trp53 is leukemogenic in this model. In addition, Ercc1-deficient myeloid progenitors gain elevated levels of miR-139-3p and miR-199a-3p with age. These microRNAs exert opposite effects on hematopoiesis. Ectopic expression of miR-139-3p strongly inhibited proliferation of myeloid progenitors, whereas inhibition of miR-139-3p activity restored defective proliferation of Ercc1-deficient progenitors. Conversely, the inhibition of miR-199a-3p functions aggravated the myeloid proliferation defect in the Ercc1-deficient model, whereas its enforced expression enhanced proliferation of progenitors. Importantly, miR-199a-3p caused AML in a pre-leukemic mouse model, supporting its role as an onco-microRNA. Target genes include HuR for miR-139-3p and Prdx6, Runx1, and Suz12 for miR-199a-3p. The latter genes have previously been implicated as tumor suppressors in de novo and secondary AML. These findings show that, in addition to TRP53-controlled mechanisms, miR-139-3p and miR-199a-3p are involved in the defective hematopoietic function of ICL-repair deficient myeloid progenitors. PMID:25778535

  7. Treatment of Chronic Lymphocytic Leukemia With del(17p)/TP53 Mutation: Allogeneic Hematopoietic Stem Cell Transplantation or BCR-Signaling Inhibitors?

    PubMed

    Montserrat, Emili; Dreger, Peter

    2016-08-01

    The treatment of patients with chronic lymphocytic leukemia (CLL) whose tumor presents the del(17p)/TP53 mutation is a major challenge. Treatment with chemo(immuno)therapy, immunomodulators, or the anti-CD52 monoclonal antibody alemtuzumab produces transient, unsatisfactory responses. Reduced-intensity-conditioning allotransplantation produces sustained progression-free survival and overall survival (40%-60% at 5 years), equivalent to the cure of the disease, even in cases with adverse biomarkers. Unfortunately, despite improvements in this procedure, the non-relapse mortality continues to be high (15%-30%), and only highly selected patients (young, physically fit, with treatment-sensitive disease, not heavily pretreated, and with a fully matched donor) may benefit from the intervention without incurring unacceptable treatment-related risks. The advent of non-cytotoxic agents, such as the inhibitors of the B-cell-antigen receptor signaling (BCRi; ibrutinib, idelasilib) and anti-BCL2 proteins (venetoclax), is rapidly changing the treatment landscape in CLL, including its high-risk forms. These agents are satisfactorily safe. Moreover, they are effective across all genetic subgroups, albeit results in del(17p)/TP53 mutated cases are inferior to those with no adverse genetics. Importantly, progression-free and overall survival decline over time. These agents are tolerated much better and are more effective than conventional therapies used in high-risk CLL, and treatment results are close to those obtained with allotransplantation. As there is no proof as to which treatment (BCRi vs. allotransplantation) is preferable, treatment recommendations should be individualized, weighing the pros and cons of each of these interventions. In most patients, however, initial therapy with BCRi (ideally in combination with monoclonal antibodies and/or other small molecules) is a reasonable approach, and allotransplantation should be considered in selected patients refractory to BCRi

  8. Cryptic translocation t(5;11)(q35;p15.5) with involvement of the NSD1 and NUP98 genes without 5q deletion in childhood acute myeloid leukemia.

    PubMed

    Panarello, Claudio; Rosanda, Cristina; Morerio, Cristina

    2002-11-01

    The cryptic translocation t(5;11)(q35;p15.5), which creates a NSD1-NUP98 fusion gene, has been associated with a deletion of the long arm of chromosome 5, del(5q), in pediatric acute myeloid leukemia (AML) patients with differentiated phenotype. We screened five pediatric cases of AML with apparently normal karyotype by use of fluorescence in situ hybridization analysis and detected one case with early myeloid phenotype and poor clinical outcome, but with the same breakpoints and no del(5q). These findings point to the involvement of t(5;11) as an early event in leukemogenesis. Screening for this translocation in AML patients with apparently normal karyotype at onset is recommended.

  9. The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q

    PubMed Central

    Borkhardt, Arndt; Bojesen, Stig; Haas, Oskar A.; Fuchs, Uta; Bartelheimer, Dominique; Loncarevic, Ivan F.; Bohle, Rainer M.; Harbott, Jochen; Repp, Reinald; Jaeger, Ulrich; Viehmann, Susanne; Henn, Traudl; Korth, Petra; Scharr, Dirk; Lampert, Fritz

    2000-01-01

    We have isolated the human GRAF gene (for GTPase regulator associated with the focal adhesion kinase pp125FAK). This gene was fused with MLL in a unique t(5;11)(q31;q23) that occurred in an infant with juvenile myelomonocytic leukemia. GRAF encodes a member of the Rho family of the GTPase-activating protein (GAP) family. On the protein level, it is 90% homologous to the recently described chicken GRAF gene that functions as a GAP of RhoA in vivo and is thus a critical component of the integrin signaling transduction pathway. The particular position of the human GRAF gene at 5q31 and the proposed antiproliferative and tumor suppressor properties of its avian homologue suggest that it also might be pathogenetically relevant for hematologic malignancies with deletions of 5q. To investigate this possibility, we sequenced 4–5 individual cDNA clones from 13 cases in which one allele of GRAF was deleted. We found point mutations within the GAP domain of the second GRAF allele in one patient. In two additional patients we found an insertion of 52 or 74 bp within the GRAF cDNA that generates a reading frame shift followed by a premature stop codon. GRAF maps outside the previously defined commonly deleted 5q31 region. Nevertheless, inactivation of both alleles in at least some cases suggests that deletions and mutations of the GRAF gene may be instrumental in the development and progression of hematopoeitic disorders with a del(5q). PMID:10908648

  10. A Zebrafish Model of 5q-Syndrome Using CRISPR/Cas9 Targeting RPS14 Reveals a p53-Independent and p53-Dependent Mechanism of Erythroid Failure.

    PubMed

    Ear, Jason; Hsueh, Jessica; Nguyen, Melinda; Zhang, QingHua; Sung, Victoria; Chopra, Rajesh; Sakamoto, Kathleen M; Lin, Shuo

    2016-05-20

    5q-syndrome is a distinct form of myelodysplastic syndrome (MDS) where a deletion on chromosome 5 is the underlying cause. MDS is characterized by bone marrow failures, including macrocytic anemia. Genetic mapping and studies using various models support the notion that ribosomal protein S14 (RPS14) is the candidate gene for the erythroid failure. Targeted disruption of RPS14 causes an increase in p53 activity and p53-mediated apoptosis, similar to what is observed with other ribosomal proteins. However, due to the higher risk for cancer development in patients with ribosome deficiency, targeting the p53 pathway is not a viable treatment option. To better understand the pathology of RPS14 deficiency in 5q-deletion, we generated a zebrafish model harboring a mutation in the RPS14 gene. This model mirrors the anemic phenotype seen in 5q-syndrome. Moreover, the anemia is due to a late-stage erythropoietic defect, where the erythropoietic defect is initially p53-independent and then becomes p53-dependent. Finally, we demonstrate the versatility of this model to test various pharmacological agents, such as RAP-011, L-leucine, and dexamethasone in order to identify molecules that can reverse the anemic phenotype. PMID:27216296

  11. Laser-spectroscopy measurement of the fine-structure splitting 2 3P1-2 3P2 of 4He

    NASA Astrophysics Data System (ADS)

    Feng, G.-P.; Zheng, X.; Sun, Y. R.; Hu, S.-M.

    2015-03-01

    Laser spectroscopy has been performed on a beam of neutral 4He atoms. By using transverse laser cooling and focusing, we are able to prepare a bright beam of atoms in the metastable state 2 3S1 deflected from the original effusive atomic beam. The initial state preparation is completed with optical pumping on the 2 3P1←2 3S1 transition at the wavelength of 1083 nm, followed by laser spectroscopy on the 2 3P1 ,2←2 3S1 transitions. The 2 3P1-2 3P2 fine-structure splitting is determined to be 2 291 177.69 ±0.36 kHz . The quantum interference effect is included in data extraction. This is the most precise laser spectroscopy measurement of the interval. Our result is in agreement with both the latest QED-based calculation and the most precise measurement conducted with microwave spectroscopy.

  12. Recurrent translocation t(10;17)(p15;q21) in minimally differentiated acute myeloid leukemia results in ZMYND11/MBTD1 fusion.

    PubMed

    de Rooij, Jasmijn D E; van den Heuvel-Eibrink, Marry M; Kollen, Wouter J W; Sonneveld, Edwin; Kaspers, Gertjan J L; Beverloo, H Berna; Fornerod, Maarten; Pieters, Rob; Zwaan, C Michel

    2016-03-01

    Pediatric acute myeloid leukemia (AML) is a heterogeneous disease, characterized by different collaborating karyotypic and molecular abnormalities, which are used in risk group stratification. In ∼20% of the pediatric AML cases a specific genetic aberration is still unknown. Minimally differentiated myeloid leukemia or FAB-type M0 is a rare morphological subtype of AML. The translocation t(10;17)(p15;q21) is described to be recurrent in minimally differentiated AML, but the involved genes and location of the breakpoints have so far not been identified. In this study, we show that this translocation results in an in-frame translocation fusing exon 12 of the tumor suppressor gene ZMYND11 to exon 3 of the chromatin protein MBTD1, encoding a protein of 1,054 amino acids, while the reciprocal fusion product is predicted to lack a productive start codon. Gene expression profiling of the leukemic cells showed high HOXA expression. ZMYND11, also known as BS69, is a tumor suppressor that specifically recognizes H3K36me3, which is linked to aberrant HOXA expression in leukemogenesis. Aberrant expression of the genes involved in this fusion may thus contribute to the HOXA-phenotype observed with gene expression profiling. PMID:26608508

  13. Physical and transcript map of the minimally deleted region III on 17p implicated in the early development of Barrett's oesophageal adenocarcinoma.

    PubMed

    Dunn, Julie R; Risk, Janet M; Langan, Joanne E; Marlee, Damian; Ellis, Anthony; Campbell, Fiona; Watson, Alastair J M; Field, John K

    2003-06-26

    Allelic imbalance (AI) studies on chromosome 17 (C17) in Barrett's oesophageal adenocarcinoma (BOA) tumours strongly suggest that a minimally deleted region on C17p harbours a BOA-associated gene with tumour suppressor function. This deleted region, designated minimal region III (MRIII), lies between the two microsatellite markers D17S1852 and D17S954. Computational sequence analysis techniques, BLAST and NIX, were used to assemble a physical map of MRIII, consisting of three overlapping bacterial artificial chromosome (BAC) clones, 297N7, 963H4 and 795F17, from the RPCI-11 library. The 270 kb genomic sequence of MRIII was analysed using the computational gene prediction methods NIX and TAP to identify putative BOA genes. A transcript map of MRIII has been generated and contains 25 candidate BOA genes, four of which are the named genes MYH3, SCO1, x006 and MAGOH-LIKE. The other candidates consist of seven genes predicted by TAP with associated ESTs identified by NIX, two genes predicted by TAP alone and 12 genes/ESTs (or pairs of ESTs) identified by NIX alone. No disease-specific mutations were identified in x006 or MAGOH-LIKE, although expression analysis of these genes suggests that they may show alternative splicing or be altered epigenetically or in regulatory regions in oesophageal cancer.

  14. The LCK gene is involved in the t(1;7)(p34;q34) in the T-cell acute lymphoblastic leukemia derived cell line, HSB-2.

    PubMed

    Burnett, R C; David, J C; Harden, A M; Le Beau, M M; Rowley, J D; Diaz, M O

    1991-11-01

    HSB-2 is a cell line derived from a patient who had T-cell acute lymphoblastic leukemia (T-cell ALL) with a t(1;7)(p34;q34). We used a genomic probe from the T-cell receptor beta (TCR beta) locus (7q34) to identify DNA rearrangements in HSB-2. Two rearranged BglII DNA fragments were cloned, and one of these clones was shown to contain the translocation breakpoint on the derivative chromosome I [der(I)]. We used a probe derived from this clone to isolate an unrearranged phage clone encompassing the breakpoint at Ip34. The restriction map of this clone was compared to the published maps of known protooncogenes located at Ip32-34. By restriction mapping, Southern blot analysis, and DNA sequencing we showed that the translocation breakpoint on chromosome I is located within the first intron of the LCK gene. The LCK gene codes for p56lck, a member of the SRC family of cytoplasmic tyrosine protein kinases. There are two classes of LCK transcripts (type I and type II), each expressed from a distinct promoter, and each having a unique 5' untranslated region (UTR); the protein coding regions of the two classes are identical. The breakpoint in the t(1;7) separates the two LCK promoters and juxtaposes the constant region of the TCR beta locus with the proximal promoter and with the protein-coding region of the LCK gene on the der(I) chromosome.

  15. Canavan disease: Genomic organization and localization of human ASPA to 17p13-ter and conservation of the ASPA gene during evolution

    SciTech Connect

    Kaul, R.; Balamurugan, K.; Gao, G.P.; Matalon, R. )

    1994-05-15

    Canavan disease, or spongy degeneration of the brain, is a severe leukodystrophy caused by the deficiency of aspartoacylase (ASPA). Recently, a missense mutation was identified in human ASPA coding sequence from patients with Canavan disease. The human ASPA gene has been cloned and found to span 29 kb of the genome. Human aspartoacylase is coded by six exons intervened by five introns. The exons vary from 94 (exon III) to 514 (exon VI) bases. The exon/intron splice junction sites follow the gt/ag consensus sequence rule. Southern blot analysis of genomic DNA from human/mouse somatic cell hybrid cell lines localized ASPA to human chromosome 17. The human ASPA locus was further mapped in the 17p13-ter region by fluorescence in situ hybridization. The bovine aspa gene has also been cloned, and its exon/intron organization is identical to that of the human gene. The 500-base sequence upstream of the initiator ATG codon in the human gene and that in the bovine gene are 77% identical. Human ASPA coding sequences cross-hybridize with genomic DNA from yeast, chicken, rabbit, cow, dog, mouse, rat, and monkey. The specificity of cross-species hybridization of coding sequences suggests that aspartoacylase has been conserved during evolution. It should now be possible to identify mutations in the noncoding genomic sequences that lead to Canavan disease and to study the regulation of ASPA. 45 refs., 4 figs., 1 tab.

  16. Review of Disrupted Sleep Patterns in Smith-Magenis Syndrome and Normal Melatonin Secretion in a Patient with an Atypical Interstitial 17p11.2 Deletion

    PubMed Central

    Boudreau, Eilis A.; Johnson, Kyle P.; Jackman, Angela R.; Blancato, Jan; Huizing, Marjan; Bendavid, Claude; Jones, MaryPat; Chandrasekharappa, Settara C.; Lewy, Alfred J.; Smith, Ann C. M.; Magenis, R. Ellen

    2009-01-01

    Smith-Magenis syndrome (SMS) is a disorder characterized by multiple congenital anomalies and behavior problems, including abnormal sleep patterns. It is most commonly due to a 3.5 Mb interstitial deletion of chromosome 17 band p11.2. Secretion of melatonin, a hormone produced by the pineal gland, is the body’s signal for nighttime darkness. Published reports of 24-hour melatonin secretion patterns in two independent SMS cohorts (US & France) document an inverted endogenous melatonin pattern in virtually all cases (96%), suggesting that this finding is pathognomic for the syndrome. We report on a woman with SMS due to an atypical large proximal deletion (∼6Mb; cen<->TNFRSFproteinB) of chromosome band (17)(p11.1p11.2) who presents with typical sleep disturbances but a normal pattern of melatonin secretion. We further describe a melatonin light suppression test in this patient. This is the second reported patient with a normal endogenous melatonin rhythm in SMS associated with an atypical large deletion. These two patients are significant because they suggest that the sleep disturbances in SMS cannot be solely attributed to the abnormal diurnal melatonin secretion versus the normal nocturnal pattern. PMID:19530184

  17. Recurrent translocation t(10;17)(p15;q21) in minimally differentiated acute myeloid leukemia results in ZMYND11/MBTD1 fusion.

    PubMed

    de Rooij, Jasmijn D E; van den Heuvel-Eibrink, Marry M; Kollen, Wouter J W; Sonneveld, Edwin; Kaspers, Gertjan J L; Beverloo, H Berna; Fornerod, Maarten; Pieters, Rob; Zwaan, C Michel

    2016-03-01

    Pediatric acute myeloid leukemia (AML) is a heterogeneous disease, characterized by different collaborating karyotypic and molecular abnormalities, which are used in risk group stratification. In ∼20% of the pediatric AML cases a specific genetic aberration is still unknown. Minimally differentiated myeloid leukemia or FAB-type M0 is a rare morphological subtype of AML. The translocation t(10;17)(p15;q21) is described to be recurrent in minimally differentiated AML, but the involved genes and location of the breakpoints have so far not been identified. In this study, we show that this translocation results in an in-frame translocation fusing exon 12 of the tumor suppressor gene ZMYND11 to exon 3 of the chromatin protein MBTD1, encoding a protein of 1,054 amino acids, while the reciprocal fusion product is predicted to lack a productive start codon. Gene expression profiling of the leukemic cells showed high HOXA expression. ZMYND11, also known as BS69, is a tumor suppressor that specifically recognizes H3K36me3, which is linked to aberrant HOXA expression in leukemogenesis. Aberrant expression of the genes involved in this fusion may thus contribute to the HOXA-phenotype observed with gene expression profiling.

  18. Molecular genetic analysis of a de novo balanced translocation t(6;17)(p21.31;q11.2) associated with hypospadias and anorectal malformation.

    PubMed

    Mansouri, Mahmoud Reza; Carlsson, Birgit; Davey, Edward; Nordenskjöld, Agneta; Wester, Tomas; Annerén, Göran; Läckgren, Göran; Dahl, Niklas

    2006-03-01

    We report a young boy with penoscrotal hypospadias, anal atresia (AA) with a recto-urethral fistula, a hypoplastic kidney and a balanced translocation t(6;17)(p21.31;q11.2). Physical mapping of the breakpoints localized the chromosome 6 breakpoint within an intron of the gene lipoma HMGIC fusion partner-like 5 (LHFPL5) whereas the chromosome 17 breakpoint was mapped to the first intron of the 182-FIP gene encoding the Fragile X Mental Retardation Protein Interacting Protein. Sequence analysis across the breakpoints revealed an almost perfectly balanced translocation with a 2 bp deletion on the derivative chromosome 6 and a 7 bp duplication on the derivative chromosome 17. We identified a fusion transcript consisting of the first exon of 182-FIP and the last exon of LHFPL5 in patient-derived cells. Quantitative expression analysis of the genes flanking the breakpoints, revealed increased transcript levels for SFRS protein kinase 1 (SRPK1) and TAO kinase 1 (TAOK1) which suggests a positional effect due to the translocation. We hypothesize that the urogenital and anorectal malformations in the patient result from one or several mechanisms including disruption of the genes 182-FIP and LHFPL5, altered expression of the genes flanking the translocation breakpoints and, a gain of function mechanism mediated by the 182-FIP-LHFPL5 fusion transcript. PMID:16395596

  19. THE SEARCH FOR THE DIFFUSE INTERSTELLAR BANDS AND OTHER MOLECULES IN COMETS 17P (HOLMES) AND C/2007 W1 (BOATTINI)

    SciTech Connect

    O'Malia, K. K. J.; Snow, T. P.; Thorburn, J. A.; Hammergren, M.; Dembicky, J.; Hobbs, L. M.; York, D. G.

    2010-01-01

    We present the search for both diffuse interstellar bands (DIBs) and molecules in Comet 17P (Holmes) and Comet C/2007 W1 (Boattini) occultation observations. Absorption spectra were taken during stellar occultations by Comet Holmes of 31 and beta Persei, and the occultation of BD+22 216 by Comet Boattini. While no signature of the comets was detected, we present upper limits for some common cometary molecules such as C{sub 2}, C{sub 3}, CH, CN and for the most common DIBs. We did not detect either comet in absorption, most likely because of the large distance between the line of sight to the star and the nucleus of the comet. Interstellar sight lines with comparable reddening to what was measured in Comet Holmes have DIB equivalent widths between 5 and 50 mA. However, future observations with closer approaches to a background star have great potential for spatially mapping molecule distributions in comets, and in discovering DIBs, if they are present, in comets. Future observations could detect DIBs and molecules if they are done: (1) less than approx10{sup 4}-10{sup 3} km from the nucleus (2) with a signal to noise in the background star of approx300 and (3) with a resolving power of at least 38,000.

  20. Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation

    PubMed Central

    Li, Defang; Liu, Jin; Guo, Baosheng; Liang, Chao; Dang, Lei; Lu, Cheng; He, Xiaojuan; Cheung, Hilda Yeuk-Siu; Xu, Liang; Lu, Changwei; He, Bing; Liu, Biao; Shaikh, Atik Badshah; Li, Fangfei; Wang, Luyao; Yang, Zhijun; Au, Doris Wai-Ting; Peng, Songlin; Zhang, Zongkang; Zhang, Bao-Ting; Pan, Xiaohua; Qian, Airong; Shang, Peng; Xiao, Lianbo; Jiang, Baohong; Wong, Chris Kong-Chu; Xu, Jiake; Bian, Zhaoxiang; Liang, Zicai; Guo, De-an; Zhu, Hailong; Tan, Weihong; Lu, Aiping; Zhang, Ge

    2016-01-01

    Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs mediate osteoclast-directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR-214-3p associates with both elevated serum exosomal miR-214-3p and reduced bone formation in elderly women with fractures and in ovariectomized (OVX) mice. Osteoclast-specific miR-214-3p knock-in mice have elevated serum exosomal miR-214-3p and reduced bone formation that is rescued by osteoclast-targeted antagomir-214-3p treatment. We further demonstrate that osteoclast-derived exosomal miR-214-3p is transferred to osteoblasts to inhibit osteoblast activity in vitro and reduce bone formation in vivo. Moreover, osteoclast-targeted miR-214-3p inhibition promotes bone formation in ageing OVX mice. Collectively, our results suggest that osteoclast-derived exosomal miR-214-3p transfers to osteoblasts to inhibit bone formation. Inhibition of miR-214-3p in osteoclasts may be a strategy for treating skeletal disorders involving a reduction in bone formation. PMID:26947250

  1. Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation.

    PubMed

    Li, Defang; Liu, Jin; Guo, Baosheng; Liang, Chao; Dang, Lei; Lu, Cheng; He, Xiaojuan; Cheung, Hilda Yeuk-Siu; Xu, Liang; Lu, Changwei; He, Bing; Liu, Biao; Shaikh, Atik Badshah; Li, Fangfei; Wang, Luyao; Yang, Zhijun; Au, Doris Wai-Ting; Peng, Songlin; Zhang, Zongkang; Zhang, Bao-Ting; Pan, Xiaohua; Qian, Airong; Shang, Peng; Xiao, Lianbo; Jiang, Baohong; Wong, Chris Kong-Chu; Xu, Jiake; Bian, Zhaoxiang; Liang, Zicai; Guo, De-An; Zhu, Hailong; Tan, Weihong; Lu, Aiping; Zhang, Ge

    2016-01-01

    Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs mediate osteoclast-directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR-214-3p associates with both elevated serum exosomal miR-214-3p and reduced bone formation in elderly women with fractures and in ovariectomized (OVX) mice. Osteoclast-specific miR-214-3p knock-in mice have elevated serum exosomal miR-214-3p and reduced bone formation that is rescued by osteoclast-targeted antagomir-214-3p treatment. We further demonstrate that osteoclast-derived exosomal miR-214-3p is transferred to osteoblasts to inhibit osteoblast activity in vitro and reduce bone formation in vivo. Moreover, osteoclast-targeted miR-214-3p inhibition promotes bone formation in ageing OVX mice. Collectively, our results suggest that osteoclast-derived exosomal miR-214-3p transfers to osteoblasts to inhibit bone formation. Inhibition of miR-214-3p in osteoclasts may be a strategy for treating skeletal disorders involving a reduction in bone formation.

  2. A Constitutional Translocation t(1;17)(p36.2;q11.2) in a Neuroblastoma Patient Disrupts the Human NBPF1 and ACCN1 Genes

    PubMed Central

    Staes, Katrien; Vandesompele, Jo; Laureys, Geneviève; De Smet, Els; Berx, Geert; Speleman, Frank; van Roy, Frans

    2008-01-01

    The human 1p36 region is deleted in many different types of tumors, and so it probably harbors one or more tumor suppressor genes. In a Belgian neuroblastoma patient, a constitutional balanced translocation t(1;17)(p36.2;q11.2) may have led to the development of the tumor by disrupting or activating a gene. Here, we report the cloning of both translocation breakpoints and the identification of a novel gene that is disrupted by this translocation. This gene, named NBPF1 for Neuroblastoma BreakPoint Family member 1, belongs to a recently described gene family encoding highly similar proteins, the functions of which are unknown. The translocation truncates NBPF1 and gives rise to two chimeric transcripts of NBPF1 sequences fused to sequences derived from chromosome 17. On chromosome 17, the translocation disrupts one of the isoforms of ACCN1, a potential glioma tumor suppressor gene. Expression of the NBPF family in neuroblastoma cell lines is highly variable, but it is decreased in cell lines that have a deletion of chromosome 1p. More importantly, expression profiling of the NBPF1 gene showed that its expression is significantly lower in cell lines with heterozygous NBPF1 loss than in cell lines with a normal 1p chromosome. Meta-analysis of the expression of NBPF and ACCN1 in neuroblastoma tumors indicates a role for the NBPF genes and for ACCN1 in tumor aggressiveness. Additionally, DLD1 cells with inducible NBPF1 expression showed a marked decrease of clonal growth in a soft agar assay. The disruption of both NBPF1 and ACCN1 genes in this neuroblastoma patient indicates that these genes might suppress development of neuroblastoma and possibly other tumor types. PMID:18493581

  3. Molecular analysis of the Smith-Magenis syndrome: a possible contiguous-gene syndrome associated with del(17)(p11.2).

    PubMed Central

    Greenberg, F; Guzzetta, V; Montes de Oca-Luna, R; Magenis, R E; Smith, A C; Richter, S F; Kondo, I; Dobyns, W B; Patel, P I; Lupski, J R

    1991-01-01

    We undertook clinical evaluation (32 cases) and molecular evaluation (31 cases) of unrelated patients affected with Smith-Magenis syndrome (SMS) associated with an interstitial deletion of band p11.2 of chromosome 17. Patients were evaluated both clinically and electrophysiologically for peripheral neuropathy, since markers showing close linkage to one form of Charcot-Marie-Tooth disease (CMT1A) map to this chromosomal region. The common clinical findings were broad flat midface with brachycephaly, broad nasal bridge, brachydactyly, speech delay, and hoarse, deep voice. Fifty-five percent of the patients showed clinical signs (e.g., decreased or absent deep tendon reflexes, pes planus or pes cavus, decreased sensitivity to pain, and decreased leg muscle mass) suggestive of peripheral neuropathy. However, unlike patients with CMT1A, these patients demonstrated normal nerve conduction velocities. Self-destructive behaviors, primarily onychotillomania and polyembolokoilamania, were observed in 67% of the patients, and significant symptoms of sleep disturbance were observed in 62%. The absence of REM sleep was demonstrated by polysomnography in two patients. Southern analysis indicated that most patients were deleted for five 17p11.2 markers--FG1 (D17S446), 1516 (D17S258), pYNM67-R5 (D17S29), pA10-41 (D17S71), and pS6.1-HB2 (D17S445)--thus defining a region which appears to be critical to SMS. The deletion was determined to be of paternal origin in nine patients and of maternal origin in six patients. The apparent random parental origin of deletion documented in 15 patients suggests that genomic imprinting does not play a role in the expression of the SMS clinical phenotype. Our findings suggest that SMS is likely a contiguous-gene deletion syndrome which comprises characteristic clinical features, developmental delay, clinical signs of peripheral neuropathy, abnormal sleep function, and specific behavioral anomalies. Images Figure 2 Figure 3 PMID:1746552

  4. Molecular analysis of the Smith-Magenis syndrome: a possible contiguous-gene syndrome associated with del(17)(p11.2).

    PubMed

    Greenberg, F; Guzzetta, V; Montes de Oca-Luna, R; Magenis, R E; Smith, A C; Richter, S F; Kondo, I; Dobyns, W B; Patel, P I; Lupski, J R

    1991-12-01

    We undertook clinical evaluation (32 cases) and molecular evaluation (31 cases) of unrelated patients affected with Smith-Magenis syndrome (SMS) associated with an interstitial deletion of band p11.2 of chromosome 17. Patients were evaluated both clinically and electrophysiologically for peripheral neuropathy, since markers showing close linkage to one form of Charcot-Marie-Tooth disease (CMT1A) map to this chromosomal region. The common clinical findings were broad flat midface with brachycephaly, broad nasal bridge, brachydactyly, speech delay, and hoarse, deep voice. Fifty-five percent of the patients showed clinical signs (e.g., decreased or absent deep tendon reflexes, pes planus or pes cavus, decreased sensitivity to pain, and decreased leg muscle mass) suggestive of peripheral neuropathy. However, unlike patients with CMT1A, these patients demonstrated normal nerve conduction velocities. Self-destructive behaviors, primarily onychotillomania and polyembolokoilamania, were observed in 67% of the patients, and significant symptoms of sleep disturbance were observed in 62%. The absence of REM sleep was demonstrated by polysomnography in two patients. Southern analysis indicated that most patients were deleted for five 17p11.2 markers--FG1 (D17S446), 1516 (D17S258), pYNM67-R5 (D17S29), pA10-41 (D17S71), and pS6.1-HB2 (D17S445)--thus defining a region which appears to be critical to SMS. The deletion was determined to be of paternal origin in nine patients and of maternal origin in six patients. The apparent random parental origin of deletion documented in 15 patients suggests that genomic imprinting does not play a role in the expression of the SMS clinical phenotype. Our findings suggest that SMS is likely a contiguous-gene deletion syndrome which comprises characteristic clinical features, developmental delay, clinical signs of peripheral neuropathy, abnormal sleep function, and specific behavioral anomalies.

  5. A firefly inspired one-pot chemiluminescence system using n-propylphosphonic anhydride (T3P).

    PubMed

    Kato, Dai-ichiro; Shirakawa, Daiki; Polz, Robin; Maenaka, Mika; Takeo, Masahiro; Negoro, Seiji; Niwa, Kazuki

    2014-12-01

    A simple reaction procedure for chemiluminescence of firefly luciferin (D-luc) using n-propylphosphonic anhydride (T3P) is reported. A luminescent photon is produced as a result of one-pot reaction, only requiring mixing with the substrate carboxylic acid and T3P in the presence of a mild organic base. PMID:25350893

  6. Surfactant-assisted synthesis and electrochemical performances of Cu{sub 3}P dendrites

    SciTech Connect

    Liu, Shuling; Li, Shu; Wang, Jingping; Shi, Qiangqiang; Li, Miaomiao

    2012-11-15

    Highlights: ► Dendrite-like Cu{sub 3}P microstructures have been synthesized by a low-temperature method. ► The surfactant SDS was used as template. ► The as-obtained Cu{sub 3}P dendrites exhibit a high first discharge capacity. -- Abstract: Well-defined Cu{sub 3}P hierarchical dendrites were successfully synthesized by a facile and effective surfactant-assisted hydrothermal approach. X-ray powder diffraction (XRD) and scanning electron microscopy (SEM) indicated that the as-obtained Cu{sub 3}P had a well-crystallized hexagonal phase and consisted of a wealth of Cu{sub 3}P dendritic microstructures. A surfactant-assisted growth accompanied by the Ostwald ripening process was proposed for the formation. As anode materials for lithium ion batteries, the electrochemical property of the Cu{sub 3}P dendrites was also examined. The results showed that the initial discharge capacity of the Cu{sub 3}P dendrites exceeded 1300 mA h/g and it still kept at 291 mA h/g after 20 cycles, which might be related to the size of Cu{sub 3}P particles and their assembly structure.

  7. A firefly inspired one-pot chemiluminescence system using n-propylphosphonic anhydride (T3P).

    PubMed

    Kato, Dai-ichiro; Shirakawa, Daiki; Polz, Robin; Maenaka, Mika; Takeo, Masahiro; Negoro, Seiji; Niwa, Kazuki

    2014-12-01

    A simple reaction procedure for chemiluminescence of firefly luciferin (D-luc) using n-propylphosphonic anhydride (T3P) is reported. A luminescent photon is produced as a result of one-pot reaction, only requiring mixing with the substrate carboxylic acid and T3P in the presence of a mild organic base.

  8. The direct measurement of the 3 3P0-3 3P1 fine-structure interval and the gJ-factor of atomic silicon by laser magnetic resonance

    NASA Technical Reports Server (NTRS)

    Evenson, K. M.; Beltran-Lopez, V.; Ley-Koo, E.; Inguscio, M.

    1984-01-01

    The J - 1 fine structure interval and the g-factor of the 3P1 state have been determined with high precision in the present laser magnetic resonance measurements of the ground 3p2 3P multiplet of atomic Si. Delta-E(3P1-3P0) = 2,311,755.6(7) MHz, and gJ(3P1) = 1.500830(70). Single-configuration calculations of gJ for 3P1 and 3P2 yield a value for the latter which, at 1.501095, is noted to differ by an unexpectedly large margin from the experimental value.

  9. Detection of G3P[3] and G3P[9] rotavirus strains in American Indian children with evidence of gene reassortment between human and animal rotaviruses.

    PubMed

    Grant, Lindsay; Esona, Mathew; Gentsch, Jon; Watt, James; Reid, Raymond; Weatherholtz, Robert; Santosham, Mathuram; Parashar, Umesh; O'Brien, Katherine

    2011-07-01

    The distribution and evolution of human rotavirus strains is important for vaccine development and effectiveness. In settings where rotavirus vaccine coverage is high, vaccine pressure could select for replacement of common strains (similar to those included in rotavirus vaccines) with uncommon strains, some of which could be generated by reassortment between human and animal rotaviruses. Between 2002 and 2004, a phase-III rotavirus vaccine clinical trial was conducted among American Indian children of the Navajo and White Mountain Apache tribes, which are known to be at high risk for rotavirus diarrhea. We evaluated the rotavirus strains collected from study participants who received placebo during the trial to determine the distribution of rotavirus genotypes and to detect emerging strains that contribute to disease and could influence rotavirus vaccine effectiveness. Three uncommon strains of human rotavirus, two G3P[3] and one G3P[9] strains were detected in stools of children aged 3 to 6 months of age. Segments of all 11 rotavirus genes were sequenced and genotyped by comparison of cognate gene fragments with reference strains. The G3P[3] strains had similar genotypes to each other and to reference dog and cat strains. The G3P[9] strain had similar genotypes to cow, cat and dog reference strains. Genetic analyses of these three strains support the known diversity generating mechanisms of rotavirus. PMID:21567432

  10. Electronic and rovibrational quantum chemical analysis of C3P-: the next interstellar anion?

    NASA Astrophysics Data System (ADS)

    Fortenberry, Ryan C.; Lukemire, Joseph A.

    2015-11-01

    C3P- is analogous to the known interstellar anion C3N- with phosphorus replacing nitrogen in a simple step down the periodic table. In this work, it is shown that C3P- is likely to possess a dipole-bound excited state. It has been hypothesized and observationally supported that dipole-bound excited states are an avenue through which anions could be formed in the interstellar medium. Additionally, C3P- has a valence excited state that may lead to further stabilization of this molecule, and C3P- has a larger dipole moment than neutral C3P (˜6 D versus ˜4 D). As such, C3P- is probably a more detectable astromolecule than even its corresponding neutral radical. Highly accurate quantum chemical quartic force fields are also applied to C3P- and its singly 13C substituted isotopologues in order to provide structures, vibrational frequencies, and spectroscopic constants that may aid in its detection.

  11. The copper-iron connection in biology: Structure of the metallo-oxidase Fet3p

    SciTech Connect

    Taylor, A. B.; Stoj, C. S.; Ziegler, L.; Kosman, D. J.; Hart, P. J.

    2005-10-17

    Fet3p is a multicopper-containing glycoprotein localized to the yeast plasma membrane that catalyzes the oxidation of Fe(II) to Fe(III). This ferrous iron oxidation is coupled to the reduction of O2 to H2O and is termed the ferroxidase reaction. Fet3p-produced Fe(III) is transferred to the permease Ftr1p for import into the cytosol. The posttranslational insertion of four copper ions into Fet3p is essential for its activity, thus linking copper and iron homeostasis. The mammalian ferroxidases ceruloplasmin and hephaestin are homologs of Fet3p. Loss of the Fe(II) oxidation catalyzed by these proteins results in a spectrum of pathological states, including death. Here, we present the structure of the Fet3p extracellular ferroxidase domain and compare it with that of human ceruloplasmin and other multicopper oxidases that are devoid of ferroxidase activity. The Fet3p structure delineates features that underlie the unique reactivity of this and homologous multicopper oxidases that support the essential trafficking of iron in diverse eukaryotic organisms. The findings are correlated with biochemical and physiological data to cross-validate the elements of Fet3p that define it as both a ferroxidase and cuprous oxidase.

  12. miR-17-3p Exacerbates Oxidative Damage in Human Retinal Pigment Epithelial Cells

    PubMed Central

    Tian, Bo; Maidana, Daniel E.; Dib, Bernard; Miller, John B.; Bouzika, Peggy; Miller, Joan W.; Vavvas, Demetrios G.; Lin, Haijiang

    2016-01-01

    Oxidative stress has been shown to contribute to the development of age-related macular degeneration (AMD). MicroRNAs (miRNA) are small non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. We showed miR-17-3p to be elevated in macular RPE cells from AMD patients and in ARPE-19 cells under oxidative stress. Transfection of miR-17-3p mimic in ARPE-19 induced cell death and exacerbated oxidative lethality that was alleviated by miR-17-3p inhibitor. The expression of antioxidant enzymes manganese superoxide dismutase (MnSOD) and thioredoxin reductase-2 (TrxR2) were suppressed by miR-17-3p mimic and reversed by miR-17-3p inhibitor. These results suggest miR-17-3p aggravates oxidative damage-induced cell death in human RPE cells, while miR-17-3p inhibitor acts as a potential protector against oxidative stress by regulating the expression of antioxidant enzymes. PMID:27505139

  13. BOT3P: Bologna Radiation Transport Analysis Pre-Post-Processors Version 4.0

    SciTech Connect

    Orsi, Roberto

    2005-07-15

    BOT3P consists of a set of standard FORTRAN-77 language programs developed at the ENEA-Bologna Nuclear Data Centre. BOT3P Version 1.0 was originally conceived to give the users of the DORT and TORT deterministic transport codes some useful diagnostic tools to prepare and check their input data files. BOT3P Version 3.0 introduced some important additions in the input geometrical model description and extended the possibility to produce the geometrical, material distribution, and fixed neutron source data to the deterministic transport codes TWODANT, THREEDANT, and PARTISN, and in the case of X-Y-Z mesh grids, a geometrical input to the MCNP Monte Carlo transport code, starting from the same input to BOT3P.BOT3P Version 4.0 extends the modeling capabilities of previous BOT3P versions, reduces CPU times, and facilitates the debugging of the computer code input. Version 4.0 also produces the geometrical entries for the sensitivity code SUSD3D, for both Cartesian and cylindrical geometries, and stores the fine-mesh arrays and the material zone map in a binary file, the contents of which can be visualized by the graphics modules of BOT3P. This new feature makes interfacing to any deterministic and Monte Carlo transport code easy and might open new promising application fields to this package.BOT3P was developed on a DIGITAL UNIX ALPHA 500/333 workstation and successfully used in some complex neutron shielding and criticality benchmarks. It was also tested on Red Hat Linux 7.1 and is designed to run on most UNIX platforms. All BOT3P versions are publicly available from the Organization for Economic Cooperation and Development/Nuclear Energy Agency Data Bank.

  14. miR-339-3p inhibits proliferation and metastasis of colorectal cancer

    PubMed Central

    ZHOU, CHANG; LU, YENXIA; LI, XUENONG

    2015-01-01

    MicroRNAs (miRNAs) serve important roles in regulating cancer cell proliferation and metastasis. The same hairpin RNA structure may produce mature products from each strand, termed miR-5p and miR-3p, which can bind different mRNAs. Previously, the present authors reported that miR-339-5p could inhibit cell proliferation and migration by targeting the 3′-untranslated region (3′-UTR) of PRL-1 mRNA. The present study analyzed the expression, function and preliminary regulatory mechanism of miR-339-3p in colorectal cancer (CRC). The results of reverse transcription-quantitative polymerase chain reaction analysis demonstrated that miR-339-3p is downregulated in CRC specimens and highly invasive cell lines. Furthermore, the low-level expression of miR-339-3p was significantly associated with lymph node metastasis in patients with CRC; however, reduced miR-339-3p expression was not associated with age, gender or the differentiation status of the tumor. Overexpression of miR-339-3p was sufficient to suppress tumor growth and metastasis in vitro. In addition, the present study demonstrated that unlike miR-339-5p, PRL-1 expression was not regulated by miR-339-3p. The findings of the present study indicate that miR-339-5p and miR-339-3p may target different mRNA. The target gene of miR-339-3p requires future identification. PMID:26722251

  15. miR-542-3p exerts tumor suppressive functions in neuroblastoma by downregulating Survivin.

    PubMed

    Althoff, Kristina; Lindner, Sven; Odersky, Andrea; Mestdagh, Pieter; Beckers, Anneleen; Karczewski, Sarah; Molenaar, Jan J; Bohrer, Anna; Knauer, Shirley; Speleman, Frank; Epple, Matthias; Kozlova, Diana; Yoon, Sena; Baek, Kwanghee; Vandesompele, Jo; Eggert, Angelika; Schramm, Alexander; Schulte, Johannes H

    2015-03-15

    MicroRNAs (miRNAs) are deregulated in a variety of human cancers, including neuroblastoma, the most common extracranial tumor of childhood. We previously reported a signature of 42 miRNAs to be highly predictive of neuroblastoma outcome. One miRNA in this signature, miR-542, was downregulated in tumors from patients with adverse outcome. Reanalysis of quantitative PCR and next-generation sequencing transcript data revealed that miR-542-5p as well as miR-542-3p expression is inversely correlated with poor prognosis in neuroblastoma patients. We, therefore, analyzed the function of miR-542 in neuroblastoma tumor biology. Ectopic expression of miR-542-3p in neuroblastoma cell lines reduced cell viability and proliferation, induced apoptosis and downregulated Survivin. Survivin expression was also inversely correlated with miR-542-3p expression in primary neuroblastomas. Reporter assays confirmed that miR-542-3p directly targeted Survivin. Downregulating Survivin using siRNA copied the phenotype of miR-542-3p expression in neuroblastoma cell lines, while cDNA-mediated ectopic expression of Survivin partially rescued the phenotype induced by miR-542-3p expression. Treating nude mice bearing neuroblastoma xenografts with miR-542-3p-loaded nanoparticles repressed Survivin expression, decreased cell proliferation and induced apoptosis in the respective xenograft tumors. We conclude that miR-542-3p exerts its tumor suppressive function in neuroblastoma, at least in part, by targeting Survivin. Expression of miR-542-3p could be a promising therapeutic strategy for treating aggressive neuroblastoma.

  16. Congenital hypothyroidism in association with chromosome 3p25.3-pter deletion.

    PubMed

    Malhotra, Atul; Bergman, Phil; Brown, Justin; Mc Gillivray, George

    2011-01-01

    This report describes a case of a neonate presenting with many of the typical phenotypic characteristics of chromosome 3p deletion including hypertelorism, flat nasal bridge, flat philtrum, thin lips and low-set ears. The hands and feet showed post axial polydactyly, single palmar creases and rocker bottom feet. A karyotype confirmed chromosome 3p25.3-pter deletion with normal parental karyotypes. A high TSH was noted on newborn screening and congenital hypothyroidism was confirmed on thyroid function tests. Thyroid nuclear imaging was suggestive of dyshormonogenesis. This is the first reported case of congenital hypothyroidism in an infant with chromosome 3p deletion. PMID:22145477

  17. Elevation of Circulating miR-210-3p in High-Altitude Hypoxic Environment

    PubMed Central

    Yan, Yan; Wang, Cheng; Zhou, Wanqing; Shi, Yonghui; Guo, Pengtao; Liu, Yuxiu; Wang, Junjun; Zhang, Chen-Yu; Zhang, Chunni

    2016-01-01

    Background: The induction of miR-210-3p, a master hypoxamir, is a consistent feature of the hypoxic response in both normal and malignant cells. However, whether miR-210-3p acts as a circulating factor in response to a hypoxic environment remains unknown. The current study aimed to examine the effect of a high-altitude hypoxic environment on circulating miR-210-3p. Methods: We examined and compared the levels of miR-210-3p using TaqMan-based qRT-PCR in both peripheral blood cells and plasma from 84 ethnic Chinese Tibetans residing at 3560 m, 46 newly arrived migrant Han Chinese (Tibet Han) and 82 Han Chinese residing at 8.9 m (Nanjing Han). Furthermore, we analyzed the correlations of miR-210-3p with hematological indices. Results: The relative concentrations of miR-210-3p to internal reference U6 in blood cells were significantly higher in the Tibet Han group (1.01 ± 0.11, P < 0.001) and in the Tibetan group (1.17 ± 0.09, P < 0.001) than in the Nanjing Han group (0.51 ± 0.04). The absolute concentrations of plasma miR-210-3p were also markedly elevated in the Tibet Han group (503.54 ± 42.95 fmol/L, P = 0.004) and in the Tibetan group (557.78 ± 39.84 fmol/L, P < 0.001) compared to the Nanjing Han group (358.39 ± 16.16 fmol/L). However, in both blood cells and plasma, miR-210-3p levels were not significantly different between the Tibet Han group and the Tibetan group (P = 0.280, P = 0.620, respectively). Plasma miR-210-3p concentrations were positively correlated with miR-210-3p levels in blood cells (r = 0.192, P = 0.005). Furthermore, miR-210-3p levels in both blood cells and plasma showed strong positive correlations with red blood cell counts and hemoglobin and hematocrit values. Conclusion: These data demonstrated, for the first time, that miR-210-3p might act as a circulating factor in response to hypoxic environments and could be associated with human adaptation to life at high altitudes. PMID:27014085

  18. Progress on the Multiphysics Capabilities of the Parallel Electromagnetic ACE3P Simulation Suite

    SciTech Connect

    Kononenko, Oleksiy

    2015-03-26

    ACE3P is a 3D parallel simulation suite that is being developed at SLAC National Accelerator Laboratory. Effectively utilizing supercomputer resources, ACE3P has become a key tool for the coupled electromagnetic, thermal and mechanical research and design of particle accelerators. Based on the existing finite-element infrastructure, a massively parallel eigensolver is developed for modal analysis of mechanical structures. It complements a set of the multiphysics tools in ACE3P and, in particular, can be used for the comprehensive study of microphonics in accelerating cavities ensuring the operational reliability of a particle accelerator.

  19. miR-483-3p regulates hyperglycaemia-induced cardiomyocyte apoptosis in transgenic mice.

    PubMed

    Qiao, Yu; Zhao, Yanli; Liu, Yan; Ma, Ning; Wang, Chuxuan; Zou, Jiaqi; Liu, Zhiyan; Zhou, Zhongqiu; Han, Dong; He, Jun; Sun, Qian; Liu, Yicong; Xu, Changqing; Du, Zhimin; Huang, Hui

    2016-09-01

    Diabetic cardiomyopathy represents severe heart complications, and is the leading cause of morbidity and mortality among patients with diabetes. Although a few microRNAs (miRNAs) have been implicated in diabetes-related complications, a functional association between miRNAs and cardiac dysfunction in diabetic cardiomyopathy remains to be demonstrated. Our results show that miR-483-3p is upregulated in streptozotocin-induced diabetic mice, and cultured cardiomyocytes mimicking hyperglycemia. Overexpressing miR-483-3p in transgenic mice with diabetes mellitus (DM) exacerbated cardiomyocyte apoptosis by transcriptionally repressing insulin growth factor 1 (IGF1). Therefore, we have uncovered a novel signaling pathway, involving miR-483-3p-IGF1, that promotes myocardial cell apoptosis under high blood-glucose condition. Further, our study indicates that miR-483-3p could be a potential therapeutic target for managing diabetes-associated heart complications. PMID:27346130

  20. Kinetics of the Reaction of O((sup 3)P) with CF3NO

    NASA Technical Reports Server (NTRS)

    Thorn, R. P.; Nicovich, J. M.; Cronkhite, J. M.; Wine, P. H.

    1997-01-01

    A laser flash photolysis-resonance fluorescence technique has been employed to study the kinetics of the reaction of O((sup 3)P) with CF3NO (k(2)) as a function of temperature. Our results are described by the Arrhenius expression k(2)(T) = (4.54 +/- 0.70) x 10(exp -l2)exp[(-560 +/- 46)/T] cu cm/molecule.s (243 K is less than or equal to T is less than or equal to 424 K); errors are 2 sigma and represent precision only. The O((sup 3)P) + CF3NO reaction is sufficiently rapid that CF3NO cannot be employed as a selective quencher for O2(alpha(1) Delta-g) in laboratory systems where O((sup 3)P) and O2(alpha 1 Delta g) coexist, and where O((sup 3)P) kinetics are being investigated.

  1. Investigation of Structural and Electronic Properties of Zn3P2: Theory and Experiment

    NASA Astrophysics Data System (ADS)

    Kaur, M.; Kabra, K.; Kumar, R.; Sharma, B. K.; Sharma, G.

    2016-06-01

    This paper deals with the structural and electronic properties of the compound Zn3P2. Equilibrium structural properties have been calculated by fitting the energy-volume data to standard equation of state. The theoretical as well as experimental spherically averaged Compton profiles are also determined. The experiment is performed using a 5 Ci 241Am gamma-rays Compton spectrometer, allowing 59.54 keV gamma rays to get scattered by the polycrystalline sample and the corresponding theoretical profiles are obtained from linear combination of atomic orbital method within density functional theory framework. Anisotropy curves using three different directions [100], [110] and [111] are obtained for the compound and an ionic model is also proposed, which supports the transfer of 2.0 electrons from Zn to P atom. At last, equal-valence-electron-density profiles for Zn3P2 and Cd3P2 are presented, confirming more ionic characters in Zn3P2.

  2. Laser gain on 3p-3d and 3s-3p transitions and X-ray line ratios for the nitrogen isoelectronic sequence

    NASA Technical Reports Server (NTRS)

    Feldman, U.; Seely, J. F.; Bhatia, A. K.

    1989-01-01

    Results are presented on calculations of the 72 levels belonging to the 2s(2)2p(3), 2s2p(4), 2p(5), 2s(2)2p(2)3s, 2s(2)2p(2)3p, and 2s(2)2p(2)3d configurations of the N I isoelectronic sequence for the ions Ar XII, Ti XVI, Fe XX, Zn XXIV, and Kr XXX, for electron densities up to 10 to the 24th/cu cm. It was found that large population inversions and gain occur between levels in the 2s(2)2p(2)3p configuration and levels in the 2s(2)2p(2)3d configuration that cannot decay to the ground configuration by an electric dipole transition. For increasing electron densities, the intensities of the X-ray transitions from the 2s(2)2p(2)3p configuration to the ground configuration decrease relative to the transitions from the 2s(2)2p(2)3s and 2s(2)2p(2)3d configurations to the ground configuration. The density dependence of these X-ray line ratios is presented.

  3. Effects of partial anion substitution on the thermoelectric properties of silver(I) chalcogenide halides in the system Ag{sub 5}Q{sub 2}X with Q=Te, Se and S and X=Br and Cl

    SciTech Connect

    Eckstein, Nadine; Nilges, Tom; Decourt, Rodolphe; Bobet, Jean-Louis; Chevalier, Bernard

    2011-04-15

    A selection of mixed conducting silver chalcogenide halides of the general formula Ag{sub 5}Q{sub 2}X with Q=sulfur, selenium and tellurium and X=chlorine and bromine has been investigated due to their thermoelectric properties. Recently, the ternary counterpart Ag{sub 5}Te{sub 2}Cl showed a defined d{sup 10}-d{sup 10} interaction in the disordered cation substructure at elevated temperatures where Ag{sub 5}Te{sub 2}Cl is present in its high temperature {alpha}-phase. A significant drop of the thermal diffusivity has been observed during the {beta}-{alpha} phase transition reducing the values from 0.12 close to 0.08 mm{sup 2} s{sup -1}. At the same transition the thermopower reacts on the increasing silver mobility and jumps towards less negative values. Thermal conductivities, thermopower and thermal diffusivity of selected compounds with various grades of anion substitution in Ag{sub 5}Q{sub 2}X were determined around the silver-order/disorder {beta}-{alpha} phase transition. A formation of attractive interactions could be observed for selenium substituted phases while no effect was detected for bromide and sulfide samples. Depending on the grade and type of substitution the thermopower changes significantly at and after the {beta}-{alpha} phase transition. Thermal conductivities are low reaching values around 0.2-0.3 W m{sup -1} K{sup -1} at 299 K. Partial anion exchange can substantially tune the thermoelectric properties in Ag{sub 5}Q{sub 2}X phases. -- Graphical abstract: A structure section of the {alpha}-Ag{sub 5}Te{sub 2}Cl structure type and the thermopower evolution of Ag{sub 5}Te{sub 2}Cl{sub 0.4}Br{sub 0.6} undergoing a silver ion order/disorder phase transition. Display Omitted Research highlights: > We report on thermoelectric properties of silver(I) chalcogenide halides. > We examine thermopower, thermal diffusivity and thermal behavior. > Silver mobility, phase transitions and order/disorder phenomena are discussed. > Partial anion exchange can

  4. miR-1207-3p Is a Novel Prognostic Biomarker of Prostate Cancer.

    PubMed

    Das, Dibash K; Osborne, Joseph R; Lin, Hui-Yi; Park, Jong Y; Ogunwobi, Olorunseun O

    2016-06-01

    MicroRNAs (miRNAs) have been found to be dysregulated in prostate cancer (PCa). In this study, we investigated if miR-1207-3p is capable of distinguishing between indolent and aggressive PCa and if it contributes to explaining the disproportionate aggressiveness of PCa in men of African ancestry (moAA). A total of 404 patients with primary adenocarcinoma of the prostate were recruited between 1988 and 2003 at the Moffitt Cancer Center, Tampa, FL, USA. Patient clinicopathological features and demographic characteristics such as race were identified. RNA samples from 404 postprostatectomy prostate tumor tissue samples were analyzed by real-time quantitative reverse transcription polymerase chain reaction for the mRNA expression of miR-1207-3p. miR-1207-3p expression in PCa that resulted in overall death or PCa-specific death is significantly higher than in PCa cases that did not. The same positive correlation holds true for other clinical characteristics such as biochemical recurrence, Gleason score, clinical stage, and prostate-specific antigen level. Furthermore, miR-1207-3p expression was significantly less in moAA in comparison to Caucasian men. We also evaluated whether miR-1207-3p is associated with clinical outcomes adjusted for age at diagnosis and tumor stage in the modeling. Using competing risk regression, the PCa patients with a high miR-1207-3p expression (≥6 vs 3) had a high risk to develop PCa recurrence (hazard rate = 2.5, P < .001) adjusting for age at diagnosis and tumor stage. In conclusion, miR-1207-3p is a promising novel prognostic biomarker for PCa. Furthermore, miR-1207-3p may also be important in explaining the disproportionate aggressiveness of PCa in moAA. PMID:27267842

  5. The minimal transactivation region of Saccharomyces cerevisiae Gln3p is localized to 13 amino acids.

    PubMed Central

    Svetlov, V; Cooper, T G

    1997-01-01

    Regulated nitrogen catabolic gene transcription in Saccharomyces cerevisiae is mediated by four positive (Gln3p and Gat1p/Nil1p) and negative (Dal80p/Uga43p and Deh1p/Nil2p/GZF3p) regulators which function in opposition to one another. All four proteins contain GATA-type zinc finger domains, and three of them (Gln3p, Dal80p, and Deh1p) have been shown to bind to GATA sequences situated upstream of genes whose expression is sensitive to nitrogen catabolite repression (NCR). The positive regulators, Gln3p and Gat1p, are able to support transcriptional activation when tethered by LexAp to the promoter of a reporter gene whose upstream activation sequences have been replaced with one or more lexA operator sites. Existing data suggest that these four proteins regulate transcription by competing with one another for binding to the GATA sequences which mediate NCR-sensitive gene expression. We show that the minimal Gln3p domain mediating transcriptional activation consists of 13 amino acids with a predicted propensity to form an alpha-helix. Genetic analysis of this region (Gln3p residues 126 to 138, QQNGEIAQLWDFN) demonstrated that alanine may be substituted for the aromatic and acidic amino acids without destroying transcriptional activation potential. Similar substitution of alanine for the two hydrophobic amino acids, isoleucine and leucine, however, destroys activation, as does introduction of basic amino acids in place of the acidic residues or introduction of proline into the center of the sequence. A point mutation in the Gln3p activation region destroys its in vivo ability to support NCR-sensitive DAL5 expression. We find no convincing evidence that NCR regulates Gln3p function by modulating the functioning of its activation region. PMID:9401021

  6. BOT3P - Bologna Transport Analysis Pre-Post-Processors Version 3.0

    SciTech Connect

    Orsi, Roberto

    2004-02-15

    BOT3P is a set of standard FORTRAN 77 language programs developed at the ENEA-Bologna Nuclear Data Centre. BOT3P Version 1.0 was originally conceived to give the users of the DORT and TORT deterministic transport codes some useful diagnostic tools to prepare and to check their input data files. BOT3P Version 3.0 contains some important additions in the input geometrical model description, such as 'rod' and 'hexagonal' geometrical objects, respecting the exact cross-sectional area value and very suitable to describe a reactor lattice in detail. Moreover, it has extended the possibility to produce the geometrical, material distribution, and fixed neutron source data for the deterministic transport codes TWODANT and THREEDANT of the DANTSYS system and for the PARTISN code too, starting from the same input to BOT3P. When users require X-Y-Z TORT/THREEDANT/PARTISN mesh grids to be generated, BOT3P Version 3.0 produces a geometrical input for the MCNP Monte Carlo transport code also, where the MCNP cells correspond to the X-Y-Z bodies created for TORT.BOT3P Version 3.0 lets users specify areas/volumes of the model where the zone/material distribution can be defined not only by a combinatorial geometry but also by an external source, such as one originated from computerized tomography scan data (only for three-dimensional applications) and from one or more external DORT/TORT input files. BOT3P was developed on a DIGITAL UNIX ALPHA 500/333 workstation and successfully used in some complex neutron shielding and criticality benchmarks. It was also tested on Red Hat Linux 7.1 and is designed to run on most UNIX platforms. All BOT3P versions are publicly available from the Organisation for Economic Co-operation and Development/Nuclear Energy Agency Data Bank (NEA-1627, NEA-1678)

  7. miR-579-3p controls melanoma progression and resistance to target therapy.

    PubMed

    Fattore, Luigi; Mancini, Rita; Acunzo, Mario; Romano, Giulia; Laganà, Alessandro; Pisanu, Maria Elena; Malpicci, Debora; Madonna, Gabriele; Mallardo, Domenico; Capone, Marilena; Fulciniti, Franco; Mazzucchelli, Luca; Botti, Gerardo; Croce, Carlo M; Ascierto, Paolo Antonio; Ciliberto, Gennaro

    2016-08-23

    Therapy of melanoma patients harboring activating mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) oncogene with a combination of BRAF and MEK inhibitors is plagued by the development of drug resistance. Mutational events, as well as adaptive mechanisms, contribute to the development of drug resistance. In this context we uncover here the role of a miRNA, miR-579-3p. We first show that low expression of miR-579-3p is a negative prognostic factor correlating with poor survival. Expression levels of miR-579-3p decrease from nevi to stage III/IV melanoma samples and even further in cell lines resistant to BRAF/MEK inhibitors. Mechanistically, we demonstrate that miR-579-3p acts as an oncosuppressor by targeting the 3'UTR of two oncoproteins: BRAF and an E3 ubiquitin protein ligase, MDM2. Moreover miR-579-3p ectopic expression impairs the establishment of drug resistance in human melanoma cells. Finally, miR-579-3p is strongly down-regulated in matched tumor samples from patients before and after the development of resistance to targeted therapies.

  8. Cu3P/RGO Nanocomposite as a New Anode for Lithium-Ion Batteries

    PubMed Central

    Liu, Shuling; He, Xiaodong; Zhu, Jianping; Xu, Liqiang; Tong, Jianbo

    2016-01-01

    Cu3P/reduced graphene oxide (Cu3P/RGO) nanocomposite was successfully synthesized by a facile one-pot method as an advanced anode material for high-performance lithium-ion batteries. Cu3P nanostructures with a polyhedral shape with the mean diameter (80–100 nm) were homogeneously anchored on the surface of RGO. The flexible RGO sheets acted as elastic buffering layer which not only reduced the volume change, but also prevented the aggregation of Cu3P nanostructures, the cracking and crumbing of electrodes. On the other hand, the presence of Cu3P nanostructures could also avoid the agglomeration of RGO sheets and retain their highly active surface area. Therefore, as an advanced anode material for high-performance lithium-ion batteries, the as-prepared Cu3P/RGO exhibited high capacity of 756.15 mAhg−1 at the current density 500 mAg−1 after 80 cycles, superior cyclic stability and good rate capability. PMID:27725701

  9. Cu3P/RGO Nanocomposite as a New Anode for Lithium-Ion Batteries

    NASA Astrophysics Data System (ADS)

    Liu, Shuling; He, Xiaodong; Zhu, Jianping; Xu, Liqiang; Tong, Jianbo

    2016-10-01

    Cu3P/reduced graphene oxide (Cu3P/RGO) nanocomposite was successfully synthesized by a facile one-pot method as an advanced anode material for high-performance lithium-ion batteries. Cu3P nanostructures with a polyhedral shape with the mean diameter (80–100 nm) were homogeneously anchored on the surface of RGO. The flexible RGO sheets acted as elastic buffering layer which not only reduced the volume change, but also prevented the aggregation of Cu3P nanostructures, the cracking and crumbing of electrodes. On the other hand, the presence of Cu3P nanostructures could also avoid the agglomeration of RGO sheets and retain their highly active surface area. Therefore, as an advanced anode material for high-performance lithium-ion batteries, the as-prepared Cu3P/RGO exhibited high capacity of 756.15 mAhg‑1 at the current density 500 mAg‑1 after 80 cycles, superior cyclic stability and good rate capability.

  10. Yeast Pmp3p has an important role in plasma membrane organization.

    PubMed

    De Block, Julien; Szopinska, Aleksandra; Guerriat, Bérengère; Dodzian, Joanna; Villers, Jennifer; Hochstenbach, Jean-François; Morsomme, Pierre

    2015-10-01

    Pmp3p-related proteins are highly conserved proteins that exist in bacteria, yeast, nematodes and plants, and its transcript is regulated in response to abiotic stresses, such as low temperature or high salinity. Pmp3p was originally identified in Saccharomyces cerevisiae, and it belongs to the sensitive to Na(+) (SNA)-protein family, which comprises four members--Pmp3p/Sna1p, Sna2p, Sna3p and Sna4p. Deletion of the PMP3 gene conferred sensitivity to cytotoxic cations, whereas removal of the other SNA genes did not lead to clear phenotypic effects. It has long been believed that Pmp3p-related proteins have a common and important role in the modulation of plasma membrane potential and in the regulation of intracellular ion homeostasis. Here, we show that several growth phenotypes linked to PMP3 deletion can be modulated by the removal of specific genes involved in sphingolipid synthesis. These genetic interactions, together with lipid binding assays and epifluorescence microscopy, as well as other biochemical experiments, suggest that Pmp3p could be part of a phosphoinositide-regulated stress sensor. PMID:26303201

  11. Endoplasmic Reticulum PI(3)P lipid binding targets malaria proteins to the host cell

    PubMed Central

    Bhattacharjee, Souvik; Stahelin, Robert V.; Speicher, Kaye D.; Speicher, David W.; Haldar, Kasturi

    2011-01-01

    SUMMARY Hundreds of effector proteins of the human malaria parasite Plasmodium falciparum constitute a `secretome', carrying a host-targeting (HT) signal, which predicts their export from the intracellular pathogen into the surrounding erythrocyte. Cleavage of the HT signal by a parasite endoplasmic reticulum (ER) protease, plasmepsin V, is the proposed export mechanism. Here we show that the HT signal exports by recognition of the lipid phosphatidylinositol-3-phosphate (PI(3)P) in the ER, prior to and independent of protease action. Secretome HT signals, including those of major virulence determinants bind PI(3)P with nanomolar affinity and amino acid specificities displayed by HT-mediated export. PI(3)P-enriched regions are detected within the parasite's ER, co-localize with endogenous HT signal on ER precursors, which also display high affinity binding to PI(3)P. A related, pathogenic oomycete's HT signal export is dependent on PI(3)P binding, without cleavage by plasmepsin V. Thus PI(3)P in the ER functions in mechanisms of secretion and pathogenesis. PMID:22265412

  12. Outcomes in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with isolated deletion 5q treated with lenalidomide: a subset analysis from the MDS-004 study

    PubMed Central

    Giagounidis, Aristoteles; Mufti, Ghulam J; Mittelman, Moshe; Sanz, Guillermo; Platzbecker, Uwe; Muus, Petra; Selleslag, Dominik; Beyne-Rauzy, Odile; te Boekhorst, Peter; del Cañizo, Consuelo; Guerci-Bresler, Agnès; Nilsson, Lars; Lübbert, Michael; Quesnel, Bruno; Ganser, Arnold; Bowen, David; Schlegelberger, Brigitte; Göhring, Gudrun; Fu, Tommy; Benettaib, Bouchra; Hellström-Lindberg, Eva; Fenaux, Pierre

    2014-01-01

    Objective A subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System (IPSS)-defined Low-/Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) with isolated del(5q). Methods Patients received lenalidomide 10 mg/d (days 1–21; n = 47) or 5 mg/d (days 1–28; n = 43) on 28-d cycles or placebo (n = 45). From the placebo and lenalidomide 5 mg groups, 84% and 58% of patients, respectively, crossed over to lenalidomide 5 or 10 mg at 16 wk, respectively. Results Rates of red blood cell-transfusion independence (RBC-TI) ≥182 d were higher in the lenalidomide 10 mg (57.4%; P < 0.0001) and 5 mg (37.2%; P = 0.0001) groups vs. placebo (2.2%). Cytogenetic response rates (major + minor responses) were 56.8% (P < 0.0001), 23.1% (P = 0.0299) and 0%, respectively. Two-year cumulative risk of acute myeloid leukaemia progression was 12.6%, 17.4% and 16.7% in the lenalidomide 10 mg, 5 mg, and placebo groups, respectively. In a 6-month landmark analysis, overall survival was longer in lenalidomide-treated patients with RBC-TI ≥182 d vs. non-responders (P = 0.0072). The most common grade 3–4 adverse event was myelosuppression. Conclusions These data support the clinical benefits and acceptable safety profile of lenalidomide in transfusion-dependent patients with IPSS-defined Low-/Int-1-risk MDS with isolated del(5q). PMID:24813620

  13. Genetic epidemiology of Paget's disease of bone in italy: sequestosome1/p62 gene mutational test and haplotype analysis at 5q35 in a large representative series of sporadic and familial Italian cases of Paget's disease of bone.

    PubMed

    Falchetti, Alberto; Di Stefano, Marco; Marini, Francesca; Ortolani, Sergio; Ulivieri, Massimo Fabio; Bergui, Simona; Masi, Laura; Cepollaro, Chiara; Benucci, Maurizio; Di Munno, Ombretta; Rossini, Maurizio; Adami, Silvano; Del Puente, Antonio; Isaia, Giancarlo; Torricelli, Francesca; Brandi, Maria Luisa

    2009-01-01

    Families affected by Paget's disease of bone frequently harbor mutations in the SQSTM1/p62 gene. In this multicentric study we collected 345 sporadic and 12 familial PDB cases throughout Italy, identifying 12 different mutations, 5 of which are newly reported and 3, D335E, A381V, and Y383X, external to the UBA domain. Subjects with truncating mutations, E396X, showed a significantly younger age at clinical diagnosis, while the Y383X subjects had a higher average number of affected skeletal sites. All the mutants exhibited the CGTG-H2 haplotype. In two pairs and one triad of unrelated Italian PDB families from different Italian regions, we detected a common SQSTM1/p62 mutation for each P392L, M404V, and G425R group. Since the CGTG-H2 haplotype frequency was also high in normal subjects, and genetic influence due to migratory fluxes of different ethnic groups exists in the Italian population, to refine the search for a more geographically specific founder effect, we extended the haplotype analysis in these families using polymorphic microsatellite repeat markers, within and flanking the SQSTM1/p62 locus, from chromosome 5q35, other than the exon 6 and 3'UTR polymorphisms. All mutant carriers from two of the three M404V families and from the G425R families exhibited common extended chromosome 5q35 haplotypes, IT01 and IT02, respectively, which may be reflecting influences of past migrations. This may be helpful in estimating the true rate of de novo mutations. We confirm the data on the existence of both a mutational hotspot at the UBA domain of SQSTM1/p62 and a founder effect in the PDB population.

  14. Transduction of Recombinant M3-p53-R12 Protein Enhances Human Leukemia Cell Apoptosis

    PubMed Central

    Lu, Tsung Chi; Zhao, Guan- Hao; Chen, Yao Yun; Chien, Chia-Ying; Huang, Chi-Hung; Lin, Kwang Hui; Chen, Shen Liang

    2016-01-01

    Tumor suppressor protein p53 plays important roles in initiating cell cycle arrest and promoting tumor cell apoptosis. Previous studies have shown that p53 is either mutated or defective in approximately 50% of human cancers; therefore restoring normal p53 activity in cancer cells might be an effective anticancer therapeutic approach. Herein, we designed a chimeric p53 protein flanked with the MyoD N-terminal transcriptional activation domain (amino acids 1-62, called M3) and a poly-arginine (R12) cell penetrating signal in its N-and C-termini respectively. This chimeric protein, M3-p53-R12, can be expressed in E. coli and purified using immobilized metal ion chromatography followed by serial refolding dialysis. The purified M3-p53-R12 protein retains DNA-binding activity and gains of cell penetrating ability. Using MTT assay, we demonstrated that M3-p53-R12 inhibited the growth of K562, Jurkat as well as HL-60 leukemia cells carrying mutant p53 genes. Results from FACS analysis also demonstrated that transduction of M3-p53-R12 protein induced cell cycle arrest of these leukemia cells. Of special note, M3-p53-R12 has no apoptotic effect on normal mesenchymal stem cells (MSC) and leukocytes, highlighting its differential effects on normal and tumor cells. To sum up, our results reveal that purified recombinant M3-p53-R12 protein has functions of suppressing the leukemia cell lines' proliferation and launching cell apoptosis, suggesting the feasibility of using M3-p53-R12 protein as an anticancer drug. In the future we will test whether this chimeric protein can preferentially trigger the death of malignant cancer cells without affecting normal cells in animals carrying endogenous or xenographic tumors. PMID:27390612

  15. Zn3P2 and Cu2O Substrates for Solar Energy Conversion

    NASA Astrophysics Data System (ADS)

    Kimball, Gregory Michael

    Zinc phosphide (Zn3P2) and cuprous oxide (Cu 2O) are promising and earth-abundant alternatives to traditional thin film photovoltaics materials such as CIGS, CdTe, and a-Si. We have prepared high purity substrates of Zn3P2 from elemental zinc and phosphorus, and Cu2O by the thermal oxidation of copper foils, to investigate their fundamental material properties and potential for solar energy conversion. Photoluminescence-based measurements of Zn3P2 substrates have revealed a fundamental indirect band gap at 1.38 eV and a direct band gap at 1.50 eV, with time-resolved data indicating minority carrier diffusion lengths of ≥7 μm. Solar cells based on Mg/Zn3P2 junctions with solar energy conversion efficiency reaching 4.5% were examined by composition profiling to elucidate the passivation reaction between Mg metal and Zn3P2 surfaces. Semiconductor/liquid junctions incorporating Cu2O substrates exhibited open-circuit voltage, Voc, values in excess of 800 mV and internal quantum yields approaching 100% in the 400-500 nm spectral range.

  16. The actin-related protein Act3p of Saccharomyces cerevisiae is located in the nucleus.

    PubMed Central

    Weber, V; Harata, M; Hauser, H; Wintersberger, U

    1995-01-01

    Actin-related proteins, a group of protein families that exhibit about 50% sequence identity among each other and to conventional actin, have been found in a variety of eukaryotic organisms. In the budding yeast Saccharomyces cerevisiae, genes for one conventional actin (ACT1) and for three actin-related proteins (ACT2, ACT3, and ACT5) are known. ACT3, which we recently discovered, is an essential gene coding for a polypeptide of 489 amino acids (Act3p), with a calculated molecular mass of 54.8 kDa. Besides its homology to conventional actin, Act3p possesses a domain exhibiting weak similarity to the chromosomal protein HMG-14 as well as a potential nuclear localization signal. An antiserum prepared against a specific segment of the ACT3 gene product recognizes a polypeptide band of approximately 55 kDa in yeast extract. Indirect immunofluorescence experiments with this antiserum revealed that Act3p is located in the nucleus. Nuclear staining was observed in all cells regardless of the stage of the cell cycle. Independently, immunoblotting experiments with subcellular fractions showed that Act3p is indeed highly enriched in the nuclear fraction. We suggest that Act3p is an essential constituent of yeast chromatin. Images PMID:8573785

  17. Activation energies for addition of O/3P/ to simple olefins.

    NASA Technical Reports Server (NTRS)

    Demore, W. B.

    1972-01-01

    Description of relative rate measurements for the addition of O(3P) to C2H4, C2F4, C3H6, and C4H8-1 in liquid argon at 87.5 K. The data strongly indicate that the activation energies for the addition of O(3P) to the double bonds of propylene and butene-1 are identical, probably to within 0.1 kcal/mole. It is very doubtful that differences in pre-exponential factors or other factors such as solvent effects, could invalidate this conclusion. A similar argument holds for the C2H4 and C2F4 reactions. Furthermore, the experiments suggest that the activation energy for addition of O(3P) to the double bond of butene-1 is about 0.1 kcal/mole.

  18. Magnetic trapping of Yb in the metastable {sup 3}P{sub 2} state

    SciTech Connect

    Pandey, Kanhaiya; Rathod, K. D.; Pal, Sambit Bikas; Natarajan, Vasant

    2010-03-15

    We report magnetic trapping of Yb in the excited {sup 3}P{sub 2} state. This state, with a lifetime of 15 s, could play an important role in studies ranging from optical clocks and quantum computation to the search for a permanent electric dipole moment. Yb atoms are first cooled and trapped in the ground state in a 399-nm magneto-optic trap. The cold atoms are then pumped into the excited state by driving the {sup 1}S{sub 0{yields}}{sup 3}P{sub 1{yields}}{sup 3}S{sub 1} transition. Atoms in the {sup 3}P{sub 2} state are magnetically trapped in a spherical quadrupole field with an axial gradient of 110 G/cm. We trap up to 10{sup 6} atoms with a lifetime of 1.5 s.

  19. Experimental and theoretical study of 3p photoionization and subsequent Auger decay in atomic chromium

    NASA Astrophysics Data System (ADS)

    Keskinen, J.; Huttula, S.-M.; Mäkinen, A.; Patanen, M.; Huttula, M.

    2015-12-01

    3p photoionization and subsequent low kinetic energy Coster-Kronig and super Coster-Kronig Auger decay have been studied in atomic chromium. The binding energies, line widths, and relative intensities for the transitions seen in the synchrotron radiation excited 3p photoelectron spectrum are determined. The high resolution M2,3 M4,5 M4,5 and M2,3 M4,5 N1 Auger electron spectra following the electron impact excited 3p ionization are presented and the kinetic energies, relative intensities, and identifications are given for the main lines. The experimental findings are compared with the theoretical predictions obtained from Hartree-Fock and multiconfiguration Dirac-Fock approaches.

  20. Rate constant for the reaction of O(3P) with diacetylene from 210 to 423 K

    NASA Technical Reports Server (NTRS)

    Mitchell, M. B.; Nava, D. F.; Stief, L. J.

    1986-01-01

    The absolute rate constant for the reaction of O(3P) with diacetylene (C4H2) has been measured as a function of pressure and temperature by the flash-photolysis/resonance-fluorescence method. At 298 K and below, no pressure dependence of the rate constant was observed, but at 423 K a moderate (factor-of-2) increase was detected in the range 3 to 75 torr Ar.Results at or near the high-pressure limit are represented by an Arrhenius expression over the temperature range 210 to 423 K. The results are compared with previous determinations, all of which employed the discharge-flow/mass-spectrometry technique. The mechanism of the reaction is considered, including both primary and secondary processes. The heats of formation of the reactants, adducts, and products for the O(3P) + C4H2 reaction are discussed and contrasted with those for O(3P) + C2H2.

  1. BOREAS Level-3p Landsat TM Imagery: Geocoded and Scaled At-sensor Radiance

    NASA Technical Reports Server (NTRS)

    Nickeson, Jaime; Knapp, David; Newcomer, Jeffrey A.; Hall, Forrest G. (Editor); Cihlar, Josef

    2000-01-01

    For BOReal Ecosystem-Atmosphere Study (BOREAS), the level-3p Landsat Thematic Mapper (TM) data were used to supplement the level-3s Landsat TM products. Along with the other remotely sensed images, the Landsat TM images were collected in order to provide spatially extensive information over the primary study areas. This information includes radiant energy, detailed land cover, and biophysical parameter maps such as Fraction of Photosynthetically Active Radiation (FPAR) and Leaf Area Index (LAI). Although very similar to the level-3s Landsat TM products, the level-3p images were processed with ground control information, which improved the accuracy of the geographic coordinates provided. Geographically, the level-3p images cover the BOREAS Northern Study Area (NSA) and Southern Study Area (SSA). Temporally, the four images cover the period of 20-Aug-1988 to 07-Jun-1994. Except for the 07-Jun-1994 image, which contains seven bands, the other three contain only three bands.

  2. Intellectual disability, muscle weakness and characteristic face in three siblings: A newly described recessive syndrome mapping to 3p24.3-p25.3.

    PubMed

    Kariminejad, Ariana; Nafissi, Shahriar; Nilipoor, Yalda; Tavasoli, Alireza; Van Veldhoven, Paul P; Bonnard, Carine; Ng, Yeng Ting; Majoie, Charles B; Reversade, Bruno; Hennekam, Raoul C

    2015-11-01

    We report on a sister and two brothers born to healthy Iranian parents with mild intellectual disability, progressive muscle weakness, and characteristic facies. including highly arched eyebrows, down-slanting palpebral fissures, prominent nasal bridge, prominent nose, columella extending below alae nasi, narrow mouth, narrow palate, and dental caries, and in one of them an inability to abduct the left eye. Electrophysiological studies showed signs of myopathy, and muscle biopsies demonstrated only nonspecific signs. Brain MRIs in two of the sibs showed leukencephalopathy with delayed myelination, frontal and parietal hyperintensities, and hippocampal atrophy in one. We have been unable to find a description of this association of features in literature. Based on the occurrence in siblings, no significant difference in phenotype between the brothers and sister, absence of manifestations in parents, and a likely consanguinity between parents we performed a homozygosity mapping. A single identical-by-descent bloc encompassing 57 genes located at 3p24.3-p25.3 was found to segregate within the family with this phenotype. © 2015 Wiley Periodicals, Inc.

  3. Angle-resolved photoemission extended fine structure of the Ni 3p, Cu 3s, and Cu 3p core levels of the respective clean (111) surfaces

    SciTech Connect

    Huff, W.R. |; Chen, Y.; Kellar, S.A.; Moler, E.J. |; Hussain, Z.; Huang, Z.Q.; Zheng, Y.; Shirley, D.A.

    1997-07-01

    We report a non-s initial-state angle-resolved photoemission extended fine-structure (ARPEFS) study of clean surfaces for the purpose of further understanding the technique. The surface structure sensitivity of ARPEFS applied to clean surfaces and to arbitrary initial states is studied using normal photoemission data taken from the Ni 3p core levels of a Ni(111) single crystal and the Cu 3s and the Cu 3p core levels of a Cu(111) single crystal. The Fourier transforms of these clean surface data are dominated by backscattering. Unlike the s initial-state data, the p initial-state data show a peak in the Fourier transform corresponding to in-plane scattering from the six nearest neighbors to the emitter. Evidence was seen for single-scattering events from the same plane as the emitters and double-scattering events. Using a recently developed, multiple-scattering calculation program, ARPEFS data from clean surfaces and from p initial states can be modeled to high precision. Although there are many layers of emitters when measuring photoemission from a clean surface, test calculations show that the ARPEFS signal is dominated by photoemission from atoms in the first two crystal layers. Thus ARPEFS applied to clean surfaces is sensitive to surface reconstruction. The best-fit calculation for clean Ni(111) indicates an expansion of the first two layers. {copyright} {ital 1997} {ital The American Physical Society}

  4. Synthesis and Structural Analysis of Pure and Mixed Zirconium Phosphonates, Zr(O 3P R) x(O 3P R') 2- x

    NASA Astrophysics Data System (ADS)

    Rosenthal, Guy L.; Caruso, James

    1993-12-01

    Several zirconium phosphonates, Zr(O 3P R) 2 ( R = (CH 2) 3COOH, CH 2C 6H 5, (CH 2) 2Cl, CHCH 2, (CH 2) 2CHCH 2), containing reactive functional groups were synthesized and structurally characterized. There were found to be nonreactive toward incorporation of small molecules and ions from solution. In an effort to synthesize microporous phosphonates, mixed phosphonates of composition Zr(O 3PCH 2C 6H 5) x(O 3PCH 3) 2- x and Zr(O 3P(CH 2) 3COOH) x(O 3POH) 2- x were prepared, varying x from 0 to 2. The interlayer spacings of the benzyl/methyl derivatives indicated a random distribution of the alkyl moieties throughout the interlayer galleries, resulting in relatively porous materials. The observed interlayer spacings of the 3-carboxypropyl/hydroxyl materials indicated products in which the alkyl groups were segregated, resulting in less porosity. A structural model for porous and nonporous materials is discussed.

  5. Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up.

    PubMed Central

    Thompson, A. M.; Crichton, D. N.; Elton, R. A.; Clay, M. F.; Chetty, U.; Steel, C. M.

    1998-01-01

    Molecular and immunohistochemical studies of genetic events on chromosome 17p were prospectively compared with conventional clinical and pathological parameters and disease behaviour at a minimum of 72 months follow-up. In a series of 91 patients with primary operable breast cancer, 37 out of 91 (41%) patients had disease relapse and 23 out of 91 (25%) had died during the follow-up period. Allelic imbalance at the YNZ22 locus (17p13.3), demonstrated in 33 out of 63 (52%) informative patients, was significantly associated with disease recurrence (P < 0.01, 2 d.f. Cox analysis) and showed a trend towards impaired survival (P = 0.08, 2 d.f. Cox analysis) after a mean follow-up of 84 months for survivors. By contrast, p53 mutation (in 10 out of 60, 17% of cancers), p53 allelic imbalance (in 23 out of 56, 41% informative patients), p53 mRNA expression (in 47 out of 87, 54% patients), p53 mRNA overexpression (in 24 out of 87, 28%) or p53 protein expression (detected in 25/76, 32%) were not associated with disease behaviour. There was no significant association between allelic imbalance at YNZ22 and any abnormality of p53 DNA, RNA or protein. Allelic imbalance at 17p13.3 (YNZ22) serves as a marker of poor prognosis in breast cancer. As yet unidentified genes on 17p13.3, distinct from and telomeric to p53, are therefore likely to be of clinical importance in breast cancer. PMID:9514060

  6. On the mechanism of populating 3p levels of neon under pumping by a hard ioniser

    SciTech Connect

    Khasenov, M U

    2011-03-31

    The effect of quenching additives on the luminescence properties of helium - neon mixtures under pumping by {alpha} particles emitted from {sup 210}Po atoms is considered. It is concluded that, under excitation by a heavy charged particle, the population of the 3p'[1/2]{sub 0} level of neon is not related to the dissociative recombination of molecular ions. It is suggested that the most likely channels for populating the 3p level are the excitation transfer from metastable helium atoms to neon atoms and direct excitation of neon by nuclear particles and secondary electrons. (lasers and active media)

  7. Reactions of atomic oxygen (O/3P/) with various polymer films

    NASA Technical Reports Server (NTRS)

    Golub, Morton A.; Wydeven, Theodore

    1988-01-01

    An attempt is made to obtain the etch rates for various polymer films exposed to O(3P) downstream from, and out of the glow of, the O2 plasma. These rates are compared with published values from the following sources: etching in the glow of an O2 plasma, the Space Shuttle STS-8 flight experiment, and beam experiments. The etch rate data for Kapton fit a logarithmic plot (with a positive slope) of the reaction probability versus O(3P) impact energy.

  8. Excitation of the 3p states in electron-sodium scattering at intermediate energies

    SciTech Connect

    Kamali, M. Z. M.; Wong, B. R.; Chin, J. H.; Ratnavelu, K.

    2014-03-05

    A coupled-channel-optical method (CCOM), to investigate the excitation of the 3p states for e{sup −}-Na scattering at intermediate energies, is reported. Nine atomic states( Na(3s), Na(3p), Na(4s), Na(3d), Na(4p), Na(5s), Na(4d), Na(5p), Na(5d) ) together with three optical potentials are used in this work. The inelastic differential cross sections (DCS) as well as the reduced Stokes parameters are compared with latest theoretical data and experimental measurements.

  9. Toward a 3-P Model of Workplace Learning: A Literature Review

    ERIC Educational Resources Information Center

    Tynjala, Paivi

    2013-01-01

    The interest in research focusing on learning taking place at work, through work and for work has considerably increased over the past two decades. The purpose of the paper is to review and structure this wide and diverse research field. A tentative holistic model--the 3-P model of workplace learning--is presented, in relation to which the…

  10. The 3P0-VERSUS 3S1-MODELS for Quark-Antiquark Annihilation

    NASA Astrophysics Data System (ADS)

    Green, A. M.; Niskanen, J. A.

    A comparison is made between the 3S1- and 3P0-models for quark-antiquark annihilation or creation. Even though the former appears, at first sight, to be superior for Nbar {N} annihilation into two mesons, it is argued from their effects in meson decays that this conclusion is premature.

  11. Repumping of ultracold strontium atoms using the ^3P2 - ^3D2 transition

    NASA Astrophysics Data System (ADS)

    Mickelson, P. G.; Martinez de Escobar, Y. N.; Traverso, A. J.; Killian, T. C.

    2008-05-01

    We discuss recent experiments involving ultracold strontium. Using a commercially-available 3 micron laser, we repump atoms out of the ^3P2 level via the ^3D2 state and gain almost a factor of 10 in the number of atoms in our system. This increase in the signal-to-noise ratio enables improved spectroscopy of strontium in our optical trap.

  12. Muenke Syndrome Mutation, FgfR3P244R, Causes TMJ Defects

    PubMed Central

    Yasuda, T.; Nah, H.D.; Laurita, J.; Kinumatsu, T.; Shibukawa, Y.; Shibutani, T.; Minugh-Purvis, N.; Pacifici, M.; Koyama, E.

    2012-01-01

    Muenke syndrome is characterized by various craniofacial deformities and is caused by an autosomal-dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3P250R). Here, using mice carrying a corresponding mutation (FgfR3P244R), we determined whether the mutation affects temporomandibular joint (TMJ) development and growth. In situ hybridization showed that FgfR3 was expressed in condylar chondroprogenitors and maturing chondrocytes that also expressed the Indian hedgehog (Ihh) receptor and transcriptional target Patched 1(Ptch1). In FgfR3P244R mutants, the condyles displayed reduced levels of Ihh expression, H4C-positive proliferating chondroprogenitors, and collagen type II- and type X-expressing chondrocytes. Primary bone spongiosa formation was also disturbed and was accompanied by increased osteoclastic activity and reduced trabecular bone formation. Treatment of wild-type condylar explants with recombinant FGF2/FGF9 decreased Ptch1 and PTHrP expression in superficial/polymorphic layers and proliferation in chondroprogenitors. We also observed early degenerative changes of condylar articular cartilage, abnormal development of the articular eminence/glenoid fossa in the TMJ, and fusion of the articular disc. Analysis of our data indicates that the activating FgfR3P244R mutation disturbs TMJ developmental processes, likely by reducing hedgehog signaling and endochondral ossification. We suggest that a balance between FGF and hedgehog signaling pathways is critical for the integrity of TMJ development and for the maintenance of cellular organization. PMID:22622662

  13. Absolute cross section for photoionization of Mn+ in the 3p region

    NASA Astrophysics Data System (ADS)

    Kjeldsen, H.; Folkmann, F.; Kristensen, B.; West, J. B.; Hansen, J. E.

    2004-03-01

    The absolute cross section for photoionization of Mn+ has been measured using the merged-beam technique, focusing on the region of the 'giant' 3p rarr 3d resonance. The main discrepancy between theory and earlier experiments has been removed. However, more extensive relativistic calculations are required for a rigorous comparison with theory.

  14. Collisional stability of localized Yb(3P2) atoms immersed in a Fermi sea of Li

    NASA Astrophysics Data System (ADS)

    Konishi, Hideki; Schäfer, Florian; Ueda, Shinya; Takahashi, Yoshiro

    2016-10-01

    We establish an experimental method for a detailed investigation of inelastic collisional properties between ytterbium (Yb) in the metastable {}3{{{P}}}2 state and ground state lithium (Li). By combining an optical lattice and a direct excitation to the {}3{{{P}}}2 state we achieve high selectivity on the collisional partners. Using this method we determine inelastic loss coefficients in collisions between 174Yb({}3{{{P}}}2) with magnetic sublevels of m J = 0 and ‑2 and ground state 6Li to be (4.4+/- 0.3)× {10}-11 {{cm}}3 {{{s}}}-1 and (4.7+/- 0.8)× {10}-11 {{cm}}3 {{{s}}}-1, respectively. Absence of spin changing processes in Yb({}3{{{P}}}2)–Li inelastic collisions at low magnetic fields is confirmed by inelastic loss measurements on the m J = 0 state. We also demonstrate that our method allows us to look into loss processes in few-body systems separately.

  15. MicroRNA-142-3p Negatively Regulates Canonical Wnt Signaling Pathway

    PubMed Central

    Hu, Tanyu; Phiwpan, Krung; Guo, Jitao; Zhang, Wei; Guo, Jie; Zhang, Zhongmei; Zou, Mangge; Zhang, Xuejie; Zhang, Jianhua

    2016-01-01

    Wnt/β-catenin signaling pathway plays essential roles in mammalian development and tissue homeostasis. MicroRNAs (miRNAs) are a class of regulators involved in modulating this pathway. In this study, we screened miRNAs regulating Wnt/β-catenin signaling by using a TopFlash based luciferase reporter. Surprisingly, we found that miR-142 inhibited Wnt/β-catenin signaling, which was inconsistent with a recent study showing that miR-142-3p targeted Adenomatous Polyposis Coli (APC) to upregulate Wnt/β-catenin signaling. Due to the discordance, we elaborated experiments by using extensive mutagenesis, which demonstrated that the stem-loop structure was important for miR-142 to efficiently suppress Wnt/β-catenin signaling. Moreover, the inhibitory effect of miR-142 relies on miR-142-3p rather than miR-142-5p. Further, we found that miR-142-3p directly modulated translation of Ctnnb1 mRNA (encoding β-catenin) through binding to its 3’ untranslated region (3’ UTR). Finally, miR-142 was able to repress cell cycle progression by inhibiting active Wnt/β-catenin signaling. Thus, our findings highlight the inhibitory role of miR-142-3p in Wnt/β-catenin signaling, which help to understand the complex regulation of Wnt/β-catenin signaling. PMID:27348426

  16. Canine-origin G3P[3] rotavirus strain in child with acute gastroenteritis.

    PubMed

    De Grazia, Simona; Martella, Vito; Giammanco, Giovanni M; Gòmara, Miren Iturriza; Ramirez, Stefania; Cascio, Antonio; Colomba, Claudia; Arista, Serenella

    2007-07-01

    Infection by an animal-like strain of rotavirus (PA260/97) was diagnosed in a child with gastroenteritis in Palermo, Italy, in 1997. Sequence analysis of VP7, VP4, VP6, and NSP4 genes showed resemblance to a G3P[3] canine strain identified in Italy in 1996. Dogs are a potential source of human viral pathogens. PMID:18214189

  17. Transition probabilities for the 3s2 3p(2P0)-3s3p2(4P) intersystem lines of Si II

    NASA Technical Reports Server (NTRS)

    Calamai, Anthony G.; Smith, Peter L.; Bergeson, S. D.

    1993-01-01

    Intensity ratios of lines of the spin-changing 'intersystem' multiplet of S II (4P yields 2P0) at 234 nm have been used to determine electron densities and temperatures in a variety of astrophysical environments. However, the accuracy of these diagnostic calculations have been limited by uncertainties associated with the available atomic data. We report the first laboratory measurement, using an ion-trapping technique, of the radiative lifetimes of the three metastable levels of the 3s3p2 4P term of Si II. Our results are 104 +/- 16, 406 +/- 33, and 811 +/- 77 micro-s for lifetimes of the J = 1/2, 5/2, and 3/2 levels, respectively. A-values were derived from our lifetimes by use of measured branching fractions. Our A-values, which differ from calculated values by 30 percent or more, should give better agreement between modeled and observed Si II line ratios.

  18. FIRST DETECTION OF [C I] {sup 3}P{sub 1}–{sup 3}P{sub 0} EMISSION FROM A PROTOPLANETARY DISK

    SciTech Connect

    Tsukagoshi, Takashi; Momose, Munetake; Saito, Masao; Kitamura, Yoshimi; Shimajiri, Yoshito

    2015-03-20

    We performed single point [C i] {sup 3}P{sub 1}–{sup 3}P{sub 0} and CO J = 4–3 observations toward three T Tauri stars (TTSs), DM Tau, LkCa 15, and TW Hya, using the Atacama Large Millimeter/submillimeter Array Band 8 qualification model receiver installed on the Atacama Submillimeter Telescope Experiment. Two protostars (PSs) in the Taurus L1551 region, L1551 IRS 5 and HL Tau, were also observed. We successfully detected [C i] emission from the protoplanetary disk around DM Tau as well as the protostellar targets. The spectral profile of the [C i] emission from the protoplanetary disk is marginally single-peaked, suggesting that atomic carbon (C) extends toward the outermost disk. The detected [C i] emission is optically thin and the column densities of C are estimated to be ≲10{sup 16} and ∼10{sup 17} cm{sup −2} for the TTS targets and the PSs, respectively. We found a clear difference in the total mass ratio of C to dust, M(C)/M(dust), between the TTSs and protostellar targets; the M(C)/M(dust) ratio of the TTSs is one order of magnitude smaller than that of the PSs. The decrease of the estimated M(C)/M(dust) ratios for the disk sources is consistent with a theoretical prediction that the atomic C can survive only in the near surface layer of the disk and C{sup +}/C/CO transition occurs deeper into the disk midplane.

  19. Multiplexed photoionization mass spectrometry investigation of the O(3P) + propyne reaction

    DOE PAGES

    Savee, John D.; Borkar, Sampada; Welz, Oliver; Sztaray, Balint; Taatjes, Craig A.; Osborn, David L.

    2015-05-18

    Here, the reaction of O(3P) + propyne (C3H4) was investigated at 298 K and 4 Torr using time-resolved multiplexed photoionization mass spectrometry and a synchrotron-generated tunable vacuum ultraviolet light source. The time-resolved mass spectra of the observed products suggest five major channels under our conditions: C2H3 + HCO, CH3 + HCCO, H + CH3CCO, C2H4 + CO, and C2H2 + H2 + CO. The relative branching ratios for these channels were found to be 1.00, (0.35 ± 0.11), (0.18 ± 0.10), (0.73 ± 0.27), and (1.31 ± 0.62). In addition, we observed signals consistent with minor production of C3H3 +more » OH and H2 + CH2CCO, although we cannot conclusively assign them as direct product channels from O(3P) + propyne. The direct abstraction mechanism plays only a minor role (≤1%), and we estimate that O(3P) addition to the central carbon of propyne accounts for 10% of products, with addition to the terminal carbon accounting for the remaining 89%. The isotopologues observed in experiments using d1-propyne (CH3CCD) and analysis of product branching in light of previously computed stationary points on the singlet and triplet potential energy surfaces (PESs) relevant to O(3P) + propyne suggest that, under our conditions, (84 ± 14)% of the observed product channels from O(3P) + propyne result from intersystem crossing from the initial triplet PES to the lower-lying singlet PES.« less

  20. Ady3p links spindle pole body function to spore wall synthesis in Saccharomyces cerevisiae.

    PubMed Central

    Nickas, Mark E; Neiman, Aaron M

    2002-01-01

    Spore formation in Saccharomyces cerevisiae requires the de novo synthesis of prospore membranes and spore walls. Ady3p has been identified as an interaction partner for Mpc70p/Spo21p, a meiosis-specific component of the outer plaque of the spindle pole body (SPB) that is required for prospore membrane formation, and for Don1p, which forms a ring-like structure at the leading edge of the prospore membrane during meiosis II. ADY3 expression has been shown to be induced in midsporulation. We report here that Ady3p interacts with additional components of the outer and central plaques of the SPB in the two-hybrid assay. Cells that lack ADY3 display a decrease in sporulation efficiency, and most ady3Delta/ady3Delta asci that do form contain fewer than four spores. The sporulation defect in ady3Delta/ady3Delta cells is due to a failure to synthesize spore wall polymers. Ady3p forms ring-like structures around meiosis II spindles that colocalize with those formed by Don1p, and Don1p rings are absent during meiosis II in ady3Delta/ady3Delta cells. In mpc70Delta/mpc70Delta cells, Ady3p remains associated with SPBs during meiosis II. Our results suggest that Ady3p mediates assembly of the Don1p-containing structure at the leading edge of the prospore membrane via interaction with components of the SPB and that this structure is involved in spore wall formation. PMID:11973299

  1. BOT3P: Bologna Transport Analysis Pre-Post-Processors Version 1.0

    SciTech Connect

    Orsi, Roberto

    2002-11-15

    BOT3P is a set of standard FORTRAN 77 language programs that were developed at the ENEA-Bologna Nuclear Data Centre. BOT3P aims to give the users of the DORT and TORT deterministic transport codes some useful diagnostic tools to prepare and to check their input data files. It also includes some plotting programs that can be employed both as preprocessors and as postprocessors of a transport analysis. The BOT3P plotting programs use the RSCORS Graphics System subroutines, included in the DOORS-3.3 and earlier software package together with the Oak Ridge National Laboratory DORT and TORT transport codes.BOT3P was developed on a DIGITAL UNIX ALPHA 500/333 workstation and successfully used in some complex applications such as the VENUS-1 and VENUS-3 neutron shielding benchmarks. BOT3P was tested on an IBM RS/6000 workstation also and is designed to run on most UNIX platforms.The following programs are included in the package: GGDM, DDM, GGTM, DTM2, DTM3, and RVARSCL. GGDM and GGTM generate the geometrical and material entries for DORT and TORT, respectively. DDM is a DORT graphics pre/post processor. DTM2 and DTM3 are graphics pre/post processors showing cuts and three-dimensional views of the TORT model, respectively. RVARSCL reads DORT/TORT 'VARSCL' sequential format files and selects and writes the data required by the user in new files to be visualized by DDM, DTM2, and DTM3 as postprocessor applications.The package is publicly available from the Organization for Economic Cooperation and Development/Nuclear Energy Agency Data Bank (NEA-1627)

  2. Selective removal of either metastable species from a mixed 3P 0,2 rare-gas metastable beam

    NASA Technical Reports Server (NTRS)

    Dunning, F. B.; Cook, T. B.; West, W. P.; Stebbings, R. F.

    1975-01-01

    A tunable CW laser has been used to selectively remove either of the two metastable species, 3P 0,2, which are initially present in a neon metastable beam. The method is applicable to other rare gases and provides the opportunity for separate investigation of effects due to atoms in either the 3P 0 or 3P 2 state.

  3. Assignment of the human pro-melanin-concentrating hormone gene (PMCH) to chromosome 12q23-q24 and two variant genes (PMCHL1 and PMCHL2) to chromosome 5p14 and 5q12-q13

    SciTech Connect

    Pedeutour, F. ); Szpirer, C. ); Nahon, J.L. )

    1994-01-01

    Melanin-concentrating hormone (MCH) is a peptide that has been isolated from salmon pituitary and rat hypothalamus. In mammals, pro-MCH (PMCH) encodes two putative peptides, named NEI and NGE, in addition to MCH. Those peptides are expressed predominantly in hypothalamus and display a broad array of functions in rat brain. The authors have previously mapped the PMCH locus on human chromosome 12q and rat chromosome 7. Genomic cloning has revealed the existence of two distinct MCH genes in human: one authentic and one variant. In this report, they describe Southern blotting analysis with DNA from a panel of somatic cell hybrids and demonstrate that the authentic human MCH (hMCH) gene is located as expected on chromosome 12, while the variant form of hMCH gene is located on chromosome 5. Direct chromosomal assignment of the authentic and variant hMCH genes was obtained by using fluorescence in situ hybridization on metaphase chromosomes. A strong signal was observed in 12q23-q24 with the authentic HMCH genomic DNA probe. Surprisingly, two signals were conspicuously found in 5p14 and 5q12-q13 with different variant hMCH genomic DNA probes. These loci were designated PMCHL1 and PMCHL2. Evidence of physiological and pathological data in rodents together with locus linkage analyses in human suggests that hMCH authentic and variant genes may be involved in human brain disorders. 44 refs., 3 figs., 1 tab.

  4. Assignment of human myocyte-specific enhancer binding factor 2C (hMEF2C) to human chromosome 5q14 and evidence that MEF2C is evolutionarily conserved

    SciTech Connect

    Krainc, D.; Lipton, S.A.; Haas, M.; Ward, D.C.

    1995-10-10

    Human myocyte-specific enhancer binding factor 2C (hMEF2C) belongs to the MEF2 subfamily of the MADS (MCM1, AGAMOUS, DEF A, serum response factor) family of transcription factors. Members of the MADS family share a conserved domain - the MADS domain - that is necessary for DNA binding. Highly conserved versions of the MADS domain and of an adjacent domain that is known as the MEF2 domain are found in members of the MEF2 subfamily. Both of these domains are necessary for binding to the MEF2 regulatory element. This regulatory element is known to be functionally important in a variety of muscle-specific genes and possibly in the brain creatine kinase gene. The MEF2C gene product activates transcription by binding to the MEF2 element. hMEF2C is expressed at high levels in postmitotic neurons in the brain, where it is most abundant in the cerebral cortex, and is also expressed in differentiated myotubes. Several lines of evidence suggest the existence of a rat homologue of MEF2C, and a mouse homologue has been cloned. The mouse gene was mapped to mouse chromosome 13 in a region that is syntenic to human 5q13-q15. 12 refs., 1 fig.

  5. Regional chromosomal assignments for four members of the myocyte-specific enhancer-binding factor 2 (MEF2) gene family to human chromosomes 15q, 19q, 5q, and 1q

    SciTech Connect

    Hobson, G.M.; Funanage, V.L.; Krahe, R.

    1994-09-01

    MEF2 genes belong to the MADS box family of transcription factors and encode proteins that bind as homo- and heterodimers to a consensus CTA(T/A){sub 4}TAG/A sequence present in the regulatory regions of numerous muscle-specific and growth inducible genes. Sequence analysis of human MEF2 cDNA clones suggested that they arose from alternatively spliced transcripts of four different genes, termed MEF2A-D. We have mapped the MEF2 genes to human chromosomal regions by identifying unique sequences in the 5{prime} or 3{prime} untranslated regions of each clone and using these sequences as PCR primers on the DNA of a human-rodent hybrid clone panel informative for different regions of the human genome. The localization of MEF2A to chromosome 15q, MEF2B to 19q, MEF2C to 5q, and MEF2D to 1q verifies the existence of at least four distinct loci for members of this gene family. The same PCR primers were used to identify individual YAC clones for each gene. Such isolated clones are now being used for fluorescence in situ hybridization for high resolution chromosomal regional assignment.

  6. Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1

    PubMed Central

    Cai, Qiuyin; Zhang, Ben; Sung, Hyuna; Low, Siew-Kee; Kweon, Sun-Seog; Lu, Wei; Shi, Jiajun; Long, Jirong; Wen, Wanqing; Choi, Ji-Yeob; Noh, Dong-Young; Shen, Chen-Yang; Matsuo, Keitaro; Teo, Soo-Hwang; Kim, Mi Kyung; Khoo, Ui Soon; Iwasaki, Motoki; Hartman, Mikael; Takahashi, Atsushi; Ashikawa, Kyota; Matsuda, Koichi; Shin, Min-Ho; Park, Min Ho; Zheng, Ying; Xiang, Yong-Bing; Ji, Bu-Tian; Park, Sue K.; Wu, Pei-Ei; Hsiung, Chia-Ni; Ito, Hidemi; Kasuga, Yoshio; Kang, Peter; Mariapun, Shivaani; Ahn, Sei Hyun; Kang, Han Sung; Chan, Kelvin Y. K.; Man, Ellen P. S.; Iwata, Hiroji; Tsugane, Shoichiro; Miao, Hui; Liao, Jiemin; Nakamura, Yusuke; Kubo, Michiaki; Delahanty, Ryan J.; Zhang, Yanfeng; Li, Bingshan; Li, Chun; Gao, Yu-Tang; Shu, Xiao-Ou; Kang, Daehee; Zheng, Wei

    2014-01-01

    In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified three novel genetic loci associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene, P = 8.82 × 10−9), rs10474352 at 5q14.3 (near the ARRDC3 gene, P = 1.67 × 10−9), and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene, P = 4.25 × 10−8). These associations were replicated in European-ancestry populations including 16,003 cases and 41,335 controls (P = 0.030, 0.004, and 0.010, respectively). Data from the ENCODE project suggest that variants rs4951011 and rs10474352 may be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer. PMID:25038754

  7. Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1.

    PubMed

    Cai, Qiuyin; Zhang, Ben; Sung, Hyuna; Low, Siew-Kee; Kweon, Sun-Seog; Lu, Wei; Shi, Jiajun; Long, Jirong; Wen, Wanqing; Choi, Ji-Yeob; Noh, Dong-Young; Shen, Chen-Yang; Matsuo, Keitaro; Teo, Soo-Hwang; Kim, Mi Kyung; Khoo, Ui Soon; Iwasaki, Motoki; Hartman, Mikael; Takahashi, Atsushi; Ashikawa, Kyota; Matsuda, Koichi; Shin, Min-Ho; Park, Min Ho; Zheng, Ying; Xiang, Yong-Bing; Ji, Bu-Tian; Park, Sue K; Wu, Pei-Ei; Hsiung, Chia-Ni; Ito, Hidemi; Kasuga, Yoshio; Kang, Peter; Mariapun, Shivaani; Ahn, Sei Hyun; Kang, Han Sung; Chan, Kelvin Y K; Man, Ellen P S; Iwata, Hiroji; Tsugane, Shoichiro; Miao, Hui; Liao, Jiemin; Nakamura, Yusuke; Kubo, Michiaki; Delahanty, Ryan J; Zhang, Yanfeng; Li, Bingshan; Li, Chun; Gao, Yu-Tang; Shu, Xiao-Ou; Kang, Daehee; Zheng, Wei

    2014-08-01

    In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified 3 genetic loci newly associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene; P=8.82×10(-9)), rs10474352 at 5q14.3 (near the ARRDC3 gene; P=1.67×10(-9)) and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene; P=4.25×10(-8)). We replicated these associations in 16,003 cases and 41,335 controls of European ancestry (P=0.030, 0.004 and 0.010, respectively). Data from the ENCODE Project suggest that variants rs4951011 and rs10474352 might be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.

  8. Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1.

    PubMed

    Cai, Qiuyin; Zhang, Ben; Sung, Hyuna; Low, Siew-Kee; Kweon, Sun-Seog; Lu, Wei; Shi, Jiajun; Long, Jirong; Wen, Wanqing; Choi, Ji-Yeob; Noh, Dong-Young; Shen, Chen-Yang; Matsuo, Keitaro; Teo, Soo-Hwang; Kim, Mi Kyung; Khoo, Ui Soon; Iwasaki, Motoki; Hartman, Mikael; Takahashi, Atsushi; Ashikawa, Kyota; Matsuda, Koichi; Shin, Min-Ho; Park, Min Ho; Zheng, Ying; Xiang, Yong-Bing; Ji, Bu-Tian; Park, Sue K; Wu, Pei-Ei; Hsiung, Chia-Ni; Ito, Hidemi; Kasuga, Yoshio; Kang, Peter; Mariapun, Shivaani; Ahn, Sei Hyun; Kang, Han Sung; Chan, Kelvin Y K; Man, Ellen P S; Iwata, Hiroji; Tsugane, Shoichiro; Miao, Hui; Liao, Jiemin; Nakamura, Yusuke; Kubo, Michiaki; Delahanty, Ryan J; Zhang, Yanfeng; Li, Bingshan; Li, Chun; Gao, Yu-Tang; Shu, Xiao-Ou; Kang, Daehee; Zheng, Wei

    2014-08-01

    In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified 3 genetic loci newly associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene; P=8.82×10(-9)), rs10474352 at 5q14.3 (near the ARRDC3 gene; P=1.67×10(-9)) and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene; P=4.25×10(-8)). We replicated these associations in 16,003 cases and 41,335 controls of European ancestry (P=0.030, 0.004 and 0.010, respectively). Data from the ENCODE Project suggest that variants rs4951011 and rs10474352 might be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer. PMID:25038754

  9. Photoelectric characteristics of CH3NH3PbI3/p-Si heterojunction

    NASA Astrophysics Data System (ADS)

    Yamei, Wu; Ruixia, Yang; Hanmin, Tian; Shuai, Chen

    2016-05-01

    Organic–inorganic hybrid perovskite CH3NH3PbI3 film is prepared on p-type silicon substrate using the one-step solution method to form a CH3NH3PbI3/p-Si heterojunction. The film morphology and structure are characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The photoelectric properties of the CH3NH3PbI3/p-Si heterojunction are studied by testing the current–voltage (I–V) with and without illumination and capacitance–voltage (C–V) characteristics. It turns out from the I–V curve without illumination that the CH3NH3PbI3/p-Si heterojunction has a rectifier feature with the rectification ratio over 70 at the bias of ±5 V. Also, there appears a photoelectric conversion phenomenon on this heterojunction with a short circuit current (Isc) of 0.16 μA and an open circuit voltage (Voc) of about 10 mV The high frequency C–V characteristic of the Ag/CH3NH3PbI3/p-Si heterojunction turns out to be similar to that of the metal–insulator–semiconductor (MIS) structure, and a parallel translation of the C–V curve along the forward voltage axis is found. This parallel translation means the existence of defects at the CH3NH3PbI3/p-Si interface and positive fixed charges in the CH3NH3PbI3 layer. The defects at the interface of the CH3NH3PbI3/p-Si heterojunction result in the dramatic decline of the Voc. Besides, the C–V test of CH3NH3PbI3 film shows a non-linear dielectric property and the dielectric value is about 4.64 as calculated. Project supported by the Hebei Province Natural Science Foundation of China (No. F2014202184) and the Tianjin Natural Science Foundation of China (No. 15JCZDJC37800).

  10. Photoelectric characteristics of CH3NH3PbI3/p-Si heterojunction

    NASA Astrophysics Data System (ADS)

    Yamei, Wu; Ruixia, Yang; Hanmin, Tian; Shuai, Chen

    2016-05-01

    Organic-inorganic hybrid perovskite CH3NH3PbI3 film is prepared on p-type silicon substrate using the one-step solution method to form a CH3NH3PbI3/p-Si heterojunction. The film morphology and structure are characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The photoelectric properties of the CH3NH3PbI3/p-Si heterojunction are studied by testing the current-voltage (I-V) with and without illumination and capacitance-voltage (C-V) characteristics. It turns out from the I-V curve without illumination that the CH3NH3PbI3/p-Si heterojunction has a rectifier feature with the rectification ratio over 70 at the bias of ±5 V. Also, there appears a photoelectric conversion phenomenon on this heterojunction with a short circuit current (Isc) of 0.16 μA and an open circuit voltage (Voc) of about 10 mV The high frequency C-V characteristic of the Ag/CH3NH3PbI3/p-Si heterojunction turns out to be similar to that of the metal-insulator-semiconductor (MIS) structure, and a parallel translation of the C-V curve along the forward voltage axis is found. This parallel translation means the existence of defects at the CH3NH3PbI3/p-Si interface and positive fixed charges in the CH3NH3PbI3 layer. The defects at the interface of the CH3NH3PbI3/p-Si heterojunction result in the dramatic decline of the Voc. Besides, the C-V test of CH3NH3PbI3 film shows a non-linear dielectric property and the dielectric value is about 4.64 as calculated. Project supported by the Hebei Province Natural Science Foundation of China (No. F2014202184) and the Tianjin Natural Science Foundation of China (No. 15JCZDJC37800).

  11. Electron Excitation Cross Sections for the S// Transitions 3s(sup 2)3p(sup 3) (sup 4)s(deg) (leads to)3s(sup 2)3p(sup 3) (sup 2)D(deg), (sup 2)p(deg) and 3s3p(sup 4) (sup 4)p

    NASA Technical Reports Server (NTRS)

    Liao, C.; Smith, S. J.; Hitz, D.; Chutjian, A.; Tayal, S. S.

    1996-01-01

    Experimental and theoretical collisional excitation cross sections are reported for the transitions 3s(sup 2)3p(sup 3) (sup 4)s(deg) (leads to)3s(sup 2)3p(sup 3)(sup 2)D(deg), (sup 2)p(deg) and 3s3p(sup 4) (sup 4)p in s//.

  12. Thermoelectric properties of Cu doped ZnSb containing Zn3P2 particles

    NASA Astrophysics Data System (ADS)

    Valset, K.; Böttger, P. H. M.; Taftø, J.; Finstad, T. G.

    2012-01-01

    We prepared ZnSb containing Zn3P2 particles of size ranging from a few tens to several hundred nanometers by melting powders of Zn, Sb, and P. Materials with Zn3P2 content up to 3.75% were made and subsequently ball-milled and hot pressed. A reduction in the thermal conductivity of 15% was achieved. By adding 0.2% Cu the carrier concentration increased an order of magnitude, to 2.0 × 1019 cm-3, while the mobility remained unaffected. The resulting increase in electrical conductivity together with the reduced thermal conductivity, led to a significant increase in the dimensionless figure of merit, in excess of 0.9 around 550 K.

  13. Synthesis and characterization of Zn 3P 2/ZnS core/shell nanowires

    NASA Astrophysics Data System (ADS)

    Sun, T.; Wu, P. C.; Guo, Z. D.; Dai, Y.; Meng, H.; Fang, X. L.; Shi, Z. J.; Dai, L.; Qin, G. G.

    2011-05-01

    Fully-surrounded Zn3P2/ZnS core/shell nanowires (NWs) were synthesized for the first time via a two-step method: a catalyst free chemical vapor deposition followed by a low-pressure vulcanization process. Field emission scanning electron microscopy, high-resolution transmission electron microscopy, and high-angle angular dark field scanning transmission electron microscopy were used to characterize the morphologies, crystal structure, and element composition of the core/shell NWs. The band structure analysis demonstrates that the Zn3P2/ZnS core-shell NW type-II heterostructures have bright potential in photovoltaic nanodevice applications. The core/shell NW growth method used here can be extended to other material system.

  14. X (3872 ) , Xb , and the χb 1(3 P ) state

    NASA Astrophysics Data System (ADS)

    Karliner, Marek; Rosner, Jonathan L.

    2015-01-01

    We discuss the possible production and discovery channels in e+e- and p p machines of the Xb, the bottomonium counterpart of X (3872 ) and the putative isoscalar analogue of the charged bottomoniumlike states Zb discovered by Belle. We suggest that the Xb may be close in mass to the bottomonium state χb 1(3 P ), mixing with it and sharing its decay channels, just as X (3872 ) is likely a mixture of a D ¯D* molecule and χc 1(2 P ) . Consequently, the experiments which reported observing χb 1(3 P ) might have actually discovered the Xb, or a mixture of the two states.

  15. Impurity scattering effect in Pd-doped superconductor SrPt3P

    NASA Astrophysics Data System (ADS)

    Hu, Kang-Kang; Gao, Bo; Ji, Qiu-Cheng; Ma, Yong-Hui; Zhang, Hui; Mu, Gang; Huang, Fu-Qiang; Cai, Chuan-Bing; Xie, Xiao-Ming

    2016-08-01

    We present a systematic study of the impurity scattering effect induced by Pd dopants in the superconductor SrPt3P. Using a solid-state reaction method, we fabricated the Pd-doped superconductor Sr(Pt1- x Pd x )3P.We found that the residual resistivity ρ 0 increases quickly with Pd doping, whereas the residual resistance ratio (RRR) displays a dramatic reduction. In addition, both the nonlinear field-dependent behavior of the Hall resistivity ρ xy and the strong temperature dependence of the Hall coefficient R H at low temperature are suppressed by Pd doping. All the experimental results can be explained by an increase in scattering by impurities induced by doping. Our results suggest that the Pt position is very crucial to the carrier conduction in the present system.

  16. WIPI proteins: essential PtdIns3P effectors at the nascent autophagosome.

    PubMed

    Proikas-Cezanne, Tassula; Takacs, Zsuzsanna; Dönnes, Pierre; Kohlbacher, Oliver

    2015-01-15

    Autophagy is a pivotal cytoprotective process that secures cellular homeostasis, fulfills essential roles in development, immunity and defence against pathogens, and determines the lifespan of eukaryotic organisms. However, autophagy also crucially contributes to the development of age-related human pathologies, including cancer and neurodegeneration. Macroautophagy (hereafter referred to as autophagy) clears the cytoplasm by stochastic or specific cargo recognition and destruction, and is initiated and executed by autophagy related (ATG) proteins functioning in dynamical hierarchies to form autophagosomes. Autophagosomes sequester cytoplasmic cargo material, including proteins, lipids and organelles, and acquire acidic hydrolases from the lysosomal compartment for cargo degradation. Prerequisite and essential for autophagosome formation is the production of phosphatidylinositol 3-phosphate (PtdIns3P) by phosphatidylinositol 3-kinase class III (PI3KC3, also known as PIK3C3) in complex with beclin 1, p150 (also known as PIK3R4; Vps15 in yeast) and ATG14L. Members of the human WD-repeat protein interacting with phosphoinositides (WIPI) family play an important role in recognizing and decoding the PtdIns3P signal at the nascent autophagosome, and hence function as autophagy-specific PtdIns3P-binding effectors, similar to their ancestral yeast Atg18 homolog. The PtdIns3P effector function of human WIPI proteins appears to be compromised in cancer and neurodegeneration, and WIPI genes and proteins might present novel targets for rational therapies. Here, we summarize the current knowledge on the roles of the four human WIPI proteins, WIPI1-4, in autophagy. This article is part of a Focus on Autophagosome biogenesis. For further reading, please see related articles: 'ERES: sites for autophagosome biogenesis and maturation?' by Jana Sanchez-Wandelmer et al. (J. Cell Sci. 128, 185-192) and 'Membrane dynamics in autophagosome biogenesis' by Sven R. Carlsson and Anne

  17. Omega3P: A Parallel Finite-Element Eigenmode Analysis Code for Accelerator Cavities

    SciTech Connect

    Lee, Lie-Quan; Li, Zenghai; Ng, Cho; Ko, Kwok; /SLAC

    2009-03-04

    Omega3P is a parallel eigenmode calculation code for accelerator cavities in frequency domain analysis using finite-element methods. In this report, we will present detailed finite-element formulations and resulting eigenvalue problems for lossless cavities, cavities with lossy materials, cavities with imperfectly conducting surfaces, and cavities with waveguide coupling. We will discuss the parallel algorithms for solving those eigenvalue problems and demonstrate modeling of accelerator cavities through different examples.

  18. Ca3P2 and other topological semimetals with line nodes and drumhead surface states

    NASA Astrophysics Data System (ADS)

    Chan, Y.-H.; Chiu, Ching-Kai; Chou, M. Y.; Schnyder, Andreas P.

    2016-05-01

    As opposed to ordinary metals, whose Fermi surfaces are two dimensional, topological (semi)metals can exhibit protected one-dimensional Fermi lines or zero-dimensional Fermi points, which arise due to an intricate interplay between symmetry and topology of the electronic wave functions. Here, we study how reflection symmetry, time-reversal symmetry, SU(2) spin-rotation symmetry, and inversion symmetry lead to the topological protection of line nodes in three-dimensional semimetals. We obtain the crystalline invariants that guarantee the stability of the line nodes in the bulk and show that a quantized Berry phase leads to the appearance of protected surfaces states, which take the shape of a drumhead. By deriving a relation between the crystalline invariants and the Berry phase, we establish a direct connection between the stability of the line nodes and the drumhead surface states. Furthermore, we show that the dispersion minimum of the drumhead state leads to a Van Hove singularity in the surface density of states, which can serve as an experimental fingerprint of the topological surface state. As a representative example of a topological semimetal, we consider Ca3P2 , which has a line of Dirac nodes near the Fermi energy. The topological properties of Ca3P2 are discussed in terms of a low-energy effective theory and a tight-binding model, derived from ab initio DFT calculations. Our microscopic model for Ca3P2 shows that the drumhead surface states have a rather weak dispersion, which implies that correlation effects are enhanced at the surface of Ca3P2 .

  19. The Participative Design of an Endoscopy Facility using Lean 3P.

    PubMed

    Smith, Iain

    2016-01-01

    In the UK, bowel cancer is the second largest cancer killer. Diagnosing people earlier can save lives but demand for endoscopies is increasing and this can put pressure on waiting times. To address this challenge, an endoscopy unit in North East England decided to improve their facilities to increase capacity and create environments that improve the experience of users. This presented a significant opportunity for step change improvement but also a problem in terms of creating designs that meet user requirements whilst addressing structural or space constraints. The Lean design process known as '3P' (standing for the production preparation process) was utilised as a participative design strategy to engage stakeholders in the design of the new department. This involved a time-out workshop (or 3P event) in which Lean and participative design tools were utilised to create an innovative design based on 'point of delivery' (POD) principles. The team created a design that demonstrated an increase in treatment room capacity by 25% and bed capacity by 70% whilst reducing travel distance for patients by 25.8% and staff by 27.1%. This was achieved with an increase in available space of only 13%. The Lean 3P method provided a structured approach for corporate and clinical staff to work together with patient representatives as cross-functional teams. This participative approach facilitated communication and learning between stakeholders about care processes and personal preferences. Lean 3P therefore appears to be a promising approach to improving the healthcare facilities design process to meet user requirements. PMID:27493744

  20. High-energy single diffractive dissociation of nucleons and the 3P-model applicability range

    NASA Astrophysics Data System (ADS)

    Godizov, A. A.

    2016-11-01

    The adequacy of the triple-Pomeron interaction approximation (the 3P-model) for description of the high-energy single diffractive dissociation of nucleons is analyzed via application to the available experimental data on nucleon-nucleon scattering, including the recent results produced by CMS Collaboration which allow to estimate reliably the triple-Pomeron coupling value. It is argued that the total contribution of secondary Reggeon exchanges is not negligible up to the Tevatron energy.

  1. Linkage of atopic dermatitis to chromosomes 4q22, 3p24 and 3q21.

    PubMed

    Christensen, Ulla; Møller-Larsen, Steffen; Nyegaard, Mette; Haagerup, Annette; Hedemand, Anne; Brasch-Andersen, Charlotte; Kruse, Torben A; Corydon, Thomas Juhl; Deleuran, Mette; Børglum, Anders D

    2009-10-01

    Atopic dermatitis (AD) is a common, itchy skin disease of complex inheritance characterized by dermal and epidermal inflammation. The heritability is considerable and well documented. To date, four genome scans have examined the AD phenotype, showing replicated linkage at 3p26-22, 3q13-21 and 18q11-21. Our previous AD scan showed evidence of linkage to loci at 3p and 18q, and furthermore at 4p15-14. In order to further investigate the genetic basis of AD, we collected and analysed a new Danish family sample consisting of 130 AD sib pair families (555 individuals including 295 children with AD). AD was diagnosed after clinical examination, AD severity was scored and specific IgE was determined. A linkage scan of chromosome 3, 4 and 18 was performed using 91 microsatellite markers. Linkage analyses were performed of dichotomous phenotypes and semi-quantitative traits including the AD severity score. We analysed the novel AD sample alone and together with the previously examined sample. AD severity showed a maximum Z-score of 3.7 at 4q22.1 suggesting the localization of a novel gene for AD severity. A maximum MOD score of 4.6 was obtained at 3p24 for the AD phenotype, providing the first significant linkage of AD at this locus. A maximum MLS score of 3.3 was obtained at 3q21 for IgE-associated AD, and evidence of linkage was also obtained at 3p22.2-21.31, 3q13, 4q35, and 18q12. The results presented should provide a firm basis for gene-targeting studies of AD and related disorders. PMID:19517137

  2. The Participative Design of an Endoscopy Facility using Lean 3P

    PubMed Central

    Smith, Iain

    2016-01-01

    In the UK, bowel cancer is the second largest cancer killer. Diagnosing people earlier can save lives but demand for endoscopies is increasing and this can put pressure on waiting times. To address this challenge, an endoscopy unit in North East England decided to improve their facilities to increase capacity and create environments that improve the experience of users. This presented a significant opportunity for step change improvement but also a problem in terms of creating designs that meet user requirements whilst addressing structural or space constraints. The Lean design process known as ‘3P' (standing for the production preparation process) was utilised as a participative design strategy to engage stakeholders in the design of the new department. This involved a time-out workshop (or 3P event) in which Lean and participative design tools were utilised to create an innovative design based on ‘point of delivery' (POD) principles. The team created a design that demonstrated an increase in treatment room capacity by 25% and bed capacity by 70% whilst reducing travel distance for patients by 25.8% and staff by 27.1%. This was achieved with an increase in available space of only 13%. The Lean 3P method provided a structured approach for corporate and clinical staff to work together with patient representatives as cross-functional teams. This participative approach facilitated communication and learning between stakeholders about care processes and personal preferences. Lean 3P therefore appears to be a promising approach to improving the healthcare facilities design process to meet user requirements. PMID:27493744

  3. The Participative Design of an Endoscopy Facility using Lean 3P.

    PubMed

    Smith, Iain

    2016-01-01

    In the UK, bowel cancer is the second largest cancer killer. Diagnosing people earlier can save lives but demand for endoscopies is increasing and this can put pressure on waiting times. To address this challenge, an endoscopy unit in North East England decided to improve their facilities to increase capacity and create environments that improve the experience of users. This presented a significant opportunity for step change improvement but also a problem in terms of creating designs that meet user requirements whilst addressing structural or space constraints. The Lean design process known as '3P' (standing for the production preparation process) was utilised as a participative design strategy to engage stakeholders in the design of the new department. This involved a time-out workshop (or 3P event) in which Lean and participative design tools were utilised to create an innovative design based on 'point of delivery' (POD) principles. The team created a design that demonstrated an increase in treatment room capacity by 25% and bed capacity by 70% whilst reducing travel distance for patients by 25.8% and staff by 27.1%. This was achieved with an increase in available space of only 13%. The Lean 3P method provided a structured approach for corporate and clinical staff to work together with patient representatives as cross-functional teams. This participative approach facilitated communication and learning between stakeholders about care processes and personal preferences. Lean 3P therefore appears to be a promising approach to improving the healthcare facilities design process to meet user requirements.

  4. RbGa3(P3O10)2: a new gallium phosphate isotypic with RbAl3(P3O10)2.

    PubMed

    Lesage, Julien; Guesdon, Anne; Raveau, Bernard

    2005-05-01

    Rubidium trigallium bis(triphosphate), RbGa3(P3O10)2 has been synthesized by solid-state reaction and studied by single-crystal X-ray diffraction at room temperature. This compound is the first anhydrous gallium phosphate containing both GaO4 tetrahedra (Ga1) and GaO6 octahedra (Ga2 and Ga3). The three independent Ga atoms are located on sites with imposed symmetry 2 (Wickoff positions 4a for Ga1 and 4b for Ga2 and Ga3). The GaO4 and GaO6 polyhedra are connected through the apices to triphosphate groups and form a three-dimensional host lattice. This framework presents intersecting tunnels running along the [001] and <110> directions, where the Rb2+ cations are located on sites with imposed symmetry 2 (Wickoff position 4a). The structure also exhibits remarkable features, such as infinite helical columns created by the junction of GaO4 and PO4 tetrahedra. PMID:15876695

  5. MiR-625-3p promotes cell migration and invasion via inhibition of SCAI in colorectal carcinoma cells

    PubMed Central

    Wang, Qizhi; Zhang, Pei; Li, Dapeng; Wang, Qiangwu; Wang, Jianchao; Li, Huabin; Liu, Hao; Wang, Zhiwei

    2015-01-01

    MicroRNAs (miRNAs) play a critical role in controlling tumor invasion and metastasis via regulating the expression of a variety of targets, which act as oncogenes or tumor suppressor genes. Abnormally expressed miR-625-3p has been observed in several types of human cancers. However, the molecular mechanisms of miR-625-3p-mediated tumorigenesis are largely elusive. Therefore, the aim of this study was to evaluate the biological function and molecular insight on miR-625-3p-induced oncogenesis in colorectal carcinoma (CRC). The effects of miR-625-3p in cell migration and invasion were analyzed by wound healing assay and transwell assay, respectively. In addition, the expression of miR-625-3p and its targets was detected in five human CRC cell lines. In the present study, we found that overexpression of miR-625-3p promoted migration and invasion in SW480 cells, whereas downregulation of miR-625-3p inhibited cell motility in SW620 cells. More importantly, we observed potential binding sites for miR-625-3p in the 3′-untranslated region of suppressor of cancer cell invasion (SCAI). Notably, we identified that overexpression of miR-625-3p inhibited the expression of SCAI, while depletion of miR-625-3p increased SCAI level, suggesting that SCAI could be a target of miR-625-3p. Additionally, we revealed that miR-625-3p exerts its oncogenic functions through regulation of SCAI/E-cadherin/MMP-9 pathways. Our findings indicate the pivotal role of miR-625-3p in invasion that warrants further exploration whether targeting miR-625-3p could be a promising approach for the treatment of CRC. PMID:26314959

  6. Crystal structure of the Saccharomyces cerevisiae monoglyceride lipase Yju3p.

    PubMed

    Aschauer, Philipp; Rengachari, Srinivasan; Lichtenegger, Joerg; Schittmayer, Matthias; Das, Krishna Mohan Padmanabha; Mayer, Nicole; Breinbauer, Rolf; Birner-Gruenberger, Ruth; Gruber, Christian C; Zimmermann, Robert; Gruber, Karl; Oberer, Monika

    2016-05-01

    Monoglyceride lipases (MGLs) are a group of α/β-hydrolases that catalyze the hydrolysis of monoglycerides (MGs) into free fatty acids and glycerol. This reaction serves different physiological functions, namely in the last step of phospholipid and triglyceride degradation, in mammalian endocannabinoid and arachidonic acid metabolism, and in detoxification processes in microbes. Previous crystal structures of MGLs from humans and bacteria revealed conformational plasticity in the cap region of this protein and gave insight into substrate binding. In this study, we present the structure of a MGL from Saccharomyces cerevisiae called Yju3p in its free form and in complex with a covalently bound substrate analog mimicking the tetrahedral intermediate of MG hydrolysis. These structures reveal a high conservation of the overall shape of the MGL cap region and also provide evidence for conformational changes in the cap of Yju3p. The complex structure reveals that, despite the high structural similarity, Yju3p seems to have an additional opening to the substrate binding pocket at a different position compared to human and bacterial MGL. Substrate specificities towards MGs with saturated and unsaturated alkyl chains of different lengths were tested and revealed highest activity towards MG containing a C18:1 fatty acid. PMID:26869448

  7. Pulsed laser photolysis study of the reaction between O(3P) and HO2

    NASA Technical Reports Server (NTRS)

    Ravishankara, A. R.; Wine, P. H.; Nicovich, J. M.

    1983-01-01

    It is pointed out that bimolecular reactions involving two free radicals are of great interest because both reactants have unpaired electrons and hence could interact at distances longer than those typical of radical-molecule encounters. A method based on laser photolysis is being developed to produce selectively free radicals in the homogeneous gas phase. This is to be done in such a way as to isolate the reaction of interest and subsequently follow the course of the reaction using spectroscopic techniques. The present investigation is concerned with a study in which the rate coefficient for the reaction of O(3P) with HO2, has been measured at N2 pressures ranging from 10 to 500 torr, taking into account the reaction O(3P)+HO2 yields OH-O2. In the described study, O(3P) and HO2 were produced by cophotolysis of O3 and H2O2 in N2 at 248.5 nm using a KrF excimer laser.

  8. miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis.

    PubMed

    Sonda, Nada; Simonato, Francesca; Peranzoni, Elisa; Calì, Bianca; Bortoluzzi, Stefania; Bisognin, Andrea; Wang, Ena; Marincola, Francesco M; Naldini, Luigi; Gentner, Bernhard; Trautwein, Christian; Sackett, Sara Dutton; Zanovello, Paola; Molon, Barbara; Bronte, Vincenzo

    2013-06-27

    Tumor progression is accompanied by an altered myelopoiesis causing the accumulation of immunosuppressive cells. Here, we showed that miR-142-3p downregulation promoted macrophage differentiation and determined the acquisition of their immunosuppressive function in tumor. Tumor-released cytokines signaling through gp130, the common subunit of the interleukin-6 cytokine receptor family, induced the LAP∗ isoform of C/EBPβ transcription factor, promoting macrophage generation. miR-142-3p downregulated gp130 by canonical binding to its messenger RNA (mRNA) 3' UTR and repressed C/EBPβ LAP∗ by noncanonical binding to its 5' mRNA coding sequence. Enforced miR expression impaired macrophage differentiation both in vitro and in vivo. Mice constitutively expressing miR-142-3p in the bone marrow showed a marked increase in survival following immunotherapy with tumor-specific T lymphocytes. By modulating a specific miR in bone marrow precursors, we thus demonstrated the feasibility of altering tumor-induced macrophage differentiation as a potent tool to improve the efficacy of cancer immunotherapy.

  9. Preparation of Polyimide/MWCNT Nanocomposites via Solid State Shearing Pulverization (S3P) Processing.

    PubMed

    Liu, Ruojin; Zhao, Fenghua; Zhang, Huanhuan; Yu, Xiaoyan; Ding, Huili; Naito, Kimiyoshi; Qu, Xiongwei; Zhang, Qingxin

    2015-05-01

    Polyimide/multiwall carbon nanotube (PI/MWCNT) nanocomposite films with homogeneous MWCNTs dispersion were prepared via a solid state shearing pulverization (S3P) approach. Polyimide precursor, viz., poly(amic acid) (PAA), was synthesized from 4,4'-oxydianiline (ODA) and pyromellitic dianhydride (PMDA). Then, 3,3',4,4'-benzophenonetetracarboxylic dianhydride (BTDA) was mixed with the PAA powder and acid functionalized MWCNTs (acid-MWCNTs) by solid state shearing pulverization (S3P) approach. Finally, PI/MWCNT nanocomposite films were prepared by thermal imidization at elevated temperatures. Using such an approach not only the MWCNTs are well-dispersed but also the mechanical and thermal properties of PI are improved. The tensile strength of PI was enhanced by 74% and the elongation at break decreased to 10.35% with 5.0 wt% acid- MWCNT loading. And the glass transition temperature of PI was increased to 341 degrees C from 303 degrees C because of the strong interfacial bonding between PI and acid-MWCNTs. The solid state shearing pulverization (S3P) approach developed in this study provides a novel method to prepare various polymer composites with desired particle dispersion. PMID:26505005

  10. Isotope branching and tunneling in O(3P)+HD-->OH+D; OD+H reactions.

    PubMed

    Sultanov, Renat A; Balakrishnan, N

    2004-12-01

    The O((3)P)+HD and O((3)P)+D(2) reactions are studied using quantum scattering calculations and chemically accurate potential energy surfaces developed for the O((3)P)+H(2) system by Rogers et al. [J. Phys. Chem. A 104, 2308 (2000)]. Cross sections and rate coefficients for OH and OD products are calculated using accurate quantum methods as well as the J-shifting approximation. The J-shifting approach is found to work remarkably well for both O+HD and O+D(2) collisions. The reactions are dominated by tunneling at low temperatures and for the O+HD reaction the hydrogen atom transfer leading to the OH product dominates at low temperatures. Our result for the OH/OD branching ratio is in close agreement with previous calculations over a wide range of temperatures. The computed OH/OD branching ratios are also in close agreement with experimental results of Robie et al. [Chem. Phys. Lett. 134, 579 (1987)] at temperatures above 400 K but the theoretical results do not reproduce the rapid rise in the experimental values of the branching ratio for temperatures lower than 350 K. We believe that new measurements could resolve the long-standing discrepancy between experiment and theory for this benchmark reaction.

  11. Chemoimmunotherapy for relapsed/refractory and progressive 17p13-deleted chronic lymphocytic leukemia (CLL) combining pentostatin, alemtuzumab, and low-dose rituximab is effective and tolerable and limits loss of CD20 expression by circulating CLL cells.

    PubMed

    Zent, Clive S; Taylor, Ronald P; Lindorfer, Margaret A; Beum, Paul V; LaPlant, Betsy; Wu, Wenting; Call, Timothy G; Bowen, Deborah A; Conte, Michael J; Frederick, Lori A; Link, Brian K; Blackwell, Sue E; Veeramani, Suresh; Baig, Nisar A; Viswanatha, David S; Weiner, George J; Witzig, Thomas E

    2014-07-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients with purine analog refractory disease or TP53 dysfunction still have limited treatment options and poor survival. Alemtuzumab-containing chemoimmunotherapy regimens can be effective but frequently cause serious infections. We report a Phase II trial testing the efficacy and tolerability of a short-duration regimen combining pentostatin, alemtuzumab, and low-dose high-frequency rituximab designed to decrease the risk of treatment-associated infections and to limit the loss of CD20 expression by CLL cells. The study enrolled 39 patients with progressive CLL that was either relapsed/refractory (n = 36) or previously untreated with 17p13 deletion (17p13-) (n = 3). Thirteen (33%) patients had both 17p13- and TP53 mutations predicted to be dysfunctional, and eight patients had purine analog refractory CLL without TP53 dysfunction. Twenty-six (67%) patients completed therapy, with only five (13%) patients having treatment-limiting toxicity and no treatment-related deaths. Twenty-two (56%) patients responded to treatment, with 11 (28%) complete responses (four with incomplete bone marrow recovery). Median progression-free survival was 7.2 months, time to next treatment was 9.1 months, and overall survival was 34.1 months. The majority of deaths (82%) were caused by progressive disease, including transformed diffuse large B-cell lymphoma (n = 6). Correlative studies showed that low-dose rituximab activates complement and natural killer cells without a profound and sustained decrease in expression of CD20 by circulating CLL cells. We conclude that pentostatin, alemtuzumab, and low-dose high-frequency rituximab is a tolerable and effective therapy for CLL and that low-dose rituximab therapy can activate innate immune cytotoxic mechanisms without substantially decreasing CD20 expression. PMID:24723493

  12. Staphylococcus aureus adherence to Candida albicans hyphae is mediated by the hyphal adhesin Als3p

    PubMed Central

    Peters, Brian M.; Ovchinnikova, Ekaterina S.; Krom, Bastiaan P.; Schlecht, Lisa Marie; Zhou, Han; Hoyer, Lois L.; Busscher, Henk J.; van der Mei, Henny C.; Jabra-Rizk, Mary Ann

    2012-01-01

    The bacterium Staphylococcus (St.) aureus and the opportunistic fungus Candida albicans are currently among the leading nosocomial pathogens, often co-infecting critically ill patients, with high morbidity and mortality. Previous investigations have demonstrated preferential adherence of St. aureus to C. albicans hyphae during mixed biofilm growth. In this study, we aimed to characterize the mechanism behind this observed interaction. C. albicans adhesin-deficient mutant strains were screened by microscopy to identify the specific receptor on C. albicans hyphae recognized by St. aureus. Furthermore, an immunoassay was developed to validate and quantify staphylococcal binding to fungal biofilms. The findings from these experiments implicated the C. albicans adhesin agglutinin-like sequence 3 (Als3p) in playing a major role in the adherence process. This association was quantitatively established using atomic force microscopy, in which the adhesion force between single cells of the two species was significantly reduced for a C. albicans mutant strain lacking als3. Confocal microscopy further confirmed these observations, as St. aureus overlaid with a purified recombinant Als3 N-terminal domain fragment (rAls3p) exhibited robust binding. Importantly, a strain of Saccharomyces cerevisiae heterologously expressing Als3p was utilized to further confirm this adhesin as a receptor for St. aureus. Although the parental strain does not bind bacteria, expression of Als3p on the cell surface conferred upon the yeast the ability to strongly bind St. aureus. To elucidate the implications of these in vitro findings in a clinically relevant setting, an ex vivo murine model of co-infection was designed using murine tongue explants. Fluorescent microscopic images revealed extensive hyphal penetration of the epithelium typical of C. albicans mucosal infection. Interestingly, St. aureus bacterial cells were only seen within the epithelial tissue when associated with the invasive

  13. miR-342-3p affects hepatocellular carcinoma cell proliferation via regulating NF-κB pathway

    SciTech Connect

    Zhao, Liang; Zhang, Yubao

    2015-02-13

    Recent research indicates that non-coding microRNAs (miRNAs) help regulate basic cellular processes in many types of cancer cells. We hypothesized that overexpression of miR-342-3p might affect proliferation of hepatocellular carcinoma (HCC) cells. After confirming overexpression of miR-342-3p with qRT-PCR, MTT assay showed that HCC cell proliferation was significantly inhibited by miR-342-3p, and that it significantly decreased BrdU-positive cell proliferation by nearly sixfold. Searching for targets using three algorithms we found that miR-342-3p is related to the NF-κB pathway and luciferase assay found that IKK-γ, TAB2 and TAB3 are miR-342-3p target genes. Results of western blot on extracted nuclear proteins of HepG2 and HCT-116 cells showed that miR-342-3p reduced and miR-342-3p-in increased p65 nuclear levels and qRT-PCR found that NF-κB pathway downstream genes were downregulated by miR-342-3p and upregulated by miR-342-3p-in, confirming that miR-342 targets NF-κB pathway. Overexpression of Ikk-γ, TAB2 and TAB3 partially rescued HCC cells proliferation inhibited by miR-342-3p. Using the GSE54751 database we evaluated expression from 10 HCC samples, which strongly suggested downregulation of miR-342-3p and we also found inverse expression between miR-342-3p and its targets IKK-γ, TAB2 and TAB3 from 71 HCC samples. Our results show that miR-342-3p has a significant role in HCC cell proliferation and is suitable for investigation of therapeutic targets. - Highlights: • MiR-342-3p suppresses hepatocellular carcinoma cell proliferation. • MiR-342-3p targets IKK-γ, TAB2 and TAB3 genes. • MiR-342-3p downregulates NF-kB signaling pathway. • MiR-342-3p is downregulated in clinical hepatocellular carcinoma samples. • The expression of miR-342-3p and its target gene is inversely related.

  14. Identification of miR-508-3p and miR-509-3p that are associated with cell invasion and migration and involved in the apoptosis of renal cell carcinoma

    SciTech Connect

    Zhai, Qingna; Zhou, Liang; Zhao, Chunjuan; Wan, Jun; Yu, Zhendong; Guo, Xin; Qin, Jie; Chen, Jing; Lu, Ruijing

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer Previous method was the second-generation sequencing technology. Black-Right-Pointing-Pointer miR-508-3p and miR-509-3p were significantly down-regulated in RCC tissues. Black-Right-Pointing-Pointer They can inhibit cell proliferation and migration and promote cell apoptosis. Black-Right-Pointing-Pointer The expression of miR-508-3p was significantly decreased in RCC patients plasma. Black-Right-Pointing-Pointer miR-508-3p may be a novel diagnostic marker of RCC. -- Abstract: MicroRNAs (miRNAs) have emerged as powerful regulators of multiple processes linked to human cancer, including cell apoptosis, proliferation and migration, suggesting that the regulation of miRNA function could play a critical role in cancer progression. Recent studies have found that human serum/plasma contains stably expressed miRNAs. If they prove indicative of disease states, miRNAs measured from peripheral blood samples may be a source for routine clinical detection of cancer. Our studies showed that both miR-508-3p and miR-509-3p were down-regulated in renal cancer tissues. The level of miR-508-3p but not miR-509-3p in renal cell carcinoma (RCC) patient plasma demonstrated significant differences from that in control plasma. In addition, the overexpression of miR-508-3p and miR-509-3p suppressed the proliferation of RCC cells (786-0), induced cell apoptosis and inhibited cell migration in vitro. Our data demonstrated that miR-508-3p and miR-509-3p played an important role as tumor suppressor genes during tumor formation and that they may serve as novel diagnostic markers for RCC.

  15. Autophagy inhibition of hsa-miR-19a-3p/19b-3p by targeting TGF-β R II during TGF-β1-induced fibrogenesis in human cardiac fibroblasts

    PubMed Central

    Zou, Meijuan; Wang, Fang; Gao, Rui; Wu, Jingjing; Ou, Yingwei; Chen, Xuguan; Wang, Tongshan; Zhou, Xin; Zhu, Wei; Li, Ping; Qi, Lian-Wen; Jiang, Ting; Wang, Weiwei; Li, Chunyu; Chen, Jun; He, Qifang; Chen, Yan

    2016-01-01

    Transforming growth factor-β1 (TGF-β1) plays an important role on fibrogenesis in heart disease. MicroRNAs have exhibited as crucial regulators of cardiac homeostasis and remodeling in various heart diseases. MiR-19a-3p/19b-3p expresses with low levels in the plasma of heart failure patients. The purpose of our study is to determine the role of MiR-19a-3p/19b-3p in regulating autophagy-mediated fibrosis of human cardiac fibroblasts. We elucidate our hypothesis in clinical samples and human cardiac fibroblasts (HCF) to provide valuable basic information. TGF-β1 promotes collagen I α2 and fibronectin synthesis in HCF and that is paralleled by autophagic activation in these cells. Pharmacological inhibition of autophagy by 3-methyladenine decreases the fibrotic response, while autophagy induction of rapamycin increases the response. BECN1 knockdown and Atg5 over-expression either inhibits or enhances the fibrotic effect of TGF-β1 in experimental HCF. Furthermore, miR-19a-3p/19b-3p mimics inhibit epithelial mesenchymal transition (EMT) and extracellular matrix (ECM) prodution and invasion of HCF. Functional studies suggest that miR-19a-3p/19b-3p inhibits autophagy of HCF through targeting TGF-β R II mRNA. Moreover, enhancement of autophagy rescues inhibition effect of miR-19a-3p/19b-3p on Smad 2 and Akt phosphorylation through TGF-β R II signaling. Our study uncovers a novel mechanism that miR-19a-3p/19b-3p inhibits autophagy-mediated fibrogenesis by targeting TGF-β R II. PMID:27098600

  16. A Whole-Genome Scan and Fine-Mapping Linkage Study of Auditory-Visual Synesthesia Reveals Evidence of Linkage to Chromosomes 2q24, 5q33, 6p12, and 12p12

    PubMed Central

    Asher, Julian E.; Lamb, Janine A.; Brocklebank, Denise; Cazier, Jean-Baptiste; Maestrini, Elena; Addis, Laura; Sen, Mallika; Baron-Cohen, Simon; Monaco, Anthony P.

    2009-01-01

    Synesthesia, a neurological condition affecting between 0.05%–1% of the population, is characterized by anomalous sensory perception and associated alterations in cognitive function due to interference from synesthetic percepts. A stimulus in one sensory modality triggers an automatic, consistent response in either another modality or a different aspect of the same modality. Familiality studies show evidence of a strong genetic predisposition; whereas initial pedigree analyses supported a single-gene X-linked dominant mode of inheritance with a skewed F:M ratio and a notable absence of male-to-male transmission, subsequent analyses in larger samples indicated that the mode of inheritance was likely to be more complex. Here, we report the results of a whole-genome linkage scan for auditory-visual synesthesia with 410 microsatellite markers at 9.05 cM density in 43 multiplex families (n = 196) with potential candidate regions fine-mapped at 5 cM density. Using NPL and HLOD analysis, we identified four candidate regions. Significant linkage at the genome-wide level was detected to chromosome 2q24 (HLOD = 3.025, empirical genome-wide p = 0.047). Suggestive linkage was found to chromosomes 5q33, 6p12, and 12p12. No support was found for linkage to the X chromosome; furthermore, we have identified two confirmed cases of male-to-male transmission of synesthesia. Our results demonstrate that auditory-visual synesthesia is likely to be an oligogenic disorder subject to multiple modes of inheritance and locus heterogeneity. This study comprises a significant step toward identifying the genetic substrates underlying synesthesia, with important implications for our understanding of the role of genes in human cognition and perception. PMID:19200526

  17. A whole-genome scan and fine-mapping linkage study of auditory-visual synesthesia reveals evidence of linkage to chromosomes 2q24, 5q33, 6p12, and 12p12.

    PubMed

    Asher, Julian E; Lamb, Janine A; Brocklebank, Denise; Cazier, Jean-Baptiste; Maestrini, Elena; Addis, Laura; Sen, Mallika; Baron-Cohen, Simon; Monaco, Anthony P

    2009-02-01

    Synesthesia, a neurological condition affecting between 0.05%-1% of the population, is characterized by anomalous sensory perception and associated alterations in cognitive function due to interference from synesthetic percepts. A stimulus in one sensory modality triggers an automatic, consistent response in either another modality or a different aspect of the same modality. Familiality studies show evidence of a strong genetic predisposition; whereas initial pedigree analyses supported a single-gene X-linked dominant mode of inheritance with a skewed F:M ratio and a notable absence of male-to-male transmission, subsequent analyses in larger samples indicated that the mode of inheritance was likely to be more complex. Here, we report the results of a whole-genome linkage scan for auditory-visual synesthesia with 410 microsatellite markers at 9.05 cM density in 43 multiplex families (n = 196) with potential candidate regions fine-mapped at 5 cM density. Using NPL and HLOD analysis, we identified four candidate regions. Significant linkage at the genome-wide level was detected to chromosome 2q24 (HLOD = 3.025, empirical genome-wide p = 0.047). Suggestive linkage was found to chromosomes 5q33, 6p12, and 12p12. No support was found for linkage to the X chromosome; furthermore, we have identified two confirmed cases of male-to-male transmission of synesthesia. Our results demonstrate that auditory-visual synesthesia is likely to be an oligogenic disorder subject to multiple modes of inheritance and locus heterogeneity. This study comprises a significant step toward identifying the genetic substrates underlying synesthesia, with important implications for our understanding of the role of genes in human cognition and perception.

  18. Ancestry of the Brazilian TP53 c.1010G>A (p.Arg337His, R337H) Founder Mutation: Clues from Haplotyping of Short Tandem Repeats on Chromosome 17p

    PubMed Central

    Paskulin, Diego Davila; Giacomazzi, Juliana; Achatz, Maria Isabel; Costa, Sandra; Reis, Rui Manoel; Hainaut, Pierre; dos Santos, Sidney Emanuel Batista; Ashton-Prolla, Patricia

    2015-01-01

    Rare germline mutations in TP53 (17p13.1) cause a highly penetrant predisposition to a specific spectrum of early cancers, defining the Li-Fraumeni Syndrome (LFS). A germline mutation at codon 337 (p.Arg337His, c1010G>A) is found in about 0.3% of the population of Southern Brazil. This mutation is associated with partially penetrant LFS traits and is found in the germline of patients with early cancers of the LFS spectrum unselected for familial history. To characterize the extended haplotypes carrying the mutation, we have genotyped 9 short tandem repeats on chromosome 17p in 12 trios of Brazilian p.Arg337His carriers. Results confirm that all share a common ancestor haplotype of Caucasian/Portuguese-Iberic origin, distant in about 72–84 generations (2000 years assuming a 25 years intergenerational distance) and thus pre-dating European migration to Brazil. So far, the founder p.Arg337His haplotype has not been detected outside Brazil, with the exception of two residents of Portugal, one of them of Brazilian origin. On the other hand, increased meiotic recombination in p.Arg337His carriers may account for higher than expected haplotype diversity. Further studies comparing haplotypes in populations of Brazil and of other areas of Portuguese migration are needed to understand the historical context of this mutation in Brazil. PMID:26618902

  19. [Allelic imbalance of loci 17p13.1 (TP53), 1p36.1 (RUNX3), 16p22 (CDH1) and microsatellite instability in gastric cancer].

    PubMed

    Nemtsova, M V; Bykov, I I; Udilova, A A; Zaletaev, D V; Khorobrykh, T V

    2013-01-01

    We examined allelic imbalance (AI) on loci 17p13.1 (TP53), 1p36.1 (RUNX) and 16p22 (CDHI) and microsatellite instability (MI) with BAT26 in 78 patients with gastric cancer. We have shown a significant difference in the frequency of allelic imbalance of the studied loci among different types of gastric cancer. Frequency of AI in 16p22.1 (CDH1) (p = 0.023), 17p13.1 (TP53) (p = 0.038), microsatellite instability (p = 0.047) and AD two and more loci in a single sample (p = 0.0176) was significantly higher in the intestinal type of gastric cancer than in the diffuse type. We have shown, that, frequency of AI in 16p22.1 (CDH1), and AD two and more loci in a single sample, was higher in thetumors with high or moderate type of tumor cells differentiation (p = 0.0414, p = 0.0057 respectively). We found no significant differences in the groups with metastases in regional lymph nodes, different tumor stage, localization of tumors and the generalization process.

  20. Structural stability and electronic properties of small gold clusters induced by 3p electron atoms

    NASA Astrophysics Data System (ADS)

    Zhang, Meng; Yang, Su-Bin; Feng, Xiao-Juan; Zhao, Li-Xia; Zhang, Hong-Yu; Luo, You-Hua

    2013-01-01

    The geometries and electronic properties of gold clusters doped with atoms containing 3 p valence electrons (MAu n ; M = Al, Si, P, S, Cl; n = 2-8) have been systematically investigated using density functional theory (DFT) at the PBE/LANL2DZ level. A number of low-energy isomers are identified for neutral MAu n clusters. It is found that doping with different 3 p impurity atoms can drastically influence the geometrical structures, relative stabilities, electronic properties, and growth-pattern behaviors of gold clusters, which is very different from the case of 3 d transition-metal impurity doped Au n clusters. Partially filled 3 p electron impurities can stabilize Au clusters. In particular, SiAu4 cluster with T d symmetry have been found to have highly stable geometries and electronic structures with binding energies of 2.43 eV per atom (0.96 eV higher than pristine Au5 clusters), large HOMO-LUMO gaps (2.17 eV), and vertical ionization potentials of 8.68 eV. Using scalar relativistic molecular dynamics at T = 300 K, we show that the T d symmetry structure of SiAu4 is stable. The frontier molecular orbitals (HOMO and LUMO) and the partial densities of states (PDOS) show that strong hybridization occurs between the atomic orbitals of Si and Au atoms, resulting in strong Si-Au bonding. In addition, the vertical ionization potential, the vertical electron affinity, and charge transfers of MAu n clusters have also been analyzed. Our results are in good agreement with available experimental data.

  1. Studies of Yb ^1S0 -- ^3P0 clock transitions

    NASA Astrophysics Data System (ADS)

    Hong, Tao

    2005-05-01

    We are exploring two quite different methods for observing the ultra-sharp 6s^2 ^1S0 -- 6s6p ^3P0 optical interval in atomic Yb, which is considered a primary candidate for future optical frequency standards [1].In the first method, we observe the 578 nm single photon transition allowed in the odd isotopes through internal hyperfine coupling of the nuclear spin.† We shine a 578 nm laser beam on cold Yb atoms held in a magneto-optical trap (MOT), and detect a decrease in MOT fluorescence when the laser is resonant with the clock transition.† Our second approach is to use the even Yb isotopes, connecting the ^1S0 and ^3P0 states† by† a multi- photon transition [2]. Sharp electromagnetically induced transparency and absorption (EITA) resonance features appear when the photon frequencies combine to equal† the ^1S0 -- ^3P0 clock interval.† We will describe our initial studies of† 2 and 3 photon resonances in Yb, including Doppler-free 3 photon EITA. [1]S. G.† Porsev, A. Derevianko, E. N. Fortson, Phys. Rev. A 69, 021403(R)† (2004); H. Katori, in Proc. 6th Symposium Frequency Standards and Metrology, edited by P. Gill (World Scienti.c, Singapore, 2002), pp. 323-330 [2]Tao Hong, Claire Cramer, Warren Nagourney, E. N. Fortson, physics/0409051 and to be published in Phys. Rev. Lett.; Robin Santra, Ennio Arimondo, Tetsuya Ido, Crhis H. Greene, Jun Ye, physics/0411197

  2. Reactions of Ar2+ (3P) ions with some neutrals at 30 K

    NASA Astrophysics Data System (ADS)

    Dupeyrat, G.; Marquette, J. B.; Rowe, B. R.; Rebrion, C.

    1991-01-01

    Measurements of reaction rate coefficients of Ar2+ (3P) with Ar, He, H2, O2 and CO2 at 30 K are reported. They have been performed using the Cinétique de Réaction en Encoulement Supersonique Uniforme apparatus with a newly designed Mach five argon nozzle which is briefly described. All the data remain close to previous selected-ion flow tube determinations at room temperature (D. Smith, D. Grief and N.G. Adams, Int. J. Mass Spectrom, Ion Phys., 30 (1979) 271). The present results are also compared to existing theoretical calculations.

  3. Scaling of collisionally pumped 3s-3p lasers in the neon isoelectronic sequence

    NASA Technical Reports Server (NTRS)

    Feldman, U.; Seely, J. F.; Bhatia, A. K.

    1984-01-01

    Atomic-number scaling in the 3p-3s population-inversion and plasma parameters of neonlike ions of Si, Ar, Ti, Fe, Ge, and Kr is investigated theoretically. The population levels are calculated; the Z-scaling relationships are defined; the results are presented in tables and graphs; and the implications for the laser gain are explored. Laser gain in excess of 1/cm are predicted for all ions except Si V, with a peak of 30/cm for Fe XVII at electron density 10 to the 21st/cu cm.

  4. Effects on sustained performance of time-sharing a three-phase code transformation task /3P-COTRAN/.

    NASA Technical Reports Server (NTRS)

    Alluisi, E. A.; Morgan, B. B., Jr.

    1971-01-01

    A group of 20 highly trained subjects were divided randomly into five equal groups to time-share the 3P-COTRAN task with a different task combination of a multitask performance battery (MTPB) used by Alluisi (1969). The effects of the time-sharing on the 3P-COTRAN performance and the effects of 3P-COTRAN on the time-shared MTPB performances are analyzed.

  5. MiR-142-3p is a RANKL-dependent inducer of cell death in osteoclasts

    PubMed Central

    Fordham, Jezrom B.; Guilfoyle, Katherine; Naqvi, Afsar Raza; Nares, Salvador

    2016-01-01

    MicroRNA are small, non-coding, single-stranded RNAs that are estimated to regulate ~60% of the human genome. MiRNA profiling of monocyte-to-osteoclast differentiation identified miR-142-3p as a miRNA that is significantly, differentially expressed throughout osteoclastogenesis. Enforced expression of miR-142-3p via transient transfection with miR-142-3p mimic inhibited cell-to-cell contact and fusion, decreased protein kinase C alpha expression, and ultimately reduced cell viability. miR-142-3p was also identified as significantly differentially expressed during monocyte-to-macrophage differentiation and overexpression of miR-142-3p prevented their conversion to osteoclasts. Furthermore, the inhibitory effect of miR-142-3p on osteoclastogenesis extended to the conversion of a third osteoclast precursor cell type- dendritic cells. These results demonstrate miR-142-3p to be a negative regulator of osteoclastogenesis from the 3 main precursor cell types: monocytes, macrophages and dendritic cells. Importantly, decreased survival was dependent upon both miR-142-3p expression and RANK-signaling, with no harmful effects detected in the absence of this combination. As such, miR-142-3p represents a novel target for the selective removal of osteoclasts by targeting of osteoclastogenic pathways. PMID:27113904

  6. Mmu-miR-126a-3p plays a role in murine embryo implantation by regulating Itga11.

    PubMed

    Li, Zhengyu; Jia, Jia; Gou, Jinhai; Tong, Aiping; Liu, Xinyu; Zhao, Xia; Yi, Tao

    2015-09-01

    miR-126a-3p has been found to be specifically up-regulated in the process of murine embryo implantation. This study aimed to further clarify the role of miR-126a-3p in embryo implantation. The expression of miR-126a-3p in implantation sites was significantly higher than that in interimplantation sites (P = 0.009). Its expression dynamics in a series of models, including pseudopregnancy, delayed implantation and artificial decidualization, suggested that the induction of miR-126a-3p is dependent on hormonal signalling and decidualization of the endometrium. Bioinformatic analysis predicted and luciferase activity assay confirmed that Itga11, a member of the integrin family, was a target gene of miR-126a-3p. miR-126a-3p bound to the 3' untranslated region of Itga11 and regulated Itga11 by inhibiting mRNA translation and affecting mRNA stability. Transwell assay showed that miR-126a-3p promoted cell migratory and invasive capacity in vitro. Loss of function of miR-126a-3p significantly reduced the number of implantation sites in vivo (P = 0.013). Collectively, miR-126a-3p may play a major role in embryo implantation by regulating Itga11, possibly through impairing cell migratory and invasive capacity. These findings should contribute to a better understanding of the miRNA-based mechanism of embryo implantation. PMID:26194885

  7. Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2

    PubMed Central

    Ahmed, Shahana; Thomas, Gilles; Ghoussaini, Maya; Healey, Catherine S; Humphreys, Manjeet K; Platte, Radka; Morrison, Jonathan; Maranian, Melanie; Pooley, Karen A; Luben, Robert; Eccles, Diana; Evans, D Gareth; Fletcher, Olivia; Johnson, Nichola; Silva, Isabel dos Santos; Peto, Julian; Stratton, Michael R; Rahman, Nazneen; Jacobs, Kevin; Prentice, Ross; Anderson, Garnet L; Rajkovic, Aleksandar; Curb, J David; Ziegler, Regina G; Berg, Christine D; Buys, Saundra S; McCarty, Catherine A; Feigelson, Heather Spencer; Calle, Eugenia E; Thun, Michael J; Diver, W Ryan; Bojesen, Stig; Nordestgaard, Børge G; Flyger, Henrik; Dörk, Thilo; Schürmann, Peter; Hillemanns, Peter; Karstens, Johann H; Bogdanova, Natalia V; Antonenkova, Natalia N; Zalutsky, Iosif V; Bermisheva, Marina; Fedorova, Sardana; Khusnutdinova, Elza; Kang, Daehee; Yoo, Keun-Young; Noh, Dong Young; Ahn, Sei-Hyun; Devilee, Peter; van Asperen, Christi J; Tollenaar, R A E M; Seynaeve, Caroline; Garcia-Closas, Montserrat; Lissowska, Jolanta; Brinton, Louise; Peplonska, Beata; Nevanlinna, Heli; Heikkinen, Tuomas; Aittomäki, Kristiina; Blomqvist, Carl; Hopper, John L; Southey, Melissa C; Smith, Letitia; Spurdle, Amanda B; Schmidt, Marjanka K; Broeks, Annegien; van Hien, Richard R; Cornelissen, Sten; Milne, Roger L; Ribas, Gloria; González-Neira, Anna; Benitez, Javier; Schmutzler, Rita K; Burwinkel, Barbara; Bartram, Claus R; Meindl, Alfons; Brauch, Hiltrud; Justenhoven, Christina; Hamann, Ute; Chang-Claude, Jenny; Hein, Rebecca; Wang-Gohrke, Shan; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Kataja, Vesa; Olson, Janet E; Wang, Xianshu; Fredericksen, Zachary; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; English, Dallas R; Hankinson, Susan E; Cox, David G; Kraft, Peter; Vatten, Lars J; Hveem, Kristian; Kumle, Merethe; Sigurdson, Alice; Doody, Michele; Bhatti, Parveen; Alexander, Bruce H; Hooning, Maartje J; van den Ouweland, Ans M W; Oldenburg, Rogier A; Schutte, Mieke; Hall, Per; Czene, Kamila; Liu, Jianjun; Li, Yuqing; Cox, Angela; Elliott, Graeme; Brock, Ian; Reed, Malcolm W R; Shen, Chen-Yang; Yu, Jyh-Cherng; Hsu, Giu-Cheng; Chen, Shou-Tung; Anton-Culver, Hoda; Ziogas, Argyrios; Andrulis, Irene L; Knight, Julia A; kConFab; Beesley, Jonathan; Goode, Ellen L; Couch, Fergus; Chenevix-Trench, Georgia; Hoover, Robert N; Ponder, Bruce A J; Hunter, David J; Pharoah, Paul D P; Dunning, Alison M; Chanock, Stephen J; Easton, Douglas F

    2009-01-01

    Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage1. To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR = 1.11, 95% CI = 1.08–1.13, P = 4.1 × 10−23) and 17q (rs6504950: per-allele OR = 0.95, 95% CI = 0.92–0.97, P = 1.4 × 10−8). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q. PMID:19330027

  8. Metalloid tolerance based on phytochelatins is not functionally equivalent to the arsenite transporter Acr3p.

    PubMed

    Wysocki, Robert; Clemens, Stephan; Augustyniak, Daria; Golik, Pawel; Maciaszczyk, Ewa; Tamás, Markus J; Dziadkowiec, Dorota

    2003-05-01

    Active transport of metalloids by Acr3p and Ycf1p in Saccharomyces cerevisiae and chelation by phytochelatins in Schizosaccharomyces pombe, nematodes, and plants represent distinct strategies of metalloid detoxification. In this report, we present results of functional comparison of both resistance mechanisms. The S. pombe and wheat phytochelatin synthase (PCS) genes, when expressed in S. cerevisiae, mediate only modest resistance to arsenite and thus cannot functionally compensate for Acr3p. On the other hand, we show for the first time that phytochelatins also contribute to antimony tolerance as PCS fully complement antimonite sensitivity of ycf1Delta mutant. Remarkably, heterologous expression of PCS sensitizes S. cerevisiae to arsenate, while ACR3 confers much higher arsenic resistance in pcsDelta than in wild-type S. pombe. The analysis of PCS and ACR3 homologues distribution in various organisms and our experimental data suggest that separation of ACR3 and PCS genes may lead to the optimal tolerance status of the cell.

  9. A New Case of an Extremely Rare 3p21.31 Interstitial Deletion

    PubMed Central

    Lovrecic, Luca; Bertok, Sara; Žerjav Tanšek, Mojca

    2016-01-01

    Interstitial 3p21.31 deletions have been very rarely reported. We describe a 7-year-old boy with global developmental delay, specific facial characteristics, hydronephrosis, and hypothyreosis with a de novo deletion of 3p21.31, encompassing 29 OMIM genes. Despite the wide use of microarrays, no similar case has been reported in the literature so far. Five overlapping cases are deposited in the DECIPHER database, 2 of which have significant overlapping chromosomal aberrations. They both share some phenotypic characteristics with our case, e.g. developmental delay, intellectual disability and facial dysmorphism (arched eyebrows, hypertelorism, low-set ears, and a large nose tip). In addition, loss-of-function mutations in the SETD2 gene (OMIM 612778) of the deleted region have been described in 3 patients, presenting with some similar clinical features, namely overgrowth, intellectual disability, speech delay, hypotonia, autism, and epilepsy. Therefore, SETD2 may explain part of the phenotype in our case. We focused on 3 other genes in the deleted region, based on their known functions, namely CSPG5 (OMIM 606775), PTH1R (OMIM 168468) and SMARCC1 (OMIM 601732), and assessed their potentially important role in describing the patient's phenotype. Additional cases with haploinsufficiency of this region are needed to elucidate further genotype-phenotype correlations. PMID:27385966

  10. Linkage of a gene for familial hypobetalipoproteinemia to chromosome 3p21.1-22.

    PubMed Central

    Yuan, B; Neuman, R; Duan, S H; Weber, J L; Kwok, P Y; Saccone, N L; Wu, J S; Liu, K Y; Schonfeld, G

    2000-01-01

    Familial hypobetalipoproteinemia (FHBL) is an apparently autosomal dominant disorder of lipid metabolism characterized by less than fifth percentile age- and sex-specific levels of apolipoprotein beta (apobeta) and low-density lipoprotein-cholesterol. In a minority of cases, FHBL is due to truncation-producing mutations in the apobeta gene on chromosome 2p23-24. Previously, we reported on a four-generation FHBL kindred in which we had ruled out linkage of the trait to the apobeta gene. To locate other loci containing genes for low apobeta levels in the kindred, a genomewide search was conducted. Regions on 3p21.1-22 with two-point LOD scores >1.5 were identified. Additional markers were typed in the region of these signals. Two-point LOD scores in the region of D3S2407 increased to 3.35 at O = 0. GENEHUNTER confirmed this finding with an nonparametric multipoint LOD score of 7.5 (P=.0004). Additional model-free analyses were conducted with the square root of the apobeta level as the phenotype. Results from the Loki and SOLAR programs further confirmed linkage of FHBL to 3p21.1-22. Weaker linkage to a region near D19S916 was also indicated by Loki and SOLAR. Thus, a heretofore unidentified genetic susceptibility locus for FHBL may reside on chromosome 3. PMID:10762553

  11. O(3P) attack on boranes. II. B5H9

    NASA Astrophysics Data System (ADS)

    Cheng, H.-Z.; Bauer, S. H.

    1991-06-01

    When B5H9 is injected into a stream of He that is carrying O(3P) atoms (approximately 100/1), at a total pressure of 5-15 Torr, a blue-green flame develops. The major chemiluminescent species is BO(A 2Π). While its translational and rotational temperatures are ≊350 K, the vibrational temperature in the A state is high, ≊3800 K. From among the many products of this reaction, the OH radical can be most easily quantitated by measuring the intensity of its laser-induced fluorescence. The central streamline from a flow-tube reactor was extracted into an evacuated plenum via a pinhole. The time-intensity profile was calibrated using C2H6 for the fuel. Check runs were made with B2H6. A multistep mechanism was developed for B5H9+O(3P) that simulates the shape as well as the magnitude of the OH concentration over a reactor residence time 0.5-10 ms. Less than a dozen crucial reactions were identified by means of an extended sensitivity analysis. Breakdown schemes for the oxidation of B2H6 and B5H9 have been developed.

  12. miR-148a-3p overexpression contributes to glomerular cell proliferation by targeting PTEN in lupus nephritis.

    PubMed

    Qingjuan, Liu; Xiaojuan, Feng; Wei, Zhang; Chao, Wu; Pengpeng, Kang; Hongbo, Li; Sanbing, Zhang; Jun, Hao; Min, Yang; Shuxia, Liu

    2016-03-15

    The objective of this study was to investigate the role of miR-148a-3p in lupus nephritis (LN) based on data from previous studies and a microRNA assay. We evaluated the miR-148a-3p expression level in LN renal tissues and blood serum to determine its clinicopathological significance and effect on glomerular cell proliferation. Then, we collected renal glomeruli from LN mice and determined the miR-148a-3p, proliferating cell nuclear antigen (PCNA), and PCNA/Thy1 expression. We performed functional analyses of miR-148a-3p in vitro and in vivo. We also investigated the target gene of miR-148a-3p in LN. The results showed that miR-148a-3p expression levels were significantly higher not only in glomeruli but also in the blood serum during LN and increased in the glomeruli of LN mice and that at the same time there was positive correlation between miR-148a-3p and PCNA expression of glomruli. Overexpression of miR-148a-3p accelerated cell proliferation and PCNA expression, while a miR-148a-3p inhibitor inhibited cell proliferation via the Akt/cyclin D1 pathway. Furthermore, miR-148a-3p overexpression reduced the phosphatase and tensin homology deleted on chromosome ten (PTEN) expression level, while miR-148a-3p silencing increased its expression in high-mobility group box 1 (HMGB1)-induced mouse mesangial cells (MMCs). Luciferase assays demonstrated that miR-148a-3p could directly bind to the PTEN 3'-UTR. PTEN overexpression inhibited MMC proliferation considerably, resembling the results observed during miR-148a-3p inhibition. Reducing miR-148a-3p expression upregulated PTEN in the glomeruli and improved renal function in LN mice. Thus miR-148a-3p may promote proliferation and contribute to LN progression by targeting PTEN.

  13. Unified interpretation of Hund's first and second rules for 2p and 3p atoms.

    PubMed

    Oyamada, Takayuki; Hongo, Kenta; Kawazoe, Yoshiyuki; Yasuhara, Hiroshi

    2010-10-28

    A unified interpretation of Hund's first and second rules for 2p (C, N, O) and 3p (Si, P, S) atoms is given by Hartree-Fock (HF) and multiconfiguration Hartree-Fock (MCHF) methods. Both methods exactly satisfy the virial theorem, in principle, which enables one to analyze individual components of the total energy E(=T+V(en)+V(ee)), where T, V(en), and V(ee) are the kinetic, the electron-nucleus attraction, and the electron-electron repulsion energies, respectively. The correct interpretation for each of the two rules can only be achieved under the condition of the virial theorem 2T+V=0 by investigating how V(en) and V(ee) interplay to attain the lower total potential energy V(=V(en)+V(ee)). The stabilization of the more stable states for all the 2p and 3p atoms is ascribed to a greater V(en) that is caused by contraction of the valence orbitals accompanied with slight expansion of the core orbitals. The contraction of the valence orbitals for the two rules is a consequence of reducing the Hartree screening of the nucleus at short interelectronic distances. The reduced screening in the first rule is due to a greater amount of Fermi hole contributions in the state with the highest total spin-angular momentum S. The reduced screening in the second rule is due to the fact that two valence electrons are more likely to be on opposite sides of the nucleus in the state with the highest total orbital-angular momentum L. For each of the two rules, the inclusion of correlation does not qualitatively change the HF interpretation, but HF overestimates the energy difference ∣ΔE∣ between two levels being compared. The magnitude of the correlation energy is significantly larger for the lower L states than for the higher L states since two valence electrons in the lower L states are less likely to be on opposite sides of the nucleus. The MCHF evaluation of ∣ΔE∣ is in excellent agreement with experiment. The present HF and MCHF calculations demonstrate the above statements

  14. Genomic profiling of the genes on chromosome 3p in sporadic clear cell renal cell carcinoma.

    PubMed

    Togo, Yoshikazu; Yoshikawa, Yoshie; Suzuki, Toru; Nakano, Yoshiro; Kanematsu, Akihiro; Zozumi, Masataka; Nojima, Michio; Hirota, Seiichi; Yamamoto, Shingo; Hashimoto-Tamaoki, Tomoko

    2016-04-01

    Somatic mutations of the BRCA1 associated protein-1 (BAP1) gene, which maps to 3p21, have been found in several tumors including malignant mesothelioma, uveal melanoma, and renal cell carcinoma (RCC). The role of BAP1 inactivation in tumor development remains unclear. It has been reported that Vhl knock-out mice did not develop RCC, but Vhl knock-out mice with single allele loss of Bap1 in nephron progenitor cells developed RCC, indicating that Bap1 inactivation may be essential in murine renal tumorigenesis. To clarify the role of BAP1 in human RCC development, we performed mutation analyses, including copy number detection of BAP1 and assessment of allelic imbalance using microsatellite polymorphisms on 3p, in 45 RCC samples derived from 45 patients without VHL or BAP1 germline mutation. Additionally, we analyzed the sequences of the VHL, PBRM1, and SETD2 genes, and examined promoter methylation of VHL. Using immunostaining, we also checked for expression of BAP1 protein, which is normally located in the nuclei. None of the RCCs had biallelic deletion of BAP1, but five (11.1%) showed a biallelic mutation (four with a sequence-level mutation with monoallelic loss and one with a biallelic sequence-level mutation); these cells were negative for nuclear BAP1 staining. These patients had worse recurrence-free survival than the patients without a biallelic mutation (p=0.046). However, there were no significant differences in worse outcome by multivariate analysis combined with age, T stage, histological subtype, infiltration and vascular invasion. In 35 RCCs (77.8%), monoallelic loss of BAP1 was accompanied by VHL biallelic mutation or VHL promoter hypermethylation. In five RCCs (11.1%), we detected 3p loss-of-heterozygosity, but the copy number of BAP1 was normal. Surprisingly, nuclear staining of BAP1 was negative in 10 out of 31 tumors (32.3%) with hemizygous normal BAP1, suggesting that haploinsufficiency may relate to RCC development.

  15. Unified interpretation of Hund's first and second rules for 2p and 3p atoms.

    PubMed

    Oyamada, Takayuki; Hongo, Kenta; Kawazoe, Yoshiyuki; Yasuhara, Hiroshi

    2010-10-28

    A unified interpretation of Hund's first and second rules for 2p (C, N, O) and 3p (Si, P, S) atoms is given by Hartree-Fock (HF) and multiconfiguration Hartree-Fock (MCHF) methods. Both methods exactly satisfy the virial theorem, in principle, which enables one to analyze individual components of the total energy E(=T+V(en)+V(ee)), where T, V(en), and V(ee) are the kinetic, the electron-nucleus attraction, and the electron-electron repulsion energies, respectively. The correct interpretation for each of the two rules can only be achieved under the condition of the virial theorem 2T+V=0 by investigating how V(en) and V(ee) interplay to attain the lower total potential energy V(=V(en)+V(ee)). The stabilization of the more stable states for all the 2p and 3p atoms is ascribed to a greater V(en) that is caused by contraction of the valence orbitals accompanied with slight expansion of the core orbitals. The contraction of the valence orbitals for the two rules is a consequence of reducing the Hartree screening of the nucleus at short interelectronic distances. The reduced screening in the first rule is due to a greater amount of Fermi hole contributions in the state with the highest total spin-angular momentum S. The reduced screening in the second rule is due to the fact that two valence electrons are more likely to be on opposite sides of the nucleus in the state with the highest total orbital-angular momentum L. For each of the two rules, the inclusion of correlation does not qualitatively change the HF interpretation, but HF overestimates the energy difference ∣ΔE∣ between two levels being compared. The magnitude of the correlation energy is significantly larger for the lower L states than for the higher L states since two valence electrons in the lower L states are less likely to be on opposite sides of the nucleus. The MCHF evaluation of ∣ΔE∣ is in excellent agreement with experiment. The present HF and MCHF calculations demonstrate the above statements

  16. Observation of the 1S0-3P0 transition in atomic ytterbium for optical clocks and qubit arrays.

    PubMed

    Hong, Tao; Cramer, Claire; Cook, Eryn; Nagourney, Warren; Fortson, E N

    2005-10-01

    We report an observation of the weak 6 1S0-6 3P0 transition in (171,173)Yb as an important step to establishing Yb as a primary candidate for future optical frequency standards, and to open up a new approach for qubits using the 1S0 and 3P0 states of Yb atoms in an optical lattice.

  17. MicroRNA-338-3p suppresses tumor growth of esophageal squamous cell carcinoma in vitro and in vivo.

    PubMed

    Li, Xinyu; Li, Zhihong; Yang, Guiyun; Pan, Zhenxiang

    2015-09-01

    Accumulating evidence has shown that microRNAs (miRNAs) are aberrantly expressed in human esophageal squamous cell carcinoma (ESCC) and are crucial in tumorigenesis, among which miR‑338‑3p has been examined to be downregulated in patients with ESCC. However, the role of miR‑338‑3p in ESCC remains to be elucidated. In the present study, the role of miR‑338‑3p on the growth and survival of an ESCC cell line was determined with several in vitro approaches and in nude mouse models. It was determined that miR‑338‑3p expression was frequently downregulated in ESCC tissue compared with corresponding adjacent non‑tumor tissue, and that its expression was significantly correlated with tumor stage and metastasis. Overexpression of miR‑338‑3p in ESCC cells suppressed cell proliferation, colony formation, migration and invasion, and induced cell arrest at the G0/G1 stage and cell apoptosis in vitro. In addition, it was demonstrated that overexpression of miR‑338‑3p significantly suppresses tumor growth of xenograft tumors in mice (P<0.05). These findings revealed that miR‑338‑3p may act as a tumor suppressor in ESCC, and its dysregulation may be involved in the initiation and development of human ESCC. In addition, it was suggested that miR‑338‑3p may be a potential therapeutic agent for treatment of ESCC.

  18. A comparative study of Li8NaV3(P2O7)3(PO4)2 and Li9V3(P2O7)3(PO4)2: Synthesis, structure and electrochemical properties

    NASA Astrophysics Data System (ADS)

    Kuang, Quan; Zhao, Yanming; Dong, Youzhong; Fan, Qinghua; Lin, Xinghao; Liu, Xudong

    2016-02-01

    The energy-density improvement for cathode materials by using the method of occupying the Li site with the lowest formation enthalpy was first presented, and successfully applied to Li9V3(P2O7)3(PO4)2. Herein, the synthesis, structure and electrochemical properties (including both Li extraction and intercalation) of mixed alkali-ion phosphate Li8NaV3(P2O7)3(PO4)2 were comprehensively studied, and compared with its isologue Li9V3(P2O7)3(PO4)2. Both Li8NaV3(P2O7)3(PO4)2 and Li9V3(P2O7)3(PO4)2 were synthesized via an original two-step method for the first time. The sintering temperature of Li8NaV3(P2O7)3(PO4)2 (650 °C) was much lower than that of Li9V3(P2O7)3(PO4)2 (750 °C). The Rietveld structure refinement indicated that Na ions occupied the Li1(2b) site of Li9V3(P2O7)3(PO4)2 as expected, and Li8NaV3(P2O7)3(PO4)2 showed a single charge plateau at 4.4 V vs. Li in the 1st cycle. However, the Na ions migrated from Li1(2b) site after the initial cycle, and the charge plateau at 3.7 V vs. Li reappeared. On the other hand, both Li9V3(P2O7)3(PO4)2 and Li8NaV3(P2O7)3(PO4)2 can deliver a high reversible capacity (∼200 mAh g-1), and reveal excellent cycle and rate performance in 3.0-0.05 V vs. Li. The gentle structure changes along with abundant Li intercalation into the bulks suggested that Li9V3(P2O7)3(PO4)2 and Li8NaV3(P2O7)3(PO4)2 were also promising anode materials for Li-ion batteries.

  19. Theoretical study of stereodynamics for reaction O(3P)+HCl

    NASA Astrophysics Data System (ADS)

    Zhu, Tong; Hu, Guo-Dong; Chen, Jian-Zhong; Liu, Xin-Guo; Zhang, Qing-Gang

    2010-08-01

    The vector correlation between products and reagents for reaction O(3P)+HCl→OH+Cl is studied using a quasi-classical trajectory (QCT) method on the benchmark potential energy surface of the ground 3A″ state [Ramachandran and Peterson, J. Chem. Phys. 119 (2003) 9550]. The generalised differential cross section (2π/σ)(dσ00/dωt) is presented in the centre of mass frame. The distribution of dihedral angles, P(phir), and the distribution of angles between k and j', P(θr), are calculated. The influence of the collision energy and the influence of the reagent rotation and vibration on the product polarization are studied in the present work. The calculated results indicate that the rotational polarization of the product molecule is almost independent of collision energy but sensitive to the reagent rotation and vibration.

  20. Mechanism of O((3)P) formation from a hydroxyl radical pair in aqueous solution.

    PubMed

    Codorniu-Hernández, Edelsys; Hall, Kyle Wm; Boese, A Daniel; Ziemianowicz, Daniel; Carpendale, Sheelagh; Kusalik, Peter G

    2015-10-13

    The reaction mechanism for the rapid formation of a triplet oxygen atom, O((3)P), from a pair of triplet-state hydroxyl radicals in liquid water is explored utilizing extensive Car-Parrinello MD simulations and advanced visualization techniques. The local solvation structures, the evolution of atomic charges, atomic separations, spin densities, electron localization functions, and frontier molecular orbitals, as well as free energy profiles, evidence that the reaction proceeds through a hybrid (hydrogen atom transfer and electron-proton transfer) and hemibond-assisted reaction mechanism. A benchmarking study utilizing high-level ab initio calculations to examine the interactions of a hydroxyl radical pair in the gas phase and the influence of a hemibonded water is also provided. The results presented here should serve as a foundation for further experimental and theoretical studies aimed at better understanding the role and potential applications of the triplet oxygen atom as a potent reactive oxygen species. PMID:26574263

  1. Above-threshold ionization near the 3p4d 1Fo autoionizing state in magnesium

    NASA Astrophysics Data System (ADS)

    Reber, A.; Baynard, T.; Martín, F.; Bachau, H.; Berry, R. S.

    2005-05-01

    Two-photon above-threshold ionization (ATI) relative cross sections from the 3P1 state of Mg have been measured using two-color ionization in the focus of a magnetic bottle spectrometer and have been calculated using the Green’s-function method in the Feshbach formalism and an L2 -integrable close-coupling approach, with a basis of L2 -integrable B -spline functions. We report these cross sections in the region of 3d4p Fo1 autoionizing state, with photon energies of 3.3-3.6eV . This is one of the few direct comparisons between ab initio theory and experiments in ATI in the vicinity of a Feshbach resonance. A good agreement between theory and experiment is found in the relative total cross sections.

  2. Collision dynamics of O(3P) + DMMP using a specific reaction parameters potential form.

    PubMed

    Conforti, Patrick F; Braunstein, Matthew; Stearns, Jaime A; Dodd, James A

    2012-03-15

    Starting from previous benchmark CBS-QB3 electronic structure calculations (Conforti, P. F.; Braunstein, M.; Dodd, J. A. J. Phys. Chem. A 2009, 113, 13752), we develop two global potential energy surfaces for O((3)P) + DMMP collisions, using the specific reaction parameters approach. Each surface is simultaneously fit along the three major reaction pathways: hydrogen abstraction, hydrogen elimination, and methyl elimination. We then use these surfaces in classical dynamics simulations and compute reactive cross sections from 4 to 10 km s(-1) collision velocity. We examine the energy disposal and angular distributions of the reactive and nonreactive products. We find that for reactive collisions, an unusually large amount of the initial collision energy is transformed into internal energy. We analyze the nonreactive and reactive product internal energy distributions, many of which fit Boltzmann temperatures up to ~2000 K.

  3. Precision Hyperfine Structure of 2;^3P State of ^3He with External Magnetic

    NASA Astrophysics Data System (ADS)

    Wu, Qixue; Drake, G. W. F.

    2007-06-01

    The theory of the Zeeman effect can be used to extrapolate precise measurements for the fine structure or the hyperfine structure to zero-field strength. In the present work, the hyperfine structure of 2;^3P state of ^3He with external magnetic fields is precisely calculated. The values of the fields for 32 crossings and five anticrossings of the magnetic sublevels are theoretically predicted for magnetic field strengths up to 1 Tesla. The results are compared with experimental work. We include the linear terms, diamagnetic terms, and the 2̂ relativistic correction terms in the Zeeman Hamiltonian. All related matrix elements are calculated with high accuracy by the use of double basis set Hylleraas type variational wave functions[1,2].[1] Z. -C. Yan and G.W.F. Drake, Phys. Rev. A 50, R1980 (1994).[2] Q. Wu and G.W.F. Drake, J. Phys. B 40, 393 (2007).

  4. Asymmetry in the triplet 3p-4s Mg lines in cool DZ white dwarfs

    NASA Astrophysics Data System (ADS)

    Allard, N. F.; Leininger, T.; Gadéa, F. X.; Brousseau-Couture, V.; Dufour, P.

    2016-04-01

    The purpose of the present work is to make an exhaustive study of the line shape of the triplet 3p-4s Mg line (Mgb triplet), which is perturbed by He in the extreme physical conditions found in the cool atmosphere of DZ white dwarfs. This study is undertaken by inferring both a unified theory of spectral line broadening and ab initio potential energies. Cool white dwarfs require a specific treatment for line broadening owing to the high helium densities that are involved. Beyond the conventional symmetrical Lorentzian core at low density, we show that the line profiles are asymmetrical and have significant additional contributions on the short wavelength side. This blue asymmetry is a consequence of low maxima in the corresponding Mg-He potential energy difference curves at short and intermediate internuclear distances. The new profiles are shown to provide a good fit to an SDSS (Sloan Digital Sky Survey) observation.

  5. Reactions of Atomic Oxygen (O(3P)) with Polybutadienes and Related Polymers

    NASA Technical Reports Server (NTRS)

    Golub, Morton A.; Lerner, Narcinda R.; Wydeven, Theodore

    1987-01-01

    Thin films of the following polymers were exposed at ambient temperature to ground-state oxygen atoms (O(3P)), generated by a radio-frequency glow discharge in O2: cis- and trans-1,4-polybutadienes (CB and TB), amorphous 1,2-polybutadiene (VB), polybutadienes with different 1,4/1,2 contents, trans polypentenamer (TP), cis and trans polyoctenamers (CO and TO), and ethylene-propylene rubber (EPM). Transmission infrared spectra of CB and TB films revealed extensive surface recession, or etching, unaccompanied by any microstructural changes within the films, demonstrating that the reactions were confined to the surface layers. Contrary to the report by Rabek, Lucki, and Ranby (1979), there was no O(3P)-induced cis-trans isomerization in CB or TB. From weight-loss measurements, etch rates for polybutadienes were found to be markedly dependent on vinyl content, decreasing by two orders of magnitude from CB (2% 1,2) to structures with 30 to 40% 1,2 double bonds, thereafter increasing by half an order of magnitude to VB (97% 1,2). Relative etch rates for EMP and the polyalkenamers were in the order: EMP is greater than CO (or TO) is greater than TP is greater than CB. The sole non-elastomer examined, TB, had an etch rate about six times that of CB, ascribable to a morphology difference. Cis/trans content had a negligible effect on the etch rate of the polyalkenamers. Mechanisms involving crosslinking through units are proposed for the unexpected protection imparted to polybutadienes by the 1,2 double bonds.

  6. Functional Expression and Characterization of Schizosaccharomyces pombe Avt3p as a Vacuolar Amino Acid Exporter in Saccharomyces cerevisiae

    PubMed Central

    Chardwiriyapreecha, Soracom; Manabe, Kunio; Iwaki, Tomoko; Kawano-Kawada, Miyuki; Sekito, Takayuki; Lunprom, Siriporn; Akiyama, Koichi; Takegawa, Kaoru; Kakinuma, Yoshimi

    2015-01-01

    In Saccharomyces cerevisiae, Avt3p and Avt4p mediate the extrusion of several amino acids from the vacuolar lumen into the cytosol. SpAvt3p of Schizosaccharomyces pombe, a homologue of these vacuolar amino acid transporters, has been indicated to be involved in spore formation. In this study, we confirmed that GFP-SpAvt3p localized to the vacuolar membrane in S. pombe. The amounts of various amino acids increased significantly in the vacuolar pool of avt3Δ cells, but decreased in that of avt3+-overexpressing avt3Δ cells. These results suggest that SpAvt3p participates in the vacuolar compartmentalization of amino acids in S. pombe. To examine the export activity of SpAvt3p, we expressed the avt3+ gene in S. cerevisiae cells. We found that the heterologously overproduced GFP-SpAvt3p localized to the vacuolar membrane in S. cerevisiae. Using the vacuolar membrane vesicles isolated from avt3+-overexpressing S. cerevisiae cells, we detected the export activities of alanine and tyrosine in an ATP-dependent manner. These activities were inhibited by the addition of a V-ATPase inhibitor, concanamycin A, thereby suggesting that the activity of SpAvt3p is dependent on a proton electrochemical gradient generated by the action of V-ATPase. In addition, the amounts of various amino acids in the vacuolar pools of S. cerevisiae cells were decreased by the overproduction of SpAvt3p, which indicated that SpAvt3p was functional in S. cerevisiae cells. Thus, SpAvt3p is a vacuolar transporter that is involved in the export of amino acids from S. pombe vacuoles. PMID:26083598

  7. Functional Expression and Characterization of Schizosaccharomyces pombe Avt3p as a Vacuolar Amino Acid Exporter in Saccharomyces cerevisiae.

    PubMed

    Chardwiriyapreecha, Soracom; Manabe, Kunio; Iwaki, Tomoko; Kawano-Kawada, Miyuki; Sekito, Takayuki; Lunprom, Siriporn; Akiyama, Koichi; Takegawa, Kaoru; Kakinuma, Yoshimi

    2015-01-01

    In Saccharomyces cerevisiae, Avt3p and Avt4p mediate the extrusion of several amino acids from the vacuolar lumen into the cytosol. SpAvt3p of Schizosaccharomyces pombe, a homologue of these vacuolar amino acid transporters, has been indicated to be involved in spore formation. In this study, we confirmed that GFP-SpAvt3p localized to the vacuolar membrane in S. pombe. The amounts of various amino acids increased significantly in the vacuolar pool of avt3Δ cells, but decreased in that of avt3+-overexpressing avt3Δ cells. These results suggest that SpAvt3p participates in the vacuolar compartmentalization of amino acids in S. pombe. To examine the export activity of SpAvt3p, we expressed the avt3+ gene in S. cerevisiae cells. We found that the heterologously overproduced GFP-SpAvt3p localized to the vacuolar membrane in S. cerevisiae. Using the vacuolar membrane vesicles isolated from avt3+-overexpressing S. cerevisiae cells, we detected the export activities of alanine and tyrosine in an ATP-dependent manner. These activities were inhibited by the addition of a V-ATPase inhibitor, concanamycin A, thereby suggesting that the activity of SpAvt3p is dependent on a proton electrochemical gradient generated by the action of V-ATPase. In addition, the amounts of various amino acids in the vacuolar pools of S. cerevisiae cells were decreased by the overproduction of SpAvt3p, which indicated that SpAvt3p was functional in S. cerevisiae cells. Thus, SpAvt3p is a vacuolar transporter that is involved in the export of amino acids from S. pombe vacuoles.

  8. MicroRNA-490-3p inhibits proliferation of A549 lung cancer cells by targeting CCND1

    SciTech Connect

    Gu, Haihua; Yang, Tao; Fu, Shaozi; Chen, Xiaofan; Guo, Lei; Ni, Yiming

    2014-01-31

    Highlights: • We examined the level of miR-490-3p in A549 lung cancer cells compared with normal bronchial epithelial cell line. • We are the first to show the function of miR-490-3p in A549 lung cancer cells. • We demonstrate CCND1 may be one of the targets of miR-490-3p. - Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate the translation of messenger RNAs by binding their 3′-untranslated region (3′UTR). In this study, we found that miR-490-3p is significantly down-regulated in A549 lung cancer cells compared with the normal bronchial epithelial cell line. To better characterize the role of miR-490-3p in A549 cells, we performed a gain-of-function analysis by transfecting the A549 cells with chemically synthesized miR-490-3P mimics. Overexpression of miR-490-3P evidently inhibits cell proliferation via G1-phase arrest. We also found that forced expression of miR-490-3P decreased both mRNA and protein levels of CCND1, which plays a key role in G1/S phase transition. In addition, the dual-luciferase reporter assays indicated that miR-490-3P directly targets CCND1 through binding its 3′UTR. These findings indicated miR-490-3P could be a potential suppressor of cellular proliferation.

  9. miR-224-3p inhibits autophagy in cervical cancer cells by targeting FIP200.

    PubMed

    Fang, Wang; Shu, Shan; Yongmei, Li; Endong, Zhu; Lirong, Yin; Bei, Sun

    2016-01-01

    Cervical cancer (CC) is a malignant solid tumor, which is one of the main causes of morbidity and mortality in women. Persistent High-risk human papillomavirus (hrHPV) infection is closely related to cervical cancer and autophagy has been suggested to inhibit viral infections. miRNAs have been reported to regulate autophagy in many solid tumors with many studies implicating miR-224-3p in the regulation of autophagy. In this study, we performed a miRNA microarray analysis on CC tissues and found that a large number of miRNAs with differential expressions in hrHPV-infected tissues. We identified miR-224-3p as a candidate miRNA selectively up regulated in HPV-infected tissues and cell lines. Further analysis revealed that miR-224-3p regulates autophagy in cervical cancer tissues and cell lines. While the overexpression of miR-224-3p inhibits autophagy in HPV-infected cells, knocking down endogenous miR-224-3p increases autophagy activity in the same cells. In addition, we found that miR-224-3p directly inhibits the expression of autophagy related gene, FAK family-interacting protein of 200 kDa (FIP200). In summary, we found that miR-224-3p regulates autophagy in hrHPV-induced cervical cancer cells through targeting FIP200 expression. PMID:27615604

  10. Expression of miR-199a-3p in human adipocytes is regulated by free fatty acids and adipokines.

    PubMed

    Gu, Nan; You, Lianghui; Shi, Chunmei; Yang, Lei; Pang, Lingxia; Cui, Xianwei; Ji, Chenbo; Zheng, Wen; Guo, Xirong

    2016-08-01

    Obesity is associated with a notable risk for disease, including risk of cardiovascular disorders, type 2 diabetes mellitus (T2DM) and hypertension. Adipose tissue modulates the metabolism by releasing free fatty acids (FFAs) and adipokines, including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL‑6). Altered secretion patterns of FFAs and adipokines have been demonstrated to result in obesity‑associated insulin resistance (IR) and inflammatory responses. MicroRNA-199a-3p (miR)-199a-3p expression is significantly induced in differentiated human adipose-derived mesenchymal stem cells and indicates the association with T2DM. However, the association between miR-199a-3p levels in adipocytes and obesity‑associated IR, as well as inflammatory responses remains to be elucidated. The present study observed an elevation of miR‑199a‑3p expression level in mature human adipocytes (visceral) compared with pre-adipocytes. In addition, miR‑199a‑3p expression was higher in visceral adipose deposits from obese subjects. FFA, TNF-α, IL‑6 and leptin significantly induced miR‑199a‑3p expression in mature human adipocytes, while resistin had the opposite effect. miR‑199a‑3p may represent a factor in the modulation of obesity‑associated IR and inflammatory responses. PMID:27279151

  11. UCS protein Rng3p is essential for myosin-II motor activity during cytokinesis in fission yeast.

    PubMed

    Stark, Benjamin C; James, Michael L; Pollard, Luther W; Sirotkin, Vladimir; Lord, Matthew

    2013-01-01

    UCS proteins have been proposed to operate as co-chaperones that work with Hsp90 in the de novo folding of myosin motors. The fission yeast UCS protein Rng3p is essential for actomyosin ring assembly and cytokinesis. Here we investigated the role of Rng3p in fission yeast myosin-II (Myo2p) motor activity. Myo2p isolated from an arrested rng3-65 mutant was capable of binding actin, yet lacked stability and activity based on its expression levels and inactivity in ATPase and actin filament gliding assays. Myo2p isolated from a myo2-E1 mutant (a mutant hyper-sensitive to perturbation of Rng3p function) showed similar behavior in the same assays and exhibited an altered motor conformation based on limited proteolysis experiments. We propose that Rng3p is not required for the folding of motors per se, but instead works to ensure the activity of intrinsically unstable myosin-II motors. Rng3p is specific to conventional myosin-II and the actomyosin ring, and is not required for unconventional myosin motor function at other actin structures. However, artificial destabilization of myosin-I motors at endocytic actin patches (using a myo1-E1 mutant) led to recruitment of Rng3p to patches. Thus, while Rng3p is specific to myosin-II, UCS proteins are adaptable and can respond to changes in the stability of other myosin motors.

  12. miR-224-3p inhibits autophagy in cervical cancer cells by targeting FIP200

    PubMed Central

    Fang, Wang; Shu, Shan; Yongmei, Li; Endong, Zhu; Lirong, Yin; Bei, Sun

    2016-01-01

    Cervical cancer (CC) is a malignant solid tumor, which is one of the main causes of morbidity and mortality in women. Persistent High-risk human papillomavirus (hrHPV) infection is closely related to cervical cancer and autophagy has been suggested to inhibit viral infections. miRNAs have been reported to regulate autophagy in many solid tumors with many studies implicating miR-224-3p in the regulation of autophagy. In this study, we performed a miRNA microarray analysis on CC tissues and found that a large number of miRNAs with differential expressions in hrHPV-infected tissues. We identified miR-224-3p as a candidate miRNA selectively up regulated in HPV-infected tissues and cell lines. Further analysis revealed that miR-224-3p regulates autophagy in cervical cancer tissues and cell lines. While the overexpression of miR-224-3p inhibits autophagy in HPV-infected cells, knocking down endogenous miR-224-3p increases autophagy activity in the same cells. In addition, we found that miR-224-3p directly inhibits the expression of autophagy related gene, FAK family-interacting protein of 200 kDa (FIP200). In summary, we found that miR-224-3p regulates autophagy in hrHPV-induced cervical cancer cells through targeting FIP200 expression. PMID:27615604

  13. miR-208-3p promotes hepatocellular carcinoma cell proliferation and invasion through regulating ARID2 expression

    SciTech Connect

    Yu, Peng; Wu, Dingguo; You, Yu; Sun, Jing; Lu, Lele; Tan, Jiaxing; Bie, Ping

    2015-08-15

    MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at post-transcriptional level. miRNA dysregulation plays a causal role in cancer progression. In this study, miR-208-3p was highly expressed and directly repressed ARID2 expression. As a result, ARID2 expression in hepatocellular carcinoma (HCC) was decreased. In vitro, miR-208-3p down-regulation and ARID2 over-expression elicited similar inhibitory effects on HCC cell proliferation and invasion. In vivo test results revealed that miR-208-3p down-regulation inhibited HCC tumorigenesis in Hep3B cells. Moreover, ARID2 was possibly a downstream element of transforming growth factor beta1 (TGFβ1)/miR-208-3p/ARID2 regulatory pathway. These findings suggested that miR-208-3p up-regulation is associated with HCC cell progression and may provide a new target for liver cancer treatment. - Highlights: • miR-208-3p was highly expressed and directly repressed the expression of ARID2 in HCC. • miR-208-3p contributed to HCC cell progression both in vitro and in vivo. • Over-expression of ARID2 inhibited the HCC cell proliferation and invasion. • Restoration of ARID2 partly reversed the the effect of miR-208-3p down-regulation on HCC cells. • Newly regulatory pathway: miR-208-3p mediated the repression of ARID2 by TGFβ1 in HCC cells.

  14. Genomic characterization of uncommon human G3P[6] rotavirus strains causing diarrhea in children in Italy in 2009.

    PubMed

    Ianiro, Giovanni; Delogu, Roberto; Fiore, Lucia; Ruggeri, Franco M

    2015-07-01

    Group A rotaviruses (RVA) are the leading cause of acute gastroenteritis in young children, causing up to 450,000 deaths worldwide, mostly in developing countries. Most of RVA human infections in developed countries are related to five major G/P combinations: G1P[8], G2P[4], G3P[8], G4P[8] and G9P[8]. During the surveillance activity of RotaNet-Italy, three uncommon G3P[6] RVA strains, designated as RVA/Human-wt/ITA/NA01/2009/G3P[6], RVA/Human-wt/ITA/NA06/2009/G3P[6], and RVA/Human-wt/ITA/NA19/2009/G3P[6], were identified in the stools of children with diarrhea hospitalized in Southern Italy in 2009. Samples NA01, NA06 and NA19 were characterized as genotype G3P[6]. To investigate the three strains further, partial sequencing of the eleven genomic segments was performed. RVA strains NA01, NA06 and NA19 were found to share the rare genotype constellation: G3-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2, which had not been reported previously in continental Italy. The phylogenetic analysis of the eleven genomic segments showed no evidence of zoonosis or inter-species reassortment at the origin of the Italian G3P[6] strains, indicating that they possessed DS-1-like genomic constellations similar to those detected previously in human cases in Africa and Europe. The analysis of the hypervariable regions of VP7 and VP4 (VP8*) revealed high amino acid identity between the Italian G3P[6] RVA strains involved in this study.

  15. Measurement of the 3s1/2-3p3/2 resonance line of sodiumlike Eu52+

    DOE PAGES

    Träbert, E.; Beiersdorfer, P.; Hell, N.; Brown, G. V.

    2015-08-20

    We have measured the 3s1/2-3p3/2 transition in sodiumlike Eu52+ situated at 41.232 Å with an uncertainty of 73 ppm. Our measurement extends previous high-precision measurements into the 56< Z< 78 range of atomic numbers. We also present measurements of 3s1/2-3p3/2 and 3p1/2-3d3/2 transitions in the neighboring magnesiumlike, aluminumlike, and siliconlike europium ions.

  16. Wakefield Computations for the CLIC PETS using the Parallel Finite Element Time-Domain Code T3P

    SciTech Connect

    Candel, A; Kabel, A.; Lee, L.; Li, Z.; Ng, C.; Schussman, G.; Ko, K.; Syratchev, I.; /CERN

    2009-06-19

    In recent years, SLAC's Advanced Computations Department (ACD) has developed the high-performance parallel 3D electromagnetic time-domain code, T3P, for simulations of wakefields and transients in complex accelerator structures. T3P is based on advanced higher-order Finite Element methods on unstructured grids with quadratic surface approximation. Optimized for large-scale parallel processing on leadership supercomputing facilities, T3P allows simulations of realistic 3D structures with unprecedented accuracy, aiding the design of the next generation of accelerator facilities. Applications to the Compact Linear Collider (CLIC) Power Extraction and Transfer Structure (PETS) are presented.

  17. Increasing the yield of Ar((sup 3)P(sub 2, 0)) and Ne((sub 3)P(sub 2, 0)) effusing from a glow discharge by using a longitudinal magnetic field

    NASA Technical Reports Server (NTRS)

    Barrios, A.; Ramos, G. B.; Hardy, K. A.; Sheldon, J. W.

    1994-01-01

    It is demonstrated that a longitudinal magnetic field applied to a low-pressure, low-voltage, hot cathode glow discharge will substantially increase the intensity of metastable atoms effusing from a central anode slit. For an argon discharge there is a fourfold increase in the effusing Ar((sup 3)P(sub 2, 0)) atom intensity and for neon there is a 14-fold increase in Ne((sup 3)P(sub 2, 0)) intensity.

  18. Utilising the `3P-model' to Characterise the Discipline of Didactics of Science

    NASA Astrophysics Data System (ADS)

    Adúriz-Bravo, Agustín; Izquierdo-Aymerich, Mercè

    In our research within didactics of science, we have been exploring contributions of the so called cognitive models from contemporary philosophy of science. We have used these philosophical frameworks on different levels. As an outcome, we have formulated a model of didactics of science according to which this discipline adapts and transforms theoretical contributions from different scholarly fields. In this paper, we concentrate on this description of didactics of science, which we have called the 3P-model (i.e., philosophy + psychology + pedagogy). This model of the internal functioning of the discipline may be useful to make innovations in science curriculum design and re-conceptualise the role of science teachers as professionals. We see didactics of science as a set of interrelated activities, performed by different individuals, and ranging from theoretical production to practice of science education at school. We find the concept of technoscience suitable to account for this diversity of goals. According to this concept, scientific disciplines are identified both with generation of knowledge and with active intervention on the world. Within current didactics of science, we recognise several kinds of research, having goals more or less directed to practical intervention in science education.

  19. Photodetachment of O^- Yielding O(1D_2, {}^3P) Atoms, Viewed with Velocity Map Imaging

    NASA Astrophysics Data System (ADS)

    Gibson, Stephen T.; Laws, Benjamin A.; Lewis, Brenton R.; Duong, Ly

    2016-06-01

    lectron photodetachment of O^-(2P3/2,1/2) is measured using velocity-map imaging at wavelengths near 350 nm, where detachment yields both O(^1D_2) and O(^3P2,1,0) atoms, simultaneously, producing slow (˜ 0.1 eV) and fast electrons (˜ 2 eV). The photoelectron spectrum resolves the fine-structure transitions, which together with the well known atomic fine-structure splittings, and intensity ratios, provide an excellent test of the spectral quality of the velocity-map imaging technique. Although the photoelectron angular distribution for the two atomic limits have the same negative anisotropy sign, the energy dependence differs. The variation is qualitatively in accordance with R-matrix cross section calculations, that indicate a more gradual d-wave onset for the ^1D limit. However, more exact evaluation is only possible with information about the matrix element phases. Research supported by the Australian Research Council Discovery Project GrantDP160102585. physics.nist.gov/cgi-bin/ASD/energy1.pl O. Scharf and M. R. Godefried, arXiv:0808.3529v1 O. Zatsarinny and K. Bartschat, Phys. Rev. A, 73, 022714 (2006). doi:10.1103/PhysRevA.73.022714

  20. Synthesis of cubic zirconium and hafnium nitride having Th3P4 structure.

    PubMed

    Zerr, Andreas; Miehe, Gerhard; Riedel, Ralf

    2003-03-01

    High-pressure synthesis is a powerful method for the preparation of novel materials with high elastic moduli and hardness. Additionally, such materials may exhibit interesting thermal, optoelectronic, semiconductuing, magnetic or superconducting properties. Here, we report on the high-pressure synthesis of zirconium and hafnium nitrides with the stoichiometry M3N4, where M = Zr, Hf. Synthesis experiments were performed in a laser-heated diamond anvil cell at pressures up to 18 GPa and temperatures up to 3,000 K. We observed formation of cubic Zr3N4 and Hf3N4 (c-M3N4) with a Th3P4-structure, where M-cations are eightfold coordinated by N anions. The c-M3N4 phases are the first binary nitrides with such a high coordination number. Both compounds exhibit high bulk moduli around 250 GPa, which indicates high hardness. Moreover, the new nitrides, c-Zr3N4 and c-Hf3N4, may be the first members of a larger group of transition metal and/or lanthanide nitrides with interesting ferromagnetic or superconducting behaviour.

  1. Time-resolved spectroscopy of the Mercury 6 3P1 state

    NASA Technical Reports Server (NTRS)

    Halstead, J. A.; Reeves, R. R.

    1981-01-01

    The time-resolved fluorescence was observed from the Hg 6 3P1 state under the influence of the earth's magnetic field and with applied fields of up to 14 G. Modulation of the fluorescence decay signal was observed as a function of both time and space and can be interpreted in terms of a classical precession of the excited atom about the magnetic field or as quantum beats resulting from interference between coherently populated Zeeman sublevels. This modulation was studied for each of the five resolvable components of the hyperfine structure separately. The fluorescence from the even isotopes was determined to be almost completely modulated while the fluorescence from the odd isotopes was only partially modulated. The frequency of modulation of the fluorescence from the mercury-202 isotope was observed as a function of the applied magnetic field and a value for the Lande factor of 1.46 + or - 0.03 was obtained. This is within experimental error of the accepted value of 1.486. In addition, the frequency of modulation as a function of applied magnetic field was determined for each of the three resolvable components with more than one contributing isotopic hyperfine line. An investigation of the effect of radiation trapping on the degree modulation was also made.

  2. Theoretical investigation of hyperthermal reactions at the gas-liquid interface: O (3P) and squalane.

    PubMed

    Kim, Dongwook; Schatz, George C

    2007-06-14

    Hyperthermal collisions (5 eV) of ground-state atomic oxygen [O ((3)P)] with a liquid-saturated hydrocarbon, squalane (C(30)H(62)), have been studied using QM/MM hybrid "on-the-fly" direct dynamics. The surface structure of the liquid squalane is obtained from a classical molecular dynamics simulation using the OPLS-AA force field. The MSINDO semiempirical Hamiltonian is combined with OPLS-AA for the QM/MM calculations. In order to achieve a more consistent and efficient simulation of the collisions, we implemented a dynamic partitioning of the QM and MM atoms in which atoms are assigned to QM or MM regions based on their proximity to "seed" (open-shell) atoms that determine where bond making/breaking can occur. In addition, the number of seed atoms is allowed to increase or decrease as time evolves so that multiple reactive events can be described. The results show that H abstraction is the most important process for all incident angles, with H elimination, double H abstraction, and C-C bond cleavage also being important. A number of properties of these reactive channels, as well as inelastic nonreactive scattering, are investigated, including angular and translational energy distributions, the effect of incident collision angle, variation with depth of the reactive event within the liquid, with the reaction site on the hydrocarbon, and the effect of dynamics before and after reaction (direct reaction versus trapping reaction-desorption).

  3. Dynamics of the gas-liquid interfacial reaction of O(3P) atoms with hydrocarbons

    NASA Astrophysics Data System (ADS)

    Kelso, Hailey; Köhler, Sven P. K.; Henderson, David A.; McKendrick, Kenneth G.

    2003-11-01

    We describe an experimental approach to the determination of the nascent internal state distribution of gas-phase products of a gas-liquid interfacial reaction. The system chosen for study is O(3P) atoms with the surface of liquid deuterated squalane, a partially branched long-chain saturated hydrocarbon, C30D62. The nascent OD products are detected by laser-induced fluorescence. Both OD (v'=0) and (v'=1) were observed in significant yield. The rotational distributions in both vibrational levels are essentially the same, and are characteristic of a Boltzmann distribution at a temperature close to that of the liquid surface. This contrasts with the distributions in the corresponding homogeneous gas-phase reactions. We propose a preliminary interpretation in terms of a dominant trapping-desorption mechanism, in which the OD molecules are retained at the surface sufficiently long to cause rotational equilibration but not complete vibrational relaxation. The significant yield of vibrationally excited OD also suggests that the surface is not composed entirely of -CD3 endgroups, but that secondary and/or tertiary units along the backbone are exposed.

  4. Dynamics of interfacial reactions between O(3 P) atoms and long-chain liquid hydrocarbons

    NASA Astrophysics Data System (ADS)

    Allan, Mhairi; Bagot, Paul A. J.; Köhler, Sven P. K.; Reed, Stewart K.; Westacott, Robin E.; Costen, Matthew L.; McKendrick, Kenneth G.

    2007-09-01

    Recent progress that has been made towards understanding the dynamics of collisions at the gas-liquid interface is summarized briefly. We describe in this context a promising new approach to the experimental study of gas-liquid interfacial reactions that we have introduced. This is based on laser-photolytic production of reactive gas-phase atoms above the liquid surface and laser-spectroscopic probing of the resulting nascent products. This technique is illustrated for reaction of O(3P) atoms at the surface of the long-chain liquid hydrocarbon squalane (2,6,10,15,19,23-hexamethyltetracosane). Laser-induced fluorescence detection of the nascent OH has revealed mechanistically diagnostic correlations between its internal and translational energy distributions. Vibrationally excited OH molecules are able to escape the surface. At least two contributions to the product rotational distributions are identified, confirming and extending previous hypotheses of the participation of both direct and trapping-desorption mechanisms. We speculate briefly on future experimental and theoretical developments that might be necessary to address the many currently unanswered mechanistic questions for this, and other, classes of gas-liquid interfacial reaction.

  5. Functional expression of pig renal organic anion transporter 3 (pOAT3).

    PubMed

    Hagos, Yohannes; Braun, Isabella M; Krick, Wolfgang; Burckhardt, Gerhard; Bahn, Andrew

    2005-05-01

    With the cloning of pig renal organic anion transporter 1 (pOAT1) (Biochimie 84 (2002) 1219) we set up a model system for comparative studies of cloned and natively isolated membrane located transport proteins. Meanwhile, another transport protein involved in p-aminohippurate (PAH) uptake on the basolateral side of the proximal tubule cells was identified, designated organic anion transporter 3 (OAT3). To explore the contribution of pOAT1 to the PAH clearance in comparison to OAT3, it was the aim of this study to extend our model by cloning of the pig ortholog of OAT3. Sequence comparisons of human organic anion transporter 3 (hOAT3) with the expressed sequence tag (EST) database revealed a clone and partial sequence of the pig renal organic anion transporter 3 (pOAT3) ortholog. Sequencing of the entire open reading frame resulted in a protein of 543 amino acid residues encoded by 1632 base pairs (EMBL Acc. No. AJ587003). It showed high homologies of 81%, 80%, 76%, and 77% to the human, rabbit, rat, and mouse OAT3, respectively. A functional characterization of pOAT3 in Xenopus laevis oocytes yielded an apparent Km (Kt) for [3H]estrone sulfate of 7.8 +/- 1.3 microM. Moreover, pOAT3 mediated [3H]estrone sulfate uptake was almost abolished by 0.5 mM of glutarate, dehydroepiandosterone sulfate, or probenecid consistent with the hallmarks of OAT3 function.

  6. ACE3P Computations of Wakefield Coupling in the CLIC Two-Beam Accelerator

    SciTech Connect

    Candel, Arno; Li, Z.; Ng, C.; Rawat, V.; Schussman, G.; Ko, K.; Syratchev, I.; Grudiev, A.; Wuensch, W.; /CERN

    2010-10-27

    The Compact Linear Collider (CLIC) provides a path to a multi-TeV accelerator to explore the energy frontier of High Energy Physics. Its novel two-beam accelerator concept envisions rf power transfer to the accelerating structures from a separate high-current decelerator beam line consisting of power extraction and transfer structures (PETS). It is critical to numerically verify the fundamental and higher-order mode properties in and between the two beam lines with high accuracy and confidence. To solve these large-scale problems, SLAC's parallel finite element electromagnetic code suite ACE3P is employed. Using curvilinear conformal meshes and higher-order finite element vector basis functions, unprecedented accuracy and computational efficiency are achieved, enabling high-fidelity modeling of complex detuned structures such as the CLIC TD24 accelerating structure. In this paper, time-domain simulations of wakefield coupling effects in the combined system of PETS and the TD24 structures are presented. The results will help to identify potential issues and provide new insights on the design, leading to further improvements on the novel CLIC two-beam accelerator scheme.

  7. Molecular Changes Involving MEK3-p38 MAPK Activation in Chronic Masticatory Myalgia.

    PubMed

    Meng, H; Gao, Y; Kang, Y F; Zhao, Y P; Yang, G J; Wang, Y; Cao, Y; Gan, Y H; Xie, Q F

    2016-09-01

    The exact mechanism underlying chronic masticatory myalgia (CMM), a conspicuous symptom in temporomandibular disorders, remains unclear. This investigation compared gene expression profiles between CMM patients and healthy subjects. Peripheral blood leukocytes were collected in 8 cases and 8 controls and subjected to whole genome microarray analyses. Data were analyzed with Gene Ontology and interactive pathways analyses. According to Gene Ontology analysis, categories such as ion transport, response to stimuli, and metabolic process were upregulated. The pathway analysis suggested overexpression of the mitogen-activated protein kinase (MAPK) pathway in CMM patients and to a higher degree in a pathway network. Overexpression of representative members of the MAPK pathway-including MAPK kinase 3 (MEK3), calcium voltage-gated channel auxiliary subunit gamma 2 (CACNG2), and growth arrest and DNA damage-inducible gamma (GADD45G)-was validated with real-time polymerase chain reaction. The upregulation of MEK3 was negatively correlated with the age of the CMM group. In the next step, the authors focused on MEK3, the gene that exhibited the greatest degree of differential expression, and its downstream target protein p38 MAPK. The results revealed upregulation of MEK3, as well as phosphorylated MEK3 and phosphorylated p38 MAPK, in CMM patients. These results provide a "fingerprint" for mechanistic studies of CMM in the future and highlight the importance of MEK3-p38 MAPK activation in CMM. PMID:27418173

  8. Controlled Pd(0)/t Bu3P Catalyzed Suzuki Cross-Coupling Polymerization of AB-Type Monomers with ArPd(t Bu3P)X or Pd2(dba)3/t Bu3P/ArX as the Initiator

    DOE PAGES

    Zhang, Honghai; Xing, Chun-Hui; Hu, Qiao-Sheng; Hong, Kunlun

    2015-02-05

    The synthesis of well-defined and functionalized conjugated polymers, which are essential in the development of efficient organic electronics, through Suzuki cross-coupling polymerizations has been a challenging task. We developed controlled Pd(0)/t-Bu3P-catalyzed Suzuki cross-coupling polymerizations of AB-type monomers via the chain-growth mechanism with a series of in situ generated ArPd(t-Bu3P)X (X = I, Br, Cl) complexes as initiators. Among them, the combinations of Pd2(dba)3/t-Bu3P/p-BrC6H4I, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br were identified as highly robust initiator systems, resulting in polymers with predictable molecular weight and narrow polydispersity (PDI~1.13-1.20). In addition, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br initiator systems afforded functional polymers with >95% fidelity. Our results pavedmore » the road to access well-defined conjugated polymers, including conjugated polymers with complex polymer architectures such as block copolymers and branch copolymers.« less

  9. Controlled Pd(0)/t Bu3P Catalyzed Suzuki Cross-Coupling Polymerization of AB-Type Monomers with ArPd(t Bu3P)X or Pd2(dba)3/t Bu3P/ArX as the Initiator

    SciTech Connect

    Zhang, Honghai; Xing, Chun-Hui; Hu, Qiao-Sheng; Hong, Kunlun

    2015-02-05

    The synthesis of well-defined and functionalized conjugated polymers, which are essential in the development of efficient organic electronics, through Suzuki cross-coupling polymerizations has been a challenging task. We developed controlled Pd(0)/t-Bu3P-catalyzed Suzuki cross-coupling polymerizations of AB-type monomers via the chain-growth mechanism with a series of in situ generated ArPd(t-Bu3P)X (X = I, Br, Cl) complexes as initiators. Among them, the combinations of Pd2(dba)3/t-Bu3P/p-BrC6H4I, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br were identified as highly robust initiator systems, resulting in polymers with predictable molecular weight and narrow polydispersity (PDI~1.13-1.20). In addition, Pd2(dba)3/t-Bu3P/p-BrC6H4CH2OH and Pd2(dba)3/t-Bu3P/p-PhCOC6H4Br initiator systems afforded functional polymers with >95% fidelity. Our results paved the road to access well-defined conjugated polymers, including conjugated polymers with complex polymer architectures such as block copolymers and branch copolymers.

  10. MicroRNA-103a-3p controls proliferation and osteogenic differentiation of human adipose tissue-derived stromal cells

    PubMed Central

    Sol Kim, Da; Young Lee, Sun; Hee Lee, Jung; Chan Bae, Yong; Sup Jung, Jin

    2015-01-01

    The elucidation of the molecular mechanisms underlying the differentiation and proliferation of human adipose tissue-derived stromal cells (hADSCs) represents a critical step in the development of hADSCs-based cellular therapies. To examine the role of the microRNA-103a-3p (miR-103a-3p) in hADSCs functions, miR-103a-3p mimics were transfected into hADSCs in order to overexpress miR-103a-3p. Osteogenic differentiation was induced for 14 days in an osetogenic differentiation medium and assessed by using an Alizarin Red S stain. The regulation of the expression of CDK6 (cyclin-dependent kinase 6), a predicted target of miR-103a-3p, was determined by western blot, real-time PCR and luciferase reporter assays. Overexpression of miR-103a-3p inhibited the proliferation and osteogenic differentiation of hADSCs. In addition, it downregulated protein and mRNA levels of predicted target of miR-103a-3p (CDK6 and DICER1). In contrast, inhibition of miR-103a-3p with 2′O methyl antisense RNA increased the proliferation and osteogenic differentiation of hADSCs. The luciferase reporter activity of the construct containing the miR-103a-3p target site within the CDK6 and DICER1 3′-untranslated regions was lower in miR-103a-3p-transfected hADSCs than in control miRNA-transfected hADSCs. RNA interference-mediated downregulation of CDK6 and DICER1 in hADSCs inhibited their proliferation and osteogenic differentiation. The results of the current study indicate that miR-103a-3p regulates the osteogenic differentiation of hADSCs and proliferation of hADSCs by direct targeting of CDK6 and DICER1 partly. These findings further elucidate the molecular mechanisms governing the differentiation and proliferation of hADSCs. PMID:26160438

  11. Theoretical study on the two-band degenerate-gaps superconductors: Application to SrPt3P

    NASA Astrophysics Data System (ADS)

    Huang, Hai; Hou, Li-Chao; Zhao, Bin-Peng

    2016-09-01

    We study the magnetic properties of two-band degenerate-gaps superconductors with two-band isotropic Ginzburg-Landau theory. The exact solutions of upper critical field and London penetration depth are obtained, and the calculations reproduce the experimental data of the recently observed superconducting crystal SrPt3P in a broad temperature range. It directly underlies that SrPt3P is a multi-band superconductor with equal gaps in two Fermi surface sheets.

  12. Are HO radicals produced in the reaction of O(3P) with 1-C4H8 ?

    NASA Technical Reports Server (NTRS)

    Luria, M.; Simonaitis, R.; Heicklen, J.

    1972-01-01

    The reaction of O(3P) with 1-C4H8 was examined in the presence of CO which scavenges HO radicals to produce CO2. From the CO2 quantum yield, an upper limit to the efficiency of HO production in the reaction of O(3P) with 1-C4H8 was found to be 0.020 at both 298 and 473 K.

  13. Regulation of Mammalian Autophagy by Class II and III PI 3-Kinases through PI3P Synthesis

    PubMed Central

    Devereaux, Kelly; Ogasawara, Yuta; Zhou, Xiang; Wang, Fan; Yamamoto, Akitsugu; De Camilli, Pietro; Di Paolo, Gilbert

    2013-01-01

    Synthesis of phosphatidylinositol-3-phosphate (PI3P) by Vps34, a class III phosphatidylinositol 3-kinase (PI3K), is critical for the initial steps of autophagosome (AP) biogenesis. Although Vps34 is the sole source of PI3P in budding yeast, mammalian cells can produce PI3P through alternate pathways, including direct synthesis by the class II PI3Ks; however, the physiological relevance of these alternate pathways in the context of autophagy is unknown. Here we generated Vps34 knockout mouse embryonic fibroblasts (MEFs) and using a higher affinity 4x-FYVE finger PI3P-binding probe found a Vps34-independent pool of PI3P accounting for ~35% of the total amount of this lipid species by biochemical analysis. Importantly, WIPI-1, an autophagy-relevant PI3P probe, still formed some puncta upon starvation-induced autophagy in Vps34 knockout MEFs. Additional characterization of autophagy by electron microscopy as well as protein degradation assays showed that while Vps34 is important for starvation-induced autophagy there is a significant component of functional autophagy occurring in the absence of Vps34. Given these findings, class II PI3Ks (α and β isoforms) were examined as potential positive regulators of autophagy. Depletion of class II PI3Ks reduced recruitment of WIPI-1 and LC3 to AP nucleation sites and caused an accumulation of the autophagy substrate, p62, which was exacerbated upon the concomitant ablation of Vps34. Our studies indicate that while Vps34 is the main PI3P source during autophagy, class II PI3Ks also significantly contribute to PI3P generation and regulate AP biogenesis. PMID:24098492

  14. Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling

    PubMed Central

    Lu, Nan; Shen, Qian; Mahoney, Timothy R.; Liu, Xianghua; Zhou, Zheng

    2011-01-01

    Apoptotic cells are swiftly engulfed by phagocytes and degraded inside phagosomes. Phagosome maturation requires phosphatidylinositol 3-phosphate [PtdIns(3)P], yet how PtdIns(3)P triggers phagosome maturation remains largely unknown. Through a genome-wide PtdIns(3)P effector screen in the nematode Caenorhabditis elegans, we identified LST-4/SNX9, SNX-1, and SNX-6, three BAR domain-containing sorting nexins, that act in two parallel pathways to drive PtdIns(3)P-mediated degradation of apoptotic cells. We found that these proteins were enriched on phagosomal surfaces through association with PtdIns(3)P and through specific protein–protein interaction, and they promoted the fusion of early endosomes and lysosomes to phagosomes, events essential for phagosome maturation. Specifically, LST-4 interacts with DYN-1 (dynamin), an essential phagosome maturation initiator, to strengthen DYN-1’s association to phagosomal surfaces, and facilitates the maintenance of the RAB-7 GTPase on phagosomal surfaces. Furthermore, both LST-4 and SNX-1 promote the extension of phagosomal tubules to facilitate the docking and fusion of intracellular vesicles. Our findings identify the critical and differential functions of two groups of sorting nexins in phagosome maturation and reveal a signaling cascade initiated by phagocytic receptor CED-1, mediated by PtdIns(3)P, and executed through these sorting nexins to degrade apoptotic cells. PMID:21148288

  15. MiRNA‑542‑3p downregulation promotes trastuzumab resistance in breast cancer cells via AKT activation.

    PubMed

    Ma, Tao; Yang, Lu; Zhang, Jin

    2015-03-01

    Trastuzumab (Herceptin) has been widely used in breast cancer treatment. However, the majority of cancers that initially respond to trastuzumab begin to progress again within 1 year. Despite the high resistance rate, the molecular mechanisms underlying this desease are not well understood. In the present study, microRNA (miRNA‑542‑3p modulated trastuzumab resistance in SKBR3 and MCF7/Her2 breast cancer cell lines. Trastuzumab induced miRNA‑542‑3p expression in SKBR3 and MCF7/Her2 cells. Furthermore, knockdown of miRNA‑542‑3p in the two cell lines resulted in decreased drug sensitivity to trastuzumab and cell apoptosis. The blockage of G1/S checkpoint by trastuzumab was rescued as well. miRNA‑542‑3p knockdown also activated the phosphatidylinositol 3‑kinase (PI3K)‑Akt pathway, while LY294002 reversed the effect of miRNA‑542‑3p knockdown. In summary, the results suggested that miRNA‑542‑3p downregulation may contribute to the trastuzumab resistance in breast cancer via, at least in part, the PI3K‑akt pathway. Our findings provide new molecular mechanisms in trastuzumab resistance. PMID:25586125

  16. miR-526b-3p functions as a tumor suppressor in colon cancer by regulating HIF-1α

    PubMed Central

    Zhang, Rui; Zhao, Jian; Xu, Jian; Wang, Jian; Jia, Jianhui

    2016-01-01

    HIF-1α is an important transcriptional factor, which plays roles in cancer development and progression. But its regulation by miRNAs is not clear. Here, to investigate the regulation of HIF-1α by miRNAs, miRNAs were predicted and miR-526b-3p was verified as a regulator of HIF-1α in colon cancer cells. Using TaqMan RT-PCR analysis, we analyzed the expression of miR-526b-3p in tumor tissues and cell lines and found that miR-526b-3p was consistently under-expressed in cancer tissues and cell lines compared with their normal controls. When miR-526b-3p was induced into the colon cancer cells, cell proliferation, metastasis and glycolysis of colon cancer cells were suppressed. We also found that miR-526b-3p was down-regulated in metastatic colon cancer tissues and negatively with HIF-1α mRNA in colon cancer tissues. In a summary, miR-526b-3p plays as a tumor suppressor by down-regulation of HIF-1α expression in colon cancer and may be a new diagnosis or therapeutic target. PMID:27398161

  17. Novel Mad2-targeting miR-493-3p controls mitotic fidelity and cancer cells’ sensitivity to paclitaxel

    PubMed Central

    Mäki-Jouppila, Jenni; Chen, Ping; Elgaaen, Bente Vilming; Straume, Anne Hege; Huhtinen, Kaisa; Cárpen, Olli; Lønning, Per Eystein; Davidson, Ben; Hautaniemi, Sampsa; Kallio, Marko J.

    2016-01-01

    The molecular pathways that contribute to the proliferation and drug response of cancer cells are highly complex and currently insufficiently characterized. We have identified a previously unknown microRNA-based mechanism that provides cancer cells means to stimulate tumorigenesis via increased genomic instability and, at the same time, evade the action of clinically utilized microtubule drugs. We demonstrate miR-493-3p to be a novel negative regulator of mitotic arrest deficient-2 (MAD2), an essential component of the spindle assembly checkpoint that monitors the fidelity of chromosome segregation. The microRNA targets the 3′ UTR of Mad2 mRNA thereby preventing translation of the Mad2 protein. In cancer cells, overexpression of miR-493-3p induced a premature mitotic exit that led to increased frequency of aneuploidy and cellular senescence in the progeny cells. Importantly, excess of the miR-493-3p conferred resistance of cancer cells to microtubule drugs. In human neoplasms, miR-493-3p and Mad2 expression alterations correlated with advanced ovarian cancer forms and high miR-493-3p levels were associated with reduced survival of ovarian and breast cancer patients with aggressive tumors, especially in the paclitaxel therapy arm. Our results suggest that intratumoral profiling of miR-493-3p and Mad2 levels can have diagnostic value in predicting the efficacy of taxane chemotherapy. PMID:26943585

  18. mir-101-3p is a key regulator of tumor metabolism in triple negative breast cancer targeting AMPK

    PubMed Central

    Li, Xing; Tang, Hailin; Li, Shuaijie; Huang, Xiaojia; Song, Cailu; Wei, Weidong; Xie, Xiaoming

    2016-01-01

    mir-101-3p has been reported to be a tumor suppressor and a promising therapeutic target in cancer. Recently, AMPK dysfunction has been highlighted in cancers, including breast cancer. The aim of this study is to investigate the biological roles of mir-101-3p and AMPK in breast cancer. Our research demonstrated that AMPK was up-regulated in breast cancer tissues and cell lines, especially in triple negative breast cancer (TNBC). High-expression of AMPK correlated with poor outcome in both total breast cancer and TNBC patients. Ectopic expression of AMPK improved glucose uptake, glycolysis, proliferation of TNBC cells in vitro and its tumorigenicity in vivo. AMPK was predicted to be a direct target of mir-101-3p. The luciferase reporter assay was performed to certificate this prediction. The expression of AMPK was suppressed by transfection of mir-101-3p in TNBC cells. Over-expression of mir-101-3p or knock-down of AMPK inhibited glucose metabolism and proliferation of TNBC cells in vitro. Our study provides evidence that mir-101-3p- AMPK axis could be a promising therapeutic target in TNBC targeting tumor metabolism. PMID:27145268

  19. Fum3p, a 2-ketoglutarate-dependent dioxygenase required for C-5 hydroxylation of fumonisins in Fusarium verticillioides.

    PubMed

    Ding, Yousong; Bojja, Ravi S; Du, Liangcheng

    2004-04-01

    Fumonisins are polyketide-derived mycotoxins produced by several agriculturally important Fusarium species. The B series fumonisins, FB(1), FB(2), FB(3), and FB(4), are fumonisins produced by wild-type Fusarium verticillioides strains, differing in the number and location of hydroxyl groups attached to the carbon backbone. We characterized the protein encoded by FUM3, a gene in the fumonisin biosynthetic gene cluster. The 33-kDa FUM3 protein (Fum3p) was heterologously expressed and purified from Saccharomyces cerevisiae. Yeast cells expressing the Fum3p converted FB(3) to FB(1), indicating that Fum3p catalyzes the C-5 hydroxylation of fumonisins. This result was verified by assaying the activity of Fum3p purified from yeast cells. The C-5 hydroxylase activity of purified Fum3p required 2-ketoglutarate, Fe(2+), ascorbic acid, and catalase, all of which are required for 2-ketoglutarate-dependent dioxygenases. The protein also contains two His motifs that are highly conserved in this family of dioxygenases. Thus, Fum3p is a 2-ketoglutarate-dependent dioxygenase required for the addition of the C-5 hydroxyl group of fumonisins.

  20. A modified TIP3P water potential for simulation with Ewald summation

    NASA Astrophysics Data System (ADS)

    Price, Daniel J.; Brooks, Charles L.

    2004-11-01

    The charges and Lennard-Jones parameters of the TIP3P water potential have been modified to improve its performance under the common condition for molecular dynamics simulations of using Ewald summation in lieu of relatively short nonbonded truncation schemes. These parameters were optimized under the condition that the hydrogen atoms do not have Lennard-Jones parameters, thus making the model independent of the combining rules used for the calculation of nonbonded, heteroatomic interaction energies, and limiting the number of Lennard-Jones calculations required. Under these conditions, this model provides accurate density (ρ=0.997 g/ml) and heat of vaporization (ΔHvap=10.53 kcal/mol) at 25 °C and 1 atm, but also provides improved structure in the second peak of the O-O radial distribution function and improved values for the dielectric constant (ɛ0=89) and the diffusion coefficient (D=4.0×10-5 cm2/s) relative to the original parametrization. Like the original parameterization, however, this model does not show a temperature density maximum. Several similar models are considered with the additional constraint of trying to match the performance of the optimized potentials for liquid simulation atom force field to that obtained when using the simulation conditions under which it was originally designed, but no model was entirely satisfactory in reproducing the relative difference in free energies of hydration between the model compounds, phenol and benzene. Finally, a model that incorporates a long-range correction for truncated Lennard-Jones interactions is presented, which provides a very accurate dielectric constant (ɛ0=76), however, the improvement in this estimate is on the same order as the uncertainty in the calculation.

  1. Numerical modelling of soil/atmosphere exchange of POPs with MIN3P

    NASA Astrophysics Data System (ADS)

    Bao, Zhongwen; Beckingham, Barbara; Maier, Uli; Haberer, Christina; Grathwohl, Peter

    2014-05-01

    Soil/atmosphere exchange processes are of vital role not only for the cycling of water and the transport of nutrients and oxygen, but also for the long-term fate of many persistent organic pollutants (POPs). This study focuses on modelling the vapor phase exchange of a representative POP, i.e. phenanthrene, across the soil/atmosphere interface using the numerical code MIN3P, which was extended to include an atmospheric boundary layer. The numerical code was validated with analytical solutions of the advection-dispersion equation and additionally considering pure diffusion with linear sorption in the porous medium. We ran several scenarios to test the relevant processes influencing soil/atmosphere exchange at various time scales, i.e. diffusion/dispersion, advection, sorption, re-volatilization, biodegradation, and temperature changes. The atmospheric boundary layer near the ground surface was assumed to be well mixed, and overall fluxes of phenanthrene were found to be limited within the soil compartment for downward migration from the atmosphere. Sorption to soil organic carbon causes strong retardation of phenanthrene in seepage water, thus affecting re-volatilization and biodegradation. After phenanthrene deposition, sorption limits the spreading in the short term while biodegradation leads to steady-state concentration profiles in the long term (e.g. centuries). Temperature increases, e.g. from nighttime to daytime, lead to a release of sorbed phenanthrene. While the model shows dynamically fluctuating atmospheric concentration gradients for diurnal temperature changes, eddy diffusion is sufficient to mix concentrations in the atmospheric boundary layer for seasonal and longer-term temperature increases. The model can be further used to estimate levels of other POPs in soils with varying physico-chemical properties and under different environmental loadings and climate scenarios to evaluate their long-term fate in soils.

  2. [The National Occupational illness surveillance and Prevention Network (RNV3P) and health monitoring].

    PubMed

    Bonneterre, Vincent; Bicout, Dominique; Bernardet, Cyril; Dupas, Dominique; de Clavière, Caroline; de Gaudemaris, Régis

    2008-01-01

    The National Occupational Illness Surveillance and Prevention Network (RNV3P) established in 2002 as a network of experts from 29 university hospitals as well as occupational physicians records and monitors occupational health problems (OHPs) based on Soccupational health consultations in university hospitals in mainland France and in occupational medical health services (approximately 5000 OHPs/year for patients seen in hospital consultations). The OHP data are collected systematically according to a standardised code which is attributed based on main variables of interest: disease and co-morbidity (CIM-10), 1-5 impact codes (INRS), an occupational code (ILO) and a code for the type and domain of professional activity (NAF-93). For certain problems recorded, the clinician also reports a degree of imputance for attributing the level of certainty for the problem's relationship to the S main illness (weak, probable, strong). At present, 30,000 OHPs diagnosed and recorded in occupational illness consultation centers have been recorded in the information database and have been utilised for epidemiological surveillance. The surveillance activity of the network is carried out on two levels. First, a planned epidemiological health activity is programmed which focuses on estimating the incidence of illness--predefined problems. In a parallel fashion, research is developed to explore the tools which can be used to highlight emerging illness and develop methodologies to detect the relationships of unknown problems to the incidence of these illnesses--including those that present a communicable nature (either temporarily or over the long term), in certain professions or sectors. PMID:18773844

  3. Vestiges of Ent3p/Ent5p function in the giardial epsin homolog.

    PubMed

    Feliziani, Constanza; Valdez Taubas, Javier; Moyano, Sofía; Quassollo, Gonzalo; Poprawski, Joanna E; Wendland, Beverly; Touz, Maria C

    2016-04-01

    An accurate way to characterize the functional potential of a protein is to analyze recognized protein domains encoded by the genes in a given group. The epsin N-terminal homology (ENTH) domain is an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated trafficking. In this work, we investigate the function of the single ENTH-containing protein from the protist Giardia lamblia by testing its function in Saccharomyces cerevisiae. This protein, named GlENTHp (for G. lamblia ENTH protein), is involved in Giardia in endocytosis and in protein trafficking from the ER to the vacuoles, fulfilling the function of the ENTH proteins epsin and epsinR, respectively. There are two orthologs of epsin, Ent1p and Ent2p, and two orthologs of epsinR, Ent3p and Ent5p in S. cerevisiae. Although the expression of GlENTHp neither complemented growth in the ent1Δent2Δ mutant nor restored the GFP-Cps1 vacuolar trafficking defect in ent3Δent5Δ, it interfered with the normal function of Ent3/5 in the wild-type strain. The phenotype observed is linked to a defect in Cps1 localization and α-factor mating pheromone maturation. The finding that GlENTHp acts as dominant negative epsinR in yeast cells reinforces the phylogenetic data showing that GlENTHp belongs to the epsinR subfamily present in eukaryotes prior to their evolution into different taxa.

  4. Vestiges of Ent3p/Ent5p function in the giardial epsin homolog.

    PubMed

    Feliziani, Constanza; Valdez Taubas, Javier; Moyano, Sofía; Quassollo, Gonzalo; Poprawski, Joanna E; Wendland, Beverly; Touz, Maria C

    2016-04-01

    An accurate way to characterize the functional potential of a protein is to analyze recognized protein domains encoded by the genes in a given group. The epsin N-terminal homology (ENTH) domain is an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated trafficking. In this work, we investigate the function of the single ENTH-containing protein from the protist Giardia lamblia by testing its function in Saccharomyces cerevisiae. This protein, named GlENTHp (for G. lamblia ENTH protein), is involved in Giardia in endocytosis and in protein trafficking from the ER to the vacuoles, fulfilling the function of the ENTH proteins epsin and epsinR, respectively. There are two orthologs of epsin, Ent1p and Ent2p, and two orthologs of epsinR, Ent3p and Ent5p in S. cerevisiae. Although the expression of GlENTHp neither complemented growth in the ent1Δent2Δ mutant nor restored the GFP-Cps1 vacuolar trafficking defect in ent3Δent5Δ, it interfered with the normal function of Ent3/5 in the wild-type strain. The phenotype observed is linked to a defect in Cps1 localization and α-factor mating pheromone maturation. The finding that GlENTHp acts as dominant negative epsinR in yeast cells reinforces the phylogenetic data showing that GlENTHp belongs to the epsinR subfamily present in eukaryotes prior to their evolution into different taxa. PMID:26851076

  5. O(3P) atoms as a chemical probe of surface ordering in ionic liquids.

    PubMed

    Waring, Carla; Bagot, Paul A J; Slattery, John M; Costen, Matthew L; McKendrick, Kenneth G

    2010-04-15

    The reactivity of photolytically generated, gas-phase, ground-state atomic oxygen, O((3)P), with the surfaces of a series of 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([NTf(2)]) ionic liquids has been investigated. The liquids differ only in the length of the linear C(n)H(2n+1) alkyl side chain on the cation, with n = 2, 4, 5, 8, and 12. Laser-induced fluorescence was used to detect gas-phase OH v' = 0 radicals formed at the gas-liquid interface. The reactivity of the ionic liquids increases nonlinearly with n, in a way that cannot simply be explained by stoichiometry. We infer that the alkyl chains must be preferentially exposed at the interface to a degree that is dependent on chain length. A relatively sharp onset of surface segregation is apparent in the region of n = 4. The surface specificity of the method is confirmed through the nonthermal characteristics of both the translational and rotational distributions of the OH v' = 0. These reveal that the dynamics are dominated by a direct, impulsive scattering mechanism at the outer layers of the liquid. The OH v' = 0 yield is effectively independent of the bulk temperature of the longest-chain ionic liquid in the range 298-343 K, also consistent with a predominantly direct mechanism. These product attributes are broadly similar to those of the benchmark pure hydrocarbon liquid, squalane, but a more detailed analysis suggests that the interface may be microscopically smoother for the ionic liquids.

  6. Identification of miR-140-3p as a marker associated with poor prognosis in spinal chordoma

    PubMed Central

    Zou, Ming-Xiang; Huang, Wei; Wang, Xiao-Bin; Lv, Guo-Hua; Li, Jing; Deng, You-Wen

    2014-01-01

    Objective: To investigate the expression profile of miR-140-3p in formalin-fixed paraffin-embedded (FFPE) tissues of spinal chordoma, and its correlation with the prognosis of spinal chordoma patients. Methods: Dysregulated miRNAs in FFPE tissues of spinal chordoma were identified by microarray analysis. MiR-140-3p expression in surgically removed spinal chordoma tissues of 42 spinal chordoma patients (27 males and 15 females, aged 29-76 years) and corresponding nucleus pulposus tissues of 14 patients with disc herniation as the healthy control group (8 males and 6 females, aged 24-73 years) was measured by real-time quantitative RT-PCR assay. The association of miR-140-3p expression with clinicopathologic characteristics of spinal chordoma patients was analyzed. Additionally, we investigated the prognostic significance of miR-140-3p with the use of Kaplan-Meier methods and a Cox proportional hazard model. Results: The expression of miR-140-3p was significantly higher in chordoma tissues than nucleus pulposus tissues (t = 3.530, P = 0.001). The expression of miR-140-3p positively correlated with surrounding muscle invasion. The Kapan-Meier survival analysis showed that the patients with high miR-140-3p expression had a significantly worse recurrence-free survival than those with a low expression (χ 2 = 31.270, P = 0.000, log-rank test). In addition, univariate and multivariate analyses for recurrence-free survival showed that miR-140-3p expression was an independent prognostic factor for patients with spinal chordoma (HR = 1.361, 95% CI: 1.135-1.633, P = 0.001). Conclusion: Over-expression of miR-140-3p is correlated with recurrence and tumor invasion, suggesting that miR-140-3p could be a new predictor for recurrence and prognosis in patients with spinal chordoma. PMID:25197358

  7. miR-148b-3p inhibits malignant biological behaviors of human glioma cells induced by high HOTAIR expression

    PubMed Central

    Wang, Guan; Li, Zhaohui; Tian, Nan; Han, Liang; Fu, Yao; Guo, Zhigang; Tian, Yu

    2016-01-01

    Increasing evidence suggests that long non coding (lnc)RNA and microRNA (miRNA/miR) both regulate the expression of key genes in tumorigenesis and have considerable theranostic potential. Rapid advances in bioinformatics indicate that miRNA may potentially interact with lncRNA to modulate their regulatory roles. miR-148b-3p has been reported to have a vital role in regulating tumor progression. However, the expression pattern of miR-148b-3p in glioma remains largely unknown, and interactions between miR-148b-3p and lncRNA has yet to be identified. The aim of the present study was to insight into the regulatory role of miR-148b-3p in glioma. Using online software, the HOTAIR gene was identified as a possible lncRNA target of miR-148b-3p in the present study. siRNA was used to suppress the expression of HOTAIR and reverse transcription-quantitative polymerase chain reaction was used to detect the expression of miR-148b-3p. The results confirmed that HOTAIR mRNA expression was inversely correlated with miR-148b-3p expression in A172 glioma cells. Furthermore, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the viability of cells, flow cytometry was performed to test cell cycle and a matrigel invasion assay was performed to test cell invasion. The results showed that HOTAIR promotes factors associated with malignancy, including cell proliferation, cell cycle progression and invasion, whereas miR-148b-3p suppresses malignancy. Bioinformatics and luciferase reporter assays showed that miR-148b-3p modulates HOTAIR expression by directly targeting the HOTAIR gene sequence. In summary, the results indicated that miR-148b-3p inhibits malignant biological behaviors of glioma cells by directly targeting HOTAIR. The current data provide important evidence for understanding the key roles of the lncRNA miRNA functional network in glioma. PMID:27446363

  8. miR-21-3p controls sepsis-associated cardiac dysfunction via regulating SORBS2.

    PubMed

    Wang, Hui; Bei, Yihua; Shen, Shutong; Huang, Peipei; Shi, Jing; Zhang, Jialiang; Sun, Qi; Chen, Yuanyuan; Yang, Yun; Xu, Tianzhao; Kong, Xiangqing; Xiao, Junjie

    2016-05-01

    Cardiac dysfunction with sepsis is a major cause of death in intensive care units. Several lines of evidence have revealed the potential of microRNAs (miRNAs, miRs) as biomarkers for detecting sepsis, though direct evidence of their functional roles in septic cardiac dysfunction is still lacking. In this study, C57BL/6 mice were exposed to lipopolysaccharide (LPS) to induce sepsis-associated cardiac dysfunction, as evidenced by reduced fractional shortening (FS) and ejection fraction (EF) and detrimental changes in cardiac contractility, inflammation, and energy metabolism. Microarray analysis and qRT-PCRs revealed that miR-21-3p was significantly induced in heart samples challenged with LPS. Impressively, pharmacological inhibition of miR-21-3p using antagomiR was able to preserve FS and EF and prevent mitochondria ultrastructural damage and autophagy in LPS-treated mice, while forced expression of miR-21-3p using agomiR aggravated that. Besides that, miR-21-3p antagomiR improved the survival of mice treated with LPS. Meanwhile, our data showed that SH3 domain-containing protein 2 (SORBS2) was inversely correlated with miR-21-3p expression level in mice hearts, and was repressed in hearts challenged with LPS, suggesting SORBS2 as a target gene of miR-21-3p. Additionally, plasma miR-21-3p was markedly elevated in septic patients with cardiac dysfunction as compared to septic patients without cardiac dysfunction. The ROC curve showed that plasma miR-21-3p could be a specific predictor of septic patients developing cardiac dysfunction with an area under the curve of 0.939. Collectively, the present study provides strong evidence that miR-21-3p controls sepsis-associated cardiac dysfunction via regulating SORBS2. Inhibition of miR-21-3p might be a protective strategy to treat sepsis-induced cardiac dysfunction.

  9. miR-21-3p controls sepsis-associated cardiac dysfunction via regulating SORBS2.

    PubMed

    Wang, Hui; Bei, Yihua; Shen, Shutong; Huang, Peipei; Shi, Jing; Zhang, Jialiang; Sun, Qi; Chen, Yuanyuan; Yang, Yun; Xu, Tianzhao; Kong, Xiangqing; Xiao, Junjie

    2016-05-01

    Cardiac dysfunction with sepsis is a major cause of death in intensive care units. Several lines of evidence have revealed the potential of microRNAs (miRNAs, miRs) as biomarkers for detecting sepsis, though direct evidence of their functional roles in septic cardiac dysfunction is still lacking. In this study, C57BL/6 mice were exposed to lipopolysaccharide (LPS) to induce sepsis-associated cardiac dysfunction, as evidenced by reduced fractional shortening (FS) and ejection fraction (EF) and detrimental changes in cardiac contractility, inflammation, and energy metabolism. Microarray analysis and qRT-PCRs revealed that miR-21-3p was significantly induced in heart samples challenged with LPS. Impressively, pharmacological inhibition of miR-21-3p using antagomiR was able to preserve FS and EF and prevent mitochondria ultrastructural damage and autophagy in LPS-treated mice, while forced expression of miR-21-3p using agomiR aggravated that. Besides that, miR-21-3p antagomiR improved the survival of mice treated with LPS. Meanwhile, our data showed that SH3 domain-containing protein 2 (SORBS2) was inversely correlated with miR-21-3p expression level in mice hearts, and was repressed in hearts challenged with LPS, suggesting SORBS2 as a target gene of miR-21-3p. Additionally, plasma miR-21-3p was markedly elevated in septic patients with cardiac dysfunction as compared to septic patients without cardiac dysfunction. The ROC curve showed that plasma miR-21-3p could be a specific predictor of septic patients developing cardiac dysfunction with an area under the curve of 0.939. Collectively, the present study provides strong evidence that miR-21-3p controls sepsis-associated cardiac dysfunction via regulating SORBS2. Inhibition of miR-21-3p might be a protective strategy to treat sepsis-induced cardiac dysfunction. PMID:27033308

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

    SciTech Connect

    Chen, K.S.; Gunaratne, P.H.; Greenberg, F.; Shaffer, L.G.; Lupski, J.R.; Hoheisel, J.D.; Young, I.G.; Miklos, G.L.G.; Campbell, H.D.

    1995-01-01

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

  11. Up- regulation of miR-328-3p sensitizes non-small cell lung cancer to radiotherapy

    PubMed Central

    Ma, Wei; Ma, Chao-nan; Zhou, Nan-nan; Li, Xian-dong; Zhang, Yi-jie

    2016-01-01

    MicroRNAs (miRNAs) are believed to be resistant against radiotherapy in certain types of cancers. The aim of our study was to determine the clinical application of miRNAs in non-small cell lung cancer (NSCLC). Sixty NSCLC tissue samples and adjacent histologically normal tissues were obtained for miRNAs microarray analysis and validated by RT-qPCR. Correlation between miRNA expression level and clinicopathological features was evaluated. Our study examined the influence of changed miRNA expression on the damaged DNA and its associated radio sensitivity. Luciferase assay was performed to determine potential effects on the targeted gene. Our study identified fifteen altered miRNAs in which miR-328-3p was down regulated in NSCLC tumour tissue as compared to normal tissues. Down-expression of miR-328-3p was positively associated with an enhanced lymph node metastasis, advanced clinical stage and a shortened survival rate. miR-328-3p expression was decreased in A549 cells compared to other NSCLC cell lines. Up-regulation of miR-328-3p demonstrated a survival inhibition effect in A549 and restored NSCLC cells’ sensitivity to radio therapy. An increased miR-328-3p expression promoted irradiation-induced DNA damage in cells. γ-H2AX was identified as the direct target of miR-328-3p. Over-expressed miR-328-3p can improve the radiosensitvity of cells by altering the DNA damage/repair signalling pathways in NSCLC. PMID:27530148

  12. miRNA-132-3p inhibits osteoblast differentiation by targeting Ep300 in simulated microgravity

    PubMed Central

    Hu, Zebing; Wang, Yixuan; Sun, Zhongyang; Wang, Han; Zhou, Hua; Zhang, Lianchang; Zhang, Shu; Cao, Xinsheng

    2015-01-01

    Recent studies have demonstrated that miRNAs can play important roles in osteoblast differentiation and bone formation. However, the function of miRNAs in bone loss induced by microgravity remains unclear. In this study, we investigated the differentially expressed miRNAs in both the femur tissues of hindlimb unloading rats and primary rat osteoblasts (prOB) exposed to simulated microgravity. Specifically, miR-132-3p was found up-regulated and negatively correlated with osteoblast differentiation. Overexpression of miR-132-3p significantly inhibited prOB differentiation, whereas inhibition of miR-132-3p function yielded an opposite effect. Furthermore, silencing of miR-132-3p expression effectively attenuated the negative effects of simulated microgravity on prOB differentiation. Further experiments confirmed that E1A binding protein p300 (Ep300), a type of histone acetyltransferase important for Runx2 activity and stability, was a direct target of miR-132-3p. Up-regulation of miR-132-3p by simulated microgravity could inhibit osteoblast differentiation in part by decreasing Ep300 protein expression, which, in turn, resulted in suppression of the activity and acetylation of Runx2, a key regulatory factor of osteoblast differentiation. Taken together, our findings are the first to demonstrate that miR-132-3p can inhibit osteoblast differentiation and participate in the regulation of bone loss induced by simulated microgravity, suggesting a potential target for counteracting decreases in bone formation. PMID:26686902

  13. Up- regulation of miR-328-3p sensitizes non-small cell lung cancer to radiotherapy.

    PubMed

    Ma, Wei; Ma, Chao-Nan; Zhou, Nan-Nan; Li, Xian-Dong; Zhang, Yi-Jie

    2016-01-01

    MicroRNAs (miRNAs) are believed to be resistant against radiotherapy in certain types of cancers. The aim of our study was to determine the clinical application of miRNAs in non-small cell lung cancer (NSCLC). Sixty NSCLC tissue samples and adjacent histologically normal tissues were obtained for miRNAs microarray analysis and validated by RT-qPCR. Correlation between miRNA expression level and clinicopathological features was evaluated. Our study examined the influence of changed miRNA expression on the damaged DNA and its associated radio sensitivity. Luciferase assay was performed to determine potential effects on the targeted gene. Our study identified fifteen altered miRNAs in which miR-328-3p was down regulated in NSCLC tumour tissue as compared to normal tissues. Down-expression of miR-328-3p was positively associated with an enhanced lymph node metastasis, advanced clinical stage and a shortened survival rate. miR-328-3p expression was decreased in A549 cells compared to other NSCLC cell lines. Up-regulation of miR-328-3p demonstrated a survival inhibition effect in A549 and restored NSCLC cells' sensitivity to radio therapy. An increased miR-328-3p expression promoted irradiation-induced DNA damage in cells. γ-H2AX was identified as the direct target of miR-328-3p. Over-expressed miR-328-3p can improve the radiosensitvity of cells by altering the DNA damage/repair signalling pathways in NSCLC. PMID:27530148

  14. 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).

  15. Reactions of N+ (3P) ions with H2 and HD molecules at low temperatures

    NASA Astrophysics Data System (ADS)

    Grozdanov, Tasko P.; McCarroll, Ronald; Roueff, Evelyne

    2016-05-01

    formation of ND+. The calculated value is consistent with the available experimental data. Conclusions: The present results allow for the determination of reaction rate coefficients for any given distribution of specific fine structure and rotational state populations of the reactants. In interstellar conditions, where N+ is in its 3P0 state and para- and ortho-H2 respectively in J = 0 and J = 1. Our results enable a study of the influence of the ortho/para evolution of molecular hydrogen on the formation of nitrogen compounds.

  16. The investigation of miR-221-3p and PAK1 gene expressions in breast cancer cell lines.

    PubMed

    Ergun, Sercan; Tayeb, Tayeb Sadiq; Arslan, Ahmet; Temiz, Ebru; Arman, Kaifee; Safdar, Muhammad; Dağlı, Hasan; Korkmaz, Murat; Nacarkahya, Gülper; Kırkbeş, Sevil; Oztuzcu, Serdar

    2015-01-25

    The most common malignancy in women is breast cancer. Drug resistance in the treatment of cancer still remains a major clinical concern. Resistance to tamoxifen is seen in half of the recurrences in breast cancer. The anti-estrogen tamoxifen gains agonistic property by transactivating ERα. PAK1-mediated phosphorylation of serine 305 (S305) of ERα leads to resistance to tamoxifen. In our study, PAK1-induced suggestive tamoxifen resistance was designed. According to our hypothesis, phosphorylation of ERα-S305 by PAK1 may be reversed by PAK1 transcriptional inhibition by miR-221-3p due to miR-221-3p targeting the 3' UTR of PAK1. For this purpose, we used Real-time PCR (qRT-PCR) to measure the expression level of miR-221-3p in ER-positive breast cancer cell lines (ZR-75-1, MCF7) and breast epithelial cell line, hTERT-HME1, as control in the laboratory in our department. The increase in the expression of PAK1 depending on miR-221-3p may be related to ZR-75-1 cell line which has invasive characteristic but other two ER+ cancer cell lines, MCF7 and HCC1500, have milder cancer severity. miR-221-3p may have a role on regulation of PAK1 expression because miR-221-3p expression level decreases while PAK1 expression level increases in SKBR3 cell line. miR-221-3p and PAK1 expressions in MDA-MB-231 cell line are higher than that of hTERT-HME1 cell line. This may mean that miR-221-3p has no regulatory effect on of PAK1 expression in this cell line. According to these results, miR-221-3p may give crucial information about molecular mechanism of the disease upon PAK1 activity or different mechanisms with respect to histopathology and severity of breast cancer.

  17. The Sin3p PAH Domains Provide Separate Functions Repressing Meiotic Gene Transcription in Saccharomyces cerevisiae ▿

    PubMed Central

    Mallory, Michael J.; Law, Michael J.; Buckingham, Lela E.; Strich, Randy

    2010-01-01

    Meiotic genes in budding yeast are repressed during vegetative growth but are transiently induced during specific stages of meiosis. Sin3p represses the early meiotic gene (EMG) by bridging the DNA binding protein Ume6p to the histone deacetylase Rpd3p. Sin3p contains four paired amphipathic helix (PAH) domains, one of which (PAH3) is required for repressing several genes expressed during mitotic cell division. This report examines the roles of the PAH domains in mediating EMG repression during mitotic cell division and following meiotic induction. PAH2 and PAH3 are required for mitotic EMG repression, while electrophoretic mobility shift assays indicate that only PAH2 is required for stable Ume6p-promoter interaction. Unlike mitotic repression, reestablishing EMG repression following transient meiotic induction requires PAH3 and PAH4. In addition, the role of Sin3p in reestablishing repression is expanded to include additional loci that it does not control during vegetative growth. These findings indicate that mitotic and postinduction EMG repressions are mediated by two separate systems that utilize different Sin3p domains. PMID:20971827

  18. miR-8-3p regulates mitoferrin in the testes of Bactrocera dorsalis to ensure normal spermatogenesis

    PubMed Central

    Tariq, Kaleem; Metzendorf, Christoph; Peng, Wei; Sohail, Summar; Zhang, Hongyu

    2016-01-01

    Genetics-enhanced sterile insect techniques (SIT) are promising novel approaches to control Bactrocera dorsalis, the most destructive horticultural pest in East Asia and the Pacific region. To identify novel genetic agents to alter male fertility of B. dorsalis, previous studies investigated miRNA expression in testes of B. dorsalis. One miRNA, miR-8-3p was predicted to bind the 3′UTR of putative B. dorsalis mitoferrin (bmfrn). The ortholog of bmfrn in D. melanogaster is essential for male fertility. Here we show that bmfrn has all conserved amino acid residues of known mitoferrins and is most abundantly expressed in B. dorsalis testes, making miR-8-3p and mitoferrin candidates for genetics-enhanced SIT. Furthermore, using a dual-luciferase reporter system, we show in HeLa cells that miR-8-3p interacts with the 3′UTR of bmfrn. Dietary treatments of adult male flies with miR-8-3p mimic, antagomiR, or bmfrn dsRNA, altered mitoferrin expression in the testes and resulted in reduced male reproductive capacity due to reduced numbers and viability of spermatozoa. We show for the first time that a mitoferrin is regulated by a miRNA and we demonstrate miR-8-3p as well as bmfrn dsRNA to be promising novel agents that could be used for genetics-enhanced SIT. PMID:26932747

  19. gga-miR-101-3p Plays a Key Role in Mycoplasma gallisepticum (HS Strain) Infection of Chicken

    PubMed Central

    Chen, Jiao; Wang, Zaiwei; Bi, Dingren; Hou, Yue; Zhao, Yabo; Sun, Jianjun; Peng, Xiuli

    2015-01-01

    Mycoplasma gallisepticum (MG), one of the most pathogenic Mycoplasma, has caused tremendous economic loss in the poultry industry. Recently, increasing evidence has suggested that micro ribonucleic acids (miRNAs) are involved in microbial pathogenesis. However, little is known about potential roles of miRNAs in MG infection of chicken. In the present study, using miRNA Solexa sequencing we have found that gga-miR-101-3p was up-regulated in the lungs of MG-infected chicken embryos. Moreover, gga-miR-101-3p regulated expression of the host enhancer of zeste homolog 2 (EZH2) through binding to the 3’ un-translated region (3’-UTR) of EZH2 gene. Over-expression of gga-miR-101-3p significantly inhibited EZH2 expression and hence inhibited proliferation of chicken embryonic fibroblast (DF-1 cells) by blocking the G1-to-S phase transition. Similar results were obtained in MG-infected chicken embryos and DF-1 cells, where gga-miR-101-3p was significantly up-regulated, while EZH2 was significantly down-regulated. This study reveals that gga-miR-101-3p plays an important role in MG infection through regulation of EZH2 expression and provides a new insight into the mechanisms of MG pathogenesis. PMID:26633386

  20. miR-129-3p controls centrosome number in metastatic prostate cancer cells by repressing CP110.

    PubMed

    Bijnsdorp, Irene V; Hodzic, Jasmina; Lagerweij, Tonny; Westerman, Bart; Krijgsman, Oscar; Broeke, Jurjen; Verweij, Frederik; Nilsson, R Jonas A; Rozendaal, Lawrence; van Beusechem, Victor W; van Moorselaar, Jeroen A; Wurdinger, Thomas; Geldof, Albert A

    2016-03-29

    The centrosome plays a key role in cancer invasion and metastasis. However, it is unclear how abnormal centrosome numbers are regulated when prostate cancer (PCa) cells become metastatic. CP110 was previously described for its contribution of centrosome amplification (CA) and early development of aggressive cell behaviour. However its regulation in metastatic cells remains unclear. Here we identified miR-129-3p as a novel metastatic microRNA. CP110 was identified as its target protein. In PCa cells that have metastatic capacity, CP110 expression was repressed by miR-129-3p. High miR-129-3p expression levels increased cell invasion, while increasing CP110 levels decreased cell invasion. Overexpression of CP110 in metastatic PCa cells resulted in a decrease in the number of metastasis. In tissues of PCa patients, low CP110 and high miR-129-3p expression levels correlated with metastasis, but not with the expression of genes related to EMT. Furthermore, overexpression of CP110 in metastatic PCa cells resulted in excessive-CA (E-CA), and a change in F-actin distribution which is in agreement with their reduced metastatic capacity. Our data demonstrate that miR-129-3p functions as a CA gatekeeper in metastatic PCa cells by maintaining pro-metastatic centrosome amplification (CA) and preventing anti-metastatic E-CA.

  1. MicroRNA-29a-3p attenuates ET-1-induced hypertrophic responses in H9c2 cardiomyocytes.

    PubMed

    Li, Man; Wang, Nan; Zhang, Jian; He, Hong-Peng; Gong, Hui-Qin; Zhang, Rui; Song, Tie-Feng; Zhang, Li-Nan; Guo, Zhi-Xia; Cao, Dong-Sun; Zhang, Tong-Cun

    2016-07-01

    Transcription factor nuclear factor of activated T cells c4 (NFATc4) is the best-characterized target for the development of cardiac hypertrophy. Aberrant microRNA-29 (miR-29) expression is involved in the development of cardiac fibrosis and congestive heart failure. However, whether miR-29 regulates hypertrophic processes is still not clear. In this study, we investigated the potential functions of miR-29a-3p in endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy. We showed that miR-29a-3p was down-regulated in ET-1-treated H9c2 cardiomyocytes. Overexpression of miR-29a-3p significantly reduced ET-1-induced hypertrophic responses in H9c2 cardiomyocytes, which was accompanied by a decrease in NFATc4 expression. miR-29a-3p targeted directly to the 3'-UTR of NFATc4 mRNA and silenced NFATc4 expression. Our results indicate that miR-29a-3p inhibits ET-1-induced cardiomyocyte hypertrophy via inhibiting NFATc4 expression.

  2. Iron-responsive miR-485-3p regulates cellular iron homeostasis by targeting ferroportin.

    PubMed

    Sangokoya, Carolyn; Doss, Jennifer F; Chi, Jen-Tsan

    2013-04-01

    Ferroportin (FPN) is the only known cellular iron exporter in mammalian cells and plays a critical role in the maintenance of both cellular and systemic iron balance. During iron deprivation, the translation of FPN is repressed by iron regulatory proteins (IRPs), which bind to the 5' untranslated region (UTR), to reduce iron export and preserve cellular iron. Here, we report a novel iron-responsive mechanism for the post-transcriptional regulation of FPN, mediated by miR-485-3p, which is induced during iron deficiency and represses FPN expression by directly targeting the FPN 3'UTR. The overexpression of miR-485-3p represses FPN expression and leads to increased cellular ferritin levels, consistent with increased cellular iron. Conversely, both inhibition of miR-485-3p activity and mutation of the miR-485-3p target sites on the FPN 3'UTR are able to relieve FPN repression and lead to decreased cellular iron levels. Together, these findings support a model that includes both IRPs and microRNAs as iron-responsive post-transcriptional regulators of FPN. The involvement of microRNA in the iron-responsive regulation of FPN offers additional stability and fine-tuning of iron homeostasis within different cellular contexts. MiR-485-3p-mediated repression of FPN may also offer a novel potential therapeutic mechanism for circumventing hepcidin-resistant mechanisms responsible for some iron overload diseases.

  3. miR-494-3p Induces Cellular Senescence and Enhances Radiosensitivity in Human Oral Squamous Carcinoma Cells

    PubMed Central

    Weng, Jui-Hung; Yu, Cheng-Chia; Lee, Yueh-Chun; Lin, Cheng-Wei; Chang, Wen-Wei; Kuo, Yu-Liang

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is the most common malignancy of head and neck. Although radiotherapy is used for OSCC treatment, the occurrence of radioresistant cancer cells limits its efficiency. MicroRNAs (miRNAs) are non-coding RNAs with lengths of 18–25 base pairs and known to be involved in carcinogenesis. We previously demonstrated that by targeting B lymphoma Mo-MLV insertion region 1 homolog (Bmi1), miR-494-3p functions as a putative tumor suppressor miRNA in OSCC. In this study, we further discovered that miR-494-3p could enhance the radiosensitivity of SAS OSCC cells and induce cellular senescence. The overexpression of miR-494-3p in SAS cells increased the population of senescence-associated β-galactosidase positive cells, the expression of p16INK4a and retinoblastoma 1 (RB1), as well as downregulated Bmi1. The knockdown of Bmi1 by lentiviral-mediated delivery of specific short hairpin RNAs (shRNAs) also enhanced the radiosensitivity of SAS cells and the activation of the senescence pathway. Furthermore, the inverse correlation between Bmi1 and miR-494-3p expression was observed among OSCC tissues. Results suggest that miR-494-3p could increase the radiosensitivity of OSCC cells through the induction of cellular senescence caused by the downregulation of Bmi1. PMID:27399693

  4. Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells.

    PubMed

    Zhang, Linlin; Lyer, Arun K; Yang, Xiaoqian; Kobayashi, Eisuke; Guo, Yuqi; Mankin, Henry; Hornicek, Francis J; Amiji, Mansoor M; Duan, Zhenfeng

    2015-01-01

    Our prior screening of microRNAs (miRs) identified that miR-199a-3p expression is reduced in osteosarcoma cells, one of the most common types of bone tumor. miR-199a-3p exhibited functions of tumor cell growth inhibition, suggesting the potential application of miR-199a-3p as an anticancer agent. In the study reported here, we designed and developed a lipid-modified dextran-based polymeric nanoparticle platform for encapsulation of miRs, and determined the efficiency and efficacy of delivering miR-199a-3p into osteosarcoma cells. In addition, another potent miR, let-7a, which also displayed tumor suppressive ability, was selected as a candidate miR for evaluation. Fluorescence microscopy studies and real-time polymerase chain reaction results showed that dextran nanoparticles could deliver both miR-199a-3p and let-7a into osteosarcoma cell lines (KHOS and U-2OS) successfully. Western blotting analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays demonstrated that dextran nanoparticles loaded with miRs could efficiently downregulate the expression of target proteins and effectively inhibit the growth and proliferation of osteosarcoma cells. These results demonstrate that a lipid-modified dextran-based polymeric nanoparticle platform may be an effective nonviral carrier for potential miR-based anticancer therapeutics. PMID:25931818

  5. MicroRNA-29a-3p attenuates ET-1-induced hypertrophic responses in H9c2 cardiomyocytes.

    PubMed

    Li, Man; Wang, Nan; Zhang, Jian; He, Hong-Peng; Gong, Hui-Qin; Zhang, Rui; Song, Tie-Feng; Zhang, Li-Nan; Guo, Zhi-Xia; Cao, Dong-Sun; Zhang, Tong-Cun

    2016-07-01

    Transcription factor nuclear factor of activated T cells c4 (NFATc4) is the best-characterized target for the development of cardiac hypertrophy. Aberrant microRNA-29 (miR-29) expression is involved in the development of cardiac fibrosis and congestive heart failure. However, whether miR-29 regulates hypertrophic processes is still not clear. In this study, we investigated the potential functions of miR-29a-3p in endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy. We showed that miR-29a-3p was down-regulated in ET-1-treated H9c2 cardiomyocytes. Overexpression of miR-29a-3p significantly reduced ET-1-induced hypertrophic responses in H9c2 cardiomyocytes, which was accompanied by a decrease in NFATc4 expression. miR-29a-3p targeted directly to the 3'-UTR of NFATc4 mRNA and silenced NFATc4 expression. Our results indicate that miR-29a-3p inhibits ET-1-induced cardiomyocyte hypertrophy via inhibiting NFATc4 expression. PMID:26992639

  6. Prm3p is a pheromone-induced peripheral nuclear envelope protein required for yeast nuclear fusion.

    PubMed

    Shen, Shu; Tobery, Cynthia E; Rose, Mark D

    2009-05-01

    Nuclear membrane fusion is the last step in the mating pathway of the yeast Saccharomyces cerevisiae. We adapted a bioinformatics approach to identify putative pheromone-induced membrane proteins potentially required for nuclear membrane fusion. One protein, Prm3p, was found to be required for nuclear membrane fusion; disruption of PRM3 caused a strong bilateral defect, in which nuclear congression was completed but fusion did not occur. Prm3p was localized to the nuclear envelope in pheromone-responding cells, with significant colocalization with the spindle pole body in zygotes. A previous report, using a truncated protein, claimed that Prm3p is localized to the inner nuclear envelope. Based on biochemistry, immunoelectron microscopy and live cell microscopy, we find that functional Prm3p is a peripheral membrane protein exposed on the cytoplasmic face of the outer nuclear envelope. In support of this, mutations in a putative nuclear localization sequence had no effect on full-length protein function or localization. In contrast, point mutations and deletions in the highly conserved hydrophobic carboxy-terminal domain disrupted both protein function and localization. Genetic analysis, colocalization, and biochemical experiments indicate that Prm3p interacts directly with Kar5p, suggesting that nuclear membrane fusion is mediated by a protein complex.

  7. miR-494-3p Induces Cellular Senescence and Enhances Radiosensitivity in Human Oral Squamous Carcinoma Cells.

    PubMed

    Weng, Jui-Hung; Yu, Cheng-Chia; Lee, Yueh-Chun; Lin, Cheng-Wei; Chang, Wen-Wei; Kuo, Yu-Liang

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is the most common malignancy of head and neck. Although radiotherapy is used for OSCC treatment, the occurrence of radioresistant cancer cells limits its efficiency. MicroRNAs (miRNAs) are non-coding RNAs with lengths of 18-25 base pairs and known to be involved in carcinogenesis. We previously demonstrated that by targeting B lymphoma Mo-MLV insertion region 1 homolog (Bmi1), miR-494-3p functions as a putative tumor suppressor miRNA in OSCC. In this study, we further discovered that miR-494-3p could enhance the radiosensitivity of SAS OSCC cells and induce cellular senescence. The overexpression of miR-494-3p in SAS cells increased the population of senescence-associated β-galactosidase positive cells, the expression of p16(INK4a) and retinoblastoma 1 (RB1), as well as downregulated Bmi1. The knockdown of Bmi1 by lentiviral-mediated delivery of specific short hairpin RNAs (shRNAs) also enhanced the radiosensitivity of SAS cells and the activation of the senescence pathway. Furthermore, the inverse correlation between Bmi1 and miR-494-3p expression was observed among OSCC tissues. Results suggest that miR-494-3p could increase the radiosensitivity of OSCC cells through the induction of cellular senescence caused by the downregulation of Bmi1. PMID:27399693

  8. Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss

    PubMed Central

    Gross, Andrew M; Orosco, Ryan K; Shen, John P; Egloff, Ann Marie; Carter, Hannah; Hofree, Matan; Choueiri, Michel; Coffey, Charles S; Lippman, Scott M; Hayes, D. Neil; Cohen, Ezra E; Grandis, Jennifer R; Nguyen, Quyen T; Ideker, Trey

    2014-01-01

    Head and neck squamous cell carcinoma (HNSCC) is characterized by aggressive behavior with a propensity for metastasis and recurrence. Here we report a comprehensive analysis of the molecular and clinical features of HNSCC that govern patient survival. We find that TP53 mutation is frequently accompanied by loss of chromosome 3p, and that the combination of both events associates with a surprising decrease in survival rates (1.9 years versus >5 years for TP53 mutation alone). The TP53-3p interaction is specific to chromosome 3p, rather than a consequence of global genome instability, and validates in HNSCC and pan-cancer cohorts. In Human Papilloma Virus positive (HPV+) tumors, in which HPV inactivates TP53, 3p deletion is also common and associates with poor outcomes. The TP53-3p event is modified by mir-548k expression which decreases survival even further, while it is mutually exclusive with mutations to RAS signaling. Together, the identified markers underscore the molecular heterogeneity of HNSCC and enable a new multi-tiered classification of this disease. PMID:25086664

  9. miR-129-3p controls centrosome number in metastatic prostate cancer cells by repressing CP110

    PubMed Central

    Bijnsdorp, Irene V.; Hodzic, Jasmina; Lagerweij, Tonny; Westerman, Bart; Krijgsman, Oscar; Broeke, Jurjen; Verweij, Frederik; Nilsson, R. Jonas A.; Rozendaal, Lawrence; van Beusechem, Victor W.; van Moorselaar, Jeroen A.

    2016-01-01

    The centrosome plays a key role in cancer invasion and metastasis. However, it is unclear how abnormal centrosome numbers are regulated when prostate cancer (PCa) cells become metastatic. CP110 was previously described for its contribution of centrosome amplification (CA) and early development of aggressive cell behaviour. However its regulation in metastatic cells remains unclear. Here we identified miR-129-3p as a novel metastatic microRNA. CP110 was identified as its target protein. In PCa cells that have metastatic capacity, CP110 expression was repressed by miR-129-3p. High miR-129-3p expression levels increased cell invasion, while increasing CP110 levels decreased cell invasion. Overexpression of CP110 in metastatic PCa cells resulted in a decrease in the number of metastasis. In tissues of PCa patients, low CP110 and high miR-129-3p expression levels correlated with metastasis, but not with the expression of genes related to EMT. Furthermore, overexpression of CP110 in metastatic PCa cells resulted in excessive-CA (E-CA), and a change in F-actin distribution which is in agreement with their reduced metastatic capacity. Our data demonstrate that miR-129-3p functions as a CA gatekeeper in metastatic PCa cells by maintaining pro-metastatic centrosome amplification (CA) and preventing anti-metastatic E-CA. PMID:26918338

  10. Microsatellite alteration at chromosome 3p loci in neuroendocrine and non-neuroendocrine lung tumors. Histogenetic and clinical relevance.

    PubMed Central

    Hurr, K.; Kemp, B.; Silver, S. A.; el-Naggar, A. K.

    1996-01-01

    Although chromosome 3p regions are the most frequent site for genetic alterations in small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), the extent of such abnormality in carcinoid tumors remained to be investigated. Moreover, the histogenetic and biological implications of these findings in non-carcinoid lung tumors remain unclear. We studied eight microsatellite loci on chromosome 3p regions by multiplex polymerase chain reaction in paired normal and tumor DNA from 17 carcinoid tumors, 5 SCLCs, and 38 NSCLCs to determine the histogenetic and the clinical significance of their alterations in these neoplasms. Our results revealed a lack of microsatellite abnormalities at all loci tested in both typical and atypical carcinoid tumors. SCLCs and NSCLCs showed loss of heterozygosity in 100% (5/5) and 58.0% (22/38), respectively. Loss of heterozygosity at more than two loci correlated significantly with poor histological differentiation and were preponderantly found in high proliferative index and DNA aneuploid NSCLCs. Microsatellite instability was noted in only one (1.7%) of the lesions. Our study suggests that 1) the difference in chromosome 3p alterations between carcinoid tumors and SCLCs favors a stochastic rather than linear evolution of these tumors, 2) 3p alterations may constitute an initial event in the development of small cell carcinomas, and 3) loss of heterozygosity at 3p loci is associated with aggressive tumor characteristics in non-small-cell carcinomas. Images Figure 2 PMID:8701999

  11. Natural Variation in the Yeast Glucose-Signaling Network Reveals a New Role for the Mig3p Transcription Factor

    PubMed Central

    Lewis, Jeffrey A.; Gasch, Audrey P.

    2012-01-01

    The Crabtree effect, in which fermentative metabolism is preferred at the expense of respiration, is a hallmark of budding yeast’s glucose response and a model for the Warburg effect in human tumors. While the glucose-responsive transcriptional repressors Mig1p and Mig2p play well-characterized roles in the Crabtree effect, little function for the related Mig3p transcription factor has been uncovered, despite numerous investigations of laboratory yeast strains. Here we studied a wild isolate of Saccharomyces cerevisiae to uncover a critical role for Mig3p that has been lost in S288c-derived laboratory strains. We found that Mig3p affects the expression of hundreds of glucose-responsive genes in the oak strain YPS163, both during growth under standard conditions and upon ethanol treatment. Our results suggest that Mig3p may act as a multifunctional activator/repressor that plays separate roles under standard vs. stress conditions and that this function has been largely lost in the lab strains. Population analysis suggests that the lab strain and several wild strains harbor mutations that diminish Mig3p function. Thus, by expanding our attention to multiple genetic backgrounds, we have uncovered an important missing link in a key metabolic response. PMID:23275883

  12. Complex translocation among chromosomes 2, 3, 9, 15, 18, 20 in a patient with 3p-syndrome.

    PubMed

    Omrani, Mir Davood; Saleh Gargari, Soraya; Azizi, Faezeh; Safavi Naini, Niloufar; Omrani, Sara

    2014-07-01

    A 3-month old girl with monosomy for distal part of the short arm of chromosome 3 is described. Physical examination showed growth retardation, microcephaly, ptosis, micrognathia, low set ears, broad nasal bridge, Simian crease, long philtrum, thin lips and hypertelorism. The patient's clinical phenotype largely resembled that of 3p- syndrome but her karyotype was more complicated than just losing the telomeric portion (3p-25.3) of the short arm of one of her chromosomes 3. Her karyotype was 46, XX, t(2;18) (p12;q12.1), del(3) (p23p26), t(3;9;15; 20) (q13;p23;q12; p12). Her parents showed a normal karyotype pattern. PMID:24979567

  13. PCR-RFLP studies on chromosome 3p in formaldehyde-fixed, paraffin-embedded cervical cancer tissues.

    PubMed

    Karlsen, F; Rabbitts, P H; Sundresan, V; Hagmar, B

    1994-09-15

    Loss of heterozygosity (LOH) has been extensively studied on the short arm of chromosome 3, and functional proofs have been obtained defining a tumor-suppressor locus at 3p21-22. We examined 31 paraffin-embedded cervical cancer samples for LOH, using 5 PCR-primer pairs, located around 3p21. Allele loss was found in 19 out of the 27 informative samples (70%) while 13 out of 23 informative samples (56%) had LOH located at 3p21-22. More of the human papillomavirus (HPV)-positive samples had LOH compared to the HPV-negative samples, giving only a weak association between loss of allele and HPV integration. Modifications of the DNA in the formaldehyde-fixed samples were detected, and further studies will be required to clarify how such artifacts may affect restriction fragment length polymorphism (RFLP) studies on fixed tissues.

  14. Doubly excited {sup 3}P{sup e} resonance states of two-electron positive ions in Debye plasmas

    SciTech Connect

    Hu, Xiao-Qing; Wang, Yang; Kar, Sabyasachi E-mail: karsabyasachi@yahoo.com; Jiang, Zishi; Jiang, Pinghui

    2015-11-15

    We investigate the doubly excited {sup 3}P{sup e} resonance states of two-electron positive ions Li{sup +}, Be{sup 2+}, B{sup 3+}, and C{sup 4+} by employing correlated exponential wave functions. In the framework of the stabilization method, we calculate two series (3pnp and 3dnd) of {sup 3}P{sup e} resonances below the N = 3 threshold. The {sup 3}P{sup e} resonance parameters (resonance energies and widths) are reported for the first time as a function of the screening parameter. For free-atomic cases, comparisons are made with the reported results and few resonance states are reported for the first time.

  15. Multicopy suppression screen in a Saccharomyces cerevisiae strain lacking the Rab GTPase-activating protein Msb3p.

    PubMed

    Biver, Sophie; Portetelle, Daniel; Vandenbol, Micheline

    2011-01-01

    The yeast proteins, Msb3p and Msb4p, are two Ypt/Rab-specific GTPase-activating proteins sharing redundant functions in exocytosis, organization of the actin cytoskeleton, and budding site selection. To see if Msb3p might play an additional, specific role, we first tested the sensitivities of msb3 and msb4 mutant strains to different drugs and then screened a genomic library for multicopy suppressors of msb3 sensitivity to CdCl(2) or to the calcium channel blocker diltiazem hydrochloride. Three genes (ADH1, RNT1, and SUI1) were found to suppress the CdCl(2) sensitivity of the msb3 strain and three others (YAP6, ZEO1, and SLM1) its diltiazem-HCl sensitivity. The results suggest a possible involvement of Msb3p in calcineurin-mediated signalling.

  16. Na/K-ATPase signaling regulates collagen synthesis through microRNA-29b-3p in cardiac fibroblasts.

    PubMed

    Drummond, Christopher A; Hill, Michael C; Shi, Huilin; Fan, Xiaoming; Xie, Jeffrey X; Haller, Steven T; Kennedy, David J; Liu, Jiang; Garrett, Michael R; Xie, Zijian; Cooper, Christopher J; Shapiro, Joseph I; Tian, Jiang

    2016-03-01

    Chronic kidney disease (CKD) is accompanied by cardiac fibrosis, hypertrophy, and dysfunction, which are commonly referred to as uremic cardiomyopathy. Our previous studies found that Na/K-ATPase ligands or 5/6th partial nephrectomy (PNx) induces cardiac fibrosis in rats and mice. The current study used in vitro and in vivo models to explore novel roles for microRNA in this mechanism of cardiac fibrosis formation. To accomplish this, we performed microRNA profiling with RT-qPCR based arrays on cardiac tissue from rats subjected to marinobufagenin (MBG) infusion or PNx. The analysis showed that a series of fibrosis-related microRNAs were dysregulated. Among the dysregulated microRNAs, microRNA (miR)-29b-3p, which directly targets mRNA of collagen, was consistently reduced in both PNx and MBG-infused animals. In vitro experiments demonstrated that treatment of primary cultures of adult rat cardiac fibroblasts with Na/K-ATPase ligands induced significant increases in the fibrosis marker, collagen protein, and mRNA expression compared with controls, whereas miR-29b-3p expression decreased >50%. Transfection of miR-29b-3p mimics into cardiac fibroblasts inhibited cardiotonic steroids-induced collagen synthesis. Moreover, a specific Na/K-ATPase signaling antagonist, pNaKtide, prevented ouabain-induced increases in collagen synthesis and decreases in miR-29b-3p expression in these cells. In conclusion, these data are the first to indicate that signaling through Na/K-ATPase regulates miRNAs and specifically, miR-29b-3p expression both in vivo and in vitro. Additionally, these data indicate that miR-29b-3p expression plays an important role in the formation of cardiac fibrosis in CKD. PMID:26702050

  17. miR-23a-3p causes cellular senescence by targeting hyaluronan synthase 2: possible implication for skin aging.

    PubMed

    Röck, Katharina; Tigges, Julia; Sass, Steffen; Schütze, Alexandra; Florea, Ana-Maria; Fender, Anke C; Theis, Florian J; Krutmann, Jean; Boege, Fritz; Fritsche, Ellen; Reifenberger, Guido; Fischer, Jens W

    2015-02-01

    Even though aging and cellular senescence appear to be linked, the biological mechanisms interconnecting these two processes remain to be unravelled. Therefore, microRNA (miRNA/miR) profiles were analyzed ex vivo by means of gene array in fibroblasts isolated from young and old human donors. Expression of several miRNAs was positively correlated with donor age. Among them, miR-23a-3p was shown to target hyaluronan synthase 2 (HAS2). HA is a polysaccharide of the extracellular matrix that critically regulates the phenotype of fibroblasts. Indeed, both aged and senescent fibroblasts showed increased miR-23a-3p expression and secreted significantly lower amounts of HA compared with young and non-senescent fibroblasts. Ectopic overexpression of miR-23a-3p in non-senescent fibroblasts led to decreased HAS2-mediated HA synthesis, upregulation of senescence-associated markers, and decreased proliferation. In addition, siRNA-mediated downregulation of HAS2 and pharmacological inhibition of HA synthesis by 4-methylumbelliferone mimicked the effects of miR-23a-3p. In vivo, miR-23a-3p was upregulated and HAS2 was downregulated in the skin of old mice compared with young mice. Inhibition of HA synthesis by 4-methylumbelliferone in mice reduced dermal hydration and viscoelasticity, thereby mimicking an aged skin phenotype. Taken together, these findings appear to link miR-23a-3p and the HA microenvironment as effector mechanisms in both dermal aging and senescence.

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

    SciTech Connect

    Chen, K.S.; Nguyen, D.; Greenberg, F.

    1994-09-01

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

  19. Solvothermal syntheses of Cu{sub 3}P via reactions of amorphous red phosphorus with a variety of copper sources

    SciTech Connect

    Ann Aitken, Jennifer; Ganzha-Hazen, Valentina; Brock, Stephanie L. . E-mail: sbrock@chem.wayne.edu

    2005-04-15

    Polycrystalline Cu{sub 3}P was successfully prepared under a wide variety of solvothermal conditions. The reaction of red phosphorus with several copper sources (copper metal, copper (I) iodide, copper (I) chloride and copper (II) chloride) at 150-200{sup o}C for 1-2 days in water produced Cu{sub 3}P. Products were examined with powder X-ray diffraction, scanning electron microscopy and energy dispersive spectroscopy. Thermal analyses and optical spectroscopy were also performed. A detailed list of reaction conditions, products and impurity phases (where applicable) are reported.

  20. Spectroscopic and Rheokinetic Properties of [(C4H9O)3P=O]2ZnCl2

    NASA Astrophysics Data System (ADS)

    Volkova, E. R.; Karmanov, V. I.; Tereshatov, V. V.

    2013-09-01

    The complex [(C4H9O)3P=O]2ZnCl2 was synthesized. Its effects on urethane-formation kinetics via reaction of hydroxyl-containing oligomers and isocyanates were studied by IR spectroscopy; on polyurethane curing kinetics, by a rheological method. It was established that [(C4H9O)3P=O]2ZnCl2 was an effective catalyst that accelerated the initial step of regular structure formation during the synthesis of multi-component polyurethanes with low curing temperatures.

  1. Measurement of the lifetimes of the lowest {sup 3}P{sub 1} state of neutral Ba and Ra

    SciTech Connect

    Scielzo, N. D.; Guest, J. R.; Schulte, E. C.; Ahmad, I.; Bailey, K.; Holt, R. J.; O'Connor, T. P.; Potterveld, D. H.; Bowers, D. L.; Lu, Z.-T.

    2006-01-15

    The lifetimes of the lowest {sup 3}P{sub 1} states of Ba and Ra were determined to be 1345{+-}14 ns and 422{+-}20 ns, respectively, by measuring the exponential decay of fluorescence after illuminating a thermal atomic beam with pulses of laser light. In addition, the {sup 1}S{sub 0}(F=1/2)-{sup 3}P{sub 1}(F=3/2) transition frequency in {sup 225}Ra was measured to be 13 999.269{+-}0.001 cm{sup -1} by referencing a nearby I{sub 2} transition.

  2. Measurements of the lifetime of the lowest {sup 3}P{sub 1} state of neutral Ba and Ra.

    SciTech Connect

    Scielzo, N. D.; Guest, J. R.; Schulte, E. C.; Ahmad, I.; Bailey, K.; Bowers, D. L.; Holt, R. J.; Lu, Z.-T.; O'Connor, T.; Potterveld, D. H.; Univ. of Chicago

    2006-01-01

    The lifetimes of the lowest {sup 3}P{sub 1} states of Ba and Ra were determined to be 1345 {+-} 14 ns and 422 {+-} 20 ns, respectively, by measuring the exponential decay of fluorescence after illuminating a thermal atomic beam with pulses of laser light. In addition, the {sup 1}S{sub 0}(F=1/2)-{sup 3}P{sub 1}(F=3/2) transition frequency in {sup 225}Ra was measured to be 13 999.269 {+-} 0.001 cm{sup -1} by referencing a nearby I{sub 2} transition.

  3. Candida albicans Als3p is required for wild-type biofilm formation on silicone elastomer surfaces

    PubMed Central

    Zhao, Xiaomin; Daniels, Karla J.; Oh, Soon-Hwan; Green, Clayton B.; Yeater, Kathleen M.; Soll, David R.; Hoyer, Lois L.

    2007-01-01

    Candida albicans ALS3 encodes a large cell-surface glycoprotein that has adhesive properties. Immunostaining of cultured C. albicans germ tubes showed that Als3p is distributed diffusely across the germ tube surface. Two-photon laser scanning microscopy of model catheter biofilms grown using a PALS3-green fluorescent protein (GFP) reporter strain showed GFP production in hyphae throughout the biofilm structure while biofilms grown using a PTPI1-GFP reporter strain showed GFP in both hyphae and yeast-form cells. Model catheter biofilms formed by an als3Δ/als3Δ strain were weakened structurally and had approximately half the biomass of a wild-type biofilm. Reintegration of a wild-type ALS3 allele restored biofilm mass and wild-type biofilm structure. Production of an Als3p-Agα1p fusion protein under control of the ALS3 promoter in the als3Δ/als3Δ strain restored some of the wild-type biofilm structural features, but not the wild-type biofilm mass. Despite its inability to restore wild-type biofilm mass, the Als3p-Agα1p fusion protein mediated adhesion of the als3Δ/als3Δ C. albicans strain to human buccal epithelial cells (BECs). The adhesive role of the Als3p N-terminal domain was further demonstrated by blocking adhesion of C. albicans to BECs with immunoglobulin reactive against the Als3p N-terminal sequences. Together, these data suggest that portions of Als3p that are important for biofilm formation may be different from those that are important in BEC adhesion, and that Als3p may have multiple functions in biofilm formation. Overexpression of ALS3 in an efg1Δ/efg1Δ strain that was deficient for filamentous growth and biofilm formation resulted in growth of elongated C. albicans cells, even under culture conditions that do not favour filamentation. In the catheter biofilm model, the ALS3 overexpression strain formed biofilm with a mass similar to that of a wild-type control. However, C. albicans cells in the biofilm had yeast-like morphology. This

  4. Hooking She3p onto She2p for myosin-mediated cytoplasmic mRNA transport

    PubMed Central

    Singh, Nimisha; Blobel, Günter; Shi, Hang

    2015-01-01

    The segregation of approximately two dozen distinct mRNAs from yeast mother to daughter cell cytoplasm is a classical paradigm for eukaryotic mRNA transport. The information for transport resides in an mRNA element 40–100 nt in length, known as “zipcode.” Targeted transport requires properly positioned actin filaments and cooperative loading of mRNA cargo to myosin. Cargo loading to myosin uses myosin 4 protein (Myo4p), swi5p-dependent HO expression 2 protein (She2p) and 3 protein (She3p), and zipcode. We previously determined a crystal structure of Myo4p and She3p, their 1:2 stoichiometry and interactome; we furthermore showed that the motor complex assembly requires two Myo4p⋅She3p heterotrimers, one She2p tetramer, and at least a single zipcode to yield a stable complex of [Myo4p⋅She3p⋅She2p⋅zipcode] in 2:4:4:1 stoichiometry in vitro. Here, we report a structure at 2.8-Å resolution of a cocrystal of a She2p tetramer bound to a segment of She3p. In this crystal structure, the She3p segment forms a striking hook that binds to a shallow hydrophobic pocket on the surface of each She2p subunit of the tetramer. Both She3p hook and cognate She2p binding pocket are composed of highly conserved residues. We also discovered a highly conserved region of She3p upstream of its hook region. Because this region consists of basic and aromatic residues, it likely represents part of She3p’s binding activity for zipcode. Because She2p also exhibits zipcode-binding activity, we suggest that “hooking” She3p onto She2p aligns each of their zipcode-binding activities into a high-affinity site, thereby linking motor assembly to zipcode. PMID:25535369

  5. Human G3P[4] rotavirus obtained in Japan, 2013, possibly emerged through a human-equine rotavirus reassortment event.

    PubMed

    Malasao, Rungnapa; Saito, Mayuko; Suzuki, Akira; Imagawa, Toshifumi; Nukiwa-Soma, Nao; Tohma, Kentaro; Liu, Xiaofang; Okamoto, Michiko; Chaimongkol, Natthawan; Dapat, Clyde; Kawamura, Kazuhisa; Kayama, Yasuko; Masago, Yoshifumi; Omura, Tatsuo; Oshitani, Hitoshi

    2015-02-01

    Two novel G3P[4] rotavirus strains were detected from children with acute diarrhea in Sendai, Japan, identified as a G3-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotype constellation by whole-genome sequence analysis. The VP7 gene of the two strains displayed the highest nucleotide sequence identity (91 %) and showed a close genetic relationship (99 % bootstrap value) to an equine rotavirus reported in India. The other gene segments were related to human group A rotaviruses. This report suggests a possible reassortment event between human and equine rotaviruses. PMID:25352228

  6. MicroRNA-19b-3p Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF11

    PubMed Central

    Ashraf, Usama; Zhu, Bibo; Ye, Jing; Wan, Shengfeng; Nie, Yanru; Chen, Zheng; Cui, Min; Wang, Chong; Duan, Xiaodong; Zhang, Hao; Chen, Huanchun

    2016-01-01

    ABSTRACT Japanese encephalitis virus (JEV) can invade the central nervous system and consequently induce neuroinflammation, which is characterized by profound neuronal cell damage accompanied by astrogliosis and microgliosis. Albeit microRNAs (miRNAs) have emerged as major regulatory noncoding RNAs with profound effects on inflammatory response, it is unknown how astrocytic miRNAs regulate JEV-induced inflammation. Here, we found the involvement of miR-19b-3p in regulating the JEV-induced inflammatory response in vitro and in vivo. The data demonstrated that miR-19b-3p is upregulated in cultured cells and mouse brain tissues during JEV infection. Overexpression of miR-19b-3p led to increased production of inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6, interleukin-1β, and chemokine (C-C motif) ligand 5, after JEV infection, whereas knockdown of miR-19b-3p had completely opposite effects. Mechanistically, miR-19b-3p modulated the JEV-induced inflammatory response via targeting ring finger protein 11, a negative regulator of nuclear factor kappa B signaling. We also found that inhibition of ring finger protein 11 by miR-19b-3p resulted in accumulation of nuclear factor kappa B in the nucleus, which in turn led to higher production of inflammatory cytokines. In vivo silencing of miR-19b-3p by a specific antagomir reinvigorates the expression level of RNF11, which in turn reduces the production of inflammatory cytokines, abrogates gliosis and neuronal cell death, and eventually improves the survival rate in the mouse model. Collectively, our results demonstrate that miR-19b-3p positively regulates the JEV-induced inflammatory response. Thus, miR-19b-3p targeting may constitute a thought-provoking approach to rein in JEV-induced inflammation. IMPORTANCE Japanese encephalitis virus (JEV) is one of the major causes of acute encephalitis in humans worldwide. The pathological features of JEV-induced encephalitis are inflammatory reactions and

  7. Circulating hsa-miR-30e-5p, hsa-miR-92a-3p, and hsa-miR-223-3p may be novel biomarkers in systemic lupus erythematosus.

    PubMed

    Kim, B-S; Jung, J-Y; Jeon, J-Y; Kim, H-A; Suh, C-H

    2016-10-01

    MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression at the post-transcriptional level, which can be measured in cells, tissues, and body fluids including plasma. Differences in miRNA expression levels suggest an epigenetic mechanism and changed expression levels are emerging as a novel biomarker for various diseases. We attempted to identify circulating miRNAs associated with susceptibility to systemic lupus erythematosus (SLE) in the Korean population and elucidate their significance for clinical phenotype. An expression profiling analysis using miRNA polymerase chain reaction (PCR) array was conducted with pooled miRNA from 10 patients with SLE and 10 healthy controls (HCs). Nine miRNAs were differentially expressed between the SLE and HC. To verify this, we performed quantitative PCR for various miRNA from SLE patients (n = 70) and HCs (n = 40). The hsa-miR-30e-5p, hsa-miR-92a-3p, and hsa-miR-223-3p were significantly up-regulated in plasma of SLE patients (P = 0.048, P = 0.039, and P = 0.046, respectively). Especially, the hsa-miR-223-3p was significantly associated with oral ulcer (P < 0.001) and lupus anticoagulant (P = 0.031). Thus, plasma hsa-miR-30e-5p, hsa-miR-92a-3p, and hsa-miR-223-3p may be promising novel biomarkers in the diagnosis and clinical manifestation of SLE. PMID:27596248

  8. Phospholipid flippases Lem3p-Dnf1p and Lem3p-Dnf2p are involved in the sorting of the tryptophan permease Tat2p in yeast.

    PubMed

    Hachiro, Takeru; Yamamoto, Takaharu; Nakano, Kenji; Tanaka, Kazuma

    2013-02-01

    The type 4 P-type ATPases are flippases that generate phospholipid asymmetry in membranes. In budding yeast, heteromeric flippases, including Lem3p-Dnf1p and Lem3p-Dnf2p, translocate phospholipids to the cytoplasmic leaflet of membranes. Here, we report that Lem3p-Dnf1/2p are involved in transport of the tryptophan permease Tat2p to the plasma membrane. The lem3Δ mutant exhibited a tryptophan requirement due to the mislocalization of Tat2p to intracellular membranes. Tat2p was relocalized to the plasma membrane when trans-Golgi network (TGN)-to-endosome transport was inhibited. Inhibition of ubiquitination by mutations in ubiquitination machinery also rerouted Tat2p to the plasma membrane. Lem3p-Dnf1/2p are localized to endosomal/TGN membranes in addition to the plasma membrane. Endocytosis mutants, in which Lem3p-Dnf1/2p are sequestered to the plasma membrane, also exhibited the ubiquitination-dependent missorting of Tat2p. These results suggest that Tat2p is ubiquitinated at the TGN and missorted to the vacuolar pathway in the lem3Δ mutant. The NH(2)-terminal cytoplasmic region of Tat2p containing ubiquitination acceptor lysines interacted with liposomes containing acidic phospholipids, including phosphatidylserine. This interaction was abrogated by alanine substitution mutations in the basic amino acids downstream of the ubiquitination sites. Interestingly, a mutant Tat2p containing these substitutions was missorted in a ubiquitination-dependent manner. We propose the following model based on these results; Tat2p is not ubiquitinated when the NH(2)-terminal region is bound to membrane phospholipids, but if it dissociates from the membrane due to a low level of phosphatidylserine caused by perturbation of phospholipid asymmetry in the lem3Δ mutant, Tat2p is ubiquitinated and then transported from the TGN to the vacuole.

  9. Accurate long-range coefficients for two excited like isotope He atoms: He(2 {sup 1}P)-He(2 {sup 1}P), He(2 {sup 1}P)-He(2 {sup 3}P), and He(2 {sup 3}P)-He(2 {sup 3}P)

    SciTech Connect

    Zhang, J.-Y.; Yan, Z.-C.; Vrinceanu, D.; Babb, J. F.; Sadeghpour, H. R.

    2007-07-15

    A general formalism is used to express the long-range potential energies in inverse powers of the separation distance between two like atomic or molecular systems with P symmetries. The long-range molecular interaction coefficients are calculated for the molecular symmetries {delta}, {pi}, and {sigma}, arising from the following interactions: He(2 {sup 1}P)-He(2 {sup 1}P), He(2 {sup 1}P)-He(2 {sup 3}P), and He(2 {sup 3}P)-He(2 {sup 3}P). The electric quadrupole-quadrupole term C{sub 5}, the van der Waals (dispersion) term C{sub 6}, and higher-order terms C{sub 8} and C{sub 10} are calculated ab initio using accurate variational wave functions in Hylleraas coordinates with finite nuclear mass effects. A comparison is made with previously published results where available.

  10. miRNA863-3p sequentially targets negative immune regulator ARLPKs and positive regulator SERRATE upon bacterial infection

    PubMed Central

    Niu, Dongdong; Lii, Yifan E.; Chellappan, Padmanabhan; Lei, Lei; Peralta, Karl; Jiang, Chunhao; Guo, Jianhua; Coaker, Gitta; Jin, Hailing

    2016-01-01

    Plant small RNAs play important roles in gene regulation during pathogen infection. Here we show that miR863-3p is induced by the bacterial pathogen Pseudomonas syringae carrying various effectors. Early during infection, miR863-3p silences two negative regulators of plant defence, atypical receptor-like pseudokinase1 (ARLPK1) and ARLPK2, both lacking extracellular domains and kinase activity, through mRNA degradation to promote immunity. ARLPK1 associates with, and may function through another negative immune regulator ARLPK1-interacting receptor-like kinase 1 (AKIK1), an active kinase with an extracellular domain. Later during infection, miR863-3p silences SERRATE, which is essential for miRNA accumulation and positively regulates defence, through translational inhibition. This results in decreased miR863-3p levels, thus forming a negative feedback loop to attenuate immune responses after successful defence. This is an example of a miRNA that sequentially targets both negative and positive regulators of immunity through two modes of action to fine-tune the timing and amplitude of defence responses. PMID:27108563

  11. Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs.

    PubMed

    Sahu, Nisebita; Stephan, Jean-Philippe; Cruz, Darlene Dela; Merchant, Mark; Haley, Benjamin; Bourgon, Richard; Classon, Marie; Settleman, Jeff

    2016-01-01

    Acquired resistance to cancer drug therapies almost always occurs in advanced-stage patients even following a significant response to treatment. In addition to mutational mechanisms, various non-mutational resistance mechanisms have now been recognized. We previously described a chromatin-mediated subpopulation of reversibly drug-tolerant persisters that is dynamically maintained within a wide variety of tumour cell populations. Here we explore a potential role for microRNAs in such transient drug tolerance. Functional screening of 879 human microRNAs reveals miR-371-3p as a potent suppressor of drug tolerance. We identify PRDX6 (peroxiredoxin 6) as a key target of miR-371-3p in establishing drug tolerance by regulating PLA2/PKCα activity and reactive oxygen species. PRDX6 expression is associated with poor prognosis in cancers of multiple tissue origins. These findings implicate miR-371-3p as a suppressor of PRDX6 and suggest that co-targeting of peroxiredoxin 6 or modulating miR-371-3p expression together with targeted cancer therapies may delay or prevent acquired drug resistance. PMID:27484502

  12. Human mitochondrial RNA turnover caught in flagranti: involvement of hSuv3p helicase in RNA surveillance

    PubMed Central

    Szczesny, Roman J.; Borowski, Lukasz S.; Brzezniak, Lien K.; Dmochowska, Aleksandra; Gewartowski, Kamil; Bartnik, Ewa; Stepien, Piotr P.

    2010-01-01

    The mechanism of human mitochondrial RNA turnover and surveillance is still a matter of debate. We have obtained a cellular model for studying the role of hSuv3p helicase in human mitochondria. Expression of a dominant-negative mutant of the hSUV3 gene which encodes a protein with no ATPase or helicase activity results in perturbations of mtRNA metabolism and enables to study the processing and degradation intermediates which otherwise are difficult to detect because of their short half-lives. The hSuv3p activity was found to be necessary in the regulation of stability of mature, properly formed mRNAs and for removal of the noncoding processing intermediates transcribed from both H and L-strands, including mirror RNAs which represent antisense RNAs transcribed from the opposite DNA strand. Lack of hSuv3p function also resulted in accumulation of aberrant RNA species, molecules with extended poly(A) tails and degradation intermediates truncated predominantly at their 3′-ends. Moreover, we present data indicating that hSuv3p co-purifies with PNPase; this may suggest participation of both proteins in mtRNA metabolism. PMID:19864255

  13. 78 FR 12130 - Social Security Ruling, SSR 13-3p; Appeal of an Initial Medical Disability Cessation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-21

    ... ADMINISTRATION Social Security Ruling, SSR 13-3p; Appeal of an Initial Medical Disability Cessation Determination... deciding an appeal of a medical cessation determination. This Ruling also clarifies how this policy applies at the Appeals Council (AC) level when the AC denies a request for review or issues a remand...

  14. Identification of critical residues for transport activity of Acr3p, the Saccharomyces cerevisiae As(III)/H+ antiporter.

    PubMed

    Markowska, Katarzyna; Maciaszczyk-Dziubinska, Ewa; Migocka, Magdalena; Wawrzycka, Donata; Wysocki, Robert

    2015-10-01

    Acr3p is an As(III)/H(+) antiporter from Saccharomyces cerevisiae belonging to the bile/arsenite/riboflavin transporter superfamily. We have previously found that Cys151 located in the middle of the fourth transmembrane segment (TM4) is critical for antiport activity, suggesting that As(III) might interact with a thiol group during the translocation process. In order to identify functionally important residues involved in As(III)/H(+) exchange, we performed a systematic alanine-replacement analysis of charged/polar and aromatic residues that are conserved in the Acr3 family and located in putative transmembrane segments. Nine residues (Asn117, Trp130, Arg150, Trp158, Asn176, Arg230, Tyr290, Phe345, Asn351) were found to be critical for proper folding and trafficking of Acr3p to the plasma membrane. In addition, we found that replacement of highly conserved Phe266 (TM7), Phe352 (TM9), Glu353 (TM9) and Glu380 (TM10) with Ala abolished transport activity of Acr3p, while mutation of Ser349 (TM9) to Ala significantly reduced the As(III)/H(+) exchange, suggesting an important role of these residues in the transport mechanism. Detailed mutational analysis of Glu353 and Glu380 revealed that the negatively charged residues located in the middle of transmembrane segments TM9 and TM10 are crucial for antiport activity. We also discuss a hypothetical model of the Acr3p transport mechanism.

  15. A 5′ cytosine binding pocket in Puf3p specifies regulation of mitochondrial mRNAs

    SciTech Connect

    Zhu, Deyu; Stumpf, Craig R.; Krahn, Joseph M.; Wickens, Marvin; Tanaka Hall, Traci M.

    2010-11-03

    A single regulatory protein can control the fate of many mRNAs with related functions. The Puf3 protein of Saccharomyces cerevisiae is exemplary, as it binds and regulates more than 100 mRNAs that encode proteins with mitochondrial function. Here we elucidate the structural basis of that specificity. To do so, we explore the crystal structures of Puf3p complexes with 2 cognate RNAs. The key determinant of Puf3p specificity is an unusual interaction between a distinctive pocket of the protein with an RNA base outside the 'core' PUF-binding site. That interaction dramatically affects binding affinity in vitro and is required for regulation in vivo. The Puf3p structures, combined with those of Puf4p in the same organism, illuminate the structural basis of natural PUF-RNA networks. Yeast Puf3p binds its own RNAs because they possess a -2C and is excluded from those of Puf4p which contain an additional nucleotide in the core-binding site.

  16. Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs

    PubMed Central

    Sahu, Nisebita; Stephan, Jean-Philippe; Cruz, Darlene Dela; Merchant, Mark; Haley, Benjamin; Bourgon, Richard; Classon, Marie; Settleman, Jeff

    2016-01-01

    Acquired resistance to cancer drug therapies almost always occurs in advanced-stage patients even following a significant response to treatment. In addition to mutational mechanisms, various non-mutational resistance mechanisms have now been recognized. We previously described a chromatin-mediated subpopulation of reversibly drug-tolerant persisters that is dynamically maintained within a wide variety of tumour cell populations. Here we explore a potential role for microRNAs in such transient drug tolerance. Functional screening of 879 human microRNAs reveals miR-371-3p as a potent suppressor of drug tolerance. We identify PRDX6 (peroxiredoxin 6) as a key target of miR-371-3p in establishing drug tolerance by regulating PLA2/PKCα activity and reactive oxygen species. PRDX6 expression is associated with poor prognosis in cancers of multiple tissue origins. These findings implicate miR-371-3p as a suppressor of PRDX6 and suggest that co-targeting of peroxiredoxin 6 or modulating miR-371-3p expression together with targeted cancer therapies may delay or prevent acquired drug resistance. PMID:27484502

  17. 75 FR 3160 - Commerce in Explosives-Storage of Shock Tube With Detonators (2005R-3P)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ... and industry on a number of proposals to amend the regulations in part 555 (Notice No. 968, 68 FR 4406... ATF Notice No. 2 (68 FR 37109, June 23, 2003). ATF received approximately 1,640 comments in response...--Storage of Shock Tube With Detonators (2005R-3P) AGENCY: Bureau of Alcohol, Tobacco, Firearms,...

  18. The t-SNARE AtVAM3p resides on the prevacuolar compartment in Arabidopsis root cells

    SciTech Connect

    Sanderfoot, A.A.; Kovaleva, V.; Zheng, H.; Raikhel, N.V.

    1999-11-01

    Protein cargo is trafficked between the organelles of the endomembrane system inside transport vesicles, a process mediated by integral membrane proteins called SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptors) that reside on the surface of the vesicle (v-SNAREs) and target membrane (t-SNAREs). In examining transport of cargo between the trans-Golgi network and the vacuole in Arabidopsis, the authors have previously characterized AtPEP12p as a t-SNARE residing on the prevacuolar compartment and AtVTl1a as a v-SNARE that interacts with AtPEP12p. Recently, they have begun to characterize AtVAM3p, another Arabidopsis t-SNARE that shows high sequence homology to AtPEP12p. They have found that AtVTl1a also interacts with AtVAM3p, suggesting a role for this t-SNARE in post-Golgi trafficking. AtVAM3p has been suggested to localize to the vacuolar membrane in Arabidopsis cells; however, using specific antisera and expression of epitope-tagged versions of each t-SNARE, the authors have discovered that AtVAM3p is found on the same prevacuolar structure as AtPEP12p in Arabidopsis root cells.

  19. Reduced miR-659-3p Levels Correlate with Progranulin Increase in Hypoxic Conditions: Implications for Frontotemporal Dementia

    PubMed Central

    Piscopo, Paola; Grasso, Margherita; Fontana, Francesca; Crestini, Alessio; Puopolo, Maria; Del Vescovo, Valerio; Venerosi, Aldina; Calamandrei, Gemma; Vencken, Sebastian F.; Greene, Catherine M.; Confaloni, Annamaria; Denti, Michela A.

    2016-01-01

    Progranulin (PGRN) is a secreted protein expressed ubiquitously throughout the body, including the brain, where it localizes in neurons and is activated microglia. Loss-of-function mutations in the GRN gene are an important cause of familial frontotemporal lobar degeneration (FTLD). PGRN has a neurotrophic and anti-inflammatory activity, and it is neuroprotective in several injury conditions, such as oxygen or glucose deprivation, oxidative injury, and hypoxic stress. Indeed, we have previously demonstrated that hypoxia induces the up-regulation of GRN transcripts. Several studies have shown microRNAs (miRNAs) involvement in hypoxia. Moreover, in FTLD patients with a genetic variant of GRN (rs5848), the reinforcement of miR-659-3p binding site has been suggested to be a risk factor. Here, we report that miR-659-3p interacts directly with GRN 3′UTR as shown by luciferase assay in HeLa cells and ELISA and Western Blot analysis in HeLa and Kelly cells. Moreover, we demonstrate the physical binding between GRN mRNA and miR-659-3p employing a miRNA capture-affinity technology in SK-N-BE and Kelly cells. In order to study miRNAs involvement in hypoxia-mediated up-regulation of GRN, we evaluated miR-659-3p levels in SK-N-BE cells after 24 h of hypoxic treatment, finding them inversely correlated to GRN transcripts. Furthermore, we analyzed an animal model of asphyxia, finding that GRN mRNA levels increased at post-natal day (pnd) 1 and pnd 4 in rat cortices subjected to asphyxia in comparison to control rats and miR-659-3p decreased at pnd 4 just when GRN reached the highest levels. Our results demonstrate the interaction between miR-659-3p and GRN transcript and the involvement of miR-659-3p in GRN up-regulation mediated by hypoxic/ischemic insults. PMID:27199656

  20. Role of miR-222-3p in c-Src-Mediated Regulation of Osteoclastogenesis

    PubMed Central

    Takigawa, Shinya; Chen, Andy; Wan, Qiaoqiao; Na, Sungsoo; Sudo, Akihiro; Yokota, Hiroki; Hamamura, Kazunori

    2016-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that play a mostly post-transcriptional regulatory role in gene expression. Using RAW264.7 pre-osteoclast cells and genome-wide expression analysis, we identified a set of miRNAs that are involved in osteoclastogenesis. Based on in silico analysis, we specifically focused on miR-222-3p and evaluated its role in osteoclastogenesis. The results show that the inhibitor of miR-222-3p upregulated the mRNA levels of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and tartrate-resistant acid phosphatase (TRAP), while its mimicking agent downregulated their mRNA levels. Western blot analysis showed that its inhibitor increased the protein levels of TRAP and cathepsin K, while its mimicking agent decreased their levels. Genome-wide mRNA expression analysis in the presence and absence of receptor activator of nuclear factor κ-B ligand (RANKL) predicted c-Src as a potential regulatory target of miR-222-3p. Live cell imaging using a fluorescence resonance energy transfer (FRET) technique revealed that miR-222-3p acted as an inhibitor of c-Src activity, and a partial silencing of c-Src suppressed RANKL-induced expression of TRAP and cathepsin K, as well as the number of multi-nucleated osteoclasts and their pit formation. Collectively, the study herein demonstrates that miR-222-3p serves as an inhibitor of osteoclastogenesis and c-Src mediates its inhibition of cathepsin K and TRAP. PMID:26891296

  1. miR-21-3p is a positive regulator of L1CAM in several human carcinomas.

    PubMed

    Doberstein, Kai; Bretz, Niko P; Schirmer, Uwe; Fiegl, Heidi; Blaheta, Roman; Breunig, Christian; Müller-Holzner, Elisabeth; Reimer, Dan; Zeimet, Alain G; Altevogt, Peter

    2014-11-28

    Expression of L1 cell adhesion molecule (L1CAM) occurs frequently in human cancers and is associated with poor prognosis in cancers such as ovarian, endometrial, breast, renal cell carcinoma and pancreatic ductal adenocarcinoma. L1CAM promotes cell motility, invasion, chemoresistance and metastasis formation. Elucidating genetic processes involved in the expression of L1CAM in cancers is of considerable importance. Transcription factors such as SLUG, β-catenin/TCF-LEF, PAX8 and VHL have been implicated in the re-activation of L1CAM in various types of cancers. There is increasing evidence that micro-RNAs can also have strong effects on gene expression. Here we have identified miR-21-3p as a positive regulator of L1CAM expression. Over-expression of miR-21-3p (miR-21*) but not the complementary sequence miR-21-5p (miR-21) could strongly augment L1CAM expression in renal, endometrial and ovarian carcinoma derived cell lines by an unknown mechanism involving transcriptional activation of the L1CAM gene. In patient cohorts from renal, endometrial and ovarian cancers we observed a strong positive correlation of L1CAM and miR-21-3p expressions. Although L1CAM alone was a reliable marker for overall and disease free survival, the combination of L1CAM and miR-21-3p expressions strongly enhanced the predictive power. Our findings shed new light on the complex regulation of L1CAM in cancers and advocate the use of L1CAM/miR-21-3p for diagnostic application. PMID:25149066

  2. Perfluorooctane Sulfonate Disturbs Nanog Expression through miR-490-3p in Mouse Embryonic Stem Cells

    PubMed Central

    Chen, Minjian; Han, Xiumei; Du, Guizhen; Ji, Xiaoli; Chang, Chunxin; Rehan, Virender K.; Wang, Xinru; Xia, Yankai

    2013-01-01

    Perfluorooctane sulfonate (PFOS) poses potential risks to reproduction and development. Mouse embryonic stem cells (mESCs) are ideal models for developmental toxicity testing of environmental contaminants in vitro. However, the mechanism by which PFOS affects early embryonic development is still unclear. In this study, mESCs were exposed to PFOS for 24 h, and then general cytotoxicity and pluripotency were evaluated. MTT assay showed that neither PFOS (0.2 µM, 2 µM, 20 µM, and 200 µM) nor control medium (0.1% DMSO) treatments affected cell viability. Furthermore, there were no significant differences in cell cycle and apoptosis between the PFOS treatment and control groups. However, we found that the mRNA and protein levels of pluripotency markers (Sox2, Nanog) in mESCs were significantly decreased following exposure to PFOS for 24 h, while there were no significant changes in the mRNA and protein levels of Oct4. Accordingly, the expression levels of miR-145 and miR-490-3p, which can regulate Sox2 and Nanog expressions were significantly increased. Chrm2, the host gene of miR-490-3p, was positively associated with miR-490-3p expression after PFOS exposure. Dual luciferase reporter assay suggests that miR-490-3p directly targets Nanog. These results suggest that PFOS can disturb the expression of pluripotency factors in mESCs, while miR-145 and miR-490-3p play key roles in modulating this effect. PMID:24098361

  3. Communication: Direct measurements of nascent O(3P0,1,2) fine-structure distributions and branching ratios of correlated spin-orbit resolved product channels CO(ã3Π; v) + O(3P0,1,2) and CO(tilde X{}^1Σ ^ + ; v) + O(3P0,1,2) in VUV photodissociation of CO2

    NASA Astrophysics Data System (ADS)

    Lu, Zhou; Chang, Yih Chung; Gao, Hong; Benitez, Yanice; Song, Yu; Ng, C. Y.; Jackson, W. M.

    2014-06-01

    We present a generally applicable experimental method for the direct measurement of nascent spin-orbit state distributions of atomic photofragments based on the detection of vacuum ultraviolet (VUV)-excited autoionizing-Rydberg (VUV-EAR) states. The incorporation of this VUV-EAR method in the application of the newly established VUV-VUV laser velocity-map-imaging-photoion (VMI-PI) apparatus has made possible the branching ratio measurement for correlated spin-orbit state resolved product channels, CO(ã3Π; v) + O(3P0,1,2) and CO(tilde X{}^1Σ ^ + ; v) + O(3P0,1,2), formed by VUV photoexcitation of CO2 to the 4s(101) Rydberg state at 97,955.7 cm-1. The total kinetic energy release (TKER) spectra obtained from the O+ VMI-PI images of O(3P0,1,2) reveal the formation of correlated CO(ã3Π; v = 0-2) with well-resolved v = 0-2 vibrational bands. This observation shows that the dissociation of CO2 to form the spin-allowed CO(ã3Π; v = 0-2) + O(3P0,1,2) channel has no potential energy barrier. The TKER spectra for the spin-forbidden CO(tilde X{}^1Σ ^ + ; v) + O(3P0,1,2) channel were found to exhibit broad profiles, indicative of the formation of a broad range of rovibrational states of CO(tilde X{}^1Σ ^ + ) with significant vibrational populations for v = 18-26. While the VMI-PI images for the CO(ã3Π; v = 0-2) + O(3P0,1,2) channel are anisotropic, indicating that the predissociation of CO2 4s(101) occurs via a near linear configuration in a time scale shorter than the rotational period, the angular distributions for the CO(tilde X{}^1Σ ^ + ; v) + O(3P0,1,2) channel are close to isotropic, revealing a slower predissociation process, which possibly occurs on a triplet surface via an intersystem crossing mechanism.

  4. Communication: direct measurements of nascent O((3)P0,1,2) fine-structure distributions and branching ratios of correlated spin-orbit resolved product channels CO(ã(3)Π; v) + O((3)P0,1,2) and CO(X̃(1)Σ(+); v) + O((3)P0,1,2) in VUV photodissociation of CO2.

    PubMed

    Lu, Zhou; Chang, Yih Chung; Gao, Hong; Benitez, Yanice; Song, Yu; Ng, C Y; Jackson, W M

    2014-06-21

    We present a generally applicable experimental method for the direct measurement of nascent spin-orbit state distributions of atomic photofragments based on the detection of vacuum ultraviolet (VUV)-excited autoionizing-Rydberg (VUV-EAR) states. The incorporation of this VUV-EAR method in the application of the newly established VUV-VUV laser velocity-map-imaging-photoion (VMI-PI) apparatus has made possible the branching ratio measurement for correlated spin-orbit state resolved product channels, CO(ã(3)Π; v) + O((3)P0,1,2) and CO(X̃(1)Σ(+); v) + O((3)P0,1,2), formed by VUV photoexcitation of CO2 to the 4s(10 (1)) Rydberg state at 97,955.7 cm(-1). The total kinetic energy release (TKER) spectra obtained from the O(+) VMI-PI images of O((3)P0,1,2) reveal the formation of correlated CO(ã(3)Π; v = 0-2) with well-resolved v = 0-2 vibrational bands. This observation shows that the dissociation of CO2 to form the spin-allowed CO(ã(3)Π; v = 0-2) + O((3)P0,1,2) channel has no potential energy barrier. The TKER spectra for the spin-forbidden CO(X̃(1)Σ(+); v) + O((3)P0,1,2) channel were found to exhibit broad profiles, indicative of the formation of a broad range of rovibrational states of CO(X̃(1)Σ(+)) with significant vibrational populations for v = 18-26. While the VMI-PI images for the CO(ã(3)Π; v = 0-2) + O((3)P0,1,2) channel are anisotropic, indicating that the predissociation of CO2 4s(10 (1)) occurs via a near linear configuration in a time scale shorter than the rotational period, the angular distributions for the CO(X̃(1)Σ(+); v) + O((3)P0,1,2) channel are close to isotropic, revealing a slower predissociation process, which possibly occurs on a triplet surface via an intersystem crossing mechanism. PMID:24952514

  5. [Genomic Characterization of an Unusual Human G3P[3] Rotavirus with Multiple Cross-species Reassortment].

    PubMed

    Dong, Huijin; Qian, Yuan; Nong, Yi; Zhang, You; Mo, Zhaojun; Li, Rongcheng

    2016-03-01

    One unusual human G3P[3] group A rotavirus (RVA) strain M2-102 was identified in stool sample collected from a child with diarrhea in Guangxi Province, China in 2014. It is well known that G3P[3] is a genotype commonly identified in feline and canine RVAs. However, the preliminary phylogenetic analyses of the VP7 and VP4 genes of strain M2-102 indicated that these two genes were closely related to bat RVA strain MYAS33 and simian strain RRV, respectively, whereas both clustered distantly to feline/canine-like RVA strains. In this study, full genome sequencing and molecular analyses were conducted to obtain the true origin of strain M2-102. It was revealed that strain RVA/Human-wt/CHN/M2-102/2014/G3P[3] exhibited a G3-P[3]-I3-R3-C3-M3-A9-N3-T3-E3-H6 genotype constellation for VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5 genes. Phylogenetic analyses revealed that 5 genes (VP7, VP1, VP2, NSP2 and NSP3) from strain M2-102 were closely related to those of bat strain MYAS33 from Yunnan Province which was thought a true bat RVA strain rather than a virus transmitted between species, while another 5 genes (VP4, VP3, NSP1, NSP4 and NSP5) clustered closely with those of simian strain RRV, yet the VP6 gene was closely related to that of human G3P[9] strain AU-1 and AU-1-like RVAs. The epidemiological data indicated that the child infected with M2-102 came from a countryside village, located in Dong Autonomous County of Sanjiang (subtropical hilly wooded area), Liuzhou city in Guangxi Province which might provide natural environment for reassortment events occurring among animal and human RVAs. Therefore, the data suggest that human strain M2-102 might originate from multiple reassortment events among bat, simian and human AU-1-like RVAs, yet it is not clear whether the genomic backbone based on bat MYAS33 (5 genes) and simian RRV (5 genes) like rotaviruses had been obtained through reassortment before being transmitted to the human. This is the first report on whole

  6. Stark parameters irregularities of Xe II lines obtained by transitions from ({sup 3}P{sub 1})6plevels

    SciTech Connect

    Mar, S.; Pelaez, R. J.; Rodriguez, F.; Aparicio, J. A.

    2008-10-22

    Stark widths and shifts of some Xe II lines belonging to the supermultiplets with upper levels ({sup 3}P{sub 1})6p were measured using a pulsed discharge lamp. Plasma parameters, i.e. electron density and temperature, in this experiment were in the range from 0.2 to 1.4x10{sup 23} m{sup -3} and from 18000 to 23000 K, respectively. Lines obtained by transitions from levels ({sup 3}P{sub 1})6p show some strong intra-supermultiplet irregularities in their Stark widths and shifts. These results and the measurements obtained in previous works were used here to analyse the main irregularities that can appear in the case of Xe II. This study may be very useful for obtaining Stark parameters of non-measured lines, using the known parameters of other lines belonging to similar transitions.

  7. Interstitial Chromosome 3p14.1 Deletion due to a Maternal Insertion: Phenotype and Association with Balanced Parental Rearrangement

    PubMed Central

    Hajek, Catherine; Wang, Jia-Chi; Mahon, Loretta W.; Martinez, Ariadna; Saitta, Sulagna C.

    2016-01-01

    Interstitial deletions of 3p14p12 are rare chromosome abnormalities. We present a patient with multiple congenital anomalies and a 15.4-Mb interstitial loss of chromosome 3p14p12 detected by chromosomal microarray (CMA). Our patient shared many phenotypic features with other reported cases involving the same region including prominent forehead, short palpebral fissures, hand and foot anomalies, genital abnormalities, and bilateral hearing loss. Given the clinical similarity of these cases with significant overlap of the deleted regions, it is likely that the phenotype is related to the deletion of specific genes within the region. Further molecular cytogenetic investigation revealed that our patient's rearrangement was derived from a cryptic insertion of a segment of chromosome 3p into chromosome 18q in the mother, which was balanced and therefore not visible on the mother's CMA. To our knowledge, this finding has not been previously reported. This case illustrates the importance of using molecular cytogenetics for structural analysis and parental studies. CMA is commonly the first-line study in patients with multiple congenital anomalies; however, it is not the appropriate modality to define a structural rearrangement that may be the cause of a deletion. The use of adjunct studies to define the mechanism of an identified copy number aberration has direct clinical application: to identify the underlying cause of the chromosomal abnormality and to define the recurrence risk. Additionally, this case adds to the current body of work regarding a recurrent phenotype that can be attributed to interstitial chromosome 3p deletions, which may help define the phenotypic implications of deletions in this region and support early clinical management. PMID:27194973

  8. MicroRNA142-3p promotes tumor-initiating and radioresistant properties in malignant pediatric brain tumors.

    PubMed

    Lee, Yi-Yen; Yang, Yi-Ping; Huang, Ming-Chao; Wang, Mong-Lien; Yen, Sang-Hue; Huang, Pin-I; Chen, Yi-Wei; Chiou, Shih-Hwa; Lan, Yuan-Tzu; Ma, Hsin-I; Shih, Yang-Hsin; Chen, Ming-Teh

    2014-01-01

    Primary central nervous system (CNS) atypical teratoid/rhabdoid tumor (ATRT) is an extremely malignant pediatric brain tumor observed in infancy and childhood. It has been reported that a subpopulation of CD133(+) cells isolated from ATRT tumors present with cancer stem-like and radioresistant properties. However, the exact biomolecular mechanisms of ATRT or CD133-positive ATRT (ATRT-CD133(+)) cells are still unclear. We have previously shown that ATRT-CD133(+) cells have pluripotent differentiation ability and the capability of malignant cells to be highly resistant to ionizing radiation (IR). By using microRNA array and quantitative RT-PCR in this study, we showed that expression of miR142-3p was lower in ATRT-CD133(+) cells than in ATRT-CD133(-) cells. miR142-3p overexpression significantly inhibited the self-renewal and tumorigenicity of ATRT-CD133(+) cells. On the contrary, silencing of endogenous miR142-3p dramatically increased the tumor-initiating and stem-like cell capacities in ATRT cells or ATRT-CD133(-) cells and further promoted the mesenchymal transitional and radioresistant properties of ATRT cells. Most importantly, therapeutic delivery of miR142-3p in ATRT cells effectively reduced its lethality by blocking tumor growth, repressing invasiveness, increasing radiosensitivity, and prolonging survival time in orthotropic-transplanted immunocompromised mice. These results demonstrate the prospect of developing novel miRNA-based strategies to block the stem-like and radioresistant properties of malignant pediatric brain cancer stem cells. PMID:24816458

  9. Recombination reactions of 5-eV O(3P) atoms on a MgF2 surface

    NASA Technical Reports Server (NTRS)

    Orient, O. J.; Chutjian, A.; Murad, E.

    1990-01-01

    A source of hyperthermal, ground-state, impurity-free, atomic oxygen of an energy variable in the range 2-100 eV has been developed. Experimental results are presented of emission spectra in the wavelength range 250-850 nm produced by collisions of 5-eV O(3P) atoms with adsorbed NO and CO molecules on a MgF2 surface.

  10. Interstitial Chromosome 3p14.1 Deletion due to a Maternal Insertion: Phenotype and Association with Balanced Parental Rearrangement.

    PubMed

    Hajek, Catherine; Wang, Jia-Chi; Mahon, Loretta W; Martinez, Ariadna; Saitta, Sulagna C

    2016-04-01

    Interstitial deletions of 3p14p12 are rare chromosome abnormalities. We present a patient with multiple congenital anomalies and a 15.4-Mb interstitial loss of chromosome 3p14p12 detected by chromosomal microarray (CMA). Our patient shared many phenotypic features with other reported cases involving the same region including prominent forehead, short palpebral fissures, hand and foot anomalies, genital abnormalities, and bilateral hearing loss. Given the clinical similarity of these cases with significant overlap of the deleted regions, it is likely that the phenotype is related to the deletion of specific genes within the region. Further molecular cytogenetic investigation revealed that our patient's rearrangement was derived from a cryptic insertion of a segment of chromosome 3p into chromosome 18q in the mother, which was balanced and therefore not visible on the mother's CMA. To our knowledge, this finding has not been previously reported. This case illustrates the importance of using molecular cytogenetics for structural analysis and parental studies. CMA is commonly the first-line study in patients with multiple congenital anomalies; however, it is not the appropriate modality to define a structural rearrangement that may be the cause of a deletion. The use of adjunct studies to define the mechanism of an identified copy number aberration has direct clinical application: to identify the underlying cause of the chromosomal abnormality and to define the recurrence risk. Additionally, this case adds to the current body of work regarding a recurrent phenotype that can be attributed to interstitial chromosome 3p deletions, which may help define the phenotypic implications of deletions in this region and support early clinical management. PMID:27194973

  11. Spectroscopy of the forbidden 1S0 -->3P0 transition on ultra-cold ytterbium atoms

    NASA Astrophysics Data System (ADS)

    Dareau, Alexandre; Scholl, Matthias; Beaufils, Quentin; Döring, Daniel; Beugnon, Jérôme; Gerbier, Fabrice

    2015-05-01

    Cold atoms in optical lattices are often considered a rich playground for emulating condensed matter systems, since they make it possible to engineer many-body Hamiltonians with tunable parameters. However, one missing feature is the ability to emulate orbital magnetism. Recent proposals for simulating orbital magnetism with neutral atoms rely on a state-dependent optical lattice with laser-driven hopping. Ytterbium, with its long lived metastable state (3P0), is a well-suited candidate for the implementation of such schemes. Addressing the forbidden transition between ytterbium ground (1S0) and meta-stable (3P0) states is experimentally challenging, and requires the use of a laser with stability close to the standards of atomic clocks. I will report on the building of a ultra-narrow laser locked on a high-finesse low-expansion cavity. I will then show how the absolute frequency of the cavity modes can be calibrated by performing high-resolution spectroscopy on molecular iodine, allowing us perform Doppler spectroscopy on the 1S0 -->3P0 transition of an ytterbium BEC.

  12. A new form of Ca{sub 3}P{sub 2} with a ring of Dirac nodes

    SciTech Connect

    Xie, Lilia S.; Schoop, Leslie M.; Seibel, Elizabeth M.; Gibson, Quinn D.; Xie, Weiwei; Cava, Robert J.

    2015-08-01

    We report the synthesis and crystal structure of a new high-temperature form of Ca{sub 3}P{sub 2}. The crystal structure was determined through Rietveld refinements of synchrotron powder x-ray diffraction data. This form of Ca{sub 3}P{sub 2} has a crystal structure of the hexagonal Mn{sub 5}Si{sub 3} type, with a Ca ion deficiency compared to the ideal 5:3 stoichiometry. This yields a stable, charge-balanced compound of Ca{sup 2+} and P{sup 3−}. We also report the observation of a secondary hydride phase, Ca{sub 5}P{sub 3}H, which again is a charge-balanced compound. The calculated band structure of Ca{sub 3}P{sub 2} indicates that it is a three-dimensional Dirac semimetal with a highly unusual ring of Dirac nodes at the Fermi level. The Dirac states are protected against gap opening by a mirror plane in a manner analogous to what is seen for graphene.

  13. miR-130b-3p Upregulation Contributes to the Development of Thyroid Adenomas Targeting CCDC6 Gene

    PubMed Central

    Leone, Vincenza; Langella, Concetta; Esposito, Francesco; De Martino, Marco; Decaussin-Petrucci, Myriam; Chiappetta, Gennaro; Bianco, Antonio; Fusco, Alfredo

    2015-01-01

    We have previously studied the function of microRNAs (miRNAs) in thyroid cells using the differentiated rat thyroid PC Cl 3 cells that need thyrotropin (TSH) for their growth. The miRNA expression profile examination allowed the detection of a set of miRNAs downregulated and upregulated by TSH. Here, we first demonstrated that upregulation of miR-130b-3p occurs through a protein kinase A-cAMP-responsive element binding protein (CREB)-dependent mechanism. Then, we analyzed its expression in human thyroid follicular adenomas, where a constitutive CREB activation is frequently present. miR-130b-3p results in upregulation with a high fold-change in most thyroid follicular adenomas. Then, we identified CCDC6, coding for a protein that interacts with CREB1 leading to the transcriptional repression of CREB1 target genes, as a target of this miRNA. The targeting of CCDC6 by miR-130b-3p likely accounts for the mechanism by which its upregulation contributes to the development of thyroid adenomas increasing CREB1 activity. PMID:26835423

  14. Measurement of the 3s3pP31 lifetime in magnesium using a magneto-optical trap

    NASA Astrophysics Data System (ADS)

    Hansen, P. L.; Therkildsen, K. T.; Malossi, N.; Jensen, B. B.; van Ooijen, E. D.; Brusch, A.; Müller, J. H.; Hald, J.; Thomsen, J. W.

    2008-06-01

    We demonstrate an accurate method for measuring the lifetime of long-lived metastable magnetic states using a magneto-optical trap (MOT). Through optical pumping, the metastable (3s3p)P31 level is populated in a standard MOT. During the optical pumping process, a fraction of the population is captured in the magnetic quadrupole field of the MOT. When the metastable atoms decay to the (3s2)S10 ground state they are recaptured into the MOT. In this system no alternative cascading transition is possible. The lifetime of the metastable level is measured directly as an exponential load time of the MOT. We have experimentally tested our method by measuring the lifetime of the (3s3p)P31 of M24g . This lifetime has been measured numerous times previously, but with quite different results. Using our method we find the (3s3p)P31 lifetime to be (4.4±0.2)ms . Theoretical values point toward a lower value for the lifetime.

  15. Identification of a novel PPARβ/δ/miR-21-3p axis in UV-induced skin inflammation.

    PubMed

    Degueurce, Gwendoline; D'Errico, Ilenia; Pich, Christine; Ibberson, Mark; Schütz, Frédéric; Montagner, Alexandra; Sgandurra, Marie; Mury, Lionel; Jafari, Paris; Boda, Akash; Meunier, Julien; Rezzonico, Roger; Brembilla, Nicolò Costantino; Hohl, Daniel; Kolios, Antonios; Hofbauer, Günther; Xenarios, Ioannis; Michalik, Liliane

    2016-01-01

    Although excessive exposure to UV is widely recognized as a major factor leading to skin perturbations and cancer, the complex mechanisms underlying inflammatory skin disorders resulting from UV exposure remain incompletely characterized. The nuclear hormone receptor PPARβ/δ is known to control mouse cutaneous repair and UV-induced skin cancer development. Here, we describe a novel PPARβ/δ-dependent molecular cascade involving TGFβ1 and miR-21-3p, which is activated in the epidermis in response to UV exposure. We establish that the passenger miRNA miR-21-3p, that we identify as a novel UV-induced miRNA in the epidermis, plays a pro-inflammatory function in keratinocytes and that its high level of expression in human skin is associated with psoriasis and squamous cell carcinomas. Finally, we provide evidence that inhibition of miR-21-3p reduces UV-induced cutaneous inflammation in ex vivo human skin biopsies, thereby underlining the clinical relevance of miRNA-based topical therapies for cutaneous disorders. PMID:27250636

  16. Nuclear and magnetic supercells in the multiferroic candidate: Pb3TeMn3P2O14

    DOE PAGES

    Silverstein, Harlyn J.; Huq, Ashfia; Lee, Minseong; Choi, Eun Sang; Zhou, Haidong; Wiebe, Christopher R.

    2014-10-18

    Here we report that the dugganites, Te6+-containing members of the langasite series, have attracted recent interest due to their complex low-temperature magnetic unit cells, magnetodielectric, and potentially multiferroic properties. For Pb2+-containing dugganites, a large monoclinic supercell was reported and was found to have a profound effect on the low temperature magnetism and spin excitation spectra. Pb3TeMn3P2O14 is another dugganite previously shown to distort away from the canonical P321 langasite unit cell, although this supercell was never fully solved. We report the full crystal and magnetic structure solution of Pb3TeMn3P2O14 using synchrotron x-ray and neutron diffraction data: a large trigonal supercellmore » is observed in this material, which is believed to be the first supercell of its kind in the langasite family. Here, the magnetic structure, high-magnetic field behavior, and dielectric properties of Pb3TeMn3P2O14 are presented. In addition to showing weak magnetoelectric behavior similar to other langasites, it was found that a phase transition occurs at 3 T near the antiferromagnetic transition temperature.« less

  17. miR-125a-3p targets MTA1 to suppress NSCLC cell proliferation, migration, and invasion.

    PubMed

    Zhang, Hong; Zhu, Xiaoxia; Li, Na; Li, Dianhe; Sha, Zhou; Zheng, Xiaokang; Wang, Haofei

    2015-07-01

    Metastasis-associated gene 1 (MTA1) is associated with cell growth, metastasis, and survival in non-small-cell lung cancer (NSCLC). Several previous reports have demonstrated that microRNAs affect gene expression through interaction between their seed region and the 3'-untranslated region of the target mRNA, resulting in post-transcriptional regulation. The aim of this study was to identify miRNAs that suppress malignancy in NSCLC cells by targeting MTA1. Two human NSCLC cell lines were analyzed for the expression of MTA1 by quantitative RT-PCR and western blotting after transfection with MTA1 mimics. A luciferase reporter assay was established to test the direct connection between MTA1 and its upstream miRNAs. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2'-deoxyuridine analysis, and colony formation assay. Cell migration and invasive capacity were evaluated by wound-healing assay and transwell assay. The miRNA/MTA1 axis was also probed by quantitative RT-PCR and western blotting in samples from eight NSCLC patients. Among the candidate miRNAs, miR-125a-3p was shown to post-transcriptionally regulate MTA1 in NSCLC cells. These data were reinforced by the luciferase reporter assay, in addition to the demonstration that MTA1 is inversely correlated with miR-125a-3p in NSCLC tissues. Furthermore, miR-125a-3p was found to inhibit NSCLC cell proliferation, migration, and invasion, through the same mechanisms of down-regulated MTA1. Our report demonstrates that miR-125a-3p inhibits the proliferation, migration, and invasion of NSCLC cells through down-regulation of MTA1, indicating the role of the miR-125a-3p/MTA1 axis in NSCLC, and may provide novel insight into the molecular mechanisms underpinning the disease and potential therapeutic targets. PMID:25998575

  18. Genetic characterization of a novel G3P[14] rotavirus strain causing gastroenteritis in 12 year old Australian child.

    PubMed

    Donato, Celeste M; Manuelpillai, Nicholas M; Cowley, Daniel; Roczo-Farkas, Susie; Buttery, Jim P; Crawford, Nigel W; Kirkwood, Carl D

    2014-07-01

    A genotype G3P[14] rotavirus strain was identified in a 12year old child presenting to the Emergency Department of the Royal Children's Hospital, Melbourne, with gastroenteritis. G3P[14] strains have been previously identified in rabbits in Japan, China, the USA and Italy and a single lapine-like strain from a child in Belgium. Full genome sequence analysis of RVA/Human-wt/AUS/RCH272/2012/G3P[14] (RCH272) revealed that the strain contained the novel genome constellation G3-P[14]-I2-R3-C3-M3-A9-N2-T6-E2-H3. The genome was genetically divergent to previously characterized lapine viruses and the genes were distantly related to a range of human bovine-like strains and animal strains of bovine, bat and canine/feline characteristics. The VP4, VP6, NSP2, NSP3, NSP4 and NSP5 genes of RCH272 clustered within bovine lineages in the phylogenetic analysis and shared moderate genetic similarity with an Australian bovine-like human strain RVA/Human-tc/AUS/MG6/1993/G6P[14]. Bayesian coalescent analysis suggested these genes of RCH272 and RVA/Human-tc/AUS/MG6/1993/G6P[14] were derived from a population of relatively homogenous bovine-like ancestral strains circulating between 1943 and 1989. The VP7, VP1, VP2 and NSP1 genes shared moderate genetic similarity with the Chinese strain RVA/Bat-tc/CHN/MSLH14/2011/G3P[3] and the VP3 gene clustered within a lineage comprised of canine and feline strains. This strain may represent the direct transmission from an unknown host species or be derived via multiple reassortment events between strains originating from various species. The patient lived in a household containing domesticated cats and dogs and in close proximity to a colony of Gray-headed Flying-foxes. However, without screening numerous animal populations it is not possible to determine the origins of this strain. PMID:24780429

  19. Myocyte-specific enhancer factor 2C: a novel target gene of miR-214-3p in suppressing angiotensin II-induced cardiomyocyte hypertrophy

    PubMed Central

    Tang, Chun-Mei; Liu, Fang-zhou; Zhu, Jie-Ning; Fu, Yong-Heng; Lin, Qiu-Xiong; Deng, Chun-Yu; Hu, Zhi-Qin; Yang, Hui; Zheng, Xi-Long; Cheng, Jian-Ding; Wu, Shu-Lin; Shan, Zhi-Xin

    2016-01-01

    The role of microRNA-214-3p (miR-214-3p) in cardiac hypertrophy was not well illustrated. The present study aimed to investigate the expression and potential target of miR-214-3p in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. In mice with either Ang-II infusion or transverse aortic constriction (TAC) model, miR-214-3p expression was markedly decreased in the hypertrophic myocardium. Down-regulation of miR-214-3p was observed in the myocardium of patients with cardiac hypertrophy. Expression of miR-214-3p was upregulated in Ang-II-induced hypertrophic neonatal mouse ventricular cardiomyocytes. Cardiac hypertrophy was attenuated in Ang-II-infused mice by tail vein injection of miR-214-3p. Moreover, miR-214-3p inhibited the expression of atrial natriuretic peptide (ANP) and β-myosin heavy chain (MHC) in Ang-II-treated mouse cardiomyocytes in vitro. Myocyte-specific enhancer factor 2C (MEF2C), which was increased in Ang-II-induced hypertrophic mouse myocardium and cardiomyocytes, was identified as a target gene of miR-214-3p. Functionally, miR-214-3p mimic, consistent with MEF2C siRNA, inhibited cell size increase and protein expression of ANP and β-MHC in Ang-II-treated mouse cardiomyocytes. The NF-κB signal pathway was verified to mediate Ang-II-induced miR-214-3p expression in cardiomyocytes. Taken together, our results revealed that MEF2C is a novel target of miR-214-3p, and attenuation of miR-214-3p expression may contribute to MEF2Cexpressionin cardiac hypertrophy. PMID:27796324

  20. MiR-100-3p and miR-877-3p regulate overproduction of IL-8 and IL-1β in mesangial cells activated by secretory IgA from IgA nephropathy patients.

    PubMed

    Liang, Yan; Zhao, Guoqiang; Tang, Lin; Zhang, Junjun; Li, Tianfang; Liu, Zhangsuo

    2016-10-01

    IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis, characterized by mesangial deposition of pathogenic IgA and the injury to mesangial cells. Our previous studies indicate that secretory IgA (SIgA) plays an important role in the pathogenesis of IgAN, and miR-16 is involved in destructive process in mesangial cells mediated by the SIgA from IgAN patients. Our current study aimed to study the role of miRNAs in the effect of SIgA from IgAN patients on mesangial cells. MicroRNA microarray and cytokines assay were performed to obtain the differential microRNAs expression profile in human renal mesangial cells stimulated by SIgA from IgAN patients (P-SIgA) with the cells treated by SIgA from healthy subjects (N-SgA) as control. The microRNAs with the most significant differences in microarray analysis were validated by quantitative RT-PCR. Among them, miR-100-3p and miR-877-3p were selected to predict target gene related to cytokines detecting in this study. Fifty-six differentially expressed microRNAs were chosen and 17 microRNAs with the most prominent changes were validated. Compared with N-SIgA, P-SIgA increased the production of interleukin (IL)-1β, IL-8, monocyte chemotactic protein-1 and transforming growth factor-β1. In addition, we for the first time demonstrated that over-production of IL-8 induced by the SIgA was regulated by down-expression of miR-100-3p in mesangial cells. Similarly, IL-1β over-production was regulated by down-expression of miR-877-3p. Our findings represent a pathogenic microRNAs expression profiling in human mesangial cells activated by P-SIgA. Furthermore, we provide a new explanation characterizing the molecular mechanism responsible for the regulation of IL-1β and IL-8 production in P-SIgA-triggered mesangial cells.

  1. Prognostic value of replication errors on chromosomes 2p and 3p in non-small-cell lung cancer.

    PubMed Central

    Pifarré, A.; Rosell, R.; Monzó, M.; De Anta, J. M.; Moreno, I.; Sánchez, J. J.; Ariza, A.; Mate, J. L.; Martińez, E.; Sánchez, M.

    1997-01-01

    As chromosomes 2p and 3p are frequent targets for genomic instability in lung cancer, we have addressed whether alterations of simple (CA)n DNA repeats occur in non-small-cell lung cancer (NSCLC) at early stages. We have analysed by polymerase chain reaction (PCR) assay replication errors (RER) and loss of heterozygosity (LOH) at microsatellites mapped on chromosomes 2p and 3p in 64 paired tumour-normal DNA samples from consecutively resected stage I, II or IIIA NSCLC. DNA samples were also examined for K-ras and p53 gene mutations by PCR-single-stranded conformational polymorphism (PCR-SSCP) analysis and cyclic sequencing, as well as their relationship with clinical outcome. Forty-two of the 64 (66%) NSCLC patients showed RER at single or multiple loci. LOH was detected in 23 tumours (36%). Among patients with stage I disease, the 5-year survival rate was 80% in those whose tumours had no evidence of RER and 26% in those with RER (P = 0.005). No correlation was established between RER phenotype and LOH, K-ras or p53 mutations. RER remained a strong predictive factor (hazard ratio for death, 2.89; 95% confidence interval, 2.23-3.79; P = 0.002) after adjustment for all other evaluated factors, including p53, K-ras, LOH, histological type, tumour differentiation and TNM stage, suggesting that microsatellite instability on chromosomes 2p and 3p may play a role in NSCLC progression through a different pathway from the traditional tumour mechanisms of oncogene activation and/or tumour-suppressor gene inactivation. Images Figure 1 PMID:9010024

  2. The effects of surface temperature on the gas-liquid interfacial reaction dynamics of O(3P)+squalane.

    PubMed

    Köhler, Sven P K; Allan, Mhairi; Kelso, Hailey; Henderson, David A; McKendrick, Kenneth G

    2005-01-01

    OH/OD product state distributions arising from the reaction of gas-phase O(3P) atoms at the surface of the liquid hydrocarbon squalane C30H62/C30D62 have been measured. The O(3P) atoms were generated by 355 nm laser photolysis of NO2 at a low pressure above the continually refreshed liquid. It has been shown unambiguously that the hydroxyl radicals detected by laser-induced fluorescence originate from the squalane surface. The gas-phase OH/OD rotational populations are found to be partially sensitive to the liquid temperature, but do not adapt to it completely. In addition, rotational temperatures for OH/OD(v'=1) are consistently colder (by 34+/-5 K) than those for OH/OD(v'=0). This is reminiscent of, but less pronounced than, a similar effect in the well-studied homogeneous gas-phase reaction of O(3P) with smaller hydrocarbons. We conclude that the rotational distributions are composed of two different components. One originates from a direct abstraction mechanism with product characteristics similar to those in the gas phase. The other is a trapping-desorption process yielding a thermal, Boltzmann-like distribution close to the surface temperature. This conclusion is consistent with that reached previously from independent measurements of OH product velocity distributions in complementary molecular-beam scattering experiments. It is further supported by the temporal profiles of OH/OD laser-induced fluorescence signals as a function of distance from the surface observed in the current experiments. The vibrational branching ratios for (v'=1)/(v'=0) for OH and OD have been found to be (0.07+/-0.02) and (0.30+/-0.10), respectively. The detection of vibrationally excited hydroxyl radicals suggests that secondary and/or tertiary hydrogen atoms may be accessible to the attacking oxygen atoms.

  3. The effects of surface temperature on the gas-liquid interfacial reaction dynamics of O(3P)+squalane

    NASA Astrophysics Data System (ADS)

    Köhler, Sven P. K.; Allan, Mhairi; Kelso, Hailey; Henderson, David A.; McKendrick, Kenneth G.

    2005-01-01

    OH/OD product state distributions arising from the reaction of gas-phase O(3P) atoms at the surface of the liquid hydrocarbon squalane C30H62/C30D62 have been measured. The O(3P) atoms were generated by 355 nm laser photolysis of NO2 at a low pressure above the continually refreshed liquid. It has been shown unambiguously that the hydroxyl radicals detected by laser-induced fluorescence originate from the squalane surface. The gas-phase OH/OD rotational populations are found to be partially sensitive to the liquid temperature, but do not adapt to it completely. In addition, rotational temperatures for OH/OD(v'=1) are consistently colder (by 34±5 K) than those for OH/OD(v'=0). This is reminiscent of, but less pronounced than, a similar effect in the well-studied homogeneous gas-phase reaction of O(3P) with smaller hydrocarbons. We conclude that the rotational distributions are composed of two different components. One originates from a direct abstraction mechanism with product characteristics similar to those in the gas phase. The other is a trapping-desorption process yielding a thermal, Boltzmann-like distribution close to the surface temperature. This conclusion is consistent with that reached previously from independent measurements of OH product velocity distributions in complementary molecular-beam scattering experiments. It is further supported by the temporal profiles of OH/OD laser-induced fluorescence signals as a function of distance from the surface observed in the current experiments. The vibrational branching ratios for (v'=1)/(v'=0) for OH and OD have been found to be (0.07±0.02) and (0.30±0.10), respectively. The detection of vibrationally excited hydroxyl radicals suggests that secondary and/or tertiary hydrogen atoms may be accessible to the attacking oxygen atoms.

  4. Theoretical investigation of the O({sup 3}P) + CHX{sub 2} (X = F, Cl) reactions

    SciTech Connect

    Hou, H.; Wang, B.; Gu, Y.

    1999-10-07

    The reactions of oxygen atoms with the CHX{sub 2} (X = F, Cl) radicals have been studied for the first time using the G2(MP2) method. The extensive calculations reveal the capture-limited association-elimination mechanism for the O + CHX{sub 2} reaction. For the O({sup 3}P) + CHF{sub 2} reaction, two energy-rich intermediates, CHF{sub 2}O* and CF{sub 2}OH*, are formed along the reaction path. CHF{sub 2}O* has four unimolecular production channels: H + CF{sub 2}O; CF{sub 2}OH; F + CHFO; and HF + FCO. The isomer CF{sub 2}OH can decompose to H + CF{sub 2}O, HF + FCO, OH + CF{sub 2}, and F + FCOH. The analogous production channels such as Cl + CHClO, H + CCl{sub 2}O, HCl + ClCO, OH + CCl{sub 2}, and Cl + ClCOH are investigated for the O({sup 3}P) + CHCl{sub 2} reaction. It should be noted that three-center direct elimination of HCl from the adduct CHCl{sub 2}O* was characterized using the semiempirical AMl method. On the basis of the ab initio potential energy surfaces, the kinetics and the dynamics for these two atom/radical reactions are discussed qualitatively. For the O + CHF{sub 2} reaction, H and CF{sub 2}O are predicted to be the major products. For the O({sup 3}P) + CHCl{sub 2} reaction, the major production channel is the formation of Cl + CHClO, while the HCl + ClCO channel may be competitive.

  5. Temperature dependence of two key interstellar reactions of H(3)(+): O((3)P) + H(3)(+) and CO + H(3)(+).

    PubMed

    Klippenstein, Stephen J; Georgievskii, Yuri; McCall, Benjamin J

    2010-01-14

    The reactions of H(3)(+) with CO and with O((3)P) are the two most important reactions for the destruction of H(3)(+) in dense interstellar clouds. These two reactions are studied with sophisticated theoretical methods that should provide accurate predictions for the rate coefficients. The potential energy surfaces are studied with high-level electronic structure methods. For both reactions, simple long-range expansions are shown to be sufficiently accurate for predicting the kinetics at room temperature and lower. The kinetics is predicted from a combination of transition state theory, trajectory simulations, and master equation analysis. For the O((3)P) reaction, the interplay between the spin-orbit and the charge-quadrupole interactions is explicitly considered. For the CO reaction, we also consider the isomerization and decomposition dynamics of the two initially formed adducts. The final predictions, which are expected to be accurate to about 10 to 20%, are compared with the available experimental data. For the O((3)P) reaction, the predicted rate coefficient is accurately reproduced by the expression 1.14 x 10(-9) (T/300)(-0.156) exp(-1.41/T) cm(3) molecule(-1) s(-1) over the 5 to 400 K temperature range. For the CO reaction, the predicted rate coefficients for the H(2) + HCO(+) and H(2) + HOC(+) channels are accurately reproduced by the expressions 1.36 x 10(-9) (T/300)(-0.142) exp(3.41/T) and 8.49 x 10(-10) (T/300)(0.0661) exp(-5.21/T) cm(3) molecule(-1) s(-1), respectively, over the 10 to 400 K temperature range. These revised rate coefficient expressions imply an increase in the destruction of H(3)(+) at temperatures that are typical of dense clouds (10-30 K) by a factor of 2.5 to 3.0.

  6. Dicer Knockdown Inhibits Endothelial Cell Tumor Growth via MicroRNA 21a-3p Targeting of Nox-4*

    PubMed Central

    Gordillo, Gayle M.; Biswas, Ayan; Khanna, Savita; Pan, Xueliang; Sinha, Mithun; Roy, Sashwati; Sen, Chandan K.

    2014-01-01

    MicroRNAs (miR) are emerging as biomarkers and potential therapeutic targets in tumor management. Endothelial cell tumors are the most common soft tissue tumors in infants, yet little is known about the significance of miR in regulating their growth. A validated mouse endothelial cell (EOMA) tumor model was used to demonstrate that post-transcriptional gene silencing of dicer, the enzyme that converts pre-miR to mature miR, can prevent tumor formation in vivo. Tumors were formed in eight of eight mice injected with EOMA cells transfected with control shRNA but formed in only four of ten mice injected with EOMA cells transfected with dicer shRNA. Tumors that formed in the dicer shRNA group were significantly smaller than tumors in the control group. This response to dicer knockdown was mediated by up-regulated miR 21a-3p activity targeting the nox-4 3′-UTR. EOMA cells were transfected with miR 21a-3p mimic and luciferase reporter plasmids containing either intact nox-4 3′-UTR or with mutation of the proposed 3′-UTR miR21a-3p binding sites. Mean luciferase activity was decreased by 85% in the intact compared with the site mutated vectors (p < 0.01). Attenuated Nox-4 activity resulted in decreased cellular hydrogen peroxide production and decreased production of oxidant-inducible monocyte chemoattractant protein-1, which we have previously shown to be critically required for endothelial cell tumor formation. These findings provide the first evidence establishing the significance of dicer and microRNA in promoting endothelial cell tumor growth in vivo. PMID:24497637

  7. Interplay between promoter methylation and chromosomal loss in gene silencing at 3p11-p14 in cervical cancer

    PubMed Central

    Lando, Malin; Fjeldbo, Christina S; Wilting, Saskia M; Snoek, Barbara C; Aarnes, Eva-Katrine; Forsberg, Malin F; Kristensen, Gunnar B; Steenbergen, Renske DM; Lyng, Heidi

    2015-01-01

    Loss of 3p11-p14 is a frequent event in epithelial cancer and a candidate prognostic biomarker in cervical cancer. In addition to loss, promoter methylation can participate in gene silencing and promote tumor aggressiveness. We have performed a complete mapping of promoter methylation at 3p11-p14 in two independent cohorts of cervical cancer patients (n = 149, n = 121), using Illumina 450K methylation arrays. The aim was to investigate whether hyperm-ethylation was frequent and could contribute to gene silencing and disease aggressiveness either alone or combined with loss. By comparing the methylation level of individual CpG sites with corresponding data of normal cervical tissue, 26 out of 41 genes were found to be hypermethylated in both cohorts. The frequency of patients with hypermethylation of these genes was found to be higher at tumor stages of 3 and 4 than in stage 1 tumors. Seventeen of the 26 genes were transcriptionally downregulated in cancer compared to normal tissue, whereof 6 genes showed a significant correlation between methylation and expression. Integrated analysis of methylation, gene dosage, and expression of the 26 hypermethylated genes identified 3 regulation patterns encompassing 8 hypermethylated genes; a methylation driven pattern (C3orf14, GPR27, ZNF717), a gene dosage driven pattern (THOC7, PSMD6), and a combined methylation and gene dosage driven pattern (FHIT, ADAMTS9, LRIG1). In survival analysis, patients with both hypermethylation and loss of LRIG1 had a worse outcome compared to those harboring only hypermethylation or none of the events. C3orf14 emerged as a novel methylation regulated suppressor gene, for which knockdown was found to promote invasive growth in human papilloma virus (HPV)-transformed keratinocytes. In conclusion, hypermethylation at 3p11-p14 is common in cervical cancer and may exert a selection pressure during carcinogenesis alone or combined with loss. Information on both events could lead to improved

  8. The microRNA miR-17-3p inhibits mouse cardiac fibroblast senescence by targeting Par4.

    PubMed

    Du, William W; Li, Xianmin; Li, Tianbi; Li, Haoran; Khorshidi, Azam; Liu, Fengqiong; Yang, Burton B

    2015-01-15

    The microRNA miR-17-92 cluster plays a fundamental role in heart development. The aim of this study was to investigate the effect of a member of this cluster, miR-17, on cardiac senescence. We examined the roles of miR-17 in senescence and demonstrated that miR-17-3p attenuates cardiac aging in the myocardium by targeting Par4 (also known as PAWR). This upregulates the downstream proteins CEBPB, FAK, N-cadherin, vimentin, Oct4 and Sca-1 (also known as stem cell antigen-1), and downregulates E-cadherin. Par4 has been reported as a tumor suppressor gene that induces apoptosis in cancer cells, but not in normal cells. Repression of Par4 by miR-17-3p enhances the transcription of CEBPB and FAK, which promotes mouse cardiac fibroblast (MCF) epithelial-to-mesenchymal transition (EMT) and self-renewal, resulting in cellular senescence and apoptosis resistance. We conclude that Par4 can bind to the CEBPB promoter and inhibit its transcription. Decreased Par4 expression increases the amount of CEBPB, which binds to the FAK promoter and enhances FAK transcription. Par4, CEBPB and FAK form a senescence signaling pathway, playing roles in modulating cell survival, gro